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Sample records for chronic liver injury

  1. Protective mechanisms of garlic and wolfberry derivatives on acute and chronic liver injury animal models

    OpenAIRE

    Xiao, Jia; 肖佳

    2012-01-01

    Liver is one of the most important organs in the body that maintains the homeostasis of metabolism, immunity, detoxification and hematopoiesis. A large number of acute and chronic intoxications and diseases can influence the normal functions of the liver, leading to irreversible liver damage and even cancer. Currently, applying herbs or herbal derivatives in the prevention and therapy of acute and chronic liver injury receive numerous attentions since they hold great potentials as food supple...

  2. Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice.

    Science.gov (United States)

    Tabet, Elise; Genet, Valentine; Tiaho, François; Lucas-Clerc, Catherine; Gelu-Simeon, Moana; Piquet-Pellorce, Claire; Samson, Michel

    2016-07-25

    Chronic liver damage due to viral or chemical agents leads to a repair process resulting in hepatic fibrosis. Fibrosis may lead to cirrhosis, which may progress to liver cancer or a loss of liver function, with an associated risk of liver failure and death. Chlordecone is a chlorinated pesticide used in the 1990s. It is not itself hepatotoxic, but its metabolism in the liver triggers hepatomegaly and potentiates hepatotoxic agents. Chlordecone is now banned, but it persists in soil and water, resulting in an ongoing public health problem in the Caribbean area. We assessed the probable impact of chlordecone on the progression of liver fibrosis in the population of contaminated areas, by developing a mouse model of chronic co-exposure to chlordecone and a hepatotoxic agent, carbon tetrachloride (CCl4). After repeated administrations of chlordecone and CCl4 by gavage over a 12-week period, we checked for liver damage in the exposed mice, by determining serum liver transaminase (AST, ALT) levels, histological examinations of the liver and measuring the expression of genes encoding extracellular matrix components. The co-exposure of mice to CCl4 and chlordecone resulted in significant increases in ALT and AST levels. Chlordecone also increased expression of the Col1A2, MMP-2, TIMP-1 and PAI-1 genes in CCl4-treated mice. Finally, we demonstrated, by quantifying areas of collagen deposition and alpha-SMA gene expression, that chlordecone potentiated the hepatic fibrosis induced by CCl4. In conclusion, our data suggest that chlordecone potentiates hepatic fibrosis in mice with CCl4-induced chronic liver injury. PMID:26853152

  3. Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Yumin Xu

    Full Text Available BACKGROUND: Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  4. Effect of WeiJia on carbon tetrachloride induced chronic liver injury

    Institute of Scientific and Technical Information of China (English)

    Pik-Yuen Cheung; Jay Chun; Hsiang-Fu Kung; Meng-su Yang; Qi Zhang; Ya-Ou Zhang; Gan-Rong Bai; Marie Chia-Mi Lin; Bernard Chan; Chi-Chun Fong; Lin Shi; Yue-Feng Shi

    2006-01-01

    AIM: To study the effect of WeiJia on chronic liver injury using carbon tetrachloride (CCl4) induced liver injury animal model.METHODS: Wistar rats weighing 180-220g were randomly divided into three groups: normal control group (Group A), CCl4 induced liver injury control group (Group B) and CCl4 induction with WeiJia treatment group (Group C). Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCl4 in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week,Group C rats also received daily intraperitoneal injection of WeiJia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week (4 male, 3 female), and eighth week (4 male, 3 female) respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid (HA), type Ⅳ collagen (CIV), γ-glutamyl transferase (γ-GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were also performed.RESULTS: CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and Y-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L (P0.05) respectively, similar to normal control group (Group A), but significantly different from CCl4 induced liver injury control group (Group B). An increase in PCNA and decrease in a-SMA expression level was also observed.CONCLUSION: WeiJia could improve liver function and reduce liver fibrosis

  5. Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis

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    Nikolaos P. Karidis

    2015-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

  6. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

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    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  7. Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury.

    Science.gov (United States)

    Wang, Yuhua; Liu, Yanlong; Kirpich, Irina; Ma, Zhenhua; Wang, Cuiling; Zhang, Min; Suttles, Jill; McClain, Craig; Feng, Wenke

    2013-09-01

    The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal gram-negative bacteria in ALD. In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-α (TNFα) production and inflammation in response to chronic alcohol ingestion. Mice were fed Lieber DeCarli liquid diet containing 5% alcohol for 8weeks, and Lactobacillus rhamnosus GG (LGG) was supplemented in the last 2 weeks. Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay. Two weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA expression of Toll-like receptors (TLRs) and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression. LGG supplementation attenuated these changes. Using human peripheral blood monocytes-derived macrophages, we also demonstrated that incubation with ethanol primes both lipopolysaccharide- and flagellin-induced TNFα production, and LGG culture supernatant reduced this induction in a dose-dependent manner. In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase. In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNFα production via inhibition of TLR4- and TLR5-mediated endotoxin activation. PMID:23618528

  8. Protective effect of corn peptides against alcoholic liver injury in men with chronic alcohol consumption: a randomized double-blind placebo-controlled study

    OpenAIRE

    Wu, Yuhong; Pan, Xingchang; Zhang, Shixiu; Wang, Wenxian; Cai, Muyi; Li, Yanrong; Yang, Fan; Guo, Hongwei

    2014-01-01

    Background Corn peptides (CPs) are a novel food prepared from corn gluten meal, which is a main by-product of the corn starch industry. Recently, significant beneficial effects of CPs on early alcoholic liver injury in rats and on acute alcoholic injury in mice were observed. To our knowledge, the present study is the first report showing that CPs supplementation has beneficial effects on lipid profile, oxidative stress and alcoholic liver injury in men with chronic alcohol consumption. Metho...

  9. Leptin is essential for the hepatic fibrogenic response to chronic liver injury

    NARCIS (Netherlands)

    Leclercq, IA; Farrell, GC; Schriemer, R; Robertson, GR

    2002-01-01

    Background/Aims: Obesity is associated with hyperleptinemia and is also a risk factor for fibrosis and severity of fibrosis in several chronic liver diseases. The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on th

  10. Decreased chronic cellular and antibody-mediated injury in the kidney following simultaneous liver-kidney transplantation.

    Science.gov (United States)

    Taner, Timucin; Heimbach, Julie K; Rosen, Charles B; Nyberg, Scott L; Park, Walter D; Stegall, Mark D

    2016-04-01

    In simultaneous liver-kidney transplantation (SLK), the liver can protect the kidney from hyperacute rejection and may also decrease acute cellular rejection rates. Whether the liver protects against chronic injury is unknown. To answer this we studied renal allograft surveillance biopsies in 68 consecutive SLK recipients (14 with donor-specific alloantibodies at transplantation [DSA+], 54 with low or no DSA, [DSA-]). These were compared with biopsies of a matched cohort of kidney transplant alone (KTA) recipients (28 DSA+, 108 DSA-). Overall 5-year patient and graft survival was not different: 93.8% and 91.2% in SLK, and 91.9% and 77.1% in KTA. In DSA+ recipients, KTA had a significantly higher incidence of acute antibody-mediated rejection (46.4% vs. 7.1%) and chronic transplant glomerulopathy (53.6% vs. 0%). In DSA- recipients at 5 years, KTA had a significantly higher cumulative incidence of T cell-mediated rejection (clinical plus subclinical, 30.6% vs. 7.4%). By 5 years, DSA+ KTA had a 44% decline in mean GFR while DSA+SLK had stable GFR. In DSA- KTA, the incidence of a combined endpoint of renal allograft loss or over a 50% decline in GFR was significantly higher (20.4% vs. 7.4%). Simultaneously transplanted liver allograft was the most predictive factor for a significantly lower incidence of cellular (odds ratio 0.13, 95% confidence interval 0.06-0.27) and antibody-mediated injury (odds ratio 0.11, confidence interval 0.03-0.32), as well as graft functional decline (odds ratio 0.22, confidence interval 0.06-0.59). Thus, SLK is associated with reduced chronic cellular and antibody-mediated alloimmune injury in the kidney allograft. PMID:26924059

  11. Effect of matrine hydrochloride on liver injury

    Institute of Scientific and Technical Information of China (English)

    CHEN Li-bo; XU Feng; MA Wen-hui

    2008-01-01

    Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、 immunity liver injury of mice and chronic liver injury of rats. Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride (CCl4), thioacetamide(TAA), D-galactosamine(D-GalN), immunity hepatic injury model of mice induced by BCG and fat polysaccharide (LPS), chronic liver injury model of rats induced by CCI, were introduced in the experiment. The serum ALT and AST were measured in acute hepatic injury experiments. Serum ALT, AST, AKP, ALB, TP, BiL-T, ereatinine, triglyceride, sialie acid, larninin, hyaluronic acid, type Ⅲ proeollagen and type Ⅳ collagen, hepatic hydroxyproline (HyP) of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride. Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4, TAA and D-GaIN. The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment. Compared with the model group, the injection may obviously inhibited serum ALT, AST, TP, AKP, TRI, BiL-T, creatinine, triglyceride, sialic acid, laminin , hyaluronic acid , type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4, elevated ALB、A/G, reduced the liver HyP, decreased the index of the liver and the spleen. The liver visual observation, the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue, restrain the liver cell damage, reduce the pseudolobuli formation. Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and

  12. Sleep apnea hypopnea syndrome and liver injury

    Institute of Scientific and Technical Information of China (English)

    TIAN Jian-li; ZHANG Yun; CHEN Bao-yuan

    2010-01-01

    Objective A general review was made of studies involving: (1) the relationship between sleep apnea hypopneasyndrome/sleep apnea style intermittent hypoxia and liver injury and (2) the mechanism that causes the liver injury.Data sources The data used in this review were mainly from Medline and PubMed published in English from 1993 toFebruary 2009. The search term was "sleep apnea hypopnea syndrome".Study selection (1) Clinical and laboratory evidence that sleep apnea hypopnea syndrome and sleep apnea styleintermittent hypoxia leads to liver injury; (2) the mechanism that causes the liver injury.Results The effect of sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the liver functionis characterized by serum aminotransferase elevation. The liver histological injury includes hepatic steatosis, hepatocyteballooning, lobular inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome and sleep apneastyle intermittent hypoxia can cause insulin resistance and oxidative stress.Conclusions Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can lead to chronic liverinjury, which, in most cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and oxidative stress causedby sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia play an important role in the mechanismof chronic liver disease development.

  13. Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury

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    Jing-Hua Peng

    2012-01-01

    Full Text Available Kudzu (Pueraria lobata is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE on chronic alcoholic liver injury as well as Kupffer cells (KCs activation to release tumor necrosis factor alpha (TNF-α induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, and hepatic gamma-glutamyl transpeptidase (GGT activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP, CD14, Toll-like receptor (TLR 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro.

  14. The occurrence and significance of fibronectin in livers from chronic alcoholics. An immunohistochemical study of early alcoholic liver injury

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Christoffersen, P

    1988-01-01

    The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular locali...... is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation....

  15. Metal Ion Imbalance-Related Oxidative Stress Is Involved in the Mechanisms of Liver Injury in a Rat Model of Chronic Aluminum Exposure.

    Science.gov (United States)

    Yang, Yang; Wang, Hong; Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Yang, Junqing; He, Qin

    2016-09-01

    The objective of the study is to investigate the effects of chronic aluminum overload on rat liver function and its induction of pathological changes in metal ion levels and oxidative stress in hepatic tissues. Wistar rats were intragastrically administered aluminum gluconate (200 mg Al(3+)/Kg) once a day, 5 days a week, for 20 weeks. HE staining was used to visualize pathological changes in rat liver tissue. A biochemical method was adopted to detect ALT, AST, ALP, and GGT levels, as well as liver SOD activity and blood plasma MDA content. A plasma atomic emission spectrophotometer was used to detect Al, Mn, Fe, Zn, and Cu ion contents in liver tissue. Our results showed obvious vacuolar degeneration, granular degeneration, and spotty necrosis in chronic Al-overload rat hepatocytes. The levels of ALT, AST, ALP, and GGT were significantly increased. Liver SOD activity was significantly decreased, and MDA content was significantly increased. In Al-overload rat liver, Al, Mn, Fe, and Cu contents were significantly increased, and in Al-overload rat serum, Mn, Fe, Zn, and Cu contents were significantly decreased. However, the Al level in Al-overload rat serum was not significantly different from that in control rat serum. These results suggest that chronic aluminum overload causes obvious damage to rat liver and causes imbalances in Al, Mn, Fe, Zn, and Cu levels in rat liver and serum. Metal ion imbalance-related oxidative stress may be involved in the mechanism of chronic liver injury caused by aluminum overload. PMID:26811106

  16. Effect of Platelet-Rich Plasma on CCl4-Induced Chronic Liver Injury in Male Rats.

    Science.gov (United States)

    Hesami, Zahra; Jamshidzadeh, Akram; Ayatollahi, Maryam; Geramizadeh, Bita; Farshad, Omid; Vahdati, Akbar

    2014-01-01

    Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1 mL/kg, i.p. 1 : 1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5 mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP. PMID:24707405

  17. Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury

    OpenAIRE

    Wang, Yuhua; Liu, Yanlong; Kirpich, Irina; Ma, Zhenhua; Wang, Cuiling; Zhang, Min; Suttles, Jill; McClain, Craig; Feng, Wenke

    2013-01-01

    The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal Gram-negative bacteria in ALD. In this study, we investigated t...

  18. Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding.

    Science.gov (United States)

    Tian, Fengwei; Chi, Feifei; Wang, Gang; Liu, Xiaoming; Zhang, Qiuxiang; Chen, Yongquan; Zhang, Hao; Chen, Wei

    2015-12-01

    Lactobacillus rhamnosus CCFM1107 was screened for high antioxidative activity from 55 lactobacilli. The present study attempted to explore the protective properties of L. rhamnosus CCFM1107 in alcoholic liver injury. A mouse model was induced by orally feeding alcohol when simultaneously treated with L. rhamnosus CCFM1107, the drug Hu-Gan- Pian (HGP), L. rhamnosus GG (LGG), and L. plantarum CCFM1112 for 3 months. Biochemical analysis was performed for both serum and liver homogenate. Detailed intestinal flora and histological analyses were also carried out. Our results indicated that the administration of L. rhamnosus CCFM1107 significantly inhibited the increase in the levels of serum aminotransferase and endotoxin, as well as the levels of triglyceride (TG) and cholesterol (CHO) in the serum and in the liver. Glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were elevated while the levels of malondialdehyde (MDA) were decreased. The enteric dysbiosis caused by alcohol was restored by increasing the numbers of both lactobacilli and bifidobacteria and decreasing the numbers of both enterococci and enterobacter. Histological analysis confirmed the protective effect of L. rhamnosus CCFM1107. Compared with the other lactobacilli and to the drug Hu-Gan-Pian, there is a high chance that L. rhamnosus CCFM1107 provides protective effects on alcoholic liver injury by reducing oxidative stress and restoring the intestinal flora. PMID:26626356

  19. Naproxen-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  20. Kidneys in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marek Hartleb; Krzysztof Gutkowski

    2012-01-01

    Acute kidney injury (AKI),defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL,occurs in about 20% of patients hospitalized for decompensating liver cirrhosis.Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state,reduced effective blood volume and stimulation of vasoconstrictor hormones.The most common causes of AKI in cirrhosis are pre-renal azotemia,hepatorenal syndrome and acute tubular necrosis.Differential diagnosis is based on analysis of circumstances of AKI development,natriuresis,urine osmolality,response to withdrawal of diuretics and volume repletion,and rarely on renal biopsy.Chronic glomeruIonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients.AKI is one of the last events in the natural history of chronic liver disease,therefore,such patients should have an expedited referral for liver transplantation.Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension,and may be prematurely triggered by bacterial infections,nonbacterial systemic inflammatory reactions,excessive diuresis,gastrointestinal hemorrhage,diarrhea or nephrotoxic agents.Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy.The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion,which is effective in about 50% of patients.The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt,renal vasoprotection or systems of artificial liver support.

  1. the Pathogenesis of acute on Chronic Hepatitis B liver Failure

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Quan-jiang Dong; Chang-xin Geng

    2014-01-01

    Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would beneift for the prognosis and raise the survival rate of patients.

  2. [Characteristics of the spermatogenic epithelium in the testis of newborn rats--the offspring of female rats with chronic liver injury of various genesis].

    Science.gov (United States)

    Sizonenko, M L; Briukhin, G V

    2014-01-01

    The effect of chronic injury of hepatobiliary system of various genesis in females rats on the formation of spermatogenic epithelium in the testis of their newborn offspring was studied. The models of toxic (CCl4) and medicinal (tetracycline, paracetamol) liver injury were used. The state of the seminiferous epithelium was assessed on the serial histological sections of the testis with the use of the morphometric device. In experimental animals, a reduction of the diameter and the area of the seminiferous tubules (ST) was detected, associated with the decline of the total number of spermatogenic cells, spermatogonia of various generations, total number of spermatocytes and Sertoli cells. At the same time, in the newborn rats of all the experimental groups, the number of ST with the desquamated epithelium, and that one of the multinucleated spermatogenic cells with fragmented and pyknotic nuclei were increased. PMID:25282824

  3. Chronic Liver Disease and African Americans

    Science.gov (United States)

    ... American > Chronic Liver Disease Chronic Liver Disease and African Americans Among African Americans, chronic liver disease is a ... white women. At a glance – Cancer Rates for African Americans (2008-2012) Cancer Incidence Rates per 100,000 – ...

  4. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

    OpenAIRE

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-Fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-Ming; Chen, Nan; Zhang, Nai-xia

    2014-01-01

    Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolo...

  5. Chronic avulsive injuries of childhood

    International Nuclear Information System (INIS)

    Children and adolescents are prone to avulsive injuries related to a combination of their propensity for great strength, ability to sustain extreme levels of activity, and immature growing apophyses. Appropriate interpretation of imaging studies showing chronic avulsive injuries is essential so that the irregularity and periostitis that can be associated with chronic avulsions is not misinterpreted as probable malignancy. This article reviews the chronic avulsive injuries of childhood. (orig.)

  6. Chronic avulsive injuries of childhood

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly, L.F.; Helms, C.A. [Dept. of Radiology, Duke Univ. Medical Center, Durham, NC (United States); Bisset, G.S. III [Dept. of Radiology, Duke Univ. Medical Center, Durham, NC (United States)]|[Department of Pediatrics, Duke University Medical Center, Durham, NC (United States); Squire, D.L. [Department of Pediatrics, Duke University Medical Center, Durham, NC (United States)

    1999-03-01

    Children and adolescents are prone to avulsive injuries related to a combination of their propensity for great strength, ability to sustain extreme levels of activity, and immature growing apophyses. Appropriate interpretation of imaging studies showing chronic avulsive injuries is essential so that the irregularity and periostitis that can be associated with chronic avulsions is not misinterpreted as probable malignancy. This article reviews the chronic avulsive injuries of childhood. (orig.) With 12 figs., 8 refs.

  7. Nutrition in Chronic Liver Disease

    OpenAIRE

    Marco Silva; Sara Gomes; Armando Peixoto; Paulo Torres-Ramalho; Hélder Cardoso; Rosa Azevedo; Carla Cunha; Guilherme Macedo

    2015-01-01

    Protein-calorie malnutrition is a transversal condition to all stages of chronic liver disease. Early recognition of micro or macronutrient deficiencies is essential, because the use of nutritional supplements reduces the risk of complications. The diet of patients with chronic liver disease is based on a standard diet with supplements addition as necessary. Restrictions may be harmful and should be individualized. Treatment management should aim to maintain an adequate protein and caloric...

  8. Review of liver injury associated with dietary supplements.

    Science.gov (United States)

    Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

    2011-05-01

    Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. PMID:21457433

  9. Fenofibrate-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Kazufumi Dohmen; Hiromi Tshibashi; Chun Yang Wen; Shinya Nagaoka; Koji Yano; Seigo Abiru; Toshihito Ueki; Atsumasa Komori; Manabu Daikoku; Hiroshi Yatsuhashi

    2005-01-01

    @@ TO THE EDITOR Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis (PBC)[1,2]. However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug.

  10. Acute liver failure and acute kidney injury: Definitions, prognosis, and outcome

    OpenAIRE

    Włodzimirow, K.A.

    2013-01-01

    The objective of this thesis was to investigate definitions, prognostic indicators and their association with adverse events, mainly mortality for acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute kidney injury (AKI).

  11. Acute alcohol-induced liver injury

    Directory of Open Access Journals (Sweden)

    Gavin Edward Arteel

    2012-06-01

    Full Text Available Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, that also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

  12. Osteoporosis across chronic liver disease.

    Science.gov (United States)

    Guarino, M; Loperto, I; Camera, S; Cossiga, V; Di Somma, C; Colao, A; Caporaso, N; Morisco, F

    2016-06-01

    Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures. PMID:26846777

  13. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    1996-01-01

    This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...... with functional renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal...... venous hypertension. In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other...

  14. Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Thioacetamide-Induced Chronic Liver Injury

    OpenAIRE

    Park, Soo Young; Shin, Hye Won; Lee, Kyoung Bun; Lee, Min-Jae; Jang, Ja-June

    2010-01-01

    Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA)-induced liver fibrogen...

  15. Therapeutic modulation of liver ischaemia reperfusion injury

    OpenAIRE

    Sheth, H.

    2011-01-01

    Liver Ischaemia Reperfusion Injury (IRI) leads to production of reactive oxygen species and cytokines, which affects hepatocellular function following liver resection and transplantation. This thesis examines 2 hypotheses: 1) The role of intravenous glycine in amelioration of liver IRI in a in vivo animal model of partial lobar liver IRI. 2) Does prophylactically administered N-acetylcysteine prevent liver IRI in patients undergoing elective liver resection. Materials ...

  16. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1996-01-01

    and neurohumoral dysregulation found in cirrhosis. Recent studies have shown that the ET system is highly activated in most cirrhotic patients. Circulating ET-1 and ET-3 levels have a positive relation to the severity of the disease and fluid retention, with the highest values recorded in patients...... venous hypertension. In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other......This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...

  17. Montelukast induced acute hepatocellular liver injury

    Directory of Open Access Journals (Sweden)

    Harugeri A

    2009-01-01

    Full Text Available A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast induced hepatocellular liver injury. Liver tests began to improve and returned to normal 55 days after drug cessation. Causality of this adverse drug reaction by the Council for International Organizations of Medical Sciences or Roussel Uclaf Causality Assessment Method (CIOMS or RUCAM and Naranjo′s algorithm was ′probable′. Liver tests should be monitored in patients receiving montelukast and any early signs of liver injury should be investigated with a high index of suspicion for drug induced liver injury.

  18. Autophagy and Liver Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  19. 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2015-01-01

    Full Text Available It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2, an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARγ, is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ2 on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ2 on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated that in vivo, 15d-PGJ2 administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and, in vitro, 15d-PGJ2 suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ2 was blocked by reactive oxygen species (ROS inhibitor, but not PPARγ antagonist, and action of 15d-PGJ2 was not reproduced by PPARγ synthetic ligands. In addition, 15d-PGJ2 triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ2 plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPARγ, which may represent a new strategy in the treatment of liver fibrosis.

  20. Anemia of Chronic Liver Diseases

    International Nuclear Information System (INIS)

    The pathogenetic mechanisms of anemia in patients with chronic liver disease were observed. Seventeen patients with moderate to advanced hepatic diseases were studied by various methods. Only patients without previous blood loss were included : 14 had cirrhosis, 2 had active chronic hepatitis, and one had inferior vena cava obstruction with associated liver cirrhosis. The followings were the results: 1. The anemia based on red blood cell count, Hb., and Ht. was found in 76.5-78.6% of the patients. 2. Red cell indices indicated that normo-macrocytic and normochromic anemia was present is the majority of the patients. 3. No evidence of megaloblastic anemia was found on the basis of the morphological examinations. 4. Serum iron, TIBC, % saturation and iron content in the bone marrow indicated that iron deficiency anemia was present in about half of the patients. 5. In the view of the erythrocyte dynamics, primary increase in the red cell destruction was ascribed to the cause of the anemia. 6. Decrease in the red cell survival time was not correlated with MCV, % saturation and S.L. ratio. Also, hemoglobin level was not correlated with MCV, % saturation and T50 Cr. Therefore, multiple causes may be involved in the pathogenesis of the anemia. 7. Anemia as determined by the red cell volume was found in only 60% of the patients. It may be possible that hemodilutional anemia is present.

  1. Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Ji-Yuan Zhang

    Full Text Available BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT carriers and 78 immune activated (IA patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+ subsets, which were closely associated with serum alanine aminotransferase (ALT levels and the liver histological activity index (HAI scores. In addition, the increased CD16(+ monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(- monocytes/macrophages. Furthermore, peripheral blood CD16(+ monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.

  2. [Strategies for paediatric spleen and liver injuries].

    Science.gov (United States)

    Zundel, S; Lieber, J; Tsiflikas, I; Henk, A-K; Schmittenbecher, P

    2014-12-01

    Traumatic injuries of the spleen and liver are typically caused by age-related falls or sports and traffic accidents. Today, the non-operative management for isolated injuries is established and evidence-based guidelines are available. The intact abdominal wall and the limited space within the peritoneum produce a compression which is the pathophysiological explanation for the limitation of the haemorrhage. Precondition for the non-operative therapy is the radiology-based classification of the injury (organ injury scale) and a haemodynamically stable patient. Haemodynamic stability is, if necessary maintained with blood transfusion, volume substitutes and the administration of catecholamines. In cases of hilar vascular injury and devascularisation or haemodynamic instability of the patient, despite utilisation of the measures mentioned above, urgent operative therapy needs to be performed. Organ sparing surgery is the therapy of choice for both liver and spleen. The spleen is required for the development of a competent immune system in the growing organism. Liver injuries can be further complicated by injury to the bile system, which might require operative reconstruction. If a patient suffers from multiple injuries and spleen or liver are involved, the decision on the management needs to be taken individually, no guidelines exist but the rate for operative therapy increases. Independent of the dimensions of injury, an experienced paediatric surgeon with his multidisciplinary team, considering the anatomic and age specific characteristics of a child, achieves the best therapeutic results. PMID:25531632

  3. Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh.

    Science.gov (United States)

    Guzman, Grace; Kallwitz, Eric R; Wojewoda, Christina; Chennuri, Rohini; Berkes, Jamie; Layden, Thomas J; Cotler, Scott J

    2009-01-01

    There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis. PMID:20130783

  4. Comparative gene and protein expression analyses of a panel of cytokines in acute and chronic drug-induced liver injury in rats

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is a significant safety issue associated with medication use, and is the major cause of failures in drug development and withdrawal in post marketing. Cytokines are signaling molecules produced and secreted by immune cells and play crucial roles in the progression of DILI. Although there are numerous reports of cytokine changes in several DILI models, a comprehensive analysis of cytokine expression changes in rat liver injury induced by various compounds has, to the best of our knowledge, not been performed. In the past several years, we have built a public, free, large-scale toxicogenomics database, called Open TG-GATEs, containing microarray data and toxicity data of the liver of rats treated with various hepatotoxic compounds. In this study, we measured the protein expression levels of a panel of 24 cytokines in frozen liver of rats treated with a total of 20 compounds, obtained in the original study that formed the basis of the Open TG-GATEs database and analyzed protein expression profiles combined with mRNA expression profiles to investigate the correlation between mRNA and protein expression levels. As a result, we demonstrated significant correlations between mRNA and protein expression changes for interleukin (IL)-1β, IL-1α, monocyte chemo-attractant protein (MCP)-1/CC-chemokine ligand (Ccl)2, vascular endothelial growth factor A (VEGF-A), and regulated upon activation normal T cell expressed and secreted (RANTES)/Ccl5 in several different types of DILI. We also demonstrated that IL-1β protein and MCP-1/Ccl2 mRNA were commonly up-regulated in the liver of rats treated with different classes of hepatotoxicants and exhibited the highest accuracy in the detection of hepatotoxicity. The results also demonstrate that hepatic mRNA changes do not always correlate with protein changes of cytokines in the liver. This is the first study to provide a comprehensive analysis of mRNA–protein correlations of factors involved in

  5. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1998-01-01

    regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric...... and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal...... neurohumoral fluid regulation in chronic liver disease....

  6. Chronic Liver Disease and Hispanic Americans

    Science.gov (United States)

    ... Program Grants Other Grants Planning and Evaluation Grantee Best Practices Hispanic/Latino Asthma Cancer Chronic Liver Disease Diabetes Heart Disease Hepatitis HIV/AIDS Immunizations Infant Heath & Mortality Mental Health Obesity Organ and Tissue Donation Stroke Stay Connected ...

  7. Lactate metabolism in chronic liver disease

    DEFF Research Database (Denmark)

    Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming;

    2013-01-01

    Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region and...... a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy...... controls underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the...

  8. Montelukast induced acute hepatocellular liver injury

    OpenAIRE

    Harugeri A; Parthasarathi G; Sharma J; D′Souza G; Ramesh M

    2009-01-01

    A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast i...

  9. Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

    DEFF Research Database (Denmark)

    Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars;

    2013-01-01

    BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... endothelial activation. Here, we tested whether CD133 MP might be shed in a CD39-dependent manner in a model of liver injury and could potentially serve as biomarkers of liver failure in the clinic. METHODS: Wild-type and Cd39-null mice were subjected to acetaminophen-induced liver injury. Mice were...... sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39...

  10. Role of cannabinoids in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Anna Parfieniuk; Robert Flisiak

    2008-01-01

    Cannabinoids are a group of compounds acting primarily via CB1 and CB2 receptors. The expression of cannabinoid receptors in normal liver is low or absent. However, many reports have proven up-regulation of the expression of CB1 and CB2 receptors in hepatic myofibroblasts and vascular endothelial cells, as well as increased concentration of endocannabinoids in liver in the course of chronic progressive liver diseases. It has been shown that CB1 receptor signalling exerts profibrogenic and proinflammatory effects in liver tissue, primarily due to the stimulation of hepatic stellate cells, whereas the activation of CB2 receptors inhibits or even reverses liver fibrogenesis. Similarly, CB1 receptor stimulation contributes to progression of liver steatosis. In end-stage liver disease, the endocannabi-noid system has been shown to contribute to hepatic encephalopathy and vascular effects, such as portal hypertension, splanchnic vasodilatation, relative pe-ripheral hypotension and probably cirrhotic cardiomy-opathy. So far, available evidence is based on cellular cultures or animal models. Clinical data on the effects of cannabinoids in chronic liver diseases are limited. However, recent studies have shown the contribution of cannabis smoking to the progression of liver fibrosis and steatosis. Moreover, controlling CB1 or CB2 signal-ling appears to be an attractive target in managing liver diseases.

  11. Liver injury in invasive aspergillus. Echographic findings

    International Nuclear Information System (INIS)

    Aspergillus is the second most common mycoses in immuno compromised patients. The invasive form is associated with a mortality of approximately 100%. We present a case of invasive aspergillus in a heart transplant recipient in whom ultrasound disclosed the presence of liver injury which was later confirmed by necropsy. We review the available literature. (Author) 15 refs

  12. Hepatic inflammation and progressive liver fibrosis in chronic liver disease

    OpenAIRE

    Czaja, Albert J

    2014-01-01

    Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to ...

  13. Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells

    OpenAIRE

    Piscaglia, Fabio; Dudás, József; Knittel, Thomas; Rocco, Paola; Kobold, Dominik; Saile, Bernhard; Zocco, Maria; Timpl, Rupert; Ramadori, Giuliano

    2009-01-01

    Fibulin-2 has previously been considered as a marker to distinguish rat liver myofibroblasts from hepatic stellate cells. The function of other fibulins in acute or chronic liver damage has not yet been investigated. The aim of this study has been to evaluate the expression of fibulin-1 and -2 in models of rat liver injury and in human liver cirrhosis. Their cellular sources have also been investigated. In normal rat liver, fibulin-1 and -2 were both mainly present in the portal field. Fibuli...

  14. Liver autophagy in anorexia nervosa and acute liver injury.

    Science.gov (United States)

    Kheloufi, Marouane; Boulanger, Chantal M; Durand, François; Rautou, Pierre-Emmanuel

    2014-01-01

    Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates' survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m(2) or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed. PMID:25250330

  15. Liver Autophagy in Anorexia Nervosa and Acute Liver Injury

    Directory of Open Access Journals (Sweden)

    Marouane Kheloufi

    2014-01-01

    Full Text Available Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates’ survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m2 or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed.

  16. Management of Pruritus in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Angeline Bhalerao

    2015-01-01

    Full Text Available Background. There continues to be uncertainty on the ideal treatment of pruritus in chronic liver disease. The aim of this study was to gather the latest information on the evidence-based management of pruritus in chronic liver disease. Methodology. A literature search for pruritus in chronic liver disease was conducted using Pubmed and Embase database systems using the MeSH terms “pruritus,” “chronic liver disease,” “cholestatic liver disease,” and “treatment.” Results. The current understanding of the pathophysiology of pruritus is described in addition to detailing research into contemporary treatment options of the condition. These medical treatments range from bile salts, rifampicin, and opioid receptor antagonists to antihistamines. Conclusion. The burden of pruritus in liver disease patients persists and, although it is a common symptom, it can be difficult to manage. In recent years there has been greater study into the etiology and treatment of the condition. Nonetheless, pruritus remains poorly understood and many patients continue to suffer, reiterating the need for further research to improve our understanding of the etiology and treatment for the condition.

  17. Antituberculous drug-induced liver injury: current perspective.

    Science.gov (United States)

    Devarbhavi, Harshad

    2011-01-01

    Drug-induced liver injury (DILI) is a minor but significant cause of liver injury across all regions. Antituberculosis drug-induced liver injury (TB DILI) is a leading cause of DILI and drug-induced acute liver failure (DIALF) in India and much of the developing world. Single center registries of DILI continue to highlight the high incidence of DILI and DIALF, much of it due to diagnostic errors and inappropriate prescriptions. The clinical spectrum includes asymptomatic elevation in liver tests to acute hepatitis and acute liver failure. TB DILI can occur across all age groups including children with significant morbidity and mortality. Although TB DILI develops more commonly in males, ALF is noted to be commoner in females with a worse prognosis. Contrasting reports on the role of genetic and environmental factors continue to be published. Since DILI is a diagnosis of exclusion, acute viral hepatitis particularly hepatitis E needs to be excluded in such cases. The presence of jaundice, hypoalbuminemia, ascites, encephalopathy and high prothrombin time are poor prognostic markers. Recent reports of the beneficial role of N-acetylcysteine in DIALF and in preventing TB DILI in elderly individuals needs further investigation. Reintroduction of antitubercular therapy must be balanced with the knowledge of adaptation a common occurrence with antituberculosis drugs. Although monitoring and rechallenge practices vary greatly, the importance of early clinical symptoms cannot be underestimated. Simultaneous rechallenge with combination drugs or sequential treatment have similar incidence of DILI, although increasing reports about the role of pyrazinamide in DILI and on rechallenge warrants its careful use. The combined affliction of HIV or chronic hepatitis B or C and tuberculosis poses multiple challenges including the greatly increased risks of DILI. PMID:22332331

  18. Etiologies of chronic liver disease in children

    Directory of Open Access Journals (Sweden)

    Farahmand F

    2001-11-01

    Full Text Available Chronic Liver diseases in children is the result of many different diseases including: metabolic, genetic, infectious, toxic and idiopathic causes. This was a case series study on 133 infants and children with age range 6 month to 12 years old, who presented clinically with manifestation of chronic liver disease and were admitted to Children Hospital Medical Center from year 1999 to 2000. In this study, 32 (24.5 percent patients had autoimmune chronic hepatitis, 15 (11.3 percent Glycogen storage diseases, 12 (9 percent extrahepatic biliary atresia, 11 (8.2 percent willson disease, 10 (7.5 percent cryptogenic cirrhosis, 6 (4.5 percent chronic hepatitis C, 5 (3.8 percen chronic hepatitic B, 5 (3.8 percent galactosemia 3 (2.25 percent congenital hepatic fibrosis, 3 (3.8 percent histiocytosis X, 3 (2.25 percent sclerosing cholangitis, 2 (1.5 percent byler’s disease 2 (1.5 percent primary tuberculosis, 1 (0.75 percent choledocalcyst, 1 (0.75 percent Alagyle syndrome. According to our data, chronic liver disease should be considered in infants and children. In our study, the most common causes are found to be: metabolic and genetic diseases (37.5 percent, chronic autoimmune hepatitis (24 percent and biliary disorders (14 percent, that encompass 86 percent of the patients.

  19. Interleukin-10 and chronic liver disease

    OpenAIRE

    ZHANG, LI-JUAN; Wang, Xiao-Zhong

    2006-01-01

    Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with liver disease susceptibility or severity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a ...

  20. Interleukin-10 and chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Li-Juan Zhang; Xiao-Zhong Wang

    2006-01-01

    Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. Numerous investigations suggest that IL-10 plays a major role in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with liver disease susceptibility or severity. Recombinant human IL-10 has been produced and is currently tested in clinical trials. These trials may give new insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10 receptor system may become a new therapeutic target.

  1. Acute liver injury induced by weight-loss herbal supplements

    OpenAIRE

    Gary C Chen, Vivek S Ramanathan, David Law, Pauline Funchain, George C Chen, Samuel French, Boris Shlopov, Viktor Eysselein, David Chung, Sonya Reicher, Binh V Pham

    2010-01-01

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a caut...

  2. Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis

    OpenAIRE

    LIAN, FAN; Wang, Yu; Xiao, Youjun; WU, XIWEN; Xu, Hanshi; Liang, Liuqin; Yang, Xiuyan

    2015-01-01

    Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, the presence of autoantibodies, regulatory T-cell dysfunction and raised plasma liver enzyme levels. The present study assessed the hepatoprotective and antiapoptotic role of farnesoid X receptor (FXR) in AIH. A mouse model of AIH was induced by treatment with concanavalin A (ConA). The FXR agonist, chenodeoxycholic acid (CDCA), was administered to mice exhibiting ConA-induced liver injury ...

  3. Chronic Liver Disease and American Indians/Alaska Natives

    Science.gov (United States)

    ... Native > Chronic Liver Disease Chronic Liver Disease and American Indians/Alaska Natives Among American Indians and Alaska Natives, ... 54. 1 At a glance – Cancer Rates for American Indian/Alaska Natives (2008-2012) Cancer Incidence Rates per ...

  4. Influence of KeGan Capsule to Mice with CC14 Chronic Hepatic Injury

    Institute of Scientific and Technical Information of China (English)

    XUYufang

    2004-01-01

    To study the action of KeGan capsule to resist injury of hepatic cells and fibrosis of liver. Methods Rephcate model of chronic hepatic injury with CC14, at the beginning of which KeGan capsule was applied; finishing experiment, respectively tested the level of liver fimction, TP,ALB, A/G, L-hydroxyproline and liver index and do pathologic examination to fiver. Results KeGan capsule can obviously reduce the degree of fibrosis of liver and the level of L - hydroxyproline, improve the fiver function. The histological examination showed that capsule has the action of protecting hepatic cells from injury and resisting fibrosis of fiver either. Conclusion For KeGan capsule has the action of resisting injury of liver cells and fibrosis of liver, it' s hoped to be applied in precaution and treatment of fibrosis of fiver.

  5. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik Sahl

    1998-01-01

    Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid...... regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric...... and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal...

  6. Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Jiang-hua Wang

    2015-01-01

    Conclusions: The present study showed that serum microRNA-122 was elevated in acute and chronic hepatitis patients. However, this biomarker for acute liver injury did not reflect the liver inflammation activity in CHC patients.

  7. Chronic liver disease in Aboriginal North Americans

    Institute of Scientific and Technical Information of China (English)

    John D Scott; Naomi Garland

    2008-01-01

    A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death.Alcoholic liver disease is the leading etiology of CLD,but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD.Future research should monitor the incidence and etiology of CLD and should be geographically inclusive.In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholicfatty liver disease (NAFLD) in this population.

  8. Chronic Liver Disease: Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Gamal MA Hassan

    2013-03-01

    Full Text Available Chronic liver diseases (CLD affect hundreds of millions of patientsworldwide. Stem Cells (SCs therapy to treat chronic liver diseasesis resorted and is considered as the dream of the future. AlthoughSCs are a promising means for treatment of liver diseases, studiesare still at the beginning of this era. SCs are undifferentiatedcells capable of renewing themselves throughout their life and ofgenerating one or more types of differentiated cells. Different typesof SCs with hepatic differentiation potential are theoretically eligiblefor liver cell replacement. These include Embryonic and fetal liverSCs, induced pluripotent SCs, hepatoblasts, annex SCs (pluripotentSCs obtained from umbilical cord and umbilical cord blood,placenta and amniotic fluid, and adult SCs, such hepatic progenitorcells, hematopoietic SCs, and mesenchymal stem cell. The optimalSCs delivery route should be easy to perform, less invasive andtraumatic, minimum side effects, and with high cells survival rate.Liver SCs can be transplanted through several routes: Intraperitonealand percutaneous intrahepatic artery catheterization in acute liverfailure, and umbilical vein catheterization, percutaneous intrahepaticroute, and portal vein or intrahepatic artery catheterization inmetabolic liver diseases. Whatever the source or delivery route ofSCs, how they can be manipulated for therapeutic interventionsin a variety of hepatic diseases is of course of great interest infuture studies. Although all clinical trials to date have shown someimprovement in liver function and CD34+ cells have been usedsafely for bone marrow transplantation for over 20 years, onlyrandomized controlled clinical trials will be able to fully assess thepotential clinical benefit of adult SCs therapy for patients with CLD.

  9. Acute-on-chronic liver failure: a review

    Directory of Open Access Journals (Sweden)

    Zamora Nava LE

    2014-04-01

    Full Text Available Luis Eduardo Zamora Nava,1 Jonathan Aguirre Valadez,2 Norberto C Chávez-Tapia,3 Aldo Torre21Department of Endoscopy, 2Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 3Obesity and Digestive Diseases Unit, Medica Sur Clinic and Foundation, Mexico City, MexicoAbstract: There is no universally accepted definition of acute-on-chronic liver failure; however, it is recognized as an entity characterized by decompensation from an underlying chronic liver disease associated with organ failure that conveys high short-term mortality, with alcoholism and infection being the most frequent precipitating events. The pathophysiology involves inflammatory processes associated with a trigger factor in susceptible individuals (related to altered immunity in the cirrhotic population. This review addresses the different definitions developed by leading research groups, epidemiological and pathophysiological aspects, and the latest treatments for this entity.Keywords: acute-on-chronic liver failure, cirrhosis, organ failure, acute kidney injury, infection

  10. Neutralization of ADAM8 ameliorates liver injury and accelerates liver repair in carbon tetrachloride-induced acute liver injury.

    Science.gov (United States)

    Li, San-Qiang; Zhu, Sha; Wan, Xue-Dong; Xu, Zheng-Shun; Ma, Zhao

    2014-04-01

    Although some studies have described the function of ADAM8 (a disintegrin and metalloprotease 8) related with rheumatoid arthritis, cancer and asthma, etc., the concrete role of ADAM8 in acute liver injury is still unknown. So mice respectively received anti-ADAM8 monoclonal antibody (mAb) of 100 μg/100 μl, 200 μg/100 μl or 300 μg/100 μl in PBS or PBS pre-injection. Then acute liver injury was induced in the mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl₄). Serum AST and ALT level, Haematoxylin-eosin (H&E) staining, the expression level of vascular endothelial growth factor (VEGF), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the mice after CCl4 administration. Our results showed that anti-ADAM8 mAb pre-injection could effectively lower AST and ALT levels (P < 0.05 or P < 0.01) and reduce liver injury (P < 0.05 or P <0.01), induce the expression of VEGF, CYP1A2 and PCNA (P <0.05 or P < 0.01) in dose-dependent manner compared with the control mice which received PBS pre-injection. In summary, our study suggested that ADAM8 might promote liver injury by inhibiting the proliferation of hepatocytes, angiogenesis and affecting the metabolism function of liver during acute liver injury induced by CCl₄. Anti-ADAM8 mAb injection might be suitable as a potential method for acute liver injury therapy. PMID:24646716

  11. Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

    OpenAIRE

    van de Poll, Marcel C. G.; Derikx, Joep P. M.; Buurman, Wim A.; Peters, Wilbert H. M.; Hennie M J Roelofs; Stephen J Wigmore; Dejong, Cornelis H C

    2007-01-01

    BACKGROUND:Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection.METHODS:Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with ...

  12. Autophagy and ethanol-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Terrence M Donohue Jr

    2009-01-01

    The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism.Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients,endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.

  13. Arterial hypertension and chronic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S

    2005-01-01

    This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic......, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during the...... development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial...

  14. Pure laparoscopic hepatectomy for hepatocellular carcinoma with chronic liver disease

    Directory of Open Access Journals (Sweden)

    Zenichi Morise

    2013-01-01

    Full Text Available Pure laparoscopic hepatectomy is a less invasive procedure than conventional open hepatectomy for the resection of hepatic lesions. Increases in experiences with the technique, in combination with advances in technology, have promoted the popularity of pure laparoscopic hepatectomy. However, indications for usage and potential contraindications of the procedure remain unresolved. The characteristics and specific advantages of the procedure, especially for hepatocellular carcinoma (HCC patients with chronic liver diseases, are reviewed and discussed in this paper. For cirrhotic patients with liver tumors, pure laparoscopic hepatectomy minimizes destruction of the collateral blood and lymphatic flow from laparotomy and mobilization, and mesenchymal injury from compression. Therefore, pure laparoscopic hepatectomy has the specific advantage of minimal postoperative ascites production that leads to lowering the risk of disturbance in water or electrolyte balance and hypoproteinemia. It minimizes complications that routinely trigger postoperative serious liver failure. Under adequate patient positioning and port arrangement, the partial resection of the liver in the area of subphrenic space, peri-inferior vena cava area or next to the attachment of retro-peritoneum is facilitated in pure laparoscopic surgery by providing good vision and manipulation in the small operative field. Furthermore, the features of reduced post-operative adhesion, good vision, and manipulation within the small area between the adhesions make this procedure safer in the context of repeat hepatectomy procedures. These improved features are especially advantageous for patients with liver cirrhosis and multicentric and/or metachronous HCCs.

  15. Vitamin D deficiency in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Paula; Iruzubieta; lvaro; Terán; Javier; Crespo; Emilio; Fábrega

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

  16. Analysis of 133 patients with severe blunt liver injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the treatment and causes of death aboutsevere blunt liver injury.Methods: The data of 133 patients with severe blunt liver injury (Grade Ⅲ to Grade Ⅴ) were analyzed retrospectively. All the patients except 2 underwent operations. Different types of surgical procedures were adopted according to the severity of liver injury.Results: Operations were the major method to treat hepatic injury. The total mortality rate was 21.0% in this study. The mortality rates of Grade Ⅲ, Grade Ⅳ and Grade Ⅴ of liver injuries were 11.3%, 24.4% and 69.2%, respectively.Conclusions: Packing treatment plays an important role in the treatment of hepatic injury. The mortality rate is related closely to the severity of hepatic injury, multiple trauma, shock and disturbance of blood coagulation.

  17. Genetic or Pharmacologic Amplification of Nrf2 Signaling Inhibits Acute Inflammatory Liver Injury in Mice

    OpenAIRE

    Osburn, William O.; YATES, Melinda S.; Dolan, Patrick D.; Liby, Karen T.; Sporn, Michael B.; Taguchi, Keiko; Yamamoto, Masayuki; Kensler, Thomas W.

