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Sample records for alcohol-induced liver disease

  1. Histone modifications and alcohol-induced liver disease: Are altered nutrients the missing link?

    Institute of Scientific and Technical Information of China (English)

    Akshata Moghe; Swati Joshi-Barve; Smita Ghare; Leila Gobejishvili; Irina Kirpich; Craig J McClain; Shirish Barve

    2011-01-01

    Alcoholism is a major health problem in the United States and worldwide, and alcohol remains the single most significant cause of liver-related diseases and deaths. Alcohol is known to influence nutritional status at many levels including nutrient intake, absorption, utilization, and excretion, and can lead to many nutritional disturbances and deficiencies. Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease (ALD). There is growing interest regarding epigenetic changes, including histone modifications that regulate gene expression during disease pathogenesis. Notably, modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation, and control gene transcription. This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD. The review is focused on four critical metabolites, namely, acetate, S-adenosylmethionine, nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

  2. Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Bode, C.;

    2006-01-01

    Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

  3. Using PG-Liposome-Based System to Enhance Puerarin Liver-Targeted Therapy for Alcohol-Induced Liver Disease.

    Science.gov (United States)

    Zhao, Ying-Zheng; Zhang, Lu; Gupta, Pardeep K; Tian, Fu-Rong; Mao, Kai-Li; Qiu, Kai-Yan; Yang, Wei; Lv, Chuan-Zhu; Lu, Cui-Tao

    2016-12-01

    A critical issue for alcohol-induced liver disease (ALD) therapeutics is the lack of a highly efficient delivery system. In this study, a Puerarin-propylene glycol-liposome system was prepared for the purpose of targeting puerarin, an isoflavon, to the liver. Transmission electron microscope (TEM) results showed the liposomes to be spherical in shape with an average diameter of 182 nm with a polydispersity index of 0.239. The zeta potential of the particles was about -30 mV. The entrapment efficiency of puerarin was above 90%. MTT-based assay in HpeG2 cells showed no significant cytotoxicity in the presence of up to 25% concentration of the system containing 3% puerarin. In vivo performance of this system was studied in mice. Pharmacokinetics and distribution of puerarin-PG-liposome system was studied relative to puerarin solution at the same dose levels. The results show that puerarin-PG-liposome prolonged drug retention time and decreased elimination of puerarin in mice (AUC of liposome system and solution was 9.5 and 4.0 mg h L(-1), respectively). Furthermore, propylene glycol (PG)-liposome system enhanced puerarin distribution into liver and spleen, while decreasing puerarin distribution in other tissues. Overall, the puerarin-PG-liposome system showed enhanced therapeutic effect in mice with ALD.

  4. Synthesis of Toll-like receptor 4 in Kupffer cells and its role in alcohol-induced liver disease

    Institute of Scientific and Technical Information of China (English)

    左国庆; 龚建平; 刘长安; 吴传新; 李生伟; 戴立里

    2003-01-01

    Objectives To observe the synthesis of Toll-like receptor (TLR) 4 protein and its mRNA expression in Kupffer cells (KCs) and evaluate the role of TLR 4 in liver injury to rats through alcohol-induced liver disease.Methods Twenty-eight Wistar rats were divided into two groups: ethanol-fed (group E) and control (group C). Group E rats were given ethanol at a dose of 5-12 g@kg-1@d -1, while group C received dextrose. Animals from bot h groups were killed at 4 and 8 weeks. The KCs were isolated and synthesis of T LR 4 protein was determined by laser scanning confocal microscopy. TLR 4 mRNA e xpression in KCs was determined by reverse transcription polymerase chain reacti on (RT-PCR) analysis. The levels of endotoxin, tumor necrosis factor-α (TN F-α) and interleukin-6 (IL-6) in plasma were determined. Changes in liver pathology were observed.Results Laser scanning confocal microscopy showed that the intensity of fluorescence of TLR 4 protein in group E was stronger than group C. Ethanol administration led to a significant increase in TLR 4 mRNA expression in group E compared with grou p C (P<0.05). The concentrations of plasma endotoxin, TNF-α and IL- 6 were higher in group E than in group C (P<0.05). Liver sections from rat s in group E demonstrated marked pathological changes.Conclusion Ethanol administration can lead to the synthesis of TLR 4 protein and its gene expression in KCs, indicating that TLR 4 may play a major role in the development of alcohol-induced liver injury.

  5. Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges.

    Science.gov (United States)

    Mathews, Stephanie; Xu, Mingjiang; Wang, Hua; Bertola, Adeline; Gao, Bin

    2014-05-15

    Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

  6. IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Bode, C.

    2002-01-01

    Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin......, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...... endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced...

  7. 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.

  8. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Science.gov (United States)

    Banerjee, Atrayee; Abdelmegeed, Mohamed A; Jang, Sehwan; Song, Byoung-Joon

    2015-01-01

    The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  9. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  10. Enzymatic modification enhances the protective activity of citrus flavonoids against alcohol-induced liver disease.

    Science.gov (United States)

    Park, Ho-Young; Choi, Hee-Don; Eom, Hyojin; Choi, Inwook

    2013-08-15

    Alcoholic liver disease (ALD) can be developed by a prolonged or large intake of alcohol in a short period of time. ALD is considered as a leading cause for a liver injury in modern dietary life. This study was aimed to investigate the effects of orally administrated citrus flavonoids (CFs) and their enzymatically modified ones (EM-CFs) to prevent ALD. Hesperidin and narirutin were extracted from peels of Citrus unshiu by ultra-sonication and purified further. These CFs were modified enzymatically through glycosylation and de-rhamnosylation by the actions of cyclodextrin glucanotransferase (CGTase) and hesperidinase, respectively. CFs and EM-CFs were fed to ICR mouse along with ethanol for 8 weeks, and changes in lipid contents, lipid peroxidation, GSH, antioxidant enzymes activity and proinflammatory cytokines in hepatic tissues were observed. Administration of CFs and EM-CFs along with alcohol significantly suppressed increases in prognostic parameters of a hepatocellular injury. Especially, EM-CFs fed groups maintained malondialdehyde, GSH levels and catalase activity in hepatic tissues close to those of the normal diet fed group. Abrupt increases in proinflammatory cytokines such as IκB-α, TNF-α, IL-1β and IL-6 in hepatocytes due to a chronic alcohol uptake were significantly suppressed by co-administration of EM-CFs. These results indicate that although the administration of CFs can alleviate ALD through preventing excessive lipid formation, protecting the antioxidant system and suppressing induction of inflammation in hepatocytes, their effectiveness can be further improved by glycosylation and de-rhamnosylation.

  11. Alcohol-induced steatosis in liver cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required,but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1)which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferatoractivated receptor-alpha (PPAR-α) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-α(TNF-α), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.

  12. Cholesterol and sphingolipids in alcohol-induced liver injury.

    Science.gov (United States)

    Fernández, Anna; Colell, Anna; Garcia-Ruiz, Carmen; Fernandez-Checa, José C

    2008-03-01

    The pathogenesis of alcohol-induced liver disease (ALD) is still poorly understood. One of the clues to its progression relates to the alcohol-mediated susceptibility of hepatocytes to cell death by reactive oxygen species (ROS) and inflammatory cytokines. Tumor necrosis factor alpha (TNF) has been considered a key ALD mediator with acidic sphingomyelinase (ASMase)-mediated ceramide generation playing a critical role. TNF receptor 1 and 2 knock-out mice or ASMase(-/-) mice exhibit resistance to alcohol-mediated fatty liver and cell death. Furthermore, alcohol feeding has been shown to sensitize hepatocytes to TNF due to the limitation of mitochondrial glutathione (mGSH) through impaired import of GSH from the cytosol due to altered membrane order parameter caused by mitochondrial cholesterol increase. Selective pharmacological depletion of mGSH sensitizes hepatocytes to TNF-mediated cell death, which reproduces the observations found with alcohol feeding. TNF signaling analyses in hepatocytes with or without mGSH depletion indicate that mGSH prevents cardiolipin peroxidation (CLOOH) formation by TNF-induced ROS via ASMase and that CLOOH cooperates with oligomerized Bax to cause mitochondrial outer membrane permeabilization through destabilization of the lipid bilayer via increased bilayer-to-inverted hexagonal phase transitions. Thus, activation of ASMase and cholesterol-mediated mGSH depletion both collaborate to promote alcohol-induced TNF-mediated hepatocellular damage, suggesting novel therapeutic opportunities in ALD.

  13. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Schwarz, E.

    2008-01-01

    of ALD in dependence on the sex of the patients. RESULTS: No significant differences between males and females with ALD were calculated for the intake (per kg body weight/day) of protein, carbohydrates, fat, and the intake (per kg body weight/day) of most micronutrients. In females with ALD, higher...... of ALD in animal experiments, the hypothesis of the present retrospective cross-sectional study was that gender-dependent (micro-) nutrient intake in patients with ALD may cause the higher susceptibility of women to this disease. METHODS: In 210 patients (male: 158, female: 52) with different stages...... of ALD (ALD1: mild stage of liver damage; ALD2: moderately severe changes of the liver with signs of hepatic inflammation; ALD3: severely impaired liver function) and in 336 controls (male: 208, female: 128), nutrient intake was determined by a computer-guided diet history, and related to the severity...

  14. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schafer, C.; Schwarz, E.

    2008-01-01

    of ALD in dependence on the sex of the patients. Results: No significant differences between males and females with ALD were calculated for the intake (per kg body weight/day) of protein, carbohydrates, fat, and the intake (per kg body weight/day) of most micronutrients. In females with ALD, higher...... of ALD in animal experiments, the hypothesis of the present retrospective cross-sectional study was that gender-dependent (micro-) nutrient intake in patients with ALD may cause the higher susceptibility of women to this disease. Methods: In 210 patients (male: 158, female: 52) with different stages...... of ALD (ALD1: mild stage of liver damage; ALD2: moderately severe changes of the liver with signs of hepatic inflammation; ALD3: severely impaired liver function) and in 336 controls (male: 208, female: 128), nutrient intake was determined by a computer-guided diet history, and related to the severity...

  15. Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

    Directory of Open Access Journals (Sweden)

    Tian Ya-ping

    2010-11-01

    Full Text Available Abstract Background Growth hormone (GH is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD and explored the underlying molecular mechanisms. Methods Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism. Results Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P P P P P Conclusions GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

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

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    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.

  17. 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

    2015-10-14

    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.

  18. 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.

  19. Ebselen prevents early alcohol-induced liver injury in rats.

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    Kono, H; Arteel, G E; Rusyn, I; Sies, H; Thurman, R G

    2001-02-15

    Oxidants have been shown to be involved in alcohol-induced liver injury. Moreover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoselenium compound and glutathione peroxidase mimic, decreases oxidative stress and protects against stroke clinically. This study was designed to test the hypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/kg twice daily, intragastrically) or vehicle (1% tylose) was administered throughout the experiment. Mean urine ethanol concentrations were not significantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (37 +/- 5 IU/l) by enteral ethanol (112 +/- 7 IU/l); ebselen blunted this increase significantly (61 +/- 8 IU/l). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes were blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathione peroxidase activity in serum or liver tissue, ebselen blocked the increase in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increased the activity of NF-kappaB over 5-fold, the number of infiltrating neutrophils 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blunted all of these effects significantly. These results indicate that ebselen prevents early alcohol-induced liver injury, most likely by preventing oxidative stress, which decreases inflammation.

  20. Ginger-derived nanoparticles protect against alcohol-induced liver damage.

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    Zhuang, Xiaoying; Deng, Zhong-Bin; Mu, Jingyao; Zhang, Lifeng; Yan, Jun; Miller, Donald; Feng, Wenke; McClain, Craig J; Zhang, Huang-Ge

    2015-01-01

    Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant-derived nanoparticles.

  1. Ginger-derived nanoparticles protect against alcohol-induced liver damage

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhuang

    2015-11-01

    Full Text Available Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN–mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2 led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant–derived nanoparticles.

  2. Effects of triterpenoid from Schisandra chinensis on oxidative stress in alcohol-induced liver injury in rats.

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    Li, Bin; Zhu, Lijie; Wu, Ting; Zhang, Jiachen; Jiao, Xinyao; Liu, Xiuying; Wang, Yanqun; Meng, Xianjun

    2015-03-01

    Alcohol-induced oxidative stress plays a crucial role in the pathological development of alcoholic liver disease. The aim of this study was to investigate the effects of triterpenoid from Schisandra chinensis on oxidative stress in alcohol-induced liver injury in rats. We found that the administration of triterpenoid attenuated alcohol-induced oxidative stress in multiple organs including liver. Moreover, the impaired liver function and histological changes resulted from alcohol consumption was improved by triterpenoid treatment. Finally, we found that pretreatment with triterpenoid from Schisandra chinensis to alcohol-fed rats increased the expression level of haem oxygenase-1 (HO-1) while inhibited the induction of cytochrome P-450 2E1 (CYP2E1) in liver microsomes. Further assays revealed that the microsomal activity of HO-1 was accordingly induced whereas CYP2E1 was suppressed in rats received triterpenoid intervention. Our findings suggest that triterpenoid from Schisandra chinensis may protect against alcohol-induced liver injury through ameliorating oxidative stress in rats.

  3. Mechanism for Prevention of Alcohol-Induced Liver Injury by Dietary Methyl Donors

    OpenAIRE

    Powell, Christine L.; Bradford, Blair U.; Craig, Christopher Patrick; Tsuchiya, Masato; Uehara, Takeki; O’Connell, Thomas M.; Pogribny, Igor P.; Melnyk, Stepan; Koop, Dennis R.; Bleyle, Lisa; Threadgill, David W.; Rusyn, Ivan

    2010-01-01

    Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors ...

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

    OpenAIRE

    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...

  5. Amelioration effects of traditional Chinese medicine on alcohol-induced fatty liver

    Institute of Scientific and Technical Information of China (English)

    Hyun-Jeong Kwon; Yun-Young Kim; Se-Young Choung

    2005-01-01

    AIM: To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida,Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata.METHODS: The rats were separated randomly into five groups. One (the CD group) was fed a control diet for 10 wk, another (the ED group) fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three (the TCM group) were fed an ethanol-containing isocaloric liquid TCM2000, respectively) weekly during the last 4 wk.RESULTS: ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride (TG) and total cholesterol (TC), liver TG and TC, serum alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group.Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group.CONCLUSION: TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation,reversing fatty liver and liver damage, and can be usedas a remedy for alcoholic fatty liver.

  6. Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

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    Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

    2016-07-01

    Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD.

  7. Alcohol-induced oxidative stress in rat liver microsomes: Protective effect of Emblica officinalis.

    Science.gov (United States)

    Reddy, Vaddi Damodara; Padmavathi, Pannuru; Hymavathi, Reddyvari; Maturu, Paramahamsa; Varadacharyulu, N Ch

    2014-06-01

    The protective effect of Emblica officinalis fruit extract (EFE) against alcohol-induced oxidative damage in liver microsomes was investigated in rats. EFE (250mg/kg b.wt/day) and alcohol (5g/kg b.wt/day, 20%, w/v) were administered orally to animals for 60 days. Alcohol administration significantly increased lipid peroxidation, protein carbonyls with decreased sulfhydryl groups in microsomes, which were significantly restored to normal levels in EFE and alcohol co-administered rats. Alcohol administration also markedly decreased the levels of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in the liver microsomes, which were prevented with EFE administration. Further, alcohol administration significantly increased the activities of cytochrome P-450, Na(+)/K(+) and Mg(2+) ATPases and also membrane fluidity. But, administration of EFE along with alcohol restored the all above enzyme activities and membrane fluidity to normal level. Thus, EFE showed protective effects against alcohol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and restoring the various membrane bound and antioxidant enzyme activities to normal levels, and also by protecting the membrane integrity in rat liver microsomes. In conclusion, the polyphenolic compounds including flavonoid and tannoid compounds present in EFE might be playing a major role against alcohol-induced oxidative stress in rats.

  8. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    Science.gov (United States)

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

  9. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

    Directory of Open Access Journals (Sweden)

    Hyo Jin Lee

    2015-06-01

    Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

  10. Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors.

    Science.gov (United States)

    Powell, Christine L; Bradford, Blair U; Craig, Christopher Patrick; Tsuchiya, Masato; Uehara, Takeki; O'Connell, Thomas M; Pogribny, Igor P; Melnyk, Stepan; Koop, Dennis R; Bleyle, Lisa; Threadgill, David W; Rusyn, Ivan

    2010-05-01

    Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors is mediated by an effect on the oxidative metabolism of alcohol in the liver. Male C57BL/6J mice were administered a control high-fat diet or diet enriched in methyl donors with or without alcohol for 4 weeks using the enteral alcohol feeding model. As expected, attenuation of ALI and an increase in reduced glutathione:oxidized glutathione ratio were achieved with methyl donor supplementation. Interestingly, methyl donors led to a 35% increase in blood alcohol elimination rate, and while there was no effect on alcohol metabolism in the stomach, a profound effect on liver alcohol metabolism was observed. The catalase-dependent pathway of alcohol metabolism was induced, yet the increase in CYP2E1 activity by alcohol was blunted, which may be mitigating production of oxidants. Additional factors contributing to the protective effects of methyl donors in ALI were increased activity of low- and high-K(m) aldehyde dehydrogenases leading to lower hepatic acetaldehyde, maintenance of the efficient mitochondrial energy metabolism, and promotion of peroxisomal beta-oxidation. Profound changes in alcohol metabolism represent additional important mechanism of the protective effect of methyl donors in ALI.

  11. 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.

  12. 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.

  13. Liver Disease

    Science.gov (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ ...

  14. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  15. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  16. Photobiomodulation on alcohol induced dysfunction

    Science.gov (United States)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  17. Neonatal androgenization exacerbates alcohol-induced liver injury in adult rats, an effect abrogated by estrogen.

    Directory of Open Access Journals (Sweden)

    Whitney M Ellefson

    Full Text Available Alcoholic liver disease (ALD affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2 and ethanol metabolizing enzymes (cytochrome P450, CYP450 are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl, androgenized females (Andro and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood.

  18. Hepatoprotective Effect of Fermented Soybean (Nutrient Enriched Soybean Tempeh against Alcohol-Induced Liver Damage in Mice

    Directory of Open Access Journals (Sweden)

    Hamidah Mohd Yusof

    2013-01-01

    Full Text Available Recently, soybean tempeh has received great attention due to many advantages such as higher nutritional value, lower production cost, and shorter fermentation time. In this study, the in vivo hepatoprotective and antioxidant effects of nutrient enriched soybean tempeh (NESTE were determined. NESTE fermentation process which involved anaerobic incubation was previously proclaimed to increase the content of amino acids and antioxidant properties remarkably. The evaluation of histological sections, serum biochemical markers (aspartate aminotransferase (AST, alanine aminotransferase (ALT, and cholesterol and triglycerides (TG, liver immune response level (nitric oxide (NO and liver antioxidant level (superoxide dismutase (SOD, ferric reducing antioxidant power (FRAP, and malondialdehyde (MDA was conducted in order to compare the effects of nonfermented soybean extract (SBE and fermented soybean extract (NESTE on alcohol-induced liver damage in mice. Results demonstrated that 1000 mg/kg of NESTE can significantly reduce the levels of AST, ALT, cholesterol, TG, MDA, and NO. On the other hand, it also raised the level of SOD and FRAP. Furthermore, the histological examination on 1000 mg/kg NESTE treatment group showed that this extract was capable of recovering the damaged hepatocytes to their normal structures. Thus, it can be concluded that NESTE produced through fermentation process was able to enhance hepatoprotective and antioxidant effects in vivo.

  19. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Liver Disease and IBD

    Science.gov (United States)

    ... Home > Resources > Liver Disease and IBD Go Back Liver Disease and IBD Email Print + Share Several complications ... be necessary to make the definitive diagnosis. FATTY LIVER DISEASE (HEPATCI STEATOSIS) This is the most common ...

  2. Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Jung Dae Lim

    2015-02-01

    Full Text Available Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1, a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

  3. Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury

    Directory of Open Access Journals (Sweden)

    Yange Liu

    2017-01-01

    Full Text Available In the present study, the components of A. cinnamomea (AC mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt and phosphor-nuclear factor-κB (NF-κB in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

  4. Fucoidan from Fucus vesiculosus protects against alcohol-induced liver damage by modulating inflammatory mediators in mice and HepG2 cells.

    Science.gov (United States)

    Lim, Jung Dae; Lee, Sung Ryul; Kim, Taeseong; Jang, Seon-A; Kang, Se Chan; Koo, Hyun Jung; Sohn, Eunsoo; Bak, Jong Phil; Namkoong, Seung; Kim, Hyoung Kyu; Song, In Sung; Kim, Nari; Sohn, Eun-Hwa; Han, Jin

    2015-02-16

    Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg) for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1), a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

  5. Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-α and prevents early alcohol-induced liver injury in mice

    DEFF Research Database (Denmark)

    Ge, Xiadong; Leung, Tung-Ming; Arriazu, Elena;

    2014-01-01

    Although osteopontin (OPN) is induced in alcoholic patients, its role in the pathophysiology of alcoholic liver disease (ALD) remains unclear. Increased translocation of lipopolysaccharide (LPS) from the gut is key for the onset of ALD because it promotes macrophage infiltration and activation...... by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining, and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower alanine aminotransferase (ALT) activity, hepatocyte ballooning degeneration, LPS levels, the inflammation...... score, and the number of macrophages and TNFα+ cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed binding affinity for LPS which prevented macrophage activation, reactive oxygen, and nitrogen species generation...

  6. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  7. Models of alcoholic liver disease in rodents: a critical evaluation

    DEFF Research Database (Denmark)

    de la M. Hall, P.; Lieber, C.S.; De Carli, L.M.

    2001-01-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were J. Christian Bode and Hiroshi Fukui. The presentations were (1) Essentials and the course of the pathological spectrum of alcoholic liver disease in humans, by P. de la M. Hall; (2......) Lieber-DeCarli liquid diet for alcohol-induced liver injury in rats, by C. S. Lieber and L. M. DeCarli; (3) Tsukamoto-French model of alcoholic liver injury, by S. W. French; (4) Animal models to study endotoxin-ethanol interactions, by K. O. Lindros and H. Järveläinen; and (5) Jejunoileal bypass...... operation in rats-A model for alcohol-induced liver injury? by Christiane Bode, Alexandr Parlesak, and J. Christian Bode....

  8. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  9. Research Areas: Liver Disease

    Science.gov (United States)

    ... and C, or by genetic mutations. Other liver diseases can be triggered by autoimmune reactions or drug toxicity. The rise in obesity in the United States has led to a rise in nonalcoholic fatty liver disease. Many liver diseases place individuals at higher risk ...

  10. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  11. Liver transplant for cholestatic liver diseases.

    Science.gov (United States)

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.

  12. Antioxidant supplements for liver diseases

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2011-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  13. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  14. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  15. Prolactin and liver disease

    NARCIS (Netherlands)

    A.G.C. Bauer (Alexander)

    1982-01-01

    textabstractCirrhosis of the liver is associated with profound endocrinological disturbances. Until recently it was thought that these disturbances were caused mainly by ineffective elimination of hormones by the diseased liver. It is now known that the pathogenesis of disturbed hormonal function in

  16. Epigenetic regulation in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Pranoti Mandrekar

    2011-01-01

    Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcohol-induced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, histone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD.

  17. Nrf2-mediated antioxidant response by ethanolic extract of Sida cordifolia provides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism.

    Science.gov (United States)

    Rejitha, S; Prathibha, P; Indira, M

    2015-03-01

    Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

  18. [Wilson disease: liver form].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Álvarez, Félix; Sumire Umeres, Julia; Cok García, Jaime

    2015-01-01

    Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients.

  19. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  20. Role of microRNAs in Alcohol-Induced Multi-Organ Injury

    Directory of Open Access Journals (Sweden)

    Sathish Kumar Natarajan

    2015-11-01

    Full Text Available Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption.

  1. Preparation of total flavonoids from loquat flower and its protective effect on acute alcohol-induced liver injury in mice

    Directory of Open Access Journals (Sweden)

    Shao-Kang Wu

    2015-03-01

    Full Text Available This study aimed to research the preparation techniques of total flavones from loquat flower (TFLF, its anti-oxidation capacity, and its protective effect on hepatic injury. The best extraction parameters by orthogonal experimentation were water at 100°C, extraction time 2.5 hours, solid/liquid ratio 1:20, and three decoctions. The chromogenic reaction to the flavones showed that loquat flowers mainly contained flavone, flavonol, and flavanone compounds combining ortho-phenolic hydroxyl group structure in the 10–30% ethanol fraction. The anti-oxidant capacity of O2−· was 26.09% and of OH−·was 83.01% by salicylic acid and pyrogallol auto-oxidation. Compared with the model group, TFLF lowered the levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, and malondialdehyde and liver index significantly, and upregulated the expression of adipose triglyceride lipase and Heine oxygenase-1 mRNA. The present findings suggest that TFLF has protective effect on acute alcoholinduced liver injury in mice and may be related to its antioxidant and free-radical scavenging activity.

  2. Liver disease and malnutrition.

    Science.gov (United States)

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  3. Liver regeneration in nonalcoholic fatty liver disease

    OpenAIRE

    Aldo Lagomarsino

    2012-01-01

    Steatosis is the accumulation of fat in hepatocytes, which may be the result of liver regeneration or pathological processes such as alcoholic and nonalcoholic fatty liver disease. Despite its importance, in both cases the exact mechanism that prevails in fatty liver regeneration is poorly understood. Previous studies have shown that patients with fatty liver express dispar regeneration, possibly due to the accumulation of reactive oxygen species generated by inflammatory processes caused by ...

  4. Gut microbiota and liver diseases.

    Science.gov (United States)

    Minemura, Masami; Shimizu, Yukihiro

    2015-02-14

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.

  5. Hepatoprotective effect of Schisandra chinensis (Turcz.) Baill. lignans and its formula with Rubus idaeus on chronic alcohol-induced liver injury in mice.

    Science.gov (United States)

    Wang, Ou; Cheng, Qian; Liu, Jia; Wang, Yong; Zhao, Liang; Zhou, Feng; Ji, Baoping

    2014-11-01

    This study aimed to investigate the liver protection effect of Schisandra chinensis (Turcz.) Baill. (SC) lignans and its combination with Rubus idaeus (RI) on chronic alcohol-induced mice. A low level of SC lignans (SL) was prepared from the clear juice of sarcocarp. Lignans were further extracted from the SC seeds and added to the SL to form high-level SC lignans (SH). Moreover, RI clear juice lyophilized powder was mixed with SL (SR), and the liver protection effects of SL, SH and SR were investigated. Male ICR mice were administered with the corresponding samples and gastrically infused with 50% alcohol (1 h later) once per day for 60 d. In the in vitro study, the characteristic lignans in the SC clear juice and the seed extract were analyzed by high performance liquid chromatography (HPLC). The total phenolic content (TPC) and antioxidant capability of SL, SH, and SR were determined. The results of the in vivo study showed that SC lignans exhibited a dose-dependent effect on the regulation of hepatic antioxidant status, serum transaminases levels, hyperlipidemia and hepatic fat deposition in mice. However, hepatic lesions were observed in the SH mice, which indicated a potential side effect caused by long-term consumption of SH under chronic alcohol administration. By contrast, SR exhibited a similar hepatoprotective effect as SH without any abnormality found in the histological analysis. After analysis with HPLC, Schizandrol A and Schizandrol B were identified in the SC clear juice, and two more kinds of lignans, Schisandrin A and Schisandrin B, were identified in the seed extracts. The SR sample had the highest TPC and exhibited the best antioxidant capability. In conclusion, RI strengthened the liver protection effect of SC lignans effectively and safely, which was probably achieved by enhancing the antioxidant status and the positive effect of their combination was possibly attributed to both lignans and polyphenols. This study demonstrated that the

  6. Systemic abnormalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Masami Minemura; Kazuto Tajiri; Yukihiro Shimizu

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  7. Research Progress of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    XU Lie-ming; JIA Ji-dong

    2005-01-01

    @@ Liver diseases are widespread in China.The disease mostly includes viral hepatitis,alcoholic or non alcoholic fatty degeneration or steatohepatitis, autoimmune liver disease,hepatic fibrosis/cirrhosis and hepatic cancer.The mechanism of most liver diseases was studied clearly in developed countries.

  8. Nonalcoholic Fatty Liver Disease

    OpenAIRE

    You, Jie; Huang, Sha; Huang, Gui-Qian; Zhu, Gui-Qi; Ma, Rui-Min; Liu, Wen-yue; Shi, Ke-Qing; Guo, Gui-Long; Chen, Yong-Ping; Braddock, Martin; Zheng, Ming-Hua

    2015-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD. We performed a large cohort study of 1314 patien...

  9. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  10. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian;

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  11. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  12. Nonalcoholic Fatty Liver Disease in Patients Investigated for Elevated Liver Enzymes

    Directory of Open Access Journals (Sweden)

    Krikor Kichian

    2003-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a common diagnosis among patients referred to gastroenterology and hepatology clinics for the evaluation of elevated liver enzymes. The diagnosis of NAFLD is supported by blood work to exclude other liver diseases, and by ultrasound evidence of fat in the liver in patients without a significant history of alcohol intake. The gold standard, however, is a liver biopsy to show the typical histological features of NAFLD, which are almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. A variety of retrospective series have linked NAFLD to obesity, diabetes, hyperlipidemia, total parenteral nutrition, jejunoileal bypass surgery and certain medications. A subset of patients with NAFLD that had an initial presentation of elevated liver enzymes was studied. Two hundred and two patients were reviewed, of whom 49 met the inclusion criteria including a liver biopsy. Patients were excluded if insufficient data were available, if the patients had a significant history of ethanol intake or if they had other coexisting liver disease. These patients were seen between 1996 and 2000 in gastroenterology and hepatology clinics in two community hospitals and one regional liver transplant centre in Edmonton, Alberta. NAFLD was associated with a spectrum of changes in the liver ranging from mild steatosis to more significant steatosis with inflammation and fibrosis. Cases of NAFLD with steatosis and mixed inflammatory infiltration but lacking ballooning degeneration or fibrosis were prevalent in young (20 to 40 years of age patients with no other significant medical history except for obesity. NAFLD with biopsies showing significant fibrosis and ballooning cell degeneration was associated with obesity, diabetes and older age. It was concluded that, in this predominantly outpatient setting, age over 40 years and diabetes at any age are risk factors for both nonalcoholic

  13. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    Science.gov (United States)

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  14. MicroRNA Signature in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Shashi Bala

    2012-01-01

    Full Text Available Alcoholic liver disease (ALD is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage and in vivo (Kupffer cells, KCs of alcohol-fed mice. Induction of miR-155 contributed to increased TNF alpha production and to the sensitization of KCs to produce more TNF alpha in response to LPS. In this paper, we summarize the current knowledge of miRNAs in ALD and also report increased expression of miR-155 and miR-132 in the total liver as well as in isolated hepatocytes and KCs of alcohol-fed mice. Our novel finding of the alcohol-induced increase of miRNAs in hepatocytes and KCs after alcohol feeding provides further insight into the evolving knowledge regarding the role of miRNAs in ALD.

  15. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  16. Hepatoprotective Activity of Herbal Preparation (Hp-4 against Alcohol Induced Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    P. Padmanabhan

    2014-03-01

    Full Text Available Free radicals include both Reactive Oxygen Species (ROS and Reactive Nitrogen Species (RNS.When free radicals are produced in a regulated manner in a healthy human body it is scavenged efficiently by antioxidant defense system. But excess generation of pro-oxidants by continuous chain reaction in the form of ROS and RNS cause several human diseases. The shift of the balance in the favour of pro-oxidants results in a condition called “oxidative stress”. Alcohol is primarily metabolized in the liver to generate ROS and RNS, leading to diseases such as cirrhosis, fatty liver and chronic hepatitis. Alcohol induced damage is associated with oxidative stress. The excess generation of prooxidants and reduced antioxidant levels provide an effective model of Hepatotoxicity which is noteworthy. Recent trend is to discover polyherbal formulation of medicinal plants which have hepatoprotective function. In the present study 80% alcoholic extract of leaves of Aloe vera, Bacopa monniera, Moringa oleifera and rhizome of Zingiber officinale were utilized to prepare Herbal Preparation or HP-4.Further the hepatoprotective effects of HP-4 was tested in alcohol induced Hepatotoxicity in mice. Silymarin is a well known hepatoprotective drug was used as a standard for comparison. Biochemical and histopathological studies provided ample evidence that HP-4 provided a hepatoprotective role in alcohol induced hepatotoxicity which was comparable to drug Silymarin. The presence of phytochemicals in HP-4 provided a synergistic, supra-additive and co-operative effects in the hepatoprotective function in alcohol induced hepatotoxicity mice model.

  17. Polycystic Liver Disease

    Energy Technology Data Exchange (ETDEWEB)

    Linda, Nguyen, E-mail: nguyenli@einstein.edu [5501 Old York Road, Philadelphia, PA 19141 (United States)

    2016-03-25

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations. The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.

  18. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2004-01-01

    to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin......Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...... hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system...

  19. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Møller, Søren

    2004-01-01

    Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic......, neuropituitary release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through nitric oxide, calcitonin gene-related peptide, adrenomedullin, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance...... to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin...

  20. Screening in liver disease

    Institute of Scientific and Technical Information of China (English)

    Paolo Del Poggio; Marzio Mazzoleni

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines,although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors,such as transfusion before 1992 and drug addiction,is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation.

  1. Fibropolycystic liver disease in children

    Energy Technology Data Exchange (ETDEWEB)

    Veigel, Myka Call [Kansas City University of Medicine and Biosciences, Kansas City, MO (United States); University of Missouri-Kansas City, St. Luke' s Hospital, Department of Radiology, Kansas City, MO (United States); Prescott-Focht, Julia; Zinati, Reza [University of Missouri-Kansas City, St. Luke' s Hospital, Department of Radiology, Kansas City, MO (United States); Rodriguez, Michael G. [University of Missouri-Kansas City School of Medicine, Kansas City, MO (United States); Shao, Lei [Children' s Mercy Hospitals and Clinics, Department of Pathology, Kansas City, MO (United States); Moore, Charlotte A.W.; Lowe, Lisa H. [University of Missouri-Kansas City, Department of Radiology, Kansas City, MO (United States); Children' s Mercy Hospitals and Clinics, Department of Radiology, Kansas City, MO (United States)

    2009-04-15

    Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders. (orig.)

  2. Fatty Liver Disease (Nonalcoholic Steatohepatitis)

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  3. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within week

  4. Liver transplantation for Wilson's disease.

    Science.gov (United States)

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  5. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  6. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  7. [Wilson's disease: clinical spectrum of liver disease].

    Science.gov (United States)

    Ochoa Palominos, Alejandra; Ibáñez Samaniego, Luis; Catalina Rodríguez, María-Vega; Pajares Díaz, José; Clemente Ricote, Gerardo

    2013-02-01

    Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism,characterized by copper accumulation in the liver and brain. This rare entity, which has a broad clinical spectrum, is often difficult to diagnose and should therefore always be suspected in patients with liver disease of unclear cause. We describe two types of manifestation of liver disease in two patients; the first developed fulminant hepatic failure requiring urgent liver transplantation and the second showed advanced chronic liver disease and received standard medical treatment. The objective of this clinical observation is to analyze the diagnosis of Wilson's disease in two patients with distinct onset, illustrating the broad clinical spectrum of the disease, and its treatment.

