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Sample records for human alcoholic liver

  1. 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 ...

  2. 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.

  3. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  4. Human leucocyte antigens in patients with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Aldershvile, J; Dietrichson, O;

    1980-01-01

    No significant differences in the frequencies of HLA-B8, -B40, and other HLA-A, -B, and -C phenotypes were found among patients with histologically verified alcoholic cirrhosis compared with normal controls when the p values were multiplied by the number of comparisons. This was found both...... in the present study of 45 patients and in the combined data of this and three other similar studies. However, these findings do not rule out that alcoholic cirrhosis might be associated with HLA factors (for example. HLA-D/DR antigens) controlling immune responses....

  5. Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action.

    Science.gov (United States)

    de Mello, Vanessa D; Matte, Ashok; Perfilyev, Alexander; Männistö, Ville; Rönn, Tina; Nilsson, Emma; Käkelä, Pirjo; Ling, Charlotte; Pihlajamäki, Jussi

    2017-04-03

    Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m(2), type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q liver. These epigenetic alterations in NASH are linked with insulin metabolism.

  6. 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....

  7. 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....

  8. 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....

  9. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... A Life After Diagnosis Support for Chronic Illness Corporate Partnerships Interview with Kristen Hanks Liver Lowdown July ... stomach • enlarged spleen • brain disorders and coma • kidney failure • liver cancer In addition alcoholic liver disease may ...

  10. Bone marrow stem cells contribute to alcohol liver fibrosis in humans.

    Science.gov (United States)

    Dalakas, Evangelos; Newsome, Philip N; Boyle, Shelagh; Brown, Rachael; Pryde, Anne; McCall, Shonna; Hayes, Peter C; Bickmore, Wendy A; Harrison, David J; Plevris, John N

    2010-09-01

    Bone marrow-derived stem cell (BMSC) contribution to liver repair varies considerably and recent evidence suggests these cells may contribute to liver fibrosis. We investigated the mobilization and hepatic recruitment of bone marrow (BM) stem cells in patients with alcohol liver injury and their contribution to parenchymal/non-parenchymal liver cell lineages. Liver biopsies from alcoholic hepatitis (AH) patients and male patients, who received a female liver transplant and developed AH, were analyzed for BM stem cell content by fluorescence in situ hybridization and immunostaining. Y chromosome analysis was performed, along with co-staining for hepatocyte, biliary, myofibroblast, and Ki-67 markers. Blood CD34(+) levels were quantified in AH patients by flow cytometry. AH patients had increased CD34(+) cell counts in liver tissue (1.834% +/- 0.605%; P < 0.05) and in blood (0.195% +/- 0.063%; P < 0.05) as compared with matched controls (0.299% + 0.208% and 0.067% +/- 0.01%). A proportion of hepatic myofibroblasts were BM-derived (7.9%-26.8%) as deemed by the co-localization of Y chromosome/alpha-smooth muscle actin (alpha-SMA) staining. In the cross-sex liver grafts with AH, 5.025% of the myofibroblasts were co-staining for CD34, suggesting that a population of CD34(+) cells were contributing to the hepatic myofibroblast population. There was no evidence of BM contribution to hepatocyte or biliary cell differentiation, nor evidence of increased hepatocyte regeneration. Alcohol liver injury mobilizes CD34(+) stem cells into the circulation and recruits them into the liver. These BMSCs contribute to the hepatic myofibroblast population but not to parenchymal lineages and do not promote hepatocyte repair.

  11. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases.

    Science.gov (United States)

    Safaei, Akram; Arefi Oskouie, Afsaneh; Mohebbi, Seyed Reza; Rezaei-Tavirani, Mostafa; Mahboubi, Mohammad; Peyvandi, Maryam; Okhovatian, Farshad; Zamanian-Azodi, Mona

    2016-01-01

    Metabolome analysis is used to evaluate the characteristics and interactions of low molecular weight metabolites under a specific set of conditions. In cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH) the liver does not function thoroughly due to long-term damage. Unfortunately the early detection of cirrhosis, HCC, NAFLD and NASH is a clinical problem and determining a sensitive, specific and predictive novel method based on biomarker discovery is an important task. On the other hand, metabolomics has been reported as a new and powerful technology in biomarker discovery and dynamic field that cause global comprehension of system biology. In this review, it has been collected a heterogeneous set of metabolomics published studies to discovery of biomarkers in researches to introduce diagnostic biomarkers for early detection and the choice of patient-specific therapies.

  12. 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.

  13. An annual topic highlight: Alcohol and liver, 2011

    Institute of Scientific and Technical Information of China (English)

    Natalia A Osna

    2011-01-01

    An annual topic highlight: Alcohol and Liver, 2011, covers the important and new aspects of pathogenesis of alcoholic liver diseases (ALD). It includes broad topics ranging from the exacerbation of ALD by infectious (viral) agents (hepatitis C virus and human immunodeficiency virus) to the influence of alcohol on liver fibrogenesis, lipid rafts, autophagy and other aspects. This issue is recommended for both basic scientists and clinicians who are involved in alcoholic liver research.

  14. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Kostrzewski, Tomasz; Cornforth, Terri; Snow, Sophie A; Ouro-Gnao, Larissa; Rowe, Cliff; Large, Emma M; Hughes, David J

    2017-01-01

    AIM To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factor-binding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantly reduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known anti-steatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium. CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. PMID:28127194

  15. Alcohol and aldehyde dehydrogenases: structures of the human liver enzymes, functional properties and evolutionary aspects.

    Science.gov (United States)

    Jörnvall, H; Hempel, J; von Bahr-Lindström, H; Höög, J O; Vallee, B L

    1987-01-01

    All three types of subunit of class I human alcohol dehydrogenase have been analyzed both at the protein and cDNA levels, and the structures of alpha, beta 1, beta 2, gamma 1, and gamma 2 subunits are known. The same applies to class II pi subunits. Extensive protein data are also available for class III chi subunits. In the class I human isozymes, amino acid exchanges occur at 35 positions in total, with 21-28 replacements between any pair of the alpha/beta/gamma chains. These values, compared with those from species differences between the corresponding human and horse enzymes, suggest that isozyme developments in the class I enzyme resulted from separate gene duplications after the divergence of the human and equine evolutionary lines. All subunits exhibit some unique properties, with slightly closer similarity between the human gamma and horse enzyme subunits and somewhat greater deviations towards the human alpha subunit. Differences are large also in segments close to the active site zinc ligands and other functionally important positions. Species differences are distributed roughly equally between the two types of domain in the subunit, whereas isozyme differences are considerably more common in the catalytic than in the coenzyme-binding domain. These facts illustrate a functional divergence among the isozymes but otherwise similar changes during evolution. Polymorphic forms of beta and gamma subunits are characterized by single replacements at one and two positions, respectively, explaining known deviating properties. Class II and class III subunits are considerably more divergent. Their homology with class I isozymes exhibits only 60-65% positional identity. Hence, they reflect further steps towards the development of new enzymes, with variations well above the horse/human species levels, in contrast to the class I forms. Again, functionally important residues are affected, and patterns resembling those previously established for the divergently related

  16. 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 ...

  17. 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.

  18. [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.

  19. Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.

    Science.gov (United States)

    Clarke, John D; Novak, Petr; Lake, April D; Hardwick, Rhiannon N; Cherrington, Nathan J

    2017-07-01

    N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression. Human liver samples diagnosed as healthy, steatosis, and non-alcoholic steatohepatitis (NASH) were analysed for gene expression of glycosylation-related genes and for protein glycosylation using immunoblot. Genes involved in protein processing in the ER and biosynthesis of N-glycans were significantly enriched for down-regulation in NAFLD progression. Included in the down regulated N-glycan biosynthesis category were genes involved in the oligosaccharyltransferase complex, N-glycan quality control, N-glycan precursor biosynthesis, N-glycan trimming to the core, and N-glycan extension from the core. N-glycan degradation genes were unaltered in the progression to NASH. Immunoblot analysis of the uptake transporters organic anion transporting polypeptide-1B1 (OATP1B1), OATP1B3, OATP2B1, and Sodium/Taurocholate Co-transporting Polypeptide (NTCP) and the efflux transporter multidrug resistance-associated protein 2 (MRP2) demonstrated a significant loss of glycosylation following the progression to NASH. These data suggest that the loss of glycosylation of key uptake and efflux transporters in humans NASH may influence transporter function and contribute to altered drug disposition observed in NASH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis.

    Science.gov (United States)

    Koliaki, Chrysi; Szendroedi, Julia; Kaul, Kirti; Jelenik, Tomas; Nowotny, Peter; Jankowiak, Frank; Herder, Christian; Carstensen, Maren; Krausch, Markus; Knoefel, Wolfram Trudo; Schlensak, Matthias; Roden, Michael

    2015-05-05

    The association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%-40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver ("hepatic mitochondrial flexibility") at early stages of obesity-related insulin resistance, which is subsequently lost in NASH.

  1. Influence of unrecorded alcohol consumption on liver cirrhosis mortality.

    Science.gov (United States)

    Lachenmeier, Dirk W; Monakhova, Yulia B; Rehm, Jürgen

    2014-06-21

    Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans (e.g., cosmetics containing alcohol). The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality. Compounds besides ethanol have been hypothesized as being responsible for this observation. On the other hand, chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds. However, illegally produced spirits regularly contain higher percentages of alcohol (above 45% by volume), but for considerably less costs compared with licit beverages, potentially causing more problematic patterns of drinking. In this review, it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates. Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking. It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits (e.g., higher levels of certain contaminants in home-produced products) and liver toxicity on a population scale. Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine, which were reported to be consumed as surrogate alcohol in Russia, leading to an outbreak of acute cholestatic liver injury, histologically different from conventional alcoholic liver disease.

  2. A meta-analysis of HLA-antigen prevalences in alcoholics and alcoholic liver disease

    DEFF Research Database (Denmark)

    List, S; Gluud, C

    1994-01-01

    In the search for genetic factors influencing susceptibility to the development of alcoholism and alcoholic liver disease, 28 studies have been published analysing the distribution of human leucocyte antigens (HLA) in alcoholics compared to healthy controls. A number of HLA-phenotypes has been...

  3. Hepatic scavenger receptor BI is associated with type 2 diabetes but unrelated to human and murine non-alcoholic fatty liver disease.

    Science.gov (United States)

    Rein-Fischboeck, Lisa; Krautbauer, Sabrina; Eisinger, Kristina; Pohl, Rebekka; Meier, Elisabeth M; Weiss, Thomas S; Buechler, Christa

    2015-11-13

    Scavenger receptor, class B type I (SR-BI) is a physiologically relevant regulator of high density lipoprotein (HDL) metabolism. Low HDL is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). Here, hepatic SR-BI expression was analyzed in human and murine NAFLD. In primary human hepatocytes NAFLD relevant factors like inflammatory cytokines, lipopolysaccharide and TGF-β did not affect SR-BI protein. Similarly, oleate and palmitate had no effect. The adipokines chemerin, adiponectin, leptin and omentin did not regulate SR-BI expression. Accordingly, hepatic SR-BI was not changed in human and murine fatty liver and non-alcoholic steatohepatits. SR-BI was higher in type 2 diabetes patients but not in those with hypercholesterolemia. The current study indicates a minor if any role of SR-BI in human and murine NAFLD.

  4. Non-alcoholic fatty liver disease

    OpenAIRE

    Neuschwander-Tetri, Brent A.

    2017-01-01

    Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. As the burden of hepatitis C abates over the next decade, non-alcoholic fatty liver disease will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation. This overview briefly summarizes the most recent data on the pathophysiology, diagnosis, and...

  5. Alcohol consumption and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    regarding per capita consumption of wine among the European countries. Also for the total consumption of alcohol, i.e. the per capita consumption of beer, wine and spirits, the hypothesis of convergence seems to hold. In the same time span the number of alcohol related diseases as e.g. liver diseases, have...... changed significantly in the same direction as the developments in alcohol consumption. The changes in the consumption levels of alcohol in general -- and wine in particular -- are influenced by many factors of which health arguments may have played a crucial role. The alcohol policies of the European...... countries have become more restrictive during the last decades. Using data on alcohol consumption, alcohol related diseases and alcohol policies of 16 European countries we discuss the questions of whether the intake of alcohol is associated with (liver) diseases. Our empirical analysis provides us...

  6. Enhanced colorectal cancer metastases in the alcohol-injured liver.

    Science.gov (United States)

    Mohr, Ashley M; Gould, John J; Kubik, Jacy L; Talmon, Geoffrey A; Casey, Carol A; Thomas, Peter; Tuma, Dean J; McVicker, Benita L

    2017-02-01

    Metastatic liver disease is a major cause of mortality in colorectal cancer (CRC) patients. Alcohol consumption is a noted risk factor for secondary cancers yet the role of alcoholic liver disease (ALD) in colorectal liver metastases (CRLM) is not defined. This work evaluated tumor cell colonization in the alcoholic host liver using a novel preclinical model of human CRC liver metastases. Immunocompromised Rag1-deficient mice were fed either ethanol (E) or isocaloric control (C) diets for 4 weeks prior to intrasplenic injection of LS174T human CRC cells. ALD and CRLM were evaluated 3 or 5 weeks post-LS174T cell injection with continued C/E diet administration. ALD was confirmed by increased serum transaminases, hepatic steatosis and expression of cytochrome P4502E1, a major ethanol-metabolizing enzyme. Alcohol-mediated liver dysfunction was validated by impaired endocytosis of asialoorosomucoid and carcinoembryonic antigen (CEA), indicators of hepatocellular injury and progressive CRC disease, respectively. Strikingly, the rate and burden of CRLM was distinctly enhanced in alcoholic livers with metastases observed earlier and more severely in E-fed mice. Further, alcohol-related increases (1.5-3.0 fold) were observed in the expression of hepatic cytokines (TNF-α, IL-1 beta, IL-6, IL-10) and other factors noted to be involved in the colonization of CRC cells including ICAM-1, CCL-2, CCL-7, MMP-2, and MMP-9. Also, alcoholic liver injury was associated with altered hepatic localization as well as increased circulating levels of CEA released from CRC cells. Altogether, these findings indicate that the alcoholic liver provides a permissive environment for the establishment of CRLM, possibly through CEA-related inflammatory mechanisms.

  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. Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease)

    DEFF Research Database (Denmark)

    Buzzetti, Elena; Kalafateli, Maria; Thorburn, Douglas

    2017-01-01

    trials (irrespective of language, blinding, or publication status) including participants with alcohol-related liver disease. We excluded trials that included participants who had previously undergone liver transplantation and those with co-existing chronic viral diseases. We considered any...... and follow-up of one to two years in order to compare the benefits and harms of different treatments in people with alcoholic hepatitis. Randomised clinical trials should include health-related quality of life and report serious adverse events separately from adverse events. Future randomised clinical trials......BACKGROUND: Alcohol-related liver disease is due to excessive alcohol consumption. It includes a spectrum of liver diseases such as alcohol-related fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Mortality associated with alcoholic hepatitis is high. The optimal pharmacological treatment...

  9. 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

  10. 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...

  11. 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.

  12. 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.

  13. 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....

  14. 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....

  15. 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.

  16. Alcohol consumption and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    on the relationship between liver cirrhosis mortality and alcohol consumption is included. The conclusion is that the total level of alcohol consumption as well as the specific beverages - beer, wine and spirits - contributes to liver cirrhosis mortality, but the present study also reveals that directly addressing......Empirical evidence gives strong support to a close association between liver cirrhosis mortality and the intake of alcohol and most often a log-linear relationship is assumed in the econometric modeling. The present analysis investigates for unit roots in a panel data set for sixteen European...... countries - covering the period 1970-2006 - where both alcohol consumption and liver cirrhosis seem best described as trend-stationary variables. Therefore a fixed effects model including individual trends is applied in the analysis but also a more flexible non-linear functional form with fewer restrictions...

  17. Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.

    Science.gov (United States)

    Zakhari, Samir

    2013-08-01

    Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy.

  18. 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.

  19. 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.

  20. Pediatric Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Haley Bush; Pegah Golabi; Younossi, Zobair M.

    2017-01-01

    Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH) are at increased risk of developing advanced stages of liver disease. It h...

  1. 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.

  2. [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.

  3. 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.

  4. Non-alcoholic fatty liver disease.

    Science.gov (United States)

    Neuschwander-Tetri, Brent A

    2017-02-28

    Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. As the burden of hepatitis C abates over the next decade, non-alcoholic fatty liver disease will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation. This overview briefly summarizes the most recent data on the pathophysiology, diagnosis, and treatment of non-alcoholic fatty liver disease. Ongoing clinical trials are focused on an array of disease mechanisms and reviewed here are how these treatments fit into the current paradigm of substrate overload lipotoxic liver injury. Many of the approaches are directed at downstream events such as inflammation, injury and fibrogenesis. Addressing more proximal processes such as dysfunctional satiety mechanisms and inappropriately parsimonious energy dissipation are potential therapeutic opportunities that if successfully understood and exploited would not only address fatty liver disease but also the other components of the metabolic syndrome such as obesity, diabetes and dyslipidemia.

  5. 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)...

  6. 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.

  7. Detection of alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Harriet Gordon

    2001-01-01

    @@ INTRODUCTION Alcohol has been used in society over centuries and all over the world for its mood-lifting properties and taste. It is probably ,however ,the commonest drug of abuse world-wide and unfortunately causes considerable morbidity, mortality and social disruption .In 1990 the cost tl the USA was more than $ 100 billion and 100 000 lives. The relationship between alcohol and mankind is well documented from the earliest tines .

  8. 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....

  9. 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.

  10. Liver Transplantation for Hepatitis C and Alcoholic Liver Disease

    Science.gov (United States)

    Carbone, Marco; Neuberger, James

    2010-01-01

    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. PMID:21209701

  11. 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....

  12. Studies on serum and hepatic ferritin in alcoholic liver diseases

    OpenAIRE

    杉山, 明

    1987-01-01

    The kinetics of serum ferritin were studied in 42 male patients with alcoholic liver diseases (17 with alcoholic fibrosis, 10 with alcoholic hepatitis and 15 with alcoholic cirrhosis). In addition, the chromatic reaction of biopsied liver tissue to ferritin staining (PAP method) was examined and compared with serum ferritin levels and the iron-staining data. Serum ferritin levels in patients with alcoholic liver diseases, determined immediately after abstinence, were significantly higher than...

  13. Alcoholic liver disease and pancreatitis: global health problems being addressed by the US National Institute on Alcohol Abuse and Alcoholism.

    Science.gov (United States)

    Warren, Kenneth R; Murray, Margaret M

    2013-08-01

    The review article summarizes the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with focus on the NIAAA's current and future research version for alcoholic liver disease and alcoholic pancreatitis.

  14. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

  15. 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…

  16. 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…

  17. Orthotopic Liver Transplantation for Alcoholic Cirrhosis

    Science.gov (United States)

    Starzl, Thomas E.; Van Thiel, David; Tzakis, Andreas G.; Iwatsuki, Shunzaburo; Todo, Satoru; Marsh, J. Wallis; Koneru, Babu; Staschak, Sandee; Stieber, Andrei; Gordon, Robert D.

    2010-01-01

    Fifteen patients with Laennec's cirrhosis underwent orthotopic liver transplantation between 1963 and the end of 1979. The first eight patients died perioperatively or within two months, but four of the next seven patients had long survival; three are still alive after 11 to 14 years. After the introduction of cyclosporine therapy, 41 more patients with alcoholic cirrhosis were treated with liver transplantation from 1980 to June 1987. The one-year survival is 73.2%, and, after one to three years, 28 (68%) of the recipients are living. Of the 35 patients in the combined old and new series who lived for six months or longer, only two returned to alcohol abuse. Social and vocational rehabilitation has been the rule in these recipients who were selected primarily because of urgency of need, because they or their families insisted on treatment, and because they and their families thereby committed themselves to long-standing programs of alcoholism care. PMID:3050180

  18. 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

  19. 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.