    2008-01-01

    Oxidative stress-mediated destruction of normal parenchymal cells during hepatic inflammatory responses contributes to the pathogenesis of immune-mediated hepatitis and is implicated in the progression of acute inflammatory liver injury to chronic inflammatory liver disease. The transcription factor NF-E2-related factor 2 (Nrf2) regulates the expression of a battery of antioxidative enzymes and Nrf2 signaling can be activated by small-molecule drugs that disrupt Keap1-mediated repression of N...

  18. Acute liver injury induced by weight-loss herbal supplements.

    Science.gov (United States)

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-11-27

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss. PMID:21173910

  19. Chronic injuries of the cruciate ligaments

    International Nuclear Information System (INIS)

    The high incidence of cruciate ligament injuries as a result of acute knee trauma with hemartrosis and abuse of diagnostic arthroscopies call for a suitable radiological imaging of the central pivot. Computed Arthrotomography (CAT) was used to examine the knee joint in 20 cases of clinically suspected chronic cruciate ligament injury. The images were correlated with arthroscopic and/or arthrotomic findings. Thirteen lesions of the anterior cruciate ligament (ACL) (65%) were found, plus 1 lesion of the posterior cruciate ligament (PCL) (5%), 2 associated lesions of ACL + PCL (10%), and 4 normal cases. Confirmation of pathology was available in all cases but one by arthroscopy and/or surgery. The central pivot diseases were classified as follows: absence, detachement, partial or complete tear. CAT findings of cruciate ligament injuries are emphasized and the role of the technique as compared to arthroscopy is discussed. CAT is useful in 3-D evaluation of central pivot and detection of different cruciate ligament injuries, with high sensitivity-specifity for ACL and high specifity-moderate sensitivity for PCL. In the evaluation of the chronic unstable knee, CAT is highly accurate and gives the surgeon useful information towards the planning of therapeutic procedures. CAT is almost non-invasive, well tolerated and easy to perform in out-patients, which make it a first-choice procedure in the screening of chronic ligament injuries

  20. Alcoholic liver injury:Influence of gender and hormones

    Institute of Scientific and Technical Information of China (English)

    Patricia; K; Eagon

    2010-01-01

    This article discusses several subjects pertinent to a consideration of the role of gender and hormones in alcoholic liver injury (ALI). Beginning with an overview of factors involved in the pathogenesis of ALI, we review changes in sex hormone metabolism resulting from alcohol ingestion, summarize research that points to estrogen as a cofactor in ALI, consider evidence that gut injury is linked to liver injury in the setting of alcohol, and briefly review the limited evidence regarding sex hormones and gut...

  1. Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice.

    Science.gov (United States)

    Yu, Su Jong; Bae, Seyeon; Kang, Jae Seung; Yoon, Jung-Hwan; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Wang Jae; Kim, Chung Yong; Lee, Hyo-Suk

    2015-09-01

    Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. PMID:26057690

  2. Diagnosis of chronic liver disease from liver scintiscans by artificial neural networks

    International Nuclear Information System (INIS)

    Artificial neural networks were used in the diagnosis of chronic liver disease based on liver scintiscanning. One hundred and thirty-seven patients with chronic liver disease (12 with chronic persistent hepatitis, 39 with chronic aggressive hepatitis, and 86 with cirrhosis) and 25 healthy controls were studied. Sixty-five subjects (10 healthy controls, 20 patients with chronic hepatitis, and 35 patients with cirrhosis of the liver) were used in the establishment of a neural network. Liver scintiscans were taken starting 20 min after the intravenous injection of 111 MBq of Tc-99m-phytate. The neural network was used to evaluate five items judged from information on liver scintiscans: the ratio of the sizes of the left and right lobes, splenomegaly, radioactivity in the bone marrow, deformity of the liver and distribution of radioactivity in the liver. The neural network was designed to distinguish between three liver conditions (healthy liver, chronic hepatitis and cirrhosis) on the basis of these five items. The diagnostic accuracy with the neural network was 86% for patients with chronic hepatitis and 93% for patients with cirrhosis. With conventional scoring, the accuracy was 77% for patients with chronic hepatitis and 87% for patients with cirrhosis. Our findings suggest that artificial neural networks may be useful for the diagnosis of chronic liver diseases from liver scintiscans. (author)

  3. Hedgehog signaling and radiation induced liver injury: a delicate balance.

    Science.gov (United States)

    Kabarriti, Rafi; Guha, Chandan

    2014-07-01

    Radiation-induced liver disease (RILD) is a major limitation of radiation therapy (RT) for the treatment of liver cancer. Emerging data indicate that hedgehog (Hh) signaling plays a central role in liver fibrosis and regeneration after liver injury. Here, we review the potential role of Hh signaling in RILD and propose the temporary use of Hh inhibition during liver RT to radiosensitize HCC tumor cells and inhibit their progression, while blocking the initiation of the radiation-induced fibrotic response in the surrounding normal liver. PMID:26202634

  4. Injury-induced changes of T1 in the liver

    International Nuclear Information System (INIS)

    The T1 of rat liver lengthens following any injury to any organ. A hypothesis explaining this holds that a substance (or substances), released from dead or injured cells, reaches liver, engaging it in healing. As a first step in testing this hypothesis, the authors injected rat liver homogenates into rates with previously measured liver T1. Homogenates are dead and injured cells, and their hypothesis predicts that liver T1 in homogenate-injected animals should lengthen. Lengthening of liver T1, measurable with their MR imager presently in clinical use, did result. Homogenates will be fractionated to determine if specific elements elicit the response

  5. Is liver biopsy mandatory in children with chronic hepatitis C?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Liver biopsy is considered the most accurate means to estimate the necroinflammatory activity and the extent of fibrosis. However, histology evaluation is an invasive procedure associated with risk to the patient, risk of sampling error and diagnostic inconsistencies due to inter- and intra-observer error. On the basis of histological studies performed so far, chronic hepatitis C in children appears morphologically benign in the majority of cases.At the Pediatric Liver Unit of our university, a total of 67 children with chronic hep, atitis C underwent liver biopsy.Liver biopsy was repeated 5.5 years after the initial histological evaluation in 21 children. On a total number of 88 liver biopsies, micronodular cirrhosis was detected only in one genotype 1b-infected obese child. Since liver histology investigation of a child with chronic hepatitis C has few chances to highlight severe lesions, we question how liver biopsy helps in the management of children with chronic hepatitis C.

  6. Severe liver injury induced by repeated use of hair dye

    Institute of Scientific and Technical Information of China (English)

    HOU Feng-qin; LIN Xiao-hong; YU Yan-yan; WANG Tai-ling; WANG Gui-qiang

    2009-01-01

    @@ Asignificant number of drugs has been proven,or at least suggested,to cause hepatotoxicity.1-3 Liver injury due to herbal medicines,chemicals or natural toxins also occur from household,occupational,or environmental exposure.4,5 However,liver toxicity due to hair dyes now is rarely recognized.Only in 2003,Tokumoto et al6 reported a case of hair dye-induced hepatitis,which presented a comparatively mild liver lesion.Here we described a case had more severe liver injury.

  7. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Vincent E de Meijer

    Full Text Available BACKGROUND: Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs. The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF-alpha-converting enzyme (TACE. We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4 administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4 was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-alpha receptors. Liver injury was quantified by alanine aminotransferase (ALT levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-alpha receptors exhibited an 80% reduction of serum ALT

  8. Liver injury associated with ketoconazole: review of the published evidence.

    Science.gov (United States)

    Greenblatt, H Karl; Greenblatt, David J

    2014-12-01

    The azole antifungal agent ketoconazole has been available since 1981 for the treatment of fungal infections. In 2013, the American Food and Drug Administration and the European Medicines Agency issued warnings or prohibitions against the clinical use of oral ketoconazole due to the risk of liver injury which may lead to liver transplantation or death. From the available published evidence it is difficult to determine the actual incidence or prevalence of liver injury during clinical use of ketoconazole as an antifungal. Hepatic injury, when it occurs, is generally evident as asymptomatic and reversible abnormalities of liver function tests. However, serious liver injury has been reported. Alternatives to ketoconazole (such as itraconazole, fluconazole, voriconazole, and terbinafine) are available, but improved safety with respect to liver injury risk is not clearly established. We are not aware of published reports of significant ketoconazole-associated liver injury in volunteer study participants when ketoconazole has been used as a CYP3A inhibitor in the context of clinical research on drug metabolism. Possible alternatives to ketoconazole as prototype CYP3A inhibitors include ritonavir and potentially itraconazole, but not clarithromycin. PMID:25216238

  9. Chronic complications of spinal cord injury

    OpenAIRE

    Sezer, Nebahat; Akkuş, Selami; Uğurlu, Fatma Gülçin

    2015-01-01

    Spinal cord injury (SCI) is a serious medical condition that causes functional, psychological and socioeconomic disorder. Therefore, patients with SCI experience significant impairments in various aspects of their life. The goals of rehabilitation and other treatment approaches in SCI are to improve functional level, decrease secondary morbidity and enhance health-related quality of life. Acute and long-term secondary medical complications are common in patients with SCI. However, chronic com...

  10. S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

    Directory of Open Access Journals (Sweden)

    Wellington Andraus

    2010-01-01

    Full Text Available BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC, an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8, IR in normal liver; II (n=8, IR in normal liver with SNAC; III (n=9, IR in steatotic liver; IV (n=9, IR in steatotic liver with SNAC; and V (n=10, SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70% liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA, and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02. CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

  11. Ovarian carcinoma in two patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Mehlika Isildak; Gulay Sain Guven; Murat Kekilli; Yavuz Beyazit; Mustafa Erman

    2005-01-01

    Ascites is a common and debilitating complication of cirrhosis. However, patients with chronic liver disease are not spared from other causes of ascites and physicians should be careful not to miss an underlying malignancy.Ovarian cancer is an insidious disease, which is difficult to diagnose and it ranks first in mortality among all gynecological cancers. Here, we present two cases of patients with chronic liver disease that developed ascites not simply because of cirrhosis but as a manifestation of ovarian cancer. We would like to emphasize that the causes of ascites, other than the liver itself, should not be overlooked in patients with chronic liver disease.

  12. Liver injury caused by drugs: an update.

    Science.gov (United States)

    Stirnimann, Guido; Kessebohm, Kerstin; Lauterburg, Bernhard

    2010-01-01

    Although severe idiosyncratic drug-induced liver injury (DILI) is a rare event, it has a large impact on the fate of affected patients and the incriminated drug. Hepatic metabolism of drugs, which occurs in the generation of chemically reactive metabolites in critical amounts, seems to underlie most instances of DILI. Genetic polymorphisms in activating and detoxifying enzymes determine, in part, the extent of cellular stress. A cascade of events, where the pathogenetic relevance of single steps is likely to vary from drug to drug, leads to the disturbance of cellular homeostasis, to mitochondrial dysfunction, to the activation of cell death promoting pathways and the release of drug-modified macromolecules and/or danger signals that initiate an innate and/or adaptive immune response. The patient's response to the initial drug-induced cellular dysfunction determines whether adaptation to the drug-induced cellular stress or DILI in one of its many forms of clinical presentation occurs. Although risk factors for developing DILI have been identified and many pathogenetic mechanisms have been elucidated in model systems, idiosyncratic drug reactions remain unpredictable. PMID:20927685

  13. Corticosteroid Therapy for Liver Abscess in Chronic Granulomatous Disease

    OpenAIRE

    Leiding, Jennifer W; FREEMAN, ALEXANDRA F.; Marciano, Beatriz E.; Anderson, Victoria L.; Uzel, Gulbu; Malech, Harry L.; DeRavin, SukSee; Wilks, David; Venkatesan, Aradhana M.; Zerbe, Christa S.; Heller, Theo; Holland, Steven M.

    2011-01-01

    Liver abscesses in chronic granulomatous disease (CGD) are typically difficult to treat and often require surgery. We describe 9 X-linked CGD patients with staphylococcal liver abscesses refractory to conventional therapy successfully treated with corticosteroids and antibiotics. Corticosteroids may have a role in treatment of Staphylococcus aureus liver abscesses in CGD.

  14. Serum endocan levels in patients with chronic liver disease

    OpenAIRE

    Tok, Duran; Ekiz, Fuat; Basar, Omer; Coban, Sahin; OZTURK, Gulfer

    2014-01-01

    Background and Aim: Early detection of fibrosis should be the main goal of treatment in liver cirrhosis. Endocan, previously called endothelial cell specific molecule-1, is expressed by endothelial cells, primarily in the lung, liver and kidney. In this study, we aimed to examine the correlation of liver fibrosis stage, histological activity and grade of steatosis between serum levels of endocan in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty live...

  15. Role of IRAK-M in alcohol induced liver injury.

    Directory of Open Access Journals (Sweden)

    Yipeng Wang

    Full Text Available Increasing evidence suggests that innate immunity plays an important role in alcohol-induced liver injury and most studies have focused on positive regulation of innate immunity. The main objective of this study was to investigate the negative regulator of innate immunity, IL-1/Toll-like receptor (TLR signaling pathways and interleukin receptor-associated kinase-M (IRAK-M in alcoholic liver injury. We established an alcohol-induced liver injury model using wild type and IRAK-M deficient B6 mice and investigated the possible mechanisms. We found that in the absence of IRAK-M, liver damage by alcohol was worse with higher alanine transaminase (ALT, more immune cell infiltration and increased numbers of IFNγ producing cells. We also found enhanced phagocytic activity in CD68(+ cells. Moreover, our results revealed altered gut bacteria after alcohol consumption and this was more striking in the absence of IRAK-M. Our study provides evidence that IRAK-M plays an important role in alcohol-induced liver injury and IRAK-M negatively regulates the innate and possibly the adaptive immune response in the liver reacting to acute insult by alcohol. In the absence of IRAK-M, the hosts developed worse liver injury, enhanced gut permeability and altered gut microbiota.

  16. Acetaminophen-induced acute liver injury in HCV transgenic mice

    International Nuclear Information System (INIS)

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  17. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  18. Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

    OpenAIRE

    An Jiang; Chang Liu; Feng Liu; Yu-Long Song; Quan-Yuan Li; Liang Yu; Yi Lv

    2012-01-01

    AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4  °C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. ...

  19. Carbon tetrachloride-induced liver injury in the rabbit.

    Science.gov (United States)

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J. A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed. Images Fig. 1 Fig. 2 PMID:6309207

  20. An Update on Drug-induced Liver Injury

    OpenAIRE

    Devarbhavi, Harshad

    2012-01-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver ...

  1. Modulation of the Colonic Bacterial Flora Affects Differently Bacterial Translocation and Liver Injury in an Acute Liver Injury Model

    OpenAIRE

    Adawi, Diya; Molin, Göran; Ahrné, Siv; Jeppsson, Bengt

    2011-01-01

    Objective: To evaluate the effects of the administration of different bacterial strains on the extent of liver injury and bacterial translocation in an acute liver injury model. Design: Experimental study. Setting: University hospital, Sweden. Subjects: Sprague–Dawley rats. Interventions: Six different bacterial strains (Bacteroides fragilis ATCC 25285T, Enterococcus faecium No.1, Enterococcus faecium No.2, Escherichia coli F131, Lactobacillus plantarum DSM 6595, and Bifidobacterium lon...

  2. Micro-RNA-122 Levels in Acute Liver Failure and Chronic Hepatitis C

    Science.gov (United States)

    Dubin, Perry H.; Yuan, Hejun; Devine, Robert K.; Hynan, Linda S.; Jain, Mamta K.; Lee, William M.

    2016-01-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV–HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P<0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P<0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. PMID:24895202

  3. Mild hypothermia protects liver against ischemia and reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Cheng-You Wang; Yong Ni; Yan Liu; Zhi-Heng Huang; Min-Jie Zhang; Yong-Qiang Zhan; Hai-Bin Gao

    2005-01-01

    AIM: To determine whether mild hypothermia could protect liver against ischemia and reperfusion injury in pigs. METHODS: Twenty-four healthy pigs were randomly divided into normothermia, mild hypothermia and normal control groups. The experimental procedure consisted of temporary interruption of blood flow to total hepatic lobe for different lengths of time and subsequent reperfusion. Hepatic tissue oxygen pressure (PtiO2) and aspartate aminotransferase (AST) values were evaluated, and ultrastructural analysis was carried out for all samples.RESULTS: Serum AST was significantly lower, and hepatic P,O2 values were significantly higher in the mild hypothermia group than in the normothermia group during liver ischemiareperfusion periods (P = 0.032, P = 0.028). Meanwhile, the histopathologic injury of liver induced by ischemiareperfusion was significantly improved in the mild hypothermia group, compared with that in the normothermia group. CONCLUSION: Mild hypothermia can protect the liver from ischemia-reperfusion injury in pigs.

  4. Role of hepatitis C virus in chronic liver disease occurring after orthotopic liver transplantation.

    OpenAIRE

    Pastore, M; Willems, M.; Cornu, C.; Buts, Jean-Paul; REDING, Raymond; de Ville de Goyet, J; Rahier, Jacques; Otte, Jean-Bernard; Yapo, Séverin; Sokal, Etienne

    1995-01-01

    Paediatric orthotopic liver transplant recipients may develop chronic hepatitis after surgery. To investigate the role of hepatitis C virus in this pathology a cohort of 249 paediatric orthotopic liver transplant recipients was studied. Sixteen children (6.4%) were found to have chronic hepatitis C virus hepatitis after orthotopic liver transplantation. All but one of them had serum transaminase values which were persistently raised two to eight times the upper limit of normal. Thirteen were ...

  5. Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease

    Institute of Scientific and Technical Information of China (English)

    Scott Grier; Adrian KP Lim; Nayna Patel; Jeremy FL Cobbold; Howard C Thomas; Isobel J Cox; Simon D Taylor-Robinson

    2006-01-01

    Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.

  6. Interleukins in chronic liver disease: lessons learned from experimental mouse models

    Directory of Open Access Journals (Sweden)

    Hammerich L

    2014-09-01

    Full Text Available Linda Hammerich, Frank Tacke Department of Medicine III, University Hospital Aachen, Aachen, Germany Abstract: Interleukins represent a class of immunomodulatory cytokines, small intercellular signaling proteins, that are critically involved in the regulation of immune responses. They are produced in large amounts by various cell types during inflammatory reactions, and the balance of cytokines determines the outcome of an immune response. Therefore, cytokines are regarded as interesting therapeutic targets for the treatment of patients with liver diseases. Mouse models provide a good tool for in vivo studies on cytokine function, as human and mouse cytokines share many homologies. Sophisticated mouse models either mimicking distinct pathological conditions or targeting cytokines and cytokine-signaling pathways in the liver or even in distinct cellular compartments have provided enormous insight into the different functions of interleukins during hepatic inflammation. Interleukins may have pro- as well as anti-inflammatory functions in chronic liver diseases, some interleukins even both, dependent on the inflammatory stimulus, the producing and the responding cell type. IL-17, for example, promotes hepatic fibrogenesis through activation of hepatic stellate cells and facilitates development of liver cancer through recruitment of myeloid-derived suppressor cells. IL-22, on the other hand, protects from development of fibrosis or steatohepatitis. IL-12 balances T-helper (Th-1 and Th2 cell responses in infectious disease models. IL-13 and IL-33, two cytokines related to Th2 cells and innate lymphoid cells, promote fibrotic responses in the liver. IL-10 is the prototypic anti-inflammatory interleukin with tissue-protective functions during chronic liver injury and fibrogenesis. Despite its critical role for inducing the acute-phase response in the liver, IL-6 signaling is protective during fibrosis progression, but promotes hepatocellular carcinoma

  7. Diphenhydramine disposition in chronic liver disease.

    Science.gov (United States)

    Meredith, C G; Christian, C D; Johnson, R F; Madhavan, S V; Schenker, S

    1984-04-01

    Diphenhydramine (DPHM) disposition was examined in nine patients with chronic alcohol-related liver disease and in eight normal subjects. Sleep of 1 to 2 hr duration was induced in all subjects by a 0.8 mg/kg iv dose without an apparent increase in cerebral sensitivity in the patients with cirrhosis. Protein binding as determined by equilibrium dialysis (3H-DPHM) revealed a 15% decrease in the cirrhotic patients, while recovery of unchanged DPHM in urine (2%) was of the same order in the two groups. Computerized biexponential curve analysis was used to compare the plasma profiles for five of the patients and six of the normal subjects. Monoexponential curve analysis of the terminal beta-phase, including all subjects, was also used to compare the two groups. The means of plasma clearance and apparent volume of distribution in cirrhotic patients were respectively less and greater than in normal subjects, but these differences were not significant. The t1/2 for the beta-phase (t1/2 beta), which reflects this reciprocal trend, was increased in the patients (15.2 +/- 1.5 and 9.3 +/- 0.9 hr). This correlated in part with severity of disease, with r = 0.723 between t1/2 beta and the serum bilirubin levels. In conclusion, a single intravenous dose of DPHM provided safe and effective sedation in patients with cirrhosis. PMID:6705445

  8. Hepatic lipogranulomas in patients with chronic liver disease: Association with hepatitis C and fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Henry; C; Bodenheimer; David; J; Clain; Albert; D; Min; Neil; D; Theise

    2010-01-01

    AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 pati...

  9. Chronic Liver Disease and Asian Americans/Pacific Islanders

    Science.gov (United States)

    ... Program Grants Other Grants Planning and Evaluation Grantee Best Practices Asian American Asthma Cancer Chronic Liver Disease Diabetes Heart Disease Hepatitis HIV/AIDS Immunizations Infant Heath & Mortality Mental Health Obesity Organ and Tissue Donation Stroke Stay Connected ...

  10. Neuroinflammation and neurological alterations in chronic liver diseases

    OpenAIRE

    Carmina Montoliu; Marta Llansola; Vicente Felipo

    2015-01-01

    Several million people with chronic liver diseases (cirrhosis, hepatitis) show neurological alterations, named hepatic encephalopathy (HE) with cognitive and motor alterations that impair quality of life and reduces life span. Inflammation acts synergistically with hyperammonemia to induce cognitive and motor alterations in patients with chronic liver disease and minimal hepatic encephalopathy (MHE). Previous studies in animal models have suggested that neuroinflammation is a major player in ...

  11. Male Rat Susceptibility for Liver and Kidney Injury

    Directory of Open Access Journals (Sweden)

    Sarkawt H. Hamad

    2016-04-01

    Full Text Available The experimental study of this paper was designed to investigate male rat susceptibility to liver injury. A combination of two experimental animal models (Lead acetate for tissue injury (80 mg / L and castration had been used on twenty male rats, they were divided into two groups sham (n = 10; castrated (n = 10. Results revealed that, liver weight reduced significantly (P < 0.05 in sham group in comparison with castrated rats, but kidney weight changed slightly. Also, serum aminotransferase (AST was significantly higher in sham versus castrated rats. Neither alanine aminotransferase (ALT and alkaline phosphatase (ALP nor malondialdehyde (MDA changed. In conclusion, the absence of male sex hormone would delay tissue injury of male rat organs especially liver organ.

  12. Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

    OpenAIRE

    Michele Barone; Maria Teresa Viggiani; Annabianca Amoruso; Serafina Schiraldi; Annapaola Zito; Fiorella Devito; Francesca Cortese; Michele Gesualdo; Natale Brunetti; Alfredo Di Leo; Pietro Scicchitano; Marco Matteo Ciccone

    2015-01-01

    Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient...

  13. The pathophysiology of thrombocytopenia in chronic liver disease

    OpenAIRE

    Sigal, Samuel

    2016-01-01

    Oscar Mitchell,1 David M Feldman,1,2 Marla Diakow,1 Samuel H Sigal3 1Department of Medicine, 2Division of Gastroenterology and Liver Diseases, New York University School of Medicine, Langone Medical Center, New York, 3Division of Gastroenterology and Liver Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA Abstract: Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CL...

  14. Telomere and telomerase in chronic liver disease and hepatocarcinoma

    OpenAIRE

    Carulli, Lucia; Anzivino, Claudia

    2014-01-01

    The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (...

  15. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B; Christoffersen, P; Jensen, L B; Sørensen, T I A; Becker, Povl Ulrik; Bendtsen, Flemming

    2004-01-01

    BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the...... risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow....... Survival estimates were significantly (p<0.01) different between the two groups, for men as well as for women, with a higher death rate in the alcoholic fatty liver group. Survival estimates in the non-alcoholic fatty liver group were not different from the Danish population. CONCLUSIONS: This study...

  16. Trimetazidine and liver preservation against ischaemia-reperfusion injury

    OpenAIRE

    Mosbah, Ismail Ben; Abdennebi, Hassen B.; Zaouali, Mohamed A.; Padrissa-Altés, Susagna; Peralta, Carmen; Roselló-Catafau, Joan

    2007-01-01

    Trimetazidine is an anti-ischaemic drug used for angina pectoris treatment. Recently, it has been shown that trimetazidine protects against hepatic ischaemia reperfusion injury. Several hypotheses have been proposed to explain the exact hepatoprotective mechanisms but they still remain unclear. This review assesses the possible mechanisms responsible for the increase of the liver's tolerance against ischaemia-reperfusion injury with special emphasis on: (1) the prevention of oxidative stress ...

  17. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove;

    2015-01-01

    animals died during the study. There were no differences between in body weight, liver weight, liver regeneration rate or biochemical markers at any time during the study. CONCLUSION: The results of this study indicate that stress and the induction of depression-like state do not affect the process of...... chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent a...

  18. Chronic liver disease related mortality pattern in northern Pakistan

    International Nuclear Information System (INIS)

    Objective: To describe the mortality pattern pertaining to chronic liver disease (CLD) in Northern Pakistan. Results: There were a total of 8529 admissions in twelve months period from August 2001 to July 2002. There were 283 (3.31%) total deaths. Out of these, 160 deaths were pertaining to medical causes. Out of these medical cases, 33 (20.6%) patients had died of chronic liver disease. Other major causes of death were cerebro-vascular accident (18.7%), malignancy (18.1%) and acute myocardial infarction (10.6%). Out of 33 patients of CLD, 12 (36%) presented with acute gastrointestinal (Gl) bleeding, 9(27%) presented with Ascites and 6(18%) presented with altered mental status due to hepatic encephalopathy. Rest of them had jaundice and fever as their initial presentation. Out of these 33 patients with CLD, 23 (70%) had hepatitis C virus (HCV) as cause of their liver disease, 4 (12%) had hepatitis B virus (HBV) infection, 3(9%) had both hepatitis B and hepatitis C virus infections and 3 (9%) had no known cause of their chronic liver disease. Conclusion: Chronic liver disease is a major cause of mortality in this part of Pakistan at a tertiary care hospital. HCV infection is the main cause of chronic liver disease followed by either HBV or a combination of these viruses. Major manifestations of CLD have been gastrointestinal bleeding, hepatic failure and portal hypertension.(author)

  19. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  20. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    International Nuclear Information System (INIS)

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

  1. [Pathogenetic correction of metabolic disturbances in chronic liver affections].

    Science.gov (United States)

    Romantsov, M G; Petrov, A Iu; Aleksandrova, L N; Sukhanov, D S; Kovalenko, A L

    2012-01-01

    The available drugs for the treatment of chronic liver affections (the adequate model is chronic hepatitis C) include agents of metabolic therapy, whose efficacy is not always enough, that required the search for original mitochondrial substrates on the basis of succinate. Such agents were composed as a pharmaceutical group named "Substrates of Energetic Metabolism" or "Substrate Antihypoxants". The review presents the description of the pharmacological effects of remaxole and cytoflavin, evident from lower levels of active metabolites of oxygen that increases the clinical efficacy of the therapy. Their role in the metabolic reactions in chronic liver affections is exclusive and rather actual. PMID:23700935

  2. Liver injury induced by herbal complementary and alternative medicine.

    Science.gov (United States)

    Navarro, Victor J; Seeff, Leonard B

    2013-11-01

    Herbal and dietary supplement use is common. Most marketed products consist of complex mixtures. Although they are perceived as safe, instances of hepatotoxicity attributable to these products underscore their potential for injury, but the exact component that is responsible for injury is difficult to discern. The lenient regulatory environment in the United States, which opens the possibility of adulteration and contamination, adds to the challenge of disease attribution. Although many different herbal and dietary supplements have been reported to cause liver injury, in the United States, products used for bodybuilding and weight loss are the most commonly implicated. PMID:24099027

  3. Liver injury-on-a-chip: microfluidic co-cultures with integrated biosensors for monitoring liver cell signaling during injury.

    Science.gov (United States)

    Zhou, Qing; Patel, Dipali; Kwa, Timothy; Haque, Amranul; Matharu, Zimple; Stybayeva, Gulnaz; Gao, Yandong; Diehl, Anna Mae; Revzin, Alexander

    2015-12-01

    Tissue injury triggers complex communication between cells via secreted signaling molecules such as cytokines and growth factors. Discerning when and where these signals begin and how they propagate over time is very challenging with existing cell culture and analysis tools. The goal of this study was to develop new tools in the form of microfluidic co-cultures with integrated biosensors for local and continuous monitoring of secreted signals. Specifically, we focused on how alcohol injury affects TGF-β signaling between two liver cell types, hepatocytes and stellate cells. Activation of stellate cells happens early during liver injury and is at the center of liver fibrosis. We demonstrated that alcohol injury to microfluidic co-cultures caused significantly higher levels of stellate cell activation compared to conditioned media and transwell injury experiments. This highlighted the advantage of the microfluidic co-culture: placement of two cell types in close proximity to ensure high local concentrations of injury-promoting secreted signals. Next, we developed a microsystem consisting of five chambers, two for co-culturing hepatocytes with stellate cells and three additional chambers containing miniature aptamer-modified electrodes for monitoring secreted TGF-β. Importantly, the walls separating microfluidic chambers were actuatable; they could be raised or lowered to create different configurations of the device. The use of reconfigurable microfluidics and miniature biosensors revealed that alcohol injury causes hepatocytes to secrete TGF-β molecules, which diffuse over to neighboring stellate cells and trigger production of additional TGF-β from stellate cells. Our results lend credence to the emerging view of hepatocytes as active participants of liver injury. Broadly speaking, our microsystem makes it possible to monitor paracrine crosstalk between two cell types communicating via the same signaling molecule (e.g. TGF-β). PMID:26480303

  4. Ito cells and fibrogenesis in chronic alcoholic liver disease.

    Science.gov (United States)

    González-Reimers, C E; Brajín-Rodríguez, M M; Santolaria-Fernández, F; Diaz-Flores, L; Conde-Martel, A; Rodríguez-Rodríguez, E; Essardas-Daryanani, H

    1992-02-01

    The relationships between the number of Ito cells; serum N-terminal type III procollagen and laminin; clinical and biochemical parameters of liver function derangement; histomorphometrically assessed total amount of liver fibrosis; and daily ethanol intake were studied in 43 patients affected by chronic alcoholic liver disease (10 cirrhotics). Significant correlations were found between serum laminin and N-terminal type III procollagen and histological, clinical and biochemical data of liver function derangement, but no correlation was found between the aforementioned parameters and the percentage of Ito cells, which in turn seemed to be related to ethanol ingestion. PMID:1559427

  5. Congenital biliary atresia: liver injury begins at birth

    DEFF Research Database (Denmark)

    Makin, Erica; Quaglia, Alberto; Kvist, Nina;

    2009-01-01

    BACKGROUND: The timing of onset of liver injury in biliary atresia (BA) is not known, although in approximately 10% of cases, biliary pathologic condition associated with the biliary atresia splenic malformation syndrome must begin well before birth. METHODS: The study involved retrospective case...

  6. Why, who and how should perform liver biopsy in chronic liver diseases

    OpenAIRE

    Sporea, Ioan; Popescu, Alina; Sirli, Roxana

    2008-01-01

    Chronic viral hepatitis is a common disease in the general population. During chronic hepatitis, the prognosis and clinical management are highly dependent on the extent of liver fibrosis. The fibrosis evaluation can be performed by FibroTest (using serological markers), by Elastography or FibroScan (a noninvasive percutaneous technique using the elastic properties of the hepatic tissue) and by liver biopsy (LB), considered to be the “gold standard”. Currently, there are three techniques for ...

  7. Chikusetsusaponin V attenuates lipopolysaccharide-induced liver injury in mice.

    Science.gov (United States)

    Dai, Yan Wen; Zhang, Chang Cheng; Zhao, Hai Xia; Wan, Jing Zhi; Deng, Li Li; Zhou, Zhi Yong; Dun, Yao Yan; Liu, Chao Qi; Yuan, Ding; Wang, Ting

    2016-06-01

    Chikusetsusaponin V (CsV), a saponin from Panax japonicus, has been reported to inhibit inflammatory responses in lipopolysaccharide (LPS)-induced macrophage cells. However, whether CsV could alleviate LPS-induced liver injury in vivo and the potential mechanisms involved remain unclear. In the present study, we investigated the anti-inflammatory effects of CsV on LPS-induced acute liver injury in mice and further explored the potential mechanisms involved. Our results showed that CsV significantly attenuated elevation of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels and improved liver histopathological changes in LPS-induced mice. In addition, CsV decreased serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β in LPS challenged mice. Furthermore, CsV inhibited nuclear factor kappa B (NF-κB) activation by downregulating phosphorylated NF-κB, IκB-α, ERK, c-Jun N-terminal kinase (JNK) and p38 levels in the liver tissue, which ultimately decreased nucleus NF-κB protein level. In conclusion, our data suggested that CsV could be a promising drug for preventing LPS challenged liver injury since it attenuated LPS-induced inflammatory responses, partly via inhibiting NF-κB and MAPK signaling pathways. PMID:26981791

  8. Mitochondrial involvement in drug-induced liver injury.

    Science.gov (United States)

    Pessayre, Dominique; Mansouri, Abdellah; Berson, Alain; Fromenty, Bernard

    2010-01-01

    Mitochondrial dysfunction is a major mechanism of liver injury. A parent drug or its reactive metabolite can trigger outer mitochondrial membrane permeabilization or rupture due to mitochondrial permeability transition. The latter can severely deplete ATP and cause liver cell necrosis, or it can instead lead to apoptosis by releasing cytochrome c, which activates caspases in the cytosol. Necrosis and apoptosis can trigger cytolytic hepatitis resulting in lethal fulminant hepatitis in some patients. Other drugs severely inhibit mitochondrial function and trigger extensive microvesicular steatosis, hypoglycaemia, coma, and death. Milder and more prolonged forms of drug-induced mitochondrial dysfunction can also cause macrovacuolar steatosis. Although this is a benign liver lesion in the short-term, it can progress to steatohepatitis and then to cirrhosis. Patient susceptibility to drug-induced mitochondrial dysfunction and liver injury can sometimes be explained by genetic or acquired variations in drug metabolism and/or elimination that increase the concentration of the toxic species (parent drug or metabolite). Susceptibility may also be increased by the presence of another condition, which also impairs mitochondrial function, such as an inborn mitochondrial cytopathy, beta-oxidation defect, certain viral infections, pregnancy, or the obesity-associated metabolic syndrome. Liver injury due to mitochondrial dysfunction can have important consequences for pharmaceutical companies. It has led to the interruption of clinical trials, the recall of several drugs after marketing, or the introduction of severe black box warnings by drug agencies. Pharmaceutical companies should systematically investigate mitochondrial effects during lead selection or preclinical safety studies. PMID:20020267

  9. Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide, Canadian survey

    OpenAIRE

    Sebastiani, Giada; Ghali, Peter; Wong, Philip; Klein, Marina B; Deschenes, Marc; Myers, Robert P

    2014-01-01

    OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases.METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey.RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessm...

  10. Acute-on-chronic liver failure due to bacterial infection in liver cirrhosis: causes and management

    OpenAIRE

    Han, Tao

    2015-01-01

    Bacterial infection is a common complication in patients with liver cirrhosis, and acute-on-chronic liver failure due to bacterial infection has become a serious clinical problem. There are still many problems in the research on the pathogenesis and management of bacterial infection in liver cirrhosis, such as insidious onset, difficult early diagnosis, and increased multi-drug resistant bacteria. This article reviews the research progress in the causes and management of bacterial infection i...

  11. IL-4 mediates dicloxacillin-induced liver injury in mice.

    Science.gov (United States)

    Higuchi, Satonori; Kobayashi, Masanori; Yoshikawa, Yukitaka; Tsuneyama, Koichi; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2011-02-01

    Drug-induced liver injury (DILI) is a major problem in drug development and clinical drug therapy. In most cases, the mechanisms are still unknown. It is difficult to predict DILI in humans due to the lack of experimental animal models. Dicloxacillin, penicillinase-sensitive penicillin, rarely causes cholestatic or mixed liver injury, and there is some evidence for immunoallergic idiosyncratic reaction in human. In this study, we investigated the mechanisms of dicloxacillin-induced liver injury. Plasma ALT and total-bilirubin (T-Bil) levels were significantly increased in dicloxacillin-administered (600 mg/kg, i.p.) mice. Dicloxacillin administration induced Th2 (helper T cells)-mediated factors and increased the plasma interleukin (IL)-4 level. Neutralization of IL-4 suppressed the hepatotoxicity of dicloxacillin, and recombinant mouse IL-4 administration (0.5 or 2.0 μg/mouse, i.p.) exacerbated it. Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a cognate receptor for prostaglandin (PG) D(2), and is suggested to be involved in Th2-dependent allergic inflammation. We investigated the effect of 13,14-Dihydro-15-keto-PGD(2) (DK-PGD(2); 10 μg/mouse, i.p.) administration on dicloxacillin-induced liver injury. DK-PGD(2)/dicloxacillin coadministration resulted in a significant increase of alanine aminotransferases and a remarkable increase of macrophage inflammatory protein 2 expression. In conclusion, to the best of our knowledge, this is the first report to demonstrate that dicloxacillin-induced liver injury is mediated by a Th2-type immune reaction and exacerbated by DK-PGD(2). PMID:21094227

  12. Neuroinflammation and neurological alterations in chronic liver diseases

    Directory of Open Access Journals (Sweden)

    Carmina Montoliu

    2015-01-01

    Full Text Available Several million people with chronic liver diseases (cirrhosis, hepatitis show neurological alterations, named hepatic encephalopathy (HE with cognitive and motor alterations that impair quality of life and reduces life span. Inflammation acts synergistically with hyperammonemia to induce cognitive and motor alterations in patients with chronic liver disease and minimal hepatic encephalopathy (MHE. Previous studies in animal models have suggested that neuroinflammation is a major player in HE. This would also be the case in patients with liver cirrhosis or hepatitis C with HE. Rats with MHE show microglial activation and neuroinflammation that is associated with cognitive impairment and hypokinesia. The anti-inflammatory drug ibuprofen reduces microglial activation and neuroinflammation and restores cognitive and motor functions in rats with MHE. Chronic hyperammonemia per se induces neuroinflammation. Both peripheral inflammation and hyperammonemia would contribute to neuroinflammation in chronic liver failure. Therefore, neuroinflammation may be a key therapeutic target to improve the cognitive and motor alterations in MHE and overt HE. Identifying new targets to reduce neuroinflammation in MHE without inducing secondary effects would serve to develop new therapeutic tools to reverse the cognitive and motor alterations in patients with HE associated with chronic liver diseases.

  13. Intestinal microflora in rats with ischemia/reperfusion liver injury

    Institute of Scientific and Technical Information of China (English)

    XING Hui-chun; LI Lan-juan; XU Kai-jin; SHEN Tian; CHEN Yun-bo; SHENG Ji-fang; YU Yun-song; CHEN Ya-gang

    2005-01-01

    Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

  14. Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury.

    Science.gov (United States)

    Origassa, Clarice Silvia Taemi; Câmara, Niels Olsen Saraiva

    2013-10-27

    The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury. PMID:24179613

  15. Chronic liver disease: evaluation by magnetic resonance

    International Nuclear Information System (INIS)

    Magnetic resonance (MR) imaging distinguished hepatitis from fatty liver and cirrhosis in a woman with a history of alcohol abuse. Anatomic and physiologic manifestations of portal hypertension were also demonstrated by MR

  16. Per-rectal portal scintigraphy in chronic liver diseases

    International Nuclear Information System (INIS)

    Portal circulation has been evaluated by per-rectal portal scintigraphy in 21 controls and in 30 pts affected by chronic liver diseases. Tc99m-pertechnetate (10 mci) was given through a Nelaton's catheter in the upper rectum; a per-rectal portal shunt index (SI) was calculated. A relevant overlap is evident between controls and CHP pts; no overlap exists between controls and B or C graded cirrhosis. We conclude that the technique may be suggested to monitor the course of chronic liver diseases and different therapeutic regimens. (orig.)

  17. Expression and function of the atypical cadherin FAT1 in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Valletta, Daniela; Czech, Barbara [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany); Thasler, Wolfgang E. [Grosshadern Tissue Bank and Center for Liver Cell Research, Department of Surgery, Ludwig-Maximilians-University Munich (Germany); Mueller, Martina [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany); Bosserhoff, Anja-Katrin [Institute of Pathology, University of Regensburg, Regensburg (Germany); Hellerbrand, Claus, E-mail: claus.hellerbrand@ukr.de [Department of Internal Medicine I, University Hospital Regensburg, Regensburg (Germany)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer The expression of the atypical cadherin FAT1 is increased in chronic liver disease. Black-Right-Pointing-Pointer FAT1 expression goes up during the activation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Activated HSCs are the cellular source of enhanced FAT1 expression in diseased livers. Black-Right-Pointing-Pointer FAT1 enhanced NFkB activity and resistance to apoptosis in activated HSCs. Black-Right-Pointing-Pointer FAT1 is a new therapeutic target for prevention and treatment of hepatic fibrosis. -- Abstract: Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these

  18. Expression and function of the atypical cadherin FAT1 in chronic liver disease

    International Nuclear Information System (INIS)

    Highlights: ► The expression of the atypical cadherin FAT1 is increased in chronic liver disease. ► FAT1 expression goes up during the activation of hepatic stellate cells (HSCs). ► Activated HSCs are the cellular source of enhanced FAT1 expression in diseased livers. ► FAT1 enhanced NFkB activity and resistance to apoptosis in activated HSCs. ► FAT1 is a new therapeutic target for prevention and treatment of hepatic fibrosis. -- Abstract: Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these cells by siRNA. We newly found that FAT1 suppression in activated HSCs caused a downregulation of NFκB activity. This

  19. Chronic alcohol ingestion delays skeletal muscle regeneration following injury

    OpenAIRE

    Dekeyser, Graham J; Clary, Caroline R; OTIS, JEFFREY S.

    2013-01-01

    Background Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-match...

  20. Betaine transport in kidney and liver: use of betaine in liver injury.

    Science.gov (United States)

    Kempson, Stephen A; Vovor-Dassu, Komi; Day, Christopher

    2013-01-01

    Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress. This process has been studied in great detail. In liver, the main role of betaine is a methyl donor in the methionine cycle. However, recent studies showed that BGT1 is much more abundant in liver compared to kidney medulla. Despite this, the role of BGT1 in liver has received little attention. Entry of betaine into liver cells is a necessary first step for its action at the cellular level. Increased interest in betaine has developed because of a number of therapeutic uses. These include treatment of nonalcoholic fatty liver and hyperhomocysteinemia, a risk factor for atherosclerotic disease. Several important questions need to be addressed to better understand the potential of betaine as a therapeutic agent for other liver diseases, such as alcohol-induced injury. Heavy alcohol consumption is the most common cause for liver-related deaths and altered liver metabolism may contribute to hepatic, vascular, coronary, and cerebral diseases. PMID:24429813

  1. [Erythrocyte changes during alcoholism and chronic liver diseases].

    Science.gov (United States)

    Triolo, L; Magris, D; Mian, G; D'Agnolo, B

    1978-01-01

    50 patients with chronic liver disease and/or alcoholism were studied. 28 cases of anemia were found and macrocytes (and target m.), spurr-cells, spherocytes and stomatocytes observed. For each of these abnormalities the authors report the observed incidence and discuss the literature's data about the pathogenesis. A personal research on the influence of the liver's impaired capability of protein synthesis was also carried out. The usefulness of a careful examination of the blood film is finally stressed, in patients with liver disease and to discover alcoholic subjects still "healthy". PMID:756712

  2. Traditional Chinese Medicine Induced Liver Injury.

    Science.gov (United States)

    Teschke, Rolf

    2014-06-01

    Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with particular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some

  3. Alcoholic liver injury: defenestration in noncirrhotic livers--a scanning electron microscopic study

    DEFF Research Database (Denmark)

    Horn, T; Christoffersen, P; Henriksen, Jens Henrik Sahl

    1987-01-01

    (fractional area of fenestrae) was observed in acinar Zone 3, both in biopsies with and without Zone 3 fibrosis as judged by light microscopy. A significant reduction of porosity as shown in this study may influence the blood hepatocytic exchange and contribute to the alcohol-induced liver injury....

  4. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation.

    Science.gov (United States)

    Zhou, Yan; Ruan, Zheng; Zhou, Lili; Shu, Xugang; Sun, Xiaohong; Mi, Shumei; Yang, Yuhui; Yin, Yulong

    2016-01-22

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. PMID:26740181

  5. The Effect of Citrus Peel Extracts on Cytokines Levels and T Regulatory Cells in Acute Liver Injury

    Directory of Open Access Journals (Sweden)

    Ia Pantsulaia

    2014-01-01

    Full Text Available Background. T cell-mediated immune responses contribute to the hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of antioxidant, anti-inflammatory mixture of citrus peel extract (CPE on the immune-mediated liver injury. Methods. The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring frequency of T regulatory cells (Tregs, cytokines (TNF-α, IL-10, and IFN-γ, and nitric oxide levels. Results. The CPE application notably prevents development of liver injury through decreasing levels of both cytokines (TNF-alpha, INF and regulatory T cells and increasing levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in evident reduction of the liver damage. Conclusion. Our findings represent the primary preclinical data indicating that the CPE in vivo could ameliorate Con A induced hepatitis. The low dose of CPE most likely can be used for the treatment of the T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis.

  6. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases.

    Science.gov (United States)

    Yu, Shan; Li, Sijia; Henke, Adam; Muse, Evan D; Cheng, Bo; Welzel, Gustav; Chatterjee, Arnab K; Wang, Danling; Roland, Jason; Glass, Christopher K; Tremblay, Matthew

    2016-07-01

    Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of immune responses. Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models. However, the adverse effects of these conventional LXR agonists in elevating liver lipids have impeded exploitation of this intriguing mechanism for chronic therapy. Here, we explore the ability of a series of sterol-based LXR agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We show that oral treatment with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine. The anti-inflammatory property of these agonists is recapitulated in vitro in mouse lamina propria mononuclear cells, human colonic epithelial cells, and human peripheral blood mononuclear cells. In addition, treatment with LXR agonists dramatically suppresses inflammatory cytokine expression in a model of traumatic brain injury. Importantly, in both disease models, the sterol-based agonists do not affect the liver, and the conventional agonist T0901317 results in significant liver lipid accumulation and injury. Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng, B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay, M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases. PMID:27025962

  7. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  8. 克肝膠囊对CCI4慢性肝损伤大鼠的影响%Influence of KeGan Capsule to Mice with CCI4 Chronic Hepatic Injury

    Institute of Scientific and Technical Information of China (English)

    徐玉芳

    2004-01-01

    Objective To study the action of KeGan capsule to resist injury of hepatic cells and fibrosis of liver. Methods Replicate model of chronic hepatic injury with CCl4, at the beginning of which KeGan capsule was applied; finishing experiment, respectively tested the level of liver function, TP,ALB, A/G, L - hydroxyproline and liver index and do pathologic examination to liver. Results KeGan capsule can obviously reduce the degree of fibrosis of liver and the level of L - hydroxyproline, improve the liver function. The histological examination showed that capsule has the action of protecting hepatic cells from injury and resisting fibrosis of liver either. Conclusion For KeGan capsule has the action of resisting injury of liver cells and fibrosis of liver, it' s hoped to be applied in precaution and treatnent of fibrosis of liver.