  8. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  9. Protective effect of rutin from buckwheat on alcohol-induced liver Injury in mice%荞麦花叶芦丁对小鼠酒精性肝损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    储金秀; 韩淑英; 余红; 张博男; 王建行

    2011-01-01

    Objective To explore the protective effects of rutin (extracted from flowers and leaves of buckwheat) on alcohol-induced liver injury in mice. Methods Sevnty-two rats were randomly derided into 6 groups of A(sham operated), B(model control), three doses of rutin [(75 (R1),150(R2) and 300(R3) mg · kg-1 · d-1] and standard rutin control The liver injury model of mice was induced by intragastrical administration of 50% alcohol 10 mg · kg-1 · d-1 for 10 days. The liver injury was evaluated by the indexes of serum AST, ALT, liver index (LI), liver superoxide dismutase(SOD) and malondialdehyde(MDA), and the morphological changes of liver tissue. Results Rutin could decrease the death rate and body weight losing rate of alcohol-induced liver injury mice,inhibit the increases of LI, AST, ALT and MDA, increase the activity of SOD in certain degree and improve the morphological changes of injured liver. Conclusion Rutin has significant protective effects on alcohol-induced liver injury in mice,which is probably related to its inhibition effects on lipid peroxidation.%目的 探讨荞麦花叶芦丁(RBFL)对小鼠酒精性肝损伤的保护作用.方法 72只小鼠随机均分为6组:正常组(A)、模型对照组(B)、三个剂量RBFL组(R1组:75 mg·kg-1·d-1 ;R2组:150 mg·kg-1·d-1;R3组:300 mg·kg-1·d-1)和RBFL,标准品对照组(D组:150 mg·Kg-1·d-1).用50%乙醇按10 ml·kg-1·d-1连续灌胃10 d,制备小鼠酒精性肝损伤模型.测定血清AST、ALT活力,计算肝重指数(LI),测定肝组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,镜下观察肝组织病理改变来判断RBFL对酒精性肝损伤小鼠的保护作用.结果 RBFL不同程度地降低了酒精性肝损伤小鼠的死亡率和体重下降率,抑制肝损伤小鼠的LI、AST和MDA,显著增强肝损伤小鼠肝组织SOD活性;病理组织学显示,RBFL能显著改善酒精损伤肝细胞的形态学变化.结论 RBFL对小鼠酒精性肝损伤有显著的保护作用,其机

  10. Muscle cramps in liver disease.

    Science.gov (United States)

    Mehta, Shivang S; Fallon, Michael B

    2013-11-01

    Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes. Treatments have focused on these particular areas with varied results. This review will focus on the clinical features of muscle cramps in patients with liver disease and review potential mechanisms and current therapies.

  11. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  12. Alcoholic liver disease: The gut microbiome and liver crosstalk

    OpenAIRE

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing ...

  13. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  14. HEMOSTATIC DISORDERS IN LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    A. F. Minov

    2010-01-01

    Full Text Available The liver is an essential player in the pathway of coagulation in both primary and secondary hemostasis as it is the site of synthesis of all coagulation factors and their inhibitors. Liver diseases are associated with complex changes in coagulation and the delicate balance between pro and antithrombotic factors is preserved but reset to a lower level. There is growing evidence that portal and hepatic vein thrombosis is cause of disease progression in cirrhotic patients and worsens hemostatic abnormalities. These hemostatic abnormalities do not always lead to spontaneous bleeding, which may be triggered only by additional factors, such as infections. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. In patients with end stage liver disease liver transplantation is the only treatment available, which can restore normal hemostasis, and correct genetic clotting defects. During liver transplantation hemorrhage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis. 

  15. Periodontal disease and liver cirrhosis

    DEFF Research Database (Denmark)

    Grønkjær, Lea Ladegaard

    2015-01-01

    OBJECTIVES: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease...... health', 'periodontal disease', 'mouth disease', 'gingivitis', and 'periodontitis'. RESULTS: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease...... in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%-79% of the patients. One study found that mortality was lower among...

  16. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  17. [Alcoholic liver disease and liver transplantation].

    Science.gov (United States)

    Testino, Gianni; Patussi, Valentino; Scafato, Emanuele

    2013-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed.

  18. Alcohol-induced protein hyperacetylation: Mechanisms and consequences

    Institute of Scientific and Technical Information of China (English)

    Blythe D Shepard; Pamela L Tuma

    2009-01-01

    Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylation. This reversible, posttranslational modification on the ε-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcoholinduced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes,histone acetyltransferases and histone deacetylases.Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We wil l then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.

  19. Pleural effusion in liver disease.

    Science.gov (United States)

    Alonso, José Castellote

    2010-12-01

    Hepatic hydrothorax is the paradigmatic pleural effusion in liver cirrhosis. It is defined as a pleural effusion in a patient with portal hypertension and no cardiopulmonary disease. The estimated prevalence of this complication in patients with liver cirrhosis is 5 to 6%. Its pathophysiology involves movement of ascitic fluid from the peritoneal cavity into the pleural space through diaphragmatic defects. Thoracentesis and pleural fluid analysis are necessary for diagnosis. Initial management consists of sodium restriction, diuretics, and therapeutic thoracentesis. A transjugular intrahepatic portosystemic shunt may provide a bridge prior to liver transplantation. Spontaneous bacterial empyema is the infection of a preexisting hydrothorax. The more frequent bacteria involved are ENTEROBACTERIACEAE and gram-positive cocci. Antibiotic therapy is the cornerstone of therapy. This article reviews etiology, clinical manifestations, and therapy of these two complications of liver cirrhosis and portal hypertension.

  20. Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Karina Reyes-Gordillo

    2016-01-01

    Full Text Available Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA that primarily regulates PGC1α and soy protein (SP that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK. Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

  1. Cholestatic liver disease masquerading as Wilson disease.

    Science.gov (United States)

    Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev; Alam, Seema

    2015-03-01

    Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.

  2. Effect of Liverubin™ on hepatic biochemical profile in patients of alcoholic liver disease: a retrospective study.

    Science.gov (United States)

    Nanda, V; Gupta, V; Sharma, S N; Pasricha, A; Karmakar, A Kumar; Patel, A; Bhatt, V M; Kantroo, B L; Kumar, B; Paul, N K Ketar; Attam, R

    2014-12-01

    Liverubin™ is an available drug in the Indian market that contains silymarin, the major active complex extracted from the medicinal plant milk thistle (Silybum marianum L.). The study retrospectively tracked and analyzed the data of 602 patients, out of which 230 were alcohol induced; 131 with alcohol-induced liver damage (ALD), 13 with liver cirrhosis, and 86 with fatty liver; to assess the effects of water soluble Silymarin (Liverubin™) on important hepatic biochemical parameters. The data was collected from 32 major cities treated by 72 physicians across India who were observed for the specified treatment duration of 11 months. Data was analyzed by using descriptive statistics. At the end of the treatment the hepatic biochemical profile was appreciably improved: the mean % of change in the levels of important hepatic biochemical parameters was observed as follows: total bilirubin 63.48% (direct bilirubin: 64.96%; indirect bilirubin: 61.63%). The serum SGOT and SGPT changed at a mean % of 65.43 and 69.31 respectively while serum alkaline phosphatase was changed at a mean % rate of 39.81. Liverubin™ proved to be safe & well-tolerated among the studied population and no significant treatment related adverse events were reported during the study. Liverubin™ treatment is found to bring about effective lowering of abnormally elevated hepatic biochemical parameters. Liverubin™, water soluble active Silymarin, in the popularly prescribed doses of 140-mg tid is observed to be a promising safe and effective drug in cases of alcoholic liver disease.

  3. Transplantation in autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marcus Mottershead; James Neuberger

    2008-01-01

    Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from nonheart-beating donors and from living donors.Post transplantation, most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in sideeffects and so improve the patient and graft survival.For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.

  4. 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...... 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 with functional....... 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 vasopressive...

  5. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    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....... 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 vasopressive...... 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 with functional...

  6. Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.

    Directory of Open Access Journals (Sweden)

    Raimundo Fernandes de Araújo Júnior

    Full Text Available To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV in rats with ethanol-induced liver injury.Liver injury was induced by gavage administration of alcohol (7 g/kg for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL-1β, IL-10, and tumor necrosis factor (TNF-α level as well as for myeloperoxidase (MPO activity and malonyldialdehyde (MDA and glutathione (GSH levels. Serum aspartate aminotransferase (AST activity and liver triglyceride (TG levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2, receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL, suppressor of cytokine signalling (SOCS1, the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1, intercellular adhesion molecule 1 (ICAM-1, superoxide dismutase (SOD-1, and glutathione peroxidase (GPx-1 expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed.CARV treatment (5 mg/kg during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01, ALT (p < 0.01, TG (p < 0.001, MPO (p < 0.001, MDA (p < 0.05, and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05, and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001 and GSH (p < 0.05, compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05, while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05 and decreasing expression of IL-1β and NF-κB (both, p < 0.05. Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI, procollagen

  7. RNA interference against discoidin domain receptor 2 ameliorates alcoholic liver disease in rats.

    Directory of Open Access Journals (Sweden)

    Zheng Luo

    Full Text Available Discoidin domain receptor 2 (DDR2 is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.

  8. RNA interference against discoidin domain receptor 2 ameliorates alcoholic liver disease in rats.

    Science.gov (United States)

    Luo, Zheng; Liu, Huimin; Sun, Xiaomeng; Guo, Rong; Cui, Ruibing; Ma, Xiangxing; Yan, Ming

    2013-01-01

    Discoidin domain receptor 2 (DDR2) is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.

  9. Fibronectin: Functional character and role in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Razia S Aziz-Seible; Carol A Casey

    2011-01-01

    Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in fact stimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this

  10. COAGULATION ACTIVITY IN LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Dr. Sheikh Sajjadieh Mohammad Reza

    2009-07-01

    Full Text Available Patients with advanced hepatic failure may present with the entire spectrum of coagulation factor deficiencies. This study was designed to determine laboratory abnormalities in coagulation in chronic liver disease and the association of these abnormalities with the extent of chronic hepatitis and cirrhosis. Coagulation markers were assayed in 60 participants: 20 patients with chronic hepatitis, 20 patients with cirrhosis, and 20 healthy individuals (control. Plasma levels of anti-thrombin III were determined by a chromogenic substrate method, and plasma concentrations of fibrinogen were analyzed by the Rutberg method. Commercially available assays were used for laboratory coagulation tests. The levels of coagualation activity markers in patients with chronic liver disease were significantly different in comparison to those in healthy participants. These results indicate the utility of measuring markers for coagulation activity in determining which cirrhosis patients are more susceptible to disseminated intravascular coagulation.

  11. Ameliorative effect of pumpkin oil (Cucurbita pepo L. against alcohol-induced hepatotoxicity and oxidative stress in albino rats

    Directory of Open Access Journals (Sweden)

    Howida Sayed Abou Seif

    2014-09-01

    Conclusion: The natural plant components found in pumpkin could improve the liver against alcohol-induced liver toxicity and oxidative stress. However, further clinical studies are required to assess the safety and benefits of pumpkin oil in human beings.

  12. Nonalcoholic Fatty Liver Disease Treatment

    Directory of Open Access Journals (Sweden)

    M Sadeghian

    2014-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasing in pediatric age group parallel to the growing prevalence of obesity and overweight all around the world. So changing in life style and   interventions on obesogenic environment is cornerstone of NAFLD therapy in obese children. Some experts recommend that children and adolescents be encouraged to follow a low-fat, low-glycemic-index diet that includes eating a minimum of 5 servings of vegetables and fruits daily, engaging in physical activity for at least 1 hour daily, and minimizing television/computer time to 2 hours daily.  In spite of effectiveness of weight loss and exercise in improvement NAFLD, this goal is very difficult to be achieved and pharmacological approaches have become necessary. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress also might slow the progression of NAFLD to NASH or cirrhosis.  On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials but there is no approved pharmacologic therapy for NAFLD or NASH. Not all obese children affected by NAFLD. Diet modification and regular exercise beside to serial medical follow up highly suggested for this group of children. Normal weight and thin children with NAFLD or NASH should be investigated appropriately in a logical manner based on causes of primary liver steatosis in children and treatment of underlying disease can cause improvement fatty liver in these patients.   Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Children; Steatosis; Treatment

  13. [Polycystic liver disease without autosomal dominant polycystic kidney disease].

    Science.gov (United States)

    Peces, R; González, P; Venegas, J L

    2003-01-01

    Polycystic liver disease is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. The natural history and clinical manifestations of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The occurrence of polycystic liver disease independently from polycystic kidney disease has been known for a long time. More recently, a gene for autosomal dominant polycystic liver disease has been identified on chromosome 19p 13.2-13.1. Isolated polycystic liver disease is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis and clinical manifestations. We report here two men with polycystic liver disease no associated with ADPKD. Ultrasound and computed tomography imaging were effective in documenting the underlying lesions non-invasively.

  14. 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.

  15. Alcoholic liver disease and the gut-liver axis

    Institute of Scientific and Technical Information of China (English)

    Gyongyi; Szabo; Shashi; Bala

    2010-01-01

    Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4...

  16. The Complement System in Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Xuebin Qin; Bin Gao

    2006-01-01

    The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors.Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.

  17. Plasma membrane proteome analysis of the early effect of alcohol on liver:implications for alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Lijun Zhang; Ye Zheng; Pengyuan Yang; Zhenghong Yuan; Xiaofang Jia; Yanling Feng; Xia Peng; Zhiyong Zhang; Wenjiang Zhou; Zhanqing Zhang; Fang Ma; Xiaohui Liu

    2011-01-01

    In humans, the over-consumption of alcohol can lead to serious liver disease. To examine the early effects of alcohol on liver disease, rats were given sufficient ethanol to develop liver cirrhosis. Rats before the onset of fibrosis were studied in this work. Plasma membranes (PM) of liver were extracted by twice sucrose density gradient centrifugation. The proteome profiles of PM from ethanol-treated rats and the controls were analyzed using two-dimensional gel electrophoresis (2-DE) and isobaric tag for relative and absolute quantitation (iTRAQ) tech-nology. Ethanol treatment altered the amount of 15 differ-ent liver proteins: 10 of them were detected by 2-DE and 5 by iTRAQ. Keratin 8 was detected by both methods.Gene ontology analysis of these differentially detected proteins indicated that most of them were involved in important cell functions such as binding activity (includ-ing ion, DNA, ATP binding, etc.), cell structure, or enzyme activity. Among these, annexin A2, keratin 8, and keratin 18 were further verified using western blot analy-sis and annexin A2 was verified by immunohistochemis-try. Our results suggested that alcohol has the potential to affect cell structure, adhesion and enzyme activity by altering expression levels of several relevant proteins in the PM. To the best of our knowledge, this is the first time to study the effect of alcohol on the liver PM pro-teome and it might be helpful for understanding the poss-ible mechanisms of alcohol-induced liver disease.

  18. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    BinGao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology. 2005;2(2):92-100.

  19. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    Bin Gao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology.2005;2(2):92-100.

  20. Targeting collagen expression in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Kyle J Thompson; Iain H McKillop; Laura W Schrum

    2011-01-01

    Alcoholic liver disease (ALD) is a leading cause of liver disease and liver-related deaths globally, particularly in developed nations. Liver fibrosis is a consequence of ALD and other chronic liver insults, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Liver fibrosis is characterized by accumulation of excess extracellular matrix components, including type Ⅰ collagen, which disrupts liver microcirculation and leads to injury. To date, there is no therapy for the treatment of liver fibrosis; thus treatments that either prevent the accumulation of type Ⅰ collagen or hasten its degradation are desirable. The focus of this review is to examine the regulation of type Ⅰ collagen in fibrogenic cells of the liver and to discuss current advances in therapeutics to eliminate excessive collagen deposition.

  1. Effect of Autophagy Over Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-qian Yi; Xue-feng Yang; Duan-fang Liao; Qing Wu; Nian Fu; Yang Hu; Ting Cao

    2016-01-01

    Abstract In recent years, increasingly evidences show that autophagy plays an important role in the pathogenesis and development of liver diseases, and the relationship between them has increasingly become a focus of concern. Autophagy refers to the process through which the impaired organelles, misfolded protein, and intruding microorganisms is degraded by lysosomes to maintain stability inside cells. This article states the effect of autophagy on liver diseases (hepatic fibrosis, fatty liver, viral hepatitis, and liver cancer), which aims to provide a new direction for the treatment of liver diseases.

  2. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yalamanchili, Kanthi; Saadeh, Sherif; Klintmalm, Göran B; Jennings, Linda W; Davis, Gary L

    2010-04-01

    Nonalcoholic steatohepatitis (NASH) may account for many cases of cryptogenic cirrhosis. If so, then steatosis might recur after liver transplantation. Two thousand fifty-two patients underwent primary liver transplantation for chronic liver disease between 1986 and 2004. Serial liver biopsy samples were assessed for steatosis and fibrosis. Two hundred fifty-seven patients (12%) had a pretransplant diagnosis of cryptogenic cirrhosis (239) or NASH (18). Fatty liver developed in 31% and was more common when the pretransplant diagnosis was NASH (45% at 5 years versus 23% for cryptogenic cirrhosis, P = 0.007). NASH developed in only 4% and occurred exclusively when steatosis had already occurred. Steatosis after liver transplantation was associated with the baseline body weight and body mass index by univariate analyses, but no pretransplant or posttransplant characteristic independently predicted steatosis after liver transplantation because obesity was so common in all groups. Five percent and 10% developed bridging fibrosis or cirrhosis after 5 and 10 years, respectively, and this was more common after NASH (31%) than in those who developed steatosis alone (6%) or had no fat (3%, P = 0.002). One-, 5-, and 10-year survival was the same in patients who underwent transplantation for cryptogenic cirrhosis or NASH (86%, 71%, and 56%) and in patients who underwent transplantation for other indications (86%, 71%, and 53%; not significant), but death was more often due to cardiovascular disease and less likely from recurrent liver disease. In conclusion, fatty liver is common after liver transplantation for cryptogenic cirrhosis or NASH but is twice as common in the latter group; this suggests that some cryptogenic cirrhosis, but perhaps not all, is caused by NASH. Posttransplant NASH is unusual, and steatosis appears to be a prerequisite. Advanced fibrosis is uncommon, and survival is the same as that of patients who undergo transplantation for other causes.

  3. STUDY ON THE MECHANISM OF GENISTEIN ON PROTECTION AGAINST ALCOHOL-INDUCED ACUTE LIVER INJURY%三羟异黄酮保护急性酒精性肝损伤机制研究

    Institute of Scientific and Technical Information of China (English)

    范远景; 张玲; 张东吟; 曹迪; 荣煜; 陈春景

    2013-01-01

    Objective To investigate the effect of protection against alcohol-induced acute liver injury and the impact on the activities of enzymes related to alcohol metabolism by genistein (Gen).Methods Ninety KM male mice (2 w old)were randomly assigned to 9 groups:control group (untreated),model group (treated with dosage of 12ml/kg bw of 50% alcohol by intragastric gavage (i.g.) to induce acute liver injury),Gen control group (treated alone with Gen of 200 mg/kg bw),Gen prevention groups (50,100 or 200 mg/kg bw of Gen,before treatment with alcohol) and Gen therapy groups (the same three dosages of Gen,after treatment with alcohol).All groups were administered once daily for 10 consecutive days,then the activities or levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),malondialdehyde (MDA),triglyceride (TG),glutathione (GSH) and superoxide dismutase (SOD) were determined in blood and liver,and the activities of alcohol dehydrogenase (ADH),aldehyde dehydrogenase (ALDH) and CYP2E1 (microsomal ethanol oxidizing system,MEOS) were also assayed in liver.Results Compared with the control and Gen control groups,the activities of AST and ALT in Gen model group in blood and liver were increased significantly (P<0.05); the activities of AST and ALT in Gen prevention and therapy groups were lower than that of model group remarkably (P< 0.05),and the levels of MDA and TG were lower and the levels of GSH and SOD were higher than those of model group significantly (P<0.05).The activities of ADH,ALDH of Gen prevention and therapy groups were increased and CYP2E1 was decreased compared to the control group.There was no significant difference of all indicators between the control and Gen control groups.Conclusion Gen could play the role of protection against alcohol-induced acute liver injury.The mechanism of actions of Gen may be associated with reduced oxidative stress via impact on the activities of ADH,ALDH and CYP2E1.%目的 探讨大豆三羟异黄

  4. Excellent survival after liver transplantation for isolated polycystic liver disease : an European Liver Transplant Registry study

    NARCIS (Netherlands)

    van Keimpema, Loes; Nevens, Frederik; Adam, Rene; Porte, Robert J.; Fikatas, Panagiotis; Becker, Thomas; Kirkegaard, Preben; Metselaar, Herold J.; Drenth, Joost P. H.

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR) d

  5. Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study

    DEFF Research Database (Denmark)

    van Keimpema, Loes; Nevens, Frederik; Adam, René

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR...

  6. Trace elements and chronic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Loguercio, C.; De Girolamo, V.; Federico A., A.; Del Vecchio Blanco, C. [Seconda Universita di Napoli, Naples (Italy). Cattedra di Gastroenterologia; Feng, S.L.; Gialanella, G. [Naples Univ. (Italy). Dipt. di Scienze Fisiche; Cataldi, V. [Naples Univ. (Italy). Prima Medicina Ospedale Ascalesi

    1997-12-31

    The relationships between chronic liver diseases and trace element (TE) contents are debated. Particularly, no defined data are available about the TE levels in viral liver disease patients with or without malnutrition. In this study we evaluated blood and plasma levels of various trace elements in patients with HCV-related chronic liver disease, at different stages of liver damage (8 patients with chronic hepatitis and 32 with liver cirrhosis) with or without malnutrition. We also studied 10 healthy volunteers as control group. We found that cirrhotic subjects had a significant decrease of blood levels of Zn and Se, independently on the nutritional status, whereas plasma levels of Fe were significantly reduced only in malnourished cirrhotic patients. Our data indicate that liver impairment is the main cause of the blood decrease of Se and Zn levels in patients with non alcoholic liver disease, whereas the malnutrition affects Fe levels only. (orig.)

  7. Anemia of Chronic Liver Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hyun Chung; Lee, Jhung Sang; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1971-09-15

    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 T{sub 50} 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.

  8. Alcoholic liver disease patients' perspective of a coping and physical activity-oriented rehabilitation intervention after hepatic encephalopathy

    DEFF Research Database (Denmark)

    Mikkelsen, Maria Rudkjær; Hendriksen, Carsten; Schiødt, Frank Vinholt;

    2016-01-01

    were conducted with 10 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy and participated in a coping and physical activity-oriented rehabilitation intervention. Richard S. Lazarus's theory of stress and coping inspired the interview guide. Results: The significance......Aim and objective: To identify and describe the impact of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients after hepatic encephalopathy in terms of their interaction with professionals and relatives. Background: Patients who have experienced...... of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients’ ability to cope with problems after surviving alcohol-induced hepatic encephalopathy in terms of their interaction with professionals and relatives was characterised by the core category ‘regain control...

  9. CKD and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Targher, Giovanni; Chonchol, Michel B; Byrne, Christopher D

    2014-10-01

    The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.

  10. Correlation between liver morphology and haemodynamics in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, J H;

    1985-01-01

    was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance....

  11. Pathophysiology of Non Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Petta, Salvatore; Gastaldelli, Amalia; Rebelos, Eleni; Bugianesi, Elisabetta; Messa, Piergiorgio; Miele, Luca; Svegliati-Baroni, Gianluca; Valenti, Luca; Bonino, Ferruccio

    2016-01-01

    The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation. PMID:27973438

  12. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    ... fats, produces several important com- pounds, stores certain vitamins, makes specific amino acids, converts glucose to glycogen, ... liver. This increased pres- sure causes blood to bypass the liver. As a result, the blood is ...

  13. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  14. Update on fatty liver disease and steatohepatitis.

    Science.gov (United States)

    Aly, Fatima Zahra; Kleiner, David E

    2011-07-01

    Non-alcoholic fatty liver disease (NAFLD) is a broad term that includes liver diseases characterized by abnormal hepatocellular accumulations of lipid that cannot be related to alcohol abuse. It may be found in both adults and children, particularly those who are obese or have insulin resistance. Steatohepatitis is a specific pattern of injury within the spectrum of NAFLD and this pattern is associated with fibrotic progression and cirrhosis. In addition to steatohepatitis, a distinct form of fibrotic fatty liver disease exists in children. There have been a number of recent advances in the characterization of histologic changes in NAFLD. In light of these recent reports, this study will: (1) review the histologic features of steatosis and nonalcoholic steatohepatitis in adults; (2) review the variation of histologic patterns of pediatric fatty liver disease; and (3) discuss the validity and use of the nonalcoholic fatty liver disease Activity Score.

  15. Cirrhosis and autoimmune liver disease: Current understanding

    Science.gov (United States)

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  16. 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.

  17. 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...

  18. Recurrence of cholestatic liver disease after living donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Sumihito Tamura; Masatoshi Hakuuchi; Yasuhiko Sugawara; Junichi Kaneko; Junichi Togashi; Yuichi Matsui; Noriyo Yamashiki; Norihiro Kokudo

    2008-01-01

    End-stage liver disease,due to cholestatic liver diseases with an autoimmune background such as primary biliary cirrhosis(PBC)and primary sclerosing cholangitis(PSC),is considered a good indication for liver transplantation.Excellent overall patient and graft outcomes,based mostly on the experience from deceased donor liver ransplantation(DDLT),have been reported.Due to the limited number of oraan donations from deceased donors in most Asian countries,living donor liver transplantation(LDLT)is the mainstream treatment for end-stage liver disease,including that resulting from PBC and PSC.Although the initial experiences with LDLT for PBC and PSC seem satisfactory or comparable to that with DLT,some aspects,including the timing of transplantation,the risk of recurrent disease,and its long-term clinical implications,require further evaluation.Whether or not the long-term outcomes of LDLT from a biologically related donor are equivalent to that of DDLT requires further observations.The clinical course following LDLT may be affected by he genetic background shared between the recipient and the living related donor.(C)2008 The WJG Press.All rights reserved.

  19. Role of liver biopsy in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nalbantoglu, I L Ke; Brunt, Elizabeth M

    2014-07-21

    Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the "gold standard" for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

  20. Recurrence of autoimmune liver diseases after livertransplantation

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Liver transplantation (LT) is the most effective treatmentmodality for end stage liver disease caused by manyetiologies including autoimmune processes. That said,the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis (PBC), but not forprimary sclerosing cholangitis (PSC), has decreasedover the years due to the availability of effective medicaltreatment. Autoimmune liver diseases have superiortransplant outcomes than those of other etiologies. WhileAIH and PBC can recur after LT, recurrence is of limitedclinical significance in most, but not all cases. RecurrentPSC, however, often progresses over years to a stagerequiring re-transplantation. The exact incidence andthe predisposing factors of disease recurrence remaindebated. Better understanding of the pathogenesis andthe risk factors of recurrent autoimmune liver diseasesis required to develop preventive measures. In thisreview, we discuss the current knowledge of incidence,diagnosis, risk factors, clinical course, and treatmentof recurrent autoimmune liver disease (AIH, PBC, PSC)following LT.

  1. Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis: a novel therapeutic target for fatty liver disease.

    Science.gov (United States)

    Chen, Shuai; Kang, Yujia; Sun, Yan; Zhong, Yanhong; Li, Yanli; Deng, Lijuan; Tao, Jin; Li, Yang; Tian, Yingpu; Zhao, Yinan; Cheng, Jianghong; Liu, Wenjie; Feng, Gen-Sheng; Lu, Zhongxian

    2016-12-01

    Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders. The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors. In this study, we investigated the role of a signaling adaptor protein, GRB2-associated-binding protein 2 (Gab2), in fatty liver using an animal disease model. Gab2 expression in hepatocytes responded to various disease factor stimulations, and Gab2 knockout mice exhibited resistance to fat-induced obesity, fat- or alcohol-stimulated hepatic steatosis, as well as methionine and choline deficiency-induced steatohepatitis. Concordantly, the forced expression or knockdown of Gab2 enhanced or diminished oleic acid (OA)- or ethanol-induced lipid production in hepatocytes in vitro, respectively. During lipid accumulation in hepatocytes, both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT, ERK, and Stat3. Therefore, Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver. Our research provides a novel potential target for the prevention and intervention of fatty liver disease.

  2. Chronic Liver Disease and Native Hawaiian/Pacific Islanders

    Science.gov (United States)

    ... Hawaiian/Other Pacific Islander > Chronic Liver Disease Chronic Liver Disease and Native Hawaiian/Pacific Islander Native Hawaiian/ ... times more likely to be diagnosed with chronic liver disease in 2006. American Samoans were 8 times ...

  3. Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies.Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease.

  4. 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 patients than...

  5. GFR Estimating Equations and Liver Disease.

    Science.gov (United States)

    Beben, Tomasz; Rifkin, Dena E

    2015-09-01

    It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients' low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine-based estimated glomerular filtration rate (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24-hour creatinine clearance has limitations. In liver disease, all creatinine-based estimates of GFR overestimate gold standard-measured GFR, and the degree of overestimation is highest at lower measured GFR values and in more severe liver disease. Cystatin C-based eGFR has shown promise in general population studies by demonstrating less bias than creatinine-based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed, and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand kidney function in liver disease.

  6. Diagnosis and management of polycystic liver disease.

    Science.gov (United States)

    Gevers, Tom J G; Drenth, Joost P H

    2013-02-01

    Polycystic liver disease (PLD) is arbitrarily defined as a liver that contains >20 cysts. The condition is associated with two genetically distinct diseases: as a primary phenotype in isolated polycystic liver disease (PCLD) and as an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD). Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation. PLD is usually a benign disease, but can cause debilitating abdominal symptoms in some patients. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use and multiple pregnancies. Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD. Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation. Medical therapies that interact with regulatory mechanisms controlling expansion and growth of liver cysts are under investigation. Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers. The purpose of this Review is to provide an update on the diagnosis and management of PLD with a focus on literature published in the past 4 years.

  7. Managing non-alcoholic fatty liver disease

    Science.gov (United States)

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

  8. TGF-β signalling and liver disease.

    Science.gov (United States)

    Fabregat, Isabel; Moreno-Càceres, Joaquim; Sánchez, Aránzazu; Dooley, Steven; Dewidar, Bedair; Giannelli, Gianluigi; Ten Dijke, Peter

    2016-06-01

    The transforming growth factor-beta (TGF-β) family signalling pathways play essential roles in the regulation of different cellular processes, including proliferation, differentiation, migration or cell death, which are essential for the homeostasis of tissues and organs. Because of the diverse and pleiotropic TGF-β functions, deregulation of its pathways contributes to human disease. In the case of the liver, TGF-β signalling participates in all stages of disease progression, from initial liver injury through inflammation and fibrosis, to cirrhosis and cancer. TGF-β has cytostatic and apoptotic effects in hepatocytes, promoting liver differentiation during embryogenesis and physiological liver regeneration. However, high levels of TGF-β, as a consequence of chronic liver damage, result in activation of stellate cells to myofibroblasts and massive hepatocyte cell death, which contributes to the promotion of liver fibrosis and later cirrhosis. During liver tumorigenesis, TGF-β may behave as a suppressor factor at early stages; however, there is strong evidence that overactivation of TGF-β signalling might contribute to later tumour progression, once cells escape from its cytostatic effects. For these reasons, targeting the TGF-β signalling pathway is being explored to counteract liver disease progression. In this review, we aim to shed light on the state-of-the-art in the signalling pathways induced by TGF-β that are involved in different stages of liver physiology and pathology.

  9. Brain MRI changes in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

    1997-08-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

  10. Pediatric Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Uppal, Vikas; Mansoor, Sana; Furuya, Katryn N

    2016-05-01

    Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

  11. Nephrogenic Systemic Fibrosis Risk and Liver Disease

    Directory of Open Access Journals (Sweden)

    Robert F. Hanna

    2014-01-01

    Full Text Available Objective. Evaluate the incidence of nephrogenic systemic fibrosis (NSF in patients with liver disease in the peritransplant period. Materials and Methods. This IRB approved study retrospectively reviewed patients requiring transplantation for cirrhosis, hepatocellular carcinoma (HCC, or both from 2003 to 2013. Records were reviewed identifying those having gadolinium enhanced MRI within 1 year of posttransplantation to document degree of liver disease, renal disease, and evidence for NSF. Results. Gadolinium-enhanced MRI was performed on 312 of 837 patients, including 23 with severe renal failure (GFR 30. Two of 23 patients with renal failure developed NSF compared to zero NSF cases in 289 patients with GFR > 30 (0/289; P<0.003. High dose gadodiamide was used in the two NSF cases. There was no increased incidence of NSF with severe liver disease (1/71 compared to nonsevere liver disease (1/241; P=0.412. Conclusion. Renal disease is a risk factor for NSF, but in our small sample our evidence suggests liver disease is not an additional risk factor, especially if a low-risk gadolinium agent is used. Noting that not all patients received high-risk gadolinium, a larger study focusing on patients receiving high-risk gadolinium is needed to further evaluate NSF risk in liver disease in the peritransplant period.

  12. Nutrition for children with cholestatic liver disease

    NARCIS (Netherlands)

    Los, E. Leonie; Lukovac, Sabina; Werner, Anniek; Dijkstra, Tietie; Verkade, Henkjan J.; Rings, Edmond H. H. M.; Cooke, RJ; Vandenplas, Y; Wahn, U

    2007-01-01

    Cholestatic liver disease (CLD) in children negatively affects nutritional status, growth and development, which all lead to an increased risk of morbidity and mortality. This is illustrated by the fact that the clinical outcome of children with CLD awaiting a liver transplantation is in part predic

  13. Alcoholic liver disease: the gut microbiome and liver cross talk.

    Science.gov (United States)

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  14. Alterations of the gut microbiome and metabolome in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Wei; Zhong; Zhanxiang; Zhou

    2014-01-01

    Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic relationship with the host. Alterations of gut microbiome by alcohol consumption are referred to bacterial overgrowth, release of bacteria-derived products, and/or changed microbiota equilibrium. Alcohol consumption also perturbs the function of gastrointestinal mucosa and elicits a pathophysiological condition. These adverse effects caused by alcohol may ultimately result in a broad change of gastrointestinal luminal metabolites such as bile acids, short chain fatty acids, and branched chain amino acids. Gut microbiota alterations, metabolic changes produced in a dysbiotic intestinal environment, and the host factors are all critical contributors to the development and progression of alcoholic liver disease. This review summarizes recent findings of how alcohol-induced alterations of gut microbiota and metabolome, and discusses the mecha-nistic link between gastrointestinal dyshomeostasis and alcoholic liver injury.

  15. Association of nonalcoholic fatty liver disease and liver cancer

    Science.gov (United States)

    Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

    2015-01-01

    AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

  16. [Treatment of parasitic liver diseases].

    Science.gov (United States)

    Lecuna, V

    1989-01-01

    Most of primary and secondary parasitic liver diseases, at present can be property treated with drugs. Venezuelan pharmaceutic market has some peculiarities that have determined the disappearance from the market of many drugs such as emetine, thiabendazole, quinacrine and niclosamide. Diloxanide never appeared. Venezuela has no commercial international treatises that protect international patents in the pharmaceutical area. In addition, government regulation of cost of drugs is very strict. This is particularly true with old drugs (such as emetine or quinacrine) which had such a low price that is non-commercial for the maker of the drug, usually a large transnational, and is withdrawn from the market. Flexibility of prices is quite easy for new antibiotics which are very expensive. Frequently small national companies import the drug from Italy and Japan which sell the drug independently from international treats. Such companies frequently produce the drug for the government social system, but are unreliable and also frequently they withdraw the drug a variable period of time. The government, through the Ministry of Public Health administer free treatment with drugs for malaria, tuberculosis and leprosy. The severe economic crisis of the country has severely impaired the preventive programs and there is an increase of malaria due to gold mining in the south of the country and falciparum chloroquine resistance and an increase of schistosomiasis in a previous free area. Also administration of drugs for malaria has been severely impaired, mainly for economic reasons. The establishment of a National Government Laboratory is an old (as far as 1946) political goal, but has remained in the political intention.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Nonalcoholic Fatty Liver Disease in Pediatrics.

    Science.gov (United States)

    Duncan, Martin; Zong, Wenjing; Biank, Vincent F; Hageman, Joseph R

    2016-02-01

    A 16-year-old Hispanic girl with an elevated body mass index in an otherwise normal state of health presented for her well-child examination. She had signs of metabolic syndrome and insulin resistance including increased waist circumference and acanthosis nigricans. Laboratory results revealed elevated transaminases with otherwise normal hepatic function. Based on the physical examination and laboratory results, she was diagnosed with nonalcoholic fatty liver disease (NAFLD). After further evaluation, she eventually underwent a liver biopsy. The biopsy revealed nonalcoholic steatohepatitis (NASH) with stage 2 fibrosis. This article reviews the definition of NAFLD and NASH, an increasingly prevalent cause of pediatric chronic liver disease associated with obesity and metabolic syndrome. The article also outlines the epidemiology, risk factors, and natural history of NAFLD, which may help identify and prevent high-risk pediatric patients from progressing to irreversible liver disease. Understanding the diagnostic and treatment options offers the best chance at preventing and reversing the early stages of this disease.