  20. Iron stores assessment in alcoholic liver disease.

    Science.gov (United States)

    Costa Matos, Luís; Batista, Paulo; Monteiro, Nuno; Ribeiro, João; Cipriano, Maria A; Henriques, Pedro; Girão, Fernando; Carvalho, Armando

    2013-06-01

    The relation between alcoholic liver disease (ALD) and iron overload is well known. Liver biopsy is the gold standard for assessing iron stores. MRI is also validated for liver iron concentration (LIC) assessment. We aimed to assess the effect of active drinking in liver iron stores and the practicability of measuring LIC by MRI in ALD patients. We measured LIC by MRI in 58 ALD patients. We divided patients into two groups - with and without active alcoholism - and we compared several variables between them. We evaluated MRI-LIC, liver iron stores grade, ferritin and necroinflammatory activity grade for significant correlations. Significant necroinflammation (40.0% vs. 4.3%), LIC (40.1 vs. 24.3 µmol/g), and ferritin (1259.7 vs. 568.7 pmol/L) were significantly higher in drinkers. LIC values had a strong association with iron stores grade (r s = 0.706). Ferritin correlated with LIC (r s = 0.615), iron stores grade (r s = 0.546), and necroinflammation (r s = 0.313). The odds ratio for elevated serum ferritin when actively drinking was 7.32. Active alcoholism is associated with increased ALD activity. It is also the key factor in iron overload. Scheuers' semiquantitative score with Perls' staining gives a fairly accurate picture of liver iron overload. Serum ferritin also shows a good correlation with LIC values and biopsy iron stores grade. As most patients present only with mild iron overload, serum ferritin measurement and semiquantitative evaluation of iron stores are adequate, considering MRI high cost. However, if MRI is required to evaluate liver structure, LIC assessment could be performed without added cost.

  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. 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.

  3. 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.

  4. Pediatric Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Haley Bush

    2017-06-01

    Full Text Available Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group.

  5. Advances in alcoholic liver disease: An update on alcoholic hepatitis.

    Science.gov (United States)

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-11-14

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory's hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey's discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline.

  6. 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.

  7. Liver proteomics in progressive alcoholic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, Harshica [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Wiktorowicz, John E.; Soman, Kizhake V. [Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Kaphalia, Bhupendra S.; Khan, M. Firoze [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Shakeel Ansari, G.A., E-mail: sansari@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-02-01

    Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber–DeCarli diet daily for 1 and 3 months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3 months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3 months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (− 1.6) at 1 month and up regulation of aldehyde dehydrogenase (2.1) at 3 months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1 month) while peroxiredoxin-1 was down regulated (− 1.5) at late fatty liver stage (3 months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified D-dopachrome tautomerase (− 1.7, at 3 months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum. -- Graphical abstract: The figure shows the Hierarchial cluster analysis of differentially expressed protein spots obtained after ethanol feeding for 1 (1–3

  8. 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.

  9. Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes.

    Science.gov (United States)

    Chi, Yu-Chou; Lee, Shou-Lun; Lai, Ching-Long; Lee, Yung-Pin; Lee, Shiao-Pieng; Chiang, Chien-Ping; Yin, Shih-Jiun

    2016-10-25

    Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex isozyme family with striking variations in kinetic function and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Their relative contributions to alcohol FPM and degrees of the inhibitions by aspirin and its metabolite salicylate, acetaminophen and cimetidine remain controversial. To address this issue, mathematical organ modeling of ethanol-oxidizing activities in target tissues and that of the ethanol-drug interactions were constructed by linear combination of the corresponding numerical rate equations of tissue constituent ADH isozymes with the documented isozyme protein contents, kinetic parameters for ethanol oxidation and the drug inhibitions of ADH isozymes/allozymes that were determined in 0.1 M sodium phosphate at pH 7.5 and 25 °C containing 0.5 mM NAD(+). The organ simulations reveal that the ADH activities in mucosae of the stomach, duodenum and jejunum with ADH1C*1/*1 genotype are less than 1%, respectively, that of the ADH1B*1/*1-ADH1C*1/*1 liver at 1-200 mM ethanol, indicating that liver is major site of the FPM. The apparent hepatic KM and Vmax for ethanol oxidation are simulated to be 0.093 ± 0.019 mM and 4.0 ± 0.1 mmol/min, respectively. At 95% clearance in liver, the logarithmic average sinusoidal ethanol concentration is determined to be 0.80 mM in accordance with the flow-limited gradient perfusion model. The organ simulations indicate that higher therapeutic acetaminophen (0.5 mM) inhibits 16% of ADH1B*1/*1 hepatic ADH activity at 2-20 mM ethanol and that therapeutic salicylate (1.5 mM) inhibits 30-31% of the ADH1B*2/*2 activity, suggesting potential significant inhibitions of ethanol FPM in these allelotypes. The result provides systematic evaluations and predictions by computer simulation on potential ethanol FPM in target tissues and hepatic

  10. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials.

    Science.gov (United States)

    Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-06-13

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  11. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Jiang, Weiwei; Wu, Na; Wang, Xuemei; Chi, Yujing; Zhang, Yuanyuan; Qiu, Xinyun; Hu, Ying; Li, Jing; Liu, Yulan

    2015-02-03

    Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-α, IL-6 and IFN-γ were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD.

  12. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    Maria Jose Sáez-Lara

    2016-06-01

    Full Text Available The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS, type 2 diabetes (T2D and non-alcoholic fatty liver disease (NAFLD in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

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

    Institute of Scientific and Technical Information of China (English)

    Cheng Ji; Neil Kaplowitz

    2004-01-01

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

  14. Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis?

    Science.gov (United States)

    Lonardo, Amedeo; Loria, Paola

    2002-04-01

    Colchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications.

  15. Alcohol consumption and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    Since the 1960s wine consumption has decreased dramatically in especially the Southern European countries whereas the countries in the northern parts of Europe have experienced a substitution from beer and spirits toward wines. In this sense there has been a process of convergence taking place re...... with strong evidence of a significantly positive relationship between alcohol consumption and the development in liver diseases; this is in accordance with many other micro studies.......Since the 1960s wine consumption has decreased dramatically in especially the Southern European countries whereas the countries in the northern parts of Europe have experienced a substitution from beer and spirits toward wines. In this sense there has been a process of convergence taking place...... regarding per capita consumption of wine among the European countries. Also for the total consumption of alcohol, i.e. the per capita consumption of beer, wine and spirits, the hypothesis of convergence seems to hold. In the same time span the number of alcohol related diseases as e.g. liver diseases, have...

  16. Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems

    DEFF Research Database (Denmark)

    Askgaard, Gro; Leon, David A; Kjaer, Mette S

    2017-01-01

    cirrhosis in these patients relative to the general population. Age and alcohol diagnosis were significant predictors of alcoholic liver cirrhosis risk in men and women, whereas civil status, education, and type of hospital care were not. In men, the 15-year absolute risk was 0.7% (95%CI 0.4, 0.8) for 20......Alcoholic liver cirrhosis is usually preceded by many years of heavy drinking, in which cessation in drinking could prevent the disease. Alcohol problems are not consistently managed in hospital patients. We followed all Danish patients with an initial hospital contact with alcohol problems...... (intoxication, harmful use, or dependence) during 1998-2002 for alcoholic liver cirrhosis development (n = 36,044). In this registry-based cohort we identified predictors of the absolute risk for alcoholic liver cirrhosis. Incidence rate ratios (IRR) were estimated as the incidence rate of alcoholic liver...

  17. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    The majority of liver fibrosis and liver cirrhosis cases in the Western World is caused by alcohol and hepatotoxic viruses. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients...... with alcoholic as well as non-alcoholic fibrosis and cirrhosis....

  18. [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.

  19. 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....

  20. 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....

  1. Peritoneoscopy of alcoholic liver cirrhosis in comparison with non-alcoholic liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Kitadai,Masahiro

    1985-04-01

    Full Text Available Peritoneoscopic findings of 39 patients with alcoholic liver cirrhosis (ALC were compared with those of 95 patients with non-alcoholic liver cirrhosis (NALC. They were selected from 245 patients with liver cirrhosis subjected to peritoneoscopy in the 7 year period from 1975 to 1981. Out of the 95 NALC patients, 24 had hepatitis B surface antigen. The ALC patients had nodules which varied in size (61%, large depressions (69%, and a markedly rounded edge of the liver (33% more often than NALC patients (18, 43 and 3%, respectively. Nodularity differed between the right and left lobes in ALC (41% more often than in NALC (16%. Interstitial reddish markings and patchy nodules were, however, more frequent in NALC (51 and 28%, respectively than in ALC (8 and 5%, respectively. Lymphatic vesicles were observed both in ALC (85% and NALC (78%. In conclusion, the peritoneoscopic features which suggested ALC were the coexistence of nodules of various sizes, large depressions and a markedly dull edge of the liver. Interstitial reddish markings and patchy nodules were more indicative of NALC than ALC.

  2. Alcohol, carcinoembryonic antigen processing and colorectal liver metastases.

    Science.gov (United States)

    McVicker, Benita; Tuma, Dean J; Lazure, Kathryn E; Thomas, Peter; Casey, Carol A

    2015-01-01

    It is well established that alcohol consumption is related to the development of alcoholic liver disease. Additionally, it is appreciated that other major health issues are associated with alcohol abuse, including colorectal cancer (CRC) and its metastatic growth to the liver. Although a correlation exists between alcohol use and the development of diseases, the search continues for a better understanding of specific mechanisms. Concerning the role of alcohol in CRC liver metastases, recent research is aimed at characterizing the processing of carcinoembryonic antigen (CEA), a glycoprotein that is associated with and secreted by CRC cells. A positive correlation exists between serum CEA levels, liver metastasis, and alcohol consumption in CRC patients, although the mechanism is not understood. It is known that circulating CEA is processed primarily by the liver, first by nonparenchymal Kupffer cells (KCs) and secondarily, by hepatocytes via the asialoglycoprotein receptor (ASGPR). Since both KCs and hepatocytes are known to be significantly impacted by alcohol, it is hypothesized that alcohol-related effects to these liver cells will lead to altered CEA processing, including impaired asialo-CEA degradation, resulting in changes to the liver microenvironment and the metastatic potential of CRC cells. Also, it is predicted that CEA processing will affect cytokine production in the alcohol-injured liver, resulting in pro-metastatic changes such as enhanced adhesion molecule expression on the hepatic sinusoidal endothelium. This chapter examines the potential role that alcohol-induced liver cell impairments can have in the processing of CEA and associated mechanisms involved in CEA-related colorectal cancer liver metastasis.

  3. Alcoholic liver injury:Influence of gender and hormones

    Institute of Scientific and Technical Information of China (English)

    Patricia; K; Eagon

    2010-01-01

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

  4. [Non-alcoholic fatty liver disease in children and adolescents].

    Science.gov (United States)

    Björklund, Jessica; Laursen, Tea Lund; Kazankov, Konstantin; Thomsen, Karen Louise; Hamilton-Dutoit, Stephen; Stenbøg, Elisabeth; Grønbæk, Henning

    2017-07-03

    Non-alcoholic fatty liver disease (NAFLD) is characterized by liver fat accumulation and non-alcoholic steatohepatitis (NASH) with inflammation and fibrosis, which may lead to cirrhosis also in childhood. NAFLD/NASH in children are related to obesity and the metabolic syndrome, and incidence and prevalence are expected to increase. Children having liver steatosis and elevated liver enzymes are most often asymptomatic, and a liver biopsy is necessary for correct diagnosis and staging. The treatment should focus on lifestyle changes, as pharmacological therapy needs further evaluation.

  5. Alcohol Intake, Alcohol Dehydrogenase Genotypes, and Liver Damage and Disease in the Danish General Population

    DEFF Research Database (Denmark)

    Tolstrup, Janne S; Grønbæk, Morten; Tybjærg-Hansen, Anne

    2009-01-01

    OBJECTIVES:We tested the hypothesis that alcohol, alone and in combination with alcohol dehydrogenase (ADH) 1B and ADH1C genotypes, affects liver damage and disease in the general population.METHODS:Information on alcohol intake and on liver disease was obtained from 9,080 men and women from...... volume.RESULTS:Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were 0.......9 (95% confidence interval (CI), 0.6-1.4), 1.4 (0.8-2.5), 1.8 (0.9-3.5), and 4.1 (2.5-7.0) for an alcohol intake of 1-13, 14-20, 21-27, and >/=28 drinks per week, respectively, compared with drinking alcoholic liver cirrhosis...

  6. Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Gronbaek, M.; Tybjaerg-Hansen, A.

    2009-01-01

    OBJECTIVES: We tested the hypothesis that alcohol, alone and in combination with alcohol dehydrogenase (ADH) 1B and ADH1C genotypes, affects liver damage and disease in the general population. METHODS: Information on alcohol intake and on liver disease was obtained from 9,080 men and women from...... volume. RESULTS: Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were...... 0.9 (95% confidence interval (CI), 0.6-1.4), 1.4 (0.8-2.5), 1.8 (0.9-3.5), and 4.1 (2.5-7.0) for an alcohol intake of 1-13, 14-20, 21-27, and > or = 28 drinks per week, respectively, compared with drinking alcoholic liver...

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

    Directory of Open Access Journals (Sweden)

    Yipeng Wang

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

  8. 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.

  9. 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.

  10. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Alcohol and hepatotropic viruses cause the majority of liver cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic or non-alcoholic...

  11. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, P;

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis....

  12. Alcohol drinking pattern and risk of alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Askgaard, Gro; Grønbæk, Morten; Kjær, Mette Skalshøi

    2015-01-01

    BACKGROUND & AIMS: Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS: We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993......-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. RESULTS......: We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50...

  13. 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...

  14. 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

  15. 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...

  16. Liver alcohol dehydrogenase immobilized on polyvinylidene difluoride.

    Science.gov (United States)

    Roig, M G; Bello, J F; Moreno de Vega, M A; Cachaza, J M; Kennedy, J F

    1990-01-01

    A physical method for immobilization of liver alcohol dehydrogenase (ADH) by hydrophobic adsorption onto a supporting membrane of polyvinylidene difluoride (PVDF) was performed. Simultaneously, a physicochemical characterization of the immobilized enzyme regarding its kinetic behaviour was performed. The activity/pH profile observed points to an effect of pH on activity that is completely different from the case of ADH in solution. The disturbance in the typical bell-shaped profile owing to the fact that the enzyme was immobilized is explained on the basis of a potent limitation to the diffusion of the protons in the support. The findings of the present work also reveal the existence of an effect that limits free external diffusion of the substrate towards and/or the product from the support; this effect seems to be the determinant of the overall rate of the enzymatic reaction and is thus of great importance in the effective kinetic behaviour (v([S])) of immobilized ADH, whose kinetic behaviour is complex (non-Michaelian), as may be seen from the lack of linearity observed in the corresponding double reciprocal and Eadie-Hofstee plots. By non-linear regression numerical analysis of the v([S]) data and application of the F-test for model discrimination, the minimum rate equation necessary to describe the intrinsic kinetic behaviour of PVDF-immobilized ADH proved to be one of the polynomial quotient type of degree 2:2 (in substrate concentration).

  17. Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease

    DEFF Research Database (Denmark)

    Pavlov, Chavdar S; Casazza, Giovanni; Semenistaia, Marianna

    2016-01-01

    system, and the endocrine and immune system, and can lead to cancer. Liver damage in turn, can present as multiple alcoholic liver diseases, including fatty liver, steatohepatitis, fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma, with presence or absence of hepatitis B or C virus infection......, but people in whom hepatocellular carcinoma has developed are often co-infected with hepatitis B or C virus.Abstinence from alcohol may help people with alcoholic disease in improving their prognosis of survival at any stage of their disease; however, the more advanced the stage, the higher the risk...... biopsy as reference standard.To determine the diagnostic accuracy of any of the ultrasonography tests, B-mode or echo-colour Doppler ultrasonography, used singly or combined, or plus ultrasonography signs, or a combination of these, for detecting hepatic cirrhosis in people with alcoholic liver disease...

  18. 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

  19. [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.

  20. 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...

  1. Alcoholic pancreatitis:Lessons from the liver

    Institute of Scientific and Technical Information of China (English)

    Dahn; L; Clemens; Katrina; J; Mahan

    2010-01-01

    The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals w...

  2. Detection of alcohol consumption in patients with alcoholic liver cirrhosis during the evaluation process for liver transplantation.

    Science.gov (United States)

    Hempel, Johann-Martin; Greif-Higer, Gertrud; Kaufmann, Thomas; Beutel, Manfred E

    2012-11-01

    Alcoholic liver cirrhosis (ALC) is a commonly accepted indication for liver transplantation (LT). Any alcohol consumption is considered a contraindication for LT. However, the assessment of abstinence in everyday practice mostly relies on patient self-reporting, which must be considered highly unreliable. After consumption, ethanol is eliminated by alcohol dehydrogenase, with methanol accumulating in the blood. Methanol, which is known to be a sensitive and specific indicator for recent alcohol consumption, has not been used for verifying alcohol consumption in LT assessments yet. Therefore, the purpose of this study was to test the feasibility of using methanol testing to identify recent alcohol consumption in LT candidates during routine and short-notice appointments. We compared methanol and ethanol measurements with self-reported alcohol consumption for 41 patients with ALC during the evaluation process before they were accepted onto the waiting list. In 32 of the 92 blood samples drawn from these 41 patients during the study, a relapse was detected by the methanol test. Both the ethanol test results and the self-reported data were positive in only 3 cases. Thus, the methanol test identified 29 additional cases of alcohol consumption. Furthermore, the methanol test discovered recent alcohol consumption in 5 of 10 transplant patients when both self-reported data and ethanol test results were negative. As a part of blood alcohol analysis, the methanol test is more sensitive than self-reporting and ethanol testing for the detection of recent alcohol consumption. Also, short-notice appointments for blood alcohol analysis reveal more cases of alcohol relapse than routine, long-term appointments. The measurement of methanol as a sensitive screening test for recent alcohol consumption should be implemented both in law and in daily, routine practice. Liver Transpl 18:1310-1315, 2012. © 2012 AASLD.

  3. Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Marco Poeta; Luca Pierri; Pietro Vajro

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A ?multiple-hit? hypothesis has been invoked to explain its pathogenesis. The ?first hit? is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as ?second hits? implicated in liver damage progre...

  4. 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...

  5. Development of an Animal Model for Alcoholic Liver Disease in Zebrafish.

    Science.gov (United States)

    Lin, Jiun-Nong; Chang, Lin-Li; Lai, Chung-Hsu; Lin, Kai-Jen; Lin, Mei-Fang; Yang, Chih-Hui; Lin, Hsi-Hsun; Chen, Yen-Hsu

    2015-08-01

    Alcoholic liver disease (ALD) continues to be a major cause of liver-related morbidity and mortality worldwide. To date, no zebrafish animal model has demonstrated the characteristic manifestations of ALD in the setting of chronic alcohol exposure. The aim of this study was to develop a zebrafish animal model for ALD. Male adult zebrafish were housed in a 1% (v/v) ethanol solution up to 3 months. A histopathological study showed the characteristic features of alcoholic liver steatosis and steatohepatitis in the early stages of alcohol exposure, including fat droplet accumulation, ballooning degeneration of the hepatocytes, and Mallory body formation. As the exposure time increased, collagen deposition in the extracellular matrix was observed by Sirius red staining and immunofluorescence staining. Finally, anaplastic hepatocytes with pleomorphic nuclei were arranged in trabecular patterns and formed nodules in the zebrafish liver. Over the time course of 1% ethanol exposure, upregulations of lipogenesis, fibrosis, and tumor-related genes were also revealed by semiquantitative and quantitative real-time reverse transcription-polymerase chain reaction. As these data reflect characteristic liver damage by alcohol in humans, this zebrafish animal model may serve as a powerful tool to study the pathogenesis and treatment of ALD and its related disorders in humans.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Histomorphologic liver abnormalities in a group of alcoholic patients

    Directory of Open Access Journals (Sweden)

    Libán Álvarez Cáceres

    2010-11-01

    Full Text Available Background: the ingestion of alcohol has been directly involved in the development of liver diseases. Nowadays, the liver damage by ethanol is a serious health problem all over the world. To achieve satisfactory results In order to face it, it is necessary to provide multidisciplinary attention. Objective: to determine the histomorphologic liver impairments in alcoholic patients. Methods: an observational, descriptive, co-relational and prospective study conducted in 23 patients with an alcoholism diagnosis at the Provincial University Hospital "Arnaldo Milián Castro" in Villa Clara. Inclusion and exclusion criteria were taken into account. The variables studied were: laparoscopic evolution, period of time consuming alcohol (in years, histologic evolution and alanine aminotransferase. Results: both trough laparoscopic and liver biopsy, the most frequent diagnosis was steatosis, followed by chronic hepatitis. In one patient cirrhosis was diagnosed through laparoscopy: a biopsy was not performed in this case. Conclusion: there were a high proportion of patients with impaired liver aminotransferases and severe histological diagnoses, especially those of chronic hepatitis and liver cirrhosis.

  12. Hepatocyte oxidant stress and alcoholic liver disease

    NARCIS (Netherlands)

    Conde de la Rosa, L.; Moshage, H.; Nieto, N.

    2008-01-01

    Acute and chronic alcohol consumption increases the production of reactive oxygen species (ROS), and enhances lipid peroxidation of lipids, proteins, and DNA. The mechanism by which alcohol causes cell injury is still not clear but a major role for ROS and lipid peroxidation-end products is consider

  13. Hepatocyte oxidant stress and alcoholic liver disease

    NARCIS (Netherlands)

    Conde de la Rosa, L.; Moshage, H.; Nieto, N.