  9. An Update on Drug-induced Liver Injury.

    Science.gov (United States)

    Devarbhavi, Harshad

    2012-09-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  10. Psychological effects of chronic injury in elite athletes.

    OpenAIRE

    Shuer, M L; Dietrich, M S

    1997-01-01

    Many athletes train in a constant state of pain or injury while meeting the demands of an elite level program. It is hypothesized that the emotional distress experienced by athletes with chronic injuries is not inconsequential. A self-report battery, the Impact of Event Scale, was administered to 280 inter-collegiate athletes at a division I institution in an attempt to examine their response to chronic injury. Of the 280, 134 (48%) had been injured by study definition, with 117 (42%) meeting...

  11. Liver fibrosis in chronic viral hepatitis: An ultrasonographic study

    Institute of Scientific and Technical Information of China (English)

    Rong-Qin Zheng; Qing-Hui Wang; Ming-De Lu; Shi-Bin Xie; Jie Ren; Zhong-Zhen Su; Yin-Ke Cai; Ji-Lu Yao

    2003-01-01

    AIM: To select valuable ultrasonographic predictors for the evaluation of hepatic inflammation and fibrosis degree in chronic hepatitis, and to study the value of ultrasonography in the evaluation of liver fibrosis and compensated liver cirrhosis in comparison with serology and histology.METHODS: Forty-four ultrasonographic variables were analyzed and screened using color Doppler ultrasound system in 225 patients with chronic viral hepatitis and compensated liver cirrhosis. The valuable ultrasonographic predictors were selected on the basis of a comparison with histopathological findings. The value of ultrasonography and serology in the evaluation of liver fibrosis degree and the diagnosis of compensated liver cirrhosis was also studied and compared. Meanwhile, the influencing factors on ultrasonographic diagnosis of compensated liver cirrhosis were also analyzed.RESULTS: By statistical analysis, the maximum velocity of portal vein and the degree of gall-bladder wall smoothness were selected as the valuable predictors for the inflammation grade (G), while liver surface, hepatic parenchymal echo pattern, and the wall thickness of gall-bladder were selected as the valuable predictors for the fibrosis stage (S). Three S-related independent ultrasonographyic predictors and three routine serum fibrosis markers (HA, HPCIII and CIV) were used to discriminate variables for the comparison of ultrasonography with serology. The diagnostic accuracy of ultrasonography in moderate fibrosis was higher than that of serology (P<0.01), while there were no significant differences in the general diagnostic accuracy of fibrosis as well as between mild and severe fibrosis (P<0.05). There were no significant differences between ultrasonography and serology in the diagnosis of compensated liver cirrhosis.However, the diagnostic accuracy of ultrasonography was higher in inactive liver cirrhosis and lower in active cirrhosis than that of serology (both P<0.05). False positive and false

  12. An Autopsy Study of Liver Injuries in a Tertiary Referral Centre of Eastern Nepal

    Science.gov (United States)

    Subedi, Nuwadatta; Yadav, B.N.; Jha, Shivendra; Gurung, Sharmila; Pradhan, Amshu

    2013-01-01

    Background: Liver is the largest gland in the body and it frequently gets wounded. The objective of this study was to determine the patterns, types and severities of liver injuries which were caused by mechanical trauma and to study the organs associated with liver injuries. Material and Methods: This was a hospital based, cross sectional study which was conducted on the autopsies showing the evidence of liver injuries in the mortuary of a tertiary hospital in eastern Nepal. All consecutive autopsy cases which were handled within one year’s time (n=46) were included in our study. The cases were studied in detail for liver injuries, which included age, sex, severity, associated injuries, site of the injury, description of the injury, etc. Results: The mean age of the victims was 33.87 years and there was a male: female ratio of 3.6:1. The injuries had resulted from blunt trauma in 41 (89.1%) cases, the most common of which was road traffic accidents, constituting 37(80.4%) cases. Grade III injuries were seen in 14 (30.4%) cases. Laceration of the liver was the most frequent finding that was evident in 34 (73.9%) cases. Right lobe of the liver was injured in 30 (74%) cases. The sole presence of liver injuries among abdomino-pelvic organs was seen in 14 (30.4%) cases. In 40 (87%) cases, liver injuries were associated with other regional injuries. Conclusion: Laceration is the most common liver injury among autopsy cases. Right lobe is mostly affected and grade III injuries are the most common ones. Liver injuries are frequently associated with other abdomino-pelvic organs and multiple regional injuries. PMID:24086875

  13. Hyperhomocysteinemia,endoplasmic reticulum stress,and alcoholic liver injury

    Institute of Scientific and Technical Information of China (English)

    Cheng Ji; Neil Kaplowitz

    2004-01-01

    Deficiencies in vitamins or other factors (B6, B12, folic acid,betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (Hhcy). Hhcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. Hhcy unleashes mediators of inflammation such as NFκB, IL-1β, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis,fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of Hhcy. ER stress may also be involved in other liver diseases such as α1-antitrypsin (α1-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans,and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of Hhcy and liver disease.

  14. Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition

    OpenAIRE

    Kim, Tae Yeob; Song, Do Seon; Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L.; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Kim, Jeong Han; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun

    2016-01-01

    Background & Aim To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and Decem...

  15. Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases

    International Nuclear Information System (INIS)

    Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-galactosyl-human-serum-albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver disease. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images were not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku, and PT values were more significantly decreased or prolonged in the patients with chronic hepatitis. Kd, Ku, and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degree of hepatic fibrosis. On the other hand, the indices obtained using Tc-99m-PMT or Tc-99m-sn-phytate did not have correlations with the histological degrees of hepatic fibrosis. It is concluded that the liver scintigraphy using Tc-99m-GSA may be useful and give different information from those with conventional liver scintigraphies in evaluating chronic liver diseases. (author)

  16. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury.

    Science.gov (United States)

    Hay, Jennifer; Johnson, Victoria E; Smith, Douglas H; Stewart, William

    2016-05-23

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article. PMID:26772317

  17. An Autopsy Study of Liver Injuries in a Tertiary Referral Centre of Eastern Nepal

    OpenAIRE

    Subedi, Nuwadatta; Yadav, B.N.; Jha, Shivendra; Gurung, Sharmila; Pradhan, Amshu

    2013-01-01

    Background: Liver is the largest gland in the body and it frequently gets wounded. The objective of this study was to determine the patterns, types and severities of liver injuries which were caused by mechanical trauma and to study the organs associated with liver injuries.

  18. Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis.

    Science.gov (United States)

    Lian, Fan; Wang, Yu; Xiao, Youjun; Wu, Xiwen; Xu, Hanshi; Liang, Liuqin; Yang, Xiuyan

    2015-10-01

    Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, the presence of autoantibodies, regulatory T‑cell dysfunction and raised plasma liver enzyme levels. The present study assessed the hepatoprotective and antiapoptotic role of farnesoid X receptor (FXR) in AIH. a mouse model of AIH was induced by treatment with concanavalin A (ConA). The FXR agonist, chenodeoxycholic acid (CDCA), was administered to mice exhibiting ConA‑induced liver injury and a normal control. Blood samples were obtained to detect the levels of aminotransferases and inflammatory cytokines. Liver specimens were collected, and hematoxylin‑eosin staining was used for histopathological examination and detection. Apoptosis was evaluated using the terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling (TUNEL) method. The expression levels of apoptosis‑associated genes and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that FXR was downregulated at the mRNA and protein level in the liver specimens of mice induced with ConA‑induced hepatitis. Increased levels of aminotransferases and inflammatory cytokines, including interferon‑γ, tumor necrosis factor‑α, interleukin (IL)‑4 and IL‑2, were detected in ConA‑treated mice. The mice pretreated with the FXR agonist, CDCA, were more resistant to ConA hepatitis, as indicated by reduced levels of alanine transaminase/aspartate aminotransferase and aminotransferases. The activation of FXR ameliorated hepatocyte apoptosis, as demonstrated by TUNEL analysis and downregulation of the Fas/Fas ligand, tumor necrosis factor‑related apoptosis‑inducing ligand and caspase‑3. Taken together, FXR activation ameliorated liver injury and suppressed inflammatory cytokines in ConA‑induced hepatitis. FXR, therefore, exerts a protective role against ConA-induced apoptosis. PMID

  19. Assessment of adult patients with chronic liver failure for liver transplantation in 2015: who and when?

    Science.gov (United States)

    McCaughan, G W; Crawford, M; Sandroussi, C; Koorey, D J; Bowen, D G; Shackel, N A; Strasser, S I

    2016-04-01

    In 2015, there are a few absolute contraindications to liver transplantation. In adult patients, survival post-liver transplant is excellent, with 1-year survival rate >90% and 5-year survival rates >80% and predicted median allograft survival beyond 20 years. Patients with a Child-Turcotte Pugh score ≥9 or a model for end-stage liver disease (MELD) score >15 should be referred for liver transplantation, with patients who have a MELD score >17 showing a 1-year survival benefit with liver transplantation. A careful selection of hepatocellular cancer patients results in excellent outcomes, while consideration of extra-hepatic disease (reversible vs irreversible) and social support structures are crucial to patient assessment. Alcoholic liver disease remains a challenge, and the potential to cure hepatitis C virus infection together with the emerging issue of non-alcoholic fatty liver disease-associated chronic liver failure will change the landscape of the who in the years ahead. The when will continue to be determined largely by the severity of liver disease based on the MELD score for the foreseeable future. PMID:27062203

  20. Liver dialysis in acute-on-chronic liver failure: current and future perspectives.

    Science.gov (United States)

    Maiwall, Rakhi; Maras, Jaswinder Singh; Nayak, Suman Lata; Sarin, Shiv Kumar

    2014-09-01

    Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients. PMID:26201332

  1. Drugs of abuse and addiction: A slippery slope toward liver injury.

    Science.gov (United States)

    Roy, Dijendra Nath; Goswami, Ritobrata

    2016-08-01

    Substances of abuse induce alteration in neurobehavioral symptoms, which can lead to simultaneous exacerbation of liver injury. The biochemical changes of liver are significantly observed in the abused group of people using illicit drugs or drugs that are abused. A huge amount of work has been carried out by scientists for validation experiments using animal models to assess hepatotoxicity in cases of drugs of abuse. The risk of hepatotoxicity from these psychostimulants has been determined by different research groups. Hepatotoxicity of these drugs has been recently highlighted and isolated case reports always have been documented in relation to misuse of the drugs. These drugs induce liver toxicity on acute or chronic dose dependent process, which ultimately lead to liver damage, acute fatty infiltration, cholestatic jaundice, liver granulomas, hepatitis, liver cirrhosis etc. Considering the importance of drug-induced hepatotoxicity as a major cause of liver damage, this review emphasizes on various drugs of abuse and addiction which induce hepatotoxicity along with their mechanism of liver damage in clinical aspect as well as in vitro and in vivo approach. However, the mechanisms of drug-induced hepatotoxicity is dependent on reactive metabolite formation via metabolism, modification of covalent bonding between cellular components with drug and its metabolites, reactive oxygen species generation inside and outside of hepatocytes, activation of signal transduction pathways that alter cell death or survival mechanism, and cellular mitochondrial damage, which leads to alteration in ATP generation have been notified here. Moreover, how the cytokines are modulated by these drugs has been mentioned here. PMID:26409324

  2. Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Aida Ortega-Alonso

    2016-05-01

    Full Text Available Idiosyncratic drug-induced liver injury (DILI caused by xenobiotics (drugs, herbals and dietary supplements presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies.

  3. Melatonin protects liver from intestine ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Yi Li; Hong-Zhuan Yin; Xi Gu; Yong Zhou; Wen-Hai Zhang; Yi-Min Qin

    2008-01-01

    AIM:To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats.METHODS:One hundred and fifty male Wistar rats,weighing 190-210 g,aged 7 wk,were randomly divided into melatonin exposure group,alcohol solvent control group and normal saline control group.Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR),rats in the alcohol solvent control group received the same concentration and volume of alcohol,and rats in the normal saline control group received the same volume of normal saline.Serum samples were collected from each group 0.5,1,6,12,and 24 h after intestinal IR.Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an auto-biochemical analyzer.Serum TNF-a was tested by enzyme-linked immunosorbent assay (ELISA).Malondialdehyde (MDA) in liver was detected by colorimetric assay.Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope.RESULTS:The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups (P<0.05).The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels (%) 6,12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups (P<0.05).CONCLUSION:Exotic melatonin can inhibit the activity of ALT,AST and TNF-a decrease the accumulation of MDA,and depress the expression of ICAM-1 in liver after intestinal IR injury,thus improving the liver function.

  4. Telomere and telomerase in chronic liver disease and hepatocarcinoma.

    Science.gov (United States)

    Carulli, Lucia; Anzivino, Claudia

    2014-05-28

    The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma. PMID:24876749

  5. Nrf2 activation prevents cadmium-induced acute liver injury

    International Nuclear Information System (INIS)

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H2DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were

  6. Nrf2 activation prevents cadmium-induced acute liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  7. Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

    Science.gov (United States)

    Okumura, Shinya; Teratani, Takumi; Fujimoto, Yasuhiro; Zhao, Xiangdong; Tsuruyama, Tatsuaki; Masano, Yuki; Kasahara, Naoya; Iida, Taku; Yagi, Shintaro; Uemura, Tadahiro; Kaido, Toshimi; Uemoto, Shinji

    2016-09-01

    Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD. PMID:27102080

  8. Clinical significance of eosinophilia in the diagnosis of halothane-induced liver injury.

    Directory of Open Access Journals (Sweden)

    Fujiwara,Masachika

    1984-02-01

    Full Text Available Three patients with severe halothane-induced liver injury are described. All patients received halothane anesthesia twice within a short period. High fever and jaundice were noticed soon after the second operation. The prothrombin time was less than 40%, and eosinophilia was greater than 7% prior to these symptoms. Other causes of liver injury were excluded. Diagnostic criteria for halothane-induced liver injury are proposed.

  9. Intraoperative injuries during liver resection: analysis of 1,005 procedures

    OpenAIRE

    Grat, Michal; Grzegorczyk, Karolina; Lewandowski, Zbigniew; Sujecki, Damian; Szwedowski, Dawid; Boltuc, Adam; Smoter, Piotr; Kornasiewicz, Oskar; Krawczyk, Marek

    2011-01-01

    Purpose Risk of liver resection has been well investigated in many studies. However, the problem of intraoperative injuries is rarely mentioned. The aim of this study was to assess the incidence, the type, and management of intraoperative injuries during liver resection. Methods A total of 1,005 liver resections between 2004 and 2009 were included in this retrospective investigation. We analyzed the incidence of intraoperative injuries, risk factors, and an impact on patients’ clinical outcom...

  10. Prediction of Liver-Related Events Using Fibroscan in Chronic Hepatitis B Patients Showing Advanced Liver Fibrosis

    OpenAIRE

    Kim, Seung Up; Lee, Ji Hoon; Kim, Do Young; Ahn, Sang Hoon; Jung, Kyu Sik; Choi, Eun Hee; Park, Young Nyun; Han, Kwang-Hyub; Chon, Chae Yoon; Park, Jun Yong

    2012-01-01

    Background Liver stiffness measurement (LSM) using transient elastography (FibroScan®) can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs) in chronic hepatitis B (CHB) patients showing histologically advanced liver fibrosis. Methods Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB) before starting nucleot(s)ide analogues and showed histologically advanced fibrosis...

  11. Hepatic miR-29ab1 expression modulates chronic hepatic injury.

    Science.gov (United States)

    Kogure, Takayuki; Costinean, Stefan; Yan, Irene; Braconi, Chiara; Croce, Carlo; Patel, Tushar

    2012-11-01

    MicroRNAs (miRNAs) are small, regulatory non-coding RNAs that have potent effects on gene expression. Several miRNA are deregulated in cellular processes involved in human liver diseases and regulation of cellular processes. Recent studies have identified the involvement of miR-29 in hepatic fibrosis and carcinogenesis. Although several targets of miR-29 have been identified, there is limited information regarding the cell-type specific roles of miR-29 in the liver, and we sought to evaluate the role of this miRNA in hepatic pathobiology. We report the generation of a tissue-specific knockout mouse to evaluate the role of miR-29 in hepatic fibrosis and carcinogenesis in response to injury. We hypothesized that miR-29 contributes to the hepatocyte driven response to chronic cellular injury that results in fibrosis. In support of this hypothesis, fibrosis and mortality were enhanced in miR29 knockout mice in response to carbon tetrachloride. Genome-wide gene expression analysis identified an over-representation of genes associated with fibrosis. The oncofetal RNA H19 was modulated in a miR-29 dependent manner following exposure to carbon tetrachloride in vivo. The impact of a hepatocyte specific miR-29 knockout on survival following chronic hepatic injury in vivo implicates this miRNA as a potential target for intervention. These results provide evidence of the involvement of miR-29 in chronic hepatic injury, and suggest a role for deregulated hepatocyte expression of miR-29 in the response to hepatic injury, fibrosis and carcinogenesis. PMID:22469499

  12. Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury

    OpenAIRE

    Borlak, Jürgen; Chatterji, Bijon; Londhe, Kishor B; Watkins, Paul B

    2013-01-01

    Background Acetaminophen (APAP) is a commonly used analgesic. However, its use is associated with drug-induced liver injury (DILI). It is a prominent cause of acute liver failure, with APAP hepatotoxicity far exceeding other causes of acute liver failure in the United States. In order to improve its safe use this study aimed to identify individuals at risk for DILI prior to drug treatment by searching for non-genetic serum markers in healthy subjects susceptible to APAP-induced liver injury (...

  13. Endothelial dysfunction correlates with liver fibrosis in chronic HCV infection.

    Science.gov (United States)

    Barone, Michele; Viggiani, Maria Teresa; Amoruso, Annabianca; Schiraldi, Serafina; Zito, Annapaola; Devito, Fiorella; Cortese, Francesca; Gesualdo, Michele; Brunetti, Natale; Di Leo, Alfredo; Scicchitano, Pietro; Ciccone, Marco Matteo

    2015-01-01

    Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan) and aspartate aminotransferase to platelet ratio index (APRI)), carotid intima-media thickness (c-IMT), and brachial artery flow-mediated vasodilatation (FMD) were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa) showed FMD values were significantly lower than second and first tertiles (4.7 ± 1.7% versus 7.1 ± 2.8%, p = 0.03). FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p = 0.02) was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors. PMID:26000012

  14. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    Science.gov (United States)

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  15. Exploring an animal model of amodiaquine-induced liver injury in rats and mice.

    Science.gov (United States)

    Liu, Feng; Cai, Ping; Metushi, Imir; Li, Jinze; Nakayawa, Tetsuya; Vega, Libia; Uetrecht, Jack

    2016-09-01

    Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4(+) T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance. PMID:27416278

  16. Gastric emptying in patients with chronic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ishizu, Hirotaka; Shiomi, Susumu; Kawamura, Etsushi; Iwata, Yoshinori; Nishiguchi, Shuhei; Kawabe, Joji; Ochi, Hironobu [Osaka City Univ. (Japan). Graduate School of Medicine

    2002-05-01

    There have been a number of reports of gastric emptying in cirrhosis, all with unconfirmed results. Moreover, the mechanism for delayed emptying in cirrhotic patients in unclear. We evaluated gastric emptying in patients with chronic hepatitis and cirrhosis by means of gastric emptying scintigraphy. The subjects were 18 normal controls and 75 patients with chronic viral hepatitis (50 patients had chronic hepatitis and 25 patients had cirrhosis). Tc-99m diethyltriamine pentaacetic acid labeled solid meals were used to evaluate gastric emptying; the half-time (T 1/2) of which was calculated. Digestive symptom scores were determined at the time of gastric emptying tests. Fourteen (28%) of 50 patients with chronic hepatitis and 16 (64%) of 25 patients with cirrhosis had delayed gastric emptying. T 1/2 in patients with cirrhosis was significantly higher than that in normal controls and patients with chronic hepatitis (p=0.0001 and 0.0003, respectively). The difference between T 1/2 in patients with chronic hepatitis and that in normal controls was not significant. On regression analysis, two indices, the serum albumin level and platelet count, were found to be significantly related to delayed gastric emptying. Gastric emptying was more delayed in cirrhotic patients than in those with chronic hepatitis and normal controls. Delayed gastric emptying may be related to liver function and portal hypertension. (author)

  17. Oroxylin A accelerates liver regeneration in CCl₄-induced acute liver injury mice.

    Directory of Open Access Journals (Sweden)

    Runzhi Zhu

    Full Text Available INTRODUCTION: Based on the previous research that oroxylin A can suppress inflammation, we investigated the hepatoprotective role of oroxylin A against CCl₄-induced liver damage in mice and then studied the possible alteration of the activities of cytokine signaling participating in liver regeneration. Wild type (WT mice were orally administrated with oroxylin A (60 mg/kg for 4 days after CCl₄ injection, the anti-inflammatory effects of oroxylin A were assessed directly by hepatic histology and indirectly by measuring serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT and Albumin. Proliferating cell nuclear antigen (PCNA staining was performed to evaluate the role of oroxylin A in promoting hepatocyte proliferation. Serum IL-1β, TNF-α, IL-6 and IL-1Ra levels were measured by enzyme-linked immunosorbent assay (ELISA and liver HGF, EGF, TNF-α, IL-6, IL-1Ra and IL-1β gene expression was determined by quantitative real-time PCR. The data indicated that the IL-6 and TNF-α mRNA of oroxylin A administered group significantly increased higher than the control within 12 hours after CCl4 treatment. Meanwhile, oroxylin A significantly enhanced the expression of IL-1Ra at the early phase, which indicated that oroxylin A could facilitate the initiating events in liver regeneration by increasing IL-1Ra which acts as an Acute-Phase Protein (APP. In addition, a lethal CCl₄-induced acute liver failure model offers a survival benefit in oroxylin A treated WT mice. However, oroxylin A could not significantly improve the percent survival of IL-1RI⁻/⁻ mice with a lethal CCl₄-induced acute liver failure. CONCLUSIONS: Our study confirmed that oroxylin A could strongly promote liver structural remodeling and functional recovery through IL-1Ra/IL-1RI signaling pathway. All these results support the possibility of oroxylin A being a therapeutic candidate for acute liver injury.

  18. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    Spósito A.C.

    1997-01-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

  19. Chronic post-traumatic headache after mild head injury

    DEFF Research Database (Denmark)

    Kjeldgaard, Dorte; Forchhammer, Hysse; Teasdale, Tom;

    2014-01-01

    BACKGROUND: The aetiology behind chronic post-traumatic headache (CPTH) after mild head injury is unclear and management is complicated. In order to optimize treatment strategies we aimed to characterize a CPTH population. METHODS: Ninety patients with CPTH and 45 patients with chronic primary he...... levels of disability for the CPTH patients suggests directions for further research into what important factors are embedded in the patients' PTSD symptoms and might explain their prolonged illness....

  20. Apoptosis pathway of liver cells in chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Nai-Ling Chen; Zhen-Qiu Zhou; Ling Bai; Lin Li; Pei-Lan Chen; Chang Zhang; Chao-Ying Liu; Tao Deng; Hao Chen; Ke-Ming Jia

    2004-01-01

    AIM: To study the pathway of apoptosis in chronic liver disease and the role of mitochondria in programmed cell death.METHODS: Liver biopsy specimens from 72 cases of chronic hepatitis and 29 cases of post hepatitis cirrhosis were studied. The pro-apoptotic protein Fas, FasL, Bax and the anti-apoptotic protein Bcl-2, Bcl-xL, Bcl-2α were studied immunohistochemically by SP method. Specimens from 15 cases of chronic hepatitis and post hepatitis cirrhosis were examined for their ultramicrostructures with special attention to their mitochondrial changes. Specimens from 3 normal adults (demised in traffic accidents) were used as control.RESULTS: The expression of proapoptotic proteins (Fas,FasL, Bax) in hepatocytes was significantly higher in the chronic hepatitis group than in the cirrhosis group (P<0.001).In the study of ultramicrostructure 364 hepatocytes were examined, from 12 cases of chronic hepatitis (including 10mild cases, 1 moderate case and 1 severe case). Out of 364 hepatocytes 40 (11.0%) hepatocytes were found with various kinds of destruction in their mitochondria. Rupture of the outer membrane of mitochondria and the leakage of matrix from the intermembrane space were definitely demonstrated. The ultramicrostructural changes of mitochondria in the chronic hepatitis group were statistically higher than that in normal adults control group (χ2=4.32, P<0.05).CONCLUSION: The result of the study was in support of the current view that the apoptotic process in chronic hepatitis patients were largely along the intrinsic pathway (mitochondrial pathway), given that the intrinsic and extrinsic pathways could interlinked (converged) at some point on their progression, also it is impossible at present to exclude the possibility that the two pathways could be chosen by hepatocytes in parallel simultaneously.

  1. Pathology of flupirtine-induced liver injury: a histological and clinical study of six cases.

    Science.gov (United States)

    Puls, Florian; Agne, Clemens; Klein, Fritz; Koch, Martin; Rifai, Kinan; Manns, Michael P; Borlak, Jürgen; Kreipe, Hans H

    2011-06-01

    Drug-induced liver injury may cause impairment of liver function and is a leading cause of acute liver failure. Identification of the causative substance in patients receiving several drugs is often difficult in clinical practice. Evaluation of liver biopsies in suspected drug-induced injury is a challenging task that requires close clinico-pathological correlation. Recognizing a characteristic morphological pattern of liver injury may contribute to identification of the causative drug. Flupirtine, a non-opioid analgesic, has been reported to cause liver injury of idiosyncratic type in rare instances. We wished to characterize the histopathological features of flupirtine-induced liver injury, which have not been reported so far. Liver biopsies of five patients with severe liver injury and one explanted liver of a patient with flupirtine-induced acute liver failure that required transplantation were assessed. In addition clinical presentation and course were reviewed and clinical follow up was performed. Extensive perivenular necrosis with associated ceroid pigment-laden macrophages and a mild to moderate lymphocytic infiltrate was a common feature in all cases. Histological extent of liver necrosis corresponded well to serum amino-transferase levels. Accidental reexposure of one patient resulted in a plasma cell rich hepatitis with perivenular necrosis. This study provides evidence that flupirtine can cause substantial liver injury of hepatocellular type. Liver damage is associated with a characteristic morphological picture, the recognition of which will aid in causality assessment of drug-induced liver injury. Clinical and histological features raise the possibility of an immune-mediated toxicity. PMID:21590308

  2. Peripheral blood lymphocytes DNA in patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Vasiliy I Reshetnyak; Tatyana I Sharafanova; Ludmila U Ilchenko; Elena V Golovanova; Gennadiy G Poroshenko

    2001-01-01

    BACKGROUND Viral replication in blood cells with nucleuses may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions.AIM Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL)DNA in the patients with chronic liver diseases.MATERIALS AND METHODS Sixteen-ninepatients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol + virus G),30 women with primary biliary cirrhosis-PBC)were examined. The condition of DNA structure of PBL-was measured by the fluorescenceanalysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (thepresence of DNA single-stranded breaks and alkalinelabile sights).RESULTS AND CONCLUSION . The quantity of DNA single-stranded breaks and alkalinelabile sightsin DNA in all patients with chronic viral hepatitis .didnt differ from the control group,excluding the patients with chronic hepatitis (CH) C + G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity.This fact may be connected with hypothesisabout the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednison was demonstrated. Probably, the tendency to increase the quantity of DNA singlestranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.

  3. Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

    OpenAIRE

    Keeffe, Emmet B.

    2006-01-01

    A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver diseas...

  4. Metabolic Disturbances in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    A Rezaeian

    2014-04-01

    Full Text Available Introduction: Liver disease results in complex pathophysiologic disturbances affecting nutrient digestion, absorption, distribution, storage, and use. This article aimed to present a classification of metabolic disturbances in chronic liver disease in children?   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"  ” metabolic disorder””children” between 1999 to 2014. Finally, 8 related articles have been found.   Results: Metabolic disorder in this population could be categorized in four set: 1carbohydrates, 2proteins,3 fats and 4vitamins. 1 Carbohydrates: Children with CLD are at increased risk for fasting hypoglycemia, because the capacity for glycogen storage and gluconeogenesis is reduced as a result of abnormal hepatocyte function and loss of hepatocyte mass. 2 Proteins: The liver’s capacity for plasma protein synthesis is impaired by reduced substrate availability, impaired hepatocyte function, and increased catabolism. This results in hypoalbuminemia, leading to peripheral edema and contributing to ascites. Reduced synthesis of insulin-like growth factor (IGF-1 and its binding protein IGF-BP3 by the chronically diseased liver results in growth hormone resistance and may contribute to the poor growth observed in these children. 3 Fats: There is increased fat oxidation in children with end-stage liver disease in the fed and fasting states compared with controls, which is probably related to reduced carbohydrate availability. The increased lipolysis results in a decrease in fat stores, which may not be easily replenished in the setting of the fat malabsorption that accompanies cholestasis. Reduced bile delivery to the gut results in impaired fat emulsification, and hence digestion. The products of fat digestion are also poorly absorbed, because bile is also required for micelle formation

  5. Economic evaluation of the artificial liver support system MARS in patients with acute-on-chronic liver failure

    OpenAIRE

    Hessel Franz P

    2006-01-01

    Abstract Background Acute-on-chronic liver failure (ACLF) is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS. Methods I...

  6. Peripheral nervous system involvement in chronic spinal cord injury

    DEFF Research Database (Denmark)

    Tankisi, Hatice; Pugdahl, Kirsten; Rasmussen, Mikkel Mylius;

    2015-01-01

    Introduction: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Methods: Twelve subjects with chronic low cervical or thoracic SCI were included...

  7. Protective effects of emodin and astragalus polysaccharides on chronic hepatic injury in rats

    Institute of Scientific and Technical Information of China (English)

    DANG Shuang-suo; ZHANG Xin; JIA Xiao-li; CHENG Ya-nan; SONG Ping; LIU En-qi; HE Qian; LI Zong-fang

    2008-01-01

    Background Chinese medicine plays an important role in hepatoprotective treatment. This study was conducted to investigate the protective effects of emodin and astragalus polysaccharides (APS) in a rat model of chronic hepatic injury.Methods Chronic hepatic injury was induced by hypodermic injection of an olive oil solution containing 40% carbon tetrachloride (CCI4) twice a week, in addition to a diet of 79.5% maizena, 20% fat, 0.5% cholesterol, and 10% alcohol in the drinking water ad libitum for 12 weeks. Meanwhile, the rats were exposed to different concentrations of emodin (40 mg·kg-1·d-1), APS (200 mg·kg-1·d-1), combination drug (emodin 40 mg.kg-1·d-1 combined with APS 200 mg.kg-1·d-1) and colchicine (0.1 mg·kg-1·d-1) in parallel by oral gavage (once a day for 12 weeks). At the end of 12 weeks, blood serum and liver tissue were taken. Serum was collected to determine the levels of total bilirubin (TBIL), alanine transaminase (ALT),aspartate transaminose (AST), and albumin (ALB). Liver and spleen indexes were assayed, followed by the measurements of the liver associated enzyme superoxide dismutase (SOD) and malondialdehyde (MDA). Histopathological changes were studied using optical microscopy.Results Splenohepatomegalia was alleviated and serum levels of TBIL and ALT were reduced in the groups treated with emodin and APS when compared to the control group. In addition, the ALB level in the APS and combination groups was higher. Similarly, the SOD activity of liver homogenates was significantly higher in the groups treated with emodin and APS, while administration of the herbal derivatives prevented the elevation in MDA levels. Histological analysis showed that the APS and combination groups significantly ameliorated the hepatic injury.Conclusions Co-administration of emodin and APS demonstrated a synergistic action in reducing ALT and restoring ALB in the serum from a rat model of chronic hepatic injury. Emodin and APS may ameliorate the CCI4-induced

  8. (Z-5-(4-methoxybenzylidenethiazolidine-2,4-dione protects rats from carbon tetrachloride-induced liver injury and fibrogenesis

    Directory of Open Access Journals (Sweden)

    Zhi-Zhi Chen

    2012-01-01

    Full Text Available AIM: To evaluate the hepatoprotective roles of (Z-5-(4-methoxybenzylidenethiazolidine-2,4-dione (SKLB010 against carbon tetrachloride (CCl4-induced acute and chronic liver injury and its underlying mechanisms of action. METHODS: In the first experiment, rats were weighed and randomly divided into 5 groups (five rats in each group to assess the protective effect of SKLB010 on acute liver injury. For induction of acute injury, rats were administered a single intraperitoneal injection of 2 mL/kg of 50% (v/v CCl4 dissolved in olive oil (1:1. Group 1 was untreated and served as the control group; group 2 received CCl4 for induction of liver injury and served as the model group. In groups 3, 4 and 5, rats receiving CCl4 were also treated with SKLB010 at doses of 25, 50 and 100 mg/kg, respectively. Blood samples were collected at 6, 12 and 24 h after CCl4 intoxication to determine the serum activity of alanine amino transferase. Tumour necrosis factor-α (TNF-α, interleukin-1β (IL-1β were determined using enzyme-linked immunosorbent assay. At 24 h after CCl4 injection,liver fibrogenesis was evaluated by hematoxylin-eosin (HE staining and immunohistochemical analyses. Cytokine transcript levels of TNF-α, IL-1β and inducible nitric oxide synthase in the liver tissues of rats were measured using a reverse transcriptase reverse transcription-polymerase chain reaction technique. In the second experiment, rats were randomly divided into 2 groups (15 rats in each group, and liver injury in the CCl4-administered groups was induced by a single intraperitoneal injection of 2 mL/kg of 50% (v/v CCl4 dissolved in olive oil (1:1. The SKLB010-treated groups received oral 100 mg/kg SKLB010 before CCl4 administration. Five rats in each group were sacrificed at 2 h, 6 h, 12 h after CCl4 intoxication and small fortions of livers were rapidly frozen for extraction of total RNA, hepatic proteins and glutathione (GSH assays. In the hepatic fibrosis model group, rats

  9. Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

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    Ivan Ćavar

    2011-12-01

    Full Text Available Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX A2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP is a major cause of acute liver failure in the Western world. We investigated whether TXA2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX B2 antibodies (anti-TXB2 and a selective inhibitor of thromboxane (TX synthase, benzylimidazole (BZI, were significantly hepatoprotective, while a selective thromboxane receptor (TPR antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA2, TXB2, and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB2. According to our results, this protection is mediated, at least in part, through decreased production of TXB2 by liver fragments ex vivo.

  10. NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants

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    Jie Liu

    2013-01-01

    Full Text Available To investigate the role of Nrf2 as a master defense against the hepatotoxicity produced by various chemicals, Nrf2-null, wild-type, Keap1-knock down (Keap1-Kd and Keap1-hepatocyte knockout (Keap1-HKO mice were used as a “graded Nrf2 activation” model. Mice were treated with 14 hepatotoxicants at appropriate doses, and blood and liver samples were collected thereafter (6 h to 7 days depending on the hepatotoxicant. Graded activation of Nrf2 offered a Nrf2-dependent protection against the hepatotoxicity produced by carbon tetrachloride, acetaminophen, microcystin, phalloidin, furosemide, cadmium, and lithocholic acid, as evidenced by serum alanine aminotransferase (ALT activities and by histopathology. Nrf2 activation also offered moderate protection against liver injury produced by ethanol, arsenic, bromobenzene, and allyl alcohol but had no effects on the hepatotoxicity produced by D-galactosamine/endotoxin and the Fas ligand antibody Jo-2. Graded Nrf2 activation reduced the expression of inflammatory genes (MIP-2, mKC, IL-1β, IL-6, and TNFα, oxidative stress genes (Ho-1, Egr1, ER stress genes (Gadd45 and Gadd153, and genes encoding cell death (Noxa, Bax, Bad, and caspase3. Thus, this study demonstrates that Nrf2 prevents the liver from many, but not all, hepatotoxicants. The Nrf2-mediated protection is accompanied by induction of antioxidant genes, suppression of inflammatory responses, and attenuation of oxidative stress.

  11. Chronic cerebrovascular dysfunction after traumatic brain injury.

    Science.gov (United States)

    Jullienne, Amandine; Obenaus, Andre; Ichkova, Aleksandra; Savona-Baron, Catherine; Pearce, William J; Badaut, Jerome

    2016-07-01

    Traumatic brain injuries (TBI) often involve vascular dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of cerebrovascular dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation. We also discuss the mechanisms that mediate these dysfunctions, focusing on the cellular components of cerebral blood vessels (endothelial cells, smooth muscle cells, astrocytes, pericytes, perivascular nerves) and their known and potential roles in the secondary injury cascade. © 2016 Wiley Periodicals, Inc. PMID:27117494

  12. Mineral Requirements in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    A Rezaeian

    2014-04-01

    Full Text Available Introduction: Decreased oral intake or impaired function / structure in the gut, such as hypertension port associated with atrophic changes in the protein nutrition - calories can lead to micronutrient deficiencies.This paper examines the status of micronutrients in chronic liver disease in children.   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"” minerals””children” between 1999 to 2014. Finally, 3 related articles have been found.   Results: In chronic liver disease changes in micronutrient metabolism lead to changes in the daily requirements, such that in certain circumstances intake increasing or decreasing  is needed. Low serum calcium and phosphate concentrations are often the reflection of malabsorption-induced bone disease that is unresponsive to vitamin D store normalization. Iron is usually deficient in children with CLD and supplementation frequently needed. The origin of iron deficiency is multifactorial and includes ongoing losses, inadequate intakes, serial blood draws and malabsorption secondary to hypertensive enteropathy. Zinc plays an important role in cognitive function, appetite and taste, immune function, wound healing, and protein metabolism. Low plasma zinc levels are frequent in children with chronic cholestasis, but unfortunately plasma concentrations are not reflective of total body zinc status. Copper and manganese, unlike other minerals, are increased in CLD, because they are normally excreted through bile. Parenteral nutrition in cholestatic patients can induce manganese intoxication and accumulation in basal ganglia.   Conclusion:  In fants with CLD are prone to multiple nutritional deficiencies. Mineral state should be evaluated, treated and reevaluated, until sufficient daily requirement achieved. Poster  Presentation, N 33  

  13. Chlorogenic acid protects d-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice.

    Science.gov (United States)

    Feng, Yan; Yu, Ying-Hua; Wang, Shu-Ting; Ren, Jing; Camer, Danielle; Hua, Yu-Zhou; Zhang, Qian; Huang, Jie; Xue, Dan-Lu; Zhang, Xiao-Fei; Huang, Xu-Feng; Liu, Yi

    2016-06-01

    Context Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. Objective The current study investigates the effects of protective effects of chlorogenic acid (CGA) on d-galactose-induced liver and kidney injury. Materials and methods Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of d-galactose (d-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included in the food (200 mg/kg of diet). The liver and renal functions were examined. Histological analyses of liver and kidney were done by haematoxylin and eosin staining. The oxidative stress markers and pro-inflammatory cytokines in the liver and the kidney were measured. Results CGA significantly reduced the serum aminotransferase, serum creatinine (SCr) and blood urea nitrogen (BUN) levels in d-gal mice (p <0.05). CGA also restored superoxide dismutase, catalase, and malondialdehyde levels and decreased glutathione content in the liver and kidney in d-gal mice (p <0.05). Improvements in liver and kidney were also noted in histopathological studies. CGA reduced tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels in the liver and kidney in d-gal mice (p <0.05). Discussion and conclusion These findings suggest that CGA attenuates d-gal-induced chronic liver and kidney injury and that this protection may be due to its antioxidative and anti-inflammatory activities. PMID:26810301

  14. A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats

    OpenAIRE

    Aroor Annayya R; Roy Lowery J; Restrepo Ricardo J; Mooney Brian P; Shukla Shivendra D

    2012-01-01

    Abstract Background Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared. Results The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-bi...

  15. Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.

    Directory of Open Access Journals (Sweden)

    Hong-Min Ni

    Full Text Available Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD. While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1α (HIF-1α, conflicting results regarding the role of HIF-1α in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1β knockout mice to eliminate the possible compensatory effects of the single knockout of the 1α subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1β knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1β knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1β knockout mice.

  16. Ethanol induced mitochondria injury and permeability transition pore opening: Role of mitochondria in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Ming Yan; Ping Zhu; Hui-Min Liu; Hai-Tao Zhang; Li Liu

    2007-01-01

    AIM: To observe changes of mitochondria and investigate the effect of ethanol on mitochondrial permeability transition pore (PTP), mitochondrial membrane potential (MMP, Δψm) and intracellular calcium concentration in hepatocytes by establishing an animal model of alcoholic liver disease (ALD).METHODS: Fourty adult male Wistar rats were randomly divided into two groups, the model group (20) was administered alcohol intragastrically plus an Oliver oil diet to establish an ALD model, and the control group (20) was given an equal amount of normal saline. The ultramicrostructural changes of mitochondria were observed under electron microscopy. Mitochondria of liver was extracted, and patency of PTP, mitochondrial membrane potential (Δψm), mitochondrial mass and intracellular calcium concentration of isolated hepacytes were detected by flow cytometry using rhodamine123 (Rh123), Nonyl-Acridine Orange and calcium fluorescent probe Fluo-3/AM, respectively.RESULTS: Membrane and cristae were broken or disappeared in mitochondria in different shapes under electron microscopy. Some mitochondria showed U shape or megamitochondrion. In the model group, liver mitochondria PTP was broken, and mitochondria swelled, the absorbance at 450 nm, A540 decreased (0.0136 ± 0.0025 vs 0.0321 ± O.0013,model vs control,P<O.01);mitochondria transmembrane potential (239.4638 ± 12.7263 vs 377.5850 ± 16.8119,P<0.01) was lowered;mitochondrial mass (17.4350 ± 1.9880 vs 31.6738 ± 3.4930,P<0.01);and [Ca2+]i was increased in liver cells (7.0020 ± 0.5008 vs 10.2050 ± 0.4701,P<0.01).CONCLUSION:Chronic alcohol intake might lead to broken mitochondria PTP,decreased mitochondria membrane potential and injury,and elevated intracellular Ca2+ production.Ethanol-induced chondriosome injury may be an important mechanism of alcoholic diseases.

  17. Acute Hepatocellular Drug-Induced Liver Injury From Bupropion and Doxycycline.

    Science.gov (United States)

    Tang, Derek M; Koh, Christopher; Twaddell, William S; von Rosenvinge, Erik C; Han, Hyosun

    2015-10-01

    The management and diagnosis of drug-induced liver injury (DILI) is often challenging, particularly when patients are taking multiple medications. We present a 29-year-old African American man who presented with jaundice and malaise after starting bupropion and doxycycline 2 weeks prior. He was found to have acute hepatocellular drug-induced liver injury with autoimmune features, and made a complete recovery with prednisone. Although bupropion and doxycycline are both known to cause liver toxicity, a closer inspection of the signature of liver injury and a review of prior related DILI cases assigns causality more to bupropion than doxycycline. PMID:26504884

  18. Liver injury following blunt abdominal trauma: a new mechanism-driven classification

    OpenAIRE

    Slotta, J. E.; Justinger, C.; Kollmar, O; Kollmar, C.; Schäfer, T.; Schilling, M. K.

    2013-01-01

    Purposes The current classifications for blunt liver trauma focus only on the extent of liver injury. However, these scores are independent from the localization of liver injury and mechanism of trauma. Methods The type of liver injury after blunt abdominal trauma was newly classified as type A when it was along the falciform ligament with involvement of segments IVa/b, III, or II, and type B when there was involvement of segments V–VIII. With the use of a prospectively established database, ...

  19. Signaling mechanisms in alcoholic liver injury: Role of transcription factors,kinases and heat shock proteins

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepatocytes,fibrotic events in liver stellate cells and activation of liver sinusoidal endothelial cells all contribute to alcoholic liver injury. The signaling mechanisms associated with alcoholic liver injury vary based on the cell type involved and the extent of alcohol consumption. In this review we will elucidate the oxidative stress and signaling pathways affected by alcohol in hepatocytes and Kupffer cells in the liver by alcohol. The toll-like receptors and their down-stream signaling events that play an important role in alcohol-induced inflammation will be discussed. Alcohol-induced alterations of various intracellular transcription factors such as NFκB, PPARs and AP-1, as well as MAPK kinases in hepatocytes and macrophages leading to induction of target genes that contribute to liver injury will be reviewed. Finally, we will discuss the significance of heat shock proteins as chaperones and their functional regulation in the liver that could provide new mechanistic insights into the contributions of stress-induced signaling mechanisms in alcoholic liver injury.

  20. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    Science.gov (United States)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  1. Chronic exercise increases insulin binding in muscles but not liver

    International Nuclear Information System (INIS)

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, the authors investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed or fasted state and after an oral glucose tolerance test. Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. Insulin binding to plasma membranes increased in S, P, and EDL but not in WG or in liver. There were insulin binding differences among muscles. Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver

  2. Glutathione treatment protects the rat liver against injury after warm ischemia and Kupffer cell activation

    OpenAIRE

    Bilzer, M.; Baron, A; Schauer, R.; Steib, C.; Ebensberger, S.; Gerbes, Alexander L.

    2002-01-01

    Background/Aim: The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity. Methods: Isolated perfused rat livers were subjected to 1 h of warm is...

  3. Acute Hepatocellular Drug-Induced Liver Injury From Bupropion and Doxycycline

    OpenAIRE

    Derek M Tang; Koh, Christopher; Twaddell, William S.; von Rosenvinge, Erik C; Han, Hyosun

    2015-01-01

    The management and diagnosis of drug-induced liver injury (DILI) is often challenging, particularly when patients are taking multiple medications. We present a 29-year-old African American man who presented with jaundice and malaise after starting bupropion and doxycycline 2 weeks prior. He was found to have acute hepatocellular drug-induced liver injury with autoimmune features, and made a complete recovery with prednisone. Although bupropion and doxycycline are both known to cause liver tox...

  4. FXR: Big fish or small fry for drug-induced liver injury?

    Science.gov (United States)

    Ballet, François

    2016-02-01

    By integrating network analysis and molecular modeling, a "system pharmacology" approach identified FXR as a potential off-target protein mediating non-steroidal anti-inflammatory drugs (NSAID)-induced liver injury. In vitro assays showed that NSAID are potent FXR antagonists that inhibit FXR transcriptional activity. Given the role of FXR in bile acid homeostasis, liver inflammation and cell proliferation, the data suggest that FXR antagonism could mediate, at least in part, NSAID-induced liver injury. PMID:26797115

  5. Prognosis and Biomarkers in Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Mookerjee, Rajeshwar P

    2016-05-01

    As formal definitions of acute-on-chronic liver failure (ACLF) have now been established, and given an increased recognition of the dynamic nature of this condition, there is a growing clinical need to assess prognosis and response to interventions. Conventional scoring systems such as Model for End-Stage Liver Disease (MELD) fail to capture the two key prognostic elements in ACLF-namely, extrahepatic organ failure and measures of systemic inflammation-and as such are limited in their prognostic accuracy. Even the best available scoring systems such as the recently described CLIF (Chronic Liver Failure) Consortium ACLF (CLIF-C ACLF) score, are at best 75% accurate and need to be applicable to all etiologies of liver disease. Thus, in the absence of "gold standard" markers of prognosis that render one scoring system superior to another, there is a need to explore other markers of pathophysiology that may better define outcome. This review addresses the evidence for markers of oxidative stress, including those reflecting the inflammasome; elements of cell death such as cytokeratins M30 and M65; and indicators of immune dysfunction, innate immune failure and gut dysbiosis. Finally, evidence for relevance of markers of organ dysfunction, including hemodynamic response, are explored along with associated mediators such as copeptin, dimethylarginines, and renin. It is anticipated that further critique and validation of emerging and relevant biomarkers will facilitate a composite score which, either alone or in combination with existing scoring systems such as CLIF-C, will enable improved prognostication and targeting of therapy in ACLF. PMID:27172354

  6. The paradox of chronic neuroinflammation, systemic immune suppression and autoimmunity after traumatic chronic spinal cord injury

    OpenAIRE

    Schwab, Jan M.; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G.