  18. 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.

  19. Role of Gut Microbiota in Liver Disease.

    Science.gov (United States)

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

  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. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  2. 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.

  3. Dame Sheila Sherlock: pioneer in liver diseases.

    Science.gov (United States)

    Ellis, Harold

    2009-04-01

    Within living memory of some of us, liver disease was a Cinderella subject. If you look up the first edition of the standard medical textbook of the time, Sir William Osler's 'Principles and Practice of Medicine', published in 1892, you will find a mere 24 of its 1079 pages devoted to the liver, compared with 38 pages on typhoid fever alone; and matters hardly changed throughout the first half of the 20th century. Although 'cirrhosis' and 'hepatitis' were well recognised conditions when I was a house surgeon in 1948, their classification, aetiologies, detailed pathology and management were little understood, while laboratory investigations of the liver diseases were few and non-specific.

  4. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID:27563875

  5. Acute renal dysfunction in liver diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (MRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

  6. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  7. Hyaluronic acid concentration in liver diseases.

    Science.gov (United States)

    Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

    2016-11-01

    The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.

  8. 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...... 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...

  9. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  10. [Non-alcoholic fatty liver disease (NAFLD)].

    Science.gov (United States)

    Rau, Monika; Weiss, Johannes; Geier, Andreas

    2015-07-01

    Non-alcoholic fatty liver disease is the most common chronic liver disease in Europe and in the USA with rising prevalence. Patients with a metabolic syndrome (diabetes mellitus, obesity, dyslipidemia) are patients at risk with the highest prevalence for NAFLD. Progression from a non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) occurs in 5-20% of patients with the potential to develop a liver fibrosis/cirrhosis. NASH patients and NAFLD patients with higher fibrosis should be identified because they are at risk of a higher mortality. A specific treatment for NASH is not available at the moment. Therefore, the treatment of risk factors and metabolic syndrome has high priority.

  11. Histopathology of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Elizabeth; M; Brunt; Dina; G; Tiniakos

    2010-01-01

    Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibros...

  12. Utility of Modeling End-Stage Liver Disease in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Kianifar

    2014-01-01

    Full Text Available Introduction: Chronic liver diseases consist of wide spectrum disorders that may be complicated by cirrhosis and therefore need to transplantation. The pediatric end-stage liver disease (PELD score and model of end-stage liver disease (MELD score has been used as predictors of mortality chronic liver diseases listed for liver transplantation. The aim of this study is evaluation of relation between PELDMELD score and evidence of cirrhosis in children with choronic liver disease.   Materials and Method: This cross-sectional study conducted on 106 patients of chronic liver disease referred to Ghaem Haspital, Mashhad University of Medical Science, Iran during 24 months period (2010-2013. PELD and MELD score were calculated for all patients. Clincal and patholoogical findings of cirrhosis were recorded.   Results: Mean age of patients was 68/3 ± 41.8 months. Mean PELDMELD score was -1/59± 9/64. There was significant correlation between PELDMELD score and clinical icter, spelenomegaly, evidence of hepatopulminary syndrome, esophageal varices, evidence of cirrhosis in tissue specimences.   Conclusion: PELDMELD score appear to be benefit for detection of cirrhotic children among paients with choronic liver disease.

  13. Vascular Disease in Patients with Nonalcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Potze, Wilma; Siddiqui, M. Shadab; Sanyal, Arun J.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is increasingly being diagnosed and is considered to be the most frequent chronic liver disorder in Western countries. It represents a histopathological spectrum ranging from simple hepatic steatosis to steatohepatitis and finally cirrhosis. NAFLD is consider

  14. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    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 neurohumoral...

  15. Transcending chronic liver disease: a qualitative study.

    Science.gov (United States)

    Wainwright, S P

    1997-01-01

    This study explores and describes experiences of chronic liver disease from the patient's perspective. No qualitative research studies appear to have examined the experiences of these patients. In-depth focused interviews and grounded theory data collection and data analysis methods were used. A two-stage theoretical framework (becoming ill, and not living) of the experience of transcending chronic liver disease is presented. Sociological and psychological literature on common sense models of health and illness are briefly reviewed. Several suggestions for further research are made. The way in which this qualitative research study is leading to a quantitative and qualitative appraisal of the psychological adjustment in end-stage chronic liver disease patients is outlined.

  16. Autoimmune hepatitis: a classic autoimmune liver disease.

    Science.gov (United States)

    Moy, Libia; Levine, Jeremiah

    2014-12-01

    AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.

  17. Hemorheological Alteration in Patients Clinically Diagnosed with Chronic Liver Diseases.

    Science.gov (United States)

    Jang, Bohyun; Han, Ji Won; Sung, Pil Soo; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Cho, Young I; Yoon, Seung Kew

    2016-12-01

    Since liver function is changed by chronic liver diseases, chronic liver disease can lead to different hemorheological alterations during the course of the progression. This study aims to compare alterations in whole blood viscosity in patients with chronic liver disease, focusing on the gender effect. Chronic liver diseases were classified into three categories by patient's history, serologic markers, and radiologic findings: nonalcoholic fatty liver disease (NAFLD) (n = 63), chronic viral hepatitis B and C (n = 50), and liver cirrhosis (LC) (n = 35). Whole blood viscosity was measured by automated scanning capillary tube viscometer, while liver stiffness was measured by transient elastography using FibroScan®. Both systolic and diastolic whole blood viscosities were significantly lower in patients with LC than NAFLD and chronic viral hepatitis (P chronic viral hepatitis. Our data suggest that whole blood viscosity test can become a useful tool for classifying chronic liver disease and determining the prognosis for different types of chronic liver diseases.

  18. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    Directory of Open Access Journals (Sweden)

    Teruaki Toyota

    2012-01-01

    Full Text Available We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  19. The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease

    Directory of Open Access Journals (Sweden)

    Adrienne L. King

    2016-10-01

    Conclusion: Collectively, these findings indicate that the hepato-protective effects of SAM against alcohol toxicity are mediated, in part, through a mitochondrial mechanism involving preservation of key mitochondrial bioenergetic parameters and the attenuation of hypoxic stress.

  20. 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.

  1. Research Progression of Cellular Autophagy in Liver System Diseases

    Directory of Open Access Journals (Sweden)

    Chunyun Liu

    2013-09-01

    Full Text Available Autophagy is a basic biological phenomenon widely existed in eukaryotic cells and an important mechanism for cells to adjust to the surrounding environment, prevent invasion of pathogenic micro-organisms and maintain homeostasis, whose activity changes evidently in multiple liver system diseases, suggesting that there is close association between autophagy and the generation and development of liver system diseases. It is also reported that autophagy develops and exerts an important function in many liver-related diseases, such as hepatic carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, viral liver disease and acute liver injury. Therefore, this study aimed to summarize the relationship between autophagy and multiple liver diseases, hoping to explore the effect of autophagy in liver system diseases and further study the regulative effect of autophagy so as to provide new thoughts for their treatment.

  2. Research Progression of Cellular Autophagy in Liver System Diseases

    Institute of Scientific and Technical Information of China (English)

    Liu Chunyun; Gong Xiangwen; Xiao Xinfa; Yuan Xiangying

    2013-01-01

    Autophagy is a basic biological phenomenon widely existed in eukaryotic cells and an important mechanism for cells to adjust to the surrounding environment, prevent invasion of pathogenic micro-organisms and maintain homeostasis, whose activity changes evidently in multiple liver system diseases, suggesting that there is close association between autophagy and the generation and development of liver system diseases. It is also reported that autophagy develops and exerts an important function in many liver-related diseases, such as hepatic carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, viral liver disease and acute liver injury. Therefore, this study aimed to summarize the relationship between autophagy and multiple liver diseases, hoping to explore the effect of autophagy in liver system diseases and further study the regulative effect of autophagy so as to provide new thoughts for their treatment.

  3. NADPH Oxidases in Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Joy X. Jiang

    2014-01-01

    Full Text Available Oxidative stress is a common feature observed in a wide spectrum of chronic liver diseases including viral hepatitis, alcoholic, and nonalcoholic steatohepatitis. The nicotinamide adenine dinucleotide phosphate (NADPH oxidases (NOXs are emerging as major sources of reactive oxygen species (ROS. Several major isoforms are expressed in the liver, including NOX1, NOX2, and NOX4. While the phagocytic NOX2 has been known to play an important role in Kupffer cell and neutrophil phagocytic activity and inflammation, the nonphagocytic NOX homologues are increasingly recognized as key enzymes in oxidative injury and wound healing. In this review, we will summarize the current advances in knowledge on the regulatory pathways of NOX activation, their cellular distribution, and their role in the modulation of redox signaling in liver diseases.

  4. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    Directory of Open Access Journals (Sweden)

    Meenu Bajpai

    2016-01-01

    Full Text Available Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181 in females and 3.17% (21/661 in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%. The most common alloantibody identified was anti-E (11/44 cases, 25%, followed by anti-C (6/44 cases, 13.63%. Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  5. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

    Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

  6. 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.

  7. Wilson's disease; increased aluminum in liver.

    Science.gov (United States)

    Yasui, M; Yoshimasu, F; Yase, Y; Uebayashi, Y

    1979-01-01

    Interaction of trace metal metabolism was studied in a patient with Wilson's dease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.

  8. Liver Transplantation for Hepatitis C and Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Marco Carbone

    2010-01-01

    Full Text Available End-stage liver disease due to hepatitis C (HCV and cirrhosis from alcohol (ALD are the commonest indications for liver transplantation in the western countries. Up to one third of HCV-infected transplant candidates have a history of significant alcohol intake prior to transplantation. However, there are few data available about the possible interaction between alcohol and HCV in the post-transplant setting. Patients with both HCV and alcohol are more likely to die on the waiting list than those with ALD and HCV alone. However, after transplantation, non-risk adjusted graft and patient survival of patients with HCV + ALD are comparable to those of patients with HCV cirrhosis or ALD cirrhosis alone. In the short and medium term HCV recurrence after transplant in patients with HCV + ALD cirrhosis does not seem more aggressive than that in patients with HCV cirrhosis alone. A relapse in alcohol consumption in patients with HCV + ALD cirrhosis does not have a major impact on graft survival. The evidence shows that, as is currently practiced, HCV + ALD as an appropriate indication for liver transplantation. However, these data are based on retrospective analyses with relatively short follow-up so the conclusions must be treated with caution.

  9. Nonalcoholic fatty liver disease in developing countries

    Institute of Scientific and Technical Information of China (English)

    Hossein Bahrami

    2005-01-01

    @@ TO THE EDITOR Nonalcoholic fatty liver disease (NAFLD) is an increasingly known medical entity with high prevalence, about 1 0 to 24 percent in general population and up to 74% in obese population[1]. The prevalence of the disease is expected to increase worldwide, as we are encountering the global obesity epidemic and the trend in developing countries toward the Western lifestyles. However, it looks that there are some differences between the demographic and epidemiologic features of NAFLD in developing and developed countries.

  10. Overlap syndromes among autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Christian Rust; Ulrich Beuers

    2008-01-01

    The three major immune disorders of the liver are autoimmune hepatitis (AIH),primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.

  11. Immunological response in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies,infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD.

  12. Medical therapy for polycystic liver disease.

    Science.gov (United States)

    Khan, S; Dennison, A; Garcea, G

    2016-01-01

    Introduction Somatostatin analogues and rapamycin inhibitors are two classes of drugs available for the management of polycystic liver disease but their overall impact is not clearly established. This article systematically reviews the literature on the medical management of polycystic liver disease. The outcomes assessed include reduction in liver volume and the impact on quality of life. Methods The English language literature published between 1966 and August 2014 was reviewed from a MEDLINE(®), PubMed, Embase™ and Cochrane Library search. Search terms included 'polycystic', 'liver', 'sirolimus', 'everolimus', 'PCLD', 'somatostatin', 'octreotide', 'lanreotide' and 'rapamycin'. Both randomised trials and controlled studies were included. References of the articles retrieved were also searched to identify any further eligible publications. The studies included were appraised using the Jadad score. Results Seven studies were included in the final review. Five studies, of which three were randomised trials, investigated the role of somatostatin analogues and the results showed a mean reduction in liver volume ranging from 2.9% at six months to 4.95 ±6.77% at one year. Only one randomised study examined the influence of rapamycin inhibitors. This trial compared dual therapy with everolimus and octreotide versus octreotide monotherapy. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively but no statistical difference was found between the two groups (p=0.73). Two randomised trials investigating somatostatin analogues assessed quality of life using SF-36(®). Only one subdomain score improved in one of the trials while two subdomain scores improved in the other with somatostatin analogue therapy. Conclusions Somatostatin analogues significantly reduce liver volumes after six months of therapy but have only a modest improvement on quality of life. Rapamycin inhibitors do not confer any additional advantage.

  13. Mitochondrial cholesterol accumulation in alcoholic liver disease: Role of ASMase and endoplasmic reticulum stress.

    Science.gov (United States)

    Marí, Montserrat; Morales, Albert; Colell, Anna; García-Ruiz, Carmen; Fernández-Checa, Jose C

    2014-01-01

    Alcoholic liver disease (ALD) is a major cause of chronic liver disease and a growing health concern in theworld. While the pathogenesis of ALD is poorly characterized key players identified in experimental models and patients, such as perturbations in mitochondrial structure and function, selective loss of antioxidant defense and susceptibility to inflammatory cytokines, contribute to ALD progression. Both oxidative stress and mitochondrial dysfunction compromise essential cellular functions and energy generation and hence are important pathogenic mechanisms of ALD. An important process mediating the mitochondrial disruption induced by alcohol intake is the trafficking of cholesterol to mitochondria, mediated by acid sphingomyelinase-induced endoplasmic reticulum stress, which contributes to increased cholesterol synthesis and StARD1upregulation. Mitochondrial cholesterol accumulation not only sensitizes to oxidative stress but it can contribute to the metabolic reprogramming in ALD, manifested by activation of the hypoxia inducible transcription factor 1 and stimulation of glycolysis and lactate secretion. Thus, a better understanding of the mechanisms underlying alcohol-mediated mitochondrial impairment and oxidative stress may lead to the identification of novel treatments for ALD. The present review briefly summarizes current knowledge on the cellular and molecular mechanisms contributing to alcohol-induced mitochondrial dysfunction and cholesterol accumulation and provides insights for potential therapeutic targets in ALD.

  14. Hemostasis and the diseased liver : a study on hemostatic disorders in liver disease and liver transplantation

    NARCIS (Netherlands)

    C.M. Bakker (Minke)

    1993-01-01

    textabstractIn this thesis studies on hemostatic disorders in liver cirrhosis and liver transplantation have been described. Aims of the work were to further investigate; 1. Whether (low-grade) DIC occurs in liver cirrhosis applying new quantitative tests, measuring thrombin-antithrombin Ill complex

  15. [Parenteral nutrition-associated liver disease].

    Science.gov (United States)

    Moreno Villares, J M

    2008-05-01

    Parenteral nutrition associated liver disease (PNALD) is an important problem in patients who require longterm parenteral nutrition as well as in preterm infants. Prevalence varies according to different series. Clinical presentation is different in adults and infants. Although since its first descriptions several hypothesis have been elucidated, the aetiology is not quite clear. It is possible that different factors could be involved. PNALD risk factors can be classified in three groups: 1) those derived from the lack of enteral nutrition stimulus; 2) parenteral nutrition components acting as toxic or the lack of specific nutrients and 3) those due to the underlying disease. If PNALD appears in short-term PN and it presents only as a mild elevation of liver enzymes, there is no need to treat. On the contrary, when direct bilirubin is > 2 mg/dL and lasts longer, there is a need to consider different causes and to minimize risk factors. We review the different approaches to manage PNALD, including optimizing enteral nutrition, modify parenteral solutions, use of specific nutrients -taurine, choline, etc.- or the use of drugs (mainly ursodeoxicolic acid). If liver disease progresses to cirrhosis a liver transplant must be considered.

  16. Intracranial hemorrhages and late hemorrhagic disease associated cholestatic liver disease.

    Science.gov (United States)

    Per, Hüseyin; Arslan, Duran; Gümüş, Hakan; Coskun, Abdulhakim; Kumandaş, Sefer

    2013-01-01

    Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver disease are at risk for developing secondary vitamin K deficiency because of fat malabsorbtion and inadequate dietary intake. In this study, we described 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH). Six patients underwent surgical evacuation of ICH, following the administration of vitamin K and/or fresh frozen plasma. The possibility of cholestatic liver disease should be considered in the treatment of ICH due to vitamin K deficiency.

  17. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, Andrea; Iaquinto, Gaetano; Gluud, Christian

    2002-01-01

    The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease.......The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease....

  18. Liver diseases in pregnancy: Diseases not unique to pregnancy

    OpenAIRE

    Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat N; Hammoud, Ghassan M; Ibdah, Jamal A

    2013-01-01

    Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail...

  19. Nonalcoholic fatty liver disease and mitochondrial dysfunction

    Institute of Scientific and Technical Information of China (English)

    Yongzhong Wei; R Scott Rector; John P Thyfault; Jamal A Ibdah

    2008-01-01

    Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis,and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood.Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

  20. Treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Juergen Siebler; Peter R Galle

    2006-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion,a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials,weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective.

  1. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Iaquinto, G; Gluud, C

    2003-01-01

    Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  2. Vitamin E reduces liver stiffness in nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Aiko; Fukui; Naoto; Kawabe; Senju; Hashimoto; Michihito; Murao; Takuji; Nakano; Hiroaki; Shimazaki; Toshiki; Kan; Kazunori; Nakaoka; Masashi; Ohki; Yuka; Takagawa; Tomoki; Takamura; Hiroyuki; Kamei; Kentaro; Yoshioka

    2015-01-01

    AIM: To evaluate the efficacy of vitamin E treatment on liver stiffness in nonalcoholic fatty liver disease(NAFLD).METHODS: Thirty-eight NAFLD patients were administered vitamin E for > 1 year. The doses of vitamin E were 150, 300, or 600 mg; three times per day after each meal. Responses were assessed by liver enzyme levels [aspartate aminotransferase(AST), alanine aminotranferease(ALT), and γ-glutamyl transpeptidase(γ-GTP)], noninvasive scoring systems of hepatic fibrosis-4 [FIB-4 index and aspartate aminotransferaseto-platelet index(APRI)], and liver stiffness [velocity of shear wave(Vs)] measured by acoustic radiation force impulse elastography. Vs measurements were performed at baseline and 12 mo after baseline. The patients were genotyped for the patatin-like phospholipase domain containing 3(PNPLA3) polymorphisms and then divided into either the CC/CG or GG group to examine each group’s responses to vitamin E treatment. RESULTS: We found marked differences in the platelet count, serum albumin levels, alkaline phosphatase levels, FIB-4 index, APRI, and Vs at baseline depending on the PNPLA3 polymorphism. AST, ALT, and γ-GTP levels(all P < 0.001); FIB-4 index(P = 0.035); APRI(P < 0.001); and Vs(P < 0.001) significantly decreased from baseline to 12 mo in the analysis of all patients. In the subset analyses of PNPLA3 genotypes, AST levels(P = 0.011), ALT levels(P < 0.001), γ-GTP levels(P = 0.005), APRI(P = 0.036), and Vs(P = 0.029) in genotype GG patients significantly improved, and AST and ALT levels(both P < 0.001), γ-GTP levels(P = 0.003), FIB-4 index(P = 0.017), and APRI(P < 0.001) in genotype CC/CG patients. CONCLUSION: One year of vitamin E treatment improved noninvasive fibrosis scores and liver stiffness in NAFLD patients. The responses were similar between different PNPLA3 genotypes.

  3. Proteasome inhibitor treatment in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Fawzia Bardag-Gorce

    2011-01-01

    Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements (glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC) were upregulated when rats fed alcohol were treated with a low dose of PS-341 (Bortezomib, Velcade(r)). This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease

  4. Obesity, fatty liver disease and intestinal microbiota.

    Science.gov (United States)

    Arslan, Nur

    2014-11-28

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

  5. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    Science.gov (United States)

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  6. Surgical management of polycystic liver disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Adult polycystic liver disease (PCLD) is an autosomal dominant condition commonly associated with autosomal dominant polycystic kidney disease (ADPKD). However in the last decade, it has been recognized that there is a distinct form of autosomal dominant PCLD that arises without concomitant ADPKD. Early knowledge of the pathogenesis was gained from the study of hepatic cysts in patients with ADPKD. Bile duct overgrowth after embryogenesis results in cystic hepatic dilatations that are known as biliary microhamartomas or von Meyenburg complexes. Further dilatation arises from cellular proliferation and fluid secretion into these cysts.There is a variable, broad spectrum of manifestations of PCLD. Although PCLD is most often asymptomatic,massive hepatomegaly can lead to disabling symptoms of abdominal pain, early satiety, persistent nausea,dyspnea, ascites, biliary obstruction, and lower body edema. Complications of PCLD include cyst rupture and cyst infection. Also, there are associated medical problems, especially intracranial aneurysms and valvular heart disease, which clinicians need to be aware of and evaluate in patients with PCLD. In asymptomatic patients, no treatment is indicated for PCLD. In the symptomatic patient, surgical therapy is the mainstay of treatment tailored to the extent of disease for each patient. Management options include cyst aspiration and sclerosis, open or laparoscopic fenestration, liver resection with fenestration, and liver transplantation.The surgical literature discussing treatment of PCLD,including techniques, outcomes, and complication rates,are summarized in this review.

  7. Alcohol Dependence and Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Karl Mann

    2015-01-01

    Full Text Available Alcohol dependence is a disabling condition that has a high prevalence, but in Europe only a small fraction of the people diagnosed with alcohol abuse and dependence are treated, representing the widest treatment gap, as compared with other mental disorders. Early diagnosis and monitoring of alcoholic liver disease (ALD is still insufficiently solved. Although ALD is the most common cause for liver disease in the Western world, it largely remains underestimated and underdiagnosed for many reasons. The recent introduction of non-invasive elastographic techniques such as transient elastography (TE has significantly improved the early diagnosis of alcoholic liver cirrhosis (ALC. As demonstrated in the literature, inflammation-associated liver stiffness (LS rapidly decreases during alcohol detoxification, and is also directly correlated to change in LS in both abstinent and relapsing patients. Newly published data show that LS could be used to monitor and validate hepatoprotective effects during nalmefene usage. Nalmefene is an opioid system modulator that diminishes the reinforcing effects of alcohol, helping the patient to reduce drinking. Three randomised, multicentre, double-blind, placebo-controlled, parallelgroup Phase III studies were designed to assess the efficacy and safety of nalmefene in reducing alcohol consumption. Patients with a high or very high drinking risk level (DRL at baseline and randomisation show a clinically significant effect from nalmefene treatment, which is generally well tolerated. Moreover, reduced alcohol consumption supported by nalmefene in combination with psychosocial support may indeed help to reduce the alcohol-related burden and the large treatment gap.

  8. Inhibition of cereblon by fenofibrate ameliorates alcoholic liver disease by enhancing AMPK.

    Science.gov (United States)

    Kim, Yong Deuk; Lee, Kwang Min; Hwang, Seung-Lark; Chang, Hyeun Wook; Kim, Keuk-Jun; Harris, Robert A; Choi, Hueng-Sik; Choi, Won-Sik; Lee, Sung-Eun; Park, Chul-Seung

    2015-12-01

    Alcohol consumption exacerbates alcoholic liver disease by attenuating the activity of AMP-activated protein kinase (AMPK). AMPK is activated by fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, and inhibited by direct interaction with cereblon (CRBN), a component of an E3 ubiquitin ligase complex. Based on these preliminary findings, we investigated that CRBN would be up-regulated in the liver by alcohol consumption and that CRBN deficiency would ameliorate hepatic steatosis and pro-inflammatory responses in alcohol-fed mice by increasing AMPK activity. Wild-type, CRBN and PPARα null mice were fed an alcohol-containing liquid diet and administered with fenofibrate. Gene expression profiles and metabolic changes were measured in the liver and blood of these mice. Expression of CRBN, cytochrome P450 2E1 (CYP2E1), lipogenic genes, pro-inflammatory cytokines, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were increased in the Lieber-DeCarli alcohol-challenged mice. Fenofibrate attenuated the induction of CRBN and reduced hepatic steatosis and pro-inflammatory markers in these mice. Ablation of the gene encoding CRBN produced the same effect as fenofibrate. The increase in CRBN gene expression by alcohol and the reduction of CRBN expression by fenofibrate were negated in PPARα null mice. Fenofibrate increased the recruitment of PPARα on CRBN gene promoter in WT mice but not in PPARα null mice. Silencing of AMPK prevented the beneficial effects of fenofibrate. These results demonstrate that activation of PPARα by fenofibrate alleviates alcohol-induced hepatic steatosis and inflammation by reducing the inhibition of AMPK by CRBN. CRBN is a potential therapeutic target for the alcoholic liver disease.

  9. Noninvasive investigations for non alcoholic fatty liver disease and liver fi brosis

    Institute of Scientific and Technical Information of China (English)

    Carmen; Fierbinteanu-Braticevici; Ion; Dina; Ana; Petrisor; Laura; Tribus; Lucian; Negreanu; Catalin; Carstoiu

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evalu...

  10. Nuclear receptors and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Cave, Matthew C; Clair, Heather B; Hardesty, Josiah E; Falkner, K Cameron; Feng, Wenke; Clark, Barbara J; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A; McClain, Craig J; Prough, Russell A

    2016-09-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  11. The effect of liver disease on the cardiovascular system

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2007-01-01

    and clinical practice discussed by the best authors.It includes unique sections on: Symptoms and signs in liver diseaseIndustrial diseases affecting the liverThe effects of diseases of other systems on the liverThe effects of liver diseases on other systemsIt 's bigger and more extensive than other books...... into the practical applications to benefit people).Edited by ten leading experts in the liver and biliary tract and their diseases, along with outstanding contributions from over 200 international clinicians, this text has global references, evidence and extensive subject matter - giving you the best science...

  12. Adipose tissue-liver axis in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Alcoholic liver disease (ALD) remains an important healthproblem worldwide. The disease spectrum is featuredby early steatosis, steatohepatitis (steatosis with inflammatorycells infiltration and necrosis), with someindividuals ultimately progressing to fibrosis/cirrhosis.Although the disease progression is well characterized,no effective therapies are currently available for thetreatment in humans. The mechanisms underlying theinitiation and progression of ALD are multifactorial andcomplex. Emerging evidence supports that adiposetissue dysfunction contributes to the pathogenesis ofALD. In the first part of this review, we discuss themechanisms whereby chronic alcohol exposure contributedto adipose tissue dysfunction, including cell death,inflammation and insulin resistance. It has been longknown that aberrant hepatic methionine metabolismis a major metabolic abnormality induced by chronicalcohol exposure and plays an etiological role in thepathogenesis of ALD. The recent studies in our groupdocumented the similar metabolic effect of chronicalcohol drinking on methionine in adipose tissue. Inthe second part of this review, we also briefly discussthe recent research progress in the field with a focuson how abnormal methionine metabolism in adiposetissue contributes to adipose tissue dysfunction and liverdamage.

  13. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    Directory of Open Access Journals (Sweden)

    Ye Han

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

  14. Stem cell differentiation and human liver disease

    Institute of Scientific and Technical Information of China (English)

    Wen-Li Zhou; Claire N Medine; Liang Zhu; David C Hay

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology.

  15. Liver involvement in Gaucher disease - Review and clinical approach.

    Science.gov (United States)

    Adar, Tomer; Ilan, Yaron; Elstein, Deborah; Zimran, Ari

    2016-10-19

    Gaucher disease (GD), one of the most prevalent lysosomal storage diseases, is associated with glucocerebroside accumulation in cells of the monocyte-macrophage system in various organs, including the liver. Evaluating and managing liver disease in patients with Gaucher disease may be challenging. While hepatic involvement is common in Gaucher disease, its severity, and clinical significance span a wide spectrum, ranging from sub-clinical involvement to liver cirrhosis with its associated complications including portal hypertension. Apart from liver involvement in Gaucher disease, patients with may also suffer from other comorbidities involving the liver. That Gaucher disease itself can mimic hepatic lesions, affect laboratory tests used to characterize liver disease, and may be associated with non-cirrhotic portal hypertension, complicates the diagnostic approach even more. Better understanding of liver involvement in Gaucher disease can spare patients unnecessary invasive testing, and assist physicians in decision making when evaluating patients with Gaucher disease suspected for significant liver disease. This review describes the various clinical manifestations, laboratory and imaging abnormalities that may be encountered when following patients with Gaucher disease for liver involvement. The mechanism for liver disease are discussed, as well as the possible hepato-protective effect of glucocerebroside, and the a diagnostic and treatment approaches.

  16. Influence of the CXCL1 rs4074 A allele on alcohol induced cirrhosis and HCC in patients of European descent.

    Directory of Open Access Journals (Sweden)

    Hans Dieter Nischalke

    Full Text Available BACKGROUND AND AIMS: CXCL1 (CXC chemokine-ligand-1 is a ligand for CXC chemokine receptor 2 expressed on hepatic stellate cells (HSC. Thus, CXCL1 might contribute to HSC activation and fibrogenesis. In the present study, we investigated the influence of the CXCL1 rs4074 polymorphism on the occurrence of alcohol induced liver cirrhosis and hepatocellular carcinoma (HCC. METHODS: The study involved 458 patients with alcoholic cirrhosis (170 with HCC, 115 alcoholics without liver disease and 342 healthy controls. All subjects were genotyped for the CXCL1 rs4074 polymorphism and CXCL1 serum levels of 132 patients were measured. In vitro CXCL1 secretion in TLR-transfected cell lines were studied by ELISA. RESULTS: Distribution of the CXCL1 genotypes (GG/GA/AA was 159/219/80 in patients with alcoholic cirrhosis, 52/44/19 in alcoholic controls and 158/140/44 in healthy controls. Patients with alcohol-induced cirrhosis were significantly more often carriers of the CXCL1 rs4074 A allele (65.3% than alcoholics without liver disease (54.8%, OR=1.55; 95%CI=1.025-2.350; p=0.04 and healthy controls (53.8%, OR=1.62; 95%CI=1.212-2.151; p=0.001. Accordingly, the frequency of the CXCL1 rs4074 A allele was significantly higher in the cirrhotic patients than in the subjects without cirrhosis (41.4% vs. 33.9%, OR=1.38, 95% CI:1.14-1.66, p=0.001. Furthermore cirrhotic carriers of the CXCL1 rs4074 A allele had significantly higher CXCL1 serum levels than carriers of the GG genotype. In contrast to sera from healthy controls, sera from patients with alcoholic cirrhosis induced CXCL1 secretion in TLR2- (p=0.016 and TLR4- (p=0.008 transfected HEK293 cells. This finding indicates that sera from patients with alcoholic cirrhosis contain soluble ligands that can induce CXCL1 production via stimulation of TLRs. CONCLUSION: The enhanced CXCL1 serum levels in carriers of the rs4074 A allele together with their increased frequency in patients with alcohol induced cirrhosis

  17. Molecular Therapy and Prevention of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Hubert E. Blum

    2008-01-01

    Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.

  18. Regenerative and fibrotic pathways in canine liver disease

    NARCIS (Netherlands)

    Spee, Bart

    2006-01-01

    Liver diseases occur quite frequently in dogs; the overall incidence in dogs has been estimated around 1-2% of the clinical cases. Most liver diseases are, like in humans, chronic and occur through chronic inflammation due to different causes. In all cases the on-going liver cell damage leads to a r

  19. Towards quantitative magnetic resonance assessment in parenchymal liver disease

    NARCIS (Netherlands)

    Runge, J.H.

    2015-01-01

    In this thesis several advanced magnetic resonance (MR) techniques for quantitative measurements in parenchymal liver disease are studied. In particular, certain important hallmarks of liver disease such as steatosis, fibrosis, iron overload and inflammation are studied. Steatosis or fatty liver dis

  20. Infectious diseases in end-stage liver disease patients.

    Science.gov (United States)

    Mehta, Aneesh K; Lyon, G Marshall

    2010-09-01

    Patients with chronic liver diseases sustain impairment to immune systems, which worsens over time. These defects in their host defense lead to risks of bacterial infections and increased morbidity. Providers should have heightened surveillance for infectious diseases and suspect one with any acute change in status. Patient history may reveal rare infections and allow initiation of early appropriate therapy. There should be a low threshold for obtaining diagnostic cultures and peritoneal fluid samples and discussing possible causes with an infectious diseases consultant or a microbiology laboratory. These maneuvers will maximize therapy in patients at high risk for death due to infectious disease.

  1. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  2. Herbal medicines and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.

  3. Herbal medicines and nonalcoholic fatty liver disease

    Science.gov (United States)

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future. PMID:27570425

  4. Hepatic encephalopathy as a complication of liver disease

    Institute of Scientific and Technical Information of China (English)

    Stephan vom Dahl; Gerald Kircheis; Dieter Haussinger

    2001-01-01

    @@INTRODUCTION Hepatic encephalopathy ( HE) is a frequent complication of chronic liver disease .It is defined as a characteristic functional and reversible alteration of the mental state ,due to impaired liver function and / or increased portosystemic shunting .

  5. Reversal of intestinal failure-associated liver disease (IFALD)

    DEFF Research Database (Denmark)

    Hvas, Christian; Kodjabashia, Kamelia; Nixon, Emma

    2016-01-01

    Patients with intestinal failure (IF) and home parenteral nutrition commonly develop abnormal liver function tests. The presentations of IF-associated liver disease (IFALD) range from mild cholestasis or steatosis to cirrhosis and decompensated liver disease. We describe the reversal of IFALD....... Multidisciplinary treatment in a tertiary IF referral centre included aggressive sepsis management, discontinuation of hepatotoxic medications and a reduction of parenteral nutrition dependency through optimisation of enteral nutrition via distal enteral tube feeding. Upon this, liver function tests normalised....

  6. Alpha-1 antitrypsin deficiency and the risk of hepatocellularcarcinoma in end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To evaluate the association between alpha-1antitrypsin deficiency (A1ATD) and hepatocellularcarcinoma (HCC) in patients with end-stage liver disease(ESLD).METHODS: Patients with cirrhosis and ESLD referred tothe Cleveland Clinic Foundation for liver transplantationbetween 2003 and 2014 were included in the study (N =675). ESLD was defined as having histological features ofcirrhosis and/or radiological evidence of cirrhosis in thecontext of portal hypertension (ascites, variceal bleeding,thrombocytopenia, or hepatic encephalopathy). A1ATDwas diagnosed using phenotype characterization (MZor ZZ), liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules, or both. Patients with othercauses of liver diseases such as hepatitis C virus (HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCCwas diagnosed by using imaging modalities, biopsyfindings, or explanted liver inspection. Follow-up timewas defined as the number of years from the diagnosisof cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow upvisit. The rate of HCC was assessed using time-tointervalanalysis for interval censored data.RESULTS: This study included 675 patients. 7% ofsubjects had A1ATD (n = 47). Out of all subjects whodid not have A1ATD, 46% had HCV, 17% had alcoholicliver disease, 19% had NASH and 18% had anotherprimary diagnosis. Of the 47 subjects with A1ATD, 15had a primary diagnosis of A1ATD (PI*ZZ phenotypeand PAS+ globules), 8 had a PI*MZ phenotype alone,14 had PAS+ alone, and 10 had both the PI*MZphenotype and PAS+. Median follow-up time was 3.4(25th, 75th percentiles: 1, 5.2) years. The overall rate ofhepatocellular carcinoma in all subjects was 29% (n =199). In the A1ATD group, the incidence rate of HCCwas 8.5% compared to 31% in the group of patientswith other causes of cirrhosis (P = 0

  7. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    Science.gov (United States)

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition.