    Acute and chronic alcohol consumption increases the production of reactive oxygen species (ROS), and enhances lipid peroxidation of lipids, proteins, and DNA. The mechanism by which alcohol causes cell injury is still not clear but a major role for ROS and lipid peroxidation-end products is

  14. Is liver biopsy necessary in the management of alcoholic hepatitis?

    Science.gov (United States)

    Dhanda, Ashwin D; Collins, Peter L; McCune, C Anne

    2013-11-28

    Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accurate diagnosis. However, there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy. We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH. In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor. Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions, we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology. It also adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology. Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.

  15. NON-ALCOHOLIC FATTY LIVER DISEASE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L.V. Chistova

    2010-01-01

    Full Text Available Metabolic syndrome that represents a totality of interrelated carbohydrate metabolism and lipid disorders, as well as a mechanism regulating arterial tension and endothelium function is one of the critical issues in pediatrics. In recent years, children with metabolic syndrome are increasingly diagnosed with liver injuries symptoms that are associated with a fatty transformation of the liver [1–3]. In this case, non-alcoholic fatty liver disease (NAFLD, a liver manifestation of metabolic syndrome is diagnosed. The diagnosis is confirmed in the absence of alcohol abuse in the past medical history, virus and autoimmune liver disease markers, elimination of toxic and drug influence, as wells as disorders of copper and iron exchange in the patient’s system. One of the key risk factors for developing NAFLD in children is overeating and reduced physical activities. It was believed in the past that NAFLD is relatively benign, however, there is evidence in current literature that this is a pathological condition that may develop and result in extreme fibrotic alterations in the liver parenchymatous tissue all the way to cirrhosis and hepatocellular carcinoma [4]. Early-stage identification and timely launch of therapy for NAFLD in children represents one of the most important objectives in modern healthcare. Key words: metabolic syndrome, non-alcoholic fatty liver disease, children, steatohepatosis. (Pediatric Pharmacology. – 2010; 7(6:68-72

  16. Hepatic venous oxygen content in alcoholic cirrhosis and non-cirrhotic alcoholic liver disease

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Widding, A

    1987-01-01

    Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty-six patients (9 non-cirrhotic liver disease, 14 cirrhosis Child-Turcotte class A, 23 class B, 10 class C) and 10 control...

  17. [A clinicopathological study of primary liver cancer associated with alcoholic liver injury].

    Science.gov (United States)

    Kohgo, Y; Ohhira, M; Ono, M

    1996-04-01

    We described a clinicopathological study of primary hepatoma associated with alcoholic liver diseases without viral liver diseases. In 150 patients with primary hepatoma, 6 patients (4%) have hepatoma associated with pure alcoholic liver disease, although 143 hepatoma were associated with chronic viral liver diseases and one was with primary biliary cirrhosis. All patients were male. The diagnosis of hepatoma was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Three cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in 3 cases and liver cirrhosis was in 3 cases. Chronic infections of hepatitis B and C viruses were ruled out by assaying serum virus markers. Autoimmune hepatitis and primary biliary cirrhosis were neglected by serum autoantibody. Hemochromatosis and Wilson's disease were also excluded. Hepatocellular carcinoma was diagnosed histologically in all the cases. Serum alpha-fetoprotein and PIVKA-II were positive in patients with advanced hepatocellular carcinoma. In cases with small hepatoma, the tumor was resected surgically in two cases and percutaneous ethanol injection against hepatoma was performed in one case. In these cases with small hepatoma, the patients were alive without tumor recurrence during observation period. In advanced hepatoma, transcatheter arterial infusion of anticancer agent was performed in two cases and no therapy was performed due to poor general condition in one case. One case was alive with recurrent hepatoma for 27 months, during which a therapy was repeated five times. Other 2 cases were died. The clinicopathological features of hepatoma associated with alcoholic liver disease were essentially same as those associated with chronic viral infection, although the incidence of hepatoma in alcoholic liver disease was lower than in viral liver disease. The mechanism of hepatocarcinogenesis in alcoholic liver disease was unclear and, therefore

  18. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick;

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140....

  19. Non-Alcoholic Fatty Liver Disease in Children

    OpenAIRE

    SINGER, CRISTINA; Stancu, Polixenia; CO?OVEANU, SIMONA; Botu, Alina

    2014-01-01

    In the last years, there has been extremely much information which reveals an alarming increase of obesity in children and, at the same time, an increase of the incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD implies a wide range of affections starting from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH); the latter can evolve to cirrhosis and hepatic carcinoma. All these affections were noticed in children, too. The article presents data on the epidemiology, pa...

  20. 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.

  1. 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

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

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Christoffersen, P

    1988-01-01

    The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular...... localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro-Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis....... It is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation....

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

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Christoffersen, P

    1988-01-01

    localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro-Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis......The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular....... It is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation....

  4. 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.

  5. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Haoyong Yu; Weiping Jia; ZengKui Guo

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans w...

  6. Risk factors for alcoholic liver disease in China

    Institute of Scientific and Technical Information of China (English)

    Xiao-Lan Lu; Jin-Yan Luo; Ming Tao; Yan Gen; Ping Zhao; Hong-Li Zhao; Xiao-Dong Zhang; Nei Dong

    2004-01-01

    AIM: To examine the association of daily alcohol intake,types of alcoholic beverage consumed, drinking patterns and obesity with alcoholic liver disease in China.METHODS: By random cluster sampling and a 3-year follow-up study, 1 270 alcohol drinkers were recruited from different occupations in the urban and suburban areas of Xi'an City. They were examined by specialists and inquired for information on: Medical history and family medical history, alcohol intake, types of alcoholic beverage consumed, drinking patterns by detailed dietary questionnaires. Routine blood tests and ultrasonography were done.RESULTS: Multivariate analysis showed that: (1) The risk threshold for developing alcoholic liver disease was ingestion of more than 20 g alcohol per day, keeping on drinking for over 5 years in men. The highest OR was at the daily alcohol consumption ≥160 g, the occurrence rate of ALD amounted to 18.7% (P<0.01). No ALD occurred when ingestion of alcohol was less than 20 g per day. (2) 87.9% of all drank only at mealtimes. The cumulative risk of developing ALD was significantly higher in those individuals who regularly drank alcohol without food than in those who drank only at mealtimes, especially for those who regularly drank hard liquors only and multiple drinks (P<0.05). (3) The alcohol consumption in those with BMI ≥25 was lower than in those with BMI <25, but the risk increased to 11.5%, significantly higher than that of general population, 6.5% (P<0.01). (4)Abstinence and weight reduction could benefit the liver function recovery.CONCLUSION: In the Chinese population the ethanol risk threshold for developing ALD is 20 g per day, and this risk increases with increased daily intake. Drinking 20 g of ethanol per day and for less than 5 years are safe from ALD. Drinking alcohol outside mealtimes and drinking hard liquors only and multiple different alcohol beverages both increase the risk of developing ALD. Obesity also increases the risk. Abstinence

  7. 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.

  8. 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.

  9. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Jacobs, B P; Gluud, C

    2007-01-01

    Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases.......Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

  10. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Jacobs, B P; Iaquinto, G

    2005-01-01

    Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases.......Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

  11. Alcohol

    Science.gov (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  12. 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).

  13. Alcoholic liver disease and changes in bone mineral density

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. Birth control pills, cigarettes, alcohol linked to liver cancer.

    Science.gov (United States)

    1992-03-01

    Data on 74 pathologically confirmed cases of liver cancer among blacks and whites living in Los Angeles County, California were compared with 162 matched controls. The study was limited to only people with no hepatitis infection and to non-Asians. The risk of liver cancer for women who have used OCs for 5 years was 5.5 times higher than that for women who had never used OCs. This risk was 3 times higher for women who had ever used OCs. The data for women who were in their reproductive years when OCs 1st entered the market in the 1960s showed that the risk for 5 years of OC use increased to almost 30 times that of women who had never used OCs. Even though estrogens were presumed to be the risk factor since they induce liver cancer in animals, no significant association was found between estrogens used in estrogen replacement therapy and liver cancer. Overall, diabetics were at 3.3 times the risk for liver cancer compared with nondiabetics. People who had diabetes for at least 10 years had 4.3 times the risk and those dependent on insulin injections had 18.5 times the risk. Cigarette smokers had a 2.1 times greater risk of liver cancer than nonsmokers. Most of the women did not drink heavily which showed the independent effect of cigarette smoking. As of December 1991, these data represented the best data on OCs and cigarette smoking to date. The risk for heavy drinkers of alcohol (80g of alcohol/day=9 cans of beer, 9 glasses of wine, or 9 shots of spirits) was 4.7 times the risk of nondrinkers or light drinkers. It is concluded that alcohol and/or cigarettes caused 56% of liver cancer cases in men and that cigarettes and/or OCs caused 54% of liver cancer cases in women.

  16. Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis.

    Science.gov (United States)

    Le, Thuy-Anh; Loomba, Rohit

    2012-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations.

  17. Human health risk assessment of long chain alcohols (LCOH)

    DEFF Research Database (Denmark)

    Veenstra, Gauke; Sanderson, Hans; Webb, Catherine

    2009-01-01

    Representative chemicals from the long chain alcohols category have been extensively tested to define their toxicological hazard properties. These chemicals show low acute and repeat dose toxicity with high-dose effects (if any) related to minimal liver toxicity. These chemicals do not show evide...... of human health are documented for the uses of these chemicals. © 2008....

  18. 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.

  19. Alcohol Abuse and Alcoholic Liver Cirrhosis Leading to Spontaneous Muscle Hematoma: An Event Fraught with Danger

    Directory of Open Access Journals (Sweden)

    Ankit Mangla

    2015-04-01

    Full Text Available Alcohol abuse is associated with both potentiating and antagonizing hemostatic states. Liver cirrhosis is an independent causal factor for many bleeding complications. The long-term effects of alcohol abuse coupled with advanced liver cirrhosis are additive in favor of bleeding. We report the case of a patient with a history of alcohol abuse who presented with liver cirrhosis and nontraumatic muscle hematoma diagnosed as a spontaneous hematoma of the gastrocnemius muscle. He was managed conservatively with infusions of fresh frozen plasma and platelets, which resulted in resolution of the hematoma. The pathogenesis of ‘spontaneous' muscle hematoma remains anecdotal, but since it is reported in patients on anticoagulant therapy or with hemostatic disorders, it is hypothetically related to severely deranged coagulation. Here we review the relevant literature pertaining to the pathogenesis, presentation and treatment options available for treating this often fatal complication of bleeding diatheses.

  20. Drinking patterns and biochemical signs of alcoholic liver disease in Danish and Greenlandic patients with alcohol addiction

    DEFF Research Database (Denmark)

    Lavik, Berit; Holmegaard, Claes; Becker, Ulrik

    2006-01-01

    . This study was designed to document the prevalence of alcoholic liver diseases in Greenlanders with a high alcohol intake, and to describe and compare the populations of patients with alcohol addiction in Greenland and Denmark. STUDY DESIGN: Clinical cross-sectional study of patients attending alcohol...

  1. [Non-alcoholic fatty liver disease (NAFLD) /non-alcoholic steatohepatitis (NASH) and nutrition].

    Science.gov (United States)

    Ishii, Kiyo-aki; Takamura, Toshinari

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the form of triglycerides in the hepatocytes. A more severe form of NAFLD with necrosis, inflammation, and fibrosis is called non-alcoholic steatohepatitis (NASH). The liver is located in the center of the body's organ network and acts as a coordinator of glucose and lipid metabolism. Therefore, it is important to perform nutritional therapy of patients with NAFLD/NASH while maintaining the energy balance in the entire body.

  2. A meta-analysis of HLA-antigen prevalences in alcoholics and alcoholic liver disease

    DEFF Research Database (Denmark)

    List, S; Gluud, C

    1994-01-01

    suspected of being associated with both alcoholism and alcoholic liver disease. In the present study a meta-analysis is carried out on the data from these studies, subdivided according to race and degree of liver injury. The conclusion is that none of the HLA-phenotypes so far investigated in Caucasians can...... be shown to be significantly more common in any of the studied patient categories than in controls, whereas the results of Japanese studies are less clear. The limitations of the data material and the design of the studies are discussed, as well as the strength and limitations of the method of meta-analysis....

  3. Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Plapp, Bryce V.; Savarimuthu, Baskar Raj; Ferraro, Daniel J.; Rubach, Jon K.; Brown, Eric N.; Ramaswamy, S. (Iowa)

    2017-07-07

    During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ~1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.

  4. Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis.

    Science.gov (United States)

    Plapp, Bryce V; Savarimuthu, Baskar Raj; Ferraro, Daniel J; Rubach, Jon K; Brown, Eric N; Ramaswamy, S

    2017-07-18

    During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme-NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ∼1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD(+) and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.

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

    Science.gov (United States)

    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.

  6. 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.

  7. 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...

  8. Contribution of liver alcohol dehydrogenase to metabolism of alcohols in rats.

    Science.gov (United States)

    Plapp, Bryce V; Leidal, Kevin G; Murch, Bruce P; Green, David W

    2015-06-05

    The kinetics of oxidation of various alcohols by purified rat liver alcohol dehydrogenase (ADH) were compared with the kinetics of elimination of the alcohols in rats in order to investigate the roles of ADH and other factors that contribute to the rates of metabolism of alcohols. Primary alcohols (ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol) and diols (1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol) were eliminated in rats with zero-order kinetics at doses of 5-20 mmol/kg. Ethanol was eliminated most rapidly, at 7.9 mmol/kgh. Secondary alcohols (2-propanol-d7, 2-propanol, 2-butanol, 3-pentanol, cyclopentanol, cyclohexanol) were eliminated with first order kinetics at doses of 5-10 mmol/kg, and the corresponding ketones were formed and slowly eliminated with zero or first order kinetics. The rates of elimination of various alcohols were inhibited on average 73% (55% for 2-propanol to 90% for ethanol) by 1 mmol/kg of 4-methylpyrazole, a good inhibitor of ADH, indicating a major role for ADH in the metabolism of the alcohols. The Michaelis kinetic constants from in vitro studies (pH 7.3, 37 °C) with isolated rat liver enzyme were used to calculate the expected relative rates of metabolism in rats. The rates of elimination generally increased with increased activity of ADH, but a maximum rate of 6±1 mmol/kg h was observed for the best substrates, suggesting that ADH activity is not solely rate-limiting. Because secondary alcohols only require one NAD(+) for the conversion to ketones whereas primary alcohols require two equivalents of NAD(+) for oxidation to the carboxylic acids, it appears that the rate of oxidation of NADH to NAD(+) is not a major limiting factor for metabolism of these alcohols, but the rate-limiting factors are yet to be identified.

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

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, Jens Henrik Sahl

    1985-01-01

    In 32 alcoholic patients the degree of hepatic architectural destruction was graded (preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) and related to portal pressure. A significant positive correlation was found between degree of architectural...... destruction and wedged-to-free hepatic vein pressure (W-FHVP) (p less than 0.001). The degree of necrosis, fatty change and inflammation showed no correlation with portal pressure, whereas a significant positive correlation was found between the occurrence of Mallory bodies and W-FHVP (p less than 0......, hepatic architectural destruction (p less than 0.01) was positively correlated to hepatic resistance. Necrosis, fatty change, occurrence of Mallory bodies or inflammation showed no significant correlation with hepatic resistance. Mean hepatocyte volume was calculated in 29 patients, but no correlation...

  10. Experimental study of bioartificial liver with cultured human liver cells

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5 h experiment.CONCLUSION EBLSS playing a metabolic role of cultured human hepatocytes, is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

  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. 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.

  13. Manifestation of Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Different Dietary Mouse Models

    Directory of Open Access Journals (Sweden)

    Vera HI Fengler

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH, which are usually associated with obesity and metabolic syndrome, are considerable health and economic issues due to the rapid increase of their prevalence in Western society. Histologically, the diseases are characterised by steatosis, hepatic inflammation, and if further progressed, fibrosis. Dietary-induced mouse models are widely used in investigations of the development and progression of NAFLD and NASH; these models attempt to mimic the histological and metabolic features of the human diseases. However, the majority of dietary mouse models fail to reflect the whole pathophysiological spectrum of NAFLD and NASH. Some models exhibit histological features similar to those seen in humans while lacking the metabolic context, while others resemble the metabolic conditions leading to NAFLD in humans but fail to mimic the whole histological spectrum, including progression from steatosis to liver fibrosis, and thus fail to mimic NASH. This review summarises the advantages and disadvantages of the different dietary-induced mouse models of NAFLD and NASH, with a focus on the genetic background of several commonly used wild-type mouse strains as well as gender and age, which influence the development and progression of these liver diseases.

  14. 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.

  15. [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

  16. Bone health and vitamin D status in alcoholic liver disease.

    Science.gov (United States)

    Kizilgul, M; Ozcelik, O; Delibasi, T

    2016-07-01

    Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.

  17. 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

  18. Is the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?

    Institute of Scientific and Technical Information of China (English)

    Duygu Dee Harrison-Findik

    2009-01-01

    Despite heavy consumption over a long period of time,only a small number of alcoholics develop alcoholic liver disease. This alludes to the possibility that other factors,besides alcohol, may be involved in the progression of the disease. Over the years, many such factors have indeed been identified, including iron. Despite being crucial for various important biological processes, iron can also be harmful due to its ability to catalyze Fenton chemistry. Alcohol and iron have been shown to interact synergistically to cause liver injury. Iron-mediated cell signaling has been reported to be involved in the pathogenesis of experimental alcoholic liver disease. Hepcidin is an iron-regulatory hormone synthesized by the liver,which plays a pivotal role in iron homeostasis. Both acute and chronic alcohol exposure suppress hepcidin expression in the liver. The sera of patients with alcoholic liver disease, particularly those exhibiting higher serum iron indices, have also been reported to display reduced prohepcidin levels. Alcohol-mediated oxidative stress is involved in the inhibition of hepcidin promoter activity and transcription in the liver. This in turn leads to an increase in intestinal iron transport and liver iron storage. Hepcidin is expressed primarily in hepatocytes.It is noteworthy that both hepatocytes and Kupffer cells are involved in the progression of alcoholic liver disease. However, the activation of Kupffer cells and TNF-α signaling has been reported not to be involved in the down-regulation of hepcidin expression by alcohol in the liver. Alcohol acts within the parenchymal cells of the liver to suppress the synthesis of hepcidin. Due to its crucial role in the regulation of body iron stores, hepcidin may act as a secondary risk factor in the progression of alcoholic liver disease. The clarification of the mechanisms by which alcohol disrupts iron homeostasis will allow for further understanding of the pathogenesis of alcoholic liver disease.

  19. Study on Alcoholic Withdrawal Score, with Questionnaire Based Session Conducted on Acute and Chronic Alcoholic Liver Disease Patients

    Directory of Open Access Journals (Sweden)

    Bandi Navyatha

    2016-07-01

    Full Text Available Alcohol liver disease is damage to the Liver and its function due to alcohol abuse. It occurs after years of heavy drinking and by through which cirrhosis can occur and which leads to the final phase of Alcoholic liver disease. It not only occurs in heavy drinkers but also there is a chance of getting liver disease go up the longer of been drinking and more alcohol consumption. A study was observational, prospective and descriptive; and was carried out one hundred and nine patients [n=109] who were with suffering from an Alcoholic liver disease, to determine the alcohol withdrawal score and there symptoms involved after they were kept on alcohol withdrawal therapy. An observational, prospective and randomized study was conducted in the hospital from March 2014-March 2016. Questionnaire based session with 10 scaled questions were framed according to CIWA (assessment and management of alcohol withdrawal and the score was noted with their symptoms occurrence after the alcohol cessation plan. CIWA score with moderate severity were found to be highest. 7 patients out of 33 patients in severe category of CIWA score were admitted in the hospital with alcohol withdrawal syndrome and psychological disturbances. Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA helps clinicians assess and treat potential alcohol withdrawal.

  20. 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.

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

    Science.gov (United States)

    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.

  2. Translational approaches: from fatty liver to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Rosso, Natalia; Chavez-Tapia, Norberto C; Tiribelli, Claudio; Bellentani, Stefano

    2014-07-21

    Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.

  3. Autophagy and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lavallard, Vanessa J; Gual, Philippe

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  4. Autophagy and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Vanessa J. Lavallard

    2014-01-01

    Full Text Available Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD, have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH, steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  5. Autophagy and Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Lavallard, Vanessa J.