    2014-01-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the “immune privileged/specialized” milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of “SCI disease” ...

  7. The antioxidant n-acetylcysteine reduced necrosis, but exacerbated liver fibrosis induced by chronic alcohol in rats fed via total enteral nutrition

    Science.gov (United States)

    Despite many years of research, the molecular mechanisms underlying progression of alcoholic liver injury from simple steatosis through steatohepatitis and fibrosis remain in dispute. In the current study male Sprague-Dawley rats (350 g) were chronically fed a high unsaturated fat diet for 120 d usi...

  8. Non invasive assessment of liver fibrosis in chronic hemodialysis patients with viral hepatitis C

    OpenAIRE

    Arrayhani, Mohamed; Sqalli, Tarik; Tazi, Nada; El Youbi, Randa; Chaouch, Safae; Aqodad, Nourdin; Ibrahimi, Sidi Adil

    2015-01-01

    The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological scores (APRI, Forns and Fib-4), and to measure the correlation between these tests. Cross-sectional study including all chronic hemodialysis patients with hepatitis C...

  9. Revisiting acute liver injury associated with herbalife products.

    Science.gov (United States)

    Appelhans, Kristy; Smith, Casey; Bejar, Ezra; Henig, Y Steve

    2011-10-27

    In the November 27, 2010 issue of the World Journal of Hepatology (WJH), three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products. The reference to Herbalife products as contaminated and generally comparable to all dietary supplements or weight loss products is not scientifically supported. The authors provided an insufficient amount of information regarding patient histories, concomitant medications and other compounds, dechallenge results, and product specifications and usage. This information is necessary to fully assess the association of Herbalife products in the WJH case reports. Therefore, the article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients. PMID:22059112

  10. The Art and Science of Diagnosing and Managing Drug-induced Liver Injury in 2015 and Beyond.

    Science.gov (United States)

    Lewis, James H

    2015-11-01

    Drug-induced liver injury (DILI) remains a leading reason why new compounds are dropped from further study or are the subject of product warnings and regulatory actions. Hy's Law of drug-induced hepatocellular jaundice causing a case-fatality rate or need for transplant of 10% or higher has been validated in several large national registries, including the ongoing, prospective U.S. Drug-Induced Liver Injury Network. It serves as the basis for stopping rules in clinical trials and in clinical practice. Because DILI can mimic all known causes of acute and chronic liver disease, establishing causality can be difficult. Histopathologic findings are often nonspecific and rarely, if ever, considered pathognomonic. A daily drug dose >50-100 mg is more likely to be hepatotoxic than does acetaminophen overdose. Although a number of drugs causing idiosyncratic DILI have HLA associations that may allow for pre-prescription testing to prevent hepatotoxicity, the cost and relatively low frequency of injury among affected patients limit the current usefulness of such genome-wide association studies. Alanine aminotransferase monitoring is often recommended but has rarely been shown to be an effective method to prevent serious DILI. Guidelines on the diagnosis and management of DILI have recently been published, although specific therapies remain limited. The LiverTox Web site has been introduced as an interactive online virtual textbook that makes the latest information on more than 650 agents available to clinicians, regulators, and drug developers alike. PMID:26116527

  11. RUCAM in Drug and Herb Induced Liver Injury: The Update.

    Science.gov (United States)

    Danan, Gaby; Teschke, Rolf

    2016-01-01

    RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common

  12. RUCAM in Drug and Herb Induced Liver Injury: The Update

    Directory of Open Access Journals (Sweden)

    Gaby Danan

    2015-12-01

    Full Text Available RUCAM (Roussel Uclaf Causality Assessment Method or its previous synonym CIOMS (Council for International Organizations of Medical Sciences is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI and herb induced liver injury (HILI. Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality

  13. Liver cirrhosis as a result of chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    A. A. Sukhoruk

    2014-09-01

    Full Text Available The incidence of chronic hepatitis C in St. Petersburg is 124.4 per 100 000 population. The number of patients with liver cirrhosis is significant.Aim of this study: to examine the demographic, clinical and epidemiological characteristics of patients with cirrhosis in the results of chronic hepatitis C.Materials and methods: 100 patients with cirrhosis due to chronic hepatitis C in age 31–70 years were included. Patients with infection hepatitis viruses A and B, HIV, alcohol abuse, drug addicts, previously received antiviral therapy were excluded. Liver cirrhosis was diagnosed on the basis clinical, laboratory and instrumental investigations.Results: most patients (86,2% male and 81,7% female are socially adapted. In 23,2% of patients antibodies to hepatitis C virus were first detected simultaneously with the diagnosis of cirrhosis. Medical procedures were the most common route of infection (25,6% male and 57,1% female. Genotype 1 was dominant (65.7%. Viral load over 800 000 IU/ml was detected in 36,7% of patients. ALT activity was normal or not more than 2 upper limit of normal in 59% of patients, AST – 47%. Normal levels of total bilirubin were recorded in 37% of cases.Conclusions: the first detection of antibodies to hepatitis C virus at the stage of cirrhosis, absence of jaundice, normal or low cytolytic activity once again confirms the need for screening for markers of hepatitis C virus. Dominance of genotype 1 is probably due on the one hand with features routes of transmission, and the other – with the speed of transformation chronic hepatitis to cirrhosis.

  14. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

    OpenAIRE

    Stutchfield, Benjamin M.; Antoine, Daniel J.; Mackinnon, Alison C; Gow, Deborah J; Bain, Calum; Hawley, Catherine A.; Hughes, Michael J.; Francis, Benjamin; Wojtacha, Davina; Man, Tak Y.; Dear, James W.; Devey, Luke R.; Mowat, Alan; Pollard, Jeffrey W; Park, B Kevin

    2015-01-01

    Background & Aims: Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods: We measured levels of CSF1 in serum samples collected from 55 patients who underwent partia...

  15. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Science.gov (United States)

    Udoh, Uduak S.; Valcin, Jennifer A.; Gamble, Karen L.; Bailey, Shannon M.

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases. PMID:26473939

  16. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  17. Why,who and how should perform liver biopsy in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Ioan Sporea; Alina Popescu; Roxana Sirli

    2008-01-01

    Chronic viral hepatitis is a common disease in the general population.During chronic hepatitis,the prognosis and clinical management are highly dependent on the extent of liver fibrosis.The fibrosis evaluation can be performed by FibroTest (using serological markers),by Elastography or FibroScan (a noninvasive percutaneous technique using the elastic properties of the hepatic tissue) and by liver biopsy (LB),considered to be the "gold standard".Currently,there are three techniques for performing LB: percutaneous,transjugular and laparoscopic.The percutaneous LB can be performed blind,ultrasound (US) guided or US assisted.There are two main categories of specialists who perform LB: gastroenterologists (hepatologists) and radiologists,and the specialty of the individual who performs the LB determines if the LB is performed under ultrasound guidance or not.There are two types of biopsy needles used for LB: cutting needles (Tru-Cut,Vim-Silverman) and suction needles (Menghini,Klatzkin,Jamshidi).The rate of major complications after percutaneous LB ranges from 0.09% to 2.3%,but the echoguided percutaneous liver biopsy is a safe method for the diagnosis of chronic diffuse hepatitis (costeffective as compared to blind biopsy) and the rate of complications seems to be related to the experience of the physician and the type of the needle used (Menghini type needle seems to be safer).Maybe,in a few years we will use non-invasive markers of fibrosis,but at this time,most authorities in the field consider that the LB is useful and necessary for the evaluation of chronic hepatopathies,despite the fact that it is not a perfect test.

  18. Anti-TGF-beta strategies for the treatment of chronic liver disease.

    Science.gov (United States)

    Breitkopf, Katja; Haas, Stephan; Wiercinska, Eliza; Singer, Manfred V; Dooley, Steven

    2005-11-01

    Permanent alcohol abuse may lead to chronic liver injury with deleterious sequelae such as liver cirrhosis and hepatocellular carcinoma. Mechanisms of fibrogenesis encompass recruitment of inflammatory cells at the site of injury and cytokine mediated activation of hepatic stellate cells (HSC) with accumulation of interstitial collagens. HSC transdifferentiation and accompanying apoptosis result in destruction of liver architecture and are therefore key steps of disease progression. TGF-beta represents the main profibrogenic cytokine in liver fibrosis and other fibroproliferative disorders by inducing extracellular matrix deposition as part of the wound healing response. In parallel, TGF-beta triggers hepatocytes that are strongly responsive for this cytokine, to undergo apoptosis, thereby providing space for HSC proliferation and generation of a collagenous matrix. Anti TGF-beta approaches were established and successfully utilized for the treatment of experimental fibrogenesis. Dominant negative TGF-beta receptors (TbetaR), generated by fusing the Fc domain of human IgG and the N-terminal (extracellular) fragment of TbetaRII (Fc:TbetaRII) were applied to suppress fibrosis. Similarly TGF-beta binding proteins like decorin, antagonistic cytokines such as bone morphogenetic protein-7, hepatocyte growth factor, IL-10, or IFN-gamma were as efficient as camostat mesilate, a protease inhibitor that possibly abrogated proteolytic activation of TGF-beta. Further, our group recently overexpressed Smad7 in bile duct ligation induced liver fibrosis and achieved efficient inhibition of intracellular TGF-beta signaling, thereby counteracting profibrogenic effects in cultured HSC and in vivo. A direct link between the effect of alcohol and TGF-beta exists through reactive oxygen species that are generated in liver cells by alcohol metabolism and represent activators of TGF-beta signaling. Thus, soluble TbetaRII expression reduced experimental fibrogenesis in vitro and in vivo

  19. Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Anna Del Prete

    2012-01-01

    Full Text Available Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology. The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.

  20. Non-invasive assessment of liver fibrosis in chronic liver diseases: Implementation in clinical practice and decisional algorithms

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani

    2009-01-01

    Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications, including decompensation, bleeding and liver cancer. Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease. Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis, while cirrhosis requires a specific follow-up including screening for esophageal varices and hepatocellular carcinoma. Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive, costly and prone to sampling errors. Recently, blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis. However, there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available. This is due to an unsatisfactory accuracy for some of them, and to an incomplete validation for others. Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they re combined. Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement noninvasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.

  1. Pilot study: bone marrow stem cells as a treatment for dogs with chronic spinal cord injury

    OpenAIRE

    Sarmento, Carlos Alberto Palmeira; Rodrigues, Marcio Nogueira; Bocabello, Renato Zonzini; Mess, Andrea Maria; Miglino, Maria Angelica

    2014-01-01

    Background Chronic Spinal Cord injury is a common, severe, and medically untreatable disease. Since the functional outcomes of acute and experimental chronic spinal cord injury have been shown to improve with stem cell therapy, a case study was conducted to test if the application of stem cell also regenerates chronic SCI dysfunction. Transplantation of foetal bone marrow stem cells was applied in seven dogs with chronic spinal cord injury. Magnetic resonance images and assessments of symptom...

  2. Proteomic analysis of liver in rats chronically exposed to fluoride.

    Directory of Open Access Journals (Sweden)

    Heloísa Aparecida Barbosa da Silva Pereira

    Full Text Available Fluoride (F is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group. At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS. Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.

  3. Warm ischemic injury is reflected in the release of injury markers during cold preservation of the human liver.

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    Bote G Bruinsma

    Full Text Available Liver transplantation plays a pivotal role in the treatment of patients with end-stage liver disease. Despite excellent outcomes, the field is strained by a severe shortage of viable liver grafts. To meet high demands, attempts are made to increase the use of suboptimal livers by both pretransplant recovery and assessment of donor livers. Here we aim to assess hepatic injury in the measurement of routine markers in the post-ischemic flush effluent of discarded human liver with a wide warm ischemic range.Six human livers discarded for transplantation with variable warm and cold ischemia times were flushed at the end of preservation. The liver grafts were flushed with NaCl or Lactated Ringer's, 2 L through the portal vein and 1 L through the hepatic artery. The vena caval effluent was sampled and analyzed for biochemical markers of injury; lactate dehydrogenase (LDH, alanine transaminase (ALT, and alkaline phosphatase (ALP. Liver tissue biopsies were analyzed for ATP content and histologically (H&E examined.The duration of warm ischemia in the six livers correlated significantly to the concentration of LDH, ALT, and ALP in the effluent from the portal vein flush. No correlation was found with cold ischemia time. Tissue ATP content at the end of preservation correlated very strongly with the concentration of ALP in the arterial effluent (P<0.0007, R2 = 0.96.Biochemical injury markers released during the cold preservation period were reflective of the duration of warm ischemic injury sustained prior to release of the markers, as well as the hepatic energy status. As such, assessment of the flush effluent at the end of cold preservation may be a useful tool in evaluating suboptimal livers prior to transplantation, particularly in situations with undeterminable ischemic durations.

  4. Characterization of chemically induced liver injuries using gene co-expression modules.

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    Gregory J Tawa

    Full Text Available Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20% genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

  5. Hepatic pseudoaneurysm after traumatic liver injury; is CT follow-up warranted?

    DEFF Research Database (Denmark)

    Østerballe, Lene; Helgstrand, Frederik; Axelsen, Thomas; Hillingsø, Jens; Svendsen, Lars Bo

    2014-01-01

    INTRODUCTION: Hepatic pseudoaneurysm (HPA) is a rare complication after liver trauma, yet it is potentially fatal, as it can lead to sudden severe haemorrhage. The risk of developing posttraumatic HPA is one of the arguments for performing follow-up CT of patients with liver injuries. The aim of...... this study was to investigate the occurrence of HPA post liver trauma. METHODS: A retrospective study from 2000-2010 of conservatively treated patients with blunt liver trauma was performed to investigate the incidence and nature of HPA. After the initial CT scan patients were admitted to the...... study shows that HPA is not correlated to the severity of liver injury and it develops in 4% of patients after traumatic liver injury. In order to avoid potentially life-threatening haemorrhage from a post trauma hepatic pseudoaneurysm, it seems appropriate to do follow-up CT as part of the conservative...

  6. Is liver biopsy still needed in children with chronic viral hepatitis?

    OpenAIRE

    Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Pluta, Magdalena; Marczyńska, Magdalena

    2015-01-01

    Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the manag...

  7. TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Mee Juhng Jeon; Jong Hee Shin; Soon Pal Suh; Yong Chai Lim; Dong Wook Ryang

    2003-01-01

    AIM: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage.METHODS: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n= 110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n= 19).TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined.RESULTS: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1% of HBsAg-positive donors, 20.3 % of antiHCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1% of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6% of patients with type B chronic liver disease, and 10.5% of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P<0.05),except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7% of TTV DNA-positive patients and 76.9% of HGV RNA-positive patients (P<0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients.CONCLUSION: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant

  8. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway.

    Science.gov (United States)

    Cardin, Romilda; Piciocchi, Marika; Bortolami, Marina; Kotsafti, Andromachi; Barzon, Luisa; Lavezzo, Enrico; Sinigaglia, Alessandro; Rodriguez-Castro, Kryssia Isabel; Rugge, Massimo; Farinati, Fabio

    2014-03-28

    The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation. PMID:24696595

  9. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  10. Protective effect of salvianolate on lung injury induced by ischemia reperfusion injury of liver in mice

    Directory of Open Access Journals (Sweden)

    Zheng-xin WANG

    2011-11-01

    Full Text Available Objective To evaluate the protective effect of salvianolate on lung injury induced by hepatic ischemia reperfusion(IR injury in mice and its underlying mechanisms.Methods A hepatic IR model of mice was reproduced,and 24 animals were assigned into 3 groups(8 each: sham operation(SO group,control group and salvianolate(SV group.Just before ischemia induction,animals in SV group received salvianolate injection at a dose of 60 mg/kg via tail vein,while in control group the mice received normal saline with an equal volume,and in SO group the mice received the same operation as in SV group but without producing liver ischemia.Four hours after reperfusion,the serum,liver and lung tissue were collected.The alanine aminotransferase(ALT and aspartate aminotransferase(AST levels in serum were detected and the histological changes in liver and lung were examined.The wet-to-dry weight ratio of pulmonary tissue was measured.The contents of tumor necrosis factor α(TNF-α,interleukin(IL-6,IL-1β and IL-10 in bronchoalveolar lavage fluid(BALF were detected by enzyme linked immunosorbent assay(ELISA,and the relative mRNA levels of TNF-α,IL-6,IL-1β and IL-10 in pulmonary tissue were analyzed by real-time reverse transcription PCR(RT-PCR.The activaty of transcription factor NF-κB was measured with Western blotting analysis.Results No significant pathologic change was found in mice of SO group.Compared with the mice in control group,those in SV group exhibited lower levels of ALT and AST(P < 0.01,lighter histological changes in liver and lung(P < 0.05,lower levels of wet-to-dry weight ratio of lung tissue(P < 0.05,lower expression levels of TNF-α,IL-6,IL-1β and IL-10 in BALF and lung tissue(P < 0.05 or P < 0.01.Further examination demonstrated that the activity of NF-κB in SV group was significantly down-regulated as compared with that in control group.Conclusion Salvianolate can attenuate lung injury induced by hepatic IR in mice,the mechanism may inclade

  11. Dual Farnesoid X Receptor/TGR5 Agonist INT-767 Reduces Liver Injury in the Mdr2−/− (Abcb4−/−) Mouse Cholangiopathy Model by Promoting Biliary HCO3− Output

    OpenAIRE

    Baghdasaryan, Anna; Claudel, Thierry; Gumhold, Judith; Silbert, Dagmar; Adorini, Luciano; Roda, Aldo; Vecchiotti, Stefania; Gonzalez, Frank J.; Schoonjans, Kristina; Strazzabosco, Mario; Fickert, Peter; Trauner, Michael

    2011-01-01

    Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. The nuclear farnesoid X receptor (FXR) and the membrane G protein-coupled receptor, TGR5, regulate bile acid (BA) homeostasis and inflammation. Therefore, we hypothesized that activation of FXR and/or TGR5 could ameliorate liver injury in Mdr2−/− (Abcb4−/−) mice, a model of chronic cholangiopathy. Hepatic inflammation, fibrosis, as well as bile secretion and key genes of ...

  12. MRI and clinical symptoms in chronic cervical cord injury

    Energy Technology Data Exchange (ETDEWEB)

    Soeda, Shuichi; Maruiwa, Hirofumi; Yokoi, Masahiro; Saitoh, Seiya (Tsukigase Rehabilitation Center, Shizuoka (Japan)); Yamauchi, Kenji

    1992-08-01

    To assess the ability of magnetic resonance (MR) imaging to determine the prognosis of spinal cord injury in the chronic stage and to detect the injured myelomere, 39 patients were examined with MR images obtained by T1-weighted spin echo method 5 months to 4 years and 8 months (mean, one year and 5 months) after they had sustained spinal cord injury. According to hypointensity area of the ventrodorsad diameter of the spinal cord, MR images were classified as non-hypointensity (I), discrete (II), central (III), large cavity (IV), and transverse (V). The most common type was III (25%), followed by IV (26%), II (18%), V (15%), and I (13%). In 21 patients with bone injury, 14 (67%) had type IV or V, in contrast to 2 (11%) of 18 patients without bone injury. Increased hypointensity on MR images was associated with severer injury of the spinal cord. When hypointensity accounted for less than 1/2 of the ventrodorsad diameter of the spinal cord, walking ability was recovered in more than 80% of the patients. When less than 1/3 of the ventrodorsad diameter of the spinal cord was seen as hypointensity, arm function was well preserved, and the anterior horn of gray matter was found less injured. In 60% of the patients, there was difference in the injured level of myelomere between MR images and the neurological examination; the injured level of myelomere tended to be more cephalad level in the neurological examination than MR appearance.(N.K.).

  13. MRI and clinical symptoms in chronic cervical cord injury

    International Nuclear Information System (INIS)

    To assess the ability of magnetic resonance (MR) imaging to determine the prognosis of spinal cord injury in the chronic stage and to detect the injured myelomere, 39 patients were examined with MR images obtained by T1-weighted spin echo method 5 months to 4 years and 8 months (mean, one year and 5 months) after they had sustained spinal cord injury. According to hypointensity area of the ventrodorsad diameter of the spinal cord, MR images were classified as non-hypointensity (I), discrete (II), central (III), large cavity (IV), and transverse (V). The most common type was III (25%), followed by IV (26%), II (18%), V (15%), and I (13%). In 21 patients with bone injury, 14 (67%) had type IV or V, in contrast to 2 (11%) of 18 patients without bone injury. Increased hypointensity on MR images was associated with severer injury of the spinal cord. When hypointensity accounted for less than 1/2 of the ventrodorsad diameter of the spinal cord, walking ability was recovered in more than 80% of the patients. When less than 1/3 of the ventrodorsad diameter of the spinal cord was seen as hypointensity, arm function was well preserved, and the anterior horn of gray matter was found less injured. In 60% of the patients, there was difference in the injured level of myelomere between MR images and the neurological examination; the injured level of myelomere tended to be more cephalad level in the neurological examination than MR appearance.(N.K.)

  14. Blunt liver injury with intact ribs under impacts on the abdomen: a biomechanical investigation.

    Directory of Open Access Journals (Sweden)

    Yu Shao

    Full Text Available Abdominal trauma accounts for nearly 20% of all severe traffic injuries and can often result from intentional physical violence, from which blunt liver injury is regarded as the most common result and is associated with a high mortality rate. Liver injury may be caused by a direct impact with a certain velocity and energy on the abdomen, which may result in a lacerated liver by penetration of fractured ribs. However, liver ruptures without rib cage fractures were found in autopsies in a series of cases. All the victims sustained punches on the abdomen by fist. Many studies have been dedicated to determining the mechanism underlying hepatic injury following abdominal trauma, but most have been empirical. The actual process and biomechanism of liver injury induced by blunt impact on the abdomen, especially with intact ribs remained, are still inexhaustive. In order to investigate this, finite element methods and numerical simulation technology were used. A finite element human torso model was developed from high resolution CT data. The model consists of geometrically-detailed liver and rib cage models and simplified models of soft tissues, thoracic and abdominal organs. Then, the torso model was used in simulations in which the right hypochondrium was punched by a fist from the frontal, lateral, and rear directions, and in each direction with several impact velocities. Overall, the results showed that liver rupture was primarily caused by a direct strike of the ribs induced by blunt impact to the abdomen. Among three impact directions, a lateral impact was most likely to cause liver injury with a minimum punch speed of 5 m/s (the momentum was about 2.447 kg.m/s. Liver injuries could occur in isolation and were not accompanied by rib fractures due to different material characteristics and injury tolerance.

  15. Extracorporeal support for patients with acute and acute on chronic liver failure.

    Science.gov (United States)

    Aron, Jonathan; Agarwal, Banwari; Davenport, Andrew

    2016-04-01

    The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds. PMID:26894968

  16. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl4, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  17. Regulation of drug-metabolizing enzymes by local and systemic liver injuries

    Science.gov (United States)

    Guo, Yan; Hu, Bingfang; Xie, Yang; Billiar, Timothy R.; Sperry, Jason L.; Huang, Min; Xie, Wen

    2016-01-01

    Introduction Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver. Areas covered This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals' sensitivity to local and systemic liver injuries is also discussed. Expert opinion Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients. PMID:26751558

  18. Chronic liver disease questionnaire:Translation and validation in Thais

    Institute of Scientific and Technical Information of China (English)

    Abhasnee Sobhonslidsuk; Chatchawan Silpakit; Ronnachai Kongsakon; Patchareeya Satitpornkul; Chaleaw Sripetch

    2004-01-01

    AIM: Quality of life (QOL) is a concept that incorporates many aspects of life beyond "health". The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL. The objectives of this study were to translate and validate a liver specific questionnaire, the CLDQ.METHODS: The CLDQ was formally translated from the original version to Thai language with permission. The translation process included forward translation, back translation, cross-cultural adaptation and a pretest. Reliability and validity of the translated version was examined in CLD patients. Enrolled subjects included CLD and normal subjects with age- and sex-matched. Collected data were demography,physical findings and biochemical tests. All subjects were asked to complete the translated versions of CLDQ and SF-36, which was previously validated. Cronbach's alpha and test-retest were performed for reliability analysis. One-way Anova or non-parametric method was used to determine discriminant validity. Spearman's rank correlation was used to assess convergent validity. P-value <0.05 was considered statistically significant.RESULTS: A total of 200 subjects were recruited into the study, with 150 CLD and 50 normal subjects. Mean ages (SD) were 47.3(11.7) and 49.1(8.5) years, respectively. The number of chronic hepatitis: cirrhosis was 76:74, and the ratio of cirrhotic patients classified as Child A:B:C was 37(50%): 26(35%): 11(15%). Cronbach's alpha of the overall CLDQ scores was 0.96 and of all domains were higher than0.93. Item-total correlation was >0.45. Test-retest reliability done at 1 to 4 wk apart was 0.88 for the average CLDQ score and from 0.68 to 0.90 for domain scores. The CLDQ was found to have discriminant validity. The highest scores of CLDQ domains were in the normal group, scores were lower in the compensated group and lowest in the decompensated group. The significant correlation between domains of the CLDQ and SF-36 was found

  19. DAMPs-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury

    Science.gov (United States)

    Huang, Hai; Tohme, Samer; Al-Khafaji, Ahmed B; Tai, Sheng; Loughran, Patricia; Chen, Li; Wang, Shu; Kim, Jiyun; Billiar, Timothy; Wang, Yanming; Tsung, Allan

    2015-01-01

    Innate immunity plays a crucial role in the response to sterile inflammation such as liver ischemia/reperfusion (I/R) injury. The initiation of liver I/R injury results in the release of damage associated molecular patterns (DAMPs), which trigger innate immune and inflammatory cascade via pattern recognition receptors. Neutrophils are recruited to the liver after I/R and contribute to the organ damage, innate immune and inflammatory responses. Formation of neutrophil extracellular trap (NET) has been recently found in response to various stimuli. However, the role of NETs during liver I/R injury remains unknown. We show that NETs form in the sinusoids of ischemic liver lobes in vivo. This was associated with increased NET markers, serum level of myeloperoxidase (MPO)-DNA complexes and tissue level of citrullinated-histone H3 compared to control mice. Treatment with peptidyl-arginine-deiminase (PAD) 4 inhibitor or DNase I significantly protected hepatocytes and reduced inflammation after liver I/R as evidenced by inhibition of NET formation, indicating the pathophysiological role of NETs in liver I/R injury. In vitro, NETs increase hepatocyte death and induce Kupffer cells to release proinflammatory cytokines. DAMPs, such as HMGB1 and histones, released by injured hepatocytes stimulate NET formation through Toll-like receptor (TLR4)- and TLR9-MyD88 signaling pathways. After neutrophil depletion in mice, the adoptive transfer of TLR4 knockout (KO) or TLR9 KO neutrophils confers significant protection from liver I/R injury with significant decrease in NET formation. In addition, we found inhibition of NET formation by PAD4 inhibitor or DNase I reduces HMGB1 and histone-mediated liver I/R injury. Conclusion DAMPs released during liver I/R promotes NET formation through TLRs signaling pathway. Development of NETs subsequently exacerbates organ damage and initiates inflammatory responses during liver I/R. PMID:25855125

  20. Chemokines in Chronic Liver Allograft Dysfunction Pathogenesis and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Bin Liu

    2013-01-01

    Full Text Available Despite advances in immunosuppressive drugs, long-term success of liver transplantation is still limited by the development of chronic liver allograft dysfunction. Although the exact pathogenesis of chronic liver allograft dysfunction remains to be established, there is strong evidence that chemokines are involved in organ damage induced by inflammatory and immune responses after liver surgery. Chemokines are a group of low-molecular-weight molecules whose function includes angiogenesis, haematopoiesis, mitogenesis, organ fibrogenesis, tumour growth and metastasis, and participating in the development of the immune system and in inflammatory and immune responses. The purpose of this review is to collect all the research that has been done so far concerning chemokines and the pathogenesis of chronic liver allograft dysfunction and helpfully, to pave the way for designing therapeutic strategies and pharmaceutical agents to ameliorate chronic allograft dysfunction after liver transplantation.

  1. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

    International Nuclear Information System (INIS)

    Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption

  2. Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut.

    Science.gov (United States)

    Araujo, James L; Worman, Howard J

    2015-01-01

    Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts. PMID:25948859

  3. Acute liver injury with severe coagulopathy in marasmus caused by a somatic delusional disorder.

    Science.gov (United States)

    Stein, Lance L; Jesudian, Arun B

    2011-01-01

    Marasmus is a severe form of protein-calorie malnutrition characterized by the depletion of fat stores, muscle wasting, and the lack of edema. In developed countries, marasmus is often the result of anorexia nervosa. Abnormal transaminases with liver synthetic dysfunction have rarely been reported with anorexia nervosa. To our knowledge, we report the first detailed case of acute liver injury with severe coagulopathy (INR > 1.5) in a patient with marasmus due to self-induced calorie restriction caused by a somatic delusional disorder. This case highlights the severity of liver injury that may occur with significant weight loss from self-induced calorie restriction and the rapid normalization of this injury with treatment. It is important for clinicians to be aware of patterns of acute liver injury in patients with severe protein-calorie malnutrition, regardless of the underlying cause. PMID:25954537

  4. Protective effects of geniposide against Tripterygium glycosides (TG)-induced liver injury and its mechanisms.

    Science.gov (United States)

    Wang, Junming; Miao, Mingsan; Qu, Lingbo; Cui, Ying; Zhang, Yueyue

    2016-02-01

    Tripterygium glycosides (TG) are commonly used for basic medicine in curing rheumatoid arthritis but with a high incidence of liver injury. Geniposide (GP) has broad and diverse bioactivities, but until now it is still unknown whether GP can protect against TG-induced liver injury. This study, for the first time, observed the possible protection of GP against TG-induced liver injury in mice and its mechanisms underlying. Oral administration of TG (270 mg/kg) induced significant elevation in the levels of serum alanine / aspartate transaminase (ALT/AST), hepatic malondialdehyde (MDA) and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) (all P tissue repair and regeneration cytokines, was enhanced by GP. Taken together, the current research suggests that GP protects against TG-induced liver injury in mice probably involved during attenuating oxidative stress and inflammation, and promoting tissue repair and regeneration. PMID:26763404

  5. Liver Injury from Herbal, Dietary, and Weight Loss Supplements: a Review.

    Science.gov (United States)

    Zheng, Elizabeth X; Navarro, Victor J

    2015-06-28

    Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury. PMID:26357638

  6. Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies

    Science.gov (United States)

    ORASAN, OLGA HILDA; CIULEI, GEORGE; COZMA, ANGELA; SAVA, MADALINA; DUMITRASCU, DAN LUCIAN

    2016-01-01

    Chronic liver diseases represent a significant public health problem worldwide. The degree of liver fibrosis secondary to these diseases is important, because it is the main predictor of their evolution and prognosis. Hyaluronic acid is studied as a non-invasive marker of liver fibrosis in chronic liver diseases, in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of fibrosis. We review the advantages and limitations of hyaluronc acid, a biomarker, used to manage patients with chronic viral hepatitis B or C infection, non-alcoholic fatty liver disease, HIV-HCV coinfection, alcoholic liver disease, primary biliary cirrhosis, biliary atresia, hereditary hemochromatosis and cystic fibrosis. PMID:27004022

  7. Insulin-like growth factor 1 and growth hormone in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Becker, Povl Ulrik

    1992-01-01

    Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of insulin-like growth factor 1 (IGF-1) is low in patients with chronic liver disease...... mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary, and...... hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver...

  8. LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

    OpenAIRE

    Gabriela P. CORAL; Aline Dal Pozzo ANTUNES; Ana Paula Almeida SERAFINI; ARAUJO, Fernanda B.; Angelo Alves de MATTOS

    2016-01-01

    Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluate...

  9. Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

    OpenAIRE

    Thudi, Kavitha; Yadav, Dhiraj; Sweeney, Kaitlyn; Behari, Jaideep

    2013-01-01

    Background and Goals Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines. Methods We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the...

  10. High prevalence of hepatitis C in Egyptian patients with chronic liver disease.

    OpenAIRE

    Waked, I A; S.M. Saleh; Moustafa, M S; Raouf, A A; Thomas, D. L.; Strickland, G T

    1995-01-01

    The highest prevalence rates of hepatitis C virus infection in the world have been recently reported among Egyptian blood donors and frequent recipients of transfusions and other blood products. This is the first report, however, demonstrating hepatitis C as the most frequent association with chronic liver disease in Egypt. Of 1023 patients referred to the Liver Institute in Menoufia governorate for evaluation of chronic liver disease, 752 (73.5%) had antibodies to hepatitis C compared with 1...

  11. Establishing a cat model of chronic optic nerve compression injury

    Institute of Scientific and Technical Information of China (English)

    Feng Yu; Shaoji Yuan; Rongwei Zhang; Yicheng Lu; Meiqing Lou

    2009-01-01

    BACKGROUND:An animal model of chronic optic nerve injury is necessary to further understand the pathological mechanisms involved.OBJECTIVE:To establish a stabilized,chronic,optic nerve crush model,which is similar to the clinical situation to explore histopathological and optic electrophysiological changes involved in this injury.DESIGN,TIME AND SETTING:A randomized and controlled animal trial was performed at Shanghai Institute of Neurosurgery from May to October 2004.MATERIALS:A BAL3XRAY undetachable balloon and Magic-BD catheter were provided by BLAT,France;JX-2000 biological signal processing system by Second Military Medical University of Chinese PLA,China;inverted phase contrast microscopy by Olympus,Japan.METHODS:A total of twenty normal adult cats were randomly assigned to control (n = 5) and model (n = 15) groups,according to different doses of contrast agent injected through balloons as follows:0.2 mL injection,0.25 mL injection,and 0.35 mL injection,with each group containing 5 animals.Imitating the clinical pterion approach,the optic nerves were exposed using micro-surgical methods.An engorged undetachable balloon was implanted beneath the nerve and connected to a catheter.Balloon size was controlled with a contrast agent injection (0.1 mL/10 min) to form an occupying lesion model similar to sellar tumors.MAIN OUTCOME MEASURES:The visually evoked potential examination was used to study optical electrophysiology changes in pre-post chronic optical nerve injury.Ultrastructural pathological changes to the optic nerve were analyzed by electron microscopy.RESULTS:During the early period (day 11 after modeling),visually evoked potential demonstrated no significant changes.In the late period (day 51 after modeling),recorded VEP demonstrated that P1 wave latency was prolonged and P1 wave amplitude was obviously reduced.Following injury,the endoneurium,myelin sheath,lamella,axolemma,and axon appeared disordered.CONCLUSION:Results demonstrated that the chronic

  12. Coagulation abnormalities in patients with chronic liver disease in Pakistan

    International Nuclear Information System (INIS)

    Objective: To determine the coagulation abnormalities and relationship between abnormal clotting tests and the risk of gastrointestinal bleeding (GI) among chronic liver disease (CLD) patients admitted at a tertiary care hospital in Pakistan. Methods: Adult CLD patients admitted at Liaquat University Hospital Jamshoro, during Nov 2004 - Oct 2005, were included in the study. The patients blood were tested for coagulation abnormalities including prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count and plasma fibrinogen. Association was seen between the abnormal clotting tests and the gastrointestinal bleeding by calculating relative risk (RR) with 95% confidence interval. Results: PT was prolonged in 88% and aPTT was raised in 71% cases of CLD. Both PT and aPTT were prolonged in 67% CLD cases. Approximately 37% CLD cases had decreased platelet count and 15% cases had decreased serum fibrinogen level. Relative risk of GI bleeding with abnormal clotting tests in CLD cases were weakly positive for PT (RR = 1.02; 95% CI, 0.49-2.10), negative for aPTT (RR=0.83; 95% CI, 0.47-1.45), strongly positive for decreased platelet counts (RR = 1.96; 95% CI, 1.08-3.56) and also for decreased fibrinogen level (RR = 1.47; 95% CI, 0.64-3.35). Conclusion: Coagulation abnormalities were profound in CLD. Decrease platelet counts and fibrinogen levels were related with GI bleeding but PT and aPTT were not significantly related with GI bleeding in patients with chronic liver disease. Nevertheless, these parameters (PT and aPTT) were still used as prognostic markers. (author)

  13. Assessing liver injury associated with antimycotics:Concise literature review and clues from data mining of the FAERS database

    Institute of Scientific and Technical Information of China (English)

    Emanuel; Raschi; Elisabetta; Poluzzi; Ariola; Koci; Paolo; Caraceni; Fabrizio; De; Ponti

    2014-01-01

    AIM: To inform clinicians on the level of hepatotoxicrisk among antimycotics in the post-marketing setting,following the marketing suspension of oral ketocon-azole for drug-induced liver injury(DILI).METHODS: The publicly available international FAERSdatabase(2004-2011) was used to extract DILI cases(including acute liver failure events), where antimycot-ics with systemic use or potential systemic absorptionwere reported as suspect or interacting agents. The re-porting pattern was analyzed by calculating the report-ing odds ratio and corresponding 95%CI, a measure ofdisproportionality, with time-trend analysis where ap-propriate.RESULTS: From 1687284 reports submitted over the8-year period, 68115 regarded liver injury. Of these,2.9% are related to antimycotics(1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics(including ketoconazole and the newer triazole deriva-tives voriconazole and posaconazole) and terbinafine(used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-market-ing signal of risk.CONCLUSION: Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is con-sidered, especially in critical poly-treated patients under chronic treatment.

  14. Diagnosis and Management of Drug-Induced Liver Injury (DILI) in Patients with Pre-Existing Liver Disease.

    Science.gov (United States)

    Teschke, Rolf; Danan, Gaby

    2016-08-01

    The relationship between drugs and pre-existing liver disease is complex, particularly when increased liver tests (LTs) or new symptoms emerge in patients with pre-existing liver disease during drug therapy. This requires two strategies to assess whether these changes are due to drug-induced liver injury (DILI) as a new event or due to flares of the underlying liver disease. Lacking a valid diagnostic biomarker, DILI is a diagnosis of exclusion and requires causality assessment by RUCAM, the Roussel Uclaf Causality Assessment Method, to establish an individual causality grading of the suspected drug(s). Flares of pre-existing liver disease can reliably be assessed in some hepatotropic virus infections by polymerase chain reaction (PCR) and antibody titers at the beginning and in the clinical course to ascertain flares during the natural course of the disease. Unfortunately, flares cannot be verified in many other liver diseases such as alcoholic liver disease, since specific tests are unavailable. However, such a diagnostic approach using RUCAM applied to suspected DILI cases includes clinical and biological markers of pre-existing liver diseases and would determine whether drugs or underlying liver diseases caused the LT abnormalities or the new symptoms. More importantly, a clear diagnosis is essential to ensure effective disease management by drug cessation or specific treatment of the flare up due to the underlying disease. PMID:27091053

  15. Fibrin glue eliminates the need for packing after complex liver injuries.

    OpenAIRE

    Feinstein, A. J.; Varela, J. E.; Cohn, S M; Compton, R. P.; McKenney, M. G.

    2001-01-01

    Hemostasis after traumatic liver injury can be extremely difficult to obtain, particularly in coagulopathic patients who have suffered extensive liver damage. We determined the ability of a fibrin glue preparation (FG) to terminate ongoing bleeding using a new, clinically relevant porcine model of complex hepatic injury. Anesthetized swine (n = 6, 18 to 19 kg) received an external blast to the right upper abdomen and were immediately anticoagulated with intravenous heparin (200 u/kg). Uncontr...

  16. A case of amoxicillin-induced hepatocellular liver injury with bile-duct damage

    OpenAIRE

    Kim, Ju Seung; Jang, Young Rock; Lee, Ji Won; Kim, Jin Yong; Jung, Young Kul; Chung, Dong Hae; Kwon, Oh Sang; Kim, Yun Soo; Choi, Duck Joo; Kim, Ju Hyun

    2011-01-01

    Amoxicillin, an antibiotic that is widely prescribed for various infections, is associated with a very low rate of drug-induced liver injury; hepatitis and cholestasis are rare complications. Here we present a case of a 39-year-old woman who was diagnosed with abdominal actinomycosis and received amoxicillin treatment. The patient displayed hepatocellular and bile-duct injury, in addition to elevated levels of liver enzymes. The patient was diagnosed with amoxicillin-induced cholestatic hepat...

  17. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

    OpenAIRE

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both ...

  18. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria

    OpenAIRE

    Han, Derick; Dara, Lily; Win, Sanda; Than, Tin Aung; Yuan, Liyun; Abbasi, Sadeea Q; Liu, Zhang-Xu; Kaplowitz, Neil

    2013-01-01

    Drugs that cause liver injury often “stress” mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and erythroid 2-related factor 2 (Nrf-2), a transcription factor that upregulates antioxidant defenses. Due to adaptation, drugs alone rarely cause liver injury, with acetaminophen being the notable excep...

  19. Internal vacuum-assisted closure device in the swine model of severe liver injury

    OpenAIRE

    Everett Christopher B; Thomas Bruce W; Moncure Michael

    2012-01-01

    Abstract Objectives The authors present a novel approach to nonresectional therapy in major hepatic trauma utilizing intraabdominal perihepatic vacuum assisted closure (VAC) therapy in the porcine model of Grade V liver injury. Methods A Grade V injury was created in the right lobe of the liver in a healthy pig. A Pringle maneuver was applied (4.5 minutes total clamp time) and a vacuum assisted closure device was placed over the injured lobe and connected to suction. The device consisted of a...

  20. The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

    OpenAIRE

    Jeschke, Marc G.

    2009-01-01

    Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury....

  1. The pathophysiology of thrombocytopenia in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Mitchell O

    2016-04-01

    Full Text Available Oscar Mitchell,1 David M Feldman,1,2 Marla Diakow,1 Samuel H Sigal3 1Department of Medicine, 2Division of Gastroenterology and Liver Diseases, New York University School of Medicine, Langone Medical Center, New York, 3Division of Gastroenterology and Liver Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA Abstract: Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CLD. In addition to being an indicator of advanced disease and poor prognosis, it frequently prevents crucial interventions. Historically, thrombocytopenia has been attributed to hypersplenism, which is the increased pooling of platelets in a spleen enlarged by congestive splenomegaly secondary to portal hypertension. Over the past decade, however, there have been significant advances in the understanding of thrombopoiesis, which, in turn, has led to an improved understanding of thrombocytopenia in cirrhosis. Multiple factors contribute to the development of thrombocytopenia and these can broadly be divided into those that cause decreased production, splenic sequestration, and increased destruction. Depressed thrombopoietin levels in CLD, together with direct bone marrow suppression, result in a reduced rate of platelet production. Thrombopoietin regulates both platelet production and maturation and is impaired in CLD. Bone marrow suppression can be caused by viruses, alcohol, iron overload, and medications. Splenic sequestration results from hypersplenism. The increased rate of platelet destruction in cirrhosis also occurs through a number of pathways: increased shear stress, increased fibrinolysis, bacterial translocation, and infection result in an increased rate of platelet aggregation, while autoimmune disease and raised titers of antiplatelet immunoglobulin result in the immunologic destruction of platelets. An in-depth understanding of the complex

  2. Calpain 2-mediated autophagy defect increases susceptibility of fatty livers to ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Q; Guo, Z; Deng, W; Fu, S; Zhang, C; Chen, M; Ju, W; Wang, D; He, X

    2016-01-01

    Hepatic steatosis is associated with significant morbidity and mortality after liver resection and transplantation. This study focuses on the role of autophagy in regulating sensitivity of fatty livers to ischemia and reperfusion (I/R) injury. Quantitative immunohistochemistry conducted on human liver allograft biopsies showed that, the reduction of autophagy markers LC3 and Beclin-1 at 1 h after reperfusion, was correlated with hepatic steatosis and poor survival of liver transplant recipients. In animal studies, western blotting and confocal imaging analysis associated the increase in sensitivity to I/R injury with low autophagy activity in fatty livers. Screening of autophagy-related proteins showed that Atg3 and Atg7 expression levels were marked decreased, whereas calpain 2 expression was upregulated during I/R in fatty livers. Calpain 2 inhibition or knockdown enhanced autophagy and suppressed cell death. Further point mutation experiments revealed that calpain 2 cleaved Atg3 and Atg7 at Atg3Δ92-97 and Atg7Δ344-349, respectively. In vivo and in vitro overexpression of Atg3 or Atg7 enhanced autophagy and suppressed cell death after I/R in fatty livers. Collectively, calpain 2-mediated degradation of Atg3 and Atg7 in fatty livers increases their sensitivity to I/R injury. Increasing autophagy may ameliorate fatty liver damage and represent a valuable method to expand the liver donor pool. PMID:27077802

  3. Prediction of compensated liver cirrhosis by ultrasonography and routine blood tests in patients with chronic viral hepatitis

    OpenAIRE

    Lee, Hong Sub; Kim, Jai Keun; Cheong, Jae Youn; Han, Eun Jin; An, So-Yeon; Song, Jun Ha; Jung, Yun Jung; Jeon, Sung Chan; Jung, Min Wook; Jang, Eun-Jung; Cho, Sung Won

    2010-01-01

    Background/Aims Liver biopsy is a standard method for diagnosis of liver cirrhosis in patients with chronic hepatitis. Because liver biopsy is an invasive method, non-invasive methods have been used for diagnosis of compensated liver cirrhosis in patients with chronic hepatitis. The current study was designed to evaluate the usefulness of ultrasonography and routine blood tests for diagnosis of compensated liver cirrhosis in patients with chronic viral hepatitis. Methods Two hundred three pat...

  4. Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases

    DEFF Research Database (Denmark)

    Almdal, T; Schroeder, T; Ranek, L

    1989-01-01

    the patients, without any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease.......The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method......, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF...

  5. Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury.