  8. New insights into the coagulopathy of liver disease and liver transplantation

    Institute of Scientific and Technical Information of China (English)

    M Senzolo; P Burra; E Cholongitas; AK Burroughs

    2006-01-01

    The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis.Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore,these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

  9. Liver Disease Recognition: A Discrete Hidden Markov Model Approach

    Directory of Open Access Journals (Sweden)

    Farzan Madadizadeh

    2016-03-01

    Full Text Available The liver alongside the heart and the brain is the largest and the most vital organ within the human body whose absence leads to certain death. In addition, diagnosis of liver diseases takes a long time and requires sufficient expertise of physicians. To this end, statistical methods as automatic prediction systems can help specialists to diagnose liver diseases quickly and accurately. The Discrete Hidden Markov Model (DHMM is an intelligent and a strong statistical model used to predict the types of liver diseases in patients in this study. The data in this crosssectional study included information elicited from the records of 1143 patients with 5 different types of liver diseases including cirrhosis of the liver, liver cancer, acute hepatitis, chronic hepatitis, and fatty liver disease admitted to Afzalipour Hospital in the city of Kerman in the time period of 2006-2013. At first, the type of diseases for each patient was identified; however, it was assumed that the type of diseases is unknown and there were attempts to diagnose the type of the disease through the DHMM to examine its accuracy. Therefore, the DHMM was fitted to the data and its performance was evaluated by using the parameters of accuracy, sensitivity, and specificity. Such parameters of the model were separately calculated for the diagnosis of liver diseases. The highest levels of accuracy, sensitivity, and specificity were associated with the diagnosis of cirrhosis of the liver and equal to 0.77, 0.82, 0.96, respectively; and the lowest levels were related to the diagnosis of fatty liver disease with an accuracy level of 0.65 and a sensitivity level of 0.69. As well, the specificity level in the diagnosis of fatty liver disease was 0.94. The results of this study indicated the potential ability of the DHMM; thus, the use of this model in terms of diagnosing liver diseases was strongly recommended.

  10. Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease : A multicenter experience

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Bozic, M. A.; Fridell, J. A.; Crull, M. H.; Molleston, J.; Avitzur, Y.; Mozer-Glassberg, Y.; Gonzalez-Peralta, R. P.; Hodik, M.; Fecteau, A.; de Angelis, M.; Durie, P.; Ng, V. L.

    2014-01-01

    Background: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver pancreas transplantation is less understood. Methods: We polled 81 pedi

  11. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis.

    Science.gov (United States)

    Malik, Shahid M; Devera, Michael E; Fontes, Paulo; Shaikh, Obaid; Sasatomi, Eizaburo; Ahmad, Jawad

    2009-12-01

    Recurrence of the original disease following liver transplantation is not uncommon and can lead to graft failure. There are limited data on recurrent fatty liver disease following liver transplantation. The aim of this study was to determine the incidence of recurrent fatty liver disease in patients with biopsy-proven nonalcoholic steatohepatitis, its effect on survival, and whether there are any predictive factors for recurrence. We analyzed patients undergoing liver transplantation for nonalcoholic steatohepatitis cirrhosis from 1997 to 2008 at a single center. Patients undergoing transplantation for cholestatic disease, alcohol, hepatitis C, or cryptogenic cirrhosis were controls. Ninety-eight patients underwent transplantation for nonalcoholic steatohepatitis cirrhosis. Recurrent fatty liver disease was seen in 70%, 25% had recurrent nonalcoholic steatohepatitis, and 18% had stage II/IV or greater fibrosis at a mean of 18 months. No patients with recurrent nonalcoholic steatohepatitis developed graft failure or required retransplantation at a follow-up of 3 years. No recipient or donor factors were associated with disease recurrence, although patients with recurrent nonalcoholic steatohepatitis had a higher incidence of diabetes, weight gain, and dyslipidemia at the time of diagnosis of recurrence. One-third of patients with recurrent nonalcoholic steatohepatitis had normal liver enzymes at the time of diagnosis post-transplantation. In conclusion, recurrent fatty liver disease is common following liver transplantation for nonalcoholic steatohepatitis cirrhosis but does not lead to early allograft failure. Recurrent nonalcoholic steatohepatitis can occur despite normal liver enzymes, and features of metabolic syndrome are associated with disease recurrence.

  12. Liver Disorders in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Victor Uko

    2012-01-01

    Full Text Available Disorders of the hepatobiliary system are relatively common extraintestinal manifestations of inflammatory bowel disease (IBD. These disorders are sometimes due to a shared pathogenesis with IBD as seen in primary sclerosing cholangitis (PSC and small-duct primary sclerosing cholangitis (small-duct PSC. There are also hepatobiliary manifestations such as cholelithiasis and portal vein thrombosis that occur due to the effects of chronic inflammation and the severity of bowel disease. Lastly, medications used in IBD such as sulfasalazine, thiopurines, and methotrexate can adversely affect the liver. It is important to be cognizant of these disorders as some do have serious long-term consequences. The management of these disorders often requires the expertise of multidisciplinary teams to achieve the best outcomes.

  13. Psychosocial stress and liver disease status

    Institute of Scientific and Technical Information of China (English)

    Cristin Constantin Vere; Costin Teodor Streba; Letitia Maria Streba; Alin Gabriel Ionescu; Felix Sima

    2009-01-01

    "Psychosocial stress" is an increasingly common concept in the challenging and highly-demanding modern society of today. Organic response to stress implicates two major components of the stress system,namely the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Stress is anamnestically reported by patients during the course of disease, usually accompanied by a decline in their overall health status. As the mechanisms involving glucocorticoids and catecholamines have been deciphered, and their actions on immune cell function deeper understood, it has become clear that stress has an impact on hepatic inflammatory response. An increasing number of articles have approached the link between psychosocial stress and the negative evolution of hepatic diseases. This article reviews a number of studies on both human populations and animal models performed in recent years, all linking stress, mainly of psychosocial nature, and the evolution of three important liver-related pathological entities: viral hepatitis, cirrhosis and hepatocellular carcinoma.

  14. [Immunity and malnutrition in alcoholic liver diseases].

    Science.gov (United States)

    Hevia Ojanguren, C; Fanjul Cabeza, B; González Vázquez, M I; Linares Rodríguez, A; Rodrigo Sáez, L

    1994-10-01

    Assessment of immunity was performed in 150 patients with alcoholic liver disease (15 steatosis, 30 hepatitis and 105 cirrhosis: 34 in grade A, 34 in grade B and 37 in grade C, according to Child-Pugh classification). This assessment was based on the total lymphocyte count and a delayed hypersensitivity skin multiple test. Likewise, nutritional status of patients was studied using anthropometric and biochemical parameters (triceps skinfold thickness, arm muscle circumference and serum albumin). The association between alcoholic liver disease, malnutrition and immunity was analyzed. The results show that lymphopenia and disorders in cell-mediate immunity were more common in those patients with cirrhosis, increasing the number of anergic patients while the degree of hepatocellular insufficiency worsens (8.8% in grade A, 11.8% in grade B and 32.4% in grade C). Although there where significantly more alterations of delayed cutaneous hypersensitivity in cirrhotics with malnutrition (hypoergy: 55.2% and anergy: 37.9%) than in those well nourished (hypoergy: 23.7% and anergy: 10.5%, p < 0.01), lymphopenia didn't show differences between these groups. We think that immunity mus'nt be considered a parameter in nutritional assessment.

  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;

    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...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...

  16. Intracranial hemorrhages and late hemorrhagic disease associated cholestatic liver disease

    OpenAIRE

    2012-01-01

    Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver dis...

  17. Bisphenol A sulfonation is impaired in metabolic and liver disease

    Science.gov (United States)

    Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L.; King, Roberta

    2016-01-01

    Background Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. Liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. PMID:26712468

  18. Liver diseases in pregnancy: diseases not unique to pregnancy.

    Science.gov (United States)

    Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat N; Hammoud, Ghassan M; Ibdah, Jamal A

    2013-11-21

    Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.

  19. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Sha Li

    2015-11-01

    Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  20. Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases

    Science.gov (United States)

    Yarygin, Konstantin N.

    2017-01-01

    The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable. PMID:28210629

  1. Molecular Basis and Current Treatment for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Juan Armendariz-Borunda

    2010-04-01

    Full Text Available Alcohol use disorders and alcohol dependency affect millions of individuals worldwide. The impact of these facts lies in the elevated social and economic costs. Alcoholic liver disease is caused by acute and chronic exposure to ethanol which promotes oxidative stress and inflammatory response. Chronic consumption of ethanol implies liver steatosis, which is the first morphological change in the liver, followed by liver fibrosis and cirrhosis. This review comprises a broad approach of alcohol use disorders, and a more specific assessment of the pathophysiologic molecular basis, and genetics, as well as clinical presentation and current modalities of treatment for alcoholic liver disease.

  2. Liver transplantation in PBC and PSC: indications and disease recurrence.

    Science.gov (United States)

    Carbone, Marco; Neuberger, James

    2011-06-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent major indications for liver transplantation (LT). Despite the steady increase in the incidence and prevalence of PBC, the number of liver transplants for PBC has fallen in recent years, whereas the number of transplants for PSC has remained stable. Indications for LT for PBC and PSC are no different from those of other causes of chronic liver disease, apart from some disease-specific indications. PBC and PSC have more favourable outcomes after LT, compared to viral hepatitis and alcohol-associated liver disease. Numerous studies have clearly demonstrated that PBC and PSC recur after LT. The diagnosis of recurrent disease should be made on agreed criteria. The impact of recurrent disease on survival is unclear. Study of recurrent PBC and PSC may provide a better understanding of the mechanisms of these diseases in the native liver.

  3. Novel approaches to assessing renal function in cirrhotic liver disease.

    Science.gov (United States)

    Portal, Andrew J; Austin, Mark; Heneghan, Michael A

    2007-09-01

    Renal dysfunction is common in patients with end-stage liver disease. Etiological factors include conditions as diverse as acute tubular necrosis, immunoglobulin A nephropathy and hepatorenal syndrome. Current standard tests of renal function, such as measurement of serum urea and creatinine levels, are inaccurate as the synthesis of these markers is affected by the native liver pathology. This article reviews novel markers of renal function and their potential use in patients with liver disease.

  4. Anti-neutrophil cytoplasm autoantibodies (ANCA) in autoimmune liver diseases

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees

    1999-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes and monocytes. ANCA have been detected in serum from patients with inflammatory bowel diseases (mainly ulcerative colitis) and autoimmune mediated liver diseases (mainl

  5. Non-Alcoholic Fatty Liver Disease: From patient to population

    NARCIS (Netherlands)

    E.M. Koehler (Edith)

    2013-01-01

    textabstractNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Western countries, in parallel with epidemics in obesity and type 2 diabetes mellitus. NAFLD comprises a wide range of histological findings, extending from simple steatosis to nonalcoholic stea

  6. S-adenosyl-L-methionine for alcoholic liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Alcohol is a major cause of liver disease in the Western world today. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for all known biological methylation reactions and participates in the synthesis of glutathione, the main cellular anti-oxidant. Randomised clinical trials have addressed...... the question whether SAMe has any efficacy in patients with alcoholic liver diseases....

  7. S-adenosyl-L-methionine for alcoholic liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed...... the question whether SAMe may benefit patients with alcoholic liver diseases....

  8. Regulation of plasma erythropoietin in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Frank Tacke; Tom Luedde; Michael P.Manns; Christian Trautwein

    2004-01-01

    @@ To the Editor: In a May-issue of the World Journal of Gastroenterology, there is a very interesting study by Bruno et al. on erythropoietin(EPO) levels in patients with chronic liver disease[1]. We have very recently reported a similar, but much larger study by Tacke et al.[2] on the role of EPO in chronic liver disease.

  9. Endocrine-Manifestations of Cirrhosis and Liver Disease

    Directory of Open Access Journals (Sweden)

    M Khalili

    2014-04-01

    Full Text Available The liver is involved in the synthesis and metabolism of many kinds of hormones, various abnormalities hormone levels are found in advanced liver disease. For example the liver is, extremely sensitive to changes in insulin or glucagon levels. The liver is the primary organ of iron storage is frequently involved, diabetes is common in patients with iron overload and may be seen in cirrhosis. Chronic infection with HCV is associated with insulin resistance. Thyroid disease often accompanies chronic hepatitis C infection .Anti thyroid autoantibodies are also found in chronic HCV infection. Nonalcoholic liver disease (NAFLDas a most common cause of chronic liver disease in western world ,as well accompanied by Type 2 diabetes and hyperlipidemia. Hypopituitarism and hypothyroidism also have been in NAFLD.The patients with NAFLD and Hypopituitarism may be susceptible to central obesity, dyslipidemia and insulin resistance leading to disease progression. Hepatic cirrhosis as the end stage of chronic liver disease is also associated with hypogonadism and signs of feminization. The peripheral metabolism of steroids is altered in many of hypogonadism, low testosterone level decreased libido, infertility, reduced secondary sex hair and gynecomastia, reduced spermatogenesis and peritubular fibrosis are found in men with cirrhosis .The normal function of the hypothalamic-pituitary gonadal axis is affected in liver disease. In cirrhotic patients the estrogen/androgen ratio is usually increased, the level of testosterone and dihydroepiandosteron are reduced while the estradiol level are normal or slightly elevated, these alterations are dependent on the severity of the liver disease.Succsesfull orthotropic liver transplantation  leads to improvement of the sex hormone disturbances. The pathogenesis of gynecomastia is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state but it is due to increased estrogen precursor in

  10. Liver diseases and aging : friends or foes?

    NARCIS (Netherlands)

    Sheedfar, Fareeba; Di Biase, Stefano; Koonen, Debby; Vinciguerra, Manlio

    2013-01-01

    The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could affe

  11. Saturated and Unsaturated Dietary Fats Differentially Modulate Ethanol-Induced Changes in Gut Microbiome and Metabolome in a Mouse Model of Alcoholic Liver Disease.

    Science.gov (United States)

    Kirpich, Irina A; Petrosino, Joseph; Ajami, Nadim; Feng, Wenke; Wang, Yuhua; Liu, Yanlong; Beier, Juliane I; Barve, Shirish S; Yin, Xinmin; Wei, Xiaoli; Zhang, Xiang; McClain, Craig J

    2016-04-01

    Alcoholic liver disease (ALD) ranks among major causes of morbidity and mortality. Diet and crosstalk between the gut and liver are important determinants of ALD. We evaluated the effects of different types of dietary fat and ethanol on the gut microbiota composition and metabolic activity and the effect of these changes on liver injury in ALD. Compared with ethanol and a saturated fat diet (medium chain triglycerides enriched), an unsaturated fat diet (corn oil enriched) exacerbated ethanol-induced endotoxemia, liver steatosis, and injury. Major alterations in gut microbiota, including a reduction in Bacteroidetes and an increase in Proteobacteria and Actinobacteria, were seen in animals fed an unsaturated fat diet and ethanol but not a saturated fat diet and ethanol. Compared with a saturated fat diet and ethanol, an unsaturated fat diet and ethanol caused major fecal metabolomic changes. Moreover, a decrease in certain fecal amino acids was noted in both alcohol-fed groups. These data support an important role of dietary lipids in ALD pathogenesis and provide insight into mechanisms of ALD development. A diet enriched in unsaturated fats enhanced alcohol-induced liver injury and caused major fecal metagenomic and metabolomic changes that may play an etiologic role in observed liver injury. Dietary lipids can potentially serve as inexpensive interventions for the prevention and treatment of ALD.

  12. Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

    Science.gov (United States)

    Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

    2010-02-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

  13. Reversibility of alcohol-induced immune depression

    DEFF Research Database (Denmark)

    Tønnesen, H; Kaiser, A H; Nielsen, B B;

    1992-01-01

    Alcohol abusers have suppressed cellular immune function. The aim of the study was to investigate the time of sobriety required to normalize immune function. Delayed hypersensitivity was investigated during disulfiram controlled abstinence in ten heavy alcoholics and in seven moderate drinkers...... without liver diseases. For comparison a control group of eight previous drinkers was tested. The skin test responses were modest initially with a median area of response of 12 mm2 (range 0-31) in the heavy alcoholics and 3 mm2 (0-15) in the moderate drinkers. It improved significantly in both groups...... after two weeks of sobriety. The responses stabilized after 8 weeks at 74 mm2 (54-102) in the heavy alcoholics and after 9 weeks at 63 mm2 (42-76) in the moderate drinking group. The control group had skin test responses of 70 mm2 (46-87), not different from the responses of the alcohol groups after two...

  14. Orthotopic liver transplantation in non-alcoholic fatty liver disease patients.

    Science.gov (United States)

    Burra, Patrizia; Germani, Giacomo

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent etiology of liver disease in Western Countries and non-alcoholic steato-hepatitis (NASH) is becoming a leading indication for liver transplantation in US, with constant increase overtime. Specific co-morbidities correlated to the presence of obesity and associated with metabolic syndrome should always be ruled out in patients affected by NASH-related end-stage liver disease, who are potential candidates for liver transplantation. Patients transplanted for NAFLD present similar outcomes compared with patients transplanted for other indications. With regards to post-transplant outcomes in obese patients, available data are contradictory, with reported increased mortality only in patients with BMI >40. A new multidisciplinary protocol of liver transplantation and sleeve gastrectomy seems to be effective and safe in obese patients who were not able to lose weight before liver transplantation. However prospective studies are needed. The NASH recurrence rate after liver transplantation ranges between 20-40%, but its variability largely depends on the methodology used for the diagnosis (i.e. liver tests, liver histology or imaging technique).

  15. Autoimmune liver disease in Noonan Syndrome.

    Science.gov (United States)

    Loddo, Italia; Romano, Claudio; Cutrupi, Maria Concetta; Sciveres, Marco; Riva, Silvia; Salpietro, Annamaria; Ferraù, Valeria; Gallizzi, Romina; Briuglia, Silvana

    2015-03-01

    Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown.

  16. Non-alcoholic fatty liver disease in children.

    Science.gov (United States)

    Janczyk, Wojciech; Socha, Piotr

    2012-06-01

    Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation.

  17. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    Directory of Open Access Journals (Sweden)

    Aggeliki Lyberopoulou

    Full Text Available Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21, HBV (n = 23, autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34, autoimmune hepatitis (AIH; n = 16 and non-alcoholic fatty liver disease (NAFLD; n = 32. Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  18. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    Science.gov (United States)

    Lyberopoulou, Aggeliki; Chachami, Georgia; Gatselis, Nikolaos K; Kyratzopoulou, Eleni; Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K; Mamalaki, Avgi; Dalekos, George N; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (Pserum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  19. Roles of liver innate immune cells in nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD can also promote the development and progression of disease in other organ systems, such as the cardiovascular and endocrine (i.e. diabetes) systems. Thus, understanding th...

  20. Cell therapy for liver diseases: current medicine and future promises.

    Science.gov (United States)

    Alejandra, Meza-Ríos; Juan, Armendáriz-Borunda; Ana, Sandoval-Rodríguez

    2015-06-01

    Liver diseases are a major health problem worldwide since they usually represent the main causes of death in most countries, causing excessive costs to public health systems. Nowadays, there are no efficient current therapies for most hepatic diseases and liver transplant is infrequent due to the availability of organs, cost and risk of transplant rejection. Therefore, alternative therapies for liver diseases have been developed, including cell-based therapies. Stem cells (SCs) are characterized by their self-renewing capacity, unlimited proliferation and differentiation under certain conditions into tissue- or organ-specific cells with special functions. Cell-based therapies for liver diseases have been successful in experimental models, showing anti-inflammatory, antifibrogenic and regenerative effects. Nowadays, clinical trials using SCs for liver pathologies are increasing in number, and those that have reached publication have achieved favorable effects, encouraging us to think that SCs will have a potential clinical use in a short time.

  1. Role of lipid rafts in liver health and disease

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc

    2011-01-01

    Liver diseases are an increasingly common cause of morbidity and mortality; new approaches for investigation of mechanisms of liver diseases and identification of therapeutic targets are emergent. Lipid rafts (LRs) are specialized domains of cellular membranes that are enriched in saturated lipids; they are small, mobile, and are key components of cellular architecture, protein partition to cellular membranes, and signaling events. LRs have been identified in the membranes of all liver cells, parenchymal and non-parenchymal; more importantly, LRs are active participants in multiple physiological and pathological conditions in individual types of liver cells. This article aims to review experimental-based evidence with regard to LRs in the liver, from the perspective of the liver as a whole organ composed of a multitude of cell types. We have gathered up-to-date information related to the role of LRs in individual types of liver cells, in liver health and diseases, and identified the possibilities of LR-dependent therapeutic targets in liver diseases.

  2. Current Status of Therapy in Autoimmune Liver Disease

    OpenAIRE

    Hirschfield, Gideon M.; Al-Harthi, Nadya; Heathcote, E. Jenny

    2009-01-01

    Therapeutic strategies for autoimmune liver diseases are increasingly established. Although proportionately uncommon, specialist centers have with time refined the best approaches for each disease, based on an improved understanding of the spectrum of presentation. The major treatment aims are to prevent end-stage liver disease and its associated complications. As a result of drugs such as ursodeoxycholic acid, predniso(lo)ne and azathioprine, both primary biliary cirrhosis ...

  3. Genetics of liver disease: From pathophysiology to clinical practice.

    Science.gov (United States)

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

    2015-04-01

    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients.

  4. Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis

    Directory of Open Access Journals (Sweden)

    Jayashree Bagchi Chakraborty

    2012-01-01

    Full Text Available Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD nonalcoholic liver disease (NAFLD including non-alcoholic steatohepatitis (NASH viral hepatitis B and C (HBV, HCV. The critical step in the development of scar is activation of hepatic stellate cells (HSCs, which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression.

  5. Impact of coffee on liver diseases: a systematic review.

    Science.gov (United States)

    Saab, Sammy; Mallam, Divya; Cox, Gerald A; Tong, Myron J

    2014-04-01

    Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed. Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase and alanine aminotransferase values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. Moreover, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged.

  6. Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease.

    OpenAIRE

    Zeybel, Müjdat; Hardy, Timothy; Robinson, Stuart M.; Fox, Christopher; Anstee, Quentin M.; Ness, Thomas; Masson, Steven; Masson, Steven; French, Jeremy; White, Steve; Mann, Jelena

    2015-01-01

    RESEARCH Open Access Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease Müjdat Zeybel1, Timothy Hardy1, Stuart M Robinson1, Christopher Fox1, Quentin M Anstee1, Thomas Ness2, Steven Masson1, John C Mathers1, Jeremy French1, Steve White1 and Jelena Mann1* Abstract Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patie...

  7. Bone changes in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Alcoholism has been associated with growth impairment,osteomalacia, delayed fracture healing, and asepticnecrosis (primarily necrosis of the femoral head), butthe main alterations observed in the bones of alcoholicpatients are osteoporosis and an increased risk offractures. Decreased bone mass is a hallmark of osteoporosis,and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanolmay affect both mechanisms. It is generally acceptedthat ethanol decreases bone synthesis, and most authorshave reported decreased osteocalcin levels (a "marker" ofbone synthesis), but some controversy exists regardingthe effect of alcohol on bone breakdown, and, indeed,disparate results have been reported for telopeptideand other biochemical markers of bone resorption.In addition to the direct effect of ethanol, systemicalterations such as malnutrition, malabsorption, liverdisease, increased levels of proinflammatory cytokines,alcoholic myopathy and neuropathy, low testosteronelevels, and an increased risk of trauma, play contributoryroles. The treatment of alcoholic bone disease should beaimed towards increasing bone formation and decreasingbone degradation. In this sense, vitamin D and calciumsupplementation, together with biphosphonates areessential, but alcohol abstinence and nutritional improvementare equally important. In this review we study thepathogenesis of bone changes in alcoholic liver diseaseand discuss potential therapies.

  8. Uncoupling protein and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    JIN Xi; XIANG Zun; CHEN Yi-peng; MA Kui-fen; YE Yue-fang; LI You-ming

    2013-01-01

    Objective To review the current advances on the role of uncoupling protein (UCP) in the pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD).Data sources A comprehensive search of the PubMed literature without restriction on the publication date was carried out using keywords such as UCP and NAFLD.Study selection Articles containing information related to NAFLD and UCP were selected and carefully analyzed.Results The typical concepts,up-to-date findings,and existing controversies of UCP2 in NAFLD were summarized.Besides,the effect of a novel subtype of UCP (hepatocellular down regulated mitochondrial carrier protein,HDMCP) in NAFLD was also analyzed.Finally,the concept that any mitochondrial inner membrane carrier protein may have,more or less,the uncoupling ability was reinforced.Conclusions Considering the importance of NAFLD in clinics and UCP in energy metabolism,we believe that this review may raise research enthusiasm on the effect of UCP in NAFLD and provide a novel mechanism and therapeutic target for NAFLD.

  9. Concepts in leptin and liver disease

    Directory of Open Access Journals (Sweden)

    El-Badawy Reda

    2004-01-01

    Full Text Available Leptin is a cytokine l6kd peptide hormone. Its crucial role is regulation of appetite and the body fat mass mainly through action on the hypothalamus. It is produced mainly in adipocytes of white fat, as well as from other tissues e.g. placenta, skeletal muscles, fundus of the stomach and activated hepatic stellate cell (HSC and recently reported that leptin is produced from B cell of islands of the pancreas. The gene responsible for production is present on chromosome 7 called obse gene (ob/gene. Leptin receptors (OB-R were present in two forms short (OB-Ra or OB-RS and long one (OB-Rb or OB-RI. The main action of leptin depends on long form (OB-Rl, where very little evidence is available implicating a role for the short form in the action of leptin. One of the unconventional areas in which leptin is now receiving great attention is liver diseases as several published studies indicate that circulating leptin level are increased in cirrhosis, hepatitis C virus (HCV and non-alcoholic steatohepatitis (NASH

  10. Soft drinks consumption and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    William; Nseir; Fares; Nassar; Nimer; Assy

    2010-01-01

    Nonalcoholic fatty liver disease(NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver,and increased hepatic triglyceride accumulation contributes to fatty liver.Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks,fructose 55% and glucose 45%.Soft drinks...

  11. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    OpenAIRE

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH ...

  12. Meta-analysis: antioxidant supplements for liver diseases - the Cochrane Hepato-Biliary Group

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, L L; Nikolova, D

    2010-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  13. Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Markus Neumeier; Jürgen Sch(o)lmerich; Christa Buechler; Claus Hellerbrand; Erwin G(a)bele; Roland Buettner; Cornelius Bollheimer; Johanna Weigert; Andreas Sch(a)ffler; Thomas S Weiss; Monika Lichtenauer

    2006-01-01

    AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level.METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA.RESULTS: Systemic adiponectin is reduced in fat fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice.CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.

  14. Role of Kupffer cells in the pathogenesis of liver disease

    Institute of Scientific and Technical Information of China (English)

    George Kolios; Vassilis Valatas; Elias Kouroumalis

    2006-01-01

    Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by producing harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.

  15. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease

    Science.gov (United States)

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-01-01

    Abstract The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined. We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating. Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN. PMID:26222864

  16. The Natural Course of Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Luis Calzadilla Bertot

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM. NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC, and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

  17. The Natural Course of Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

  18. The role of oxidative stress in alcoholic liver injury

    Directory of Open Access Journals (Sweden)

    Radosavljević Tatjana

    2009-01-01

    Full Text Available Introduction. Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. Role of cytochrome P4502E1 in ethanol-induced oxidative stress. Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in alcohol-induced oxidative stress. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanolfed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. Role of Kupffer cells in alcohol-induced liver injury. Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. Role of neutrophils in alcohol-induced liver injury. Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. Role of nitric oxide in alcohol-induced oxidative stress. High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. Role of antioxidants in ethanol-induced oxidative stress. Chronic ethanol consumption is associated with reduced liver glutathione and α-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity. Conclusion. Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.

  19. Hepatocyte xenotransplantation for treating liver disease.

    Science.gov (United States)

    Bonavita, André Gustavo; Quaresma, Kátia; Cotta-de-Almeida, Vinícius; Pinto, Marcelo Alves; Saraiva, Roberto Magalhães; Alves, Luiz Anastácio

    2010-01-01

    The treatment of acute and chronic liver failure is still a challenge despite modern therapeutic innovations. While liver transplantation can restore liver function and improve patient survival, donor shortages limit this treatment to a small number of patients. Cellular xenotransplantation has emerged as an alternative for treating liver failure. Xenohepatocytes could be readily available in sufficient quantities to treat patients in critical condition and thereby reduce the donor shortage. The use of isolated encapsulated or non-encapsulated cells can reduce the immunorejection response. Several studies using animal models of acute or chronic liver failure have demonstrated improved survival and recovery of liver function after xenotransplantation of adult hepatocytes. Porcine liver cells are a potential source of xenohepatocytes due to similarities with human physiology and the great number of hepatocytes that can be obtained. The recent development of less immunogenic transgenic pigs, new immunosuppressive drugs, and cellular encapsulation systems represents important advances in the field of cellular xenotransplantation. In this study, we review the work carried out in animal models that deals with the advantages and limitations of hepatocyte xenotransplantation, and we propose new studies needed in this field.

  20. Model for End-Stage Liver Disease and liver cirrhosis-related complications.

    Science.gov (United States)

    Bertot, Luis Calzadilla; Gomez, Eduardo Vilar; Almeida, Linnet Alonso; Soler, Enrique Arus; Perez, Luis Blanco

    2013-06-01

    The Model for End-Stage Liver Disease (MELD) score has gained wide acceptance for predicting survival in patients undergoing liver transplantation. The strength of this score remains in the mathematical formula derived from a multivariate Cox regression analysis; it is a continuous scale and lacks a ceiling or a floor effect with a wide range of discrimination. It is based on objective, reproducible, and readily available laboratory data and the wide range of samples which have been validated. Liver cirrhosis complications such as ascites, encephalopathy, spontaneous bacterial peritonitis and variceal bleeding were not considered in the MELD score underestimating their direct association with the severity of liver disease. In this regard, several recent studies have shown that clinical manifestations secondary to portal hypertension are good prognostic markers in cirrhotic patients and may add additional useful prognostic information to the current MELD. We review the feasibility of MELD score as a prognostic predictor in patients with liver cirrhosis-related complications.

  1. Encephalopathy in Wilson disease: copper toxicity or liver failure?

    Science.gov (United States)

    Ferenci, Peter; Litwin, Tomasz; Seniow, Joanna; Czlonkowska, Anna

    2015-03-01

    Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis.

  2. Epidemiology of alcoholic liver disease in Denmark 2006-2011

    DEFF Research Database (Denmark)

    Deleuran, Thomas; Vilstrup, Hendrik; Becker, Ulrik

    2015-01-01

    AIMS: To describe incidence, prevalence, hospitalization rates and survival for alcoholic liver disease (ALD) in Denmark 2006-2011. METHODS: Using nationwide healthcare registries we identified all Danish residents with a hospital diagnosis of ALD and computed standardized incidence, prevalence...

  3. Association between nonalcoholic fatty liver disease and coronary artery disease

    Directory of Open Access Journals (Sweden)

    Consuelo P. Vilar

    2013-06-01

    Full Text Available OBJECTIVE: Although some investigations have shown a relationship between nonalcoholic fatty liver disease (NAFLD and cardiovascular diseases, there are few studies analyzing the relationship between NAFLD and coronary artery disease (CAD. The aim of this article was to review the relationship between NAFLD and CAD and the methods of diagnosis used to assess such relationship. METHODS: A review was performed using search engines of indexed scientific material, including MEDLINE (by PubMed, Web of Science, IBECS, and LILACS, to identify articles published in Portuguese, English, and Spanish until August, 2012. The studies were eligible if they included the following data: place and year of publication, prevalence and methods used to diagnose NAFLD (ultrasound, computed tomography, nuclear magnetic resonance, or biopsy and CAD (coronary angiography, or computed tomography, and the exclusion of patients due to alcohol consumption greater than 20 g/day. RESULTS: Ten articles were selected, most of which were cross-sectional studies. The studies mostly observed the association between NAFLD and the presence and severity of CAD. CONCLUSION: The analysis of the review showed that evaluating the existence of NAFLD in patients with CAD from its subclinical form up to the symptomatic clinical form is important due to the higher risk of acute myocardial infarction and consequent increase of mortality.

  4. Adiponectin, a key adipokine in obesity related liver diseases

    Institute of Scientific and Technical Information of China (English)

    Christa Buechler; Josef Wanninger; Markus Neumeier

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries. Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance. Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients. Besides liver biopsy no diagnostic tools to identify patients with NASH are available, and no effective treatment has been established. Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage, insulin resistance, and progressive liver damage. Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage. Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH. Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis. This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.

  5. [Hepatic cell transplantation: a new therapy in liver diseases].

    Science.gov (United States)

    Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

    2010-07-01

    Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program.

  6. Role of spleen elastography in patients with chronic liver diseases.

    Science.gov (United States)

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-09-21

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

  7. MicroRNA signatures in liver diseases

    OpenAIRE

    Chen, Xian-Ming

    2009-01-01

    MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregu...

  8. Anaphylaxis from intravascular rupture of Hydatid disease following liver trauma

    Directory of Open Access Journals (Sweden)

    Paul J Marriott

    2010-09-01

    Full Text Available Cystic Echinococcosis also known as cystic hydatid disease is a parasitic infection endemic in many parts of the world. Humans are accidental intermediate hosts with cysts most commonly developing in the liver. This case describes a rare presentation of hydatid disease following trauma to the liver. Intraparenchymal cyst rupture led to haemodynamic instability with release of the parasites protoscolices into hepatic venules producing severe life threatening anaphylaxis.

  9. Periodontal disease and liver cirrhosis: A systematic review

    OpenAIRE

    Lea Ladegaard Grønkjær

    2015-01-01

    Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conduct...

  10. DIFFERENT MODELS OF HEPATOTOXICITY AND RELATED LIVER DISEASES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Singh Robin

    2012-07-01

    Full Text Available The liver is among the most complex and important organs in the human body. Its primary function is to control the flow and safety of substances absorbed from the digestive system before distribution of these substances to the systemic circulatory system. Hepatotoxicity implies chemical-driven liver damage. Chemicals that cause liver injury are called hepatotoxins. Hepatic injury leads to disturbances in transport function of hepatocytes resulting in leakage of plasma membrane thereby causing an increased enzyme level in serum. There are many diseases that are related with hepatotoxicity caused by certain chemicals or hepatotoxins. Herbal medicines are great demand in various chemicals and drugs disordered hepatic, the developed world for primary health care because of their efficacy, safety, lesser side effects and narrow therapeutic window. This review focus on liver, its function, liver diseases and different models of hepatotoxicity.

  11. Nonalcoholic fatty liver disease – an etiological approach

    Directory of Open Access Journals (Sweden)

    Florentina Ioniță Radu

    2014-06-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is defined as the presence of fat in the liver (hepatic steatosis either on imaging or on liver histology only after the exclusion of secondary causes of fat accumulation in the liver (e.g. high alcohol drinking, drugs and other medical ailments. Considering the fact that there are many causes of hepatic steatosis, the term NAFLD is reserved for the liver disease that is predominantly associated with obesity and metabolic syndrome. The presence of inflammation and cell injury defines steatohepatitis (NASH which has the potential to evolve into cirrhosis and hepatocarcinoma, being, therefore, the stage of NAFLD most amenable to treatment. Among the treatments available, the most important are: weight loss, vitamin E and, last but not least, probiotics.

  12. Alcoholic liver disease and hepatitis C: A frequently underestimated combination

    Institute of Scientific and Technical Information of China (English)

    Sebastian Mueller; Gunda Millonig; Helmut K Seitz

    2009-01-01

    Alcoholic liver disease (ALD) and hepatitis C virus (HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world. This review discusses the epidemiology and combined impact of ALD and HCV on the progression of liver disease. ALD and HCV affect the progression of liver disease to liver cirrhosis and hepatocellular carcinoma (HCC) in a synergistic manner. Thus, the risk for HCC increases five times with a daily alcohol consumption of 80 g; in the presence of HCV it is increased 20-fold, and a combination of both risk factors leads to a more than 100-fold risk for HCC development. Alcohol consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV replication. Several molecular mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease progression. They include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of iron. Thus, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liver-secreted systemic iron hormone hepcidin. A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the future. For now, it can be generally concluded that HCV-infected patients should abstain from alcohol and alcoholics should be encouraged to participate in detoxification programs.