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma. PMID:25295245

  6. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Tilg, Herbert; Moschen, Alexander R; Szabo, Gyongyi

    2016-09-01

    Both alcoholic liver disease (ALD) and nonalcoholic fatty liver disease are characterized by massive lipid accumulation in the liver accompanied by inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma in a substantial subgroup of patients. At several stages in these diseases, mediators of the immune system, such as cytokines or inflammasomes, are crucially involved. In ALD, chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides through Toll-like receptors, e.g., Toll-like receptor 4. This sensitization enhances the production of various proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha, thereby contributing to hepatocyte dysfunction, necrosis, and apoptosis and the generation of extracellular matrix proteins leading to fibrosis/cirrhosis. Indeed, neutralization of IL-1 by IL-1 receptor antagonist has recently been shown to potently prevent liver injury in murine models of ALD. As IL-1 is clearly linked to key clinical symptoms of acute alcoholic hepatitis such as fever, neutrophilia, and wasting, interfering with the IL-1 pathway might be an attractive treatment strategy in the future. An important role for IL-1-type cytokines and certain inflammasomes has also been demonstrated in murine models of nonalcoholic fatty liver disease. IL-1-type cytokines can regulate hepatic steatosis; the NLR family pyrin domain containing 3 inflammasome is critically involved in metabolic dysregulation. IL-1 cytokine family members and various inflammasomes mediate different aspects of both ALD and nonalcoholic fatty liver disease. (Hepatology 2016;64:955-965). © 2016 by the American Association for the Study of Liver Diseases.

  7. Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Yoshikuni; Kawaguchi; Yasuhiko; Sugawara; Nobuhisa; Akamatsu; Junichi; Kaneko; Tomohiro; Tanaka; Sumihito; Tamura; Taku; Aoki; Yoshihiro; Sakamoto; Kiyoshi; Hasegawa; Norihiro; Kokudo

    2014-01-01

    Although alcoholic liver disease(ALD) is regarded as a common indication for liver transplantation(LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.

  8. Consumption of Coprinus comatus polysaccharide extract causes recovery of alcoholic liver damage in rats

    NARCIS (Netherlands)

    Ozalp, F.O.; Canbek, M.; Yamac, M.; Kanbak, G.; Griensven, van L.J.L.D.; Uyanoglu, M.; Senturk, H.; Karlkava, K.; Oglakci, A.

    2014-01-01

    Excess use of alcohol is known to be associated with liver diseases such as fatty liver, alcoholic hepatitis, and cirrhosis. Various practices may be applied to prevent or treat the damage caused by chronic alcoholism. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) is a macrofungus that has been

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  10. Hepatoprotective effect of kaempferol against alcoholic liver injury in mice.

    Science.gov (United States)

    Wang, Meng; Sun, Jianguo; Jiang, Zhihui; Xie, Wenyan; Zhang, Xiaoying

    2015-01-01

    Kaempferol is a biologically active component present in various plants. The hepatoprotective effect of kaempferol in drug-induced liver injury has been proven, while its effect against alcoholic liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of liver tissue; oxidative stress by hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods. The ALI mice (untreated) showed clear symptoms of liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1. These findings show the hepatoprotective properties of kaempferol against alcohol-induced liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.

  11. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-11-07

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

  12. Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

    Science.gov (United States)

    Fernández-Rodríguez, Camino; González-Reimers, Emilio; Quintero-Platt, Geraldine; de la Vega-Prieto, María José; Pérez-Hernández, Onán; Martín-González, Candelaria; Espelosín-Ortega, Elisa; Romero-Acevedo, Lucía; Santolaria-Fernández, Francisco

    2016-11-01

    Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis

  13. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

    Science.gov (United States)

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches. PMID:27391242

  14. 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.

  15. Baicalin Attenuates Alcoholic Liver Injury through Modulation of Hepatic Oxidative Stress, Inflammation and Sonic Hedgehog Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Huifen Wang

    2016-08-01

    Full Text Available Background/Aims: Lipid accumulation, inflammatory responses and oxidative stress have been implicated in the pathology of alcoholic liver disease (ALD. Targeting inhibition of these features may provide a promising therapeutic strategy for ALD. Baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has been shown to exert a hepatoprotective effect. However, its effects on ALD remain obscure. This study was aimed to investigate the effects of baicalin on alcohol-induced liver injury and its related mechanisms. Methods: For in vivo experiments, rats were supplied intragastrical administration of alcohol continuously for 4 or 8 weeks, and then received baicalin treatment in the latter 4 weeks in the presence / absence of alcohol intake. Liver histology and function, inflammatory cytokines, oxidative mediators, and the components of the Sonic hedgehog pathway were evaluated. For in vitro experiments, alcohol-stimulated human normal liver cells LO2 were used. Results: Baicalin treatment significantly alleviated alcoholic liver injury, improved liver function impaired by alcohol, and inhibited hepatocytes apoptosis. In addition, baicalin decreased the expression levels of proinflammatory cytokines TNF-α, IL-1β, IL-6 and malonyldialdehyde (MDA, and increased the activities of antioxidant enzymes SOD and GSH-Px. Furthermore, baicalin modulated the activation of Sonic hedgehog (Shh pathway. Administration of baicalin upregulated the expression of sonic hedgehog (Shh, patched (Ptc, Smoothened (Smo, and Glioblastoma-1(Gli-1. Blockade of the Shh pathway in cyclopamine abolished the effects of baicalin in vitro. Conclusion: Both in vivo and in vitro experimental results indicate that baicalin exerts hepatoprotective roles in alcohol-induced liver injury through inhibiting oxidative stress, inflammatory response, and the regulation of the Shh pathway.

  16. 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.

  17. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Marina Galicia-Moreno

    2016-01-01

    Full Text Available Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC. This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

  18. Experimental models of non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Kucera, Otto; Cervinkova, Zuzana

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

  19. Paediatric non-alcoholic fatty liver disease: an overview.

    Science.gov (United States)

    AlKhater, S A

    2015-05-01

    Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non-hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research. © 2015 World Obesity.

  20. 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.

  1. An empirical analysis of the relationship between the consumption of alcohol and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    The question whether intake of alcohol is associated with liver cirrhosis mortality is analyzed using aggregate data for alcohol consumption, alcohol related diseases and alcohol policies of 16 European countries. The empirical analysis gives support to a close association between cirrhosis...

  2. 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.

  3. Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Poeta, Marco; Pierri, Luca; Vajro, Pietro

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising. PMID:28767077

  4. Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Marco Poeta

    2017-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH. Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

  5. Targeting Kupffer cells in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why and how?

    Institute of Scientific and Technical Information of China (English)

    Nicolas; Lanthier

    2015-01-01

    Mechanisms for non-alcoholic steatohepatitis(NASH)development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. Previous findings have pointed to the role of adipose tissue, adipose tissue macrophages and their secretory products in the development of a chronic inflammatory status inducing insulin resistance and a higher risk of liver steatosis called non-alcoholic fatty liver disease. The activation of resident macrophages [Kupffer cells(KC)] and the recruitment of blood derived monocytes/macrophages into the diseased liver have now been identified as key elements for disease initiation and progression. Those cells could be activated through gut flora modifications and an altered gut barrier function but also through the internalization of toxic lipid compounds in adjacent hepatocytes or in KC themselves. Due to the role of activated KC in insulin resistance, fibrosis development and inflammation amplification, they became a target in clinical trials. A shift towards an anti-inflammatory KC phenotype through peroxisome proliferator activator-receptorδ agonists, an inhibition of macrophage recruitment through anti-C-C chemokine receptor 2 action and a specific blocking of internalization of toxic lipoxidation or glycation compounds into KC by galectin-3 receptor inhibitors are now under investigation in human NASH.

  6. 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.

  7. Protective Action of Se-Supplement Against Acute Alcoholism Is Regulated by Selenoprotein P (SelP) in the Liver.

    Science.gov (United States)

    Zhang, Zhenbiao; Guo, Yingfang; Qiu, Changwei; Deng, Ganzhen; Guo, Mengyao

    2017-02-01

    Acute alcoholism is a major cause of cirrhosis and liver failure around the world. Selenium (Se) is an essential micronutrient promoting liver health in humans and animals. Selenoprotein P (SelP) is a glycoprotein secreted within the liver, which interacts with cytokines and the growth factor pathway to provide protection for hepatic cells. The present study was conducted to confirm the effect and mechanism of Se and SelP action in livers affected by acute alcoholism. In this study, a mouse model of acute alcoholism, as well as a hepatocyte model, was successfully established. The Se content of the liver was detected by atomic fluorescence spectrophotometry. The expression of messenger RNA (mRNA) was analyzed by quantitative polymerase chain reaction (qPCR). The protein expression of inflammatory factors was detected by ELISA. The other proteins were analyzed by western blotting. The results showed that pathological damage to the liver was gradually weakened by Se-supplementation, which was evaluated by hematoxylin and eosin (H&E) and TUNEL staining. Se-supplementation inhibited expression of pro-inflammatory factors TNF-α and IL-1β and promoted production of anti-inflammatory cytokine IL-10 in the liver with acute alcoholism. Se-supplementation also prevented the apoptosis of hepatocytes by suppressing the cleavage of caspases-9, 3, 6, 7, and poly(ADP-ribose) polymerase (PARP). Through correlational analysis, it was determined that the effects of Se-supplement were closely related to SelP expression, inflammatory cytokines, and apoptosis molecule production. The sienna of SelP further confirmed the protective action of Se-supplementation on the liver and that the mechanism of SelP involves the regulation of inflammatory cytokines and apoptosis molecules in acute alcoholism. These findings provide information regarding a new potential target for the treatment of acute alcoholism.

  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. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

    Directory of Open Access Journals (Sweden)

    Timon E. Adolph

    2017-07-01

    Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  10. A concise review of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Than, Nwe Ni; Newsome, Philip N

    2015-03-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and the incidence of which is rising rapidly due to the increasing epidemic of obesity in both adults and children. The initial accumulation of fat followed by subsequent inflammation is central to the development of liver damage, and is critically influenced by host factors including age, gender, presence of diabetes, genetic polymorphisms and more recently by the gut microbiome. An increasing body of data suggest that NAFLD is also an independent risk factor of cardiovascular disease, which remains the commonest cause of mortality in such patients. This review focusses on the pathogenesis of NAFLD, and the evolution of new approaches to the management and treatment of NAFLD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    Science.gov (United States)

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical

  13. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical tri

  14. 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.

  15. Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

    Institute of Scientific and Technical Information of China (English)

    Henry V(o)lzke

    2012-01-01

    Apart from alcohol,there are other factors that may induce complications,which resemble alcohol-related liver disorders.In particular,obesity has been brought into focus as a risk factor for fatty liver disease.The term "non-alcoholic" fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis.This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and "non-alcoholic" fatty liver disease.The MEDLINE database was searched using the PubMed search engine,and a review of reference lists from original research and review articles was conducted.The concept to distinguish between alcoholic and "non-alcoholic" fatty liver disease is mainly based on specific pathomechanisms.This concept has,however,several limitations including the common overlap between alcohol misuse and obesityrelated metabolic disorders and the non-consideration of additional causal factors.Both entities share similar histopathological patterns.Studies demonstrating differences in clinical presentation and outcome are often biased by selection.Risk factor reduction is the main principle of prevention and treatment of both disease forms.In conclusion,alcoholic and "non-alcoholic" fatty liver diseases are one and the same disease caused by different risk factors.A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level.

  16. Molecular pathways in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Berlanga A

    2014-07-01

    Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA

  17. Non-alcoholic fatty liver disease in children: focus on nutritional interventions.

    Science.gov (United States)

    Yang, Min; Gong, Sitang; Ye, Shui Qing; Lyman, Beth; Geng, Lanlan; Chen, Peiyu; Li, Ding-You

    2014-10-28

    With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.

  18. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

    Directory of Open Access Journals (Sweden)

    Min Yang

    2014-10-01

    Full Text Available With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.

  19. Mallory bodies in alcoholic and non-alcoholic liver disease contain a common antigenic determinant.

    Science.gov (United States)

    Fleming, K A; Morton, J A; Barbatis, C; Burns, J; Canning, S; McGee, J O

    1981-05-01

    An immunohistochemical technique is described for the detection of Mallory bodies (MBs) in paraffin sections of liver tissue. This is based on proteolytic digestion of sections before exposure to an antiserum which recognises a unique antigenic determinant in MBs. With the use of this procedure it has been shown in alcoholic liver disease, primary biliary cirrhosis. Indian childhood cirrhosis, Wilson's disease, diabetes mellitus, and hepatocellular cancer that the MBs found in these disorders contain this unique antigenic determinant. It is postulated, therefore, that the mechanism of formation of MBs is similar in liver diseases of diverse aetiology. In addition, it has been demonstrated that the immunohistochemical procedure is more sensitive than routine staining; MBs were detected in five out of 12 fatty livers by immunohistochemical and only in one by H and E staining. As MBs in fatty livers were not associated with polymorph filtration or fibrogenesis it is argued that MB formation is not an absolute prerequisite for the progression of acute to chronic liver disease.

  20. Human serum fetuin A/α2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores

    Directory of Open Access Journals (Sweden)

    Prohászka Zoltán

    2007-03-01

    Full Text Available Abstract Background Serum concentration of fetuin A/α2HS-glycoprotein (AHSG is a good indicator of liver cell function and 1-month mortality in patients with alcoholic liver cirrhosis and liver cancer. We intended to determine whether decreased serum AHSG levels are associated with long-term mortality and whether the follow-up of serum AHSG levels can add to the predictive value of the Child-Pugh (CP and MELD scores. Methods We determined serum AHSG concentrations in 89 patients by radial immunodiffusion. Samples were taken at the time of enrolment and in the 1st, 3rd, 6th, and the 12th month thereafter. Results Forty-one patients died during the 1-year follow-up period, 37 of them had liver failure. Data of these patients were analysed further. Deceased patients had lower baseline AHSG levels than the 52 patients who survived (293 ± 77 vs. 490 ± 106 μg/ml, mean ± SD, p Conclusion Serum AHSG concentration is a reliable and sensitive indicator of 1-year mortality in patients with alcoholic liver cirrhosis that compares well to the predictive value of CP score and may further improve that of MELD score.

  1. Predictors of heavy drinking after liver transplantation for alcoholic liver disease in Denmark (1990-2013)

    DEFF Research Database (Denmark)

    Askgaard, Gro; Tolstrup, Janne S.; Gerds, Thomas A.

    2016-01-01

    incidence of heavy drinking among patients transplanted for alcoholic liver disease in Denmark 1990-2013. We then analyzed pre-transplant demographic and psychiatric characteristics as predictors of post-transplant heavy drinking. Information was obtained from medical records, from nationwide registries.......007), anxiety (p = 0.04), personality disorder (p = 0.05) and no lifetime diagnosis of alcohol dependence (p = 0.03) were associated with heavy drinking after transplantation. Smoking (p = 0.06) tended to be associated, whereas depression (p = 0.7) or being married was not (p = 0.7). In the multivariate...... analysis, only younger age (p = 0.03), being retired (p = 0.007) and no lifetime diagnosis of alcohol dependence (p = 0.003) remained significant predictors. Heavy drinking after transplantation decreased survival beyond 5 years post-transplant (p = 0.004). CONCLUSIONS: There is a high incidence of heavy...

  2. From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease

    OpenAIRE

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia del Giudice, Emanuele; Santoro, Nicola

    2017-01-01

    In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnorma...

  3. 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

  4. Muscle hematoma: A critically important complication of alcoholic liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Chiyo Sugiyama; Akifumi Akai; Noriyoshi Yamakita; Tsuneko Ikeda; Keigo Yasuda

    2009-01-01

    An iliopsoas hematoma can occur either spontaneously or secondary to trauma or bleeding tendency due to hemophilia and anticoagulant therapy. Although liver cirrhosis is commonly associated with coagulopathy, iliopsoas hematoma is very rare. We herein, present a case of bilateral iliopsoas hematoma in a patient with alcoholic cirrhosis, and review the literature on muscle hematoma associated with cirrhosis. A 56-year-old man with alcoholic cirrhosis was admitted in a state of shock with anemia. The cause of anemia could not be detected, and the patient was treated conservatively. The site of bleeding was not detected with either gastroduodenal endoscopy or upper abdominal computed tomography, the latter of which did not include the iliopsoas muscle. He died on the 10th day of admission and bilateral iliopsoas hematomas were found on autopsy. An iron stain was positive in the iliopsoas muscle. Eight cases of muscle hematoma associated with cirrhosis, including the present case, were found in a review of the literature. Four of these cases involved the rectus abdominis muscle, 3 involved the iliopsoas muscle and 1 involved combined muscles. Alcoholic cirrhosis accounted for 75% of the cases. One case (12.5%) was associated with virus-related cirrhosis, and another with combined virus-and alcohol-related cirrhosis. The mortality rate was 75% despite early diagnosis and low risk scores for cirrhosis. Muscle hematoma in patients with cirrhosis isclosely related to alcoholism, and the mortality rate of the condition is extremely high. In conclusion, muscle hematoma should be recognized as an important complication of cirrhosis.

  5. The contribution of alcohol, thiamine deficiency and cirrhosis of the liver to cerebral cortical damage in alcoholics.

    Science.gov (United States)

    Kril, J J

    1995-03-01

    The relative roles of alcohol toxicity, thiamine deficiency and cirrhosis of the liver in the pathogenesis of alcohol-related brain damage are unclear. Brain shrinkage and neuronal loss from four regions of the cortex was determined in 22 alcoholics with the Wernicke-Korsakoff Syndrome (WKS), cirrhosis of the liver or neither of these complications and compared to 22 age-matched non-alcoholic controls. Brain shrinkage was most marked in those alcoholics with WKS. Neuronal loss occurred only from the superior cortex and was of equal magnitude in all alcoholic subgroups. In an animal model of alcohol abuse and thiamine deficiency, neuronal loss from the cerebral cortex occurred in a time-dependent manner. Furthermore, those cells which contained the calcium-binding protein parvalbumin appeared to be preferentially damaged in this model.

  6. The inflammasome in liver injury and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Mehal, Wajahat Zafar

    2014-01-01

    The liver possesses a strong inflammatory response, as seen experimentally and clinically with liver inflammation due to toxic and metabolic stress, sepsis and ischemia. Initiation of this inflammatory response requires the interaction of two types of extracellular signals which collectively upregulate and activate a cytosolic molecular complex termed the inflammasome. Signal 1 is via activation of pattern recognition receptors, and signal 2 is delivered by diverse stimuli including particulates and adenosine triphosphate. The common end result of inflammasome activation is the activation of the protease caspase-1 with release of active interleukin-1β. The inflammasome is important in a wide range of conditions including alcoholic and non-alcoholic steatohepatitis. Kupffer cells are known to be important, but the consequences of inflammasome activation in other hepatic immune cells have not been well characterized. The inflammasome pathway is also known to be required for a full fibrotic response, as demonstrated by reduced lung, skin and liver fibrosis in inflammasome-deficient mice. Identification of the inflammasome machinery has opened up novel therapeutic avenues by the use of antagonists for Toll-like receptors as well as the adenosine triphosphate receptor P2X7, and the interleukin-1 receptor. There is now great interest in how inflammasome pathways are regulated. The initial challenge is to understand how an acute inflammatory response is sustained. This is a significant issue as the known stimuli result in an acute response that is self-limited to under 24 h. This suggests that there are significant regulators which allow sustained inflammasome activation in conditions such as non-alcoholic steatohepatitis and alcoholic hepatitis.

  7. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Yu, Haoyong; Jia, Weiping; Guo, ZengKui

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate ( 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. PMID:25411646

  8. Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Courtney S Schaffert; Michael J Duryee; Carlos D Hunter; Bartlett C Hamilton 3rd; Amy L DeVeney; Mary M Huerter; Lynell W Klassen; Geoffrey M Thiele

    2009-01-01

    The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol- induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts,and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore,the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflammation inflammation and fibrosis, and play a role in the development and/or progression of ALD.

  9. Low incidence of non-alcoholic steatohepatitis in a Danish liver unit

    DEFF Research Database (Denmark)

    Semb, Synne; Dam-Larsen, Sanne; Mogensen, Anne Mellon

    2012-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify...

  10. Implication of altered proteasome function in alcoholic liver injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The proteasome is a major protein-degrading enzyme,which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels: low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation.Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins.Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling (Ⅰ-κB and SOCS), thereby blocking cytokine signal transduction.Finally, ethanol-elicited blockade of interferon type 1 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class Ⅰ-restricted antigen presentation.

  11. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Albanian overweight children.