    Science.gov (United States)

    Yao, Lu; Chen, Weina; Han, Chang; Wu, Tong

    2016-06-01

    Microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme for the synthesis of prostaglandin E2 (PGE2), a proproliferative and antiapoptotic lipid molecule important for tissue regeneration and injury repair. In this study, we developed transgenic (Tg) mice with targeted expression of mPGES-1 in the liver to assess Fas-induced hepatocyte apoptosis and acute liver injury. Compared with wild-type (WT) mice, the mPGES-1 Tg mice showed less liver hemorrhage, lower serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, less hepatic necrosis/apoptosis, and lower level of caspase cascade activation after intraperitoneal injection of the anti-Fas antibody Jo2. Western blotting analysis revealed increased expression and activation of the serine/threonine kinase Akt and associated antiapoptotic molecules in the liver tissues of Jo2-treated mPGES-1 Tg mice. Pretreatment with the mPGES-1 inhibitor (MF63) or the Akt inhibitor (Akt inhibitor V) restored the susceptibility of the mPGES-1 Tg mice to Fas-induced liver injury. Our findings provide novel evidence that mPGES-1 prevents Fas-induced liver injury through activation of Akt and related signaling and suggest that induction of mPGES-1 or treatment with PGE2 may represent important therapeutic strategy for the prevention and treatment of Fas-associated liver injuries. PMID:27102561

  6. A metabolomic perspective of griseofulvin-induced liver injury in mice.

    Science.gov (United States)

    Liu, Ke; Yan, Jiong; Sachar, Madhav; Zhang, Xinju; Guan, Ming; Xie, Wen; Ma, Xiaochao

    2015-12-01

    Griseofulvin (GSF) causes hepatic porphyria in mice, which mimics the liver injury associated with erythropoietic protoporphyria (EPP) in humans. The current study investigated the biochemical basis of GSF-induced liver injury in mice using a metabolimic approach. GSF treatment in mice resulted in significant accumulations of protoporphyrin IX (PPIX), N-methyl PPIX, bile acids, and glutathione (GSH) in the liver. Metabolomic analysis also revealed bioactivation pathways of GSF that contributed to the formation of GSF-PPIX, GSF-GSH and GSF-proline adducts. GSF-PPIX is the precursor of N-methyl PPIX. A six-fold increase of N-methyl PPIX was observed in the liver of mice after GSF treatment. N-methyl PPIX strongly inhibits ferrochelatase, the enzyme that converts PPIX to heme, and leads to PPIX accumulation. Excessive PPIX in the liver results in bile duct blockage and disturbs bile acid homeostasis. The accumulation of GSH in the liver was likely due to Nrf2-mediated upregulation of GSH synthesis. In summary, this study provides the biochemical basis of GSF-induced liver injury that can be used to understand the pathophysiology of EPP-associated liver injury in humans. PMID:26343413

  7. Ligularia fischeri extract attenuates liver damage induced by chronic alcohol intake.

    Science.gov (United States)

    Kim, Dongyeop; Kim, Gyeong-Woo; Lee, Seon-Ho; Han, Gi Dong

    2016-08-01

    Context Ligularia fischeri (Ledebour) Turcz. (Compositae) has been used as a leafy vegetable and in traditional medicine to treat hepatic disorder in East Asia. Objective The present study explores the antioxidant activity of LF aqueous extract on EtOH-induced oxidative stress accompanied by hepatotoxicity both in vitro and in vivo. Materials and methods In vitro study using the mouse liver NCTC-1469 cell line was conducted to estimate the cytotoxicity as well as the inhibitory effect of LF extract against alcohol-treated cell damage. In vivo study used an alcohol-fed Wister rat model orally administered EtOH (3.95 g/kg of body weight/d) with or without LF extract (100 or 200 mg/kg body weight) for 6 weeks. Serum and liver tissue were collected to evaluate hepatic injury and antioxidant-related enzyme activity. Results The EC50 value for the DPPH radical scavenging capacity of LF extract was 451.5 μg/mL, whereas the IC50 value of LF extract in terms of EtOH-induced reactive oxygen species (ROS) generation was 98.3 μg/mL without cell cytotoxicity. LF extract (200 mg/kg body weight) significantly reduced the triglyceride content of serum (33%) as well as hepatic lipid peroxidation (36%), whereas SOD activity was elevated three-fold. LF extract suppressed expression of CYP2E1 and TNF-α, and attenuated alcohol-induced abnormal morphological changes. Discussion and conclusion LF extract attenuated liver damage induced by alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the liver by LF extract mitigated hepatic disorder following chronic alcohol intake. PMID:26799831

  8. Evaluation of the liver function for patients with chronic liver diseases using 99mTc-galactosyl human serum albumin [99mTc-GSA] liver scintigraphy

    International Nuclear Information System (INIS)

    99mTc-galactosyl human serum albumin [99mTc-GSA] is a new scintigraphic agent which binds specifically to asialoglycoprotein-receptor on the hepatic cell membrane. The new liver scintigraphy using 99mTc-GSA was performed in 30 patients with chronic liver disease to evaluate the residual liver function. Two parameters were obtained from 99mTc-GSA time activity curves of both the heart and the liver. One was [HH15] (clearance index), which was the ratio of radioactivity of the liver at 15 min over that at 3 min after injection. The other was [LHL15] (receptor index), the ratio of radioactivity of the liver over that of the liver plus heart at 15 min. Significant decrease in LHL15 and increase in HH15 value were observed in accordance with severities of the liver damage and clinical aggravation. These parameters correlated significantly with Child-Pugh score, glucagon test, ICG-R15, serum albumin levels, cholinesterase, prothrombin time and hepaplastin test also. In conclusion, these findings indicate that 99mTc-GSA liver scintigraphy is useful for evaluating the liver flunction in patients with chronic liver disease. (author)

  9. Radioisotopic examinations of the functional state of reticuloendothelial cells of the liver in chronic bronchitis

    International Nuclear Information System (INIS)

    Radioisotopic hepatography carried out in 65 patients with chronic obstructive bronchitis and respiratory insufficiency (grades 1-2 and 3) at the phase of remission revealed disorders of the liver circulation and absorptive capacity of reticuloendothelial liver cells. There was a direct dependence between the degree of liver circulation disorders, inhibition of absorptive function of the reticuloendothelial cells of the liver and degree of respiratory insufficiency in these patients

  10. Colchicine reduces procollagen Ⅲ and increases pseudocholinesterase in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Sergio; Muntoni; Marcos; Rojkind; Sandro; Muntoni

    2010-01-01

    AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patient...

  11. Protective effects of ω-3 PUFA on the second liver injury in rats with traumatic brain injury and hemorrhagic shock

    Institute of Scientific and Technical Information of China (English)

    许会彬

    2014-01-01

    Objective To investigate the effects of preconditioning withω-3 polyunsaturated fatty acid(ω-3 PUFA)on the second liver injury in rats with traumatic brain injury and hemorrhagic shock(TBIS)and explore the underlying mechanism.Methods Total of 36 male Wistar rats were assigned randomly(random number)into 3 groups(n=12 in each):sham

  12. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  13. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    International Nuclear Information System (INIS)

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport

  14. Liver fibrosis of patients with chronic viral hepatitis B+C

    OpenAIRE

    Sarsekeyeva Nazgul Yesentaevna

    2015-01-01

    The article deals with the problem of combined chronic viral hepatitis B and C. The paper presents the results of clinical and laboratory studies of patients with chronic viral hepatitis B+C. The author analyzes the results of liver elastomers in patients with chronic viral hepatitis B+C.

  15. Alterations in the Rat Serum Proteome During Liver Injury from Acetaminophen Exposure

    OpenAIRE

    Merrick, B. Alex; Bruno, Maribel E.; Madenspacher, Jennifer H.; Wetmore, Barbara A.; Foley, Julie; Pieper, Rembert; Zhao, Ming; Makusky, Anthony J.; McGrath, Andrew M.; ZHOU, JEFF X.; Taylor, John; Tomer, Kenneth B.

    2006-01-01

    Changes in the serum proteome were identified during early, fulminant and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, non-injury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 hr to 120 hr. Two-dimensional gel electrophoresis of immunodepleted serum separated about 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum ALT/AST levels and histopatho...

  16. Redox factor-1 may mediate the repair of multiple organ injuries after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    SUN Zhi-peng; ZHU Yu-bing; Aminbuhe; GONG Ke; ZHU Bin; FAN Qing; LIAN Dong-bo

    2013-01-01

    Background Apurinic apyrimidinic endonuclease/redox effector factor 1 (APE1/Ref-1) is an important enzyme in the repair of reactive oxygen species-induced DNA damage,and its expression/activation can be induced by reactive oxygen species.The aim of this research was to investigate the relationship between multiple-organ injuries and expression of Ref-1 in the early period after liver transplantation.Methods One hundred and fifty adult male Wistar rats were divided randomly into three groups:liver transplantation,sham surgery,and untreated control.After liver transplantation,animals were sacrificed at different time points.Hepatic and renal functions were analyzed by serology.Histology,apoptotic levels,and Ref-1 expression were examined by immunohistochemistry in the liver,kidneys,intestines,and lungs.Results Serum levels of alanine aminotransferase and aspartate aminotransferase peaked 6 hours after liver transplantation and decreased appreciably after 12 hours in the transplantation group,suggesting that the degree of liver injury in the early period after transplantation peaked at 6 hours and then decreased.Pathological analyses showed that hepatic tissues were more severely injured in the transplantation group than in the sham and untreated groups.A considerable number of infiltrating inflammatory cells was observed around the portal vein in the transplantation group.Injuries to the kidneys,intestines,and lungs were milder after liver transplantation.Apoptotic levels increased after liver transplantation in all four organs examined.Ref-1 expression was higher in the transplantation group in the early period after liver transplantation than in the sham surgery and untreated control groups.Conclusion Ref-1 expression induced by ischemia-reperfusion injury may have a critical role in repairing multiple-organ injuries after liver transplantation.

  17. Carbon tetrachloride-induced liver injury in the rabbit.

    OpenAIRE

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J.A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h...

  18. The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury.

    Science.gov (United States)

    Schwab, Jan M; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G

    2014-08-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the "immune privileged/specialized" milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of "SCI disease" and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because inflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, "compartimentalized" investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS are influenced by systemic immune challenges and that the immune system is 'hardwired' into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and "neurogenic" spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired "host-defense" and trauma-induced autoimmunity. PMID:25017893

  19. Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.

    Directory of Open Access Journals (Sweden)

    Arya J Bahrami

    Full Text Available Liver fibrosis is mediated by hepatic stellate cells (HSCs, which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR-mediated signaling, via endothelin-1 (ET-1 and angiotensin II (AngII, increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5, an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs. Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury.

  20. Internal vacuum-assisted closure device in the swine model of severe liver injury

    Directory of Open Access Journals (Sweden)

    Everett Christopher B

    2012-12-01

    Full Text Available Abstract Objectives The authors present a novel approach to nonresectional therapy in major hepatic trauma utilizing intraabdominal perihepatic vacuum assisted closure (VAC therapy in the porcine model of Grade V liver injury. Methods A Grade V injury was created in the right lobe of the liver in a healthy pig. A Pringle maneuver was applied (4.5 minutes total clamp time and a vacuum assisted closure device was placed over the injured lobe and connected to suction. The device consisted of a perforated plastic bag placed over the liver, followed by a 15 cm by 15cm VAC sponge covered with a nonperforated plastic bag. The abdomen was closed temporarily. Blood loss, cardiopulmonary parameters and bladder pressures were measured over a one-hour period. The device was then removed and the animal was euthanized. Results Feasibility of device placement was demonstrated by maintenance of adequate vacuum suction pressures and seal. VAC placement presented no major technical challenges. Successful control of ongoing liver hemorrhage was achieved with the VAC. Total blood loss was 625 ml (20ml/kg. This corresponds to class II hemorrhagic shock in humans and compares favorably to previously reported estimated blood losses with similar grade liver injuries in the swine model. No post-injury cardiopulmonary compromise or elevated abdominal compartment pressures were encountered, while hepatic parenchymal perfusion was maintained. Conclusion These data demonstrate the feasibility and utility of a perihepatic negative pressure device for the treatment of hemorrhage from severe liver injury in the porcine model.

  1. Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study.

    Science.gov (United States)

    Douros, Antonios; Bronder, Elisabeth; Andersohn, Frank; Klimpel, Andreas; Kreutz, Reinhold; Garbe, Edeltraut; Bolbrinker, Juliane

    2016-01-01

    Herb-induced liver injury (HILI) has recently attracted attention due to increasing reports of hepatotoxicity associated with use of phytotherapeutics. Here, we present data on HILI from the Berlin Case-Control Surveillance Study. The study was initiated in 2000 to investigate the serious toxicity of drugs including herbal medicines. Potential cases of liver injury were ascertained in more than 180 Departments of all 51 Berlin hospitals from October 2002 to December 2011. Drug or herb intake was assessed through a standardized face-to-face interview. Drug or herbal aetiology was assessed based on the updated Council for International Organizations of Medical Sciences scale. In ten of all 198 cases of hepatotoxicity included in the study, herbal aetiology was assessed as probable (once ayurvedic herb) or possible (Valeriana five times, Mentha piperita once, Pelargonium sidoides once, Hypericum perforatum once, Eucalyptus globulus once). Mean age was 56.4 ± 9.7 years, and the predominant pattern of liver injury was hepatocellular. No cases of acute liver failure or death were observed. This case series corroborates known risks for ayurvedic herbs, supports the suspected association between Valeriana use and liver injury, and indicates a hepatotoxic potential for herbs such as Pelargonium sidoides, Hypericum perforatum or Mentha piperita that were rarely associated with liver injury before. However, given that possible causality does not prove clinical significance, further studies in this field are needed. PMID:26784183

  2. Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study

    Directory of Open Access Journals (Sweden)

    Antonios Douros

    2016-01-01

    Full Text Available Herb-induced liver injury (HILI has recently attracted attention due to increasing reports of hepatotoxicity associated with use of phytotherapeutics. Here, we present data on HILI from the Berlin Case-Control Surveillance Study. The study was initiated in 2000 to investigate the serious toxicity of drugs including herbal medicines. Potential cases of liver injury were ascertained in more than 180 Departments of all 51 Berlin hospitals from October 2002 to December 2011. Drug or herb intake was assessed through a standardized face-to-face interview. Drug or herbal aetiology was assessed based on the updated Council for International Organizations of Medical Sciences scale. In ten of all 198 cases of hepatotoxicity included in the study, herbal aetiology was assessed as probable (once ayurvedic herb or possible (Valeriana five times, Mentha piperita once, Pelargonium sidoides once, Hypericum perforatum once, Eucalyptus globulus once. Mean age was 56.4 ± 9.7 years, and the predominant pattern of liver injury was hepatocellular. No cases of acute liver failure or death were observed. This case series corroborates known risks for ayurvedic herbs, supports the suspected association between Valeriana use and liver injury, and indicates a hepatotoxic potential for herbs such as Pelargonium sidoides, Hypericum perforatum or Mentha piperita that were rarely associated with liver injury before. However, given that possible causality does not prove clinical significance, further studies in this field are needed.

  3. Ethanol extracts of Scutellaria baicalensis protect against lipopolysaccharide-induced acute liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Hai Nguyen Thanh; Hue Pham Thi Minh; Tuan Anh Le; Huong Duong Thi Ly; Tung Nguyen Huu; Loi Vu Duc; Thu Dang Kim; Tung Bui Thanh

    2015-01-01

    To investigated the protective potential of ethanol extracts of Scutellaria baicalensis (S. baicalensis ) against lipopolysaccharide (LPS)-induced liver injury. Methods: Dried roots of S. baicalensis were extracted with ethanol and concentrated to yield a dry residue. Mice were administered 200 mg/kg of the ethanol extracts orally once daily for one week. Animals were subsequently administered a single dose of LPS (5 mg/kg of body weight, intraperitoneal injection). Both protein and mRNA levels of cytokines, such as tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in liver tissues were evaluated by ELISA assay and quantitative PCR. Cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB protein levels in liver tissues were analyzed by western blotting. Results: Liver injury induced by LPS significantly increased necrosis factor alpha, interleukin-1β, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB in liver tissues. Treatment with ethanol extracts of S. baicalensis prevented all of these observed changes associated with LPS-induced injury in liver mice. Conclusions: Our study showed that S. baicalensis is potentially protective against LPS-induced liver injury in mice.

  4. Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

    Directory of Open Access Journals (Sweden)

    Lili Ji

    Full Text Available Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

  5. The Role of Iron and Iron Overload in Chronic Liver Disease

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  6. The Role of Iron and Iron Overload in Chronic Liver Disease.

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  7. Severe starvation-induced hepatocyte autophagy as a cause of acute liver injury in anorexia nervosa: a case report.

    Science.gov (United States)

    Restellini, S; Spahr, L; Rubbia Brandt, L

    2013-01-01

    Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common causes of liver injury, the patient was carefully refed. As liver tests remained abnormal, liver biopsy was performed. At histology and electron microscopy, numerous signs suggestive of starvation-induced hepatocyte autophagy were found. Discussion. Severe starvation can be associated with acute liver injury that is slowly reversible with careful enteral nutrition. In this clinical situation, profound hepatic glycogen depletion in association with autophagy appears as the leading cause of liver injury. PMID:25379300

  8. Baicalein pretreatment reduces liver ischemia/reperfusion injury via induction of autophagy in rats.

    Science.gov (United States)

    Liu, Anding; Huang, Liang; Guo, Enshuang; Li, Renlong; Yang, Jiankun; Li, Anyi; Yang, Yan; Liu, Shenpei; Hu, Jifa; Jiang, Xiaojing; Dirsch, Olaf; Dahmen, Uta; Sun, Jian

    2016-01-01

    We previously demonstrated that baicalein could protect against liver ischemia/reperfusion (I/R) injury in mice. The exact mechanism of baicalein remains poorly understood. Autophagy plays an important role in protecting against I/R injury. This study was designed to determine whether baicalein could protect against liver I/R injury via induction of autophagy in rats. Baicalein was intraperitoneally injected 1 h before warm ischemia. Pretreatment with baicalein prior to I/R insult significantly blunted I/R-induced elevations of serum aminotransferase levels and significantly improved the histological status of livers. Electron microscopy and expression of the autophagic marker LC3B-II suggested induction of autophagy after baicalein treatment. Moreover, inhibition of the baicalein-induced autophagy using 3-methyladenine (3-MA) worsened liver injury. Furthermore, baicalein treatment increased heme oxygenase (HO)-1 expression, and pharmacological inhibition of HO-1 with tin protoporphyrin IX (SnPP) abolished the baicalein-mediated autophagy and the hepatocellular protection. In primary rat hepatocytes, baicalein-induced autophagy also protected hepatocytes from hypoxia/reoxygenation injury in vitro and the beneficial effect was abrogated by 3-MA or Atg7 siRNA, respectively. Suppression of HO-1 activity by SnPP or HO-1 siRNA prevented the baicalein-mediated autophagy and resulted in increased hepatocellular injury. Collectively, these results suggest that baicalein prevents hepatocellular injury via induction of HO-1-mediated autophagy. PMID:27150843

  9. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  10. Kupffer cell-mediated exacerbation of methimazole-induced acute liver injury in rats.

    Science.gov (United States)

    Akai, Sho; Uematsu, Yasuaki; Tsuneyama, Koichi; Oda, Shingo; Yokoi, Tsuyoshi

    2016-05-01

    Methimazole (MTZ), an anti-thyroid drug, is known to cause liver injury in humans. It has been demonstrated that MTZ-induced liver injury in Balb/c mice is accompanied by T helper (Th) 2 cytokine-mediated immune responses; however, there is little evidence for immune responses associated with MTZ-induced liver injury in rats. To investigate species differences in MTZ-induced liver injury, we administered MTZ with a glutathione biosynthesis inhibitor, L-buthionine-S,R-sulfoximine (BSO), to F344 rats and subsequently observed an increase in plasma alanine aminotransferase (ALT) and high-mobility group box 1 (HMGB1), which are associated with hepatic lesions. The hepatic mRNA expression of innate immune-related genes significantly increased in BSO- and MTZ-treated rats, but the change in Th2-related genes was not much greater than the change observed in the previous mouse study. Moreover, an increase in Kupffer cells and an induction of the phosphorylation of extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) proteins were accompanied by an increase in Toll-like receptor 4 (TLR4) expression, indicating that Kupffer cell activation occurs through HMGB1-TLR4 signaling. To elucidate the mechanism of liver injury in rats, gadolinium chloride, which inactivates the function of Kupffer cells, was administered before BSO and MTZ administration. The gadolinium chloride treatment significantly suppressed the increased ALT, which was accompanied by decreased hepatic mRNA expression related to innate immune responses and ERK/JNK phosphorylation. In conclusion, Kupffer cell-mediated immune responses are crucial factors for the exacerbation of MTZ-induced liver injury in rats, indicating apparent species differences in the immune-mediated exacerbation of liver injury between mice and rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26177832

  11. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    Science.gov (United States)

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application. PMID:26617183

  12. Evaluation of the liver function for patients with chronic liver damage using 99mTc-galactosyl human serum albumin

    International Nuclear Information System (INIS)

    99mTc-Galactosyl human serum albumin (99mTc-GSA) is a new liver imaging radiopharmaceutical which specifically binds to the asialoglycoprotein-receptor on the liver cell membrane. We investigated the usefulness of 99mTc-GSA for evaluation of the liver function in patients with chronic liver damage. We calculated LHL15 for the index of hepatic uptake and HH15 for the index of clearance. In patients with liver cirrhosis, LHL15 value was higher and HH15 value was lower than those of other groups. Both decrease in LHL15 value and increase in HH15 value were correlated with the severity of the liver damage. Significant correlation ws also observed between the prolongation of ICG clearance and both decrease in LHL15 value and increase in HH15 value. In conclusion, these findings indicate that 99mTc-GAS can be a useful agent for evaluation of the liver function in patients with chronic liver damage. (author)

  13. Liver trauma from penetrating injuries. Miscellanea, personal series, clinical and CT findings

    International Nuclear Information System (INIS)

    Penetrating liver wounds are related to many causes and rank second after blunt abdominal and liver trauma. In this report are examined the clinical and radiological findings of personal series of patients with penetrating trauma, especially by firearms and stab and cut wounds. It will also tried to define the diagnostic workup of these traumas, which is especially based on CT signs of liver damage and associated changes and which is of basic importance for following treatment, both surgical or conservative. In the last seven years it was retrospectively reviewed 31 cases of penetrating liver trauma. The patients were 19 men and 12 women, ranging in age 18 to 73 (mean 42), with penetrating liver injuries from firearms (16 patients) and stab (9 cases) wounds; 6 patients had injuries from different cases. Abdominal CT was carried out in emergency with the CT Angiography (CTA) technique in all patients. In the patients with suspected chest and abdomen involvement CT was performed from the mid-chest for accurate assessment of diaphragm and lung bases and to exclude associated pleuropulmonary damage. Penetrating liver wounds were caused by firearms in 70% of cases, by stabbing in 12% and, in the extant 18%, by other cases such as home accidents, road and work traumas, and liver biopsy. In this series, the liver was most frequently involved, especially by firearms wounds; in the 16 cases the most frequent injuries were hemorrhagic tears. It was found bullets in the liver in 6 cases. In one case of home accident the patient wounded himself while slicing bread with a long knife, which cut into the anterior abdominal wall and tore the anterior liver capsule, as seen at CTA. Penetrating wounds to liver and abdomen are less frequent than those to the chest. In the past decade the use of CT has changed the diagnostic and therapeutic approach to such injuries completely, decreasing the resort to explorative laparotomy and hepatorrhaphy. Indeed, CT provides a clear picture of

  14. IRF-1 promotes liver transplant ischemia/reperfusion injury via hepatocyte IL-15/IL-15Rα production

    OpenAIRE

    Yokota, Shinichiro; Yoshida, Osamu; Dou, Lei; Spadaro, Anthony V.; Isse, Kumiko; Ross, Mark A.; Stolz, Donna B.; Kimura, Shoko; Du, Qiang; DEMETRIS, ANTHONY J.; Thomson, Angus W.; Geller, David A.

    2015-01-01

    Ischemia and reperfusion (I/R) injury following liver transplantation (LTx) is an important problem that significantly impacts clinical outcomes. Interferon regulatory factor-1 (IRF-1) is a nuclear transcription factor that plays a critical role in liver injury. Our objective was to determine the immunomodulatory role of IRF-1 during I/R injury following allogeneic LTx. IRF-1 was induced in liver grafts immediately after reperfusion in both human and mouse LTx. IRF-1 contributed significantly...

  15. Modification of radiation-induced latent injury of rat liver by thioctacid and flavobion

    International Nuclear Information System (INIS)

    The effect of hepatoprotective drugs (flavobion and thioctacid) and a single whole-body irradiation (5,7 Gy of gamma radiation) on the regeneration of rat liver was examined. Liver regeneration was estimated on the basis of chosen morphological parameters on hour 30 after partial hepatectomy. Rediation-induced latent injury to intact rat liver 30 min bedore partial hepatectomy manifested in remaining regenerating liver by slowing-down of the increase in liver weight, cellularity and inhibition of the mitotic activity and in more frequent chromosome aberrations. Both hepatoprotective agents, especially thioctacid, used i.p. 60 min before irradiation, i. e. 90 min before partial hepatectomy, alleviate the manifestations of latent injury in this low proliferating organ as indicated by an increase in cellularity and mitotic index as compared with unprotected animals. Furthermore, the preparations tested decreased the frequency of radiation-induced chromosome aberrations

  16. Impact of asialoglycoprotein receptor deficiency on the development of liver injury

    Institute of Scientific and Technical Information of China (English)

    Serene ML Lee; Carol A Casey; Benita L McVicker

    2009-01-01

    The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously,we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease (ALD). The studies revealed profound ethanolmediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations,studies were performed utilizing knockout mice (lacking a functional ASGP receptor) to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti-Fas (CD95) antibody, carbon tetrachloride (CCl4) and lipopolysaccharide (LPS)/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels,histopathological scores, as well as hepatocellular death.Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

  17. Activation of a Novel c-Myc-miR27-Prohibitin 1 Circuitry in Cholestatic Liver Injury Inhibits Glutathione Synthesis in Mice

    OpenAIRE

    YANG, Heping; Li, Tony W. H.; Zhou, Yu; Peng, Hui; Liu, Ting; Zandi, Ebrahim; Martínez-Chantar, María Luz; Mato, José M.; Lu, Shelly C.

    2015-01-01

    Aims: We showed that chronic cholestatic liver injury induced the expression of c-Myc but suppressed that of glutamate-cysteine ligase (GCL, composed of catalytic and modifier subunits GCLC and GCLM, respectively). This was associated with reduced nuclear antioxidant response element (ARE) binding by nuclear factor-erythroid 2 related factor 2 (Nrf2). Here, we examined whether c-Myc is involved in this process. Results: Similar to bile duct ligation (BDL), lithocholic acid (LCA) treatment in ...

  18. STUDY OF SERUM URIC ACID IN CHRONIC LIVER DISEASE AND ITS RELATION WITH OTHER PARAMETERS

    Directory of Open Access Journals (Sweden)

    Rudrajit Paul

    2013-07-01

    Full Text Available In chronic liver disease, high uric acid levels are independently associated with severe disease and poor prognosis. However, studies regarding the relation of uric acid levels with different parameters of liver dysfunction are rare from India. Our aim was to study uric acid (UA levels in chronic liver disease and find any association of UA with different blood parameters and prognosis. We selected patients of chronic liver disease of any etiology. We did the serum UA test along with full liver function tests. Child Turcot Pugh (CTP score was calculated for each patient. Then by suitable statistical tests, any association or correlation was studied. We had total of 52 patients with 31 % female. 19 (36.5 % of the cases had liver disease secondary to alcoholism followed by 15 cases of non alcoholic fatty liver disease. 69.2 % of the patients were in CTP class B or C. Serum UA levels were significantly higher in chronic viral hepatitis cases (p<0.001. UA levels showed significant correlation with serum bilirubin (r=0.567, SGOT (r=0.464 and mortality. The UA levels showed significant correlation with severe disease and mortality. However, whether UA can be included in risk stratification of chronic liver disease can only be determined by larger randomized trials.

  19. Osseous and Nonosseous Bone Scan Findings in Liver Transplant Candidates with end-stage Chronic Liver Disease

    OpenAIRE

    Seval Erhamamcı; Ayşe Aktaş; Tatiana Bahçeci; Kevser Kavak

    2013-01-01

    Objective: End-stage chronic liver disease (CLD) adversely affects the function of multiple organ systems including the skeletal system. The aim of this study was to assess osseous and nonosseous bone scintigraphy (BS) findings in liver transplant (LT) candidates with end-stage CLD. Methods: We retrospectively evaluated BS findings in 50 consecutive patients with end-stage CLD who were undergoing preoperative assessment for LT from January 2006 to December 2011. All the patients were analyzed...

  20. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers

    OpenAIRE

    Lai, G.Y.; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; R. Sinha; Freedman, N D

    2013-01-01

    Background: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease...

  1. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas.

    Science.gov (United States)

    Paradis, V; Youssef, N; Dargère, D; Bâ, N; Bonvoust, F; Deschatrette, J; Bedossa, P

    2001-03-01

    There is growing evidence that senescent cells accumulate in vivo and are associated with the aging process in parallel with the progressive erosion of telomeres. Because recent data show that telomere shortening is involved in the pathogenesis of liver cirrhosis, we looked for replicative senescence cells in normal livers, chronic hepatitis C, and hepatocellular carcinoma (HCC). Replicative senescent cells were detected on liver tissue cryosections using expression of a specific marker, senescence-associated beta-galactosidase, a cytoplasmic enzyme detected at pH 6. A total of 57 frozen liver samples (15 normal liver, 32 chronic hepatitis C, and 10 HCCs) were studied. Replicative senescence was graded as absent in 56% of cases (32 of 57) and present in 44% (25 of 57). Replicative senescence was considered present in 3 of 15 normal livers (20%), 16 of 32 chronic hepatitis cases (50%), and 6 of 10 HCCs (60%). In the group of nontumoral livers, the presence of senescent cells in liver was associated with older age (P =.03). In the group with chronic hepatitis C, fibrosis stage, but not activity grade, was significantly correlated with the accumulation of replicative senescent cells (P HCC in the surrounding liver (P HCC development. Detection of replicative senescent cells may then serve as a predictive marker of a hepatocellular carcinoma in the surrounding tissue. HUM PATHOL 32:327-332. PMID:11274643

  2. Complications of high grade liver injuries: management and outcomewith focus on bile leaks

    Directory of Open Access Journals (Sweden)

    Bala Miklosh

    2012-03-01

    Full Text Available Abstract Background Although liver injury scale does not predict need for surgical intervention, a high-grade complex liver injury should alert the physician to expect an increased risk of hepatic complications following trauma. The aim of the current study was to define hepatic related morbidity in patients sustaining high-grade hepatic injuries that could be safely managed non-operatively. Patients and methods This is a retrospective study of patients with liver injury admitted to Hadassah-Hebrew University Medical Centre over a 10-year period. Grade 3-5 injuries were considered to be high grade. Collected data included the number and types of liver-related complications. Interventions which were required for these complications in patients who survived longer than 24 hours were analysed. Results Of 398 patients with liver trauma, 64 (16% were found to have high-grade liver injuries. Mechanism of injury was blunt trauma in 43 cases, and penetrating in 21. Forty patients (62% required operative treatment. Among survivors 22 patients (47.8% developed liver-related complications which required additional interventional treatment. Bilomas and bile leaks were diagnosed in 16 cases post-injury. The diagnosis of bile leaks was suspected with abdominal CT scan, which revealed intraabdominal collections (n = 6, and ascites (n = 2. Three patients had continuous biliary leak from intraabdominal drains left after laparotomy. Nine patients required ERCP with biliary stent placement, and 2 required percutaneous transhepatic biliary drainage. ERCP failed in one case. Four angioembolizations (AE were performed in 3 patients for rebleeding. Surgical treatment was found to be associated with higher complication rate. AE at admission was associated with a significantly higher rate of biliary complications. There were 24 deaths (37%, the majority from uncontrolled haemorrhage (18 patients. There were only 2 hepatic-related mortalities due to liver failure

  3. Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent

    Science.gov (United States)

    Vatsalya, Vatsalya; Avila, Diana; Frimodig, Jane C.; Barve, Shirish S; McClain, Craig J; Gobejishvili, Leila

    2016-01-01

    Background and aim Liver injury is estimated by serum alanine aminotransferases (ALT) levels in experimental animal models. Laboratories use various techniques to measure ALT levels including assay reagents and chemistry analyzers. VetScan VS2 (VS2) is widely used in veterinary clinics and research laboratories for highly reproducible, convenient and effective testing. Alternatively, ALT liquid reagent is used by laboratories to estimate liver injury in animal studies. The aim of this study was to perform comparative analyses of data obtained from these two assays in two different animal models. Methods In this study, we used two different mouse models and compared the ALT levels measured using VetScan VS2 chemistry analyzer and ALT liquid reagent. Immunohistochemical analysis of hepatic tissue was also performed to document liver pathology. The first model is a high fat diet feeding model that results in a mild hepatic steatosis (fat accumulation in the liver) without elevation of ALT levels. For a severe liver injury model, we employed a hepatotoxin-induced liver injury model (carbon tetrachloride, CCl4), which leads to the development of hepatic fibrosis and very high ALT levels. Results VetScan VS2 and ALT reagent gave different values of ALT for all animal groups. However, linear regression analysis showed a significantly high association between ALT levels obtained by VS2 and ALT liquid reagent in a high-fat feeding model with no liver injury. For the CCl4 induced liver injury model, serum dilution (5 and 10 times) was performed to obtain accurate results with ALT reagent. ALT levels acquired from both techniques showed a close association. Interestingly, this correlation was closer when serum was diluted 5 fold. Conclusion This study demonstrates that both methods give similar results when evaluating liver injury in animal studies. However, the serum dilution factor is critical for severe liver injury assessment when using ALT reagent and requires some

  4. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

    Institute of Scientific and Technical Information of China (English)

    Ioan; Sporea; Roxana; Sirli; Alexandra; Deleanu; Adriana; Tudora; Alina; Popescu; Manuela; Curescu; Simona; Bota

    2010-01-01

    AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV p...

  5. Association between serum 25(OH) vitamin D, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case–control study

    OpenAIRE

    Wang, J-B; Abnet, C. C.; Chen, W.; Dawsey, S M; Fan, J-H; Yin, L-Y; Yin, J.; Major, J M; Taylor, P R; Qiao, Y-L; Freedman, N D

    2013-01-01

    Background: Although vitamin D deficiency has been noted in cross-sectional studies of chronic liver disease and laboratory studies suggest possible benefits of vitamin D in preventing liver cancer, little epidemiologic data are available. Methods: We performed a nested case–control study in the Linxian Nutrition Intervention Trials on participants developing incident liver cancer or dying from chronic liver disease over 22 years of follow-up. Baseline serum 25(OH) vitamin D was measured for ...

  6. Involvement of immune-related factors in diclofenac-induced acute liver injury in mice

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. However, the underlying mechanism of DILI is little known. It is difficult to predict DILI in humans due to the lack of experimental animal models. Diclofenac, a non-steroidal anti-inflammatory drug rarely causes severe liver injury in human, but there is some evidence for immunoallergic idiosyncratic reactions. In this study, the mechanism of diclofenac-induced liver injury in mice was investigated. First, we established the dosing condition for liver injury in normal mice. Plasma ALT and AST levels were significantly increased in diclofenac-administered (80 mg/kg, i.p.) mice in a dose- and time-dependent manner. Among several interleukins (ILs) and chemokines, mRNA expression of helper T (Th) 17 cell-mediated factors, such as retinoid orphan receptor (ROR)-γt, and signal transducers and activators of transcription factor (STAT) 3 in the liver, and the plasma IL-17 level were significantly increased. Neutralization of IL-17 tended to suppress the hepatotoxicity of diclofenac, suggesting that IL-17 was partly involved. Gadolinium chloride (GdCl3) administration demonstrated that Kupffer cells are not likely to be involved in diclofenac hepatotoxicity. Hepatic expressions of IL-1β mRNA and plasma IL-1β were significantly increased soon after the diclofenac administration. Then, the results of an in vivo neutralization study of IL-1β suggested that IL-1β was involved early in the time of pathogenesis of the diclofenac-induced liver injury. In conclusion, we firstly developed a diclofenac-induced acute liver injury model in normal mice, and the involvement of IL-17 and IL-1β was clarified.

  7. Total Flavonoids from Mimosa Pudica Protects Carbon Tetrachloride -Induced Acute Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Zhen-qin QIU

    2015-03-01

    Full Text Available Objective: To observe the protective effect of total flavonoids from Mimosa pudica on carbon tetrachloride (CCl4-induced acute liver injury in mice. Methods: CCl4-induced acute liver injury model in mice was established. The activity of ALT and AST, the content of serum albumin (Alb and total antioxidant capacity (T-AOC were determined. The content of malondiadehyde (MDA was measured and the activity of superoxide dismutase (SOD was determined. The histopathological changes of liver were observed.Results: Compared with CCl4 modle group, each dose group of total flavonouida from Mimosa pudica couldreduced the activity of ALT and AST in mice obviously (P<0.01, indicating they had remarkably protective effect on CCl4-induced acute liver injury in mice. high and middle dose groups of total flavonouida from Mimosa pudica couldincrease the content of Alb in mice (P<0.01. Each dose group of total flavonouida from Mimosa pudica could enhance the level of T-AOC (P<0.01. each dose group of total flavonouida from Mimosa pudica could lower the content of liver homogenate MDA but enhance the activity of SOD in a dose-depended manner (P<0.01. Conclusion: Total flavones from Mimosa Pudica have obvious protective effect on CCl4-induced acute liver injury in mice.

  8. The role of osteopontin in D-galactosamine-induced liver injury in genetically obese mice

    International Nuclear Information System (INIS)

    Various epidemiological studies have shown that obesity increases the risk of liver disease, but the precise mechanisms through which this occurs are poorly understood. In the present study, we hypothesized that osteopontin (OPN), an extracellular matrix and proinflammatory cytokine, has an important role in making obese mice more susceptible to inflammatory liver injury. After exposure of genetically obese ob/ob and db/db mice to a single dose of D-galactosamine (GalN), the plasma liver enzyme levels, histology and expression levels of cytokines and OPN were evaluated. The ob/ob and db/db mice, which were more sensitive to GalN-induced inflammatory liver injury compared with wild-type mice, had significantly higher plasma and hepatic OPN expression levels. Increased OPN expression was mainly found in hepatocytes and inflammatory cells and was correlated with markedly up-regulated interleukin (IL)-12 and IL-18 levels. Furthermore, pretreatment with a neutralizing OPN (nOPN) antibody attenuated the GalN-induced inflammatory liver injury in ob/ob and db/db mice, which was accompanied by significantly reduced macrophages recruitment and IL-12 and IL-18 productions. Taken together, these results suggest that up-regulated OPN expression is a contributing factor to increased susceptibility of genetically obese mice to GalN-induced liver injury by promoting inflammation and modulating immune response.

  9. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    Energy Technology Data Exchange (ETDEWEB)

    Massey, Veronica L. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Stocke, Kendall S. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Schmidt, Robin H.; Tan, Min [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Ajami, Nadim [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Neal, Rachel E. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Petrosino, Joseph F. [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Barve, Shirish [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2015-05-01

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria.

  10. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    International Nuclear Information System (INIS)

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria

  11. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria.

    Science.gov (United States)

    Han, Derick; Dara, Lily; Win, Sanda; Than, Tin Aung; Yuan, Liyun; Abbasi, Sadeea Q; Liu, Zhang-Xu; Kaplowitz, Neil

    2013-04-01

    Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythroid 2-related factor 2 (Nrf-2), a transcription factor that upregulates antioxidant defenses. Owing to adaptation, drugs alone rarely cause liver injury, with acetaminophen (APAP) being the notable exception. Drug-induced liver injury (DILI) usually involves other extrinsic factors, such as the adaptive immune system, that cause 'stressed' hepatocytes to become injured, leading to idiosyncratic DILI, the rare and unpredictable adverse drug reaction in the liver. Hepatocyte injury, due to drug and extrinsic insult, causes a second wave of signaling changes associated with adaptation, cell death, and repair. If the stress and injury reach a critical threshold, then death signaling pathways such as c-Jun N-terminal kinase (JNK) become dominant and hepatocytes enter a failsafe mode to undergo self-destruction. DILI can be seen as an active process involving recruitment of death signaling pathways that mediate cell death rather than a passive process due to overwhelming biochemical injury. In this review, we highlight the role of signal transduction pathways, which frequently involve mitochondria, in the development of DILI. PMID:23453390

  12. Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods

    Science.gov (United States)

    Zhang, Dong; Song, Xiao-jing; Li, Shun-yue; Wang, Shu-you; Chen, Bing-jun; Bai, Xiao-Dong; Tang, Li-mei

    2016-01-01

    Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy. PMID:27443832

  13. Relationship Between Serum GGT Levels and Liver Fibrosis in Chronic Hepatitis B Patients

    OpenAIRE

    AYGÜN, Cem; Gözel, Nevzat; DEMİREL, Ulvi; Yalniz, Mehmet; ÖZERCAN, İbrahim Hanifi; BAHCECİOĞLU, İbrahim Halil

    2010-01-01

    Objective: The aim of this study was to evaluate the relationship between serum GGT levels and liver fibrosis among patients with chronic hepatitis B in Fırat University Medical School. Materials and Methods: In Gastroenterology Clinics of Fırat University Medical School, data regarding 140 chronic hepatitis B patients and laboratory results were analysed retrospectively. All patients had undergone liver biopsies and according to histopathological stages of fibrosis (Knodell's classificatio...

  14. Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

    Science.gov (United States)

    Chu, Michael JJ; Premkumar, Rakesh; Hickey, Anthony JR; Jiang, Yannan; Delahunt, Brett; Phillips, Anthony RJ; Bartlett, Adam SJR

    2016-01-01

    AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.

  15. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury

    OpenAIRE

    Ajay Kumar Jain; Teckman, Jeffrey H.

    2014-01-01

    Total parenteral nutrition (TPN), a lifesaving therapy, involves providing nutrition by bypassing the gut. Unfortunately it is associated with significant complications including gut atrophy and parenteral nutrition associated liver disease (PNALD). PNALD includes steatosis, cholestasis, disrupted glucose metabolism, disrupted lipid metabolism, cirrhosis, and liver failure. The etiopathogenesis remains poorly defined; however, an altered enterohepatic circulation, disrupting nuclear receptor ...

  16. Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

    OpenAIRE

    Wang, Bin; Zhang, Xiao-Hua; Miao-fan YANG; Xiao-wei WU; Xu, Xiao-Bing; Mei-xia GUO; Min-li LI

    2012-01-01

    Objective  To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 (SOCS3) in liver tissue of rats with experimental severe acute pancreatitis (SAP) concurring with liver injury. Methods  The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Thirty-two male SD rats were randomly assigned into 4 groups (8 each): normal control group (NC), SAP 6h, 12h, and 18h groups. The levels of serum amylase (...

  17. The role of lifestyle changes in the management of chronic liver disease

    OpenAIRE

    Feldstein Ariel E; Carter-Kent Christine; Nobili Valerio

    2011-01-01

    Abstract The prevalence of obesity worldwide has dramatically increased during the last three decades. With obesity comes a variety of adverse health outcomes which are grouped under the umbrella of metabolic syndrome. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several liver conditions which are directly affected by overweight and obese status, including non-alcoholic fatty liver disease, chronic infectio...

  18. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital.

    Science.gov (United States)

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both agents were stopped and corticosteroids were initiated. Five months later the patient had fully recovered. Although in the literature the hepatotoxicity of noni juice remains speculative, sporadic but emerging cases of noni juice-associated liver injury address the need to clarify and investigate potential harmful effects associated with this supplement. PMID:23467452

  19. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection.

    NARCIS (Netherlands)

    Poll, M.C. van de; Derikx, J.P.M.; Buurman, W.A.; Peters, W.H.M.; Roelofs, H.M.J.; Wigmore, S.J.; Dejong, C.H.

    2007-01-01

    BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injur

  20. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Davide Povero

    Full Text Available BACKGROUND & AIM: Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. DESIGN: Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. RESULTS: We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. CONCLUSIONS: These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

  1. MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice.

    Science.gov (United States)

    Uematsu, Yasuaki; Akai, Sho; Tochitani, Tomoaki; Oda, Shingo; Yamada, Toru; Yokoi, Tsuyoshi

    2016-09-15

    MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. PMID:27421576

  2. Role of bile acids in liver injury and regeneration following acetaminophen overdose.

    Science.gov (United States)

    Bhushan, Bharat; Borude, Prachi; Edwards, Genea; Walesky, Chad; Cleveland, Joshua; Li, Feng; Ma, Xiaochao; Apte, Udayan

    2013-11-01

    Bile acids play a critical role in liver injury and regeneration, but their role in acetaminophen (APAP)-induced liver injury is not known. We tested the effect of bile acid modulation on APAP hepatotoxicity using C57BL/6 mice, which were fed a normal diet, a 2% cholestyramine (CSA)-containing diet for bile acid depletion, or a 0.2% cholic acid (CA)-containing diet for 1 week before treatment with 400 mg/kg APAP. CSA-mediated bile acid depletion resulted in significantly higher liver injury and delayed regeneration after APAP treatment. In contrast, 0.2% CA supplementation in the diet resulted in a moderate delay in progression of liver injury and significantly higher liver regeneration after APAP treatment. Either CSA-mediated bile acid depletion or CA supplementation did not affect hepatic CYP2E1 levels or glutathione depletion after APAP treatment. CSA-fed mice exhibited significantly higher activation of c-Jun N-terminal protein kinases and a significant decrease in intestinal fibroblast growth factor 15 mRNA after APAP treatment. In contrast, mice fed a 0.2% CA diet had significantly lower c-Jun N-terminal protein kinase activation and 12-fold higher fibroblast growth factor 15 mRNA in the intestines. Liver regeneration after APAP treatment was significantly faster in CA diet-fed mice after APAP administration secondary to rapid cyclin D1 induction. Taken together, these data indicate that bile acids play a critical role in both initiation and recovery of APAP-induced liver injury. PMID:24007882

  3. Mechanism of exacerbative effect of progesterone on drug-induced liver injury.

    Science.gov (United States)

    Toyoda, Yasuyuki; Endo, Shinya; Tsuneyama, Koichi; Miyashita, Taishi; Yano, Azusa; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-03-01

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. However, the underlying mechanism of DILI is little known. It is generally believed that women exhibit worse outcomes from DILI than men. Recently, we found that pretreatment of mice with estradiol attenuated halothane (HAL)-induced liver injury, whereas pretreatment with progesterone exacerbated it in female mice. To investigate the mechanism of sex difference of DILI, we focused on progesterone in this study. We found the exacerbating effect of progesterone in thioacetamide (TA), α-naphthylisothiocyanate, and dicloxacillin-induced liver injury only in female mice. Higher number of myeloperoxidase-positive mononuclear cells infiltrated into the liver and increased levels of Chemokine (C-X-C motif) ligand 1 and 2 (CXCL1 and CXCL2) and intercellular adhesion molecule-1 in the liver were observed. Interestingly, CXCL1 was slightly increased by progesterone pretreatment alone. Progesterone pretreatment increased the extracellular signal-regulated kinase (ERK) phosphorylation in HAL-induced liver injury. Pretreatment with U0126 (ERK inhibitor) significantly suppressed the exacerbating effect of progesterone and the expression of inflammatory mediators. In addition, pretreatment with gadolinium chloride (GdCl(3): inhibitor of Kupffer cells) significantly suppressed the exacerbating effect of progesterone pretreatment and the expression of inflammatory mediators. Moreover, posttreatment of RU486 (progesterone receptor antagonist) 1 h after the HAL or TA administration ameliorated the HAL- or TA-induced liver injury, respectively, in female mice. In conclusion, progesterone exacerbated the immune-mediated hepatotoxic responses in DILI via Kupffer cells and ERK pathway. The inhibition of progesterone receptor and decrease of the immune response may have important therapeutic implications in DILI. PMID:22157104

  4. Coagulation in liver toxicity and disease: Role of hepatocyte tissue factor

    OpenAIRE

    Kopec, Anna K.; Luyendyk, James P.