  13. Clinical Presentation and Patient Evaluation in Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Patel, Vaishali; Sanyal, Arun J; Sterling, Richard

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a diagnosis of exclusion. Most patients are asymptomatic and diagnosed incidentally. Most patients remain undiagnosed. A high index of suspicion and serologic work-up to rule out alternative causes of liver disease is required. In NALFD, fibrosis correlates with outcomes, including mortality. To diagnose, assess severity, and monitor fibrosis, 2 noninvasive methods can be used. However, noninvasive tests are more helpful at extremes of fibrosis: excluding it or diagnosing advanced fibrosis. Liver biopsy is usually reserved for cases whereby noninvasive tests fail to accurately determine the degree of fibrosis or the diagnosis is unclear.

  14. Histopathology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    Science.gov (United States)

    Brown, Gregory Thomas; Kleiner, David E

    2016-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver injury most often associated with disorders of insulin resistance, including obesity, diabetes and the metabolic syndrome. The term encompasses several patterns of liver injury, including a relatively benign condition of steatosis without hepatocellular injury, nonalcoholic steatohepatitis (NASH), and a pattern of zone 1 steatosis, inflammation and fibrosis mainly observed in prepubertal children. Staging and grading systems have been developed to characterize the histological changes in NAFLD, mainly as a tool for clinical research. The histological features of NAFLD across these different manifestations and the scoring systems used to evaluate disease severity are discussed.

  15. From liver biopsy to non-invasive markers in evaluating fibrosis in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Cătălina Diaconu

    2015-08-01

    Full Text Available Chronic liver disease is a late stage of progressive hepatic fibrosis. It consists of functional and structural disruptions in most chronic liver diseases. An accurate diagnosis allows us to establish the degree of fibrosis and the stage of the disease, the prognosis of the patient and to predict a treatment response. Despite the fact that liver biopsy is considered a gold standard, noninvasive methods for diagnosing liver fibrosis have gained more and more importance. Whether we talk about serum biomarkers or imagistic methods from transient elastography to 3-D magnetic resonance elastography, the question remains: are these useful or useless? Serum biomarkers represent blood components that can reflect liver histological changes, thus they can monitor the continuous process of fibrosis. These can be subcategorized in direct (that show extracellular matrix turnover and indirect markers (that reflect disturbances in the hepatic function. However these markers alone are not as accurate in the staging of fibrosis, only help differentiate patients without or with low grade of fibrosis from those with significant fibrosis and cannot be considered alone in the diagnosis of liver fibrosis. Imagistic methods include: ultrasound-based transient elastography, magnetic resonance elastography (MRE, 2D-shear wave elastography, acoustic radiation impulse imaging (ARFI and cross sectional imaging, the first being the most used. Using a combination of non-invasive tools allows us to diminish the number of patients in need of liver biopsy. However, the patient must always be informed of the advantages and disadvantages of each method and its limitations.

  16. Downregulation of sulfotransferase expression and activity in diseased human livers.

    Science.gov (United States)

    Yalcin, Emine B; More, Vijay; Neira, Karissa L; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L; King, Roberta S

    2013-09-01

    Sulfotransferase (SULT) function has been well studied in healthy human subjects by quantifying mRNA and protein expression and determining enzyme activity with probe substrates. However, it is not well known if sulfotransferase activity changes in metabolic and liver disease, such as diabetes, steatosis, or cirrhosis. Sulfotransferases have significant roles in the regulation of hormones and excretion of xenobiotics. In the present study of normal subjects with nonfatty livers and patients with steatosis, diabetic cirrhosis, and alcoholic cirrhosis, we sought to determine SULT1A1, SULT2A1, SULT1E1, and SULT1A3 activity and mRNA and protein expression in human liver tissue. In general, sulfotransferase activity decreased significantly with severity of liver disease from steatosis to cirrhosis. Specifically, SULT1A1 and SULT1A3 activities were lower in disease states relative to nonfatty tissues. Alcoholic cirrhotic tissues further contained lower SULT1A1 and 1A3 activities than those affected by either of the two other disease states. SULT2A1, on the other hand, was only reduced in alcoholic cirrhotic tissues. SULT1E1 was reduced both in diabetic cirrhosis and in alcoholic cirrhosis tissues, relative to nonfatty liver tissues. In conclusion, the reduced levels of sulfotransferase expression and activity in diseased versus nondiseased liver tissue may alter the metabolism and disposition of xenobiotics and affect homeostasis of endobiotic sulfotransferase substrates.

  17. MR imaging features of focal liver lesions in Wilson disease.

    Science.gov (United States)

    Dohan, Anthony; Vargas, Ottavia; Dautry, Raphael; Guerrache, Youcef; Woimant, France; Hamzi, Lounis; Boudiaf, Mourad; Poujois, Aurelia; Faraoun, Sid Ahmed; Soyer, Philippe

    2016-09-01

    Hepatic involvement in Wilson disease (WD) manifests as a diffuse chronic disease in the majority of patients. However, in a subset of patients focal liver lesions may develop, presenting with a wide range of imaging features. The majority of focal liver lesions in patients with WD are benign nodules, but there are reports that have described malignant liver tumors or dysplastic nodules in these patients. Because of the possibility of malignant transformation of liver nodules, major concerns have been raised with respect to the management and follow-up of patients with WD in whom focal liver lesions have been identified. The assessment of liver involvement in patients with WD is generally performed with ultrasonography. However, ultrasonography conveys limited specificity so that magnetic resonance (MR) imaging is often performed to improve lesion characterization. This review was performed to illustrate the spectrum of MR imaging features of focal liver lesions that develop in patients with WD. It is assumed that familiarity with the MR imaging presentation of focal liver lesions in WD may help clarify the actual nature of hepatic nodules in patients with this condition.

  18. [Non-alcoholic fatty liver disease and steatohepatitis].

    Science.gov (United States)

    Pár, Gabriella; Horváth, Gábor; Pár, Alajos

    2013-07-21

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

  19. Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

    Directory of Open Access Journals (Sweden)

    Klementina Fon Tacer

    2011-01-01

    Full Text Available Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver, through nonalcoholic steatohepatitis (NASH to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD, and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.

  20. Increased Porphyrins in Primary Liver Cancer Mainly Reflect a Parallel Liver Disease

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    Jerzy Kaczynski

    2009-01-01

    Full Text Available Hepatic porphyries have been associated with an increased risk of primary liver cancer (PLC, which on the other hand may cause an increased porphyrin production. To evaluate the role of an underlying liver disorder we analyzed porphyrins in patients with hepatocellular carcinoma (HCC (n=65, cholangiocellular carcinoma (n=3, or suspected PLC, which turned out to be metastases (n=18 or a benign disorder (n=11. None of the patients had a family history of porphyry or clinical signs of porphyry. Increased aminolevulinic acid or porphyrin values were common not only in patients with PLC (43% but also in metastatic (50% and benign (64% liver disorders. The corresponding proportion for HCC patients with liver cirrhosis (55% was higher (P<.05 than in those without cirrhosis (17%. We conclude that symptomatic porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins are common, primarily reflecting a parallel liver disease and not the PLC.

  1. Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated fatty acids and iron load

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    S N Patere

    2011-01-01

    Full Text Available The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography, polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.

  2. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests

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    Kukuk, Guido M.; Schaefer, Stephanie G.; Hadizadeh, Dariusch R.; Schild, Hans H.; Willinek, Winfried A. [University of Bonn, Department of Radiology, Bonn (Germany); Fimmers, Rolf [University of Bonn, Department of Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Ezziddin, Samer [Department of Nuclear Medicine, Bonn (Germany); Spengler, Ulrich [Department of Internal Medicine I, Bonn (Germany)

    2014-10-15

    To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. (orig.)

  3. Impact of Aging on Liver Histological Findings of Autoimmune Liver Diseases

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    Yuki Haga

    2014-11-01

    Full Text Available Our aim is to investigate the recent liver biopsy findings of autoimmune liver diseases at a university hospital located in an urban area of Japan. The study included 259 patients (mean age 56.8 ± 12.5; male/female, 46/213 who underwent a liver biopsy for primary biliary cirrhosis (PBC or autoimmune hepatitis (AIH. We analyzed their liver biopsy findings according to age and gender. Among 127 PBC patients, Scheuer stages 1, 2, 3, and 4 were 42, 54, 18, and 13, respectively. Among 101 AIH patients, fibrosis stages F1, F2, F3, and F4 were 37, 32, 19, and 13, respectively, and inflammatory activity grades A1, A2, and A3 were 22, 25, and 54, respectively. Among PBC aged ≥65 years, Scheuer stages 1–3 and 4 patients were 27 and 6, respectively. The proportion of Scheuer stage 4 patients in PBC aged ≥65 years tended to be higher than that in PBC aged <65 years (p = 0.0659. Of interest, the proportion of AIH patients with moderate or severe activity (A2 or A3 in males was higher than in females (p = 0.0311. From the point of view of fibrosis stage or inflammatory activity grade of the liver, the proportion of AIH patients aged ≥65 years was similar to that aged <65 years. Although we identified six older cirrhotic patients with AIH, three of them were male. The progression of fibrosis and inflammatory activity of the liver should be noted when we treat older patients suffering from autoimmune liver diseases. Liver biopsy plays an important role in obtaining accurate information on autoimmune liver diseases in older patients.

  4. End-stage nonalcoholic fatty liver disease: evaluation of pathomorphologic features and relationship to cryptogenic cirrhosis from study of explant livers in a living donor liver transplant program.

    Science.gov (United States)

    Nayak, Nabeen C; Vasdev, Nandini; Saigal, Sanjiv; Soin, Arvinder S

    2010-03-01

    In a proportion of liver cirrhosis, the etiology continues to remain elusive. It is uncertain whether and to what extent cirrhosis evolving from nonalcoholic fatty liver disease contributes to this group of cryptogenic cirrhosis because the clinicopathologic features of nonalcoholic fatty liver disease cirrhosis are largely unknown. We explored these facets by examining the explant livers and clinical data in living donor liver transplant recipients. Among 103 adult liver transplant recipients with different types of chronic liver disease, 30 had a pre-liver transplant diagnosis of cryptogenic cirrhosis. A final categorization of the native liver disease was attempted in these cases on the basis of detail pathomorphological findings in adequately sampled explant liver correlated with careful review of pre-liver transplant clinical data. Of the 30 cryptogenic cirrhosis cases, 19 (63.3%) finally labeled as nonalcoholic fatty liver disease cirrhosis showed histologic features in several respects different from those reported for the early and established phases of nonalcoholic fatty liver disease. Steatosis was infrequent and focal or even absent, whereas variable grades of Mallory hyaline and inflammation were consistently present. Ductular proliferation and hydropic change of hepatocytes were also frequent. Only 9 (47%) of the 19 cases had nonalcoholic fatty liver disease associated risk factors like diabetes and obesity. It was concluded that appreciation of quantitative and qualitative differences in hepatic morphology between the cirrhotic and the early/established stage of nonalcoholic fatty liver disease will help in making a correct diagnosis of nonalcoholic fatty liver disease cirrhosis in the proper clinical setting. When appropriate criteria are used, nonalcoholic fatty liver disease appears to account for close to two thirds of cases currently labeled as cryptogenic cirrhosis.

  5. Automated segmentation of liver and liver cysts from bounded abdominal MR images in patients with autosomal dominant polycystic kidney disease

    Science.gov (United States)

    Kim, Youngwoo; Bae, Sonu K.; Cheng, Tianming; Tao, Cheng; Ge, Yinghui; Chapman, Arlene B.; Torres, Vincente E.; Yu, Alan S. L.; Mrug, Michal; Bennett, William M.; Flessner, Michael F.; Landsittel, Doug P.; Bae, Kyongtae T.

    2016-11-01

    Liver and liver cyst volume measurements are important quantitative imaging biomarkers for assessment of disease progression in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD). To date, no study has presented automated segmentation and volumetric computation of liver and liver cysts in these populations. In this paper, we proposed an automated segmentation framework for liver and liver cysts from bounded abdominal MR images in patients with ADPKD. To model the shape and variations in ADPKD livers, the spatial prior probability map (SPPM) of liver location and the tissue prior probability maps (TPPMs) of liver parenchymal tissue intensity and cyst morphology were generated. Formulated within a three-dimensional level set framework, the TPPMs successfully captured liver parenchymal tissues and cysts, while the SPPM globally constrained the initial surfaces of the liver into the desired boundary. Liver cysts were extracted by combined operations of the TPPMs, thresholding, and false positive reduction based on spatial prior knowledge of kidney cysts and distance map. With cross-validation for the liver segmentation, the agreement between the radiology expert and the proposed method was 84% for shape congruence and 91% for volume measurement assessed by the intra-class correlation coefficient (ICC). For the liver cyst segmentation, the agreement between the reference method and the proposed method was ICC  =  0.91 for cyst volumes and ICC  =  0.94 for % cyst-to-liver volume.

  6. Prevalence of Hepatitis G Virus in Liver Disease

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    Hitoshi Takagi

    1999-01-01

    Full Text Available The prevalence of hepatitis G virus (HGV in liver disease of non-A, -B, -C viral hepatitis, hepatitis B and hepatitis C was determined. Two of 44 patients (4.5% with liver injury without any hepatitis A, B or C marker were positive for HGV. One of five cases of hepatocellular carcinoma was positive for HGV. One of three cases with fulminant hepatitis was positive for HGV. This case was negative at the onset of fulminant hepatitis and became positive after plasmapheresis. No patient with acute (n=8 or chronic (n=5 hepatitis or liver cirrhosis (n=8 was positive for HGV in non-A, -B, -C liver disease. One of 30 patients with various HBV-positive liver diseases and nine (17.3 of 52 patients with type C liver disease were positive for HGV. In patients with hepatitis C, four (28.6% of 14 HGV-co-infected patients were complicated with diabetes mellitus compared with four (10.5% of 38 single hepatitis C virus (HCV-infected patients (not significant. In 12 HGV-positive patients, eight of 10 (80% had a history of blood transfusion. In HCV-positive patients, co-infection with HGV was not a risk factor in patients with diabetes mellitus as a complication. HGV appeared to cause non-A, -B, -C hepatitis rarely, and its main route of infection was blood transfusion.

  7. Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Claudia; Paternostro; Ezio; David; Erica; Novo; Maurizio; Parola

    2010-01-01

    Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,th...

  8. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

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    Varalaxmi Bhavani Nannaka

    2016-01-01

    Full Text Available Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses.

  9. Liver stiffness by transient elastography predicts liver-related complications and mortality in patients with chronic liver disease.

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    Jack X Q Pang

    Full Text Available BACKGROUND: Liver stiffness measurement (LSM by transient elastography (TE, FibroScan is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease. METHODS: In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation. The performance of LSM to predict complications was determined using the c-statistic. RESULTS: Among 2,052 patients (median age 51 years, 65% with hepatitis B or C, 87 patients (4.2% died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months. Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005. The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and ≥40 kPa, respectively (P<0.00005. After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06. The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85. A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%; however, the positive predictive value of higher results was sub-optimal (20%. CONCLUSIONS: Liver stiffness by TE accurately predicts the risk of death or hepatic complications in patients with chronic liver disease. TE may facilitate the estimation of prognosis and guide management of these patients.

  10. Chronic liver disease in Kuala Lumpur, Malaysia: a clinical study.

    Science.gov (United States)

    Kudva, M V; Zawawi, M M

    1990-08-01

    This study was undertaken to analyse the clinical spectrum of chronic liver disease (cirrhosis, and others with portal hypertension) in Kuala Lumpur. Eighty patients were diagnosed over a 6-year period. Twenty-two had biopsy proven cirrhosis while 58 others had portal hypertension with clinical and biochemical evidence of chronic liver disease. The commonest aetiology was alcohol (36%), followed by the idiopathic variety and hepatitis B. The male to female ratio was 4.4:1. Indians had a high prevalence of alcohol-associated chronic liver disease. Overall, ascites was the commonest presentation. Eight patients presented with hepatocellular carcinoma. Spontaneous bacterial peritonitis was diagnosed in 13% of patients undergoing abdominal paracentesis. Gallstones were detected in 37% of patients who underwent ultrasonography. Diabetes mellitus and peptic ulcer disease were noted in 22% and 31% of patients respectively.

  11. Hepatic stellate cells and innate immunity in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Yang-Gun Suh; Won-Il Jeong

    2011-01-01

    Constant alcohol consumption is a major cause of chronic liver disease, and there has been a growing concern regarding the increased mortality rates worldwide. Alcoholic liver diseases (ALDs) range from mild to more severe conditions, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The liver is enriched with innate immune cells (e.g. natural killer cells and Kupffer cells) and hepatic stellate cells (HSCs), and interestingly, emerging evidence suggests that innate immunity contributes to the development of ALDs (e.g. steatohepatitis and liver fibrosis). Indeed, HSCs play a crucial role in alcoholic steatosis via production of endocannabinoid and retinol metabolites. This review describes the roles of the innate immunity and HSCs in the pathogenesis of ALDs, and suggests therapeutic targets and strategies to assist in the reduction of ALD.

  12. Somatostatin analogues for treatment of polycystic liver disease

    NARCIS (Netherlands)

    Gevers, T.J.G.; Drenth, J.P.H.

    2011-01-01

    PURPOSE OF REVIEW: The present review summarizes the existing knowledge on polycystic liver disease (PCLD) and highlights the progress made in medical treatment for this condition in the past year. RECENT FINDINGS: PCLD is associated with autosomal dominant polycystic kidney disease (ADPKD) and auto

  13. Does vitamin C deficiency promote fatty liver disease development?

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance...

  14. Orthotropic liver transplantation for intractable neurological manifestations of Wilson's disease.

    Science.gov (United States)

    Sutariya, Vaibhav K; Tank, Anad H; Modi, Pranjal R

    2015-01-01

    Wilson's disease (WD) is an inherited autosomal recessive disorder characterized by copper accumulation and toxicity, affecting mainly the liver and brain. Orthotopic liver transplantation (OLT) is the definitive therapy for patients with WD. Acute fulminant hepatic failure and decompensated cirrhosis are well-established indications for OLT. Patients with severe neurologic impairment can also be benefited by OLT. Here, we present a patient who underwent OLT for isolated neurological WD.

  15. Understanding mechanisms of the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Metin; Basaranoglu; Serra; Kayacetin; Nevin; Yilmaz; Ertugrul; Kayacetin; Orhan; Tarcin; Abdullah; Sonsuz

    2010-01-01

    A central issue in the understanding of the pathogenesis of nonalcoholic fatty liver disease is the problem of the underlying mechanisms which are not fully understood.In the setting of excessive central adiposity,insulin resistance is the major underlying cause of fat accumulation in hepatocytes.Because of the difficulties with human trials,several animal models have been developed for this purpose mainly characterized as follows:genetically disturbed or murine fatty liver,methionine-choline deficient diet...

  16. Combined 'en bloc' liver and pancreas transplantation in patients with liver disease and type 1 diabetes mellitus.

    Science.gov (United States)

    Pirenne, Jacques; Deloose, Koen; Coosemans, Willy; Aerts, Raymond; Van Gelder, Frank; Kuypers, Dirk; Maes, Bart; Verslype, Chris; Yap, Paul; Van Steenbergen, Werner; Roskams, Tania; Mathieu, Chantal; Fevery, Johan; Nevens, Frederik

    2004-11-01

    Liver disease alters the glucose metabolism and may cause diabetes, but this condition is potentially reversible with liver transplantation (LTx). Type 1 diabetes mellitus may be coincidentally present in a LTx candidate and immunosuppressive drugs will aggravate diabetes and make its management more difficult for posttransplant. In addition, diabetes negatively influences outcome after LTx. Therefore, the question arises as to why not transplanting the pancreas in addition to the liver in selected patients suffering from both liver disease and Type 1 diabetes. We report two cases of en bloc combined liver and pancreatic transplantation, a technique originally described a decade ago in the treatment of upper abdominal malignancies but rarely used for the treatment of combined liver disease and Type 1 diabetes. Both recipients are currently liver disease-free and insulin-free more than 2 and 4 years posttransplant, respectively. Surgical, medical and immunological aspects of combined liver-pancreas transplantation are discussed in the light of the existing relevant literature.

  17. Comparison of liver enzymes level and sonographic findings value with liver biopsy findings in nonalcoholic fatty liver disease patients

    Science.gov (United States)

    Khodadoostan, Mahsa; Shariatifar, Behzad; Motamedi, Narges; Abdolahi, Hadi

    2016-01-01

    Background: This study aimed to examine the relationship between sonographic diagnosis of fatty liver and liver enzyme level with histopathologic abnormalities and liver biopsy findings in patient with the nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This cross-sectional study conducted on 109 patients with diagnosed and under treatment NAFLD refer to Gastroenterology Clinics of AL Zahra Hospital in Isfahan, Iran. Age, sex, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) level recorded for all patients. Liver ultrasonography was performed for all patients. Steatosis grading and fibrosis stage were evaluated by liver biopsy. Results: We enrolled 109 subjects with NAFLD who had an indication for liver biopsy and met inclusion criteria of our study. Of these, 78 subjects (71.6%) were male and 31 subjects (28.4) were female. Mean age was 40.17 ± 11.01 years old. Our results showed there was a statistically significant relationship between ultrasonographic findings and histologic findings based on biopsy. There was statistically significant relationship between liver enzyme (ALT, AST and ALP) level and ultrasonographic findings, but there was no significant relationship between AST and ALT level and histologic findings, but the relationship between ALP level and histologic findings (steatosis and fibrosis) was statistically significant (P = 0.01). Conclusion: Ultrasonographic finding may be can use to identify nonalcoholic steatohepatitis and stage of fibrosis in patients with NAFLD, but AST and ALT level is not reliable screening test to identify stage of fibrosis and steatosis in these patients. Therefore, liver biopsy remains the gold standard for establishing steatohepatitis and advanced fibrosis in patients with NAFLD. PMID:27099853

  18. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    C.P.M.S. Oliveira

    2006-02-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  19. Cellular senescence in livers from children with end stage liver disease.

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    Gabriela Gutierrez-Reyes

    Full Text Available BACKGROUND: Senescent cells occur in adults with cirrhotic livers independent of the etiology. AIM: Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease. METHODOLOGY/PRINCIPAL FINDINGS: Livers of five children aged three years or less undergoing liver transplantation due to tyrosinemia (n = 1, biliary atresia (n = 2, or fulminant hepatitis (n = 2 were analyzed for senescence associated beta-galactosidase (SA-betagal activity and p16INK4a, p21cip1 and p53. All livers displayed positive cellular staining for SA-betagal in the canals of Hering and interlobular biliary ducts. In the presence of cirrhosis (3/5 cases SA-betagal was found at the cholangioles and hepatocytes surrounding the regenerative nodules. Children with fulminant hepatic failure without cirrhosis had significant ductular transformation with intense SA-betagal activity. No SA-betagal activity was evident in the fibrous septa. Staining for p53 had a similar distribution to that observed for SA-betagal. Staining for p16(INK4a and p21(cip1 was positive in the explanted liver of the patient with tyrosinemia, in the hepatocytes, the canals of Hering, cholangioles and interlobular bile ducts. In the livers with fulminant hepatitis, p21(cip1 staining occurred in the areas of ductular transformation and in the interlobular bile ducts. CONCLUSIONS/SIGNIFICANCE: Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression.

  20. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Oliveira C.P.M.S.

    2006-01-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  1. Liver transplantation for nonalcoholic fatty liver disease: new challenges and new opportunities.

    Science.gov (United States)

    Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim

    2014-05-14

    Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options.

  2. Review article: hepatitis vaccination in patients with chronic liver disease.

    Science.gov (United States)

    Reiss, G; Keeffe, E B

    2004-04-01

    Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.

  3. Systematic review: Preventive and therapeutic applicationsof metformin in liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Metformin, a biguanide derivative, is the most commonlyprescribed medication in the treatment of type 2 diabetesmellitus. More recently, the use of metformin has shownpotential as a preventive and therapeutic agent for abroad spectrum of conditions, including liver diseaseand hepatic malignancies. In this systematic review,we critically analyze the literature behind the potentialuse of metformin across the spectrum of liver diseaseand malignancies. The PubMed and Ovid MEDLINEdatabases were searched from 2000 to March 2015,using a combination of relevant text words and MeSHterms: metformin and mammalian target of rapamycin,hepatitis B virus (HBV), hepatitis B virus (HCV), nonalcoholicfatty liver disease (NAFLD), hepatocellularcarcinoma (HCC) or cholangiocarcinoma. The searchresults were evaluated for pertinence to the issue ofmetformin in liver disease as well as for quality of studydesign. Metformin has a number of biochemical effectsthat would suggest a benefit in treating chronic liverdiseases, particularly in the context of insulin resistanceand inflammation. However, the literature thus far doesnot support any independent therapeutic role in NAFLDor HCV. Nonetheless, there is Level Ⅲ evidence fora chemopreventive role in patients with diabetes andchronic liver disease, with decreased incidence of HCCand cholangiocarcinoma. The use of metformin seemsto be safe in patients with cirrhosis, and provides asurvival benefit. Once hepatic malignancies are alreadyestablished, metformin does not offer any therapeuticpotential. In conclusion, there is insufficient evidence torecommend use of metformin in the adjunctive treatmentof chronic liver diseases, including NAFLD and HCV.However, there is good evidence for a chemopreventiverole against HCC among patients with diabetes andchronic liver disease, and metformin should be continuedin patients even with cirrhosis to provide this benefit.

  4. Celiac disease markers in patients with liver diseases: A single center large scale screening study

    Institute of Scientific and Technical Information of China (English)

    Pavel Drastich; Eva Honsová; Alena Lodererová; Marcela Jare(s)ová; Aneta Pekáriková; Iva Hoffmanová; Ludmila Tu(c)ková

    2012-01-01

    AIM:To study the coincidence of celiac disease,we tested its serological markers in patients with various liver diseases.METHODS:Large-scale screening of serum antibodies against tissue transglutaminase (tTG),and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry,in patients with various liver diseases (n =962) and patients who underwent liver transplantation (OLTx,n =523) was performed.The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out.The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy.RESULTS:We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies.However,celiac disease was biopsy-diagnosed in 16 patients:4 with autoimmune hepatitis type Ⅰ,3 with Wilson's disease,3 with celiac hepatitis,2 with primary sclerosing cholangitis,1with primary biliary cirrhosis,1 with Budd-Chiari syndrome,1 with toxic hepatitis,and 1 with non-alcoholic steatohepatitis.Unexpectedly,the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%),with which it is only rarely associated.On the other hand,no OLTx patients were diagnosed with celiac disease in our study.A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis,primary sclerosing cholangitis or autoimmune hepatitis type Ⅰ.CONCLUSION:We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases,but also in patients with Wilson's disease.

  5. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

    Institute of Scientific and Technical Information of China (English)

    Maud Lemoine; Aurélie Revaux; Claire Francoz; Guillaume Ducarme; Sabine Brechignac; Emmanuel Jacquemin; Michèle Uzan; Nathalie Ganne-Carrié

    2008-01-01

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of HARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.C 2008 The WJG Press. All rights reserved.

  6. Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

    Directory of Open Access Journals (Sweden)

    Jian-yuan Li

    2014-01-01

    Full Text Available Glycyrrhizic acid (GA is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra. GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.

  7. microRNAs: Fad or future of liver disease

    Institute of Scientific and Technical Information of China (English)

    Ashley M Lakner; Herbert L Bonkovsky; Laura W Schrum

    2011-01-01

    microRNAs (miRs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes, which results in alterations in mRNA stability or translation inhibition. miRs influence at least one third of all human transcripts and are known regulators of various important cellular growth and differentiation factors. miRs have recently emerged as key regulatory molecules in chronic liver disease. This review details recent contributions to the field of miRs that influence liver development and the broad spectrum of disease, from non-alcoholic fatty liver disease to fibrosis/cirrhosis, with particular emphasis on hepatic stellate cells and potential use of miRs as therapeutic tools.

  8. Peran Antioksidan pada Non Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Yusri Diane Jurnalis

    2014-01-01

    Full Text Available AbstrakNonalcoholic Fatty Liver Disease (NAFLD merupakan penyebab tersering penyakit hati kronik pada anak dan remaja diseluruh dunia. NAFLD berhubungan dengan obesitas, diabetes melitus tipe 2 dan sindrom metabolik. Resistensi insulin memegang peranan penting dalam patogenesis molecular terjadinya NAFLD. Ketidakseimbangan prooksidan dan antioksidan pada sel hepatosis menentukan progresifitas penyakit ini. Sebagai antioksidan telah dilakukan penelitian mengenai efek antioksidan vitamin E, vitamin C, betaine, N-asetil sistein, probucol dan silymarin. Antioksidan tersebut memperlihatkan perbaikan fungsi hepar dan gambaran histopatologis.Kata kunci: Arial 9 NAFLD, resistensi insulin, antioksidanAbstractNonalcoholic fatty liver disease (NAFLD is the most common cause of liver disease in pediatric and adolescent population. NAFLD related with obesity, type 2 diabetes mellitus and metabolic syndrome. Insulin resistance and oxidative stress have important role in molecular pathogenesis of NAFLD. Prooxidant and antioxidant factor in hepatosit can determine progressivity of liver disease. As antioxidant agent for treatment NAFLD have been studied effect of vitamin E, vitamin C, betaine, N-acetyl cystein, probucol and sylimarin. They have been shown improvement of liver function test and histopathologycal feature.Keywords:NAFLD, insulin resistance, antioxidant

  9. Focal inflammatory diseases of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-10-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics.

  10. Carbohydrate 19.9 Antigen Serum Levels in Liver Disease

    Directory of Open Access Journals (Sweden)

    Gaetano Bertino

    2013-01-01

    Full Text Available Background. Carbohydrate 19.9 antigen (CA19.9 has been used in the diagnosis and followup of gastrointestinal tumours. The aim of this prospective longitudinal study was the evaluation of CA19.9 levels in patients with chronic hepatitis and hepatic cirrhosis hepatitis C virus and B virus correlated. Materials and Methods. 180 patients were enrolled, 116 with HCV-related chronic liver disease (48% chronic hepatitis, 52% cirrhosis and 64 with HBV-related chronic liver disease (86% chronic hepatitis, 14% cirrhosis. Patients with high levels of CA19.9 underwent abdominal ecography, gastroendoscopy, colonoscopy, and abdominal CT scan. Results. 51.7% of patients with HCV-related chronic liver disease and 48.4% of those with HBV-related chronic liver disease presented high levels of CA19.9. None was affected by pancreatic or intestinal neoplasia, cholestatic jaundice, or other diseases potentially able to induce Ca19.9 elevations. CA19.9 levels were elevated in 43.3% of HCV chronic hepatitis, in 56.3% of HCV cirrhosis, in 45.1% of HBV chronic hepatitis, and in 58% of HBV cirrhosis. Conclusions. CA19.9 commonly increases in the serum of patients with chronic viral hepatitis. Elevation of CA 19.9 is not specific for neoplastic disease and is related to the severity of fibrosis and to the viral aetiology of hepatitis.

  11. Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage.

    Science.gov (United States)

    Saka, W A; Akhigbe, R E; Ishola, O S; Ashamu, E A; Olayemi, O T; Adeleke, G E

    2011-07-15

    There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague-Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract-treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction.

  12. Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

    Institute of Scientific and Technical Information of China (English)

    Katriina; Nemes; Fredrik; ?berg; Helena; Gylling; Helena; Isoniemi

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

  13. Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

    Science.gov (United States)

    Boursier, Jerome; Diehl, Anna Mae

    2016-05-01

    Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice. Gut microbiota adds complexity to the pathophysiology of nonalcoholic fatty liver disease but represents an opportunity to discover new therapeutic targets.

  14. [Non-alcoholic fatty liver disease--new view].

    Science.gov (United States)

    Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

    2008-06-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

  15. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Ozçay, Figen; Canan, Oğuz; Bilezikçi, Banu; Torgay, Adnan; Karakayali, Hamdi; Haberal, Mehmet

    2006-01-01

    We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

  16. 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.

  17. Severe liver dysfunction in an infant with cystic fibrosis masquerading as metabolic liver disease

    Directory of Open Access Journals (Sweden)

    K P Srikanth

    2016-01-01

    Full Text Available We present a rare presentation of cystic fibrosis with neonatal cholestasis. Histological features of mucoviscidosis were present in liver involving the biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare association with autosomal dominant type of polycystic renal disease.

  18. Cure of HCV related liver disease.

    Science.gov (United States)

    Shiffman, Mitchell L; Benhamou, Yves

    2015-01-01

    Chronic hepatitis C virus (HCV) causes chronic liver injury and can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV can also interact with the immune system to cause several HCV related disorders including essential mixed cryoglobulinemia, vasculitis, dermatitis, glomerulonephritis and lymphoma. A strong association between HCV and diabetes mellitus also exists. These extrahepatic features may lead to increased fatigue and a reduced quality of life. It is now possible to cure most patients with chronic HCV using oral antiviral therapy. Many of these HCV-related disorders and symptoms can be cured when HCV is eradicated. However, some patients may have irreversible injury to extrahepatic sites, cirrhosis that cannot resolve, an increased risk for HCC, persistent fatigue and a reduced quality of life, despite achieving sustained virological response.

  19. Liver histology according to the presence of metabolic syndrome in nonalcoholic fatty liver disease cases

    Institute of Scientific and Technical Information of China (English)

    Hüseyin Saadettin Uslusoy; Selim Giray Nak; Macit Gülten; Zeynep Blylkll

    2009-01-01

    AIM: To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components.METHODS: We enrolled 81 patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic scan and fulfilled the inclusion criteria. First anamnesis, anthropometric, clinical, laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification.RESULTS: Sixty-nine of the 81 patients had nonalcoholic steatohepatitis (NASH), 11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation.Comparisons were made between two groups of NASH patients, those with and without metabolic syndrome.We did not detect statistically significant differences in liver histology between NASH patients with and without metabolic syndrome.CONCLUSION: NASH can progress without metabolic risk factors or the presence of metabolic syndrome.

  20. Nutrition and Nonalcoholic Fatty Liver Disease: The Significance of Cholesterol

    Directory of Open Access Journals (Sweden)

    Munechika Enjoji

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a common chronic liver disease that ranges in severity from simple steatosis to cirrhosis. NAFLD is considered to be associated with hepatic metabolic disorders, resulting in overaccumulation of fatty acids/triglycerides and cholesterol. The pathogenesis and progression of NAFLD are generally explained by the “two-hit theory.” Most studies of lipid metabolism in the NAFLD liver have focused on the metabolism of fatty acids/triglycerides; therefore, the impact of cholesterol metabolism is still ambiguous. In this paper, we review recent studies on NAFLD from the viewpoint of hepatic lipid metabolism-associated factors and discuss the impact of disordered cholesterol metabolism in the etiology of NAFLD. The clinical significance of managing cholesterol metabolism, an option for the treatment of NAFLD, is also discussed.

  1. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

    Science.gov (United States)

    Gitto, Stefano; Villa, Erica

    2016-04-02

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  2. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis

    Science.gov (United States)

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis. PMID:27347998

  3. Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

    Institute of Scientific and Technical Information of China (English)

    Qing Liu; Zhong-Ping Duan; Chun Huang; Chun-Hui Zhao

    2004-01-01

    AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multipl eorgan dysfunction syndrome (MODS).METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia,endotoxin TNF-α, IL-6 and prothrombin activity (PTA),cholinesterase (CHE) were recorded before, dudng and after treatment. The end-stage liver disease (MELD) was used for the study.RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully.Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P<0.01), while the serum TBIL,endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities.CONCLUSION: The proinflammatory cytokines (TNFα, IL6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome.

  4. Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

    Science.gov (United States)

    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 disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

  5. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Ogawa, Yuji; Maeda, Shin; Sumida, Yoshio; Hyogo, Hideyuki; Eguchi, Yuichiro; Wada, Koichiro; Nakajima, Atsushi

    2013-11-04

    Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the disease's pathogenesis.