    Science.gov (United States)

    Kodhelaj, K; Resuli, B; Petrela, E; Malaj, V; Jaze, H

    2014-02-01

    Overweight and obesity has emerged as a significant global health problem in the pediatric population. Childhood non-alcoholic fatty liver disease (NAFLD) has become a common and important liver disease. Although mostly benign, some children with NAFLD develop fibrosis and in some case cirrhosis. The aims of this study were to determine the prevalence of NAFLD/non-alcoholic steatohepatitis (NASH) in overweight Albanian children, to evaluate the demographic and biochemical details and to assess the association between the severity of fatty liver changes and demographic and biochemical abnormalities. A total of 80 school aged children, 24 overweight (85th≤BMI≤94th percentile) and 55 obese (BMI≥94th percentile), aged 10.43±2.2 years (M±SD) were included in the current study, in January-December 2010. Their age was in the range of 7-15 years. Their sex distribution was 36 female and 44 male. The children were enrolled to the Tirana schools and none of them were part of any weight or diet programmer. Children who were found to have TBC, evidence of HBV or HCV, infections, drug toxicity, autoimmune hepatitis, inborn error of metabolism or concomitant cortisteroid therapy were excluded. Laboratory parameters were measured at the time of bioclinical examinations. Fatty liver was diagnosed by ultrasonography detection of the most characteristic features of fatty infiltration. The scoring system was used in order to graduate the severity of the disease. The child was considered to have mild, moderate and severe fatty liver changes if the overall score was 1-3, 4-6 and 7-9, respectively. Multivariate regression analysis was used to assess the association between the different variables and the severity of NAFLD. NAFLD was present in 55/80 (68.7%) of the overweight children, 34 (61.8%) boys and 21 (38.2%) girls. Mild, moderate and severe degree of fatty liver were found in 35 (43.7%), 19 (23.7%) and 1 (1.3%), respectively. Nash was seen in 13 (23.7%) of the children

  12. CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    You-Chen Chao; Heng-Cheng Chu; Wei-Kuo Chang; Hsin-Hung Huang; Tsai-Yuan Hsieh

    2005-01-01

    AIM: To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations.METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of CD14 gene and aldehyde dehydrogenase gene 2 (ALDH 2) in 335 alcoholic patients with different organ complications i.e., cirrhosis of liver (n = 100), acute pancreatitis (n = 100), esophageal cancer (n = 82) and avascular necrosis of hip joint (AVN) (n = 53)and 194 non-alcoholic controls in a Chinese group.RESULTS: The results showed that the carriage of T allele was not different among alcoholic patients with cirrhosis of liver, alcoholic patients with other complication and non-alcoholic controls. On the other hand, the carriage of the C allele was significantly more prevalent for alcoholic pancreatitis than for esophageal cancer (0.79 vs 0.60,P<0.001), alcoholic AVN (0.79 vs 0.65, P<0.025) and nonalcoholic controls (0.79 vs 0.68, P<0.025). Furthermore,when only subjects with ALDH2 1-1 genotype were examined, the C allele frequency was significantly more prevalent for alcoholic pancreatitis than for alcoholic liver cirrhosis (0.82 vs 0.69, P<0.025), esophageal cancer (0.82 vs 0.61, P<0.01), alcoholic AVN (0.82 vs 0.64,P<0.01) and non-alcoholic controls (0.82 vs 0.69, P<0.05).CONCLUSION: The C allele may be associated with some mechanism, which is important in the pathogenesis of alcoholic pancreatitis, and that alcoholic patients with acute pancreatitis and cirrhosis of liver are probably two different subpopulations.

  13. The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Yu-Jie Zhang

    2016-09-01

    Full Text Available Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST, alanine transaminase (ALT, total bilirubin (TBIL, triglyceride (TG, malondialdehyde (MDA, and decreased total protein (TP. Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage.

  14. Addiction specialist's role in liver transplantationprocedures for alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Although liver transplantation (LT) is performed increasinglyfor patients with end-stage alcoholic liver disease(ALD), the topic remains controversial. Traditionally, therole of an addiction specialist focused on the screeningand identification of patients with a high risk on relapsein heavy alcohol use. These patients were in many casessubsequently excluded from a further LT procedure.Recently, awareness is growing that not only screeningof patients but also offering treatment, helping patientsregain and maintain abstinence is essential, openingup a broader role for the addiction specialist (team)within the whole of the transplant procedure. Withinthis context, high-risk assessment is proposed to be anindication of increasing addiction treatment intensity,instead of being an exclusion criterion. In this review wepresent an overview regarding the state of the art onalcohol relapse assessment and treatment in patientswith alcohol use disorders, both with and without ALD.Screening, treatment and monitoring is suggested ascentral roles for the addiction specialist (team) integratedwithin transplant centers.

  15. 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.

  16. Dysbiosis-induced intestinal inflammation activates TNFRI and mediates alcoholic liver disease in mice

    Science.gov (United States)

    Chen, Peng; Stärkel, Peter; Turner, Jerrold R.; Ho, Samuel B.; Schnabl, Bernd

    2014-01-01

    Intestinal barrier dysfunction is an important contributor to alcoholic liver disease. Translocated microbial products trigger an inflammatory response in the liver and contribute to steatohepatitis. Our aim was to investigate mechanisms of barrier disruption following chronic alcohol feeding. A Lieber-DeCarli model was used to induce intestinal dysbiosis, increased intestinal permeability and liver disease in mice. Alcohol feeding for 8 weeks induced intestinal inflammation in the jejunum, which is characterized by an increased number of TNFα producing monocytes and macrophages. These findings were confirmed in duodenal biopsies from patients with chronic alcohol abuse. Intestinal decontamination with non-absorbable antibiotics restored eubiosis, decreased intestinal inflammation and permeability, and reduced alcoholic liver disease in mice. TNF-receptor I (TNFRI) mutant mice were protected from intestinal barrier dysfunction and alcoholic liver disease. To investigate whether TNFRI on intestinal epithelial cells mediates intestinal barrier dysfunction and alcoholic liver disease, we used TNFRI mutant mice carrying a conditional gain-of-function allele for this receptor. Reactivation of TNFRI on intestinal epithelial cells resulted in increased intestinal permeability and liver disease that is similar to wild type mice after alcohol feeding, suggesting that enteric TNFRI promotes intestinal barrier dysfunction. Myosin light chain kinase (MLCK) is a downstream target of TNFα and was phosphorylated in intestinal epithelial cells following alcohol administration. Using MLCK deficient mice, we further demonstrate a partial contribution of MLCK to intestinal barrier dysfunction and liver disease following chronic alcohol feeding. In conclusion, dysbiosis-induced intestinal inflammation and TNFRI signaling on intestinal epithelial cells are mediating a disruption of the intestinal barrier. Therefore, intestinal TNFRI is a crucial mediator of alcoholic liver disease

  17. Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo; Bahnsen, M

    1981-01-01

    Titres and immunoglobulin classes of autoantibodies were examined in 69 male patients with alcoholic liver cirrhosis and the findings were related to particular human leucocyte antigens and serum concentration of testosterone. Both anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA...... had higher titres of ANA (n.s.) and SMA (P less than 0.05) than patients without these HLA antigens. Serum concentrations of testosterone were significantly lower in ANA-positive patients than in those negative (P less than 0.05), and a similar tendency was found in SMA-positive patients...

  18. Correlation between liver morphology and portal pressure in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, Jens Henrik Sahl

    1984-01-01

    In 14 alcoholic patients, the degree of hepatic architectural destruction was graded (preserved architecture; nodules alternating with preserved architecture; totally destroyed architecture) and related to portal pressure. A positive correlation was found between the degree of architectural...... 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...

  19. 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.

  20. 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.

  1. 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...

  2. '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

  3. '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

  4. Docosahexaenoic acid and non-alcoholic fatty liver disease in obese children: a novel approach?

    Science.gov (United States)

    Verduci, Elvira; Lassandro, Carlotta; Radaelli, Giovanni; Soldati, Laura

    2015-04-02

    Non-alcoholic fatty liver disease represents the most common chronic liver disease in obese children of industrialized countries. Nowadays the first line of treatment of pediatric non-alcoholic fatty liver disease is based on dietary and lifestyle intervention; however compliance to these interventions is very difficult to maintain in long term period. This editorial discusses about docosahexaenoic acid treatment as possible novel approach for non-alcoholic fatty liver disease in obese children. Docosahexaenoic acid may modulate the inflammatory response, improve insulin sensitivity and could be effective in enhancing intestinal barrier integrity, essential to protect a healthy gut-liver axis. Indeed alteration of gut microbiota composition and increased intestinal permeability may rise the exposure of liver to gut-derived bacterial products, causing activation of signalling pathways implicated in liver inflammation and fibrogenesis. This mechanism has been observed in vitro and animal models of non-alcoholic fatty liver disease but also in a clinical study in adults. While evidence suggests that n-3 long-chain polyunsaturated fatty acids supplementation may decrease liver fat in adults, in pediatric population only a study examined this topic. In obese children with non-alcoholic fatty liver disease well designed randomized controlled trials are needed to better clarify the possible efficacy of docosahexaenoic acid treatment, and underlying mechanisms, to identify the optimal required dose and to evaluate if the docosahexaenoic acid effect is limited to the duration of the treatment or it may continue after the end of treatment.

  5. Increased activity of the complement system in the liver of patients with alcoholic hepatitis.

    Science.gov (United States)

    Shen, Hong; French, Barbara A; Liu, Hui; Tillman, Brittany C; French, Samuel W

    2014-12-01

    Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH.

  6. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

    Science.gov (United States)

    Kakehashi, Anna; Stefanov, Vasily E.; Ishii, Naomi; Okuno, Takahiro; Fujii, Hideki; Kawai, Kazuaki; Kawada, Norifumi; Wanibuchi, Hideki

    2017-01-01

    To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis. PMID:28218651

  7. Elevated endotoxin levels in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Kumar Sudhesh

    2010-03-01

    Full Text Available Abstract Background Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD patients, with and without type 2 diabetes mellitus (T2DM, and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status. Methods Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14, soluble tumour necrosis factor receptor II (sTNFRII and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6 or diet plus Orlistat (n = 8. Results Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8 EU/mL; controls: 3.9(3.2, 5.2 EU/mL, p Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006, weight (p = 0.005 and endotoxin (p = 0.004 compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively. Conclusions Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.

  8. The pattern of fibrosis in the acinar zone 3 areas in early alcoholic liver disease

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Vyberg, M;

    1991-01-01

    The degree of fibrosis and the pattern of collagen distribution in the acinar zone 3, as well as the thickness of the terminal hepatic vein walls (THV) were analyzed in 48 consecutive liver needle biopsies from 48 alcoholics with preserved liver architecture. The fibrosis occurred to more or less....... No relationship was found between TTHV and PSF. The results were compared to similar data obtained in liver biopsies from 117 non-alcoholics with normal morphology or slight non-specific changes. No significant difference concerning TTHV and THV diameter was found between alcoholic and non-alcoholic patients....... The results suggest that the initial liver fibrosis in alcoholics is slightly asymmetrical distributed in each acinar zone 3 area. With progression, the fibrosis tends to be more uniformly distributed and septa appear, eventually linking THV with portal tracts. Apparently, thickening of the THV walls does...

  9. Alcohol-related brain damage in humans.

    Directory of Open Access Journals (Sweden)

    Amaia M Erdozain

    Full Text Available Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA 9 from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics.

  10. 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.

  11. 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.

  12. Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model.

    Science.gov (United States)

    Müller, Peter; Messmer, Marie; Bayer, Monika; Pfeilschifter, Josef M; Hintermann, Edith; Christen, Urs

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) and its more severe development non-alcoholic steatohepatitis (NASH) are increasing worldwide. In particular NASH, which is characterized by an active hepatic inflammation, has often severe consequences including progressive fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Here we investigated how metabolic liver injury is influencing the pathogenesis of autoimmune hepatitis (AIH). We used the CYP2D6 mouse model in which wild type C57BL/6 mice are infected with an Adenovirus expressing the major liver autoantigen cytochrome P450 2D6 (CYP2D6). Such mice display several features of human AIH, including interface hepatitis, formation of LKM-1 antibodies and CYP2D6-specific T cells, as well as hepatic fibrosis. NAFLD was induced with a high-fat diet (HFD). We found that pre-existing NAFLD potentiates the severity of AIH. Mice fed for 12 weeks with a HFD displayed increased cellular infiltration of the liver, enhanced hepatic fibrosis and elevated numbers of liver autoantigen-specific T cells. Our data suggest that a pre-existing metabolic liver injury constitutes an additional risk for the severity of an autoimmune condition of the liver, such as AIH.

  13. Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I. [Ural State Technical University - UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University - UPI, Faculty of Experimental Physics (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation)

    2004-12-15

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  14. Comparative Study of Human Liver Ferritin and Chicken Liver by Mössbauer Spectroscopy. Preliminary Results

    Science.gov (United States)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-12-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Mössbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Mössbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  15. Coping and rehabilitation in alcoholic liver disease patients after hepatic encephalopathy

    DEFF Research Database (Denmark)

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

    2015-01-01

    ' coping and rehabilitation. DESIGN: A grounded theory study. METHODS: Semi-structured interviews, conducted with 11 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy. The interview guide was inspired by Richard S. Lazarus's theory of stress and coping. RESULTS: The elements...... PRACTICE: It can be assumed that professionals should support alcoholic liver disease patients' appraisal of, and coping with, physical and psychosocial problems based on acknowledgment, understanding and a sympathetic attitude. Professionals should proactively approach patients when they withdraw. It may...... be useful for professionals to be aware of alcoholic liver disease patients' individual coping strategies and thereby their individual requirements for professional supportive intervention....

  16. The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids

    Directory of Open Access Journals (Sweden)

    Suzanne M. de la Monte

    2009-07-01

    Full Text Available Alcohol abuse causes progressive toxicity and degeneration in liver and brain due to insulin resistance, which exacerbates oxidative stress and pro-inflammatory cytokine activation. Alcohol-induced steatohepatitis promotes synthesis and accumulation of ceramides and other toxic lipids that cause insulin resistance. Ceramides can readily cross the blood-brain barrier, and ceramide exposure causes neurodegeneration with insulin resistance and oxidative stress, similar to the effects of alcohol. Therefore, in addition to its direct neurotoxic effects, alcohol misuse establishes a liver-brain axis of neurodegeneration mediated by toxic lipid trafficking across the blood-brain barrier, leading to progressive white matter degeneration and cognitive impairment.

  17. 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.

  18. Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

    Institute of Scientific and Technical Information of China (English)

    Fang Song; Mei-Lin Xie; Lu-Jia Zhu; Ke-Ping Zhang; Jie Xue; Zhen-Lun Gu

    2006-01-01

    AIM: To evaluate the effects of osthole on fatty liver,and investigate the possible mechanism.METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured.RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved.In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation.CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fatinduced fatty liver. The mechanism might be associated with its antioxidation.

  19. Diagnosis and classification of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: Current concepts and remaining challenges.

    Science.gov (United States)

    Hashimoto, Etsuko; Tokushige, Katsutoshi; Ludwig, Jurgen

    2015-01-01

    The high prevalence of non-alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular, hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clinicopathological criteria; it always requires both clinical and biopsy-based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are: (i) the lack of a clear threshold alcohol intake for defining "non-alcoholic"; (ii) a lacking consensus for the classification of fatty liver disease; and (iii) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.

  20. [Gender difference of clinical features in Japanese patients with alcoholic liver cirrhosis].

    Science.gov (United States)

    Kawashima, Osamu; Ohata, Mitsuru; Sakamoto, Kazuhiko; Hashimoto, Kenichi; Nakajima, Hisato; Yamauchi, Masayoshi

    2003-02-01

    Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin.

  1. From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele; Santoro, Nicola

    2017-01-18

    In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction.

  2. A Mechanistic Review of Mitophagy and Its Role in Protection against Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Jessica A. Williams

    2015-10-01

    Full Text Available Alcoholic liver disease (ALD is a major health problem worldwide, and alcohol is well-known to cause mitochondrial damage, which exacerbates alcohol-induced liver injury and steatosis. No successful treatments are currently available for treating ALD. Therefore, a better understanding of mechanisms involved in regulation of mitochondrial homeostasis in the liver and how these mechanisms may protect against alcohol-induced liver disease is needed for future development of better therapeutic options for ALD. Mitophagy is a key mechanism for maintaining mitochondrial homeostasis by removing damaged mitochondria, and mitophagy protects against alcohol-induced liver injury. Parkin, an E3 ubiquitin ligase, is well-known to induce mitophagy in in vitro models although Parkin-independent mechanisms for mitophagy induction also exist. In this review, we discuss the roles of Parkin and mitophagy in protection against alcohol-induced liver injury and steatosis. We also discuss Parkin-independent mechanisms for mitophagy induction, which have not yet been evaluated in the liver but may also potentially have a protective role against ALD. In addition to mitophagy, mitochondrial spheroid formation may also provide a novel mechanism of protection against ALD, but the role of mitochondrial spheroids in protection against ALD progression needs to be further explored. Targeting removal of damaged mitochondria by mitophagy or inducing formation of mitochondrial spheroids may be promising therapeutic options for treatment of ALD.

  3. CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Sila; Cocciolillo; Giustino; Parruti; Leonardo; Marzio

    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.METHODS: This prospective study included 15 patients with NAFLD, 17 patients with NASH and 16 healthy controls.In each patient, real-time ultrasound was used to locate the portal vein (PV) and the right liver lobe, and 5 mL of SonoVue? was then injected intravenous in a peripheral vein of the left arm over a 4-s span. Digital recording was performed for 3 min thereafter. The recording was subsequently retrieved to identify an area of interest in the PV area and in the right liver parenchyma(LP) to assess the blood flow by processing the data using dedicated software (Qontrast?, Bracco, Italy).The following parameters were evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP, s), regional blood volume (RBV, cm3), regional blood flow (RBF, cm3/s) and mean transit time (MTT, s).At 24-48 h post-injection, liver stiffness was evaluated using Fibroscan and measured in kPa. The statistical evaluation was performed using Student’s t test.RESULTS: In the PV, the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patientscompared with the controls (Peak%: NAFLD 26.3 ± 6.6,NASH 28.1 ± 7.3 vs controls 55.8 ± 9.9, P < 0.001;RBV: NAFLD 4202.3 ± 3519.7, NASH 3929.8 ± 1941.3vs controls 7473 ± 3281, P < 0.01; RBF: NAFLD 32.5± 10.8, NASH 32.7 ± 12.1 vs controls 73.1 ± 13.9, P< 0.001). The TTP in the PV was longer in both patient groups but reached statistical significance only in the NASH patients compared with the controls (NASH 79.5± 37.8 vs controls 43.2 ± 30, P < 0.01). In the LP,the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patients compared with the controls (Peak%: NAFLD 43.2 ± 7.3, NASH 41.7 ± 7.7 vs controls 56.6 ± 6.3, P < 0.001; RBV: NAFLD 4851.5± 2009, NASH 5069.4 ± 2292.5 vs

  4. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease

    Directory of Open Access Journals (Sweden)

    Stefano Gitto

    2016-01-01

    Full Text Available Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption.

  5. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease.

    Science.gov (United States)

    Gitto, Stefano; Golfieri, Lucia; Caputo, Fabio; Grandi, Silvana; Andreone, Pietro

    2016-01-15

    Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption.

  6. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    Science.gov (United States)

    Meikle, Peter J; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K; Duly, Alastair M P; Haber, Paul S; Whitfield, John B; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

  7. AGE WISE HISTOMORPHOLOGICAL CHANGES IN HUMAN LIVER

    Directory of Open Access Journals (Sweden)

    Tribeni

    2015-11-01

    Full Text Available CONTEXT: Hepato cellular carcinoma (HCC results in between 2.5 lakhs to 1million deaths globally per annum. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. AIMS: Keeping this concept in view, a study was conducted in the Guwahati Zone of Northeast India, to compare the histomorphological features of the human liver in different age groups. SETTING AND DESIGN: Apparently healthy livers were obtained from 21 subjects on whom medicolegal post-mortems had been performed. Their ages varied from newborn to 90 years. Subjects were divided into 3 groups. 7 specimens were taken from each group. (1 Pediatric (2 Adult (3 Old age. METHODS AND MATERIALS: In all the above age groups, immediately after removal of the livers, they were washed in normal saline, dried with blotting paper and weighed in an electronic weighing machine. Sections of liver were fixed, processed, cut and stained with Harris Haematoxylin and Eosin stain. RESULTS: The liver loses weight from 50 years onwards. There appears to be racial and environmental differences in the change in liver weight in old age. Autopsy studies show a diminution of nearly 46% in liver weight between the 3rd and 10th decades of life. The liver decreases in size with age. The hepatocytes are radially disposed in the liver lobule. They are piled up, forming a layer one cell thick (except in young children in a fashion similar to the bricks of a wall. These plates are directed from the periphery of the lobule to its centre and anastomose freely forming a complex labyrinthine and sponge-like structure. CONCLUSIONS: From the findings in the present study it can be concluded that: 1. Nowadays, the measurement of liver volume has gained practical use in relation to liver transplantation. 2. We have compared the histomorphology of adult liver with a child. The findings in both the groups are very similar. This feature is important, since in

  8. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    Science.gov (United States)

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  9. Fatty liver disease in Sudan is not alcohol related | Nail | Sudan ...