    2014-01-01

    The liver is the primary source of a number of circulating coagulation factors, and acute liver injury and chronic liver disease are each associated with alterations in blood coagulation. Current views of the connection between liver injury and coagulation extend beyond the impact of liver disease on synthesis of coagulation factors to include a role for coagulation factor activity in the initiation and progression of liver disease. Mechanisms of coagulation initiation in liver disease are no...

  5. Protection against acetaminophen-induced liver injury by allopurinol is dependent on aldehyde oxidase-mediated liver preconditioning

    International Nuclear Information System (INIS)

    Acetaminophen (APAP) overdose causes severe and occasionally fatal liver injury. Numerous drugs that attenuate APAP toxicity have been described. However these compounds frequently protect by cytochrome P450 inhibition, thereby preventing the initiating step of toxicity. We have previously shown that pretreatment with allopurinol can effectively protect against APAP toxicity, but the mechanism remains unclear. In the current study, C3HeB/FeJ mice were administered allopurinol 18 h or 1 h prior to an APAP overdose. Administration of allopurinol 18 h prior to APAP overdose resulted in an 88% reduction in liver injury (serum ALT) 6 h after APAP; however, 1 h pretreatment offered no protection. APAP-cysteine adducts and glutathione depletion kinetics were similar with or without allopurinol pretreatment. The phosphorylation and mitochondrial translocation of c-jun-N-terminal-kinase (JNK) have been implicated in the progression of APAP toxicity. In our study we showed equivalent early JNK activation (2 h) however late JNK activation (6 h) was attenuated in allopurinol treated mice, which suggests that later JNK activation is more critical for the toxicity. Additional mice were administered oxypurinol (primary metabolite of allopurinol) 18 h or 1 h pre-APAP, but neither treatment protected. This finding implicated an aldehyde oxidase (AO)-mediated metabolism of allopurinol, so mice were treated with hydralazine to inhibit AO prior to allopurinol/APAP administration, which eliminated the protective effects of allopurinol. We evaluated potential targets of AO-mediated preconditioning and found increased hepatic metallothionein 18 h post-allopurinol. These data show metabolism of allopurinol occurring independent of P450 isoenzymes preconditions the liver and renders the animal less susceptible to an APAP overdose. - Highlights: • 18 h allopurinol pretreatment protects against acetaminophen-induced liver injury. • 1 h allopurinol pretreatment does not protect from APAP

  6. Protection against acetaminophen-induced liver injury by allopurinol is dependent on aldehyde oxidase-mediated liver preconditioning

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. David; McGill, Mitchell R.; Lebofsky, Margitta; Bajt, Mary Lynn; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu

    2014-02-01

    Acetaminophen (APAP) overdose causes severe and occasionally fatal liver injury. Numerous drugs that attenuate APAP toxicity have been described. However these compounds frequently protect by cytochrome P450 inhibition, thereby preventing the initiating step of toxicity. We have previously shown that pretreatment with allopurinol can effectively protect against APAP toxicity, but the mechanism remains unclear. In the current study, C3HeB/FeJ mice were administered allopurinol 18 h or 1 h prior to an APAP overdose. Administration of allopurinol 18 h prior to APAP overdose resulted in an 88% reduction in liver injury (serum ALT) 6 h after APAP; however, 1 h pretreatment offered no protection. APAP-cysteine adducts and glutathione depletion kinetics were similar with or without allopurinol pretreatment. The phosphorylation and mitochondrial translocation of c-jun-N-terminal-kinase (JNK) have been implicated in the progression of APAP toxicity. In our study we showed equivalent early JNK activation (2 h) however late JNK activation (6 h) was attenuated in allopurinol treated mice, which suggests that later JNK activation is more critical for the toxicity. Additional mice were administered oxypurinol (primary metabolite of allopurinol) 18 h or 1 h pre-APAP, but neither treatment protected. This finding implicated an aldehyde oxidase (AO)-mediated metabolism of allopurinol, so mice were treated with hydralazine to inhibit AO prior to allopurinol/APAP administration, which eliminated the protective effects of allopurinol. We evaluated potential targets of AO-mediated preconditioning and found increased hepatic metallothionein 18 h post-allopurinol. These data show metabolism of allopurinol occurring independent of P450 isoenzymes preconditions the liver and renders the animal less susceptible to an APAP overdose. - Highlights: • 18 h allopurinol pretreatment protects against acetaminophen-induced liver injury. • 1 h allopurinol pretreatment does not protect from APAP

  7. Screening for significant chronic liver disease by using three simple ultrasound parameters

    Energy Technology Data Exchange (ETDEWEB)

    Lignon, Grégoire [Department of Radiology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Boursier, Jérome [Department of Hepatology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Laboratory HIFIH, UPRES 3859, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Delumeau, Stéphanie [Department of Radiology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Michalak-Provost, Sophie [Department of Pathology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Lebigot, Jérome [Department of Radiology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Oberti, Frederic [Department of Hepatology, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); Laboratory HIFIH, UPRES 3859, LUNAM Université, France Université d’Angers, CHU Angers, Angers F-49100 (France); and others

    2015-08-15

    Highlights: • Three US parameters have diagnosis accuracy for the diagnosis of severe fibrosis equal to 66%. • These three signs detect unidentified fibrosis with a predictive positive value of 32%. • It would be an easy way to detect patients with silent chronic liver diseases. - Abstract: Objectives: Chronic liver diseases remain asymptomatic for many years. Consequently, patients are diagnosed belatedly, when cirrhosis is unmasked by lifethreatening complications. We aimed to identify simple ultrasound parameters for the screening of patients with unknown significant chronic liver disease. Methods: Three hundred and twenty seven patients with chronic liver disease, liver biopsy, and ultrasound examination were included in the derivation set. 283 consecutive patients referred for ultrasound examination were included in the validation set; those selected according to the ultrasound parameters identified in the derivation set were then referred for specialized consultation including non-invasive fibrosis tests and ultimately liver biopsy if liver fibrosis was suspected. Results: In the derivation set, three ultrasound parameters were independent predictors of severe fibrosis: liver surface irregularity, spleen length (>110 mm), and demodulation of hepatic veins. The association of ≥2 of the three above parameters provided 49.1% sensitivity and 86.9% specificity. In the validation set, at ≥2 of the three parameters were present in 23 (8%) of the patients. Among these patients, 8 had liver fibrosis (F ≥ 1), 5 had significant fibrosis (F ≥2) and two cirrhosis. Conclusion: The generalized search of three simple ultrasound signs in patients referred for abdominal ultrasound examination may be an easy way to detect those with silent but significant chronic liver disease.

  8. Screening for significant chronic liver disease by using three simple ultrasound parameters

    International Nuclear Information System (INIS)

    Highlights: • Three US parameters have diagnosis accuracy for the diagnosis of severe fibrosis equal to 66%. • These three signs detect unidentified fibrosis with a predictive positive value of 32%. • It would be an easy way to detect patients with silent chronic liver diseases. - Abstract: Objectives: Chronic liver diseases remain asymptomatic for many years. Consequently, patients are diagnosed belatedly, when cirrhosis is unmasked by lifethreatening complications. We aimed to identify simple ultrasound parameters for the screening of patients with unknown significant chronic liver disease. Methods: Three hundred and twenty seven patients with chronic liver disease, liver biopsy, and ultrasound examination were included in the derivation set. 283 consecutive patients referred for ultrasound examination were included in the validation set; those selected according to the ultrasound parameters identified in the derivation set were then referred for specialized consultation including non-invasive fibrosis tests and ultimately liver biopsy if liver fibrosis was suspected. Results: In the derivation set, three ultrasound parameters were independent predictors of severe fibrosis: liver surface irregularity, spleen length (>110 mm), and demodulation of hepatic veins. The association of ≥2 of the three above parameters provided 49.1% sensitivity and 86.9% specificity. In the validation set, at ≥2 of the three parameters were present in 23 (8%) of the patients. Among these patients, 8 had liver fibrosis (F ≥ 1), 5 had significant fibrosis (F ≥2) and two cirrhosis. Conclusion: The generalized search of three simple ultrasound signs in patients referred for abdominal ultrasound examination may be an easy way to detect those with silent but significant chronic liver disease

  9. Molecular changes associated with chronic liver damage and neoplastic lesions in a murine model of hereditary tyrosinemia type 1.

    Science.gov (United States)

    Angileri, Francesca; Roy, Vincent; Morrow, Geneviève; Scoazec, Jean Yves; Gadot, Nicolas; Orejuela, Diana; Tanguay, Robert M

    2015-12-01

    Hereditary tyrosinemia type 1 (HT1) is the most severe inherited metabolic disease of the tyrosine catabolic pathway, with a progressive hepatic and renal injury and a fatal outcome if untreated. Toxic metabolites accumulating in HT1 have been shown to elicit endoplasmic reticulum (ER) stress response, and to induce chromosomal instability, cell cycle arrest and apoptosis perturbation. Although many studies have concentrated on elucidating these events, the molecular pathways responsible for development of hepatocellular carcinoma (HCC) still remain unclear. In this study the fah knockout murine model (fah(-/-)) was used to investigate the cellular signaling implicated in the pathogenesis of HT1. Fah(-/-) mice were subjected to drug therapy discontinuation (Nitisinone withdrawal), and livers were analyzed at different stages of the disease. Monitoring of mice revealed an increasing degeneration of the overall physiological conditions following drug withdrawal. Histological analysis unveiled diffuse hepatocellular damage, steatosis, oval-like cells proliferation and development of liver cell adenomas. Immunoblotting results revealed a progressive and chronic activation of stress pathways related to cell survival and proliferation, including several stress regulators such as Nrf2, eIF2α, CHOP, HO-1, and some members of the MAPK signaling cascade. Impairment of stress defensive mechanisms was also shown by microarray analysis in fah(-/-) mice following prolonged therapy interruption. These results suggest that a sustained activation of stress pathways in the chronic HT1 progression might play a central role in exacerbating liver degeneration. PMID:26360553

  10. Protective effect of mycelial polysaccharides from Cordyceps sinensis on immunological liver injury in mice

    OpenAIRE

    Kai-zhong DONG; GAO, YONG-SHENG; Xiao-heng WANG; Ma, Yan-Qing; Su, Lu

    2016-01-01

    Objective  To explore the protective effects of mycelial polysaccharides from Cordyceps sinensis (MPCS) on BCG+LPS-induced liver injury in mice. Methods  The immunological liver injury mice model was reproduced by giving bacillus Calmette-Guerin (BCG) and lipopolysaccharide (LPS). Sixty NIH mice were randomly assigned into 6 groups (10 each): normal control group, model group, mycelium polysaccharide in high (100mg/kg), medium (50mg/kg) and low (25mg/kg) dose group, and bifendate (150mg/kg) t...

  11. Liver Injury from Herbal, Dietary, and Weight Loss Supplements: a Review

    OpenAIRE

    Zheng, Elizabeth X.; Navarro, Victor J.

    2015-01-01

    Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have he...

  12. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Zong, L. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China); No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Yu, Q.H. [Second Military Medical University, Changhai Hospital, Department of Gastroenterology, Shanghai, China, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai (China); Du, Y.X. [No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Deng, X.M. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2014-03-03

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  13. Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

    OpenAIRE

    B. Tang; Qiao, H.; Meng, F.; Sun, X.

    2007-01-01

    Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats...

  14. Hepatoprotective effects of Rubus coreanus miquel concentrates on liver injuries induced by carbon tetrachloride in rats

    OpenAIRE

    Chae, Hyun-Jung; Yim, Jung-Eun; Kim, Kyung-Ah; Chyun, Jong-Hee

    2014-01-01

    As well-being foods pursuing healthy life are becoming popular, interest in Rubus coreanus Miquel (RCM) fruit, a type of Korean blackberry, is increasing due to its medicinal actions including protecting the liver, brightening the eyes, and alleviating diabetes. This study was carried out to evaluate the hepatoprotective effects of RCM concentrates on liver injuries induced by carbon tetrachloride (CCl4) in rats. RCM, produced in June ~ July 2008 at Chunbook, Gochang (South Korea), was finely...

  15. Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist

    OpenAIRE

    Kiat-Hon Lim; Jason Pik-Eu Chang; Chee-Kiat Tan; Lynette Lin-Ean Oon; Boon-Huan Tan; Hoe-Nam Leong; Hui-Hui Tan

    2011-01-01

    Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.

  16. Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

    Directory of Open Access Journals (Sweden)

    Maria Ausiliatrice Puglisi

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs, represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

  17. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury

    OpenAIRE

    Ferguson, Michael A.; Vaidya, Vishal S.; Waikar, Sushrut S.; Collings, Fitz B.; Sunderland, Kelsey E.; Gioules, Costas J.; Bonventre, Joseph V.

    2009-01-01

    Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. The insensitivity and non-specificity of traditional markers of renal dysfunction prevent timely diagnosis, estimation of the severity of renal injury, and the administration of possible therapeutic agents. Here, we determine the prognostic ability of urinary liver-type fatty acid-binding protein (L-FABP), and further characterize its sensitivity and specificity as a biomarker of AKI. Initial ...

  18. Liver fibrosis in vitro : Cell culture models and precision-cut liver slices

    NARCIS (Netherlands)

    de Bovenkamp, M. Van; Groothuis, G. M. M.; Meijer, D. K. F.; Olinga, P.

    2007-01-01

    Chronic liver injury of various etiologies can cause liver fibrosis, which is characterized by the progressive accumulation of connective tissue in the liver. As no effective treatment for liver fibrosis is available yet, extensive research is ongoing to further study the mechanisms underlying the d

  19. 76 FR 4918 - Drug-Induced Liver Injury: Are We Ready to Look?; Public Conference; Request for Comments

    Science.gov (United States)

    2011-01-27

    ... for industry entitled ``Drug-Induced Liver Injury: Premarketing Clinical Evaluation'' (see 74 FR 38035... HUMAN SERVICES Food and Drug Administration Drug-Induced Liver Injury: Are We Ready to Look?; Public Conference; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice of...

  20. Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver

    DEFF Research Database (Denmark)

    Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Grønbæk, Henning; Hamilton-Dutoit, Stephen Jacques; Nyengaard, Jens Randel; Funch-Jensen, Peter; Mortensen, Frank Viborg

    2013-01-01

    Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver......Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver...

  1. Steatosis as a co-factor in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marcello; Persico; Achille; Iolascon

    2010-01-01

    The finding of lipid accumulation in the liver, so-called hepatic steatosis or non-alcoholic fatty liver disease, is a common condition frequently found in healthy subjects. Its prevalence, in fact, has been estimated by magnetic resonance studies to be about 35% in the general population and 75% in obese persons. Nevertheless, its presence generates liver damage only in a small percentage of subjects not affected by other liver diseases. It should be defined as a "co-factor" capable of affecting severity a...

  2.  Early initiation of MARS® dialysis in Amanita phalloides-induced acute liver injury prevents liver transplantation.

    Science.gov (United States)

    Pillukat, Mike Hendrik; Schomacher, Tina; Baier, Peter; Gabriëls, Gert; Pavenstädt, Hermann; Schmidt, Hartmut H J

    2016-01-01

     Amanita phalloides is the most relevant mushroom intoxication leading to acute liver failure. The two principal groups of toxins, the amatoxins and the phallotoxins, are small oligopeptides highly resistant to chemical and physical influences. The amatoxins inhibit eukaryotic RNA polymerase II causing transcription arrest affecting mainly metabolically highly active cells like hepatocytes and renal cells. The clinically most characteristic symptom is a 6-40 h lag phase before onset of gastrointestinal symptoms and the rapid progression of acute liver failure leading to multi-organ failure and death within a week if left untreated. Extracorporeal albumin dialysis (ECAD) was reported to improve patient's outcome or facilitate bridging to transplantation. In our tertiary center, out of nine intoxicated individuals from five non-related families six patients presented with acute liver injury; all of them were treated with ECAD using the MARS® system. Four of them were listed on admission for high urgency liver transplantation. In addition to standard medical treatment for Amanita intoxication we initiated ECAD once patients were admitted to our center. Overall 16 dialysis sessions were performed. All patients survived with full native liver recovery without the need for transplantation. ECAD was well tolerated; no severe adverse events were reported during treatment. Coagulopathy resolved within days in all patients, and acute kidney injury in all but one individual. In conclusion, ECAD is highly effective in treating intoxication with Amanita phalloides. Based on these experiences we suggest early initiation and repeated sessions depending on response to ECAD with the chance of avoiding liver transplantation. PMID:27493118

  3. Liver histopathology of the southern watersnake, Nerodia fasciata fasciata, following chronic exposure to trace element-contaminated prey from a coal ash disposal site

    Energy Technology Data Exchange (ETDEWEB)

    Ganser, L.R.; Hopkins, W.A.; O' Neil, L.; Hasse, S.; Roe, J.H.; Sever, D.M. [St Marys College, Notre Dame, IN (USA). Dept. of Biology

    2003-03-01

    Previous studies have demonstrated the accumulation of arsenic, cadmium, selenium, strontium, and vanadium in livers of Southern Watersnakes fed fish from a coal-ash contaminated site. Our study is the first to investigate effects of trace element accumulation on cytology of snake liver. Snakes were born in the laboratory and raised for one or two years on diets consisting of varying proportions of contaminated fish. The majority (71%) of snakes fed contaminated prey did not exhibit any differences in liver histology when compared to control snakes fed an uncontaminated diet. In the remaining contaminant-exposed snakes, some aberrations were noted. The most prevalent pathology involved the proliferation of collagen fibers that resulted in narrowing or occlusion of sinusoids and increasing the mass of the intersinsuoidal parenychma. Fibrosis of the liver as a result of chronic injury has been reported previously in reptiles, but this is the first report that links such tissue damage to dietary contamination.

  4. AgNORs, PCNA and Histologic Activity Index in Chronic Liver Disease

    OpenAIRE

    , Koray CEYHAN

    1999-01-01

    Chronic hepatitis is a clinical and pathological syndrome, which has several causes and it is characterized by varying degrees of hepatocellular necrosis and inflammation. Several systems have been proposed to evaluate the diagnosis, grading and staging of chronic hepatitis. A histologic activity index (HAI) has been developed which generates a numerical score for liver biopsy specimens obtained from patients with chronic hepatitis. The aim of this study was to evaluate the correlation betwee...

  5. Risk factors for alcohol-related liver injury in the island population of China: A population-based case-control study

    OpenAIRE

    Shen, Zhe; Li, You-ming; Yu, Chao-Hui; Shen, Yi; Xu, Lei; Xu, Cheng-fu; Chen, Jin-jin; Ye, Hua; Xu, Gen-yun

    2008-01-01

    AIM: To investigate the association of alcohol dose, duration of drinking and obesity with abnormal alcohol-related liver injury indicators, the prevalence of alcohol-related liver injury in the island population of China.

  6. Relationship between clinical and pathologic findings in patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Lun-Gen Lu; Jun Ye; Xiong Cai; Cheng-Wei Chen; Ji-Yao Wang; Shan-Ming Wu; Jin-Shui Zhu; Xia-Qiu Zhou; Min-De Zeng; Yi-Min Mao; Ji-Qiang Li; De-Kai Qiu; Jing-Yuan Fang; Ai-Ping Cao; Mo-Bin Wan; Cheng-Zhong Li

    2003-01-01

    AIM: To explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues.METHODS: The inflammatory activity and fibrosis of consecutive liver biopsies from 200 patients were determined according to the diagnosis criteria of chronic hepatitis in China established in 1995. A comparative analysis was carried out for 200 patients with chronic liver diseases by comparing their clinical manifestations, serum biochemical markers with the grading and staging of liver tissues.RESULTS: It was revealed that age, index of clinical symptoms and physical signs were obviously relevant to the pathologic grading and staging of liver tissues (P<0.05). Blood platelet, red blood cells, aspartate aminotransferase (AST),N-terminal procollagen Ⅲ (PⅢ NP) were apparently correlated with the degree of inflammation. PGA (prothrombin time,GGT, apoprotein A1) index, PGAA (PGA+△2-macroglobublin)index, albumin and albumin/globulin were relevant to both inflammation and fibrosis. Hyaluronic acid (HA) was an accurate variable for the severity of hepatic inflammation and fibrosis. The combination of serum markers for fibrosis could increase the diagnostic accuracy. It was notable that viral replication markers were not relevant to the degree of inflammation and fibrosis.CONCLUSION: There is a good correlation between clinical findings and the pathologic grading and staging of liver tissues, which may give aid to the noninvasive diagnosis of liver fibrosis.

  7. Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease.

    Science.gov (United States)

    Peres, W A F; Chaves, G V; Gonçalves, J C S; Ramalho, A; Coelho, H S M

    2011-12-01

    Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin A possesses antioxidant activity. The objective of the present study was to investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), according to biochemical, functional and dietetic indicators correlating these findings with liver function, liver damage and death. Vitamin A nutritional status was analysed by serum retinol levels, dietetic indicators and functional indicators. A total of 140 patients with HCV-related liver disease were enrolled. Vitamin A deficiency was detected in 54·3 % of all patients, and there was a progressive drop in serum retinol levels from chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total bilirubin, liver transaminases and prothrombin time, presence of hepatic encephalopathy and ascites were related to reduced serum retinol levels, and values ≤ 0·78 μmol/l of serum retinol were associated with liver-related death. A high prevalence of inadequate intake of vitamin A was observed in all stages of chronic liver disease. The functional indicator was not an adequate parameter for evaluating the vitamin A nutritional status. Therefore, serum retinol concentration is related to severity of the disease, liver complications and mortality. The effectiveness of nutritional counselling and measures of intervention in this group in improving vitamin A nutritional status should be examined further in a controlled study. PMID:21736776

  8. Radionuclide studies of the liver and spleen with colloid sup(99m)Tc after traumatic injuries at birth

    International Nuclear Information System (INIS)

    Liver and spleen functions were studied in 15 patients after birth injury by means of polyposition scintigraphy with sulphuric colloid-sup(99m)Tc. The study was performed over the period from 3 months up to 18 years following injury. Scintigraphy revealed disorders of liver function in 73.3% of the patients. The results obtained have shown that the organ involvement is not determined by the site injury established at operation but affects the entire organ. Scintigraphy of the liver and spleen is a reliable method for a study of long-term results of the treatment of birth injury of the liver and spleen in children. The frequency of changes in liver function after birth injury necessitates rehabilitation measures and a long regular medical check-up of these children

  9. ER stress contributes to alpha-naphthyl isothiocyanate-induced liver injury with cholestasis in mice.

    Science.gov (United States)

    Yao, Xiaomin; Li, Yue; Cheng, Xiaoyan; Li, Hongwei

    2016-06-01

    Endoplasmic reticulum (ER) stress is involved in the development of several liver diseases and tumors. This study investigated the underlying mechanisms of α-naphthyl isothiocyanate (ANIT)-induced liver injury with cholestasis in mice and found ER stress contributes to the injury. All animals were randomly divided into three groups. In the ANIT-intoxicated group, mice were intragastrically given 100mg/kg ANIT (dissolved in corn oil), while the other groups received an equal volume of vehicle as control. After 24 and 48h of ANIT administration, blood samples and liver tissues of all animals were collected for serum biochemistry and hepatic histopathological examinations to evaluate liver injuries with cholestasis. Hepatocellular apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression of hepatic ER stress-related markers was determined by real-time PCR, immunohistochemical assay and Western blot. ANIT was found to significantly induce liver injury with cholestasis compared with control mice as evidenced by the increase of serum transaminases and total bilirubin (TBil), and histopathological changes in mice. ANIT remarkably induced hepatocellular apoptosis, upregulated the expression of caspase-9 and cytochrome c, and inhibited the gene and protein expression of proliferating cell nuclear antigen (PCNA). The gene expression of ER stress-related markers, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), eukaryotic initiation factor 2α (eIF2α), inositol requiring enzyme-1α (IRE-1α) and activating transcription factor 6 (ATF6) was upregulated by ANIT in mice. ANIT also upregulated the protein expression of GRP78 and activated the phosphorylation of IRE1. These results suggested that ANIT induced liver injury with cholestasis partly due to its ability to activate the ER stress pathway. PMID:27173049

  10. Interactions between Myc and Mediators of Inflammation in Chronic Liver Diseases

    OpenAIRE

    Ting Liu; Yu Zhou; Kwang Suk Ko; Heping Yang

    2015-01-01

    Most chronic liver diseases (CLDs) are characterized by inflammatory processes with aberrant expressions of various pro- and anti-inflammatory mediators in the liver. These mediators are the driving force of many inflammatory liver disorders, which often result in fibrosis, cirrhosis, and liver tumorigenesis. c-Myc is involved in many cellular events such as cell growth, proliferation, and differentiation. c-Myc upregulates IL-8, IL-10, TNF-α, and TGF-β, while IL-1, IL-2, IL-4, TNF-α, and TGF...

  11. Effects of quercetin on polychlorinated biphenyls-induced liver injury in rats

    Directory of Open Access Journals (Sweden)

    Cléia Rocha de Oliveira

    2014-05-01

    Full Text Available Introduction: Polychlorinated biphenyls (PCBs, used as pesticides in agriculture, can lead to irreversible injuries in living organisms, particularly in liver. Oxidative stress has been implicated in the liver pathogenesis induced by different molecules, including PCBs. It has been demonstrated that quercetin, an antioxidant flavonoid found in the diet, exhibits a potent antioxidant effect in different liver pathologies. Objective: To evaluate oxidative stress caused by PCBs in liver and the antioxidant activity of quercetin. Methodology: We used male Wistar rats (n = 36, divided in 4 groups: control, quercetin (50 mg/kg/day, PCBs (0.4 ml/kg/day, and rats treated with both PCBs and quercetin. On day 25 blood was collected to assess liver integrity (enzymes AST, ALT and ALP, and liver samples to measure oxidative stress (TBARS, activity of antioxidant enzymes (SOD, CAT, GPx and DNA damage (micronucleus assay, and histological damage. Results: TBARS concentration and SOD activity were significantly higher in PCBs animals as compared to the PCB group receiving quercetin. CAT and GPx decreased in PCBs and increased when quercetin was added. The histological analysis showed damage to hepatocytes in PCBs, but quercetin was able to afford protection against such damage. The micronucleus test showed there was an increase in the production of microclenucleus compared to control, and quercetin was able to reduce this effect. Conclusion: Contamination with PCBs led to increased lipid peroxidation and DNA damage, and the use of antioxidant quercetin was effective in reducing PCBs-induced liver injury.

  12. Effects of retrorsine on mouse hepatocyte proliferation after liver injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-Fei Zhou; Qian Wang; Jian-Xin Chu; Ai-Lian Liu

    2006-01-01

    AIM: To study the effect of retrorsine on mouse hepatocyte proliferation.METHODS: Mice and rats were treated respectively with two injections of retrorsine (as retrosine-treated group) or saline (as non-treated group) at 2 wk intervals.They received a single injection of carbon tetrachloride (CCl4) 4 wk later. On d 0, 1, 2, 3, 4, 6, 15 after CCl4 administration, the animals were killed and their livers were excised. Hematoxylin and eosin (HE) staining and Ki-67 antibody immunohistochemical analysis of liver samples were used to evaluate the pathological changes and hepatocyte proliferation.RESULTS: In rats treated with retrorsine and CCl4, the liver displayed obvious megalocytosis, proliferation of mild bile duct, small hepatocyte-forming nodule, which were not found in liver samples from non-treated group.However, in mice treated with retrorsine combined with CCl4, the liver displayed hepatocyte degeneration and necrosis in perivenous areas. There was no obvious difference between retrorsine-treated group and nontreated group. Ki-67 immunohistochemical analysis showed that in rats treated with retrorsine, the positive hepatocytes mainly found in small hepatocyte nodules,were obviously less than those in non-treated group. The mice treated with retrorsine showed that the number of Ki-67 positive hepatocytes was very high and more than that in non-treated group.CONCLUSION: Retrorsine has no effect on mouse hepatocyte proliferation.

  13. Neurotherapy for chronic headache following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    David V Nelson; Mary Lee Esty

    2015-01-01

    Background:Chronic headache following traumatic brain injury (TBI) sustained in military service, while common, is highly challenging to treat with existing pharmacologic and non-pharmacologic interventions, and it may be complicated by co-morbid posttraumatic stress. Recently, a novel form of brainwave-based intervention known as the Flexyx Neurotherapy System (FNS), which involves minute pulses of electromagnetic energy stimulation of brainwave activity, has been suggested as a means to address symptoms of TBI. This study reports on a clinical series of patients with chronic headache following service-connected TBI treated with FNS. Methods: Nine veterans of the wars in Afghanistan and Iraq with moderate to severe chronic headaches following service-connected TBI complicated by posttraumatic stress symptoms were treated in 20 individual FNS sessions at the Brain Wellness and Biofeedback Center of Washington (in Bethesda, Maryland, USA). They periodically completed measures including the Brief Pain Inventory-Headache (BPI-HA), previous week worst and average pain ratings, the Posttraumatic Stress Disorder Checklist-Military version (PCL-M), and an individual treatment session numerical rating scale (NRS) for the degree of cognitive dysfunction. Data analyses included beginning-to-end of treatmentt-test comparisons for the BPI-HA, PCL-M, and cognitive dysfunction NRS. Results: All beginning-to-end of treatmentt-test comparisons for the BPI-HA, PCL-M, and cognitive dysfunction NRS indicated statistically significant decreases. All but one participant experienced a reduction in headaches along with reductions in posttraumatic stress and perceived cognitive dysfunction, with a subset experiencing the virtual elimination of headaches. One participant obtained modest headache relief but no improvements in posttraumatic stress or cognitive dysfunction. Conclusions: FNS may be a potentially efficacious treatment for chronic posttraumatic headache sustained in military

  14. Avulsion fractures and chronic avulsion injuries of the knee: role of MR imaging

    International Nuclear Information System (INIS)

    Avulsion fractures and chronic avulsion injuries of the knee are common lesions in sports-related trauma, especially among adolescents. Magnetic resonance imaging may prove useful in detecting and characterizing such lesions, and has several advantages with regard to other imaging modalities. We review, illustrate, and discuss the MR imaging features of some of the more frequent avulsion fractures and chronic avulsion injuries of the knee, including avulsion fractures of the cruciate ligaments, avulsion fractures of lateral and medial stabilizers, avulsion fractures and chronic avulsion injuries of the extensor mechanism, and avulsive cortical irregularities of the distal femur. The role of MR imaging in evaluating such lesions is emphasized. (orig.)

  15. Avulsion fractures and chronic avulsion injuries of the knee: role of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mellado, J.M.; Ramos, A.; Salvado, E.; Camins, A.; Sauri, A. [Institut de Diagnostic per la Imatge, Hospital Universitari de Tarragona Joan XXIII, 43007 Tarragona (Spain); Calmet, J. [Department of Orthopaedic Surgery, Hospital Universitari de Tarragona Joan XXIII, 43007 Tarragona (Spain)

    2002-10-01

    Avulsion fractures and chronic avulsion injuries of the knee are common lesions in sports-related trauma, especially among adolescents. Magnetic resonance imaging may prove useful in detecting and characterizing such lesions, and has several advantages with regard to other imaging modalities. We review, illustrate, and discuss the MR imaging features of some of the more frequent avulsion fractures and chronic avulsion injuries of the knee, including avulsion fractures of the cruciate ligaments, avulsion fractures of lateral and medial stabilizers, avulsion fractures and chronic avulsion injuries of the extensor mechanism, and avulsive cortical irregularities of the distal femur. The role of MR imaging in evaluating such lesions is emphasized. (orig.)

  16. Role of caspase-1 and interleukin-1β in acetaminophen-induced hepatic inflammation and liver injury

    International Nuclear Information System (INIS)

    Acetaminophen (APAP) overdose can result in serious liver injury and potentially death. Toxicity is dependent on metabolism of APAP to a reactive metabolite initiating a cascade of intracellular events resulting in hepatocellular necrosis. This early injury triggers a sterile inflammatory response with formation of cytokines and innate immune cell infiltration in the liver. Recently, IL-1β signaling has been implicated in the potentiation of APAP-induced liver injury. To test if IL-1β formation through caspase-1 is critical for the pathophysiology, C57Bl/6 mice were treated with the pan-caspase inhibitor Z-VD-fmk to block the inflammasome-mediated maturation of IL-1β during APAP overdose (300 mg/kg APAP). This intervention did not affect IL-1β gene transcription but prevented the increase in IL-1β plasma levels. However, APAP-induced liver injury and neutrophil infiltration were not affected. Similarly, liver injury and the hepatic neutrophilic inflammation were not attenuated in IL-1-receptor-1 deficient mice compared to wild-type animals. To evaluate the potential of IL-1β to increase injury, mice were given pharmacological doses of IL-1β after APAP overdose. Despite increased systemic activation of neutrophils and recruitment into the liver, there was no alteration in injury. We conclude that endogenous IL-1β formation after APAP overdose is insufficient to activate and recruit neutrophils into the liver or cause liver injury. Even high pharmacological doses of IL-1β, which induce hepatic neutrophil accumulation and activation, do not enhance APAP-induced liver injury. Thus, IL-1 signaling is irrelevant for APAP hepatotoxicity. The inflammatory cascade is a less important therapeutic target than intracellular signaling pathways to attenuate APAP-induced liver injury.

  17. Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase.

    Science.gov (United States)

    Fang, H; Liu, A; Dahmen, U; Dirsch, O

    2013-01-01

    The anti-malaria drug chloroquine is well known as autophagy inhibitor. Chloroquine has also been used as anti-inflammatory drugs to treat inflammatory diseases. We hypothesized that chloroquine could have a dual effect in liver ischemia/reperfusion (I/R) injury: chloroquine on the one hand could protect the liver against I/R injury via inhibition of inflammatory response, but on the other hand could aggravate liver I/R injury through inhibition of autophagy. Rats (n=6 per group) were pre-treated with chloroquine (60 mg/kg, i.p.) 1 h before warm ischemia, and they were continuously subjected to a daily chloroquine injection for up to 2 days. Rats were killed 0.5, 6, 24 and 48 h after reperfusion. At the early phase (i.e., 0-6 h after reperfusion), chloroquine treatment ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines and fewer histopathologic changes. In contrast, chloroquine worsened liver injury at the late phase of reperfusion (i.e., 24-48 h after reperfusion). The mechanism of protective action of chloroquine appeared to involve its ability to modulate mitogen-activated protein kinase activation, reduce high-mobility group box 1 release and inflammatory cytokines production, whereas chloroquine worsened liver injury via inhibition of autophagy and induction of hepatic apoptosis at the late phase. In conclusion, chloroquine prevents ischemic liver damage at the early phase, but aggravates liver damage at the late phase in liver I/R injury. This dual role of chloroquine should be considered when using chloroquine as an inhibitor of inflammation or autophagy in I/R injury. PMID:23807223

  18. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury

    OpenAIRE

    Celaj, Stela; Gleeson, Michael W; Jie DENG; O'Toole, George A.; Hampton, Thomas H.; Toft, Martin F.; Morrison, Hilary G; Sogin, Mitchell L.; Putra, Juan; Suriawinata, Arief A.; Gorham, James D.

    2014-01-01

    Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in lab...

  19. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

    OpenAIRE

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Kuur, E.C. van der; Morava, E.; Wevers, R A; Augustijn, K.D.; Touw, D.J.; Sandel, M.H.; Masereeuw, R.; Russel, F. G. M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of >/=275 mg/kg bw APAP resulted in hepatic centrilobular...

  20. Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

    OpenAIRE

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0–350 mg/kg bw) followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necr...

  1. Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

    Directory of Open Access Journals (Sweden)

    Sayed M. Mizar

    2015-03-01

    Full Text Available Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg and/or chrysin (25 mg/kg by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT and aspartate transaminase (AST, as well as hepatic Myeloperoxidase (MPO, total nitrate (NOx, glutathione (GSH and liver malondialdehyde (MDA were measured at the end of the experiment. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS subtypes, endothelial (eNOS and inducible (iNOS in liver samples were assessed by Western blotting and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

  2. Influence of zinc sulfate intake on acute ethanol-induced liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Sema Bolkent; Pelin Arda-Pirincci; Sehnaz Bolkent; Refiye Yanardag; Sevim Tunali; Sukriye Yildirim

    2006-01-01

    AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury.METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group Ⅱ; control rats given only zinc, group Ⅲ; animals given absolute ethanol, group Ⅳ; rats given zinc and absolute ethanol.Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol.RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione.CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate.

  3. Pharmaco-epidemiological, clinical and laboratory characteristics of drug-induced liver injury in tuberculosis

    Directory of Open Access Journals (Sweden)

    M. V. Koroleva

    2015-01-01

    Full Text Available Objective: improving the efficiency of pharmacotherapy of drug-induced liver injury in tuberculosis by clarifying pharmaco-epidemiological, clinical and laboratory features.Materials and Methods: A retrospective analysis of primary medical records of 250 patients with pulmonary tuberculosis, patients «Volgograd Regional Clinical TB Dispensary № 1». We evaluated the dynamics of biochemical parameters characterizing the development of hepatic cytolytic syndrome, examined the impact of gender and age on the incidence of liver damage, we investigated the relationship of clinical tuberculosis and chemotherapy regimen with the incidence of drug-induced liver injury, examined the clinical manifestations of liver disease.Results: Drug-induced liver injury as a complication of a specific anti-TB treatment was diagnosed in 67 patients (26,8%. In 170 patients (68,0% showed increase in alanine aminotransferase and asparaginaminotrasferazy. Hepatotoxicity significantly more common in patients with disseminated tuberculosis with the collapse of the lung tissue, smear, and a high degree of disease severity. Risk factors for drug liver damage were female gender and age older than 50 years. Women develop liver disease at an earlier date, and displays it harder than men. The earliest and most informative routine biochemical tests, reflecting the state of the liver in the dynamics are ALT and AST. It was found that the mode of the standard anti-TB treatment determines the type of liver injury: the first, 2a and 3rd modes prevails cytolytic hepatocellular type, with 2b mode – combined (mixed type 4th – type of cholestatic liver damage. It was found that repeated, after the development of hepatotoxic reactions, the appointment of anti-TB drugs without gepatoprotektsii in 94% of patients leads to repeated drug-induced liver damage. Cancel specific therapy against the background of cytolytic syndrome promotes the formation of

  4. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

    Directory of Open Access Journals (Sweden)

    Ismail Ben Mosbah

    Full Text Available Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP, a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging

  5. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

    Science.gov (United States)

    Ben Mosbah, Ismail; Mouchel, Yann; Pajaud, Julie; Ribault, Catherine; Lucas, Catherine; Laurent, Alexis; Boudjema, Karim; Morel, Fabrice; Corlu, Anne; Compagnon, Philippe

    2012-01-01

    Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS) upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP), a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg) group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO) production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging, this preservation

  6. Ascertainment of acute liver injury in two European primary care databases

    NARCIS (Netherlands)

    Ruigómez, A.; Brauer, R.; Rodríguez, L. A García; Huerta, C.; Requena, G.; Gil, M.; de Abajo, Francisco; Downey, G.; Bate, A.; Tepie, M. Feudjo; de Groot, M.C.H.; Schlienger, R.; Reynolds, R.; Klungel, O.

    2014-01-01

    Purpose The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI. Methods T

  7. Protective effects of exogenous glutathione and related thiol compounds against drug-induced liver injury.

    Science.gov (United States)

    Masubuchi, Yasuhiro; Nakayama, Junpei; Sadakata, Yuka

    2011-01-01

    An overdose of acetaminophen (APAP) causes liver injury both in experimental animals and humans. N-acetylcysteine (NAC) is clinically used as an antidote for APAP intoxication, and it is thought to act by providing cysteine as a precursor of glutathione, which traps a reactive metabolite of APAP. Other hepatoprotective mechanisms of NAC have also been suggested. Here, we examined the effects of thiol compounds with different abilities to restore hepatic glutathione, on hepatotoxicity of APAP and furosemide in mice. Overnight-fasted male CD-1 mice were given APAP or furosemide intraperitoneally. NAC, cysteine, glutathione, or glutathione-monoethyl ester was administered concomitantly with APAP or furosemide. All thiol compounds used in this study effectively protected mice against APAP-induced liver injury. Only glutathione-monoethyl ester completely prevented APAP-induced early hepatic glutathione depletion. Cysteine also significantly restored hepatic glutathione levels. NAC partially restored glutathione levels. Exogenous glutathione had no effect on hepatic glutathione loss. NAC and glutathione highly stimulated the hepatic expression of cytokines, particularly interleukin-6, which might be involved in the alleviation of APAP hepatotoxicity. Furosemide-induced liver injury, which does not accompany hepatic glutathione depletion, was also attenuated by NAC and exogenous glutathione, supporting their protective mechanisms other than replenishment of glutathione. In conclusion, exogenous thiols could alleviate drug-induced liver injury. NAC and glutathione might exert their effects, at least partially, via mechanisms that are independent of increasing hepatic glutathione, but probably act through cytokine-mediated and anti-inflammatory mechanisms. PMID:21372386

  8. Epigenetic effects of ethanol on liver and gastrointestinal injury

    Institute of Scientific and Technical Information of China (English)

    Shivendra D Shukla; Annayya R Aroor

    2006-01-01

    Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.

  9. Interleukin-17 is involved in α-naphthylisothiocyanate-induced liver injury in mice

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. The pathogenesis of DILI usually involves the participation of the parent drug or metabolites that either directly affect the cell biochemistry or elicit an immune response. However, in most cases the mechanisms are unknown. Alpha-naphthylisothiocyanate (ANIT) is known as a hepatotoxicant that causes biliary cell and hepatocyte damage and induces intense neutrophil infiltration in the liver. To investigate whether an immune-mediated mechanism is involved in ANIT-induced liver injury, we examined the plasma AST, ALT and T-Bil levels, hepatic expression of transcriptional factors, cytokines and CXC chemokine genes, plasma IL-17 level and histopathological changes in liver after ANIT administration in mice. Hepatic mRNA expression of retinoid related orphan receptor γt (RORγt) and macrophage inflammatory protein (MIP-2) and plasma IL-17 level was significantly increased in ANIT-administered mice as well as the plasma AST, ALT and T-Bil. Neutralization of IL-17 using anti-IL-17 antibody (100 μg/mouse, single i.p.) suppressed the hepatotoxic effect of ANIT. Co-administration of recombinant IL-17 (1 μg/mouse, single i.p.) to ANIT-administered mice resulted in a remarkable increase of the plasma AST, ALT and T-Bil levels. In conclusion, it was firstly demonstrated that IL-17 is involved in the ANIT-induced liver injury in mice.

  10. Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights.

    Science.gov (United States)

    Greuter, Thomas; Shah, Vijay H

    2016-06-01

    Changes of hepatic sinusoids are crucial in the pathogenesis of liver cirrhosis and portal hypertension. Liver injury leads to distinct morphological abnormalities such as loss of sinusoidal fenestration, vasoconstriction, and angiogenesis as well as molecular changes. Communication between the two key cells in this hepatic microenvironment-hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC)-has been studied for many years and several canonical pathways have been elucidated, such as decreased eNOS activity or increased PDGF and TGF-β production leading to activation and migration of HSC. In recent studies, alternative pathways of intercellular communication in liver diseases have been described such as cell-derived extracellular vesicles called exosomes, which deliver cell compounds to their target cells. Moreover, such extracellular vesicles may link injury to inflammation in alcoholic hepatitis. While inflammation leading to liver fibrosis has been studied in detail, in some circumstances pathways other than the known canonical inflammatory pathways may contribute to hepatic fibrogenesis. For example, in congestive hepatopathy, sinusoidal dilatation and fibrosis have been shown to be mediated by non-inflammatory mechanisms and associated with sinusoidal thrombi. A recently developed murine model further enables experimental studies of this disease entity. Increasing knowledge about these alternative disease pathways in liver injury, inflammation, and fibrosis may reveal possible target molecules for future therapies. This article builds upon a seminar given at the recent 3rd JSGE International Topic Conference in Sendai, Japan, and reviews the areas outlined above. PMID:26939970

  11. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    Institute of Scientific and Technical Information of China (English)

    Banwari; Agarwal; Andrew; Davenport

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease(MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period.

  12. Management of ischemic-type biliary injury induced by hepatic artery stricture after orthotopic liver transplantation

    International Nuclear Information System (INIS)

    Objective: To discuss the treatment of ischemic-type biliary injury due to hepatic artery stricture after orthotopic liver transplantation and to estimate its prognosis. Methods: The clinical data of 11 patients with ischemic-type biliary injury due to hepatic artery stricture after orthotopic liver transplantation encountered during the period of June 2004-June 2008, who underwent hepatic artery stenting together with endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic cholangial drainage (PTCD), were retrospectively analyzed. Results: A total of 12 balloon-expandable coronary stents was successfully implanted in 11 patients. In 5 patients only ERCP was adopted and in 3 patients only PTCD was used. The remaining 3 patients received PTCD after they failed to respond to ERCP. During a follow-up period of 4 months-4 years, 6 cases died of infection, of which 5 died within one year. Three patients accepted liver transplantation once more. The other 2 patients survived so far. Conclusion: The overall therapeutic result of ischemic-type biliary injury due to hepatic artery stricture after orthotopic liver transplantation is not ideal at present. Hepatic artery stenting combined with longstanding PTCD may prolong the survival time of the grafted liver and, therefore, provide opportunity for re-transplantation. (authors)

  13. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  14. Effects of primary suture and fibrin sealant on hemostasis and liver regeneration in an experimental liver injury

    Institute of Scientific and Technical Information of China (English)

    Arif Hakan Demirel; Ozgur Taylan Basar; All Ulvi Ongoren; Erkut Bayram; Mustafa Kisakurek

    2008-01-01

    AIM:To investigate the effects of fibrin sealant on hemostasis and liver regeneration and intra-abdominal adhesions in an experimental liver injury.METHODS: Thirty-six Wistar rats were randomly divided into primary suture group (n=15), fibrin sealant group (n=15) and control group (n=6). A wedge resection was performed on the left lobe of the liver. In primary suture group, liver was sutured using polypropylene material, while fibrin glue was administrated on the liver surface in fibrin sealant group.RESULTS: More intra-abdominal adhesions were observed in the primary suture group compared to the fibrin sealant group on 3rd (2.50.5 vs 0.25.5, P =0.015), 10th(2.75.5 vs 0.50.6, P = 0.06) and 20th(1.75.5 vs 0.70.5, P = 0.015) postoperative days. Histopathological scores were better in the fibrin sealant group in comparison with the primary suture group on 3rd (8.75.5 vs 6.75.5, P = 0.006), 10th (7.50.0 vs 5.5.6, P = 0.021) and 20th(6.40.7 vs 3.20.6, P = 0.025) postoperative days.CONCLUSION: Out data suggest that fibrin sealant is preferred over primary suture in appropriate cases including liver trauma since it causes less intra-abdominal adhesions while allowing shorter hemostasis time as assessed in experimental liver trauma.