  6. Assessment of thyroid and gonadal function in liver diseases

    Directory of Open Access Journals (Sweden)

    Sandeep Kharb

    2015-01-01

    Full Text Available Introduction: Liver is involved with the synthesis of carrier proteins and metabolism of various hormones and liver diseases may, therefore, be associated with various endocrine disturbances. This study was conducted to assess thyroid and gonadal function in subjects with acute hepatitis (AH, chronic liver disease (CLD, and those who had undergone liver transplantation (LT. Materials and Methods: Patients with AH, CLD with Child-Pugh stage A (CLD-1 and Child-Pugh stage B or C (CLD-2, and LT seen at our tertiary level hospital were assessed clinically, biochemically, and for thyroid and gonadal functions besides 25 healthy controls. Results: Thyroid dysfunction and hypogonadism were present in 14 (16% and 24 (28% patients with liver diseases respectively. Among thyroid dysfunction, the commonest was sick euthyroid syndrome six (7%, followed by subclinical hypothyroidism in three patients (3.5%, subclinical hyperthyroidism and thyrotoxicosis in two patients each (2.3% and overt hypothyroidism in one patient. Among patients with LT and AH groups, the only abnormality was significantly lower total T3 compared with healthy controls. The CLD2 group had significantly lower levels of all thyroid hormones compared with controls and CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50% followed by LT (3; 33%, CLD-1 (4; 20%, and AH (3; 14%. Hypogonadism was predicted by older age, lower levels of serum albumin, total cholesterol, and triglycerides and higher levels of plasma glucose, serum bilirubin, aspartate transaminases, and international normalized ratio. Gonadal functions showed recovery following LT. Conclusions: Thyroid dysfunction and hypogonadism form an important part of the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic functions of liver disease predicts presence of hypogonadism.

  7. Nonalcoholic fatty liver disease and polycystic ovary syndrome.

    Science.gov (United States)

    Vassilatou, Evangeline

    2014-07-14

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.

  8. Protection effect of trigonelline on liver of rats with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-Fang Zhang; Fan Zhang; Jin Zhang; Rui-Ming Zhang; Ran Li

    2015-01-01

    Objective:To study the effect of trigonelline on the change of indicators of serum transaminase, lipoprotein and liver lipid of model rats with non-alcoholic fatty liver diseases and on the expression level of Bcl-2 and Bax proteins.Methods:A total of 45 SD rats were randomly divided into Fthe control group, model group and trigonelline intervention group. Rats in the control group were fed with the common diet, while rats in the model group and intervention group were fed with the high fat diet. 8 weeks later, the intervention group received the intragastric administration of trigonellin e (with the dosage of 40 mg/kg/d) for 8 weeks; while control group and model group received the intragastric administration of saline with the equal dosage. Blood was taken from the abdominal aorta of rats 8 weeks later, detecting the level of a series of indicators of ALT, AST, TG, TC, HDL-C and LDL-C in the serum. After the rats were sacrificed, detect the indicators of TG, TC, SOD and MDA in the liver tissue of rats, as well as the expression of Bcl-2 and Bax in the liver tissue.Results: Results of histopathologic examination showed that the damage degree of liver for rats in the trigonellineintervention group was smaller than the one in the model group, with significantly reduced hepatic steatosis and the partially visible hepatic lobule. The levels of ALT, AST, TC and LDL-C in the serum of rats in the trigonelline group were significantly reduced, while the change in the levels of TG and HDL-C was not significantly different. The levels of TG, TC and MDA in the liver tissues were significantly decreased, while the level of SOD significantly increased; the expression of Bcl-2 protein in the liver tissues of rats in the trigonelline intervention group was significantly increased, while the expression of Bax protein significantly decreased.Conclusions: The trigonelline contributes to the therapeutic effect of non-alcoholic fatty liver diseases. It can also increase the

  9. Sonographic fatty liver, overweight and ischemic heart disease

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Huey-Ming Lo; Jong-Dar Chen

    2005-01-01

    AIM: To demonstrate the prevalence of sonographic fatty liver, overweight and ischemic heart disease (IHD) among the male workers in Taiwan, and to investigate the possible association of these three factors.METHODS: From July to September 2003, a total of 2 088 male aircraft-maintenance workers aged from 22to 65 years (mean 40.5) underwent an annual health examination, including anthropometrical evaluation, blood pressure measurement, personal medical history assessment,biochemical blood analysis, abdominal ultrasonographic examination and digital electrocardiography (ECG). The Student's t-test, x2 test and multivariate logistic regression analysis were utilized to evaluate the relationship between IHD and salient risk factors.RESULTS: The all-over prevalence of overweight was 41.4%, and that of fatty liver was 29.5% (mild, moderate and severe fatty liver being 14.5%, 11.3%, and 3.7%,respectively); while the prevalence of ischemic changes on ECG was 17.1% in this study. The abnormal rates for conventional IHD risk factors including hypertension,dyslipidemia, hyperglycemia and overweight increased in accordance with the severity of fatty liver. Overweight and severity of fatty liver were independently associated with increased risks for developing IHD. Overweight subjects had a 1.32-fold (95%CI: 1.01-1.73) increased IHD risk. Participants with mild, moderate, and severe fatty liver had a 1.88-fold (95%CI: 1.37-2.6), 2.37-fold (95%CI: 1.66-3.37) and 2.76-fold (95%CI: 1.62-4.72)increased risk for developing IHD. The prevalence of ischemic ECG for the fatty liver-affected subjects with or without overweight was 30.1% and 19.1%, while that of overweight subjects free from fatty liver was 14.4%.Compared to the subjects without fatty liver nor overweight,IHD risk for the three subgroups above was as follows:OR: 2.95 (95%CI:2.31-4.09), OR: 1.60 (95%CI: 1.07-2.39)and OR: 1.11 (95%CI: 0.78-1.56), respectively.CONCLUSION: The presence of fatty liver and its severity should

  10. Prognostic Significance of the Systemic Inflammatory and Immune Balance in Alcoholic Liver Disease with a Focus on Gender-Related Differences.

    Directory of Open Access Journals (Sweden)

    Beata Kasztelan-Szczerbińska

    Full Text Available Mechanisms of immune regulation in alcoholic liver disease (ALD are still unclear. The aim of our study was to determine an impact of Th17 / regulatory T (Treg cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed.147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated. Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentrations assessment. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications.IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort.We conclude that IL-6 revealed the highest diagnostic and prognostic potential among studied biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury.

  11. [Research advances in pediatric nonalcoholic fatty liver disease].

    Science.gov (United States)

    Dai, Dong-Ling

    2015-01-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because of the growing prevalence of obesity and overweight in the pediatric population. It has become the most common form of chronic liver diseases in children and the related research on NAFLD is expanded. The "two-hit" and "multiple hit" hypothesis have been widely accepted, and some research has shown that genetic, diet structure and environmental factors appear to play a crucial role in the development of pediatric NAFLD. Though it is expected by researchers, there is not an available satisfactory noninvasive marker for the diagnosis of this disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD have been developed. There is currently no established special therapy, and lifestyle intervention should be adequate for most cases of NAFLD in children. This article reviews the advances in the current knowledge and ideas concerning pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring methods for this disease.

  12. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review.

    Science.gov (United States)

    Nseir, William; Mahamid, Mahmud

    2013-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The most common cause of mortality in patients with NAFLD or NASH is cardiovascular disease (CVD). Currently, the treatment of NAFLD focuses on gradual weight loss and life style modifications. However, multifactorial treatment of NAFLD or NASH risk factors may be needed to reduce the likelihood of these patients developing CVD. This review discusses the mechanisms that link hyperlipidemia and NAFLD. In addition, the review focuses on the safety and efficacy of statins in patients with NAFLD or NASH, and their effect on the extent of hepatic steatosis and fibrosis based on human studies.

  13. Alcoholism and liver disease in Mexico: genetic and environmental factors.

    Science.gov (United States)

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-11-28

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.

  14. Alcoholic liver disease: pathogenesis and new targets for therapy.

    Science.gov (United States)

    Altamirano, José; Bataller, Ramón

    2011-08-09

    Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. The spectrum of disease ranges from fatty liver to hepatic inflammation, necrosis, progressive fibrosis and hepatocellular carcinoma. In developed countries, ALD is a major cause of end-stage liver disease that requires transplantation. The most effective therapy for ALD is alcohol abstinence. However, for patients with severe forms of ALD (that is, alcoholic hepatitis) and for those who do not achieve abstinence from alcohol, targeted therapies are urgently needed. The development of new drugs for ALD is hampered by the scarcity of studies and the drawbacks of existing animal models, which do not reflect all the features of the human disease. However, translational research using liver samples from patients with ALD has identified new potential therapeutic targets, such as CXC chemokines, osteopontin and tumor necrosis factor receptor superfamily member 12A. The pathogenetic roles of these targets, however, remain to be confirmed in animal models. This Review summarizes the epidemiology, natural history, risk factors and current knowledge of the pathogenetic mechanisms of ALD. In addition, this article provides a detailed description of the findings of these translational studies and of the animal models used to study ALD.

  15. The Platelet and Platelet Function Testing in Liver Disease

    NARCIS (Netherlands)

    Hugenholtz, Greg G. C.; Porte, Robert J.; Lisman, Ton

    2009-01-01

    Patients who have liver disease commonly present with alterations in platelet number and function. Recent data have questioned the contribution of these changes to bleeding complications in these patients. Modern tests of platelet function revealed compensatory mechanisms for the decreased platelet

  16. The occurrence of Helicobacter pylori in hydatid liver disease

    Institute of Scientific and Technical Information of China (English)

    Adil Edan Alsaimary; Hayder M Abdulnbi; Abdulhadi Laibi; Ahmed Rasheed Jwad

    2012-01-01

    Objective: To detect the prevalence of Helicobacter pylori (H. pylori) in hydatid liver disease. Methods: A total of 58 patients with hydatid liver disease attending AL-Sadder Teaching Hospital in Al-Najaf and Al-Basrah governorate from February to August, 2008 were included in the study and served as group A. One hundred and twenty 1st degree relative patients (group B) and 20 normal persons including 10 male and 10 female (group C) as control were detected for the presence of H. pylori infection in general population. Chest X-ray was done for the above groups to exclude lung hydrated cyst. The patients were screened by ultrasound to obtain intra abdominal hydrated cyst and enzyme-linked immuno sorbent assay (ELISA) test was utilized to detect the H. pylori infection. Results: Fifty eight patients from group A with hydatid liver disease, 30 male (51.7%) and 28 female (48.3%) were screened for the presence of H. pylori infection by using ELISA test. We found that 28 patients from group A had positive ELISA test including 19 male (32.8%) and 9 female (15.5%) (P<0.01). However, there were no positive results of H. pylori infection in group B and C by chest X-ray, ultrasound and ELISA test. Conclusions: It can be concluded that there is a strong relationship between hydatid liver disease and presence of H. pylori.

  17. Palliative care for patients with end-stage liver disease.

    Science.gov (United States)

    Larson, Anne M

    2015-05-01

    Liver disease results in over four million physician visits and over 750,000 hospitalizations per year in the USA. Those with chronic liver disease frequently progress to cirrhosis, end-stage liver disease (ESLD), and death. Patients with ESLD experience numerous complications, including muscle cramps, confusion (hepatic encephalopathy), protein calorie malnutrition, muscle wasting, fluid overload (ascites, edema), bleeding (esophagogastric variceal hemorrhage), infection (spontaneous bacterial peritonitis), fatigue, anxiety, and depression. Despite significant improvements in palliation of these complications, patients still suffer reduced quality of life and must confront the fact that their disease will often inexorably progress to death. Liver transplantation is a valid option in this setting, increasing the duration of survival and palliating many of the symptoms. However, many patients die waiting for an organ or are not candidates for transplantation due to comorbid illness. Others receive a transplant but succumb to complications of the transplant itself. Patients and families must struggle with simultaneously hoping for a cure while facing a life-threatening illness. Ideally, the combination of palliative care with life-sustaining therapy can maximize the patients' quality and quantity of life. If it becomes clear that life-sustaining therapy is no longer an option, these patients are then already in a system to help them with end-of-life care.

  18. Models of alcoholic liver disease in rodents: a critical evaluation

    DEFF Research Database (Denmark)

    de la M. Hall, P.; Lieber, C.S.; De Carli, L.M.;

    2001-01-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were J. Christian Bode and Hiroshi Fukui. The presentations were (1) Essentials and the course of the pathological spectrum of alcoholic liver disease in humans, by P. de la M. Hall; (2)...

  19. Is transient elastography a useful tool for screening liver disease?

    Institute of Scientific and Technical Information of China (English)

    Paolo Del Poggio; Silvia Colombo

    2009-01-01

    Transient elastography (TE) is a new non invasive tool for measuring liver stiffness, which is correlated to the histologic stage of liver fibrosis. Several studies in chronic liver disease (CLD) have determined a good accuracy of TE in predicting significant fibrosis and an optimal accuracy in predicting cirrhosis. Normal liver stiffness ranges between 3.3-7.8 KPa and using a cut off of 7.1 KPa, significant fibrosis and cirrhosis can be excluded with a very high negative predictive value (NPV). Positive predictive value (PPV) for the diagnosis of cirrhosis is lower using just a single scan but increases to 90% if high stiffness values are confirmed by a second independent scan. However the presence of fatty liver and metabolic syndrome slightly increases the readings and may reduce the accuracy of the test. It is uncertain if this increase is related to the presence of steatofibrosis or if it is caused by steatosis itself. TE can be used in screening patients attending the liver clinics to identify those with significant fibrosis or cirrhosis and may be particularly useful in discriminating HBV inactive carriers from chronic hepatitis B patients. TE, however, is not reliable in predicting the presence of esophageal varices in cirrhotics. Another potential indication for TE is the systematic screening of populations at high risk for CLD, such as intravenous drug users and alcoholics, but further studies are needed to determine its diagnostic accuracy in these settings.

  20. 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

  1. Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Sebastian; Mueller; Gunda; Millonig; Lucie; Sarovska; Stefanie; Friedrich; Frank; M; Reimann; Maria; Pritsch; Silke; Eisele; Felix; Stickel; Thomas; Longerich; Peter; Schirmacher; Helmut; Karl; Seitz

    2010-01-01

    AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been m...

  2. Probiotics and gut health: A special focus on liver diseases

    OpenAIRE

    Gratz, Silvia Wilson; Mykkanen, Hannu; El-Nezami, Hani S.

    2010-01-01

    Probiotic bacteria have well-established beneficial effects in the management of diarrhoeal diseases. Newer evidence suggests that probiotics have the potential to reduce the risk of developing inflammatory bowel diseases and intestinal bacterial overgrowth after gut surgery. In liver health, the main benefits of probiotics might occur through preventing the production and/or uptake of lipopolysaccharides in the gut, and therefore reducing levels of low-grade inflammation. Specific immune sti...

  3. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kirpich, Irina A; Marsano, Luis S; McClain, Craig J

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development.

  4. Association of Hepatic Hydatid Cyst Disease and Liver Tuberculosis

    Directory of Open Access Journals (Sweden)

    Songul Ozyurt

    2013-10-01

    Full Text Available Hydatid cyst and tuberculosis are common infectious diseases in our country. However, co-incidence of these two diseases is a rare case. This refers to spontaneous emergence of cyst hydatid and tuberculosis lesion in liver which is presented in this paper. Liver tuberculosis can be detected either as a component of miliary tuberculosis or isolated liver tuberculosis. Herein we report a case of 46 year-old male. He applied to the emergency due to the severe right-side pain which coupled with breathing and movement. This was reported to last for 10 days. Lesion compatible to cyst hydatid with a size of 151 x 144 x 128 mm was detected in the right lobe anterior in his abdomen ultrasonography. Echinococcus indirect hemagglutination test resulted in 1/640 positive. The patient had liver cystectomy by general surgery clinic. After microscopic examination of excision material, chronic granulomatous inflamation with caseous necrosis was detected in parenchyma to which cyst hydatid and lesion were attached. PPD result was 16 mm. The patient, whose lungs were normal, received antituberculosis treatment due to primary liver tuberculosis.

  5. Hepcidin levels in children with chronic liver disease

    Directory of Open Access Journals (Sweden)

    Murat Cakir

    2015-01-01

    Full Text Available Background/Aim: We aimed to analyze serum hepcidin level in children with chronic liver disease (CLD and its relationship with serum cytokines level, liver function tests, hepatic iron content, and liver fibrosis. Patients and Methods: The study included 34 children with CLD, and 15 age- and gender-matched healthy children. Serum hepcidin, ferritin, iron level, interleukin-6 (IL-6, transforming growth factor-β (TGF-β , total oxidant status (TOS, and antioxidant status (TAS were studied in all patients and in the control group. Liver iron content (LIC was measured from the liver biopsy specimen. Results: Serum ferritin levels were higher in patients with CLD than control group (100.1 ± 98.2 ng/mL vs 50.5 ± 32.2 ng/mL, P = 0.016. No significant difference was found in hepcidin levels. Hepcidin levels in children with CLD was positively correlated with ferritin (r = 0.75, P = 0.001, pediatric end-stage liver disease (PELD score (r = 0.56, P = 0.001, TAS (r = 0.42,P = 0.02, but negatively correlated with albumin level (r = −0.45,P = 0.008. Transferrin saturation and hepcidin:ferritin ratio were significantly low in patients with severe fibrosis compared with patients with mild/without fibrosis (15.5 ± 5.5 vs 34.3 ± 30.1, P = 0.017 and 1 ± 0.5 vs 1.9 ± 1.4,P = 0.04, respectively. Conclusion: Serum hepcidin levels in children with CLD reflect both liver functions and TAS, and severe fibrosis is associated with low hepcidin:ferritin ratio in children with CLD.

  6. Liver biopsy interpretation in the differential diagnosis of autoimmune liver disease in children

    Directory of Open Access Journals (Sweden)

    Clara Gerosa

    2013-06-01

    Full Text Available Autoimmune liver disease  (AILD represents a group of complex inflammatory liver diseases, all characterized by an aberrant autoreactivity against hepatocytes and/or biliary structures. AILD may be subclassified into four major diseases: autoimmune hepatitis (AIH, primary biliary cirrhosis (PBC, primary sclerosing cholangitis (PSC, and autoimmune cholangitis (AIC. Recently a new entity frequently associated with autoimmune pancreatitis and defined IgG4-related cholangitis (IgG4-RC,  has been added to the spectrum of AILD. The most frequent autoimmune liver diseases  of the AILD spectrum occurring in children and in young adults are  AIH  and PSC, overlap syndrome between AIH and PSC, also defined as autoimmune sclerosing cholangitis (ASC, representing a frequent finding in pediatric patients. Here,  the morphological findings that may help liver pathologists in the differential diagnosis of AILD in pediatric patients are reviewed, underlying the frequency in liver biopsy interpretation of complex cases in which a precise diagnosis may remain controversial, due to overlap of hepatocytic and bile duct cell lesions. Among the multiple morphological changes typical of AILD,  the detection of an high number of plasma cell clusters in the portal and periportal regions is generally considered one of the main clue for the diagnosis of AIH. The recent report in a 13-year old  boy of IgG4-associated cholangitis, induces  pathologists when detecting a huge number of plasmacells, to consider the differential diagnosis between AIH and IgG4-RC.Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  7. 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.

  8. Liver transplantation in polycystic liver disease: a relevant treatment modality for adults?

    DEFF Research Database (Denmark)

    Krohn, P.S.; Hillingso, J.G.; Kirkegaard, P.

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  9. NON-ALCOHOLIC FATTY LIVER DISEASE AT OUR INSTITUTE

    Directory of Open Access Journals (Sweden)

    Madhavi

    2015-12-01

    Full Text Available INTRODUCTION A Correlation clinical observational hospital based clinical study with 50 patients were undertaken to study the Clinical Profile of incidentally detected Non Alcoholic Fatty Liver Disease. The cases for the study were selected retrospectively who were diagnosed as fatty liver by ultrasound imaging who attended the Department of General Medicine, Government General Hospital Kakinada Rangaraya Medical College. Data has been enumerated for those who fulfilled the inclusion criteria. This study was conducted between January 2013-January 2015. The study has limitations of observer variant dependent diagnostic ultrasound for inclusion in to study. A BMI of>25 kg/m2 taken as definition for obesity for analysis.

  10. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

    2014-07-25

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

  11. Nitrofurantoin-induced immune-mediated lung and liver disease

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    Milić Rade

    2012-01-01

    Full Text Available Introduction. Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI. Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. Case report. We presented a 55-year-old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with druginduced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. Conclusion. Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy.

  12. Ethanol metabolism and oxidative stress are required for unfolded protein response activation and steatosis in zebrafish with alcoholic liver disease

    Science.gov (United States)

    Tsedensodnom, Orkhontuya; Vacaru, Ana M.; Howarth, Deanna L.; Yin, Chunyue; Sadler, Kirsten C.

    2013-01-01

    SUMMARY Secretory pathway dysfunction and lipid accumulation (steatosis) are the two most common responses of hepatocytes to ethanol exposure and are major factors in the pathophysiology of alcoholic liver disease (ALD). However, the mechanisms by which ethanol elicits these cellular responses are not fully understood. Recent data indicates that activation of the unfolded protein response (UPR) in response to secretory pathway dysfunction can cause steatosis. Here, we examined the relationship between alcohol metabolism, oxidative stress, secretory pathway stress and steatosis using zebrafish larvae. We found that ethanol was immediately internalized and metabolized by larvae, such that the internal ethanol concentration in 4-day-old larvae equilibrated to 160 mM after 1 hour of exposure to 350 mM ethanol, with an average ethanol metabolism rate of 56 μmol/larva/hour over 32 hours. Blocking alcohol dehydrogenase 1 (Adh1) and cytochrome P450 2E1 (Cyp2e1), the major enzymes that metabolize ethanol, prevented alcohol-induced steatosis and reduced induction of the UPR in the liver. Thus, we conclude that ethanol metabolism causes ALD in zebrafish. Oxidative stress generated by Cyp2e1-mediated ethanol metabolism is proposed to be a major culprit in ALD pathology. We found that production of reactive oxygen species (ROS) increased in larvae exposed to ethanol, whereas inhibition of the zebrafish CYP2E1 homolog or administration of antioxidants reduced ROS levels. Importantly, these treatments also blocked ethanol-induced steatosis and reduced UPR activation, whereas hydrogen peroxide (H2O2) acted as a pro-oxidant that synergized with low doses of ethanol to induce the UPR. Collectively, these data demonstrate that ethanol metabolism and oxidative stress are conserved mechanisms required for the development of steatosis and hepatic dysfunction in ALD, and that these processes contribute to ethanol-induced UPR activation and secretory pathway stress in hepatocytes. PMID

  13. Highly active antiretroviral therapy and changing spectrum of liver diseases in HIV infected patients

    Directory of Open Access Journals (Sweden)

    Kavita S. Joshi

    2016-08-01

    Conclusions: Although hepatitis B and alcoholic liver disease are major causes of liver diseases in HIV patients in India, incidence of drug related hepato toxicities are increasing. [Int J Res Med Sci 2016; 4(8.000: 3125-3129

  14. Assessment of Liver Viscoelasticity for the Diagnosis of Early Stage Fatty Liver Disease Using Transient Elastography

    Science.gov (United States)

    Remenieras, Jean-Pierre; Dejobert, Maelle; Bastard, Cécile; Miette, Véronique; Perarnau, Jean-Marc; Patat, Frédéric

    Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of fat within the Liver. The main objective of this work is (1) to evaluate the feasibility of measuring in vivo in the liver the shear wave phase velocity dispersion cs(ω) between 20 Hz and 90 Hz using vibration-controlled transient elastography (VCTE); (2) to estimate through the rheological Kelvin-Voigt model the shear elastic μ and shear viscosity η modulus; (3) to correlate the evolution of these viscoelastic parameters on two patients at Tours Hospital with the hepatic fat percentage measured with T1-weighted gradient-echo in-and out-phase MRI sequence. For the first volunteer who has 2% of fat in the liver, we obtained μ = 1233 ± 133 Pa and η = 0.5 ± 0.4 Pa.s. For the patient with 22% of fat, we measure μ = 964 ± 91 Pa and η = 1.77 ± 0.3 Pa.s. In conclusion, this novel method showed to be sensitive in characterizing the visco-elastic properties of fatty liver.

  15. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease

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    Claudia P. Oliveira

    2016-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM, but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD.

  16. Genetics of Nonalcoholic Fatty Liver Disease: An Overview

    Institute of Scientific and Technical Information of China (English)

    Jharna Puppala; Siva Prasad Siddapuram; Jyothy Akka; Anjana Munshi

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today.Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes.Hence,it has become a global public health issue.Environmental factors have been found to play a major role in the etiology of NAFLD,especially for genetically susceptible populations.Among these,one of the most important factors is junk food,especially the typical "Western-style" diet rich in simple carbohydrates,saturated fat,and highly processed food materials.Genetic predisposition to NAFLD does occur; however,a precise definition of genetic factors responsible for NAFLD is still lacking.Specific variants of different genes have been shown to present a risk for NAFLD.Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual's genotype.

  17. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Fengyuan Li

    2016-01-01

    Full Text Available Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.

  18. Angiogenesis-Related Biomarkers in Patients with Alcoholic Liver Disease: Their Association with Liver Disease Complications and Outcome

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    Beata Kasztelan-Szczerbinska

    2014-01-01

    Full Text Available Angiogenesis is believed to be implicated in the pathogenesis of alcoholic liver disease (ALD. We aimed to explore the usefulness and accuracy of plasma angiogenic biomarkers for noninvasive evaluation of the severity of liver failure and ALD outcome. One hundred and forty-seven patients with ALD were prospectively enrolled and assessed based on their (1 gender, (2 age, (3 severity of liver dysfunction according to the Child-Turcotte-Pugh and MELD scores, and (4 the presence of ALD complications. Plasma levels of vascular endothelial growth factor (VEGF-A and angiopoietins 1 and 2 (Ang1 and Ang2 were investigated using ELISAs. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Significantly higher concentrations of Ang2 and VEGF-A in ALD patients as compared to controls were found. There was no difference in Ang1 levels in both groups. A positive correlation of Ang2 levels with INR (Rho 0.66; P<0.0001 and its inverse correlation with plasma albumin levels (Rho –0.62; P<0.0001 were found. High Ang2 concentrations turned out to be an independent predictor of severe liver dysfunction, as well as hepatic encephalopathy and renal impairment. Ang2 possessed the highest diagnostic and prognostic potential among three studied angiogenesis-related molecules.

  19. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk

    Institute of Scientific and Technical Information of China (English)

    Lucia Pacifico; Valerio Nobili; Caterina Anania; Paola Verdecchia; Claudio Chiesa

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, nonalcoholic steatohepatitis, includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. NAFLD has become the most common cause of chronic liver disease in children and adolescents. The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome (MetS), a highly atherogenic condition, and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis. Accumulating evidence suggests that NAFLD is associated with a significantly greater overall mortality than in the general population, as well as with increased prevalence of cardiovascular disease (CVD), independently of classical atherosclerotic risk factors. Yet, several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS. Therefore, the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes. In children, the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively. Therapeutic goals for NAFLD should address nutrition, physical activity, and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

  20. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-08-02

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD.

  1. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yoshihisa Takahashi; Yurie Soejima; Toshio Fukusato

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis (NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  2. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-05-21

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  3. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Science.gov (United States)

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. PMID:22654421

  4. A Case of Wilson's Disease in Patient with Mildly Elevated Liver Enzymes

    OpenAIRE

    Cho, Young-Hye; Jeong, Dong-Wook; Lee, Sang-Yeoup; Park, Son-Ki; Yoon, Ki-Tae; Kim, Yun-Jin; Lee, Jeong-Ku; Lee, Yu-Hyun

    2011-01-01

    Wilson's disease is an autosomal recessive disorder affecting copper transport; it results in the accumulation of copper in the liver, brain, and other organs. Wilson's disease is the most common inherited liver disease with more than 500 cases reported in Korea. An impairment in biliary excretion process leads to copper accumulation in the liver, which progressively damages the liver, leading to cirrhosis. Since effective treatment is available for this disease, early and correct diagnosis i...

  5. Update on Berberine in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2013-01-01

    Full Text Available Berberine (BBR, an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD. The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD.

  6. Intrahepatic synthese of immunoglobulin G in chronic liver disease.

    Science.gov (United States)

    Kronborg, I J; Knopf, P M

    1980-04-01

    A method has been developed to measure the in vitro production of immunoglobulin (Ig) by liver biopsy specimens. Five to 30 mg of liver tissue was cultured for 24 h in Dulbecco's modified Eagle's medium/10% foetal calf serum (FCS) containing radiolabelled leucine (L-[4,5-3H] leucine). The culture medium was collected, centrifuged and the supernatant dialysed to remove labelled leucine. The residual radioactivity was a measure of newly synthesized 3H-labelled proteins released into the medium. The quantity of IgG was determined by immunoprecipitation with monospecific antisera to IgG heavy chains. The presence of IgG in the supernatant was confirmed by chromatography on protein-A Sepharose column. In 6 biopsies without evidence of active inflammation (4 normal and 2 fatty liver by histological criteria) less than 1% of the protein synthesized was IgG. In contrast in the presence of active inflammation in 4 cases of alcoholic hepatitis the IgG percentage ranged from 2 to 6%. Maximal levels of IgG production were detected in 3 cases of chronic active hepatitis (CAH) and ranged from 5 to 30%. The increased Ig synthesis by the liver in alcoholic hepatitis and CAH is presumed to be an index of the intrahepatic host response and may have important implications for mechanisms of liver damage in these diseases.

  7. Liver biopsy histopathology for diagnosis of Johne's disease in sheep.

    Science.gov (United States)

    Smith, S L; Wilson, P R; Collett, M G; Heuer, C; West, D M; Stevenson, M; Chambers, J P

    2014-09-01

    Sheep with Johne's disease develop epithelioid macrophage microgranulomas, specific to Mycobacterium avium subsp. paratuberculosis (Map) infection, in the terminal ileum, mesenteric lymph nodes, and organs distant to the alimentary tract such as the liver. The objectives of this study were to determine whether liver pathology was present in ewes affected by Map and whether liver cores provide adequate tissue for this potential diagnostic marker. One hundred and twenty-six adult, low body condition ewes were euthanized, necropsied, and underwent simulated liver biopsy. Ileal lesions typical of Map were found in 60 ewes. Hepatic epithelioid microgranulomas were observed in all ewes with Type 3b (n = 40) and 82% (n = 11) with Type 3c ileal lesions. None were found in ewes unaffected by Map or with Type 1, 2, or 3a ileal lesions. Liver biopsy core samples provided adequate tissue for histopathology with a sensitivity and specificity of 96% (95% confidence interval [CI], 0.87-0.99) and 100% (95% CI, 0.95-1), respectively for detection of types 3b and 3c ileal lesions.

  8. Reduced-size liver transplantation for glycogen storage disease

    Institute of Scientific and Technical Information of China (English)

    Hao-Feng Ji; Wei-Lin Wang; Yan Shen; Min Zhang; Ting-Bo Liang; Jian Wu; Xiao Xu; Sheng Yan; Shu-Sen Zheng

    2009-01-01

    BACKGROUND: Glycogen storage disease (GSD) is an inherited metabolic disorder in which the concentration and/or structure of glycogen in tissues is abnormal. Essentially, abnormalities in all known enzymes involved in the synthesis or degradation of glycogen and glucose have been found to cause some type of GSD. Liver and muscle have abundant quantities of glycogen and are the most common and seriously affected tissues. This study was to assess reduced-size liver transplantation for the treatment of GSD. METHODS: The clinical data from one case of GSD typeⅠ with hepatic adenoma was retrospectively analyzed. The clinical manifestations were hepatomegaly, delayed puberty, growth retardation, sexual immaturity, hypoglycemia, and lactic acidosis, which made the young female patient eligible for reduced-size liver transplantation. RESULTS: The patient recovered uneventfully with satisfactory outcome, including 12 cm growth in height and 5 kg increase in weight during 16 months after successful reduced-size liver transplantation. She has been living a normal life for 4 years so far. CONCLUSIONS: Reduced-size liver transplantation is an effective treatment for GSD with hepatomegaly and hepatic adenoma. Delayed puberty, growth retardation, hypoglycemia and lactic acidosis can be cured by surgery.

  9. Liver transplantation for hepatic and neurological Wilson's disease.

    Science.gov (United States)

    Geissler, I; Heinemann, K; Rohm, S; Hauss, J; Lamesch, P

    2003-06-01

    Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

  10. Stereotactic Ablative Radiotherapy for Oligometastatic Disease in Liver

    Directory of Open Access Journals (Sweden)

    Myungsoo Kim

    2014-01-01

    Full Text Available Liver metastasis in solid tumors, including colorectal cancer, is the most frequent and lethal complication. The development of systemic therapy has led to prolonged survival. However, in selected patients with a finite number of discrete lesions in liver, defined as oligometastatic state, additional local therapies such as surgical resection, radiofrequency ablation, cryotherapy, and radiotherapy can lead to permanent local disease control and improve survival. Among these, an advance in radiation therapy made it possible to deliver high dose radiation to the tumor more accurately, without impairing the liver function. In recent years, the introduction of stereotactic ablative radiotherapy (SABR has offered even more intensive tumor dose escalation in a few fractions with reduced dose to the adjacent normal liver. Many studies have shown that SABR for oligometastases is effective and safe, with local control rates widely ranging from 50% to 100% at one or two years. And actuarial survival at one and two years has been reported ranging from 72% to 94% and from 30% to 62%, respectively, without severe toxicities. In this paper, we described the definition and technical aspects of SABR, clinical outcomes including efficacy and toxicity, and related parameters after SABR in liver oligometastases from colorectal cancer.

  11. Olive oil consumption and non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy; Faris Nassar; Gattas Nasser; Maria Grosovski

    2009-01-01

    The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased lowdensity lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

  12. DMPD: Pathophysiological roles of interleukin-18 in inflammatory liver diseases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10807517 Pathophysiological roles of interleukin-18 in inflammatory liver diseases....l) Show Pathophysiological roles of interleukin-18 in inflammatory liver diseases. PubmedID 10807517 Title P...athophysiological roles of interleukin-18 in inflammatory liver diseases. Authors

  13. The spectrum of renal changes in patients with liver diseases: an immunofluorescent and light microscopic study

    Directory of Open Access Journals (Sweden)

    Gireesh K. Bhasin

    2016-03-01

    Conclusions: There is a wide spectrum of morphological lesions in the kidney in patients with liver diseases. These were mainly glomerular lesions and were directly related to the severity and chronicity of liver diseases. Immune deposits were commonly present in patients with chronic liver disease. [Int J Res Med Sci 2016; 4(3.000: 722-733

  14. Transfemoral Transcatheter Aortic Valve Replacement for Mixed Aortic Valve Disease in Child's Class C Liver Disease Prior to Orthotopic Liver Transplantation: A Case Report.

    Science.gov (United States)

    Wilkey, Barbara J; Hanson, Ross; Reece, T Brett; Forman, Lisa; Burton, James R; Messenger, John C; Kim, Michael S; Cleveland, Joseph C; Fiegel, Matt J; Nydam, Trevor L; Mandell, M Susan

    2016-06-01

    The American Association for the Study of Liver Diseases practice guidelines list severe cardiac disease as a contraindication to liver transplantation. Transcatheter aortic valve replacement has been shown to decrease all-cause mortality in patients with severe aortic stenosis who are not considered candidates for surgical aortic valve replacement. We report our experience of liver transplantation in a patient with severe aortic stenosis and moderate aortic insufficiency who underwent transcatheter aortic valve replacement with Child-Pugh Class C disease at a Model For End-Stage Liver Disease score of 29. The patient had a difficult post procedure course that was successfully medically managed. After liver transplantation the patient was discharged to home on postoperative day 11. The combination of cardiac disease and end stage liver disease is challenging but these patients can have a successful outcome despite very severe illness.

  15. Pharmacologic therapy for nonalcoholic fatty liver disease in adults.

    Science.gov (United States)

    Malinowski, Scott S; Byrd, Jennifer S; Bell, Allison M; Wofford, Marion R; Riche, Daniel M

    2013-02-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.