    African Journals Online (AJOL)

    Fatty liver disease in Sudan is not alcohol related. ... Objectives: The aim of this study is to find out the prevalence, clinical ... Data was collected using a well designed questionnaire and results were analyzed by using SPSS computer system.

  10. Role of farnesoid X receptor and bile acids in alcoholic liver disease

    Directory of Open Access Journals (Sweden)

    Sharon Manley

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a and PPARα (peroxisome proliferator-activated receptor alpha in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

  11. [Electron microscopic study of cytoplasmic crystals in liver damages caused by alcoholism].

    Science.gov (United States)

    Schaff, Z; Lapis, K

    1975-01-01

    Liver biopsy of 50 patients with liver disease of alcoholic etiology was examined electronmicroscopically. In every stage of the disease presence of intramitochondrial paracrystalloids was revealed. Hyalin of alcoholic origin of fibrillar structure was seen in cases of alcoholic hepatitis. By the electronmicroscopic examination of three cases of alcoholic fatty liver a special form of cytoplasmatic paracristalloid inclusion could be seen. This inclusion consists of membranless parallely lying fibrills. Changing the plain of the preparats containing inclusions by the aid of a goniometer the structure of the inclusions appeared in a form of "honey-comb". Inclusion in the question can not be regarded identical neither with intramitochondrial inclusions nor with the fibrills of the so called alcoholic hyalin. Formation and function of these inclusions are as yet unknown.

  12. Epigallocatechin-3-Gallate Ameliorates Alcohol-Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Xi Li

    2006-07-01

    Full Text Available Endotoxemia is a common event in alcoholic liver disease. Elevated intestinalpermeability is the major factor involved in the mechanism of alcoholic endotoxemia andthe pathogenesis of alcoholic liver disease. This study examined the effect ofepigallocatechin-3-gallate (EGCG on alcohol-induced gut leakiness, and explored therelated mechanisms involved in its protection against alcohol-induced liver injury in rats.Four groups of female Sprague-Dawley rats were studied. Alcohol and alcohol/EGCGgroups rats received fish oil along with alcohol daily via gastrogavage for 6 weeks, anddextrose and dextrose/EGCG groups rats were given fish oil along with isocaloric dextroseinstead of alcohol. The dextrose/EGCG and alcohol/EGCG groups received additionaltreatment of EGCG (100mg.kg-1 body weight daily intragastrically by gavage. Intestinalpermeability was assessed by urinary excretion of lactulose and mannitol (L/M ratio. Liverinjury was evaluated histologically and by serum alanine aminotransferase (ALT. Plasmaendotoxin and serum tumor necrosis factor-α (TNF-α levels were assayed; livermalondialdehyde (MDA contents determined. CD14 and inflammatory factors, such asTNF-α, cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS mRNAs inthe liver were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR. Ratsgiven fish oil plus alcohol had gut leakiness (L/M ratio was increased, which wasassociated with both endotoxemia and liver injury. The above responses were accompaniedby increased CD14, TNF-α, COX-2 and iNOS mRNA expressions in the liver. EGCGsupplementation partly blocked the gut leakiness, reduced endotoxemia and lipidperoxidation, and blunted the elevated expressions of CD14, TNF-α, COX-2 and iNOS, allof which were associated with improved liver injury. These results show that EGCG can block alcohol-induced gut leakiness, reduce endotoxemia, and inhibit inflammatory factors expressions in

  13. 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.

  14. Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models.

    Science.gov (United States)

    Bility, Moses T; Li, Feng; Cheng, Liang; Su, Lishan

    2013-08-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system's contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8-hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8-hu HSC/Hep mouse, which supports HCV infection, human T-cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long-term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV-infected humanized mice. HCV infection also induced HCV-specific T-cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti-human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV-infected humanized mice. We discuss the limitation and future improvements of the AFC8-hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer.

  15. SIRT3 as a Regulator of Non-alcoholic Fatty Liver Disease

    OpenAIRE

    Cho, Eun-Hee

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. NAFLD includes a large spectrum of hepatic pathologies that range from simple steatosis and non-alcoholic steatohepatitis (NASH), to liver cirrhosis without an all-encompassing approved therapeutic strategy. Mitochondrial dysfunction is a key component of many metabolic diseases, such as obesity, type 2 diabetes, cancer, NAFLD, and aging. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase tha...

  16. Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Masahide Hamaguchi; Takao Kojima; Akihiro Ohbora; Noriyuki Takeda; Michiaki Fukui; Takahiro Kato

    2012-01-01

    AIM: To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women. METHODS: A cross-sectional study was conducted in a medical health checkup program at a general hospital. This study involved 18 571 Japanese men and women, 18-88 years of age, with a mean body mass index of 22.6 kg/m2. A standardized questionnaire was administered. The total amount of alcohol consumed per week was calculated, and categorized into four grades. Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Education Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation. RESULTS: The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption, whereas the prevalence of MS was not so changed. The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption. In women with light to moderate alcohol consumption, prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption. By logistic regression analysis, the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0, but this change was not clear in men. The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption. CONCLUSION: Light to moderate alcohol consumption has a favorable effect for fatty liver, but not for MS in Japanese men and women.

  17. The outcome of critical illness in decompensated alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Kavli, M; Strøm, T; Carlsson, M;

    2012-01-01

    with the Child-Pugh score. METHODS: A single-centre retrospective cohort analysis was conducted in a university-affiliated ICU. Eighty-seven adult patients with decompensated liver alcoholic cirrhosis were admitted from January 2007 to January 2010. RESULTS: The patients were severely ill with median scores......: SAPS II 60, SOFA (day 1) 11, APACHE II 31, and Child-Pugh 12. Receiver operating characteristic curves area under curve was 0.79 for APACHE II, 0.83 for SAPS II, and 0.79 for SOFA (day1) compared with 0.59 for Child-Pugh. In patients only in need of mechanical ventilation, the 90-day mortality was 76......, SAPS II, and SOFA were better at predicting mortality than the Child-Pugh score. With three or more organ failures, the ICU mortality was > 90%. APACHE II > 30, SAPS II > 60, and SOFA at day 1 > 12 were all associated with a mortality of > 90%. Referral criteria of patients suffering from decompensated...

  18. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver.

    Science.gov (United States)

    Kersten, Sander; Stienstra, Rinke

    2017-05-01

    The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver. Here, an overview is provided of the role and regulation of PPARα in human liver. The main outcomes are: 1) the level of PPARA mRNA expression in human and mouse liver is similar. 2) Expression of PPARA in human liver is reduced in patients with non-alcoholic steatohepatitis or infected with the hepatitis C virus. 3) PPARα in human liver is able to effectively induce the expression of numerous genes involved in numerous lipid metabolic pathways, including microsomal, peroxisomal and mitochondrial fatty acid oxidation, fatty acid binding and activation, fatty acid elongation and desaturation, synthesis and breakdown of triglycerides and lipid droplets, lipoprotein metabolism, gluconeogenesis, bile acid metabolism, and various other metabolic pathways and genes. 4) PPARα activation in human liver causes the down-regulation of a large number of genes involved in various immunity-related pathways. 5) Peroxisome proliferators do not promote tumour formation in human liver as opposed to mouse liver because of structural and functional differences between human and mouse PPARα. 6) In addition to helping to correct dyslipidemia, PPARα agonists may hold promise as a therapy for patients with cholestatic liver diseases, non-alcoholic fatty liver disease, and/or type 2 diabetes. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  19. Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Johansen, Julia S; Christensen, Erik;

    2003-01-01

    patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated......BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy...... in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information....

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

    Science.gov (United States)

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

    2016-03-01

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

  1. 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

    evaluation of liver biopsies, no significant correlation was found between mean hepatocyte volume or relative sinusoidal vascular volume and portal pressure. To test whether an increase in hepatocyte volume compresses the vascular structures and causes portal hypertension, the ratio of relative sinusoidal...... vascular volume to mean hepatocyte volume, which expresses the compression of the vascular structures exerted by enlargement of hepatocytes, was related to portal pressure. No significant correlation was found. Further, mean hepatocyte volume was not significantly correlated to relative sinusoidal vascular......In 14 alcoholic patients, the degree of hepatic architectural destruction was graded (preserved architecture; nodules alternating with preserved architecture; totally destroyed architecture) and related to portal pressure. A positive correlation was found between the degree of architectural...

  2. Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances.

    Science.gov (United States)

    Lau, Jennie Ka Ching; Zhang, Xiang; Yu, Jun

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field. This review presents a critical analysis of the histopathology and pathogenesis of NAFLD, the most frequently used and recently developed animal models for each stage of NAFLD and NAFLD-induced HCC, the main mechanisms involved in the experimental pathogenesis of NAFLD in different animal models, and a brief summary of recent therapeutic targets found by the use of animal models. Integrating the data from human disease with those from animal studies indicates that, although current animal models provide critical guidance in understanding specific stages of NAFLD pathogenesis and progression, further research is necessary to develop more accurate models that better mimic the disease spectrum, in order to provide both increased mechanistic understanding and identification/testing of novel therapeutic approaches. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  3. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Haoyong Yu

    2014-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal and low carbohydrate (<10% for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004. Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05. The suppression of post-load HGP was improved by 22% (p = 0.002 whereas glucose disposal was not affected (p = 0.3. Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05. Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment.

  4. 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.

  5. 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.

  6. 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.

  7. Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hannele Yki-Järvinen

    2015-11-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL to non-alcoholic steatohepatitis (NASH and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD. Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA as compared to monounsaturated (MUFA or polyunsaturated (PUFA fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

  8. 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.

  9. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Gemma Aragonès

    2016-04-01

    Full Text Available Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3 in the pathology of non-alcoholic fatty liver disease (NAFLD. Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18, simple steatosis (SS, n = 20, and non-alcoholic steatohepatitis (NASH, n = 17. Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

  10. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis. PMID:27128907

  11. Adipose tissue-derived stem cells promote the reversion of non-alcoholic fatty liver disease: An in vivo study.

    Science.gov (United States)

    Liao, Naishun; Pan, Fan; Wang, Yingchao; Zheng, Youshi; Xu, Bo; Chen, Wenwei; Gao, Yunzhen; Cai, Zhixiong; Liu, Xiaolong; Liu, Jingfeng

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver injury and seriously affects human health. In the present study, we aimed to investigate whether adipose tissue-derived stem cell (ADSC) transplantation in combination with dietary modification was capable of reversing the progression of NAFLD. After establishing a rat model of NAFLD by feeding them a high-fat diet (HFD), ADSCs were transplanted via the portal vein into rats with HFD-induced NAFLD, and simultaneously fed a modified diet. Thereafter, gross liver morphology, the hepatosomatic (HSI) index and indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were evaluated. Subsequently, the serum levels of total cholesterol (TC), triglycerides (TGs) and fatty acids (FAs) were also assayed. Furthermore, H&E and oil red O staining were used to confirm the pathological effects of NAFLD in the rat livers. Although dietary modification alone caused liver function to recover, ADSC transplantation in combination with dietary modification further decreased the HSI index, the serum levels of ALT, TBIL, TC, TGs, FAs, reduced lipid accumulation to normal levels, and reversed the hepatic pathological changes in the rat livers. Taken together, these findings suggest that ADSC transplantation assists in the reversion of NAFLD by improving liver function and promoting lipid metabolism, thereby exerting hepatoprotective effects. Thus, we suggest that ADSC transplantation is a promising, potential therapeutic strategy for NAFLD treatment.

  12. Discrimination of individuals in a general population at high-risk for alcoholic and non-alcoholic fatty liver disease based on liver stiffness: a cross section study

    Directory of Open Access Journals (Sweden)

    Kasai Kenji

    2011-06-01

    Full Text Available Abstract Background Factors associated with liver stiffness (LS are unknown and normal reference values for LS have not been established. Individuals at high risk for alcoholic (ALD and non-alcoholic fatty (NAFLD liver disease need to be non-invasively discriminated during routine health checks. Factors related to LS measured using a FibroScan and normal reference values for LS are presented in this report. Methods We measured LS using a FibroScan in 416 consecutive individuals who presented for routine medical checks. We also investigated the relationship between LS and age, body mass index (BMI, liver function (LF, alcohol consumption, and fatty liver determined by ultrasonography. We identified individuals at high-risk for ALD and NAFLD as having a higher LS value than the normal upper limit detected in 171 healthy controls. Results The LS value for all individuals was 4.7 +/- 1.5 kPa (mean +/- SD and LS significantly and positively correlated with BMI and LF test results. The LS was significantly higher among individuals with, than without fatty liver. Liver stiffness in the 171 healthy controls was 4.3 +/- 0.81 kPa and the upper limit of LS in the normal controls was 5.9 kPa. We found that 60 (14.3% of 416 study participants had abnormal LS. The proportion of individuals whose LS values exceeded the normal upper limit was over five-fold higher among those with, than without fatty liver accompanied by abnormal LF test results. Conclusions Liver stiffness could be used to non-invasively monitor the progression of chronic liver diseases and to discriminate individuals at high risk for ALD and NAFLD during routine health assessments.

  13. Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, J H

    1987-01-01

    Liver haemodynamics and liver function were measured in 34 alcoholic cirrhotic men before entry and after 12 months (median) in a double-blind, placebo-controlled study on the effect of oral testosterone treatment (200 mg t.i.d.). Comparing data at entry with those at follow-up in the total patie...

  14. The Potential of Flavonoids in the Treatment of Non-alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    van de Wier, B.; Koek, Ger H.; Bast, Aalt; Haenen, Guido R.M.

    2015-01-01

    The contemporary pathophysiological model of non-alcoholic fatty liver disease (NAFLD) consists of multiple parallel pathways with a dynamic cross talk that cumulate in steatosis and inflammation and ultimately fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. So far, no pharmacologic

  15. Budd-Chiari like syndrome in decompensated alcoholic steatohepatitis and liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Carlos Robles-Medranda; Hannah Lukashok; Beatriz Biccas; Vera L Pannain; Homero S Fogaca

    2006-01-01

    A rare case of pseudo-Budd-Chiari Syndrome in a patient with decompensated alcoholic liver disease is reported.Although clinical and radiological findings suggested Budd-Chiari Syndrome, the liver biopsy revealed micronodular cirrhosis and absence of histological signs of hepatic outflow obstruction.

  16. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  17. 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.

  18. 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.

  19. Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Petta, S; Ciminnisi, S; Di Marco, V; Cabibi, D; Cammà, C; Licata, A; Marchesini, G; Craxì, A

    2017-02-01

    Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass index ≤37 in males and ≤28 in females. The prevalence of sarcopenia showed a linear increase with the severity of fibrosis, and severe fibrosis (F3-F4) was more than doubled in sarcopenia (48.3% vs. 20.4% in fibrosis ≤F2, P sarcopenia with severe fibrosis was maintained (OR 2.36, CI 1.16-4.77, P = 0.01), together with age > 50 (OR 6.53, CI 2.95-14.4, P sarcopenia and NASH (P = 0.01), steatosis severity (P = 0.006), and ballooning (P = 0.01), but only the association with severe steatosis was maintained (OR 2.02, CI 1.06-3.83, P = 0.03) after adjusting for confounders. In Western patients with NAFLD, with high prevalence of metabolic disorders and advanced liver disease, sarcopenia was associated with the severity of fibrosis and steatosis, independently of hepatic and metabolic risk factors. Studies are needed to assess the impact of interventions to reduce sarcopenia on NAFLD progression. © 2016 John Wiley & Sons Ltd.

  20. 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.

  1. Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

    Science.gov (United States)

    Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

    2016-10-01

    Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. Copyright © 2016 by the Research Society on Alcoholism.

  2. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

    OpenAIRE

    Min Yang; Sitang Gong; Shui Qing Ye; Beth Lyman; Lanlan Geng; Peiyu Chen; Ding-You Li

    2014-01-01

    With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention an...

  3. Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage

    Science.gov (United States)

    Schreiter, Thomas; Sowa, Jan-Peter; Schlattjan, Martin; Treckmann, Jürgen; Paul, Andreas; Strucksberg, Karl-Heinz; Baba, Hideo A.; Odenthal, Margarete; Gieseler, Robert K.; Gerken, Guido; Arteel, Gavin E.; Canbay, Ali

    2016-01-01

    Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients. PMID:27550092

  4. Obesity accelerates epigenetic aging of human liver.

    Science.gov (United States)

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

  5. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

    Science.gov (United States)

    Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

    2015-06-01

    Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Relevant Aspects of Nutritional and Dietary Interventions in Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Maria Catalina Hernandez-Rodas

    2015-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the main cause of liver disease worldwide. NAFLD is linked to circumstances such as type 2 diabetes, insulin resistance, obesity, hyperlipidemia, and hypertension. Since the obesity figures and related comorbidities are increasing, NAFLD has turned into a liver problem that has become progressively more common. Currently, there is no effective drug therapy for NAFLD; therefore, interventions in lifestyles remain the first line of treatment. Bearing in mind that adherence rates to this type of treatment are poor, great efforts are currently focused on finding novel therapeutic agents for the prevention in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis and cirrhosis. This review presents a compilation of the scientific evidence found in the last years showing the results of interventions in lifestyle, diet, and behavioral therapies and research results in human, animal and cell models. Possible therapeutic agents ranging from supplementation with vitamins, amino acids, prebiotics, probiotics, symbiotics, polyunsaturated fatty acids and polyphenols to interventions with medicinal plants are analyzed.

  7. Iron homeostasis and H63D mutations in alcoholics with and without liver disease

    Institute of Scientific and Technical Information of China (English)

    Mariana Verdelho Machado; Paula Ravasco; Alexandra Martins; Maria Ermelinda Camilo; Helena Cortez-Pinto; Maria Rosario Almeida

    2009-01-01

    AIM: To evaluate the prevalence of HFE gene mutation and indices of disturbed iron homeostasis in alcoholics with and without liver disease. METHODS: One hundred and fifty-three heavy drinkers (defined as alcohol consumption > 80 g/d for at least 5 years) were included in the study. These comprised 78 patients with liver disease [liver disease alcoholics (LDA)] in whom the presence of liver disease was confirmed by liver biopsy or clinical evidence of hepatic decompensation, and 75 subjects with no evidence of liver disease, determined by normal liver tests on two occasions [non-liver disease alcoholics (NLDA)], were consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D mutations were determined. HFE genotyping was compared with data obtained in healthy blood donors from the same geographical area. RESULTS: Gender ratio was similar in both study groups. LDA patients were older than NLDA patients third and one fifth of the study population had serum transferrin saturation (TS) greater than 45% and 60% respectively. Serum iron levels were similar in both groups. However, LDA patients had higher TS for having liver disease with TS greater than 45% was 2.20 (95% confidence interval (CI): 1.37-3.54). There was no difference in C282Y allelic frequency between the two groups. However, H63D was more frequent in LDA patients (0.25 vs 0.16, P = 0.03). LDA patients had a greater probability of carrying at least one HFE mutation than NLDA patients (49.5% vs 31.6%, P = 0.02). The odds ratio for LDA in patients with H63D mutation was 1.57 (95% CI: 1.02-2.40).CONCLUSION: The present study confirms the presence of iron overload in alcoholics, which was more severe in the subset of subjects with liver disease,in parallel with an increased frequency of H63D HFE mutation.

  8. The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers.

    Science.gov (United States)

    Takeshita, T; Yang, X; Morimoto, K

    2000-06-01

    A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2) may influence alcohol-induced liver injury because of higher production of acetaldehyde in the liver. In the present study, we examined relationships between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. Study subjects were 385 male workers in a metal plant in Japan, who were free from hepatic viruses and did not have higher aminotransferase activities (alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined by the PCR method followed by restriction-enzyme digestion. In the moderately and heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower levels than those with ALDH2*1/*1 for all three parameters of liver function, whereas no such differences were observed in the least-drinking group. Multiple linear-regression analysis, adjusting for age, obesity, and smoking habits, revealed that aspartate aminotransferase activity was positively associated with alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine transferase activity was negatively associated with alcohol intake only in those with ALDH2*1/*2. The present study indicates that effects of alcohol intake on liver-function biomarkers are likely to be modified by the ALDH2 genotype in adult males.