  15. High prevalence of hepatitis C in Egyptian patients with chronic liver disease.

    Science.gov (United States)

    Waked, I A; Saleh, S M; Moustafa, M S; Raouf, A A; Thomas, D L; Strickland, G T

    1995-07-01

    The highest prevalence rates of hepatitis C virus infection in the world have been recently reported among Egyptian blood donors and frequent recipients of transfusions and other blood products. This is the first report, however, demonstrating hepatitis C as the most frequent association with chronic liver disease in Egypt. Of 1023 patients referred to the Liver Institute in Menoufia governorate for evaluation of chronic liver disease, 752 (73.5%) had antibodies to hepatitis C compared with 168 (16.4%) with hepatitis B surface antigen. Hepatitis C antibody was more common in patients with active schistosomiasis and patients without hepatitis B surface antigenaemia. Of 100 patients having liver biopsies, histological findings consistent with chronic viral hepatitis or its complications were found in 89 and antibody to hepatitis C was present in 75 (84.3%) of these patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma. These data pointing to the importance of hepatitis C as a cause of chronic liver disease in Egypt emphasise the necessity of studies delineating its routes of transmission in this country. PMID:7545630

  16. Non invasive assessment of liver fibrosis in chronic hemodialysis patients with viral hepatitis C.

    Science.gov (United States)

    Arrayhani, Mohamed; Sqalli, Tarik; Tazi, Nada; El Youbi, Randa; Chaouch, Safae; Aqodad, Nourdin; Ibrahimi, Sidi Adil

    2015-01-01

    The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological scores (APRI, Forns and Fib-4), and to measure the correlation between these tests. Cross-sectional study including all chronic hemodialysis patients with hepatitis C virus, in two public hemodialysis centers of Fez. All patients were evaluated for liver fibrosis using noninvasive methods (FibroScan and laboratory tests). Subsequently, the correlation between different tests has been measured. 95 chronic hemodialysis were studied, twenty nine patients (30.5%) with chronic hepatitis C. The average age was 52.38 ± 16.8 years. Nine liver fibrosis cases have been concluded by forns score. Fibroscan has objectified significant fibrosis in 6 cases. On the other side APRI has objectified sgnifivant fibrosis only in 3 cases. The Fib-4 showed severe fibrosis in five cases. The results have been most consistent between APRI and Fib-4, followed by Fibroscan and Forns, then APRI and FibroScan. PMID:26958136

  17. The role of lifestyle changes in the management of chronic liver disease

    Directory of Open Access Journals (Sweden)

    Feldstein Ariel E

    2011-06-01

    Full Text Available Abstract The prevalence of obesity worldwide has dramatically increased during the last three decades. With obesity comes a variety of adverse health outcomes which are grouped under the umbrella of metabolic syndrome. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several liver conditions which are directly affected by overweight and obese status, including non-alcoholic fatty liver disease, chronic infection with hepatitis C virus and post-liver transplant status. The deleterious effects of obesity on liver disease and overall health can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting non-pharmacological, lifestyle interventions that lead to weight reduction, improved physical activity and better nutrition as part of the management and treatment of these liver conditions.

  18. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, R.A.; Crews, F.T. (Department of Pharmacology, University of Texas, Austin (USA))

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  19. Protective effect of mycelial polysaccharides from Cordyceps sinensis on immunological liver injury in mice

    Directory of Open Access Journals (Sweden)

    Kai-zhong DONG

    2016-04-01

    Full Text Available Objective  To explore the protective effects of mycelial polysaccharides from Cordyceps sinensis (MPCS on BCG+LPS-induced liver injury in mice. Methods  The immunological liver injury mice model was reproduced by giving bacillus Calmette-Guerin (BCG and lipopolysaccharide (LPS. Sixty NIH mice were randomly assigned into 6 groups (10 each: normal control group, model group, mycelium polysaccharide in high (100mg/kg, medium (50mg/kg and low (25mg/kg dose group, and bifendate (150mg/kg treatment group. The serum transaminase levels of alanine ALT and AST were assayed with ELISA, nitric oxide (NO in serum was measured by nitrate reductase method, and the liver homogenate was prepared for the determination of the contents of interleukin-1β(IL-1β and tumor necrosis factor-α(TNF-α. The mRNA expression levels of IL-6 and iNOS in hepatic tissue were assessed using RT-PCR . Results  In the mice of immunological liver injury, mycelial polysaccharides from Cordyceps sinensis obviously lowered the serum ALT and AST levels (P<0.01, high dose MPCS significantly reduced the serum NO and liver tissue IL-1βand TNF-αlevels (P<0.01. Compared with the model group, high and medium dose MPCS significantly reduced the expression levels of IL-6 and iNOS mRNA in hepatic tissues (P<0.01. Conclusion  MPCS shows a certain protective effect on immunological liver injury induced by BCG plus LPS in mice. DOI: 10.11855/j.issn.0577-7402.2016.04.05

  20. Effect of fasting on the metabolic response of liver to experimental burn injury.

    Directory of Open Access Journals (Sweden)

    Mehmet A Orman

    Full Text Available Liver metabolism is altered after systemic injuries such as burns and trauma. These changes have been elucidated in rat models of experimental burn injury where the liver was isolated and perfused ex vivo. Because these studies were performed in fasted animals to deplete glycogen stores, thus simplifying quantification of gluconeogenesis, these observations reflect the combined impact of fasting and injury on liver metabolism. Herein we asked whether the metabolic response to experimental burn injury is different in fed vs. fasted animals. Rats were subjected to a cutaneous burn covering 20% of the total body surface area, or to similar procedures without administering the burn, hence a sham-burn. Half of the animals in the burn and sham-burn groups were fasted starting on postburn day 3, and the others allowed to continue ad libitum. On postburn day 4, livers were isolated and perfused for 1 hour in physiological medium supplemented with 10% hematocrit red blood cells. The uptake/release rates of major carbon and nitrogen sources, oxygen, and carbon dioxide were measured during the perfusion and the data fed into a mass balance model to estimate intracellular fluxes. The data show that in fed animals, injury increased glucose output mainly from glycogen breakdown and minimally impacted amino acid metabolism. In fasted animals, injury did not increase glucose output but increased urea production and the uptake of several amino acids, namely glutamine, arginine, glycine, and methionine. Furthermore, sham-burn animals responded to fasting by triggering gluconeogenesis from lactate; however, in burned animals the preferred gluconeogenic substrate was amino acids. Taken together, these results suggest that the fed state prevents the burn-induced increase in hepatic amino acid utilization for gluconeogenesis. The role of glycogen stores and means to increase and/or maintain internal sources of glucose to prevent increased hepatic amino acid

  1. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Singh, Nandita; Kamath, Vasudeva; Narasimhamurthy, K; Rajini, P S

    2008-09-01

    Our earlier studies have shown that extracts derived from potato peel (PPE) are rich in polyphenols and possess strong antioxidant activity both in vitro and in vivo. The objective of the present study was to investigate its potential to offer protection against acute liver injury in rats. Rats pretreated with PPE (oral, 100mg/kgb.w./day for 7 days) were administered a single oral dose carbon tetrachloride (CCl(4), 3ml/kg b.w., 1:1 in groundnut oil) and sacrificed 8h of post-treatment. Hepatic damage was assessed by employing biochemical parameters (transaminase enzyme levels in plasma and liver [AST-aspartate transaminase; ALT-alanine transaminase, LDH-lactate dehydrogenase]). Further, markers of hepatic oxidative damage were measured in terms of malondialdehyde (MDA), enzymic antioxidants (CAT, SOT, GST, GPX) and GSH (reduced glutathione) levels. In addition, the CCl(4)-induced pathological changes in liver were evaluated by histopathological studies. Our results demonstrated that pretreatment of rats with PPE significantly prevented the increased activities of AST and ALT in serum, prevented the elevation of hepatic MDA formation as well as protected the liver from GSH depletion. PPE pretreatment also restored CCl(4)-induced altered antioxidant enzyme activities to control levels. The protective effect of PPE was further evident through the decreased histological alterations in liver. Our findings provide evidences to demonstrate that PPE pretreatment significantly offsets CCl(4)-induced liver injury in rats, which may be attributable to its strong antioxidant propensity. PMID:21791371

  2. Protective effects of garcinol in mice with lipopolysaccharide/D-galactosamine-induced apoptotic liver injury.

    Science.gov (United States)

    Jing, Yuping; Ai, Qing; Lin, Ling; Dai, Jie; Jia, Mengying; Zhou, Dan; Che, Qian; Wan, Jingyuan; Jiang, Rong; Zhang, Li

    2014-04-01

    Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica. Recent researches have revealed the antioxidant, anticancer and anti-inflammatory properties of garcinol. In the present study, the pharmacological effects of garcinol in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice were investigated. We found that treatment with garcinol significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections and reduced malondialdehyde (MDA) content in liver homogenates. Garcinol significantly reduced the acetylation level of NF-κB, but it had no obvious effects on the elevation of TNF-α or IL-6 in plasma or liver tissue. Garcinol significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by reduced number of TUNEL-positive cells in liver sections. Our experiments also showed that garcinol markedly suppressed the cleavage of caspase-3 and significantly decreased the activities of caspase-3, -8, and -9 in liver tissues. In addition, garcinol obviously reduced the induction of Bax but did not alter the level of Bcl-2. These results indicated that garcinol might provide protective benefits in LPS/D-Gal-induced liver injury through suppressing apoptosis. PMID:24560905

  3. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    International Nuclear Information System (INIS)

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

  4. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  5. Correlation between ultrasound imaging and serum markers of liver fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jian-Xia Liu

    2016-01-01

    Objective:To investigate the clinical value of ultrasonic imaging in the assessment of liver fibrosis in patients with chronic hepatitis B. Methods:A total of 20 cases of liver biopsy in chronic hepatitis B, according to the degree of hepatic fibrosis were divided into mild hepatic fibrosis group, moderate fibrosis group, severe fibrosis group, the other selected healthy volunteers as control group, using color Doppler ultrasound, the use of imaging technology and automatic tracking. Strengthen the quantitative analysis, using the second generation microbubble contrast agent SonoVue contrast analysis, contrast agent reach the portal time (PVAT), hepatic artery time (HAAT), hepatic vein (HVVT), the calculation time of hepatic arteriovenous transit time (VAT) and hepatic portal vein transit time (VVT), using chemiluminescence detection of serum liver fiber hyaluronic acid (HA), laminin (LN) and collagen type IV (CIV) index. Results:there was no significant difference in HAAT, PVAT, VAT, VVT and HVAT in all groups, and there was no significant difference, mild, moderate and severe liver fibrosis group, and HA, LN and C levels were significantly higher than those in control group. Conclusion:serum liver fibrosis indexes can guide the degree of liver fibrosis. The ultrasound contrast can reflect the changes of liver blood flow dynamics, and it has a certain guiding significance to the assessment of the degree of liver fibrosis, the monitoring of the disease and the clinical treatment.

  6. Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation

    Directory of Open Access Journals (Sweden)

    Xiaxia Cai

    2016-03-01

    Full Text Available Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water, alcohol control group (basal diet, 50% alcohol (v/v, dextrose control group (basal diet, isocaloric amount of dextrose, and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg−1 respectively, 50% alcohol (v/v. The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS was applied to identify liver metabolite profiles. Results: Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid, as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, l-leucine, alanyl-leucine and l-phenylalanine. Conclusion: These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.

  7. A Metabolic Index of Ischemic Injury for Perfusion-Recovery of Cadaveric Rat Livers

    Science.gov (United States)

    Tolboom, Herman; Uygun, Basak; Berthiaume, Francois; Yarmush, Martin L.; Uygun, Korkut

    2011-01-01

    With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine. PMID:22194843

  8. Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol.

    Science.gov (United States)

    Lim, S P; Andrews, F J; O'Brien, P E

    1995-12-01

    Studies into the mechanism of acetaminophen (APAP)-induced hepatotoxicity have focused mainly at the hepatocellular level. This study aimed to investigate the effect of acetaminophen on the hepatic microvasculature using a vascular casting technique. Acetaminophen was administered at a dose of 650 mg/kg body weight (intraperitoneally) to fasted male Long Evans rats. Microvascular casting was performed at various points after drug administration. Liver casts from control rats showed good patency with normal hepatic microvasculature. Thirty-six hours after overdose with acetaminophen, liver casts showed rounded centrilobular cavities of various sizes, representing regions in which cast-filled sinusoids were absent with relatively normal microvasculature within periportal regions. Evidence of microvascular injury occurred as early as 5 hours after acetaminophen overdose. This injury consisted of changes to centrilobular sinusoids including areas of incomplete filling and dilated centrilobular sinusoids. Misoprostol (a prostaglandin E1 analog) treatment (6 x 25 micrograms/kg) given before and after acetaminophen administration markedly reduced the extent of microvascular injury with only small focal unfilled areas in the casts and a generally intact microvasculature. In conclusion, this study shows that overdosage with APAP resulted in an extensive, characteristic pattern of hepatic microvascular injury in the centrilobular region. The results also suggest that microvascular injury is an early event in the pathogenesis of acetaminophen hepatotoxicity. Misoprostol was found to protect against injury occurring at the microvascular level. PMID:7489988

  9. HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury

    Directory of Open Access Journals (Sweden)

    Manuela G. Neuman

    2012-01-01

    Full Text Available The present paper describes possible connections between antiretroviral therapies (ARTs used to treat human immunodeficiency virus (HIV infection and adverse drug reactions (ADRs encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.

  10. Implication of altered proteasome function in alcoholic liver injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The proteasome is a major protein-degrading enzyme,which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels: low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation.Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins.Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling (Ⅰ-κB and SOCS), thereby blocking cytokine signal transduction.Finally, ethanol-elicited blockade of interferon type 1 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class Ⅰ-restricted antigen presentation.

  11. Changes of sphingolipids profiles after ischemia-reperfusion injury in the rat liver

    Institute of Scientific and Technical Information of China (English)

    ZHAI Shu-ting; LIANG Ting-bo; LIU Guang-yi; XUE Fei; SUN Gong-ping; LIANG Liang; CHEN Wei; XU Guo-dong; LI Jun-jian; YANG Jun

    2009-01-01

    Background Hepatic ischemia-reperfusion (I/R) injury occurs in many clinical procedures. The molecular mechanisms responsible for hepatic I/R injury however remain unknown. Sphingolipids, in particular ceramide, play a role in stress and death receptor-induced hepatocellular death, contributing to the progression of several liver diseases including liver I/R injury. In order to further define the role of sphingolipids in hepatic I/R, systemic analysis of sphingolipids after reperfusion is necessary.Methods We investigated the lipidomic changes of sphingolipids in a rat model of warm hepatic I/R injury, by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS). Results The total amounts of ceramide and sphingomyelin and the intensity of most kinds of sphingolipids, mainly sphingomyelin, significantly increased at 1 hour after reperfusion (P <0.05) and reached peaks at 6 hours after reperfusion (P<0.01) compared to controls. Six new forms of ceramide and sphingomyelins appeared 6 hours after reperfusion, they were (m/z) 537.8, 555.7, 567.7, 583.8, 683.5 and 731.4 respectively. A ceramide-monohexoside (m/z) 804.4 (CMH(d18:1C22:1+Na)~+) also increased after reperfusion and correlated with extent of liver injury after reperfursion.Conclusions Three main forms of sphingolipids, ceramide, sphingomyelin and ceramide-monohexoside, are related to hepatic I/R injury and provide a new perspective in understanding the mechanisms responsible for hepatic I/R injury.

  12. Concomitant use of corticosteroid and antimicrobials for liver abscesses in patients with chronic granulomatous disease

    OpenAIRE

    Shin, Kyung-Sue; Lee, Mu Suk

    2016-01-01

    Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complicati...

  13. Serum Lipoprotein (a) Levels in Chronic Renal Failure and Liver Cirrhosis Patients. Relationship with Atherosclerosis

    OpenAIRE

    Essam Mady; Gehane Wissa; Ali Khalifa; Mahmoud El-Sabbagh

    1999-01-01

    This study was carried out to investigate the relationship between lipoprotein (a) levels and the development of atherosclerosis in chronic renal failure (CRF) patients with the possible role of the liver. Serum Lp (a) levels were measured in samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (transa...

  14. Exploring the effects of tert-butylhydroperoxide induced liver injury using proteomic approach

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • t-BHP's involvement in the ER stress pathway and liver cells injury. • ETFA as an important molecular target of t-BHP involving hepatotoxicity. • ETFA of t-BHP's action results in endoplasmic reticulum stress pathway. - Abstract: Tert-butyl hydroperoxide (t-BHP), an organic lipid hydroperoxide analog, has been demonstrated to exert pro-oxidant effects to evaluate mechanisms involving oxidative stress in hepatocyte cells and rat liver. Herein, we present an investigation of the event of molecular mechanism of t-BHP related acute liver injury. A proteomic approach was used to identify proteins which are differentially expressed in liver cells following t-BHP treatment and the mechanism of its action in apoptotic and endoplasmic reticulum stress pathways. Our results demonstrate that the t-BHP treatment of liver cells increased cell cytoxicity and apoptosis. t-BHP dose-dependent induction of cell apoptosis and stained liver sections relieved the acute rat liver injury were accompanied by sustained phosphorylation of JNK1/2 and p65. In addition, there were 13 differentially displayed proteins between the t-BHP-induced and untreated were assayed and validated in vivo. Furthermore, we demonstrated that t-BHP induced human Chang liver cell viability and apoptosis properties by up-regulating the levels of ETFA (electron transfer flavoprotein subunit alpha). This study demonstrated that there was an increase in the cellular levels of ETFA in the t-BHP induction in viability and apoptosis via the activation of JNK1/2 and NFκB signaling modules. NAC administration and shRNA ETFA conferred resistance to t-BHP-increased ETFA and CHOP expression via IRE1-alpha/TRAF2 complex formation, activation of JNK1/2 and p50. We concluded that the mechanism of t-BHP-induced an apoptosis cascade and endoplasmic reticulum stress in hepatocyte cells by up-regulation of ETFA, providing a new mechanism for liver injury

  15. Evaluation of CT perfusion imaging for the hemodynamics on liver ischemia reperfusion injury

    International Nuclear Information System (INIS)

    Objective: To evaluate the value of CT perfusion imaging (CTPI) on liver ischemia reperfusion injury. Methods: Twenty-one adult dogs were divided into three groups randomly: CON group, IV group and SMA group, each group consisted of 7 dogs. Under general anesthesia and laparotomy, porta hepatis were occluded for 45 minutes and reperfused 60 minutes later to establish IR injury models. Lipo- PGE1 administration was conducted 5 minutes before porta occlusion and 60 minutes after reperfusion in IV and SMA group, the dosage of Lipo-PGE1 was 1 μg/kg and rate of injection was 0.05 μg·kg-1·min- sodium chloride administration was slowly conducted 5 minutes before porta occlusion and 60 minutes after reperfusion in CON group as control, the rate of injection was 2 ml/kg. CTPI free portal pressure measurement (FPP) and pathological sampling were performed in succession and compared before and after IR. Paired-sample t test was used for self control study on parameters of liver perfusion before and after IR in each group, and One-way ANOVA was used for comparison of different values of each parameter of liver perfusion among groups. Results: (1) Each liver blood perfusion value decreased in different levels after IR. The different values of hepatic arterial perfusion (HAP), portal vein perfusion (PVP), total liver perfusion (TLP) before and after IR was (0.091±0.028), (0.149±0.011), (0.239±0.038) ml· min-1·ml-1 in CON group, and (0.053±0.013), (0.117±0.000), (0.171±0.012)ml·min-1· ml-1 in IV group, and(0.043±0.015), (0.104±0.005), (0.147±0.021) ml·min-1·ml-1 in SMA group, respectively. There were significant difference in each parameter of liver perfusion among groups (F=5.286, 2.894, 4.705; P 0.05). (3) Microscopically, the structures of liver were poorly defined with cloudy swelling of hepatocytes, stasis of erythrocytes in hepatic sinusoid, and neutrophilic granulocyte infiltration of portal area in control group. Evidence of liver injury was moderately

  16. Chronic spinal cord injury impairs primary antibody responses, but spares existing humoral immunity in mice

    OpenAIRE

    Oropallo, Michael A.; HELD, KATHERINE S.; Goenka, Radhika; Ahmad, Sifat A.; O’Neill, Patrick J.; Steward, Oswald; Lane, Thomas E.; Cancro, Michael P.

    2012-01-01

    Spinal cord injury (SCI) results in immune depression. To better understand how injury inhibits humoral immunity, the effects of chronic thoracic SCI on B cell development and immune responses to thymus-independent (TI) type-2 and thymus-dependent (TD) antigens were determined. Mice received complete crush injury or control laminectomy at either thoracic level 3 (T3), which disrupts descending autonomic control of the spleen, or at T9, which conserves most splenic sympathetic activity. Althou...

  17. Radiographic changes of lumbar spine and pelvis in chronic spinal injury

    Directory of Open Access Journals (Sweden)

    Shamsa Shariatpanahi

    2014-12-01

    Conclusion: The most frequent cause of chronic spinal injuries of our patients has been the injury by quiver, it seems our results may not be extended to all patients with spinal cord injury. In lumbar spine radiography of the patients, osteophytes, the quiver and psoriasis like ossifications were mostly seen. In the pelvis x-rays the most changes were hip joint narrowing, sacroiliitis and the heterotopic ossification.

  18. Chronic Multiple Knee Ligament Injuries: Epidemiological Analysis of More Than One Hundred Cases

    OpenAIRE

    Rosalvo Zosimo Bispo Júnior; Cezar Teruyuki Kawano; Alexandre Vieira Guedes

    2008-01-01

    INTRODUCTION: Diagnosis and treatment of multiple ligament injuries of the knee remain a real challenge for most surgeons. OBJECTIVE: To find out the epidemiological profile of patients surgically treated at a Reference Service with more than one chronic ligament injury in the knee joint. MATERIALS AND METHODS: Of a total of 978 operated patients, 109 presented at least two associated ligament injuries in the same knee. Demographic and clinical variables were evaluated. RESULTS: The anterior ...

  19. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Karvellas, Constantine J; Subramanian, Ram M

    2016-07-01

    Artificial (nonbiological) extracorporeal liver support devices aim to remove albumin-bound and water-soluble toxins to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. The following beneficial effects have been documented: improvement of jaundice, amelioration of hemodynamic instability, reduction of portal hypertension, and improvement of hepatic encephalopathy. The only randomized prospective multicenter controlled trial to show an improvement in transplant-free survival was for high-volume plasmapheresis. Biological (cell-based) extracorporeal liver support systems aim to support the failing liver through detoxification and synthetic function and warrant further study for safety and benefit. PMID:27339682

  20. Epidemiology and Healthcare Burden of Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Allen, Alina M; Kim, W Ray

    2016-05-01

    Chronic liver disease and cirrhosis, a common end result of viral hepatitis, alcohol abuse, and the emerging epidemic of nonalcoholic fatty liver disease are a significant source of morbidity and premature mortality globally. Acute clinical deterioration of chronic liver disease exemplifies the pinnacle of healthcare burden due to the intensive medical needs and high mortality risk. Although a uniformly accepted definition for epidemiological studies is lacking, acute-on-chronic liver failure (ACLF) is increasingly recognized as an important source of disease burden. At least in the United States, hospitalizations for ACLF have increased several fold in the last decade and have a high fatality rate. Acute-on-chronic liver failure incurs extremely high costs, exceeding the yearly costs of inpatient management of other common medical conditions. Although further epidemiological data are needed to better understand the true impact and future trends of ACLF, these data point to the urgency in the clinical investigation for ACLF and the deployment of healthcare resources for timely and effective interventions in affected patients. PMID:27172353

  1. Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Rolf J. Schauer; Sinan Kalmuk; Alexander L. Gerbes; Rosemarie Leiderer; Herbert Meissner; Friedrich W. Schildberg; Konrad Messmer; Manfred Bilzer

    2004-01-01

    AIM: To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.METHODS: Livers of male Lewis rats were transplantedafter 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n=8) or GSH administered via the jugular vein.RESULTS: Two hours after starting reperfusion plasma ALT increased to 1 457±281 U/L (mean±SE) in controls but to only 908±187 U/L (P<0.05) in animals treated with morphological findings on electron microscopy: GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatooytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50 μmol and and 97±18 mol/L, but to only 20±3 mol/L in untreated recipients. Furthermore, plasma glutathione disulfide (GSSG) increased untreated controls (1.8±0.5 mol/L vs 2.2±0.2 mol/L).CONCLUSION: Plasma GSH levels above a critical level may act as a "sink" for ROS produced in the hepatic vasculature during reperfusion of liver grafts. Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.

  2. Barley Sprouts Extract Attenuates Alcoholic Fatty Liver Injury in Mice by Reducing Inflammatory Response

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Joung-Hee; Kim, Sou Hyun; Oh, Ji Youn; Seo, Woo Duck; Kim, Kyung-Mi; Jung, Jae-Chul; Jung, Young-Suk

    2016-01-01

    It has been reported that barley leaves possess beneficial properties such as antioxidant, hypolipidemic, antidepressant, and antidiabetic. Interestingly, barley sprouts contain a high content of saponarin, which showed both anti-inflammatory and antioxidant activities. In this study, we evaluated the effect of barley sprouts on alcohol-induced liver injury mediated by inflammation and oxidative stress. Raw barley sprouts were extracted, and quantitative and qualitative analyses of its components were performed. The mice were fed a liquid alcohol diet with or without barley sprouts for four weeks. Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used to study the effect of barley sprouts on inflammation. Alcohol intake for four weeks caused liver injury, evidenced by an increase in serum alanine aminotransferase and aspartate aminotransferase activities and tumor necrosis factor (TNF)-α levels. The accumulation of lipid in the liver was also significantly induced, whereas the glutathione (GSH) level was reduced. Moreover, the inflammation-related gene expression was dramatically increased. All these alcohol-induced changes were effectively prevented by barley sprouts treatment. In particular, pretreatment with barley sprouts significantly blocked inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in LPS-stimulated RAW 264.7. This study suggests that the protective effect of barley sprouts against alcohol-induced liver injury is potentially attributable to its inhibition of the inflammatory response induced by alcohol. PMID:27455313

  3. Proteomic analysis of protective effects of polysaccharides from Salvia miltiorrhiza against immunological liver injury in mice.

    Science.gov (United States)

    Sun, Xue-Gang; Fu, Xiu-Qiong; Cai, Hong-Bing; Liu, Qiang; Li, Chun-Hua; Liu, Ya-Wei; Li, Ying-Jia; Liu, Zhi-Feng; Song, Yu-Hong; Lv, Zhi-Ping

    2011-07-01

    This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guérin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation. PMID:21480413

  4. Sodium aescinate ameliorates liver injury induced by methyl parathion in rats.

    Science.gov (United States)

    DU, Yuan; Wang, Tian; Jiang, Na; Ren, Ru-Tong; Li, Chong; Li, Chang-Kun; Fu, Feng-Hua

    2012-05-01

    Methyl parathion, a highly cytotoxic insecticide, has been used in agricultural pest control for several years. The present study investigated the protective effect of sodium aescinate (SA, the sodium salt of aescin) against liver injury induced by methyl parathion. Forty male Sprague-Dawley rats were randomly divided into 5 groups of 8 animals: the control group; the methyl parathion (15 mg/kg) poisoning (MP) group; and the MP plus SA at doses of 0.45, 0.9 and 1.8 mg/kg groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetylcholinesterase (AChE) in the plasma were assayed. Nitric oxide (NO) and antioxidative parameters were measured. Histopathological examination of the liver was also performed. The results revealed that SA had no effect on AChE. Treatment with SA decreased the activities of ALT and AST, and the levels of malondialdehyde and NO. Treatment with SA also increased the level of glutathione and the activities of superoxide dismutase and glutathione peroxidase. SA administration also ameliorated liver injury induced by methyl parathion poisoning. The findings indicate that SA protects against liver injury induced by methyl parathion and that the mechanism of action is related to the antioxidative and anti-inflammatory effects of SA. PMID:22969975

  5. Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.

    Science.gov (United States)

    Zhang, Weixin; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Zheng, Lingli; Han, Xu; Xu, Youwei; Wang, Changyuan; Peng, Jinyong

    2016-07-01

    In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future. PMID:27317992

  6. Biochemical mechanisms in drug-induced liver injury: Certainties and doubts

    Institute of Scientific and Technical Information of China (English)

    Ignazio Grattagliano; Leonilde Bonfrate; Catia V Diogo; Helen H Wang; David QH Wang; Piero Portincasa

    2009-01-01

    Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local O_2 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca~(2+)-dependent ATPase, reduced capability to sequester Ca~(2+) within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.

  7. Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos

    International Nuclear Information System (INIS)

    Although the effects of acute pesticide poisoning are well known but, hardly any data exists regarding the health effects after long-term low-level exposure. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The present study elucidates a possible mechanism by which chronic organophosphate exposure (dichlorvos 6 mg/kg b.wt., s.c. for 12 weeks) causes liver dysfunction. Mitochondria, a primary site of cellular energy generation and oxygen consumption represent a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic dichlorvos exposure on liver mitochondrial electron transport chain (ETC), mitochondrial calcium uptake and its implications on the induction of liver enzymes and liver dysfunction in rodent model. Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I and II activity. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria isolated from dichlorvos (DDVP) treated rat liver. Mitochondrial preparation from DDVP treated rat liver demonstrated significant increase in mitochondrial Ca2+ uptake and increase ROS levels. The alterations in the mitochondrial calcium uptake, mitochondrial electron transfer enzyme activities and increase ROS levels in turn might have caused an increase in liver enzymes (ALT, AST and ALP). The electron micrographs of liver cells depicted morphological changes in mitochondria as well as nucleus following 12 weeks of exposure to DDVP. These studies provide an evidence of impaired mitochondrial bioenergetics which may lead to liver dysfunction after chronic exposure to dichlorvos.

  8. Liver injury in HIV-1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    LI Zai-cun; LI Hong-jun; DAI Li-li; GAO Yan-qing; CAI Wei-ping; LI Hai-ying; HUANG Xiao-jie; ZHANG Tong; WU Hao

    2010-01-01

    Background Liver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.Methods Seventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n=45) and group 2(without liver injury, n=30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.Results Forty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (3g±9)years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%)patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%)and 12 (40%), respectively; P=0.018, 0.033, 0

  9. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    Directory of Open Access Journals (Sweden)

    Z.G. Zhao

    2014-02-01

    Full Text Available The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL on lipopolysaccharide (LPS-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1, myeloperoxidase (MPO, and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  10. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J. [Institute of Microcirculation, Hebei North University, Zhangjiakou, China, Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei (China)

    2014-02-17

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na{sup +}-K{sup +}-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na{sup +}-K{sup +}-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na{sup +}-K{sup +}-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  11. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    International Nuclear Information System (INIS)

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis

  12. Role of the Nalp3 inflammasome in acetaminophen-induced sterile inflammation and liver injury

    International Nuclear Information System (INIS)

    Acetaminophen (APAP) overdose is the leading cause of acute liver failure in the US and UK. Recent studies implied that APAP-induced injury is partially mediated by interleukin-1β (IL-1β), which can activate and recruit neutrophils, exacerbating injury. Mature IL-1β is formed by caspase-1, dependent on inflammasome activation. The objective of this invetstigation was to evaluate the role of the Nalp3 inflammasome on release of damage associated molecular patterns (DAMPs), hepatic neutrophil accumulation and liver injury (ALT, necrosis) after APAP overdose. Mice deficient for each component of the Nalp3 inflammasome (caspase-1, ASC and Nalp3) were treated with 300 mg/kg APAP for 24 h; these mice had similar neutrophil recruitment and liver injury as APAP-treated C57Bl/6 wildtype animals. In addition, plasma levels of DAMPs (DNA fragments, keratin-18, hypo- and hyper-acetylated forms of high mobility group box-1 protein) were similarly elevated with no significant difference between wildtype and gene knockout mice. In addition, aspirin treatment, which has been postulated to attenuate cytokine formation and the activation of the Nalp3 inflammasome after APAP, had no effect on release of DAMPs, hepatic neutrophil accumulation or liver injury. Together, these data confirm the release of DAMPs and a sterile inflammatory response after APAP overdose. However, as previously reported minor endogenous formation of IL-1β and the activation of the Nalp3 inflammasome have little impact on APAP hepatotoxicity. It appears that the Nalp3 inflammasome is not a promising therapeutic target to treat APAP overdose.

  13. Liver disease and the e antigen in HBsAg carriers with chronic renal failure.

    Science.gov (United States)

    Coughlin, G P; Van Deth, A G; Disney, A P; Hay, J; Wangel, A G

    1980-02-01

    This study was undertaken to assess the frequency of development and the stages of evolution of chronic liver disease in patients with renal failure who are chronic carriers of hepatitis B surface antigen. Cirrhosis or chronic active hepatitis developed in five of 21 patients and could not be predicted by the initial histological appearance or by HLA-A and B typing but was associated with the e antigen in four of the five patients. However, the antigen was not a consistent indicator of a poor prognosis, as the four other e antigen positive patients did not develop chronic liver disease during the period of the study. Transmission of hepatitis B to spouses occurred in four cases, was fatal in one instance, and was associated with e antigen in three of the four. Determination of e antigen status in renal unit patients who are carriers of hepatitis B surface antigen may be of value to the patient and his home environment. PMID:7380332

  14. Chronic Liver Failure after Treatment with Infliximab for Ankylosing Spondylitis in a Patient with Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    A 50-year-old man with ankylosing spondylitis was treated successfully with inlfiximab, who was also a HBV carrier for about twenty-ifve years. After injection with inlfiximab for four times, he developed jaundice and HBV DNA was detectable in serum. Serum aminotransferase and total bilirubin levels were higher than normal. Then he was hospitalized and treated with entacavir and Chinese herb medicine. But his liver damage aggravated and was diagnosed as acute on chronic liver failure. Finally, liver transplantation was carried out and he was cured successfully.

  15. Chronic copper poisoning and copper retention in the liver of sheep of different types

    Energy Technology Data Exchange (ETDEWEB)

    Lueke, F.; Wiemann, H.

    1970-01-01

    During the first breeding tests research on sheep for fattening and value at slaughter in the Institute for Efficiency in Animal Breeding for North Rhine Westphalia at Eickelborn, signs of chronic copper poisoning were found and the copper contents of the liver in some of the slaughtered sheep were tested. Copper retention in the liver was found to depend on the type of sheep. Texel sheep retained more copper in the liver than sheep used for milk and blackheads. Within the different types, the copper retention differed from progeny group to progeny group.

  16. The effect of chronic khat chewing on liver enzyme levels ( a Yemenian study)

    OpenAIRE

    Iman Ramzy; Mohammad Abdelbary; Hanan Abdelhafez; Dalia Omran; Mansour Al-Amrany; Aqeel M. Al-Shami

    2013-01-01

    Background Khat is a natural stimulant from the Catha edulis plant, which grows mainly in Yemen. The liver has been suspected to be vulnerable to the harmful effects of khat use. AimThe aim of the study was to investigate the effect of khat chewing on the liver function in healthy Yemeni individuals. MethodsLiver function tests were performed on 30 chronic khat chewers (group I) and 20 individuals who did not chew khat (group II). Results Twenty percent of group I and only 5% of grou...

  17. The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Piscaglia, Fabio, E-mail: fabio.piscaglia@unibo.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Marinelli, Sara, E-mail: sara_marinelli@libero.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Bota, Simona, E-mail: bota_simona1982@yahoo.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy “Victor Babeş”, Timişoara (Romania); Serra, Carla, E-mail: carla.serra@aosp.bo.it [Division of Medical Liver Transplant Care, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Venerandi, Laura, E-mail: laura.venerandi@gmail.com [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Leoni, Simona, E-mail: leonisimona@yahoo.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy); Salvatore, Veronica, E-mail: veronica.salvatore@unibo.it [Division of Internal Medicine, University of Bologna, General and University Hospital S. Orsola-Malpighi, Bologna (Italy)

    2014-03-15

    This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation.

  18. The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

    International Nuclear Information System (INIS)

    This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation

  19. Neutrophil-mediated liver injury during hepatic ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Yu-Xin Chen; Motomichi Sato; Kanji Kawachi; Yuji Abe

    2006-01-01

    BACKGROUND: Neutrophil plays an important role in hepatic ischemia-reperfusion injury. We investigated neutrophil inifltration in liver tissue, Kupffer cells' role in neutrophil accumulation, and apoptosis and regeneration of hepatocytes in liver ischemia-reperfusion injury. METHODS:Vascular microclamps were placed across the pedicles of the median and left lateral lobes for 90 minutes after 30% hepatectomy with the resection of caudate, right lateral and quadrate lobes and papillary process. Gadolinium chloride (GdCl3) was used to destroy Kupffer cells. Neutrophil activity was inhibited with Urge-8, a monoclonal antibody against neutrophil produced in our laboratory. GdCl3 (10 mg/kg) and Urge-8 (50 mg/kg) were given intravenously in respective groups. Ischemia control, GdCl3 and Urge-8 groups were compared. RESULTS: Following hepatic reperfusion, serum interleukin-8 (IL-8) levels and hepatic neutrophil counts peaked at 3 hours, and peak concentrations of alanine aminotransferase (ALT) occurred at 6 hours. Animals of the control group showed increases in neutrophil inifltration in liver tissue, liver enzyme levels, and apoptosis index of hepatocytes and decreases in overall survival rate and proliferating cell nuclear antigen (PCNA) expression of hepatocytes. The survival rates and PCNA proportion of hepatocytes were higher and the levels of hepatic neutrophil inifltration, liver enzymes, and hepatocyte apoptosis after reperfusion were lower in the GdCl3 and Urge-8 groups than those in the ischemia control group. CONCLUSIONS: Blockades of Kupffer cells' activity and neutrophil inifltration by GdCl3 and Urge-8 eliminate neutrophil-mediated hepatic injury and enhance subsequent hepatic regeneration during liver ischemia-reperfusion.

  20. Hepatic Xbp1 Gene Deletion Promotes Endoplasmic Reticulum Stress-induced Liver Injury and Apoptosis.

    Science.gov (United States)

    Olivares, Shantel; Henkel, Anne S

    2015-12-11

    Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR), a highly conserved signaling cascade that functions to alleviate stress and promote cell survival. If, however, the cell is unable to adapt and restore homeostasis, then the UPR activates pathways that promote apoptotic cell death. The molecular mechanisms governing the critical transition from adaptation and survival to initiation of apoptosis remain poorly understood. We aim to determine the role of hepatic Xbp1, a key mediator of the UPR, in controlling the adaptive response to ER stress in the liver. Liver-specific Xbp1 knockout mice (Xbp1(LKO)) and Xbp1(fl/fl) control mice were subjected to varying levels and durations of pharmacologic ER stress. Xbp1(LKO) and Xbp1(fl/fl) mice showed robust and equal activation of the UPR acutely after induction of ER stress. By 24 h, Xbp1(fl/fl) controls showed complete resolution of UPR activation and no liver injury, indicating successful adaptation to the stress. Conversely, Xbp1(LKO) mice showed ongoing UPR activation associated with progressive liver injury, apoptosis, and, ultimately, fibrosis by day 7 after induction of ER stress. These data indicate that hepatic XBP1 controls the adaptive response of the UPR and is critical to restoring homeostasis in the liver in response to ER stress. PMID:26504083

  1. Liver regeneration - The best kept secret: A model of tissue injury response

    Directory of Open Access Journals (Sweden)

    Javier A. Cienfuegos

    2014-03-01

    Full Text Available Liver regeneration (LR is one of the most amazing tissue injury response. Given its therapeutic significance has been deeply studied in the last decades. LR is an extraordinary complex process, strictly regulated, which accomplishes the characteristics of the most evolutionary biologic systems (robustness and explains the difficulties of reshaping it with therapeutic goals. TH reproduces the physiological tissue damage response pattern, with a first phase of priming of the hepatocytes -cell-cycle transition G0-G1-, and a second phase of proliferation -cell-cycle S/M phases- which ends with the liver mass recovering. This process has been related with the tissue injury response regulators as: complement system, platelets, inflammatory cytokines (TNF-α, IL-1β, IL-6, growth factors (HGF, EGF, VGF and anti-inflammatory factors (IL-10, TGF-β. Given its complexity and strict regulation, illustrates the unique alternative to liver failure is liver transplantation. The recent induced pluripotential cells (iPS description and the mesenchymal stem cell (CD133+ plastic capability have aroused new prospects in the cellular therapy field. Those works have assured the cooperation between mesenchymal and epithelial cells. Herein, we review the physiologic mechanisms of liver regeneration.

  2. Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

    Institute of Scientific and Technical Information of China (English)

    Hao Chen; Ying-Yan Yu; Ming-Jun Zhang; Xia-Xing Deng; Wei-Ping Yang; Jun Ji; Cheng-Hong Peng; Hong-Wei Li

    2004-01-01

    AIM: To observe the protective effect of heat shock protein 72 (HSP 72) induced by pretreatment of doxorubicin (DXR)on long-term cold preservation injury of rat livers.METHODS: Sprague-Dawley rats were administered intravenously DXR at a dose of 1 mg/kg body mass in DXR group and saline in control group. After 48 h, the rat liver was perfused with cold Linger′s and University of Wisconsin (UW) solutions and then was preserved in UW solution at 4 ℃ for 24, 36 and 48 h. AST, ALT, LDH and hyaluronic acid in preservative solution were determined. Routine HE,immunohistochemical staining for HSP 72 and electron microscopic examination of hepatic tissues were performed.RESULTS: After 24, 36 and 48 h, the levels of AST, ALT and hyaluronic acid in preservative solution were significantly higher in control group than in DXR group (P<0.05), while LDH level was not significantly different between the 2 groups (P>0.05). Hepatic tissues in DXR group were morphologically normal and significantly injured in control group. HSP 72was expressed in hepatocytes and sinusoidal endothelial cells in DXR group but not in control group.CONCLUSION: Pretreatment of DXR may extend the time of rat liver cold preservation and keep liver alive. The expression of HSP 72 in liver can prevent hepatocytes and sinusoidal endothelial cells from long-term cold preservation injury.

  3. A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death.

    Science.gov (United States)

    Catrysse, L; Farhang Ghahremani, M; Vereecke, L; Youssef, S A; Mc Guire, C; Sze, M; Weber, A; Heikenwalder, M; de Bruin, A; Beyaert, R; van Loo, G

    2016-01-01

    An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-κB (NF-κB) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-κB-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor. PMID:27253414

  4. The role of macrophages in obesity-driven chronic liver disease.

    Science.gov (United States)

    Devisscher, Lindsey; Verhelst, Xavier; Colle, Isabelle; Van Vlierberghe, Hans; Geerts, Anja

    2016-05-01

    Overnutrition and a sedentary lifestyle have resulted in the expansion of human obesity and associated metabolic complications. Nonalcoholic fatty liver disease has become the most common chronic liver disease in Western developed countries and can range from simple hepatic steatosis to a combination of steatosis, inflammation, and ballooning degeneration (nonalcoholic steatohepatitis). Obesity and its related liver disease are both risk factors for hepatocellular carcinoma, the incidence of which is expected to increase rapidly. The pathogenesis of nonalcoholic fatty liver disease and its progression to nonalcoholic steatohepatitis and hepatocellular carcinoma involve a deregulated lipid metabolism and a disruption of immune homeostasis and tissue integrity and are associated with a state of chronic inflammation. Macrophages are immune cells essential for maintenance of organ function and homeostasis but can also contribute to tissue damage and maintain a proinflammatory response. Their function depends on their origin, and tissue and can be converted based on local environmental cues. Resident liver macrophages, Kupffer cells, which function as sentinels, provide a first defense and are assisted by infiltrating monocytes in cases of hepatic insult. Until now, the contribution of tissue-residing and infiltrating macrophages to the onset and progression of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and hepatocellular carcinoma has been only partially unraveled. This review summarizes the current knowledge on the contribution of macrophage subsets to obesity-driven fatty liver disease and its complications and sheds light on still unexplored areas. PMID:26936934

  5. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Jain

    2014-01-01

    Full Text Available Total parenteral nutrition (TPN, a lifesaving therapy, involves providing nutrition by bypassing the gut. Unfortunately it is associated with significant complications including gut atrophy and parenteral nutrition associated liver disease (PNALD. PNALD includes steatosis, cholestasis, disrupted glucose metabolism, disrupted lipid metabolism, cirrhosis, and liver failure. The etiopathogenesis remains poorly defined; however, an altered enterohepatic circulation, disrupting nuclear receptor signaling, is emerging as a promising mechanism. Rodent models and our piglet TPN model have shown that, during regular feeding, bile acids activate farnesoid X receptor (FXR in the gut and enhance fibroblast growth factor 19 (FGF19 level. FGF19 regulates bile acid, lipid, and glucose metabolism. We noted reduced FGF19 with TPN use and substantial improvement in FGF19, bilirubin, and metabolic profiles with the FXR agonist chenodeoxycholic acid (CDCA. Additionally, CDCA caused gut growth and enhanced expression of glucagon like peptides (GLPs. GLPs regulate gut trophic effects, insulin, glucose homeostasis, and hepatic steatosis. GLP secretion is regulated by the CDCA activated receptor TGR5. This leads to an important conclusion that, in addition to a disrupted FXR-FGF19 axis, a disrupted TGR5-GLP axis may contribute to TPN related pathologies. Thus modulators of FXR-FGF19 and the TGR5-GLP axis could help bring forward novel treatment strategies.

  6. Hodgkin’s lymphoma coexisting with liver failure secondary to acute on chronic hepatitis B

    OpenAIRE

    Palta, Renee; McClune, Amy; Esrason, Karl

    2013-01-01

    Acute on chronic liver failure (ACLF) is rarely the initial manifestation of a malignant process or precipitated by the initiation of anti-viral treatment with a nucleoside or nucleotide agent. We report an unusual case of ACLF temporally associated with initiation of Entecavir for treatment of chronic hepatitis B. Early Hodgkin’s lymphoma (HL) was unmasked with initiation of the anti-viral treatment which may have exacerbated ACLF. To the best of our knowledge, this has not been described in...

  7. Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions

    Science.gov (United States)

    Tan, Cher Heng; Venkatesh, Sudhakar Kundapur

    2016-01-01

    Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including non-alcoholic fatty liver disease, will be elaborated. PMID:27563019

  8. Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kovač, Jelena Djokić, E-mail: jelenadjokic2003@yahoo.co.uk [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Daković, Marko [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Physical Chemistry, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Stanisavljević, Dejana [Institute for Statistics, Faculty of Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade (Serbia); Alempijević, Tamara; Ješić, Rada [Clinic for Gastroenterohepatology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Seferović, Petar [Institute for Cardiovascular Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Maksimović, Ružica [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade (Serbia)

    2012-10-15

    Purpose: To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. Materials and methods: Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b = 0, 50, 200, 400 and 800 s/mm{sup 2}. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. Results: The mean ADCs (×10{sup −3} mm{sup 2}/s; b = 0–800 s/mm{sup 2}) were significantly different at stage F1 versus F ≥ 2 (p < 0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV = 9.54 ± 6.3%). Conclusion: DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution.