  16. Current status in the therapy of liver diseases.

    Science.gov (United States)

    Uhl, Philipp; Fricker, Gert; Haberkorn, Uwe; Mier, Walter

    2014-01-01

    Hepatic diseases, like viral hepatitis, autoimmune hepatitis, hereditary hemochromatosis, non-alcoholic fatty liver disease (NAFLD) and Wilson's disease, play an important role in the development of liver cirrhosis and, hence, hepatocellular carcinoma. In this review, the current treatment options and the molecular mechanisms of action of the drugs are summarized. Unfortunately, the treatment options for most of these hepatic diseases are limited. Since hepatitis B (HBV) and C (HCV) infections are the most common causes of liver cirrhosis and hepatocellular carcinoma, they are the focus of the development of new drugs. The current treatment of choice for HBV/HCV infection is an interferon-based combination therapy with oral antiviral drugs, like nucleos(t)ide analogues, which is associated with improving the therapeutic success and also preventing the development of resistances. Currently, two new protease inhibitors for HCV treatment are expected (deleobuvir, faldaprevir) and together with the promising drug, daclatasvir (NS5A-inhibitor, currently in clinical trials), adequate therapy is to be expected in due course (circumventing the requirement of interferon with its side-effects), while in contrast, efficient HBV therapeutics are still lacking. In this respect, entry inhibitors, like Myrcludex B, the lead substance of the first entry inhibitor for HBV/HDV (hepatitis D) infection, provide immense potential. The pharmacokinetics and the mechanism of action of Myrcludex B are described in detail.

  17. A nontumorigenic variant of FGF19 treats cholestatic liver diseases.

    Science.gov (United States)

    Luo, Jian; Ko, Brian; Elliott, Michael; Zhou, Mei; Lindhout, Darrin A; Phung, Van; To, Carmen; Learned, R Marc; Tian, Hui; DePaoli, Alex M; Ling, Lei

    2014-07-30

    Hepatic accumulation of bile acids is central to the pathogenesis of cholestatic liver diseases. Endocrine hormone fibroblast growth factor 19 (FGF19) may reduce hepatic bile acid levels through modulation of bile acid synthesis and prevent subsequent liver damage. However, FGF19 has also been implicated in hepatocellular carcinogenesis, and consequently, the potential risk from prolonged exposure to supraphysiological levels of the hormone represents a major hurdle for developing an FGF19-based therapy. We describe a nontumorigenic FGF19 variant, M70, which regulates bile acid metabolism and, through inhibition of bile acid synthesis and reduction of excess hepatic bile acid accumulation, protects mice from liver injury induced by either extrahepatic or intrahepatic cholestasis. Administration of M70 in healthy human volunteers potently reduces serum levels of 7α-hydroxy-4-cholesten-3-one, a surrogate marker for the hepatic activity of cholesterol 7α-hydroxylase (CYP7A1), the enzyme responsible for catalyzing the first and rate-limiting step in the classical bile acid synthetic pathway. This study provides direct evidence for the regulation of bile acid metabolism by FGF19 pathway in humans. On the basis of these results, the development of nontumorigenic FGF19 variants capable of modulating CYP7A1 expression represents an effective approach for the prevention and treatment of cholestatic liver diseases as well as potentially for other disorders associated with bile acid dysregulation.

  18. Dietary Anthocyanins as Nutritional Therapy for Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Luca Valenti

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD, defined by excessive lipid accumulation in the liver, is the hepatic manifestation of insulin resistance and the metabolic syndrome. Due to the epidemics of obesity, NAFLD is rapidly becoming the leading cause of altered liver enzymes in Western countries. NAFLD encompasses a wide spectrum of liver disease ranging from simple uncomplicated steatosis, to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Diet may affect the development of NAFLD either by increasing risk or by providing protective factors. Therefore, it is important to investigate the role of foods and/or food bioactives on the metabolic processes involved in steatohepatitis for preventive strategies. It has been reported that anthocyanins (ACNs decrease hepatic lipid accumulation and may counteract oxidative stress and hepatic inflammation, but their impact on NAFLD has yet to be fully determined. ACNs are water-soluble bioactive compounds of the polyphenol class present in many vegetable products. Here, we summarize the evidence evaluating the mechanisms of action of ACNs on hepatic lipid metabolism in different experimental setting: in vitro, in vivo, and in human trials. Finally, a working model depicting the possible mechanisms underpinning the beneficial effects of ACNs in NAFLD is proposed, based on the available literature.

  19. Serum Lp(a)levels in patients with liver disease

    Institute of Scientific and Technical Information of China (English)

    Sharanabasappa M; Sudhakar Nayak

    2008-01-01

    Objective:The study was conducted to evaluate the effect of liver diseases on serum Lp(a)levels and also to study the relationship between Lp(a)levels with other lipid parameters and liver function tests in 32 hyperbil-irubinemia patients with total bilirubin >3mg/dL.The results were compared with 20 healthy age matched in-dividuals.Methods:Serum obtained from venous blood sample are used for estimating total cholesterol (TC), triglyceride(TG),high density lipoprotein cholesterol(HDL-c),low density lipoprotein cholesterol(LDL-c), very low density lipoprotein cholesterol(VLDL-c),total protein(TP),albumin(ALB),total bilirubin,direct bilirubin,aspartate amino tranferase(AST),alanine amino transferase(ALT),alkaline phosphatase(ALP), gamma glutamyl transferase (GGT),lipoprotein (a)[Lp(a)],serum phospholipids.Results:There was significant decrease in serum Lp(a)levels in liver disease patients and the decrease was directly correlated with reduced serum albumin levels and inversely with liver function parameters.Conclusion:Thus the present study indicates hepatic synthetic damage has possible biochemical basis for the reduction of serum Lp(a)lev-els.

  20. The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Sharma, Mithun; Mitnala, Shasikala; Vishnubhotla, Ravi K; Mukherjee, Rathin; Reddy, Duvvur N; Rao, Padaki N

    2015-06-01

    Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.

  1. Prognostic factors for late mortality after liver transplantation for benign end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying-cai; LU Min-qiang; YANG Yang; CHEN Gui-hua; ZHANG Qi; LI Hua; ZHANG Jian; WANG Gen-shu; XU Chi; YI Shu-hong; YI Hui-min; CAI Chang-jie

    2011-01-01

    Background There are increasing numbers of patients who survive more than one year after liver transplantation.Many studies have focused on the early mortality of these patients.However,the factors affecting long-term survival are not fully understood.This study aims to evaluate prognostic factors predicting long-term survival and to explore measures for improving the survival outcomes of patients who underwent liver transplantation for benign end-stage liver diseases.Methods The causes of late death after liver transplantation and potential prognostic factors were retrospectively analyzed for 221 consecutive patients who underwent liver transplantation from October 2003 to June 2008.Twenty-seven variables were assessed using the Kaplan-Meier method,and those variables found to be univariately significant at P <0.10 were entered into a backward step-down Cox proportional hazard regression analysis to identify the independent prognostic factors influencing the recipients' long-term survival.Results Twenty-eight recipients died one year after liver transplantation.The major causes of late mortality were infectious complications,biliary complications,and Hepatitis B virus recurrence/reinfection.After Cox analysis,the five remaining co-variables were:age,ABO blood group,cold ischemia time,post-infection region,and biliary complications.Conclusions The major causes of late mortality were infection,biliary complications and Hepatitis B virus recurrence/reinfection.Five variables (Age,ABO blood group,cold ischemia time,infection,and biliary complications) had significant impacts on patient survival.

  2. Liver hemangioma and vascular liver diseases in patients with systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    Annalisa Berzigotti; Marco Zoli; Marilena Frigato; Elena Manfredini; Lucia Pierpaoli; Rita Mulè; Carolina Tiani; Paola Zappoli; Donatella Magalotti; Nazzarena Malavolta

    2011-01-01

    AIM: To investigate whether systemic lupus erythematosus (SLE) is associated with benign focal liver lesions and vascular liver diseases, since these have been occasionally reported in SLE patients. METHODS: Thirty-five consecutive adult patients with SLE and 35 age- and sex-matched healthy controls were evaluated. Hepatic and portal vein patency and presence of focal liver lesions were studied by colour- Doppler ultrasound, computerized tomography and magnetic resonance were used to refine the diagnosis, clinical data of SLE patients were reviewed. RESULTS: Benign hepatic lesions were common in SLE patients (54% vs 14% controls, P < 0.0001), with hemangioma being the most commonly observed lesion in the two groups. SLE was associated with the presence of single hemangioma [odds ratios (OR) 5.05; 95% confidence interval (CI) 1.91-13.38] and multiple hemangiomas (OR 4.13; 95% CI 1.03-16.55). Multiple hemangiomas were associated with a longer duration of SLE (9.9 ± 6.5 vs 5.5 ± 6.4 years; P = 0.04). Imaging prior to SLE onset was available in 9 patients with SLE and hemangioma, showing absence of lesions in 7/9. The clinical data of our patients suggest that SLE possibly plays a role in the development of hemangioma. In addition, a Budd-Chiari syndrome associated with nodular regenerative hyperplasia (NRH), and a NRH associated with hepatic hemangioma were observed, both in patients hospitalized for abdominal symptoms, suggesting that vascular liver diseases should be specifically investigated in this population. CONCLUSION: SLE is associated with 5-fold increased odds of liver hemangiomas, suggesting that these might be considered among the hepatic manifestations of SLE.

  3. Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device

    Science.gov (United States)

    Simonelli, Maria Chiara; Giannitelli, Sara Maria; Businaro, Luca; Trombetta, Marcella; Rainer, Alberto

    2016-01-01

    Background and Aim Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions. The present liver-on-a-chip approach aims at filling the gap between conventional in vitro models, often scarcely predictive of in vivo conditions, and animal models, potentially biased by their xenogeneic nature. Methods HepG2 cells were cultured into a microfluidically perfused device under free fatty acid (FFA) supplementation, namely palmitic and oleic acid, for 24h and 48h. The device mimicked the endothelial-parenchymal interface of a liver sinusoid, allowing the diffusion of nutrients and removal of waste products similar to the hepatic microvasculature. Assessment of intracellular lipid accumulation, cell viability/cytotoxicity and oxidative stress due to the FFA overload, was performed by high-content analysis methodologies using fluorescence-based functional probes. Results The chip enables gradual and lower intracellular lipid accumulation, higher hepatic cell viability and minimal oxidative stress in microfluidic dynamic vs. 2D static cultures, thus mimicking the chronic condition of steatosis observed in vivo more closely. Conclusions Overall, the liver-on-a-chip system provides a suitable culture microenvironment, representing a more reliable model compared to 2D cultures for investigating NAFLD pathogenesis. Hence, our system is amongst the first in vitro models of human NAFLD developed within a microfluidic device in a sinusoid

  4. Prevalence of psoriasis in patients with alcoholic liver disease.

    LENUS (Irish Health Repository)

    Tobin, A M

    2012-02-01

    BACKGROUND: Excessive alcohol use has been implicated as a risk factor in the development of psoriasis, particularly in men. Despite this, little is known of the incidence or prevalence of psoriasis in patients who misuse alcohol. OBJECTIVE: To assess the prevalence of psoriasis in patients with alcoholic liver disease. METHODS: In total, 100 patients with proven alcoholic liver disease were surveyed for a history of psoriasis and a full skin examination was performed if relevant. RESULTS: Of the 100 patients, 15 reported a history of psoriasis and another 8 had evidence of current activity, suggesting a prevalence (past or present) of 15% in this group of patients. CONCLUSION: It would appear that the prevalence of psoriasis in patients who misuse alcohol is much higher than the 1-3% variously quoted in the general population.

  5. Parenteral nutrition-associated liver disease and lipid emulsions.

    Science.gov (United States)

    Zugasti Murillo, Ana; Petrina Jáuregui, Estrella; Elizondo Armendáriz, Javier

    2015-01-01

    Parenteral nutrition-associated liver disease (PNALD) is a particularly important problem in patients who need this type of nutritional support for a long time. Prevalence of the condition is highly variable depending on the series, and its clinical presentation is different in adults and children. The etiology of PNALD is not well defined, and participation of several factors at the same time has been suggested. When a bilirubin level >2 mg/dl is detected for a long time, other causes of liver disease should be ruled out and risk factors should be minimized. The composition of lipid emulsions used in parenteral nutrition is one of the factors related to PNALD. This article reviews the different types of lipid emulsions and the potential benefits of emulsions enriched with omega-3 fatty acids.

  6. Probiotics and gut health: a special focus on liver diseases.

    Science.gov (United States)

    Gratz, Silvia Wilson; Mykkanen, Hannu; El-Nezami, Hani S

    2010-01-28

    Probiotic bacteria have well-established beneficial effects in the management of diarrhoeal diseases. Newer evidence suggests that probiotics have the potential to reduce the risk of developing inflammatory bowel diseases and intestinal bacterial overgrowth after gut surgery. In liver health, the main benefits of probiotics might occur through preventing the production and/or uptake of lipopolysaccharides in the gut, and therefore reducing levels of low-grade inflammation. Specific immune stimulation by probiotics through processes involving dendritic cells might also be beneficial to the host immunological status and help prevent pathogen translocation. Hepatic fat metabolism also seems to be influenced by the presence of commensal bacteria, and potentially by probiotics; although the mechanisms by which probiotic might act on the liver are still unclear. However, this might be of major importance in the future because low-grade inflammation, hepatic fat infiltration, and hepatitis might become more prevalent as a result of high fat intake and the increased prevalence of obesity.

  7. [Pediatric nonalcoholic fatty liver disease/nonalcoholic steatohepatitis].

    Science.gov (United States)

    Takahashi, Yoshihisa; Fukusato, Toshio; Inui, Ayano; Fujisawa, Tomoo

    2012-10-01

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is a hepatic disease associated with metabolic syndrome. In recent years, pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity. The estimated prevalence of pediatric NAFLD is 2.6-9.6%. With regard to the pathogenesis of NAFLD/ NASH, the "two-hit" or "multiple-hit" hypothesis is widely accepted, and many genetic and environmental factors are associated with the development of NAFLD/NASH. Liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH. Pediatric NAFLD has different histopathological characteristics from those of adult NAFLD. Although pharmacotherapy has been studied in clinical trials, lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.

  8. Glycosyltransferases and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

    2016-02-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.

  9. Polyarthritis associated with hydatid disease of the liver

    Directory of Open Access Journals (Sweden)

    Rawdha Tekaya

    2009-08-01

    Full Text Available Clinical presentation of hydatid disease is depending on immunological background of the patient. Articular site of the parasite can give rise either to a veritable echinococcal arthritis or to a synovial affection that do not depend on living larva. A 77-year old man who had hydatid disease of the liver since two years, presented with progressive onset arthritis. Laboratory studies showed inflammatory changes but no evidence of immunological disorders was noticed. Abdominal imaging revealed multiple hydatid cysts of the liver. Ankle synovial fluid evaluation was positive of antibodies for hydatid antigen and negative of echinococcal larva. Excision of the hydatid cyst was accompanied by full remission of the arthritis with no recurrence. A reactive immune mechanism triggered by a parasite located at a distant side appears to be responsible for this type of arthritis. This data support the potential of echinococcosis granulosus in inducing a veritable aseptic arthritis as a response to intense immunological disorders.

  10. TLR4-dependent immune response promotes radiation-induced liver disease by changing the liver tissue interstitial microenvironment during liver cancer radiotherapy.

    Science.gov (United States)

    Zhi-Feng, Wu; Le-Yuan, Zhou; Xiao-Hui, Zhou; Ya-Bo, Gao; Jian-Ying, Zhang; Yong, Hu; Zhao-Chong, Zeng

    2014-12-01

    Liver tissue interstitial fluid (TIF) a special microenvironment around liver cells, which may play a vital role in cell communication during liver injury. Moreover, toll-like receptor 4 (TLR4) is an important trigger of the immune response that may also play a role in liver injuries, including radiation-induced liver disease (RILD). Therefore, the purpose of this study was to identify the roles of the TLR4-dependent immune response and TIFs in RILD after radiation therapy (RT) for liver cancer. This study consisted of two phases, and in the primary phase, the livers of TLR4 mutant (TLR4(-)) and normal (TLR4(+)) mice were irradiated with 30 Gy. TIF was then obtained from mouse livers and assessed by cytokine array analysis 20 days after irradiation, and cytokines in the TIFs, TLR4 and RILD were analyzed. In the second or validation phase, hepatocytes were isolated from TLR4(+) or TLR4(-) mice irradiated with 8 Gy and were co-cultured with TIFs from mouse livers, apoptosis of the hepatocytes was then measured using flow cytometry. We found that severe RILD was accompanied by higher expression of granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2(VEGFR-2) in liver TIFs, from in TLR4(+) mice compared with TLR4(-) mice (P livers irradiated, compared with TIFs from TLR4(-) mice that had their livers irradiated or TIFs from unirradiated mice (P liver TIFs.

  11. Regulation of microRNAs and their role in liver development, regeneration and disease.

    Science.gov (United States)

    Finch, Megan L; Marquardt, Jens U; Yeoh, George C; Callus, Bernard A

    2014-09-01

    Since their discovery more than a decade ago microRNAs have been demonstrated to have profound effects on almost every aspect of biology. Numerous studies in recent years have shown that microRNAs have important roles in development and in the etiology and progression of disease. This review is focused on microRNAs and the roles they play in liver development, regeneration and liver disease; particularly chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, viral hepatitis and primary liver cancer. The key microRNAs identified in liver development and chronic liver disease will be discussed together with, where possible, the target messenger RNAs that these microRNAs regulate to profoundly alter these processes. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.

  12. Liver disease in women: the influence of gender on epidemiology, natural history, and patient outcomes.

    Science.gov (United States)

    Guy, Jennifer; Peters, Marion G

    2013-10-01

    Women more commonly present with acute liver failure, autoimmune hepatitis, benign liver lesions, primary biliary cirrhosis, and toxin-mediated hepatotoxicity. Women less commonly have malignant liver tumors, primary sclerosing cholangitis, and viral hepatitis. There is a decreased rate of decompensated cirrhosis in women with hepatitis C virus infection, no survival difference in alcohol-related liver disease, and improved survival from hepatocellular carcinoma. In general, men are 2-fold more likely to die from chronic liver disease and cirrhosis than are women. Liver transplant occurs less commonly in women than in men, with variable disease outcomes based on etiology. This review highlights the epidemiology, natural history, treatment outcomes, and pathophysiology of common liver diseases in women and discusses how gender influences disease incidence, presentation, progression, and outcomes. Pregnancy-related liver disease is not covered.

  13. Effect of tea polyphenols on alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Guo-rongHE; Guan-huaDU

    2004-01-01

    AIM: To investigate the scavenging effects of tea polyphenols on aldehyde in vitro and searching for the preliminary mechanism of tea polyphenols (TP) on alcoholic liver disease.METHODS: The effect of aldehyde absorption is tested at gaseous and liquid phases. High performance liquid chromatography (HPLC, HPll00Series) and UV-visible Detector(Wavelength: 235 nm) are used to analyze the components of the outcome of solution reaction. RESULTS: In vitro study showed

  14. Accuracy of ultrasound to identify chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Richard; Allan; Kerry; Thoirs; Maureen; Phillips

    2010-01-01

    AIM:To identify and assess studies reporting the diagnostic performance of ultrasound imaging for identifying chronic liver disease(CLD)in a high risk population. METHODS:A search was performed to identify studies investigating the diagnostic accuracy of ultrasound imaging for CLD.Two authors independently used the quality assessment of diagnostic accuracy studies(QUADAS)checklist to assess the methodological quality of the selected studies.Inter-observer reliability of the QUADAS tool was assessed by measu...

  15. Spontaneous expulsive suprachoroidal hemorrhage caused by decompensated liver disease

    Directory of Open Access Journals (Sweden)

    Krishnagopal Srikanth

    2013-01-01

    Full Text Available Expulsive suprachoroidal hemorrhage can be surgical or spontaneous. Spontaneous expulsive suprachoroidal hemorrhage (SESCH is a rare entity. Most of the reported cases of SESCH were caused by a combination of corneal pathology and glaucoma. We are reporting a rare presentation of SESCH with no pre-existing glaucoma or corneal pathology and caused by massive intra- and peri-ocular hemorrhage due to decompensated liver disease.

  16. Acute Kidney Disease After Liver and Heart Transplantation.

    Science.gov (United States)

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  17. Liver needle biopsy in Iraninan pediatric patients: Diagnostic significance and pattern of liver diseases

    Directory of Open Access Journals (Sweden)

    Monajemzadeh Maryam

    2009-01-01

    Full Text Available We aimed at determining the pattern of liver disease in the Iranian children referred to the Medical Center of Children affiliated with the Tehran University of Medical Sciences. Materials and Methods: In a cross-sectional study conducted over 2 years, 425 liver needle biopsies were sent to the pathology laboratory of our center. Slides were prepared from paraffin-embedded blocks, stained by routine H & E and special stains and were then reviewed. The frequency of each disorder, separately and in combination with the age group or gender of the patients was calculated and compared with other similar studies. Results: The male to female ratio was 1.42:1. The age range was between 1 month and 18 years old and 41.4% were less than 2 years old. The most common histological diagnosis was iron overload due to major thalassemia (17.5% followed by biliary atresia (9.7%, no significant pathologic change (8.7%, neonatal hepatitis (8.7%, chronic hepatitis (8.5%, cirrhosis (6.5%, metabolic disease (5.5% and progressive familial intrahepatic cholestasis (5%. Results of the hemosiderosis grading in patients with thalassemia revealed no or minimal, mild, medium, or marked increase in 10%, 27.1%, 10%, 21.4% and 31.5% of the cases, respectively and the degree of iron deposition rose in parallel with age and also the stage of fibrosis (p< 0.05. Conclusion: A liver biopsy is a useful and practical tool for the appropriate diagnosis of pediatric liver diseases. Also, we found that in non thalassemic children, biliary atresia, chronic hepatitis and neonatal hepatitis, in the stated order, are the most prevalent histologic diagnoses in Iranian pediatrics.

  18. Tuberculous Peritonitis in Hemodialysis Patients with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Al Shohaib Saad

    2000-01-01

    Full Text Available Tuberculous peritonitis (TBP remains a major medical problem in many developing countries, wherein the incidence of tuberculosis (TB is still high. Since the clinical presentation may be insidious and variable, diagnosis of TBP may be delayed or missed, resulting in undue patient morbidity and mortality. Tests frequently associated with TB such as chest radiograph and Mantoux test are not usually sensitive enough for the diagnosis of TBP. The diagnosis becomes all the more difficult in the presence of chronic liver disease and/or renal failure, since the ascitic fluid may not be of the exudative type and lymphocytosis may not be the predominant cell picture. We present here three cases of TBP in diabetic Saudi patients on maintenance hemodialysis who also had associated chronic liver disease. All three patients responded satisfactorily to standard anti-tuberculous therapy. We stress that high index of suspicion is required to establish early diagnosis of TBP particularly in patients with chronic renal and/or liver disease. Laparoscopy with tissue biopsy for histology and, microbiological examination including culture are the most sensitive and specific diagnostic procedures.

  19. Alcoholic liver disease and changes in bone mineral density

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    Germán López-Larramona

    2013-12-01

    Full Text Available Osteoporosis and osteopenia are alterations in bone mineral density (BMD that frequently occur in the context of chronic liver disease (CLD. These alterations have been studied predominantly in chronic cholestatic disease and cirrhosis of the liver. Alcohol consumption is an independent risk factor for the onset of osteoporosis, whose estimated prevalence in patients with alcoholic liver disease (ALD ranges between 5 % and 40 %. The loss of BMD in ALD is the result of an imbalance between bone formation and resorption. Its pathogenesis is multifactorial and includes the toxic effects of alcohol on bone and endocrine and nutritional disorders secondary to alcoholism and a deficiency of osteocalcin, vitamin D and insulin growth factor-1. The diagnosis of BMD alterations in ALD is based on its measurement using bone densitometry. Treatment includes smoking and alcohol cessation and general measures such as changes in nutrition and exercise. Calcium and vitamin D supplements are recommended in all patients with ALD and osteoporosis. Bisphosphonates are the most commonly prescribed drugs for the specific treatment of this condition. Alternatives include raloxifene, hormone replacement therapy and calcitonin. This review will address the most important aspects involved in the clinical management of abnormal BMD in the context of ALD, including its prevalence, pathogenesis and diagnosis. We will also review the treatment of osteoporosis in CLD in general, focusing on specific aspects related to bone loss in ALD.

  20. Nutritional recommendations for patients with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy

    2011-01-01

    Fatty liver is the most common liver disease worldwide.Patients with fatty liver disease die primarily from cardiovascular disease and not from chronic liver diseases. Hyperglycemia and hyperinsulinemia induce lipogenesis, thereby increasing the hepatic pool of fatty acids. This pool is also increased by increased delivery of fatty acids through the diet or lipolysis in adipose tissue. Nutritional consultations and lifestyle modification are important in the treatment of non-alcoholic fatty liver disease (NAFLD). Among the dietary constituents, combination of vitamin D, vitamin E, and omega-3 fatty acids shows promise for the treatment of NAFLD.

  1. The heart-liver metabolic axis: defective communication exacerbates disease.

    Science.gov (United States)

    Baskin, Kedryn K; Bookout, Angie L; Olson, Eric N

    2014-04-01

    The heart has been recognized as an endocrine organ for over 30 years (de Bold, 2011); however, little is known about how the heart communicates with other organs in the body, and even less is known about this process in the diseased heart. In this issue of EMBO Molecular Medicine, Magida and Leinwand (2014) introduce the concept that a primary genetic defect in the heart results in aberrant hepatic lipid metabolism, which consequently exacerbates hypertrophic cardiomyopathy (HCM). This study provides evidence in support of the hypothesis that crosstalk occurs between the heart and liver, and that this becomes disrupted in the diseased state.

  2. Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

    LENUS (Irish Health Repository)

    O'Donnell, D H

    2012-02-01

    Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

  3. Nonalcoholic fatty liver disease: Noninvasive methods of diagnosing hepatic steatosis

    Directory of Open Access Journals (Sweden)

    Rasha AlShaalan

    2015-01-01

    Full Text Available Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD. It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD.

  4. Soft drinks consumption and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nseir, William; Nassar, Fares; Assy, Nimer

    2010-06-07

    Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and inflammation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD.

  5. Non-alcoholic fatty liver disease: is iron relevant?

    Science.gov (United States)

    O'Brien, Julia; Powell, Lawrie W

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common and ubiquitous disorder (Bedogni et al. in Hepatology 42:44-52, 2005; Bellentani et al. in Ann Intern Med 132:112-117, 2000) which in a proportion of subjects leads to non-alcoholic steatohepatitis (NASH), advanced liver disease and hepatocellular carcinoma. Although the factors responsible for progression of disease are still uncertain, there is evidence that insulin resistance (IR) is a key operative mechanism (Angulo et al. in Hepatology 30:1356-1362, 1999) and that two stages are involved. The first is the accumulation of triglycerides in hepatocytes followed by a "second hit" which promotes cellular oxidative stress. Several factors may be responsible for the induction of oxidative stress but hepatic iron has been implicated in various studies. The topic is controversial, however, with early studies showing an association between hepatic iron (with or without hemochromatosis gene mutations) and the progression to hepatic fibrosis. Subsequent studies, however, could not confirm an association between the presence of hepatic iron and any of the histological determinants of NAFLD or NASH. Recent studies have reactivated interest in this subject firstly, with the demonstration that hepatic iron loading increases liver cholesterol synthesis with increased lipid deposition in the liver increasing the cellular lipid burden and secondly, a large clinical study has concluded that hepatocellular iron deposition is associated with an increased risk of hepatic fibrosis, thus, strongly supporting the original observation made over a decade ago. An improvement in insulin sensitivity has been demonstrated following phlebotomy therapy but a suitably powered controlled clinical trial is required before this treatment can be implemented.

  6. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Spengler, Erin K; Loomba, Rohit

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease in the United States, afflicting an estimated 80 to 100 million Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Although nonalcoholic fatty liver has a negligible risk of progression, patients with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver biopsy is required to diagnose NASH, only patients with a high risk of NASH or advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD, well-defined screening recommendations are currently lacking. In this review, suggestions for screening, diagnosis, and initial work-up of NAFLD are given on the basis of established guidelines and recent publications. Proposed drug treatments of NASH are also discussed, highlighting the study outcomes, as well as proposed uses and limitations of these drugs. The literature was searched in PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, with filters of "English language." A date range of January 1, 2000, to May 1, 2015, was used for the search. The bibliographies of key references were also searched manually, and seminal publications before the year 2000 were included.

  7. ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Juliana Ayres de Alencar Arrais GUERRA

    2015-09-01

    Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

  8. Non-alcohol fatty liver disease in Asia: Prevention andplanning

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To review all of epidemiological aspects of nonalcoholicfatty liver disease (NAFLD) and also preventthis disease is examined.METHODS: We conducted a systematic reviewaccording to the PRISMA guidelines. All searches forwriting this review is based on the papers was foundin PubMed (MEDLINE), Cochrane database and Scopusin August and September 2014 for topic of NAFLD inAsia and the way of prevention of this disease, with nolanguage limitations. All relevant articles were accessedin full text and all relevant materials was evaluated andreviewed.RESULTS: NAFLD is the most common liver disorder inworldwide, with an estimated with 20%-30% prevalencein Western countries and 2%-4% worldwide. Theprevalence of NAFLD in Asia, depending on location(urban vs rural), gender, ethnicity, and age is variablebetween 15%-20%. According to the many studies inthe world, the relationship between NAFLD, obesity,diabetes mellitus, and metabolic syndrome (MS) isquiet obvious. Prevalence of NAFLD in Asian countriesseems to be lower than the Western countries but, ithas increased recently due to the rise of obesity, type 2diabetes and MS in this region. One of the main reasonsfor the increase in obesity, diabetes and MS in Asia isa lifestyle change and industrialization. Today, NAFLDis recognized as a major chronic liver disease in Asia.Therefore, prevention of this disease in Asian countriesis very important and the best strategy for preventionand control of NAFLD is lifestyle modifications. Lifestylemodification programs are typically designed to changebad eating habits and increase physical activity that isassociated with clinically significant improvements inobesity, type 2 diabetes and MS.CONCLUSION: Prevention of NAFLD is very important in Asian countries particularly in Arab countries becauseof high prevalence of obesity, diabetes and MS.

  9. Evaluation of nutritional indicators and body composition in patients with advanced liver disease enrolled for liver transplantation

    OpenAIRE

    Vulcano, Daniela Salate Biagioni [UNESP; Carvalhaes, Maria Antonieta de Barros Leite [UNESP; Bakonyi Neto, Alexandre [UNESP

    2013-01-01

    PURPOSE: Malnutrition is prevalent in patients with advanced liver disease (LD) related to multifactorial causes. Fluid retention can underestimate the nutritional status based on anthropometric measures. We evaluated nutritional indicators and body composition (BC) in patients with liver cirrhosis and correlated them with LD severity. METHODS: Forty three patients with LD enrolled for liver transplantation were evaluated by Anthropometric measures, subjective evaluation (Global Assessment of...

  10. Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

    NARCIS (Netherlands)

    Edens, M. A.; Kuipers, F.; Stolk, R. P.

    2009-01-01

    Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessi

  11. Compensation for work-related hematologic, liver, and infectious diseases.

    Science.gov (United States)

    Kim, Jung-Won; Kang, Dong-Mug

    2014-06-01

    Occupational diseases may be defined only medically or scientifically, and even then, their definition is not simple. However, compensable occupational diseases involve the additional layer of legal systems and social welfare policies as well. Their multifaceted nature makes determining the work-relatedness of these diseases more complex. Korea has established standards for the recognition of occupational diseases in Schedule 5 of the Enforcement Decree of the Labor Standards Act, and specific criteria for the recognition of occupational diseases are listed in Schedule 3 of the Enforcement Decree of the Industrial Accident Compensation Insurance Act. The new list of compensable occupational diseases comprises 13 articles as an open-ended system. The newly added articles pertain to lymphohematopoietic (Article 5) and infectious diseases (Article 9), as well as diseases of other target organs. Furthermore, the article on liver diseases (Article 8) has been partially revised. The new act has been changed to clarify the meaning as it has been presented in recent research. It is necessary to achieve agreement among concerned parties, including experts from the legal, medical, and social domains to resolve the issues of work-relatedness, causation, notion of aggravation, and so on for preparing a list and a process that are more reasonable.

  12. Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease Proven by Transient Elastography

    Directory of Open Access Journals (Sweden)

    Ivana Mikolasevic

    2013-09-01

    Full Text Available Background/Aim: Preliminary data suggest an association between chronic kidney disease (CKD and non-alcoholic fatty liver disease (NAFLD. The aim of this study was to further investigate the association between NAFLD and decreased kidney function. Methods: A total of 62 patients with CKD were enrolled in the study. Liver stiffness was used to detect liver fibrosis and CAP (controlled attenuation parameter was used to detect and quantify liver steatosis (Fibroscan®. NAFLD was defined by CAP values ≥238 dB.m-1. Results: CKD stage III was present in 29 patients (46.8% and CKD stage IV in 33 patients (53.2%. Out of 62 CKD patients 53 (85.5% had NAFLD and of these 14/53 patients (26.4% had also liver stiffness >7 kPa. The severity of liver steatosis was positively correlated with serum creatinine (r=0.399;pConclusion: The results suggest a high prevalence of NAFLD in CKD patients. The severity of liver steatosis is negatively correlated with kidney function. The study documents the value of ultrasonographic elastography as an effective non-invasive screening method for the diagnosis of NAFLD.

  13. Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Kei Nakajima

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1 inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

  14. Probiotics as a complementary therapeutic approach innonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Silvia Marinho Ferolla; Geyza Nogueira de Almeida Armiliato; Cláudia Alves Couto; Teresa Cristina Abreu Ferrari

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currentlyrecognized as one of the most common causes ofchronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation,steatohepatitis, fibrosis and cirrhosis. The key factorin the pathophysiology of NAFLD is insulin resistancethat determines lipid accumulation in the hepatocytesand, thus, oxidative stress, which is followed byinflammatory response. However, NAFLD pathogenesisis still largely unknown and has been extensivelyinvestigated. Although life style modification with theaim of losing weight has been advocated to treat thisdisorder, its effectiveness is limited; additionally, thereis no specific pharmacologic treatment until nowadays.Recent evidence suggests that the gut microbiota mayplay a role in the development of insulin resistance,hepatic steatosis, necroinflammation and fibrosis.Differences in gut microbiota between NAFLD patientsand lean individuals as well as presence of smallintestinal bacterial overgrowth in NAFLD subjects havebeen demonstrated. Furthermore, some data indicatethat the immunoregulatory effects of probiotics maybe beneficial in NAFLD treatment as they modulatethe intestinal microbiota; improve epithelial barrierfunction and strengthen the intestinal wall decreasingits permeability; reduce bacterial translocation andendotoxemia; improve intestinal inflammation; andreduce oxidative and inflammatory liver damage. Inthis article, we review the clinical trials on the useof probiotics in the treatment of NAFLD and discussthe effects of these agents and their efficacy as anemerging therapeutic resource to treat NAFLD patients.

  15. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-11-14

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.

  16. Hepatic enzyme concentrations as indicators of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Alvina Alvina

    2016-02-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has emerged as a world-wide problem because it runs an asymptomatic course, ultimately leading to cirrhosis of the liver and portal hypertension, resulting in death. The prevalence of the disease accounts for 3-24% of the population in several countries. Generally there are increased concentrations of hepatic enzymes as markers of liver damage, such as serum glutamic oxaloacetic transaminase (SGOT, serum glutamic pyruvic transaminase (SGPT and gamma glutamyl transferase (GGT. The aim of the present study was to determine the concentrations of hepatic enzymes as markers of NAFLD. The study design was cross-sectional, involving 90 subjects meeting the inclusion and exclusion criteria. The degree of severity NAFLD was determined by ultrasonography and the concentrations of SGOT, SGPT and GGT by automated clinical chemistry analyzer. The results indicated that there were 32 subjects with mild NAFLD (35.6%, 35 subjects with moderate NAFLD (38.9% and 23 subjects with severe NAFLD (25.6%. There was a significant difference in degree of NAFLD by gender (p<0.05, where severe NAFLD was more frequent in males than in females. Concentrations of SGOT, SGPT and GGT were significantly different between degrees of NAFLD (p<0.05. The conclusion is that SGOT, SGPT and GGT concentrations are indicators of degree of NAFLD.