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

    Science.gov (United States)

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

    2015-12-01

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

  10. Ubiquitin: an immunohistochemical marker of Mallory bodies and alcoholic liver disease

    DEFF Research Database (Denmark)

    Vyberg, Mogens; Leth, Peter Mygind

    1991-01-01

    One hundred forty eight liver needle biopsies, comprising 88 consecutive biopsies from patients with clinically diagnosed or suspected alcoholic liver disease and 60 selected biopsies from non-alcoholics, were immunostained for the cell stress protein ubiquitin (Ub). Ub + cells were detected in all...... duct obstruction, or various hepatitides. Thus Ub-immunostaining appears to be a highly sensitive and specific method in the detection of MBs and MB precursor stages, making it a valuable tool in the study of alcoholic liver disease, and particularly a more objective method (compared to conventional...... of 33 biopsies with alcoholic hepatitis (AH). Practically all Mallory bodies (MBs) showed intense Ub-staining. In addition, many cells revealed Ub + granules lying aggregated (pre-MBs) or dispersed in the cytoplasm of ballooned cells. The mean number of Ub + cells in 10 biopsies with AH was more than 30...

  11. Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver.

    Science.gov (United States)

    McVicker, Benita L; Thiele, Geoffrey M; Tuma, Dean J; Casey, Carol A

    2014-09-01

    The consumption of alcohol is associated with many health issues including alcoholic liver disease (ALD). The natural history of ALD involves the development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis. During the stage of steatohepatitis, the combination of inflammation and cellular damage can progress to a severe condition termed alcoholic hepatitis (AH). Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations have been identified in host defense and liver immunity mechanisms during AH that highlight the role of intrahepatic lymphocyte accumulation and associated inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced injury to liver cells may significantly contribute to the aberrant lymphocytic distribution that is seen in AH. In particular, the regulation of lymphocytes by hepatocytes may be disrupted in the alcoholic liver resulting in altered immunologic homeostasis and perpetuation of disease. In recent studies, it was demonstrated that the direct killing of activated T lymphocytes by hepatocytes is facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well-characterized glycoprotein receptor that is exclusively expressed by hepatocytes. This hepatic receptor is known for its role in the clearance of desialylated glycoproteins or cells, yet neither its physiological function nor its role in disease states has been determined. Interestingly, alcohol markedly impairs ASGPR function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of lymphocytes remains to be elucidated. This review discusses the contribution of hepatocytes in immunological regulation and, importantly, how pathological effects of ethanol disrupt hepatocellular-mediated defense mechanisms.

  12. 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.

  13. Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Johansen, Julia S; Christensen, Erik

    2003-01-01

    BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy...... patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated...... in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated...

  14. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been show...

  15. Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation

    Directory of Open Access Journals (Sweden)

    Xiaxia Cai

    2016-03-01

    Full Text Available Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water, alcohol control group (basal diet, 50% alcohol (v/v, dextrose control group (basal diet, isocaloric amount of dextrose, and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg−1 respectively, 50% alcohol (v/v. The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS was applied to identify liver metabolite profiles. Results: Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid, as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, l-leucine, alanyl-leucine and l-phenylalanine. Conclusion: These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.

  16. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  17. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices.

    Science.gov (United States)

    Vickers, Alison E M; Ulyanov, Anatoly V; Fisher, Robyn L

    2017-03-07

    Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM). Oxidative stress genes were affected by TBF (18%), CBZ, APAP, and ETM (12%-11%), and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%-6%). Apoptosis genes were affected by DCF (14%), while apoptosis plus necrosis were altered by APAP and ETM (15%). Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%), ETM (66%), DCF, TBF, MMI (61%-60%), APAP, CBZ (57%-56%), and DTL (48%). Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%), CBZ and ETM (44%-43%), APAP and DCF (40%-38%), MMI, TBF and CSA (37%-35%). This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  18. Photoacoustic physio-chemical analysis of liver conditions in animal and human subjects

    Science.gov (United States)

    Wang, Xueding; Xu, Guan; Tian, Chao; Wan, Shanshan; Welling, Theodore H.; Lok, Anna S. F.; Rubin, Jonathan M.

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a common liver disease affecting 30% of the population in the United States. Biopsy is the gold standard for diagnosing NAFLD. Liver histology assesses the amount of fat, and determines type and extent of cell injury, inflammation and fibrosis. However, liver biopsy is invasive and is limited by sampling error. Current radiological diagnostic modalities can evaluate the 'physical' morphology in liver by quantifying the backscattered US signals, but cannot interrogate the 'histochemical' components forming these backscatterers. For example, ultrasound (US) imaging can detect the presence of fat but cannot differentiate steatosis alone from steatohepatitis. Our previous study of photoacoustic physiochemical analysis (PAPCA) has demonstrated that this method can characterize the histological changes in livers during the progression of NAFLD in animal models. In this study, we will further validate PAPCA with human livers. Ex vivo human liver samples with steatosis, fibrosis and cirrhosis will be scanned using optical illumination at wavelengths of 680-1700 nm and compared to histology results. In vivo study on human subjects with confirmed steatosis is planned using our PA-ultrasound (US) parallel imaging system based on Verasonic US imaging flatform with an L7-4 probe. 10 mJ/cm2 per pulse optical energy at 755 nm will be delivered to the skin surface, which is under the safety limit of American National Standard Institute. Preliminary study with ex vivo human tissue has demonstrated the potential of the proposed approach in differentiating human liver conditions.

  19. Sexual dysfunction in men with alcoholic liver cirrhosis. A comparative study

    DEFF Research Database (Denmark)

    Jensen, S B; Gluud, C

    1985-01-01

    Sexual dysfunction in men with alcoholic cirrhosis was investigated in young (less than 56 years) outpatients with steady female partners. Sixty-one per cent (11/18) claimed sexual dysfunction, with erectile dysfunction and/or reduced sexual desire being the most common symptoms. Comparing patients...... not significantly different comparing alcoholic cirrhotic men to chronic alcoholic men without overt liver disease (matched for duration of alcoholism, age and duration of partnership) and to insulin-dependent diabetic men (matched for age and duration of partnership). However, all groups had a significantly (p...

  20. Host factors are dominant in the development of post-liver transplant non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Salih; Boga; Armando; Salim; Munoz-Abraham; Manuel; I; Rodriguez-Davalos; Sukru; H; Emre; Dhanpat; Jain; Michael; L; Schilsky

    2016-01-01

    Non-alcoholic fatty liver disease(NAFLD) is a recognized problem in patients after orthotopic liver transplantation and may lead to recurrent graft injury. As the increased demand for liver allografts fail to match the available supply of donor organs, split liver transplantation(SLT) has emerged as an important technique to increase the supply of liver grafts. SLT allows two transplants to occur from one donor organ, and provides a unique model for observing the pathogenesis of NAFLD with respect to the role of recipient environmental and genetic factors. Here we report on two recipients of a SLT from the same deceased donor where only one developed non-alcoholic steatohepatitis(NASH), suggesting that host factors are critical for the development of NASH.

  1. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but it

  2. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but

  3. Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models

    OpenAIRE

    Bility, Moses T.; Li, Feng; Cheng, Liang; Su, Lishan

    2013-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system’s contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mous...

  4. Histomorphological features of pancreas and liver in chronic alcoholics - an analytical study in 390 autopsy cases

    Directory of Open Access Journals (Sweden)

    Pallavi Agrawal

    2014-01-01

    Full Text Available Introduction: Chronic pancreatitis and liver disease are two conditions that commonly co-exist in chronic alcoholics with variable incidences. Aim: To evaluate frequency pancreatitis in patients with a history of chronic alcohol abuse. Materials and Methods: A total of 390 autopsies over 11 year′s period were included in the study. Gross and microscopic assessment of liver and pancreas were performed. Available clinical and laboratory parameters were recorded. Results: Age ranged from 22 to 65 years with a mean age of 45.32 years. All 390 consecutive patients included in the study were males. Majority of the patients had primarily presented with alcohol related liver diseases whereas few had presented with features of pancreatitis. Micronodular cirrhosis was present in 292 cases. Features of chronic pancreatitis were observed in 42 cases and 8 of these cases had associated changes of acute hemorrhagic pancreatitis. Prevalence of pancreatitis was more in cirrhotics as compared to non-cirrhotics, and acute pancreatitis was mostly seen in non-cirrhotics. Dominant pattern of fibrosis was perilobular followed by periductal, intralobular and diffuse. Conclusion: Chronic pancreatitis as evidence by the presence of parenchymal fibrosis was more frequently observed in alcoholic cirrhosis cases than that in non-cirrhotic alcoholic liver disease, thereby suggesting common underlying pathobiology in the development of fibrosis in liver as well as in pancreas.

  5. 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.

  6. 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.

  7. Human herpesvirus 6 infections after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Rima Camille Abdel Massih; Raymund R Razonable

    2009-01-01

    Human herpesvirus 6 (HHV-6) infections occur in > 95% of humans. Primary infection, which occurs in early childhood as an asymptomatic illness or manifested clinically as roseola infantum, leads to a state of subclinical viral persistence and latency. Reactivation of latent HHV-6 is common after liver transplantation, possibly induced and facilitated by allograft rejection and immunosuppressive therapy. Since the vast majority of humans harbor the virus in a latent state, HHV-6 infections after liver transplantation are believed to be mostly due to endogenous reactivation or superinfection (reactivation in the transplanted organ). In a minority of cases, however,primary HHV-6 infection may occur when an HHV-6 negative individual receives a liver allograft from an HHV-6 positive donor. The vast majority of documented HHV-6 infections after liver transplantation are asymptomatic. In a minority of cases, HHV-6 has been implicated as a cause of febrile illness with rash and myelosuppression, hepatitis, pneumonitis, and encephalitis after liver transplantation. In addition,HHV-6 has been associated with a variety of indirect effects such as allograft rejection, and increased predisposition and severity of other infections including cytomegalovirus (CMV), hepatitis C virus, and opportunistic fungi. Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6, there is currently no recommended HHV-6- specific approach to prevention. However, ganciclovir and valganciclovir, which are primarily intended for the prevention of CMV disease, are also active against HHV-6 and may prevent its reactivation after transplantation. The treatment of established HHV-6 disease is usually with intravenous ganciclovir, cidofovir,or foscarnet, complemented by reduction in the degree of immunosuppression. This article reviews the current advances in the pathogenesis, clinical diagnosis, and therapeutic modalities against HHV6 in the setting of liver transplantation.

  8. Barley Sprouts Extract Attenuates Alcoholic Fatty Liver Injury in Mice by Reducing Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Yun-Hee Lee

    2016-07-01

    Full Text Available It has been reported that barley leaves possess beneficial properties such as antioxidant, hypolipidemic, antidepressant, and antidiabetic. Interestingly, barley sprouts contain a high content of saponarin, which showed both anti-inflammatory and antioxidant activities. In this study, we evaluated the effect of barley sprouts on alcohol-induced liver injury mediated by inflammation and oxidative stress. Raw barley sprouts were extracted, and quantitative and qualitative analyses of its components were performed. The mice were fed a liquid alcohol diet with or without barley sprouts for four weeks. Lipopolysaccharide (LPS-stimulated RAW 264.7 cells were used to study the effect of barley sprouts on inflammation. Alcohol intake for four weeks caused liver injury, evidenced by an increase in serum alanine aminotransferase and aspartate aminotransferase activities and tumor necrosis factor (TNF-α levels. The accumulation of lipid in the liver was also significantly induced, whereas the glutathione (GSH level was reduced. Moreover, the inflammation-related gene expression was dramatically increased. All these alcohol-induced changes were effectively prevented by barley sprouts treatment. In particular, pretreatment with barley sprouts significantly blocked inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2 expression in LPS-stimulated RAW 264.7. This study suggests that the protective effect of barley sprouts against alcohol-induced liver injury is potentially attributable to its inhibition of the inflammatory response induced by alcohol.

  9. 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.

  10. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Schütz, Tanja

    2000-01-01

    BACKGROUND/AIMS: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse ...... the translocation of bacterial toxins, thereby contributing to inflammatory processes in alcoholic liver disease....

  11. 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.

  12. 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.

  13. 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.

  14. Aerobic exercise training in the treatment of non‐alcoholic fatty liver disease related fibrosis

    Science.gov (United States)

    Linden, Melissa A.; Sheldon, Ryan D.; Meers, Grace M.; Ortinau, Laura C.; Morris, E. Matthew; Booth, Frank W.; Kanaley, Jill A.; Vieira‐Potter, Victoria J.; Sowers, James R.; Ibdah, Jamal A.; Thyfault, John P.; Laughlin, M. Harold

    2016-01-01

    Key points Physiologically relevant rodent models of non‐alcoholic steatohepatitis (NASH) that resemble the human condition are limited.Exercise training and energy restriction are first‐line recommendations for the treatment of NASH.Hyperphagic Otsuka Long–Evans Tokushima fatty rats fed a western diet high in fat, sucrose and cholesterol for 24 weeks developed a severe NASH with fibrosis phenotype.Moderate intensity exercise training and modest energy restriction provided some improvement in the histological features of NASH that coincided with alterations in markers of hepatic stellate cell activation and extracellular matrix remodelling.The present study highlights the importance of lifestyle modification, including exercise training and energy restriction, in the regulation of advanced liver disease. Abstract The incidence of non‐alcoholic steatohepatitis (NASH) is rising but the efficacy of lifestyle modifications to improve NASH‐related outcomes remain unclear. We hypothesized that a western diet (WD) would induce NASH in the Otsuka Long–Evans Tokushima Fatty (OLETF) rat and that lifestyle modification would improve this condition. Eight‐week‐old Long–Evans Tokushima Otsuka (L) and OLETF (O) rats consumed a control diet (10% kcal fat, 3.5% sucrose) or a WD (45% kcal fat, 17% sucrose, 1% cholesterol) for 24 weeks. At 20 weeks of age, additional WD‐fed OLETFs were randomized to sedentary (O‐SED), food restriction (O‐FR; ∼25% kcal reduction vs. O‐SED) or exercise training (O‐EX; treadmill running 20 m min–1 with a 15% incline, 60 min day–1, 5 days week–1) conditions for 12 weeks. WD induced a NASH phenotype in OLETFs characterized by hepatic fibrosis (collagen 1α1 mRNA and hydroxyproline content), as well as elevated inflammation and non‐alcoholic fatty liver disease activity scores, and hepatic stellate cell activation (α‐smooth muscle actin) compared to Long–Evans Tokushima Otsuka rats. FR and EX modestly

  15. Pediatric non-alcoholic fatty liver disease: an increasing public health issue.

    Science.gov (United States)

    Berardis, S; Sokal, E

    2014-02-01

    Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that encompasses a wide spectrum of liver abnormalities ranging from simple liver steatosis to steatohepatitis (non-alcoholic steatohepatitis), which may be associated with fibrosis and progress to cirrhosis and end-stage liver disease. NAFLD has recently become the most common cause of chronic liver disease in children and adolescents. NAFLD prevalence, alongside obesity, continues to increase among pediatric patients. Obesity is believed to represent a major risk factor for NAFLD, which is considered to be the liver presentation of the metabolic syndrome. Although the pathogenesis of NAFLD is not fully understood, the notion that multiple factors affect disease development and progression is widely accepted. Both genetic background and environmental factors contribute to NAFLD development. A more complete understanding of the pathogenesis may aid in developing non-invasive diagnostic tools and identifying new therapeutic targets. Liver biopsy currently remains the gold standard for NAFLD diagnosis and staging. Although lifestyle and diet modifications are key in NAFLD treatment, the development of new pharmacological therapies is crucial for patients who are unresponsive to first-line therapy. Pediatric NAFLD is an increasing public health issue that remains underdiagnosed. A large-scale screening in the high-risk population, especially among the overweight pediatric patients, should be considered, including measurement of serum transaminases and liver ultrasound. It is crucial to treat this condition as soon as possible in order to avoid the progression to end-stage liver disease.

  16. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Pietrobattista Andrea

    2009-05-01

    Full Text Available Abstract Background Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. Methods The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69% of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI, which varies between 0 and 10. Results The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI with bias correction 0.80 to 0.90 for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0 could be used to rule in liver fibrosis without performing liver biopsy. Conclusion PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

  17. ADH1B and ADH1C Genotype, Alcohol Consumption and Biomarkers of Liver Function

    DEFF Research Database (Denmark)

    Lawlor, Debbie A; Benn, Marianne; Zuccolo, Luisa;

    2014-01-01

    1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), γ-glutamyl-transferase (γ-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56). RESULTS......BACKGROUND: The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol. METHODS: We used variants in ADH1B and ADH......: In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic...

  18. The role of oxidative stress in the development of alcoholic liver disease.

    Science.gov (United States)

    Galicia-Moreno, M; Gutiérrez-Reyes, G

    2014-01-01

    Alcohol is the most accepted addictive substance worldwide and its consumption is related to multiple health, economic, and social problems. The liver is the organ in charge of ethanol metabolism and it is susceptible to alcohol's toxic effects. To provide a detailed review of the role of oxidative stress in alcoholic liver disease and the mechanisms of damage involved, along with current information on the hepatoprotective effectiveness of the molecules that have been studied. A search of the PubMed database was conducted using the following keywords oxidative stress, alcoholic liver damage, alcoholic cirrhosis, and antioxidants. There was no time limit for gathering all available information on the subject at hand. According to the literature reviewed, oxidative stress plays an important role in the pathogenesis of alcoholic liver damage. Molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), formed during ethanol metabolism, structurally and functionally modify organic molecules. Consequently, biologic processes are altered and hepatocytes are sensitized to the action of cytokines like tumor necrosis factor-α, as well as to the action of endotoxins, activating signaling pathways such as those controlled by nuclear factor kappa B, extracellular signal regulated kinases, and mitogen activated protein kinase. Oxidative stress plays an important role in the development of liver damage resulting from alcohol consumption. The molecules that have currently displayed a hepatoprotective effect in preclinical and clinical trials must be studied further so that their effectiveness can be confirmed and they can possibly be used as adjuvant treatments for this disease. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  19. Bacterial infections in alcoholic and nonalcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Sargenti, Konstantina; Prytz, Hanne; Bertilsson, Sara

    2015-01-01

    of 600,000 inhabitants) were retrospectively identified. All bacterial infections resulting in or occurring during an inpatient hospital episode during this period were registered. The etiology of cirrhosis (alcoholic vs. nonalcoholic), infection localization, and outcome as well as bacterial resistance...... predicted pneumonia and infections caused by Gram-positive bacteria in multivariate analysis (Pbacterial infections increased over time, which, in the case of alcoholic cirrhosis, was associated with pneumonia and bacterial resistance...... to antibiotics. However, alcoholic etiology was not related indepedently to the occurrence of bacterial infections....

  20. The Role of Dietary Sugars and De novo Lipogenesis in Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    J. Bernadette Moore

    2014-12-01

    Full Text Available Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD. Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL, stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.

  1. Dynamic changes of capillarization and peri-sinusoid fibrosis in alcoholic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Guang-Fu Xu; Xin-Yue Wang; Gui-Ling Ge; Peng-Tao Li; Xu Jia; De-Lu Tian; Liang-Duo Jiang; Jin-Xiang Yang

    2004-01-01

    AIM: To investigate the dynamic changes of capillarization and peri-sinusoid fibrosis in an alcoholic liver disease model induced by a new method.METHODS: Male SD rats were randomly divided into 6 groups, namely normal, 4 d, 2 w, 4 w, 9 w and 11 w groups.The animals were fed with a mixture of alcohol for designated days and then decollated, and their livers were harvested to examine the pathological changes of hepatocytes, hepatic stellate cells, sinusoidal endothelial cells, sinusoid, peri-sinusoid. The generation of three kinds of extra cellular matrix was also observed.RESULTS: The injury of hepatocytes became severer as modeling going on. Under electronic microscope, fatty vesicles and swollen mitochondria in hepatocytes, activated hepatic stellate cells with fibrils could been seen near or around it. Fenestrae of sinusoidal endothelial cells were decreased or disappeared, sinusoidal basement was formed.Under light microscopy typical peri-sinusoid fibrosis, gridding-like fibrosis, broaden portal areas, hepatocyte's fatty and balloon denaturation, iron sediment, dot necrosis,congregated lymphatic cells and leukocytes were observed.Type Ⅰ collagen showed an increasing trend as modeling going on, slightly recovered when modeling stopped for 2 weeks. Meanwhile, type Ⅳ collagen decreased rapidly when modeling began and recovered after modeling stopped for 2 weeks. Laminin increased as soon as modeling began and did not recover when modeling stopped for 2 weeks.CONCLUSION: The pathological changes of the model were similar to that of human ALD, but mild in degree. It had typical peri-sinusoid fibrosis; however, capillarization seemed to be instable. It may be related with the reduction of type Ⅳ collagen in the basement of sinusoid during modeling.