  9. Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases

    International Nuclear Information System (INIS)

    Purpose: To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. Materials and methods: Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b = 0, 50, 200, 400 and 800 s/mm2. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. Results: The mean ADCs (×10−3 mm2/s; b = 0–800 s/mm2) were significantly different at stage F1 versus F ≥ 2 (p < 0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV = 9.54 ± 6.3%). Conclusion: DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution

  10. Correlation between ultrasonographic and pathologic diagnosis of liver fibrosis due to chronic virus hepatitis

    Institute of Scientific and Technical Information of China (English)

    Lei Shen; Ji-Qiang Li; Min-De Zeng; Lun-Gen Lu; Si-Tao Fan; Han Bao

    2006-01-01

    AIM: To evaluate the validity of ultrasonographic and pathologic diagnosis of liver fibrosis in patients with chronic viral hepatitis.METHODS: The liver fibrosis status in 324 patients was evaluated by both needle biopsy and ultrasonography.Liver fibrosis was divided into S0 -S4 stages. S4 stage was designated as definite cirrhosis. The ultrasonographic examination included qualitative variables, description of liver surface and parenchyma, and quantitative parameters, such as diameter of vessels, blood flow velocity and spleen size.RESULTS: Ultrasonographic qualitative description of liver surface and parenchyma was related with the severity of fibrosis. Among the quantitative ultrasonographic parameters, cut-off value of spleen length (12.1 cm) had a sensitivity of 0.600 and a specificity of 0.753 for diagnosis of liver cirrhosis. The diameters of spleen (8 mm) and portal vein (12 mm) had a diagnostic sensitivity of 0.600and 0.767, and a diagnostic specificity of 0.781 and 0.446,respectively. The diagnostic accuracy for liver cirrhosis was moderately satisfactory, and the negative predictive values of these parameters reached near 0.95.CONCLUSION: Ultrasonography can predict the degree of liver fibrosis or cirrhosis. A single ultrasonographic parameter is limited in sensitivity and specificity for the diagnosis of early cirrhosis. The presence or absence of liver cirrhosis in patients with chronic virus hepatitis can be detected using 2 or 3 quantitative and qualitative parameters, especially the length of spleen, the diameter of spleen vein and echo pattern of liver surface.

  11. The Association of HIV Viral Load with Indirect Markers of Liver Injury

    OpenAIRE

    Forrester, Janet E; Rhee, Martin S.; McGovern, Barbara H; Sterling, Richard K; Knox, Tamsin A; Terrin, Norma

    2011-01-01

    This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV) co-infected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs. undetectable, 1.45 in the HIV/HCV co-infected group and 70% greater odds of ...

  12. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    OpenAIRE

    Zhao, Z. G.; L. L. Zhang; C.Y. Niu; J. Zhang

    2014-01-01

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg...

  13. Liver Oxidative Stress after Renal Ischemia-Reperfusion Injury is Leukocyte Dependent in Inbred Mice

    OpenAIRE

    Khastar, Hossein; Kadkhodaee, Mehri; Sadeghipour, Hamid Reza; Seifi, Behjat; Hadjati, Jamshid; Najafi, Atefeh; Soleimani, Manoocher

    2011-01-01

    Objective(s) There are some reports in recent years indicating that renal ischemia – reperfusion (IR) induces deleterious changes in remote organs such as liver. The aim of this study was to investigate whether leukocytes have a role on the induction of oxidative stress in liver after renal IR. Materials and Methods Inbred mice in IR donor group were subjected to renal IR injury. In sham donor group the procedure was almost the same except that ischemia was not induced. Then, mice were anesth...

  14. Exploring BSEP Inhibition-Mediated Toxicity with a Mechanistic Model of Drug-Induced Liver Injury

    OpenAIRE

    Woodhead, Jeffrey L; Kyunghee eYang; Siler, Scott Q.; Paul Brent Watkins; Brouwer, Kim L.R.; Barton, Hugh A.; Howell, Brett A.

    2014-01-01

    Inhibition of the bile salt export pump (BSEP) has been linked to incidence of drug-induced liver injury (DILI), presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors bosentan and CP-724,714 and the non-hepatotoxic BSEP inhibitor telmisartan in humans in order to ex...

  15. Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury

    OpenAIRE

    Woodhead, Jeffrey L; Yang, Kyunghee; Siler, Scott Q.; Watkins, Paul B.; Brouwer, Kim L.R.; Barton, Hugh A.; Howell, Brett A.

    2014-01-01

    Inhibition of the bile salt export pump (BSEP) has been linked to incidence of drug-induced liver injury (DILI), presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors bosentan and CP-724,714 and the non-hepatotoxic BSEP inhibitor telmisartan in humans in order to ex...

  16. Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

    Science.gov (United States)

    Moreira, Sara Tatiana; Silva, Giovanni Faria; de Moraes, Camila Fernanda Verdichio; Grotto, Rejane Maria Tomasini; de Moura Campos Pardini, Maria Inês; Bicalho, Maria da Graça; Moliterno, Ricardo Alberto

    2016-09-01

    Hepatic fibrosis may be the result of repetitive injury to hepatocytes caused by HCV infection and the immune response to it. Cytokines regulate the inflammatory response to injury and modulate hepatic fibrogenesis. Single nucleotide polymorphisms (SNPs) located in cytokine genes may influence the cytokine expression and secretion that may contribute to hepatic fibrogenesis in HCV infection. The aim of this study was to determine the genotype of 22 SNPs found in the genes of 13 cytokines/cytokine receptors to assess the influence of polymorphic variants on the stage of liver damage in Brazilian patients chronically infected with HCV genotype 1 only. 141 unrelated patients were grouped according to their stage of fibrosis: absence of fibrosis or patients in the initial stages of fibrosis (F0-F2, n = 84), patients with advanced stages of fibrosis or cirrhosis (F3-F4, n = 57), without cirrhosis (F0-F3, n = 103), and with cirrhosis (F4, n = 38). The comparison of frequencies in each sub-sample was performed by 2 × 2 contingency tables using the chi-square or Fisher's exact test. Stepwise logistic regression was also used to assess independent associations between cirrhosis or fibrosis with polymorphic variants. The TNFA-308G:A genotype conferred increased risk of fibrosis and cirrhosis. The TNFA-238G:G genotype was associated with protection from cirrhosis. The IL10-819C:T genotype conferred protection from fibrosis and the IL1B-511C:T genotype conferred increased risk of cirrhosis. Some of these genotypes showed results on the borderline of statistical significance in the bivariate analysis. We conclude that gene variants of cytokines/receptors may influence liver damage in patients chronically infected by HCV genotype 1. PMID:27200267

  17. Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach

    OpenAIRE

    Hicham Khallafi; Kamran Qureshi

    2015-01-01

    Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infections has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive techni...

  18. Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury.

    Science.gov (United States)

    Hadi, Mackenzie; Westra, Inge M; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, Marjolijn T; Groothuis, Geny M M

    2013-05-20

    Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict IDILI in humans. According to the inflammatory stress hypothesis, the effects of inflammation interact with the effects of a drug or its reactive metabolite, precipitating toxic reactions in the liver. As a follow-up to our recently published mouse precision-cut liver slices model, an ex vivo model involving human precision-cut liver slices (hPCLS), co-incubated for 24 h with IDILI-related drugs and lipopolysaccharide (LPS), was developed to study IDILI mechanisms related to inflammatory stress in humans and to detect potential biomarkers. LPS exacerbated the effects of ketoconazole and clozapine toxicity but not those of their non-IDILI-related comparators, voriconazole and olanzapine. However, the IDILI-related drugs diclofenac, carbamazepine, and troglitazone did not show synergistic toxicity with LPS after incubation for 24 h. Co-incubation of ketoconazole and clozapine with LPS decreased the levels of glutathione in hPCLS, but this was not seen for the other drugs. All drugs affected LPS-induced cytokine release, but interestingly, only ketoconazole and clozapine increased the level of LPS-induced TNF release. Decreased levels of glutathione and cysteine conjugates of clozapine were detected in IDILI-responding livers following cotreatment with LPS. In conclusion, we identified ketoconazole and clozapine as drugs that exhibited synergistic toxicity with LPS, while glutathione and TNF were found to be potential biomarkers for IDILI-inducing drugs mediated by inflammatory stress. hPCLS appear to be suitable for further unraveling the mechanisms of inflammatory stress-associated IDILI. PMID:23565644

  19. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    International Nuclear Information System (INIS)

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  20. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, Shizuyo [Institute of Radiation Epidemiology, Radiation Effects Association, Tokyo (Japan); Kodama, Kazunori; Yoshizawa, Hiroshi [Hiroshima University School of Medicine, Hiroshima (Japan)

    2000-05-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  1. Seroprevalence of anti-HAV among patients with chronic viral liver disease

    Institute of Scientific and Technical Information of China (English)

    Hyun Chin Cho; Seung Woon Paik; Yu Jin Kim; Moon Seok Choi; Joon Hyeok Lee; Kwang Cheol Koh; Byung Chul Yoo; Hee Jung Son; Seon Woo Kim

    2011-01-01

    AIM: To investigate the current seroprevalence of hepatitis A virus (HAV) antibodies in patients with chronic viral liver disease in Korea. We also tried to identify the factors affecting the prevalence of HAV antibodies.METHODS: We performed an analysis of the clinical records of 986 patients (mean age: 49 ± 9 years, 714males/272 females) with chronic hepatitis B virus (HBV)or hepatitis C virus (HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS: The overall prevalence of IgG anti-HAV was 86.61% (854/986) in patients with chronic liver disease and was 88.13% (869/986) in age- and gendermatched patients from the Center for Health Promotion.The anti-HAV prevalence was 80.04% (405/506)in patients with chronic hepatitis B, 86.96% (20/23)in patients with chronic hepatitis C, 93.78% (422/450)in patients with HBV related liver cirrhosis, and 100%(7/7) in patients with HCV related liver cirrhosis. The anti-HAV prevalence according to the decade of age was as follows: 20s (6.67%), 30s (50.86%), 40s (92.29%), 50s (97.77%), and 60s (100%). The anti-HAV prevalence was significantly higher in patients older than 40 years compared with that in patients younger than 40 years of age. Multivariable analysis showed that age ≥ 40 years, female gender and metropolitan cities as the place of residence were independent risk factors for IgG anti-HAV seropositivity.CONCLUSION: Most Korean patients with chronic liver disease and who are above 40 years of age have already been exposed to hepatitis A virus.

  2. The relationship between serum thrombopoietin (TPO) levels and hepatic fibrosis markers in patients with chronic liver diseases

    International Nuclear Information System (INIS)

    Objective: This study evaluated the relationship between thrombopoietin (TPO) levels and Hepatic Fibrosis Markers with chronic liver diseases. Methods: Serum thrombopoietin levels was detected in patients with chronic liver disease and healthy controls with ELISA method, Hepatic Fibrosis Markers were measured with RIA. Results: TPO levels was no significance among chronic hepatits (120.41 ± 39.73) pg/ml vary stage, liver cirrhosis (125.84 ± 44.40) pg/ml and healthy controls (143.62 ± 47.97) pg/ml (P>0.05), serum TPO levels is correlated with Type IV Collagen in liver cirrhosis (r=0.517, P<0.05). Conclusion: Serum TPO levels is not associated with severity degree in chronic liver disease, and there is relative to hepatic fibrosis degree in liver cirrhosis. (authors)

  3. Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Mei-Zhu Hong

    Full Text Available Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers.The training set included chronic hepatitis B patients (n = 327, and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement.An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+ patients and 0.978, 85.0%, and 94.0% in the HBeAg(- patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+ patients and 0.977, 95.2%, and 95.8% in the HBeAg(- patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+ and HBeAg(- patients for recognizing significant inflammation (G ≥3.Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

  4. Liver Stiffness Measurement-Based Scoring System for Significant Inflammation Related to Chronic Hepatitis B

    Science.gov (United States)

    Hong, Mei-Zhu; Zhang, Ru-Mian; Chen, Guo-Liang; Huang, Wen-Qi; Min, Feng; Chen, Tian; Xu, Jin-Chao; Pan, Jin-Shui

    2014-01-01

    Objectives Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers. Methods The training set included chronic hepatitis B patients (n = 327), and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement. Results An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+) patients and 0.978, 85.0%, and 94.0% in the HBeAg(−) patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+) patients and 0.977, 95.2%, and 95.8% in the HBeAg(−) patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+) and HBeAg(−) patients for recognizing significant inflammation (G ≥3). Conclusions Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation. PMID:25360742

  5. Dynamic CT imaging of intrahepatic arterial blood flow in patients with chronic liver disease

    International Nuclear Information System (INIS)

    Using dynamic CT, the parenchymal hemodynamics of the livers was studied in patients with chronic liver disease. Dynamic CT was performed on 34 patients: 8 cases of chronic inactive hepatitis (CIH), 15 cases of chronic active hepatitis (CAH) and 11 cases of liver cirrhosis (LC). After rapid intravenous administration of contrast medium (61.2% iopamidol, 20 ml), 25 consecutive scans of the liver and spleen were performed and imaged on a single slice. The single scan time was one sec. Then, the following program was performed: 15 scans at 2 sec intervals, 7 scans at 15 sec intervals and 3 scans at 20 sec intervals. The fit curve for a single pass of the medium was obtained from the analysis of time-density curves in the right and left lobes of the liver and the spleen using a gamma variate function and the least square method. Three parameters were measured on the fit curve: the peak time (PT) was defined as the time to peak enhancement, the total volume component (TVC) was defined as the area beneath the curve between the rise point and the PT point for each lobe of the liver, and the arterial flow volume component (AVC) was defined as the area beneath the curve between the rise point and the PT point of the spleen. AVC in the right liver lobe did not significantly differ between groups, but significantly differed in the manner of CIH< CAH< LC (p<0.05) in the left lobe of the liver. The ratio of intrahepatic arterial blood flow to total hepatic blood flow (AVC/TVC) did not significantly differ between groups in the right lobe. In the left liver lobe, however, AVC/TVC significantly differed in the manner of CIH≤CAH< LC (p<0.01), and was significantly higher in LC patients than in CIH or CAH patients. These results suggest that the ratio of intrahepatic arterial blood flow in the left liver lobe increases as chronic liver disease progresses. (author)

  6. Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic liver injury.

    Science.gov (United States)

    Zhang, Youcai; Csanaky, Iván L; Cheng, Xingguo; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2012-06-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis. PMID:22461449

  7. Effects of liver inflammation on FibroScan diagnosis of hepatic fibrosis in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    刘志权

    2013-01-01

    Objective To investigate the influence of liver inflammation on the ability of the FibroScan non-invasive elastrography scanner to diagnose hepatic fibrosis in patients with chronic hepatitis B (CHB) .Methods A total of 124 CHB patients who received liver biopsy and concomitant liver stiffness measurement (LSM) by FibroScan

  8. The prevalence of chronic knee injury in triathletes

    OpenAIRE

    Clements, K.; Yates, B.; Curran, M

    1999-01-01

    OBJECTIVES: To add to the area of triathlon research by providing much needed prevalence data on knee injury in triathletes. METHOD: An incidental "in field" sampling technique was used to interview 58 triathletes aged between 15 and 55 years about knee injury during a triathlon event. The sample comprised 46 men and 12 women. RESULTS: Most knee injuries occurred during the running event (72%) and affected the lateral side of the knee (38%). In all, 78% of the sample sought treatment fr...

  9. Gut flora and bacterial translocation in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    John Almeida; Sumedha Galhenage; Jennifer Yu; Jelica Kurtovic; Stephen M Riordan

    2006-01-01

    Increasing evidence suggests that derangement of gut flora is of substantial clinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen, in particular, predispose to an increased potential for bacterial infection in this group. Recent studies suggest that, in addition to their role in the pathogenesis of overt infective episodes and the clinical consequences of sepsis, gut flora contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection.Furthermore, manipulation of gut flora to augment the intestinal content of lactic acid-type bacteria at the expense of other gut flora species with more pathogenic potential may favourably influence liver function in cirrhotic patients. Here we review current concepts of the various inter-relationships between gut flora, bacterial translocation, bacterial infection, pro-inflammatory cytokine production and liver function in this group.

  10. Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver

    Institute of Scientific and Technical Information of China (English)

    Samuel Wyllie; Neal R Barshes; Feng-Qin Gao; Saul J Karpen; John A Goss

    2008-01-01

    AIM: To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS: The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution.RESULTS: In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 min of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-κB was found between control and P-selectin antibody-treated livers.CONCLUSION: In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.

  11. Tetrahydroxystilbene glucoside protects against ethanol-induced liver injury in mice by inhibition of expression of inflammatuion-related factors

    Institute of Scientific and Technical Information of China (English)

    熊章鄂

    2013-01-01

    Objective To investigate the protective effects of tetrahydroxystilbene glucoside(TSG)against acute ethanol-induced liver injury in mice and to explore the possible mechanisms involved.Methods Kunming mice were

  12. Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice

    OpenAIRE

    Zhu, Run-Zhi; Xiang, Di; Xie, Chao; Li, Jing-Jing; Hu, Jian-Jun; He, Hong-Lin; Yuan, Yun-Sheng; GAO, JIN; HAN, WEI; Yu, Yan

    2010-01-01

    AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl4).

  13. Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

    OpenAIRE

    Mario Pirisi; Carlo Fabris; Maria Piera Panozzo; Giorgio Soardo; Pierluigi Toniutto; Ettore Bartou

    1993-01-01

    Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P

  14. Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver.

    Directory of Open Access Journals (Sweden)

    Tetsuo Nakajima

    Full Text Available Sake is a traditional Japanese alcoholic beverage that is gaining popularity worldwide. Although sake is reported to have beneficial health effects, it is not known whether chronic sake consumption modulates health risks due to radiation exposure or other factors. Here, the effects of chronic administration of sake on radiation-induced metabolic alterations in the livers of mice were evaluated. Sake (junmai-shu was administered daily to female mice (C3H/He for one month, and the mice were exposed to fractionated doses of X-rays (0.75 Gy/day for the last four days of the sake administration period. For comparative analysis, a group of mice were administered 15% (v/v ethanol in water instead of sake. Metabolites in the liver were analyzed by capillary electrophoresis-time-of-flight mass spectrometry one day following the last exposure to radiation. The metabolite profiles of mice chronically administered sake in combination with radiation showed marked changes in purine, pyrimidine, and glutathione (GSH metabolism, which were only partially altered by radiation or sake administration alone. Notably, the changes in GSH metabolism were not observed in mice treated with radiation following chronic administration of 15% ethanol in water. Changes in several metabolites, including methionine and valine, were induced by radiation alone, but were not detected in the livers of mice who received chronic administration of sake. In addition, the chronic administration of sake increased the level of serum triglycerides, although radiation exposure suppressed this increase. Taken together, the present findings suggest that chronic sake consumption promotes GSH metabolism and anti-oxidative activities in the liver, and thereby may contribute to minimizing the adverse effects associated with radiation.

  15. A prospective study to evaluate a new residential community reintegration programme for severe chronic brain injury: the Brain Integration Programme.

    NARCIS (Netherlands)

    Geurtsen, G.J.; Martina, J.D.; Heugten, C.M. van; Geurts, A.C.H.

    2008-01-01

    PURPOSE: To assess the effectiveness of a residential community reintegration programme for participants with chronic sequelae of severe acquired brain injury that hamper community functioning. DESIGN: Prospective cohort study. SUBJECTS: Twenty-four participants with acquired brain injury (traumatic

  16. Clinical practice of L-1-13C-phenylalanine in staging of chronic liver disease

    International Nuclear Information System (INIS)

    Twelve healthy controls, eight patients with chronic hepatitis graded G2S2, twelve patients with compensated liver cirrhosis, twelve patients with decompensated liver cirrhosis are studied by L-1-13C-phenylalanine breath test which is longed for 6 hours and 24 breath samples per subject are collected. 13CO2 enrichment are measured by isotope ratio mass spectrometer. The results show that 13CO2 half excretion time T1/2 can significantly differentiate the four groups (P13CER30 and 13Ccum60 can differentiate normal subjects, patients with compensated liver cirrhosis and decompensated liver cirrhosis, but the discrepancy of the them are not significant between patients with chronic hepatitis and healthy controls or patients with compensated (P>0.05). The three parameters are significantly correlated with some standard clinical serum-biochemical datum (P13C-phenylalanine breath test may be a promising clinical tool to grade chronic liver disease, which is safe, simple, quantificational and effective

  17. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

    Institute of Scientific and Technical Information of China (English)

    Sheilla Andrade Oliveira; Bruno Solano Freitas Souza; Cada Adriana Guimar(a)es-Ferreira; Elton Sá Barreto; Siane Campos Souza; Luiz Antonio Rodrigues Freitas; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2008-01-01

    AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.rnansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

  18. Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Liliana SC Mendes; Marcelo E Nita; Suzane K Ono-Nita; Evandro S Mello; Luiz Caetano da Silva; Ven(a)ncio AF Alves; Flair J Carrilho

    2008-01-01

    AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies.METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised.Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System.RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease.The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22+0.50 vs -0.15 ± 0.46, P = 0.0053).Immuno-expression of interferon receptor is not a relevant factor.CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis.Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients.

  19. Air Manganese Levels and Chronic Liver Disease Mortality in North Carolina Counties: An Ecological Study

    Directory of Open Access Journals (Sweden)

    John G. Spangler

    2012-09-01

    Full Text Available Manganese is an essential trace element which is toxic in high doses. Over the past several decades, manganese has replaced lead as the anti-knock agent in gasoline, raising concern about air and road-side contamination with this element. In addition, manganese is absorbed by the liver, making specific populations (e.g., pregnant women, infants and children, and patients with liver disease susceptible to its toxic effects. Using data from the US Census Bureau, the North Carolina State Center for Health Statistics, and the US Environmental Protection Agency, this ecological study evaluated chronic liver disease mortality rates in North Carolina’s 100 counties. It correlated these rates with county-level demographics as well as on-road and non-road air borne manganese concentrations. Median income by county was inversely associated with chronic liver disease mortality, while the logarithmically transformed airborne concentrations of on-road manganese were positively correlated with county-level chronic liver disease mortality. Because environmental manganese near roads is likely to increase over time, these pilot findings potentially have regulatory implications and argue for further research.

  20. Liver disease and the e antigen in HBsAg carriers with chronic renal failure.

    OpenAIRE

    Coughlin, G P; Van Deth, A G; Disney, A P; Van Hay, J.; Wangel, A. G.

    1980-01-01

    This study was undertaken to assess the frequency of development and the stages of evolution of chronic liver disease in patients with renal failure who are chronic carriers of hepatitis B surface antigen. Cirrhosis or chronic active hepatitis developed in five of 21 patients and could not be predicted by the initial histological appearance or by HLA-A and B typing but was associated with the e antigen in four of the five patients. However, the antigen was not a consistent indicator of a poor...

  1. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Bañares, Rafael; Nevens, Frederik; Larsen, Fin Stolze;

    2013-01-01

    Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189...

  2. Functional activity of sphingomyelin cycle in rat liver in chronic toxic hepatitis.

    Science.gov (United States)

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2008-12-01

    Activities of sphingomyelinase and ceramidase decreased in the liver in chronic toxic hepatitis and the balance between the levels of proapoptotic ceramide and antiapoptotic sphyngosine-1-phosphate shifts towards the latter substance. Pronounced changes in the qualitative and quantitative composition of fatty acids in the sphingomyelin cycle effector molecules were revealed. PMID:19513367

  3. Factors influencing health-related quality of life in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Abhasnee Sobhonslidsuk; Chatchawan Silpakit; Ronnachai Kongsakon; Patchareeya Satitpornkul; Chaleaw Sripetch; Anya Khanthavit

    2006-01-01

    AIM: To investigate the factors contributing to healthrelated quality of life (HRQL) in chronic liver disease (CLD).METHODS: Patients with CLD and age- and sexmatched normal subjects performed the validated Thai versions of the short-form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ). Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD,socioeconomic factors, and self-rating health perception on HRQL.RESULTS: Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed,blue-collar career and poor health perception increased significantly from chronic hepatitis to Child's Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL.In overall, the positive impact of self-rating health perception on HRQL was consistently showed.CONCLUSION: Advanced stages of chronic liver disease, old age, female sex, low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease.

  4. Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury.

    Science.gov (United States)

    Roy, Sanchari; Benz, Fabian; Alder, Jan; Bantel, Heike; Janssen, Joern; Vucur, Mihael; Gautheron, Jeremie; Schneider, Anne; Schüller, Florian; Loosen, Sven; Luedde, Mark; Koch, Alexander; Tacke, Frank; Luedde, Tom; Trautwein, Christian; Roderburg, Christoph

    2016-07-01

    miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury. PMID:27129188

  5. Antioxidant Activity of The Ancient Herb, Holy Basil in CCl4-Induced Liver Injury in Rats

    OpenAIRE

    Ponnusam, Yuvaraj; Louis, Therasilin; Madhavachandran, V; Kumar, Suresh; Thoprani, Neelam; Hamblin, Michael R.; Lakshmanan, Shanmugamurthy

    2015-01-01

    An herbal preparation called “holy basil plus herbal powder” (HBPP) containing Ocimum santum, Withania somnifera, Pongamia pinnata, Plumbago indica, Emblica officinalis and Curcuma longa was investigated as an antioxidant and hepatoprotective agent. The antioxidant activity of HBPP was investigated in rats with liver injury induced by oral administration of carbon tetrachloride:olive oil (1:1). HBPP was administered orally at 500 mg/kg daily for 7 days before. HBPP exhibited statistically sig...

  6. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

    OpenAIRE

    Guo-Yu Li; Ya-Xin Zheng; Fu-Zhou Sun; Jian Huang; Meng-Meng Lou; Jing-Kai Gu; Jin-Hui Wang

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectr...

  7. Caspase-1 Is Hepatoprotective during Trauma and Hemorrhagic Shock by Reducing Liver Injury and Inflammation

    OpenAIRE

    Menzel, Christoph L.; Sun, Qian; Loughran, Patricia A.; Pape, Hans-Christoph; Billiar, Timothy R; Scott, Melanie J.

    2011-01-01

    Adaptive immune responses are induced in liver after major stresses such as hemorrhagic shock (HS) and trauma. There is emerging evidence that the inflammasome, the multiprotein platform that induces caspase-1 activation and promotes interleukin (IL)-1β and IL-18 processing, is activated in response to cellular oxidative stress, such as after hypoxia, ischemia and HS. Additionally, damage-associated molecular patterns, such as those released after injury, have been shown to activate the infla...

  8. Protective effects from Houttuynia cordata aqueous extract against acetaminophen-induced liver injury

    OpenAIRE

    Chen, Wei-Ting; Yang, Chieh-ling; Yin, Mei-chin

    2014-01-01

    Background Protective effects of Houttuynia cordata aqueous extract (HCAE) against acetaminophen-induced hepatotoxicity in Balb/cA mice were examined. Methods HCAE, at 1 or 2 g/L, was added into the drinking water for 4 weeks. Acute liver injury was induced by acetaminophen treatment intraperitoneally (350 mg/kg body weight). Results Acetaminophen treatment significantly depleted hepatic glutathione (GSH) content, increased hepatic malonyldialdehyde (MDA), reactive oxygen species (ROS) and ox...

  9. Multiple compound-related adverse properties contribute to liver injury caused by endothelin receptor antagonists.

    Science.gov (United States)

    Kenna, J Gerry; Stahl, Simone H; Eakins, Julie A; Foster, Alison J; Andersson, Linda C; Bergare, Jonas; Billger, Martin; Elebring, Marie; Elmore, Charles S; Thompson, Richard A

    2015-02-01

    Drug-induced liver injury has been observed in patients treated with the endothelin receptor antagonists sitaxentan and bosentan, but not following treatment with ambrisentan. The aim of our studies was to assess the possible role of multiple contributory mechanisms in this clinically relevant toxicity. Inhibition of the bile salt export pump (BSEP) and multidrug resistance-associated protein 2 was quantified using membrane vesicle assays. Inhibition of mitochondrial respiration in human liver-derived HuH-7 cells was determined using a Seahorse XF(e96) analyzer. Cytochrome P450 (P450)-independent and P450-mediated cell toxicity was assessed using transfected SV40-T-antigen-immortalized human liver epithelial (THLE) cell lines. Exposure-adjusted assay ratios were calculated by dividing the maximum human drug plasma concentrations by the IC50 or EC50 values obtained in vitro. Covalent binding (CVB) of radiolabeled drugs to human hepatocytes was quantified, and CVB body burdens were calculated by adjusting CVB values for fractional drug turnover in vitro and daily therapeutic dose. Sitaxentan exhibited positive exposure-adjusted signals in all five in vitro assays and a high CVB body burden. Bosentan exhibited a positive exposure-adjusted signal in one assay (BSEP inhibition) and a moderate CVB body burden. Ambrisentan exhibited no positive exposure-adjusted assay signals and a low CVB body burden. These data indicate that multiple mechanisms contribute to the rare, but potentially severe liver injury caused by sitaxentan in humans; provide a plausible rationale for the markedly lower propensity of bosentan to cause liver injury; and highlight the relative safety of ambrisentan. PMID:25467130

  10. Severe Starvation-Induced Hepatocyte Autophagy as a Cause of Acute Liver Injury in Anorexia Nervosa: A Case Report

    OpenAIRE

    Rubbia Brandt, L.; Spahr, L; S. Restellini

    2013-01-01

    Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common c...

  11. The Role of Mesothelial Cells in Liver Development, Injury, and Regeneration.

    Science.gov (United States)

    Lua, Ingrid; Asahina, Kinji

    2016-03-23

    Mesothelial cells (MCs) cover the surface of visceral organs and the parietal walls of cavities, and they synthesize lubricating fluids to create a slippery surface that facilitates movement between organs without friction. Recent studies have indicated that MCs play active roles in liver development, fibrosis, and regeneration. During liver development, the mesoderm produces MCs that form a single epithelial layer of the mesothelium. MCs exhibit an intermediate phenotype between epithelial cells and mesenchymal cells. Lineage tracing studies have indicated that during liver development, MCs act as mesenchymal progenitor cells that produce hepatic stellate cells, fibroblasts around blood vessels, and smooth muscle cells. Upon liver injury, MCs migrate inward from the liver surface and produce hepatic stellate cells or myofibroblast depending on the etiology, suggesting that MCs are the source of myofibroblasts in capsular fibrosis. Similar to the activation of hepatic stellate cells, transforming growth factor β induces the conversion of MCs into myofibroblasts. Further elucidation of the biological and molecular changes involved in MC activation and fibrogenesis will contribute to the development of novel approaches for the prevention and therapy of liver fibrosis. PMID:26934883

  12. Liver, biliary and pancreatic injuries in pancre-aticobiliary maljunction model in cats

    Institute of Scientific and Technical Information of China (English)

    Feng Chen; Lin Tang; Zhi-Qi Zhang; Bing-Wei Jin; Wei-Feng Dong; Jian Wang; Shun-Gen Huang

    2015-01-01

    BACKGROUND: Pancreaticobiliary maljunction is a high risk factor of pancreatitis and biliary tract cancer. How this mal-junction affects the liver remains obscure. This study aimed to examine the effects of pancreaticobiliary maljunction on the liver, pancreas and gallbladder in a cat model. METHODS: A model of choledocho-pancreatic side-to-side ductal anastomosis was created in ten cats.Before the procedure, a small piece of tissue from the liver, pancreas and gallbladder was collected as a control. The common channel formation was checked by cholecystography. The livers, pancreases and gall-bladders of these cats were harvested for histological examina-tion. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry. RESULTS: Seven of the 10 cats survived for 6 months after surgery. The color of the liver was darker in the PBM model than the control specimen, with nodules on the surface. His-tological examination showed ballooning changes and inflam-matory infiltrations and the histopathological score increased significantly (P CONCLUSION: The present study demonstrated that pancreatico-biliary maljunction can lead to the injuries of the liver, pancreas and gallbladder.

  13. Influence Of Whey Protein For Abrogating Liver Injury In Female Rats

    International Nuclear Information System (INIS)

    The objective of this study was to determine the possible benefits of whey protein concentrate (44% protein, 5% fat and 4.6% ash in dry weight) against liver injury induced by CCl4 . It was carried out by evaluating the effect of the daily feeding of female rats on diet containing 15% whey protein instead of soybean protein for four weeks on some biochemical and histological changes in liver of female rats.The data showed that injection with CCl4 (1 ml /kg body weight 3 times / week) caused significant decrease in body weight with disturbances in liver functions as significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and bilirubin and significant decrease in serum albumin, FT3 and an increase in AFP levels. A marked significant decrease in glutathione content and significant increase in lipid peroxidation was also observed in hepatic tissues. The histological examination revealed that CCl4 treatment showed marked degenerative changes in liver hepatocytes and sinusoids.The results also showed that feeding on diet containing whey protein for two or four weeks during CCl4 treatment minimized the disturbance of the liver functions and liver histology.

  14. Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

    Science.gov (United States)

    Kappus, Matthew R; Mendoza, Mardeli Saire; Nguyen, Douglas; Medici, Valentina; McClave, Stephen A

    2016-08-01

    Sarcopenia, a loss of muscle mass, is being increasingly recognized to have a deleterious effect on outcomes in patients with chronic liver disease. Factors related to diet and the inflammatory nature of chronic liver disease contribute to the occurrence of sarcopenia in these patients. Sarcopenia adversely influences quality of life, performance, morbidity, success of transplantation, and even mortality. Specific deficiencies in macronutrients (protein, polyunsaturated fatty acids) and micronutrients (vitamins C, D, and E, carotenoids, and selenium) have been linked to sarcopenia. Lessons learned from nutritional therapy in geriatric patient populations may provide strategies to manage sarcopenia in patients with liver disease. Combining diet modification and nutrient supplementation with an organized program of exercise may help ameliorate or even reverse the effects of sarcopenia on an already complex disease process. PMID:27372291

  15. The relationship between cardiac and liver iron evaluated by MR imaging in haematological malignancies and chronic liver disease

    International Nuclear Information System (INIS)

    Although iron overload is clinically significant, only limited data have been published on iron overload in haematological diseases. We investigated cardiac and liver iron accumulation by magnetic resonance imaging (MRI) in a cohort of 87 subjects who did not receive chelation, including 59 haematological patients. M-HIC (MRI-based hepatic iron concentration, normal values <36 μmol/g) is a non-invasive, liver biopsy-calibrated method to analyse iron concentration. This method, calibrated to R2 (transverse relaxation rate), was used as a reference standard (M-HIC(R2)). Transfusions and ferritin were evaluated. Mean M-HIC(R2) and cardiac R* of all patients were 142 μmol/g (95% CI, 114–170) and 36.4 1/s (95% CI, 34.2–38.5), respectively. M-HIC(R2) was higher in haematological patients than in patients with chronic liver disease or normal controls (P<0.001). Clearly elevated cardiac R2* was found in two myelodysplastic syndrome (MDS) patients with severe liver iron overload. A poor correlation was found between liver and cardiac iron (n=82, r=0.322, P=0.003), in contrast to a stronger correlation in MDS (n=7, r=0.905, P=0.005). In addition to transfusions, MDS seemed to be an independent factor in iron accumulation. In conclusion, the risk for cardiac iron overload in haematological diseases other than MDS is very low, despite the frequently found liver iron overload

  16. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury.

    Science.gov (United States)

    Li, Guo-Yu; Zheng, Ya-Xin; Sun, Fu-Zhou; Huang, Jian; Lou, Meng-Meng; Gu, Jing-Kai; Wang, Jin-Hui

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury. PMID:26389883

  17. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

    Directory of Open Access Journals (Sweden)

    Guo-Yu Li

    2015-09-01

    Full Text Available This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory in acute liver injury. Pathological observation, reactive oxygen species (ROS detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS. Similarity ensemble approach (SEA docking, molecular modeling, molecular docking, and molecular dynamics (MD simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.

  18. Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.

    Science.gov (United States)

    Dai, Jie; Liu, Mingwei; Ai, Qing; Lin, Ling; Wu, Kunwei; Deng, Xinyu; Jing, Yuping; Jia, Mengying; Wan, Jingyuan; Zhang, Li

    2014-06-01

    Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl₂)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl₂-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl₄-induced elevation of hepatic H₂O₂ levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl₄-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT. PMID:24717679

  19. Chronic hepatitis E virus infection after living donor liver transplantation via blood transfusion: a case report.

    Science.gov (United States)

    Kurihara, Takeshi; Yoshizumi, Tomoharu; Itoh, Shinji; Harimoto, Norifumi; Harada, Noboru; Ikegami, Toru; Inagaki, Yuki; Oshiro, Yukio; Ohkohchi, Nobuhiro; Okamoto, Hiroaki; Maehara, Yoshihiko

    2016-12-01

    Although it occurs worldwide, hepatitis E virus (HEV) infection in developed countries is generally foodborne. HEV infection is subclinical in most individuals. Although fulminant liver failure may occur, progression to chronic hepatitis is rare. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. His liver function was classified as Child-Pugh grade C. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy. PMID:27059470

  20. Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients

    OpenAIRE

    Somaya Hashem; Gamal Esmat; Wafaa Elakel; Shahira Habashy; Safaa Abdel Raouf; Samar Darweesh; Mohamad Soliman; Mohamed Elhefnawi; Mohamed El-Adawy; Mahmoud ElHefnawi

    2016-01-01

    Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate...

  1. Penicillin-induced liver injury during treatment for ocular neurosyphilis.

    Science.gov (United States)

    Wilkinson, Janelle; Zainal, Abir; Naqvi, Syed Yaseen

    2016-01-01

    A 51-year-old man, homosexual, recently diagnosed with ocular neurosyphilis, presented to the emergency room with a 1-day history of fevers and chills. His vital signs were significant for a temperature of 102.8°F and tachycardia of 125 bpm. The patient had experienced blurred vision in his left eye and was diagnosed with ocular neurosyphilis 10 days prior to the current presentation. He was treated with a 14-day course of high-dose intravenous penicillin and oral prednisone. His laboratory studies were significant for transaminitis, with an aspartate aminotransferase of 1826 U/L, alanine aminotransferase of 1743 U/L, total bilirubin of 1.2 mg/dL and alkaline phosphatase of 68 U/L. After ruling out viral aetiologies and toxin-induced hepatic injury, penicillin was discontinued on the day following admission and transaminases promptly improved with resolution of symptoms. The patient's vision returned to normal within 2 weeks after discharge from hospital. PMID:27389728

  2. Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Abeer El-Sayed Abd El-Wahab

    2012-04-01

    Full Text Available Background: Chronic liver disease (CLD is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1.Objectives: This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers.Patients and Methods: Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA, and erythrocyte-reduced glutathione (GSH were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis and 15 healthy controls.Results: HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients.Conclusions: HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD.

  3. The experimental study of radiation injury on bile duct and liver tissue

    International Nuclear Information System (INIS)

    Objective: To investigate the safety, acceptance and the effective extent of 192Ir-internal irradiation, providing theoretical guidelines for HC. Methods: Sixteen male healthy hybrid dogs enrolled in the experiment were divided into 4 groups of 4 each. The brachytherapy applicator was introduced from gall bladder into the convergence of cystic duct with common hepatic duct during the operation and a small chip of 1 cm3 liver tissue was cut off and taken for control later on. The animals in group A-D were irradiated by 192Ir-internal irradiation with 30 Gy, 40 Gy, 50 Gy arid 60 Gy at the correlative dose points respectively. Animals were put to death after 10 days subsequently, with sampling specimens obtained from radiation cystic duct and the in between liver tissue with the distant cystic duct. The radiation injury of the cystic duct and liver tissue near bile ducts were observed and studied by light microscope and transmission election microscope. Results: By the limit of the safest endurance dose(50 Gy) of Bile duct, unreversed injury of the nuclei of liver cells occurred at 0 to 15 mm from bile duct revealed by transmission electron microscope and light microscope. The whole biliary duct wall would be undergone necrosis with irradiation dose over 60 Gy. Conclusions: Normal bile duct possesses good endurance to 192Ir-internal irradiation. Within the safest endurance limit of 50 Gy the effective irradiation field could reach 15 mm from the involved bile duct. (authors)

  4. Hepatoprotective Effects of Panus giganteus (Berk. Corner against Thioacetamide- (TAA- Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Wei-Lun Wong

    2012-01-01

    Full Text Available Panus giganteus, a culinary and medicinal mushroom consumed by selected indigenous communities in Malaysia, is currently being considered for large scale cultivation. This study was undertaken to investigate the hepatoprotective effects of P. giganteus against thioacetamide- (TAA- induced liver injury in Sprague-Dawley rats. The rats were injected intraperitoneally with TAA thrice weekly and were orally administered freeze-dried fruiting bodies of P. giganteus (0.5 or 1 g/kg daily for two months, while control rats were given vehicle or P. giganteus only. After 60 days, rats administered with P. giganteus showed lower liver body weight ratio, restored levels of serum liver biomarkers and oxidative stress parameters comparable to treatment with the standard drug silymarin. Gross necropsy and histopathological examination further confirmed the hepatoprotective effects of P. giganteus. This is the first report on hepatoprotective effects of P. giganteus. The present study showed that P. giganteus was able to prevent or reduce the severity of TAA-induced liver injury.

  5. Effect of oophorectomy and exogenous estrogen replacement on liver injury in experimental obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Hamdi Bülent Ucan; Mehmet Kaplan; Bülent Salman; Utku Yilmaz; B Bülent Mentes; Cemalettin Aybay

    2008-01-01

    AIM: To investigate the role of estrogen on liver injury in an experimental obstructive jaundice model. METHODS: Three groups of female rats were constituted; group 1 was oophorectomized and given E2 (n = 14), group 2 was oophorectomized and given placebo (n = 14), and group 3 was sham operated (n = 14). Fourteen days following constitution of bile duct ligation, all groups were compared in terms of serum tests, histopathologic parameters, and tissue levels of IFN-γ, and IL-6. RESULTS: The parameters representing both the injury and/or the reactive response and healing were more pronounced in groups 1 and 2 (χ2 = 17. 2, χ2 =10. 20; χ2 = 12. 4, P < 0. 05). In the sham operated or E2 administered groups significantly lower tissue levels of IFN-γ, and higher IL-6 levels were found. In contrast, high IFN-γ, and low IL-6 tissue levels were found in the oophorectomized and placebo group (P < 0. 001). Kupffer cell alterations were observed to be more pronounced in the groups i and 3 (χ2 = 6. 13, P < 0. 05). CONCLUSION: Our study indicates that E2 impaired liver functions, accelerated both the liver damage and healing. In the conditions of bile duct obstruction, estrogen significantly changed the cytokine milieu in the liver.

  6. Stem cell injury and restitution after ionizing irradiation in intestine, liver, salivary gland, mesenteric lymph node

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Hyun; Cho, Kyung Ja; Lee, Sun Joo; Jang, Won Suk [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    There is little information about radiation injury on stem cell resident in other organs. In addition there is little experimental model in which radiation plays a role on proliferation stem cell in adult organ. This study was carried out to evaluate the early response of tissue injury and restitution in intestine, liver, salivary gland and lymph node, and to develop in vivo model to investigate stem cell biology by irradiation. The study is to assay the early response to radiation and setup an animal model for radiation effect on cellular response. Duodenal intestine, liver, submandibular salivary gland and mesenteric lymph node were selected to compare apoptosis and proliferating cell nuclear antigen (PCNA) expression to radiosensitivity. For the effect of radiation on cellular responses, rats were irradiated during starvation. Conclusionly, this study showed the value of apoptosis in detection system for evaluating cellular damage against radiation injury. Because apoptosis was regularly inducted depending on tissue-specific pattern, dose and time sequence as well as cellular activity. Furthermore in vivo model in the study will be helped in the further study to elucidate the relationship between radiation injury and starvation or malnutrition. (author). 22 refs., 6 figs

  7. Stem cell injury and restitution after ionizing irradiation in intestine, liver, salivary gland, mesenteric lymph node

    International Nuclear Information System (INIS)

    There is little information about radiation injury on stem cell resident in other organs. In addition there is little experimental model in which radiation plays a role on proliferation stem cell in adult organ. This study was carried out to evaluate the early response of tissue injury and restitution in intestine, liver, salivary gland and lymph node, and to develop in vivo model to investigate stem cell biology by irradiation. The study is to assay the early response to radiation and setup an animal model for radiation effect on cellular response. Duodenal intestine, liver, submandibular salivary gland and mesenteric lymph node were selected to compare apoptosis and proliferating cell nuclear antigen (PCNA) expression to radiosensitivity. For the effect of radiation on cellular responses, rats were irradiated during starvation. Conclusionly, this study showed the value of apoptosis in detection system for evaluating cellular damage against radiation injury. Because apoptosis was regularly inducted depending on tissue-specific pattern, dose and time sequence as well as cellular activity. Furthermore in vivo model in the study will be helped in the further study to elucidate the relationship between radiation injury and starvation or malnutrition. (author). 22 refs., 6 figs

  8. Baclofen reversed thermal place preference in rats with chronic constriction injury.

    Science.gov (United States)

    Salte, K; Lea, G; Franek, M; Vaculin, S

    2016-06-20

    Chronic constriction injury to the sciatic nerve was used as an animal model of neuropathic pain. Instead of frequently used reflex-based tests we used an operant thermal place preference test to evaluate signs of neuropathic pain and the effect of baclofen administration in rats with neuropathy. Chronic constriction injury was induced by four loose ligations of the sciatic nerve. Thermal place preference (45 °C vs. 22 °C and 45 °C vs. 11 °C) was measured after the ligation and after the administration of baclofen in sham and experimental rats. Rats with the chronic constriction injury spent significantly less time on the colder plate compared to sham operated animals at the combination 45 °C vs. 11 °C. After administration of baclofen (10 mg/kg s.c.), the aversion to the colder plate in rats with chronic constriction injury disappeared. At the combination 45 °C vs. 22 °C, no difference in time spent on colder and/or warmer plate was found between sham and experimental animals. These findings show the importance of cold allodynia evaluation in rats with chronic constriction injury and the effectiveness of baclofen in this neuropathic pain model. PMID:26447518

  9. [A case of multiple liver abscesses associated with Streptococcus salivarius in a patient with chronic periodontitis].

    Science.gov (United States)

    Kamachi, Saori; Otsuka, Taiga; Tsuji, Chika; Nakashita, Shunya; Ide, Yasushi; Mizuta, Toshihiko

    2014-08-01

    Streptococcus salivarius is an oral commensal bacterium that rarely causes disease in humans. Here, we report a case of liver abscess associated with S. salivarius in a 41-year-old woman who presented with continuous abdominal discomfort, fatigue, and fever. She was diagnosed with multiple liver abscesses; she underwent percutaneous transhepatic abscess drainage. Thereafter, S. salivarius was isolated in all bacterial cultures of the drained abscesses, and it was sensitive to penicillins. She made a good recovery after treatment. In the absence of an infective source other than chronic periodontitis, the cause of liver abscesses was attributed to oral S. salivarius. S. salivarius is a normal oral commensal, and oral commensals must be considered if the infective origin of liver abscess cannot be determined. PMID:25100350

  10. 75 FR 14602 - Guidance for Industry on Drug-Induced Liver Injury: Premarketing Clinical Evaluation; Opening of...

    Science.gov (United States)

    2010-03-26

    ... on Drug-Induced Liver Injury: Premarketing Clinical Evaluation; Opening of Comment Period for Future Revision of Guidance Dated July 2009; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION... industry published in the Federal ] Register July 30, 2009, entitled ``Drug-Induced Liver...

  11. Silencing of Id2 Alleviates Chronic Neuropathic Pain Following Chronic Constriction Injury.

    Science.gov (United States)

    Jiang, Liuming; Wu, Qun; Yang, Tao

    2016-05-01

    Inhibitor of DNA binding/differentiation 2 (Id2) belongs to a helix-loop-helix family of proteins. Recent studies have showed that Id2 plays a pivotal role in neuronal survival and neuroprotection. However, under neuropathic pain conditions, the role of Id2 is still unclear. In this study, we investigated the effect of Id2 on neuropathic pain in a rat chronic constriction injury (CCI) model. Our results demonstrated that Id2 was upregulated in the dorsal root ganglion (DRG) in a CCI rat in a time-dependent manner. Intrathecal short-hairpin RNA (shRNA)-Id2 attenuates mechanical allodynia and thermal hyperalgesia in CCI rats, and inhibits the expression of TNF-α and IL-1β in the DRG in CC