  17. Non-alcoholic fatty liver disease in 2015

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There is worldwide epidemic of non-alcoholic fatty liverdisease (NAFLD). NAFLD is a clinical entity related tometabolic syndrome. Majority of the patients are obesebut the disease can affect non-obese individuals aswell. Metabolic factors and genetics play important rolesin the pathogenesis of this disorder. The spectrum ofdisorders included in NAFLD are benign macrovesicularhepatic steatosis, non-alcoholic steatohepatitis, hepaticfibrosis, cirrhosis of liver and hepatocellular carcinoma.Although the disease remains asymptomatic mostof the time, it can slowly progress to end stage liverdisease. It will be the most common indication of livertransplantation in the future. It is diagnosed by abnormalliver chemistry, imaging studies and liver biopsy. Asthere are risks of potential complications during liverbiopsy, many patients do not opt for liver biopsy. Thereare some noninvasive scoring systems to find outwhether patients have advanced hepatic fibrosis. At thepresent time, there are limited treatment options whichinclude lifestyle modification to loose weight, vitaminE and thioglitazones. Different therapeutic agents arebeing investigated for optimal management of thisentity. There are some studies done on incretin basedtherapies in patients with NAFLD. Other potential agentswill be silent information regulator protein Sirtuin andantifibrotic monoclonal antibody Simtuzumab againstlysyl oxidase like molecule 2. But they are still in theinvestigational phase.

  18. 'Non-alcoholic fatty liver disease' bij kinderen : een nieuwe complicatie van obesitas

    NARCIS (Netherlands)

    Bocca, Gianni; Stolk, R.P.; Scheenstra, R.; Sauer, P.J.

    2008-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and

  19. Gender-based differences in the relationship between fatty liver disease and atherosclerosis

    Science.gov (United States)

    Kim, Hyun-Jin; Lim, Chae-Wan; Lee, Jae hyuk; Park, Hyung-Bok; Suh, Yongsung; Cho, Yoon-Hyeong; Choi, Tae-Young; Hwang, Eui-Seok; Cho, Deok-Kyu; Kim, Hyun-Jin

    2016-01-01

    Summary Background Carotid intima–media thickness (CIMT) is a surrogate of subclinical atherosclerosis. Fatty liver disease is also linked to increased risk of cardiovascular events. The aim of this study was to evaluate the association between fatty liver disease and CIMT according to gender. Methods Patients who had undergone carotid and abdominal ultrasound between June 2011 and December 2013 were retrospectively evaluated. The differences between the CIMT values measured in the common carotid artery and the prevalence of carotid plaque in patients with fatty liver disease and those with normal livers were investigated. Results Out of a total of 1 121 patients, the men had more fatty liver disease than the women. The mean CIMT of the men was significantly higher than that of the women, and the men had more plaque than the women. The women with fatty liver disease had a significantly higher mean CIMT value and more plaque than the women with normal livers. The differences between the men with fatty liver and those with normal livers in mean CIMT values and in the prevalence of plaque were not significant. In the women, multivariate analysis showed that fatty liver disease was independently associated with subclinical atherosclerosis [adjusted hazards ratio (HR) 1.65, 95% confidence interval (CI) 1.007–2.697, p = 0.047]. Conclusions The men had more fatty liver disease, carotid plaque and higher CIMT values than the women. Fatty liver disease was a useful predictor of atherosclerosis, especially for the female study patients. PMID:26972662

  20. 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 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 range...... 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....

  1. Diagnostic criteria for acute liver failure due to Wilson disease

    Institute of Scientific and Technical Information of China (English)

    Christoph Eisenbach; Olivia Sieg; Wolfgang Stremmel; Jens Encke; Uta Merle

    2007-01-01

    AIM: To describe the diagnostic criteria for acute liver failure due to Wilson disease (WD), which is an uncommon cause of acute liver failure (ALF).METHODS: We compared findings of patients presenting with ALF due to WD to those with ALF of other etiologies.RESULTS: Previously described criteria, such as low alkaline phosphatase activity, ratio of low alkaline phosphatase to total bilirubin or ratio of high aspartate aminotransferase (AST) to alanine aminotransferase (ALT), failed to identify patients with ALF due to WD. There were significant differences in low ALT and AST activities (53 ± 43 vs 1982 ± 938, P < 0.0001 and 87 ± 44 vs 2756 ± 2941, P = 0.037, respectively), low choline esterase activity (1.79 ± 1.2 vs 4.30 ± 1.2, P = 0.009), high urine copper concentrations (93.4 ± 144.0 vs 3.5 ± 1.8, P = 0.001) and low hemoglobin (7.0 ± 2.2 vs 12.6 ± 1.8, P < 0.0001) in patients with ALF caused by WD as compared with other etiologies. Interestingly, 4 of 7 patients with ALF due to WD survived without liver transplantation.CONCLUSION: In ALF, these criteria can help establish a diagnosis of WD. Where applicable, slit-lamp examination for presence of Kayser-Fleischer rings and liver biopsy for determination of hepatic copper concentration still remain important for the diagnosis of ALF due to WD. The need for liver transplantation should be evaluated carefully as the prognosis is not necessarily fatal.

  2. Regenerative medicine using dental pulp stem cells for liver diseases

    Science.gov (United States)

    Ohkoshi, Shogo; Hara, Hajime; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko

    2017-01-01

    Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review. PMID:28217369

  3. Probiotics in Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Cirrhosis.

    Science.gov (United States)

    Qamar, Amir A

    2015-01-01

    With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.

  4. Epidemiology of Hepatitis B and Associated Liver Diseases in China

    Institute of Scientific and Technical Information of China (English)

    Yao Zhang; Hua Zhang; Au Elizabeth; Xiao-qing Liu

    2012-01-01

    Hepatitis B virus (HBV) infection has long been a critical public health challenge in China.National surveys revealed a prevalence of approximate 10% for chronic HBV infection in general population.HBV has been the leading cause of chronic hepatitis,cirrhosis,and liver cancers in Chinese population and a common pathogen of acute viral hepatitis.Meanwhile,the epidemic provided important opportunities to research the natural history,public health impact,and therapeutic and preventive interventions for HBV in China.In this review,we summarized the selected key epidemiological studies since 1970s regarding HBV infection and its associated liver diseases in China,and provided considerations for future research,prevention and treatment of HBV.

  5. Noninvasive diagnosis of pediatric nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Hye Ran Yang

    2013-02-01

    Full Text Available Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

  6. Serious drug-induced liver disease secondary to ezetimibe

    Institute of Scientific and Technical Information of China (English)

    José Castellote; Javier Adza; Rosa Rota; Anna Girbau; Xavier Xiol

    2008-01-01

    Ezetimibe is the first member of a new family of lipidlowering drugs that inhibits uptake of dietary and biliary cholesterol. It was approved by the FDA in 2002for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years.Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce serious toxic hepatitis and prompt withdrawal is mandatory in case of a significant abnormality in liver testing after beginning or during treatment with ezetimibe.

  7. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  8. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Kamran Qureshi; Gary A Abrams

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality.It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR,metabolic syndrome and NAFLD.

  9. Impact of liver diseases on the development of type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Po-Shiuan Hsieh; Yen-Ju Hsieh

    2011-01-01

    The prevalence of type 2 diabetes mellitus (T2DM) is higher in patients who have liver diseases such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease and cirrhosis. It is suggested that there is a pathogenic link between the presence of T2DM and the severity of liver injury. However, evidence related to the impact of hepatic inflammation on the development of T2DM has not yet emerged. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases, the impact of liver diseases on insulin resistance and β cell dysfunction, and the potential mechanisms whereby coexistent liver diseases exacerbate the development of T2DM.

  10. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    McMahan, Rachel H; Porsche, Cara E; Edwards, Michael G; Rosen, Hugo R

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  11. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Rachel H McMahan

    Full Text Available Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1, CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  12. Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids

    DEFF Research Database (Denmark)

    Orešic, Matej; Hyötyläinen, Tuulia; Kotronen, Anna

    2013-01-01

    We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based...

  13. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    McMahan, Rachel H.; Porsche, Cara E.; Edwards, Michael G.; Rosen, Hugo R.

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease. PMID:27454769

  14. 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  

  15. CYP2E1 autoantibodies in liver diseases

    Science.gov (United States)

    Sutti, Salvatore; Rigamonti, Cristina; Vidali, Matteo; Albano, Emanuele

    2014-01-01

    Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression. PMID:25462068

  16. Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Azadeh Nabizadeh Haghighi

    2016-03-01

    Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

  17. CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

    OpenAIRE

    Cocciolillo, Sila; Parruti, Giustino; Marzio, Leonardo

    2014-01-01

    AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.

  18. Fructose, high fructose corn syrup, sucrose, and non-alcoholic liver disease

    Science.gov (United States)

    Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...

  19. Study on Antibodies to Liver Antigens in Chinese Patients with Different Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    闫惠平; 孔淑玲; WinfriedStoecker; 贺立香; 张世斌; 刘燕敏; 黄德庄; 赵春惠

    2003-01-01

    In order to observe several antibodies to liver antigens in Chinese patients with different fiver diseases and to discuss the characteristics of the autoantibodies in autoimmune liver diseases, from 1412 patients, detected by indirect immumofluoreseence (IIF) initially, 230 patients with abnormal ALT were chosen and divided into 5 groups: ① autoimmune diseases group, 42 cases: 18 with autoimmtme hepatitis (AIH), 21 with primary biliary cirrhosis (PBC), 3 with primary sclerosing cholangitis(PSC). ② HAV group, 23 cases; ③ HBV group, 70 cases; ④ HCV group, 35 cases and ⑤ Non A-Egroup, 60 cases. First, ANA, AMA, SMA, liver-kidney microsomal antibody (LKM) and so on were tested by 1/F.Then,LKM-1, fiver cytosofic-1 (LC-1), soluble liver antigen/fiver pancreas (SLA/LP) and subtype of AMA (M2) as well as ANA profile such as SS-A, SS-B and dsDNA were tested by Western blot and immtmoblot strips assay, respectively. The results were that among 1412 cases, those diagnosed as AIH, PBC and PSC accotmted for 12.7‰, 14.9‰ and 2.1‰, respectively, of the samples being tested. 2/230 with LKM-1 and 2/230 with SLA/LP were seen in individuals infected withAIH and HCV, respectively. All patients with PBC showed AMA and M2 antibodies. No specific ANA pattern was seen in AIH by 1/F but anti-actin was only found in patients with AIH. In Non A-E group, four cases were positive of AMA andM2; three had high titer of SMA and other 4 had SS-A, SS-B or dsDNA antibodies, etc. It was concluded that the detection of anti-fiver antigens, ANA profile and AMA subtypes were helpful for the diagnosis of autoimmune fiver diseases and overlap syndromes. In patients with Non A-E hepatitis, the diagnosis of PBC or AIH should be taken into consideration.

  20. Correlation between liver morphology and portal pressure in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, J H;

    1984-01-01

    destruction and both wedged hepatic vein pressure (r = 0.72, p less than 0.01) and wedged-to-free hepatic vein pressure (r = 0.67, p less than 0.02). Degree of fatty change, fibrosis, inflammation, necrosis and occurrence of Mallory bodies showed no correlation with portal pressure. After morphometrical...... volume. The present findings are in accordance with the hypothesis that elevated hepatic vascular resistance and portal pressure in alcoholic liver disease are in part determined by the severity of the hepatic architectural destruction and subsequent distorsion and compression of the efferent vein system...

  1. Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis.

    Directory of Open Access Journals (Sweden)

    Pei Lin

    Full Text Available The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD. We investigated whether 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG could reverse NAFLD induced by a high-fat diet (HFD and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

  2. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-11-14

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a "low bacterial richness" may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier ("leaky gut"), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

  3. Comparative Study of TCM Syndrome Scale for Liver Disease and Chronic Liver Disease Questionnaire Based on Assessment of Posthepatitic Cirrhosis

    Directory of Open Access Journals (Sweden)

    Hua Zhang

    2012-01-01

    Full Text Available Objective. To compare and analyze the relevance and applied value of chronic liver disease questionnaire (CLDQ and Traditional Chinese Medicine liver disease questionnaire (TCMLDQ in patients with posthepatitic cirrhosis. Methods. The data of 146 patients' scales of CLDQ and TCMLDQ which based on the characteristics of chinese medical symptoms were collected. We made comparative analysis of the relationship between these two scales by the linear regression model and canonical correlation method and evaluated the advantages and disadvantages of two scales about its items setting and dimension definition. Result. There is a negative correlation in total scores between the two scales and the linear regression equation: CLDQ=239.38−1.232TCMLDQ. The further canonical correlation analysis was used to analyze the two extracted canonical correlative variables with significances (P<0.05, and the results showed that the overall negative correlation between the two scales mainly came from contributions of both the four dimensions of TCMLDQ (CS, GSYX, GYPX, and OS and the five dimensions of CLDQ (AS, FA, SS, AC, and EF. Conclusion. These two scales have good consistency in the evaluation of severity and life quality of liver cirrhosis patients, so we suggested that TCMLDQ can be used to evaluate the severity and life quality of patients with posthepatitic cirrhosis.

  4. Highly active antiretroviral therapy and changing spectrum of liver diseases in HIV infected patients

    OpenAIRE

    Kavita S. Joshi; Rohit R. Shriwastav

    2016-01-01

    Background: HIV is now considered as chronic disease than a fatal disease. HIV infected individual is having normal life expectancy post highly active antiretroviral therapy (HAART) era. Liver disease is the major cause of morbidity and mortality in HIV infected patients. The objective was to study the prevalence, clinical profile of various liver diseases in HIV infected individuals on HAART and also to study aetiologies of liver involvement in HIV patients. Methods: It was a cross secti...

  5. 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.

  6. Does vitamin C deficiency promote fatty liver disease development?

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance...... se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA) in NAFLD...... in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH....

  7. [Enteral Nutritional Support in Gastrointestinal and Liver Diseases].

    Science.gov (United States)

    Kim, Eun Ran

    2015-06-01

    Nutritional support is important because malnutrition is a major contributor to increased morbidity and mortality, decreased quality of life, increased length of hospital stay, and higher healthcare costs. Patients with gastrointestinal disease are at an increased risk of nutritional deterioration due to therapeutic dietary restriction, fasting for the diagnostic tests, loss of appetite due to anorexia or altered nutritional requirement caused by the disease itself. Therefore, it is important that gastroenterologists are aware of the nutritional status of patients and plan a treatment strategy considering patient's nutritional status. Enteral nutrition is preferred to parenteral nutrition as it is more physiologic, has fewer complications, help to prevent mucosal atrophy and maintain gut barrier function, which decrease intestinal bacterial translocation. Hence, enteral nutrition has been considered to be the most effective route for nutritional support. In this article, we will review enteral nutrition (oral nutritional supplements, enteral tube feeding) as a treatment for the patients with gastrointestinal, liver and pancreatic disease at risk of malnutrition.

  8. Stem Cells in Liver Diseases and Cancer: Recent Advances on the Path to New Therapies

    OpenAIRE

    Rountree, C. Bart; Mishra, Lopa; Willenbring, Holger

    2012-01-01

    Stem cells have potential for therapy of liver diseases, but may also be involved in the formation of liver cancer. Recently, the AASLD Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation. This report summarizes...

  9. Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

  10. Cryptogenic cirrhosis: Metabolic liver disease due to insulin resistance

    Directory of Open Access Journals (Sweden)

    Binay K De

    2010-01-01

    Full Text Available Objective: Etiopathogenesis of cryptogenic cirrhosis (CC is not yet well established. Up to 20% of non-alcoholic fatty liver disease (NAFLD may progress to cirrhosis, mostly termed as cryptogenic. Insulin resistance and altered metabolic parameters form a major pathogenic link between NAFLD and CC. CC may thus be actually a metabolic liver disease. Materials and Methods: Thirty-four patients of CC and 32 patients having cirrhosis due to chronic hepatitis B (Hep B were assessed in a cross-sectional study in a tertiary hospital for insulin resistance, % β-cell activity, obesity indices, plasma glucose, lipid profiles, and many other parameters. Results: CC patients had higher homeostasis model assessment (HOMA-IR compared to Hep B group (P = 0.000016. A positive correlation between IR values and Child-Pugh score among CC patients was found ("r" = 0.87; P < 0.00001. Out of 34 CC patients, 15 (44.1% had obesity contrary to 6 (18.8% in the control group (P = 0.0022. Differences were observed in subcutaneous fat (P = 0.0022, intra-abdominal fat (P = 0.0055, waist circumference (P = 0.014, and percentage body fat (P = 0.047 between the two groups. Significant differences were observed in the levels of triglyceride, total cholesterol, and very low density lipoprotein (VLDL. Conclusion: Most of the CC patients showed significantly higher prevalence of HOMA-IR, obesity indices, and various parameters of "lipotoxicity" and metabolic syndrome, suggesting that CC may be the long-term consequence of a type of "metabolic liver disease." Further studies are required to evaluate the role of therapeutic interventions to enhance insulin sensitivity in such patients.

  11. Drug dosage recommendations in patients with chronic liver disease.

    Science.gov (United States)

    Periáñez-Párraga, Leonor; Martínez-López, Iciar; Ventayol-Bosch, Pere; Puigventós-Latorre, Francesc; Delgado-Sánchez, Olga

    2012-04-01

    Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens. A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease- was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDex-Micromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet. Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs. The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%). In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.

  12. The prevalence of nonalcoholic fatty liver disease in the Americas.

    Science.gov (United States)

    López-Velázquez, Jorge A; Silva-Vidal, Karen V; Ponciano-Rodríguez, Guadalupe; Chávez-Tapia, Norberto C; Arrese, Marco; Uribe, Misael; Méndez-Sánchez, Nahum

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem. The disease is one of the main causes of chronic liver disease worldwide and is directly linked to the increased prevalence of obesity and type 2 diabetes mellitus (T2DM) in the general population. The worldwide prevalence of NAFLD has been estimated at 20-30%, but the prevalence is unknown in the Americas because of a lack of epidemiological studies. However, given the trends in the prevalence of diabetes and obesity, the prevalence of NAFLD and its consequences are expected to increase in the near future. The aim of the present study is to present the current data on the prevalence of NAFLD in the Americas. We performed an electronic search of the main databases from January 2000 to September 2013 and identified 356 reports that were reviewed. We focused on the epidemiology and prevalence of known NAFLD risk factors including obesity, T2DM, and the metabolic syndrome (MS). The prevalence of the MS was highest in the United States, Mexico, Costa Rica, Puerto Rico, Chile, and Venezuela. In addition, Puerto Rico, Guyana, and Mexico have the highest prevalence of T2DM in the Americas, while USA has the most people with T2DM. In conclusion, the prevalence rates of NAFLD and obesity were highest in the United States, Belize, Barbados, and Mexico.

  13. MicroRNAs in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    György Baffy

    2015-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD.

  14. Non-alcoholic fatty liver disease, diet and gut microbiota.

    Science.gov (United States)

    Finelli, Carmine; Tarantino, Giovanni

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is increasing in prevalence with the worldwide epidemic of obesity and its related insulin-resistance state. Evidence for the role of the gut microbiota in energy storage and the subsequent development of obesity and some of its related diseases is now well established. More recently, a new role of gut microbiota has emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade inflammation and immune balance, it modulates dietary choline metabolism, regulates bile acid metabolism and produces endogenous ethanol. All of these factors are molecular mechanisms by which the microbiota can induce NAFLD or its progression toward overt non-alcoholic steatohepatitis. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may advantageously affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are fervently awaited.

  15. Recent advances in natural products from plants for treatment of liver diseases.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Wang, Xijun

    2013-05-01

    Liver disease is any condition that may cause liver inflammation or tissue damage and affects liver function. Natural products that are found in vegetables, fruits, plant extracts, herbs, insects, and animals, have been traditionally used for treating liver diseases. They are chemical compounds that usually have biological activities for use in drug discovery and design. Many natural products have been clinically available as potent hepatoprotective agents against commonly occurring liver diseases. This review summarizes the current progress in the basic, clinical, and translational research on natural products in treatment of various liver diseases. Furthermore, we will focus on the discovery and biological evaluation of the natural products, which shows potential as a new therapeutic agent of liver diseases.

  16. Iron and non-alcoholic fatty liver disease

    Science.gov (United States)

    Britton, Laurence J; Subramaniam, V Nathan; Crawford, Darrell HG

    2016-01-01

    The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis. PMID:27688653

  17. Role of transmethylation reactions in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, induding ours,have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism.Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn,result in serious functional consequences which include decreases in essential methylation reactions via inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase,isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteinsall of which are hallmark features of alcoholic liver injury.Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine,removes both toxic metabolites (homocysteine and S-adenosylhomocysteine), restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse.

  18. Management of non-alcoholic fatty liver disease in 2015

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There is no single pharmacologic therapy that hasbeen approved to treat nonalcoholic fatty liver diseasein the general population. The backbone of therapycurrently includes intensive lifestyle modification withestablished targets for diet and weight loss. The useof unsweetened, unfiltered coffee along with limitinghigh fructose corn syrup have emerged as beneficialdietary recommendations. The use of empiric oralhypoglycemic agents and vitamin E, however, has notbeen widely accepted. Developing bariatric surgicaltechniques are promising, but additional studies withlong-term follow up are needed before it can be widelyrecommended. Finally, liver transplantation is an increasinglyfrequent consideration once complications of endstagedisease have developed. The future treatmentof those with nonalcoholic fatty liver disease will likelyinvolve a personalized approach. The importance of thegut microbiome in mediating hepatocyte inflammationand intestinal permeability is emerging and may offeravenues for novel treatment. The study of anti-fibroticagents such as pentoxifylline and FXR agonists holdpromise and new pathways, such as hepatocyte cannabinoidreceptor antagonists are being studied. Withthe incidence of obesity and the metabolic syndromeincreasing throughout the developed world, the futurewill continue to focus on finding novel agents and newapplications of existing therapies to help prevent andto mediate the progression of nonalcoholic fatty liverdisease.

  19. Cystic fibrosis-related liver disease: a single-center experience

    Directory of Open Access Journals (Sweden)

    Paula Catarino Costa

    2011-10-01

    Full Text Available Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases. All patients had ΔF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3-15 years, revealed by hepatomegaly or hepatosplenomegaly (3 cases and/ or abnormalities of liver function tests (3 cases changes of liver ultrasound (7 cases with evidence of portal hypertension (2 cases. Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis, progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group.

  20. Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    Science.gov (United States)

    Beaton, Melanie D

    2012-06-01

    Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.

  1. Should nonalcoholic fatty liver disease be regarded as a hepatic illness only?

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino

    2007-01-01

    The highly increasing prevalence of obesity and type 2 diabetes mellitus in the general population makes nonalcoholic fatty liver disease the most common diagnosis in every-day practices. Lifestyle changes (mainly exercise withdrawal and weight gain) have probably heightened the prevalence of nonalcoholic fatty liver disease. Mortality in patients with Nonalcoholic Fatty Liver Disease is significantly higher when compared with that of the same age-gender general population.Hepatologists claim to bear a new burden, being Nonalcoholic Fatty Liver Disease strongly linked to systemic diseases.

  2. Determination of glycated hemoglobin in patients with advanced liver disease

    Institute of Scientific and Technical Information of China (English)

    Theresa Lahousen; Karin Hegenbarth; Rottraut Ille; Rainer W. Lipp; Robert Krause; Randie R. Little; Wolfgang J. Schnedl

    2004-01-01

    AIM: To evaluate the glycated hemoglobin (HbA1c)determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin.METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods.Fructosamine was determined using nitroblue tetrazolium.RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis)had HbA1c results below the non-diabetic reference range by at least one HbA1c method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA1c results were below the non-diabetic reference using at least one of the HbA1c methods.CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA1c results should be used in patients with advanced liver disease. HbA1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment.

  3. Does Vitamin C Deficiency Promote Fatty Liver Disease Development?

    Directory of Open Access Journals (Sweden)

    David Højland Ipsen

    2014-12-01

    Full Text Available Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH. The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

  4. Non-alcoholic fatty liver disease: a new epidemic in children.

    Science.gov (United States)

    Ciocca, Mirta; Ramonet, Margarita; Álvarez, Fernando

    2016-12-01

    Non-alcoholic fatty liver disease is considered one of the most common causes of liver disease in adults and children, consistent with the increased prevalence of obesity in both populations worldwide. It is a multifactorial condition involving a broad spectrum of liver diseases than range from simple steatosis to steatohepatitis, and characterized by histological findings of inflammation and fibrosis. Its pathogenesis and progression are not fully understood yet, and a more complete understanding of liver disease may aid in developing new therapies and noninvasive diagnostic tools. Liver biopsy remains the gold standard for disease staging. Although lifestyle and diet modifications are the keys in non-alcoholic fatty liver disease treatment, the development of new drugs may be promising for patients failing first-line therapy.

  5. 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.

  6. Leptospira Exposure and Patients with Liver Diseases: A Case-Control Seroprevalence Study

    Science.gov (United States)

    Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Ramos-Nevárez, Agar; Margarita Cerrillo-Soto, Sandra; Alberto Guido-Arreola, Carlos

    2016-01-01

    The seroepidemiology of Leptospira infection in patients suffering from liver disease has been poorly studied. Information about risk factors associated with infection in liver disease patients may help in the optimal planning of preventive measures. We sought to determine the association of Leptospira IgG seroprevalence and patients with liver diseases, and to determine the characteristics of the patients with Leptospira exposure. We performed a case-control study of 75 patients suffering from liver diseases and 150 age- and gender-matched control subjects. Diagnoses of liver disease included liver cirrhosis, steatosis, chronic hepatitis, acute hepatitis, and amoebic liver abscess. Sera of participants were analyzed for the presence of anti- Leptospira IgG antibodies using a commercially available enzyme immunoassay. Anti-Leptospira IgG antibodies were found in 17 (22.7%) of 75 patients and in 15 (10.0%) of 150 control subjects (OR = 2.32; 95% CI: 1.09-4.94; P=0.03). This is the first age- and gender-matched case control study about Leptospira seroprevalence in patients with liver diseases. Results indicate that Leptospira infection is associated with chronic and acute liver diseases. Results warrants for additional studies on the role of Leptospira exposure in chronic liver disease. PMID:27493589

  7. Successful treatment of fulminant Wilson's disease without liver transplantation.

    Science.gov (United States)

    Motobayashi, Mitsuo; Fukuyama, Tetsuhiro; Nakayama, Yoshiko; Sano, Kenji; Noda, Shunsuke; Hidaka, Yoshihiko; Amano, Yoshiro; Ikeda, Shu-Ichi; Koike, Kenichi; Inaba, Yuji

    2014-06-01

    Fulminant Wilson's disease (WD) is life-threatening. The revised WD prognostic index (RWPI) has been used to predict the severity of the disease, with a score ≥11 indicating fatal outcome without liver transplantation (LTx). We here report the case of a 10-year-old female patient with fulminant WD (RWPI, 16) who recovered fully after plasma exchange and continuous hemodiafiltration, followed by treatment with copper chelate agents. To the best of our knowledge, there have been five fulminant WD patients with RWPI ≥ 11 including the present patient, in whom LTx was not done. Based on the therapeutic modalities in these five cases, non-surgical treatment (blood purification and copper chelate agents) may be able to avoid LTx in fulminant WD even with very high RWPI, although preparation for LTx is necessary.

  8. Gene therapy: Regulations, ethics and its practicalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Xi Jin; Yi-Da Yang; You-Ming Li

    2008-01-01

    Gene therapy is a new and promising approach which opens a new door to the treatment of human diseases.By direct transfer of genetic materials to the target cells, it could exert functions on the level of genes and molecules. It is hoped to be widely used in the treatment of liver disease, especially hepatic tumors by using different vectors encoding the aim gene for anti-tumor activity by activating primary and adaptive immunity,inhibiting oncogene and angiogenesis. Despite the huge curative potential shown in animal models and some pilot clinical trials, gene therapy has been under fierce discussion since its birth in academia and the public domain because of its unexpected side effects and ethical problems. There are other challenges arising from the technique itself like vector design, administration route test and standard protocol exploration. How well we respond will decide the fate of gene therapy clinical medical practice.

  9. Copper metabolic defects and liver disease: environmental aspects.

    Science.gov (United States)

    Pankit, Anand N; Bhave, Sheila A

    2002-12-01

    Copper (Cu) is an essential trace element for many biological processes. Cu homeostasis is generally well maintained by inbuilt controls in intestinal absorption, biliary excretion and intrahepatic storage. Copper deficiency disorders are rare. Acute Cu toxicity occurs occasionally in accidental poisoning with Cu sulfate. Chronic Cu toxicity in the form of liver cirrhosis and damage to other organs is seen classically in Wilson's Disease (genetic abnormality of Cu metabolism) and in the presumed environmental disorder Indian Childhood Cirrhosis (ICC). The clinical, epidemiological and treatment aspects of ICC are described. The evidence linking ICC to environmental Cu is (i) greatly increased hepatic Cu; (ii) early introduction of Cu contaminated milk boiled or stored in brass vessels; (iii) dramatic decline in ICC throughout the country coincident with change in feeding vessels; and (iv) continued long-term remission in d-penicillamine-treated patients after withdrawal of the drug. The nature and role of a second factor in the causation of ICC remains unclear, although a genetic predisposition is strongly suspected. Scattered reports of an ICC-like illness from the West (Idiopathic Cu Toxicosis, Endemic Tyrolean Infantile Cirrhosis), suggest that different mechanisms (environmental, genetic or both) can lead to the same end stage liver disease-'ecogenetic' disorders.

  10. Dietary approach in the treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Silvia; Marinho; Ferolla; Luciana; Costa; Silva; Maria; de; Lourdes; Abreu; Ferrari; Aloísio; Sales; da; Cunha; Flaviano; dos; Santos; Martins; Cláudia; Alves; Couto; Teresa; Cristina; Abreu; Ferrari

    2015-01-01

    Nonalcoholic fatty liver disease(NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome(MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis(NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.

  11. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States,nonalcoholic fatty liver disease (NAFLD) has inevitablybecome a very prevalent chronic liver disease and isnow emerging as one of the leading indications for livertransplantation. Insulin resistance and derangementof lipid metabolism, accompanied by activation ofthe pro-inflammatory response and fibrogenesis, areessential pathways in the development of the moreclinically significant form of NAFLD, known as nonalcoholicsteatohepatitis (NASH). Recent advances inthe functional characterization of bile acid receptors,such as farnesoid X receptor (FXR) and transmembraneG protein-coupled receptor (TGR) 5, have providedfurther insight in the pathophysiology of NASH andhave led to the development of potential therapeutictargets for NAFLD and NASH. Beyond maintaining bileacid metabolism, FXR and TGR5 also regulate lipidmetabolism, maintain glucose homeostasis, increaseenergy expenditure, and ameliorate hepatic inflammation.These intriguing features have been exploitedto develop bile acid analogues to target pathways inNAFLD and NASH pathogenesis. This review providesa brief overview of the pathogenesis of NAFLD andNASH, and then delves into the biological functions ofbile acid receptors, particularly with respect to NASHpathogenesis, with a description of the associatedexperimental data, and, finally, we discuss the prospectsof bile acid analogues in the treatment of NAFLD andNASH.

  12. Still's Disease in a Pediatric Patient after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Juan-Carlos Meza

    2013-01-01

    Full Text Available Still's disease (SD is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

  13. 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.

  14. Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation

    Institute of Scientific and Technical Information of China (English)

    Ajay Duseja; Naveen Kaita; Ashim Das; Radha Krishan Dhiman; Yogesh Kumar Chawla; Reena Das; Sanjay Bhadada; Ravinder Sialy; Kiran Kumar Thumburu; Anil Bhansali

    2007-01-01

    @@ TO THE EDITOR We read with great interest the article, "Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians" by Madan et al in the recent issue of WJG. Twenty-eight (55%) out of 51 patients with nonalcoholic fatty liver disease (NAFLD) who presented with abnormal transaminases had histological evidence of nonalcoholic steatohepatitis (NASH).

  15. Studies on bile acid and bilirubin in liver diseases Part 2. Clinical significance of serum bilirubin sulfate in various liver diseases

    OpenAIRE

    石川, 泰祐

    1980-01-01

    The clinical significance of serum bilirubin sulfate, one of the direct bilirubin, was evaluated in various liver diseases with over 2 mg/dl of serum bilirubin concentration. The diagnosis included 25 cases of acute hepatitis, 8 cases of chronic hepatitis, 8 cases of liver cirrhosis and 16 cases of liver cirrhosis with hepatoma. Bilirubin sulfate was fractioned by Yonei's solvent partition method. The clinical significance of bilirubin sulfate was assessed by comparison of bilirubin sulfate w...

  16. 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.

  17. Gross hepatomegaly due to ‘minimal change’ liver disease in a young female alcoholic

    OpenAIRE

    Majumdar, Sisir K.; Shaw, G K; Aps, E. J.; Thomson, Allan D.; O Gorman, P.; Bugler, J.

    1982-01-01

    The case of a grossly enlarged liver due to alcohol excess in a woman of 21 is reported. This case further demonstrates that a chronic alcoholic can have gross hepatomegaly with normal histology and normal liver function tests. The possible pathogenetic basis of ethanol-induced hepatomegaly (‘minimal change’ liver disease) is discussed.

  18. Association between noninvasive fibrosis markers and chronic kidney disease among adults with nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Giorgio Sesti

    Full Text Available Evidence suggests that nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are associated with an increased risk of chronic kidney disease (CKD. In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To this end NAFLD fibrosis score and estimated glomerular filtration rate (eGFR were assessed in 570 White individuals with ultrasonography-diagnosed NAFLD. As compared with subjects at low probability of liver fibrosis, individuals at high and intermediate probability showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein, fibrinogen, uric acid and lower insulin-like growth factor-1 levels. Individuals at high and intermediate probability of liver fibrosis have lower eGFR after adjustment for gender, smoking, glucose tolerance status, homeostasis model assessment index of insulin resistance (HOMA-IR index, diagnosis of metabolic syndrome, statin therapy, anti-diabetes and anti-hypertensive treatments (P = 0.001. Individuals at high probability of liver fibrosis had a 5.1-fold increased risk of having CKD (OR 5.13, 95%CI 1.13-23.28; P = 0.03 as compared with individuals at low probability after adjustment for age, gender, and BMI. After adjustment for glucose tolerance status, statin therapy, and anti-hypertensive treatment in addition to gender, individuals at high probability of liver fibrosis had a 3.9-fold increased risk of CKD (OR 3.94, 95%CI 1.11-14.05; P = 0.03 as compared with individuals at low probability. In conclusion, advanced liver fibrosis, determined by noninvasive fibrosis markers, is associated with CKD independently from other known factors.

  19. Cardiovascular disease risk factors in patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Novaković Tatjana

    2013-01-01

    Full Text Available Introduction. Clinical, epidemiological and biochemical studies strongly support the concept that the non-alcoholic fatty liver disease is a hepatic manifestation of the metabolic syndrome. Insulin resistance is a common factor connecting obesity, diabetes, hypertension and dyslipidemia with fatty liver and the progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. Since identification of cardiovascular risk factors is the first step in their prevention, the aim of this study was to analyze the prevalence of some risk factors in patients with fatty liver. Material and Methods. The study included 130 patients who met metabolic syndrome criteria; their demographic and anthropometric characteristics were analyzed and some clinical characteristics were determined, such as smoking habit, arterial pressure and alcohol intake. Routine biochemical analyses were carried out by a standard laboratory procedure. Hepatic steatosis was detected by the abdominal ultrasound. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to describe the metabolic syndrome. Results. The study group consisted of 72 subjects (55.38%, who had been found by ultrasound to have fatty liver, whereas the control group included 58 respondents (44.62% without pathological ultrasound findings. Differences in the number of fatty liver were highly statistically significant between the groups. The values of body mass index (33.56±6.05 vs 30.56±4.23 kg/m2; p = 0.001, glucose (6.23±0.95 vs 5.76±0.88 mmol/l; p<0.01 and cholesterol (6.66±1.30 vs 6.23±0.95; p <0.05 were significantly higher in the patients with fatty liver than in those without fatty liver. Conclusion. Our results indicate that the patients from the study group had a high percentage of cardiovascular risk factors.

  20. Management of adults