  2. Alcohol-Attributable Fraction in Liver Disease: Does GDP Per Capita Matter?

    Science.gov (United States)

    Kröner, Paul T; Mankal, Pavan Kumar; Dalapathi, Vijay; Shroff, Kavin; Abed, Jean; Kotler, Donald P

    2015-01-01

    The alcohol-attributable fraction (AAF) quantifies alcohol's disease burden. Alcoholic liver disease (ALD) is influenced by alcohol consumption per capita, duration, gender, ethnicity, and other comorbidities. In this study, we investigated the association between AAF/alcohol-related liver mortality and alcohol consumption per capita, while stratifying to per-capita gross domestic product (GDP). Data obtained from the World Health Organization and World Bank for both genders on AAF on liver disease, per-capita alcohol consumption (L/y), and per-capita GDP (USD/y) were used to conduct a cross-sectional study. Countries were classified as "high-income" and "very low income" if their respective per-capita GDP was greater than $30,000 or less than $1,000. Differences in total alcohol consumption per capita and AAF were calculated using a 2-sample t test. Scatterplots were generated to supplement the Pearson correlation coefficients, and F test was conducted to assess for differences in variance of ALD between high-income and very low income countries. Twenty-six and 27 countries met the criteria for high-income and very low income countries, respectively. Alcohol consumption per capita was higher in high-income countries. AAF and alcohol consumption per capita for both genders in high-income and very low income countries had a positive correlation. The F test yielded an F value of 1.44 with P = .357. No statistically significant correlation was found among alcohol types and AAF. Significantly higher mortality from ALD was found in very low income countries relative to high-income countries. Previous studies had noted a decreased AAF in low-income countries as compared to higher-income countries. However, the non-statistically significant difference between AAF variances of low-income and high-income countries was found by this study. A possible explanation is that both high-income and low-income populations will consume sufficient amount of alcohol, irrespective of its

  3. Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

    Science.gov (United States)

    Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; N Ch, Varadacharyulu

    2016-10-01

    Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity. In-vitro studies revealed that PSE possess strong DPPH (1,1-diphenyl-2-picryl hydrazyl) and nitric oxide radical scavenging activity. For in vivo studies male albino Wistar rats were treated with 20% alcohol (5g/kg b.wt/day) and PSE (250mg/kg b.wt/day) for 60days. Results showed that alcohol administration significantly altered plasma lipid profile with marked increase in the levels of plasma transaminases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (γGT). Moreover, lipid peroxides, nitric oxide (NOx) levels in plasma and liver were increased with increased iNOS protein expression in liver was noticed in alcohol administered rats and these levels were significantly brought back close to normal level by PSE administration except iNOS protein expression. Alcohol administration also decreased the content of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-s transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in liver, which were significantly enhanced by administration of PSE. The active compounds pterostilbene, lignan and lupeols present in PSE might have shown protection against alcohol-induced hepatic damage by possibly reducing the rate of lipid peroxidation, NOx levels and increasing the antioxidant defence mechanism in alcohol administered rats. Both biochemical and histopathological results in the alcohol-induced liver damage model emphasize beneficial action of PSE as a hepatoprotective agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. 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 ...

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

    Science.gov (United States)

    Zhang, Dong; Song, Xiao-Jing; Li, Shun-Yue; Wang, Shu-You; Chen, Bing-Jun; Bai, Xiao-Dong; Tang, Li-Mei

    2016-07-22

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

  6. Non-alcoholic fatty liver disease: is bariatric surgery the answer?

    Science.gov (United States)

    Pillai, Anjana A; Rinella, Mary E

    2009-11-01

    As the worldwide obesity epidemic continues to increase, the prevalence of non-alcoholic fatty liver disease (NAFLD) and specifically non-alcoholic steatohepatitis (NASH) will become increasingly prominent. NASH will surpass chronic hepatitis C infection as the primary indication for orthotopic liver transplantation in the near future. With the evolution of surgical techniques, bariatric surgery is currently recognized as the most effective method for achieving sustained weight loss and reversing numerous comorbidities in severely obese individuals. This review focuses on the potential risks and benefits of bariatric surgery in subjects with NAFLD and explores its role in the management of NASH in the obese patient.

  7. The benefits of exercise for patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Keating, Shelley E; George, Jacob; Johnson, Nathan A

    2015-01-01

    As exercise is now an established therapy for the management of non-alcoholic fatty liver disease (NAFLD), recent investigations have sought to identify the optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here, the authors discuss the following: the role of aerobic exercise for the modulation of hepatic steatosis; the limited evidence for the role of resistance training in reducing liver fat; the lack of evidence from clinical trials on the role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise for patients with NAFLD, beyond steatosis. Based on current evidence, the authors provide recommendations for exercise prescription for patients with NAFLD.

  8. Evaluation of coagulation parameters and liver enzymes among alcohol drinkers in Port Harcourt, Nigeria

    Directory of Open Access Journals (Sweden)

    Adias TC

    2013-06-01

    Full Text Available Teddy Charles Adias,1 Everton Egerton,2 Osaro Erhabor3 1Bayelsa College of Health Technology, Bayelsa State, Nigeria; 2Department of Medical Laboratory Science, Rivers State University of Science and Technology, Port Harcourt, Nigeria; 3Faculty of Medical Laboratory Science, Department of Haematology and Transfusion Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria Abstract: Alcohol is a major contributor to the global burden of disease, disability, and death in high, middle, and low-income countries. Harmful use of alcohol is one of the main factors contributing to premature deaths and avoidable disease burden worldwide and has a major impact on public health. The aim of this present cross-sectional study was to investigate the effect of alcohol consumption on coagulation parameters and liver enzymes of subjects in Port Harcourt, Nigeria. Two hundred adults consisting of 120 alcohol dependent subjects and 80 age, gender-matched nondrinkers aged 25–65 years (mean age 45.25 ± 11.50 years were enrolled in this study. Of the 120 chronic alcohol drinkers, 37 were dependent on local dry gin, while 83 were dependent on other alcoholic beverages. The mean values of the liver enzymes, aspartate aminotransferase and gamma glutamyl transferase, were significantly higher (P = 0.002 and P = 0.02 respectively among the chronic alcohol consumers compared with their nondrinker counterparts. Although the value of alanine aminotransferase was higher in the chronic drinkers, it did not reveal any significant difference (P = 0.11. The coagulation parameters, prothrombin time and activated partial thromboplastin time were investigated among chronic drinkers and nondrinkers. The mean value of prothrombin time and activated partial thromboplastin time was significantly higher in the chronic alcohol drinkers compared to the nondrinkers (P = 0.04 and P = 0.02 respectively. We observed a positive and significant correlation between values of liver enzymes, serum

  9. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

    2017-06-01

    This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Lispro insulin in people with non-alcoholic liver cirrhosis and type 2 diabetes mellitus.

    Science.gov (United States)

    Gentile, S; Guarino, G; Strollo, F; Romano, M; Genovese, S; Masarone, M; Ceriello, A

    2016-03-01

    To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD). 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead. CGM showed higher glycemic excursions under RHI than under lispro (p<0.01) with lower glucose levels in the late post-absorption phase (p<0.05) and even more during the night (p<0.01). Post-challenge incremental areas under the curve (ΔAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.05liver glucose output expected from its earlier hepatic distribution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lebensztejn, Dariusz M; Wierzbicka, Aldona; Socha, Piotr; Pronicki, Maciej; Skiba, Elżbieta; Werpachowska, Irena; Kaczmarski, Maciej

    2011-01-01

    There is a need to replace liver biopsy with non-invasive markers that predict the degree of liver fibrosis in fatty liver disease related to obesity. Therefore, we studied four potential serum markers of liver fibrosis and compared them with histopathological findings in liver biopsy in children with non-alcoholic fatty liver disease (NAFLD). We determined fasting serum level of hyaluronic acid (HA), laminin, YKL-40 and cytokeratin-18 M30 in 52 children (age range 4-19, mean 12 years, 80 % of them were overweight or obese) with biopsy-verified NAFLD. Viral hepatitis, autoimmune and metabolic liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis) were excluded. Fibrosis stage was assessed in a blinded fashion by one pathologist according to Kleiner. Receiver operating characteristics (ROC) analysis was used to calculate the power of the assays to detect liver fibrosis (AccuROC, Canada). Liver fibrosis was diagnosed in 19 children (37 %). The levels of HA and CK18M30 were significantly higher in children with fibrosis compared to children without fibrosis (p=0.04 and 0.05 respectively). The ability of serum HA (cut-off 19.1 ng/ml, Se=84 %, Sp=55 %, PPV=52 %, NPV=86 %) and CK18M30 (cut-off 210 u/l, Se=79 %, Sp=60 %, PPV=56 %, NPV=82 %) to differentiate children with fibrosis from those without fibrosis was significant (AUC=0.672 and 0.666, respectively). The combination of both markers was superior (AUC=0.73, p=0.002). Laminin and YKL-40 levels did not allow a useful prediction. Cytokeratin-18 and hyaluronic acid are suitable serum markers predicting liver fibrosis in children with NAFLD. Studying these markers may identify patients at risk of disease progression.

  12. [Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis].

    Science.gov (United States)

    Sakizono, Kenji; Oita, Tatsuo; Eto, Masaaki; Bito, Sanae; Takegawa, Hiroshi; Kasakura, Shinpei

    2002-03-01

    We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken

  13. Towards a Humanized Mouse Model of Liver Stage Malaria Using Ectopic Artificial Livers

    Science.gov (United States)

    Ng, Shengyong; March, Sandra; Galstian, Ani; Gural, Nil; Stevens, Kelly R.; Mota, Maria M.; Bhatia, Sangeeta N.

    2017-01-01

    The malaria liver stage is an attractive target for antimalarial development, and preclinical malaria models are essential for testing such candidates. Given ethical concerns and costs associated with non‐human primate models, humanized mouse models containing chimeric human livers offer a valuable alternative as small animal models of liver stage human malaria. The best available human liver chimeric mice rely on cellular transplantation into mice with genetically engineered liver injury, but these systems involve a long and variable humanization process, are expensive, and require the use of breeding-challenged mouse strains which are not widely accessible. We previously incorporated primary human hepatocytes into engineered polyethylene glycol (PEG)-based nanoporous human ectopic artificial livers (HEALs), implanted them in mice without liver injury, and rapidly generated human liver chimeric mice in a reproducible and scalable fashion. By re-designing the PEG scaffold to be macroporous, we demonstrate the facile fabrication of implantable porous HEALs that support liver stage human malaria (P. falciparum) infection in vitro, and also after implantation in mice with normal liver function, 60% of the time. This proof-of-concept study demonstrates the feasibility of applying a tissue engineering strategy towards the development of scalable preclinical models of liver stage malaria infection for future applications. PMID:28361899

  14. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease

    OpenAIRE

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia del Giudice, Emanuele

    2015-01-01

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the poss...

  15. Dietary supplements and pediatric non-alcoholic fatty liver disease: Present and the future

    OpenAIRE

    Rahimlou, Mehran; Ahmadnia, Hoda; Hekmatdoost, Azita

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. High prevalence of pediatric obesity and sedentary lifestyle has augmented the incidence of NAFLD in children. Obesity is associated with an increased risk of NAFLD through various mechanisms such as intensification of insulin resistance and increased levels of inflammatory markers. There is no approved medical intervention for treatment of pediatric NAFLD; the only proven strategy in management of...

  16. The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

    OpenAIRE

    Anna Di Sessa; Giuseppina Rosaria Umano; Emanuele Miraglia del Giudice

    2017-01-01

    The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and fun...

  17. Estrogen inhibits the effects of obesity and alcohol on mammary tumors and fatty liver.

    Science.gov (United States)

    Hong, Jina; Holcomb, Valerie B; Kushiro, Kyoko; Núñez, Nomelí P

    2011-12-01

    The risk of developing breast cancer and fatty liver is increased by alcohol consumption. The objective of the present study was to determine if obesity and exogenous estrogen supplementation alter the effects of alcohol on mammary tumorigenesis and fatty liver. Ovariectomized female mice were (1) fed diets to induce overweight and obese phenotypes, (2) provided water or 20% alcohol, (3) implanted with placebo, low- or high-dose estrogen pellets and (4) injected with Met-1 mouse mammary cancer cells. Alcohol-consuming mice were more insulin sensitive and developed larger tumors than water consuming mice. Obese mice developed slightly larger tumors than control mice. Alcohol consumption and obesity increased growth factors, hepatic steatosis, activation of Akt, and inhibited the caspase-3 cascade. Estrogen treatment triggered the loss of body fat, induced insulin sensitivity, suppressed tumor growth, reduced growth factors and improved hepatic steatosis. Results show that the effects of alcohol on mammary tumor and fatty liver are modified by obesity and estrogen supplementation.

  18. Meta-analysis of propylthiouracil for alcoholic liver disease--a Cochrane Hepato-Biliary Group Review

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease.......The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-03

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

  20. Current experimental perspectives on the clinical progression of alcoholic liver disease.

    Science.gov (United States)

    Breitkopf, Katja; Nagy, Laura E; Beier, Juliane I; Mueller, Sebastian; Weng, Honglei; Dooley, Steven

    2009-10-01

    Chronic alcohol abuse is an important cause of morbidity and mortality throughout the world. Liver damage due to chronic alcohol intoxication initially leads to accumulation of lipids within the liver and with ongoing exposure this condition of steatosis may first progress to an inflammatory stage which leads the way for fibrogenesis and finally cirrhosis of the liver. While the earlier stages of the disease are considered reversible, cirrhotic destruction of the liver architecture beyond certain limits causes irreversible damage of the organ and often represents the basis for cancer development. This review will summarize current knowledge about the molecular mechanisms underlying the different stages of alcoholic liver disease (ALD). Recent observations have led to the identification of new molecular mechanisms and mediators of ALD. For example, plasminogen activator inhibitor 1 was shown to play a central role for steatosis, the anti-inflammatory adipokine, adiponectin profoundly regulates liver macrophage function and excessive hepatic deposition of iron is caused by chronic ethanol intoxication and increases the risk of hepatocellular carcinoma development.

  1. Efficacy of Qianggan capsule in treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun He; Meng-Xian Wang; Min-Man Ning

    2016-01-01

    Objective:To observe the clinical effects of Qianggan capsule and silibinin capsule in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia. Methods:A total of 112 patients with non-alcoholic fatty liver disease were included in the study and divided into the control group (n=50) and the observation group (n=62). The patients in the control group were given silibinin capsule, while the patients in the observation group were given Qianggan capsule. The patients in the two groups were treated for 24 weeks. The liver/spleen CT was performed before and after treatment. BMI was measured. The liver function, serum lipid, and leptin were detected. Results:TG, LDL-C, BMI, and liver/spleen CT ratio in the observation group were significantly reduced when compared with the control group. The levels of HDL-C and adiponectin in the observation group were significantly elevated when compared with the control group. The differences of ALT, GGT, and AST after treatment between the two groups were not statistically significant. Conclusions:Qianggan capsule and silibinin capsule has an accurate efficacy and high safety in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia.

  2. Correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Guo; Ya-Min Li; Qing-Chun Li

    2015-01-01

    Objective:To study the correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model.Methods:Adult SD rats were selected and alcoholic fatty liver rat models were established by alcohol administration and high-fat diet feeding. Liver tissue was collected and contents of HIF-1α, PPARγ and lipid metabolism-related enzymes were detected; serum was collected and contents of lipid metabolism indexes and liver cell damage indexes were detected.Results:(1) one week, two weeks, three weeks and four weeks after models were established, HIF-1αα in livers of the model group showed an increasing trend and PPARγ showed a decreasing trend; HIF-1α content was higher than that of the control group and PPARγ content was lower than that of the control group; (2) contents of apoCII, apoCIII,α-GST and GLDH in serum as well as levels of FAT, FABP1, FAS, ACC and ACAT-2 in liver tissue of the model group all significantly increased, and were positively correlated with HIF-1α and negatively correlated with PPARγ.Conclusion:Transcription factor HIF-1α content abnormally increases and PPARγ content abnormally decreases in liver tissue of alcoholic fatty liver rat models; it results in abnormal lipid metabolism and liver cell damage through increasing the expression of lipid metabolism-related enzymes in the liver.

  3. Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis

    DEFF Research Database (Denmark)

    Thiele, Maja; Detlefsen, Sönke; Møller, Linda Maria Sevelsted;

    2016-01-01

    BACKGROUND & AIMS: Alcohol abuse causes half of all deaths from cirrhosis in the West, but few tools are available for noninvasive diagnosis of alcoholic liver disease. We evaluated 2 elastography techniques for diagnosis of alcoholic fibrosis and cirrhosis; liver biopsy with Ishak score...... and collagen-proportionate area were used as reference. METHODS: We performed a prospective study of 199 consecutive patients with ongoing or prior alcohol abuse, but without known liver disease. One group of patients had a high pretest probability of cirrhosis because they were identified at hospital liver...... clinics (in Southern Denmark). The second, lower-risk group, was recruited from municipal alcohol rehabilitation centers and the Danish national public health portal. All subjects underwent same-day transient elastography (FibroScan), 2-dimensional shear wave elastography (Supersonic Aixplorer), and liver...

  4. Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance.

    Science.gov (United States)

    Toonen, Erik J M; Mirea, Andreea-Manuela; Tack, Cees J; Stienstra, Rinke; Ballak, Dov B; van Diepen, Janna A; Hijmans, Anneke; Chavakis, Triantafyllos; Dokter, Wim H; Pham, Christine T N; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B

    2016-05-24

    Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential.

  5. Enhanced expression of c-myc in hepatocytes promotes initiation and progression of alcoholic liver disease.

    Science.gov (United States)

    Nevzorova, Yulia A; Cubero, Francisco J; Hu, Wei; Hao, Fengjie; Haas, Ute; Ramadori, Pierluigi; Gassler, Nikolaus; Hoss, Mareike; Strnad, Pavel; Zimmermann, Henning W; Tacke, Frank; Trautwein, Christian; Liedtke, Christian

    2016-03-01

    Progression of alcoholic liver disease (ALD) can be influenced by genetic factors, which potentially include specific oncogenes and tumor suppressors. In the present study, we tested the hypothesis that aberrant expression of the proto-oncogene c-myc might exert a crucial role in the development of ALD. Expression of c-myc was measured in biopsies of patients with ALD by quantitative real-time PCR and immunohistochemistry. Mice with transgenic expression of c-myc in hepatocytes (alb-myc(tg)) and wild-type (WT) controls were fed either control or ethanol (EtOH) containing Lieber-DeCarli diet for 4weeks to induce ALD. Hepatic c-myc was strongly upregulated in human patients with advanced ALD and in EtOH-fed WT mice. Transcriptome analysis indicated deregulation of pathways involved in ER-stress, p53 signaling, hepatic fibrosis, cell cycle regulation, ribosomal synthesis and glucose homeostasis in EtOH-fed alb-myc(tg) mice. Transgenic expression of c-myc in hepatocytes with simultaneous EtOH-uptake led to early ballooning degeneration, increased liver collagen deposition and hepatic lipotoxicity, together with excessive CYP2E1-derived reactive oxygen species (ROS) production. Moreover, EtOH-fed alb-myc(tg) mice exhibited substantial changes in mitochondrial morphology associated with energy dysfunction. Pathway analysis revealed that elevated c-myc expression and ethanol uptake synergistically lead to strong AKT activation, Mdm2 phosphorylation and as a consequence to inhibition of p53. Expression of c-myc and EtOH-uptake synergistically accelerate the progression of ALD most likely due to loss of p53-dependent protection. Thus, c-myc is a new potential marker for the early detection of ALD and identification of risk patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Role of innate immune response in non alcoholic fatty liver disease: metabolic complications and therapeutic tools

    Directory of Open Access Journals (Sweden)

    Rosaria eMeli

    2014-04-01

    Full Text Available Non alcoholic fatty liver disease (NAFLD is currently the most common liver disease worldwide, both in adults and children. It is characterized by an aberrant lipid storage in hepatocytes, named hepatic steatosis. Simple steatosis remains a benign process in most affected patients, while some of them develop superimposed necroinflammatory activity with a nonspecific inflammatory infiltrate and a progression to non alcoholic steatohepatitis with or without fibrosis. Deep similarity and interconnections between innate immune cells and those of liver parenchyma have been highlighted and showed to play a key role in the development of chronic liver disease. The liver can be considered as an immune organ because it hosts non lymphoid cells, such as macrophage Kupffer cells, stellate and dendritic cells, and lymphoid cells. Many of these cells are components of the classic innate immune system, enabling the liver to play a major role in response to pathogens. Although the liver provides a tolerogenic environment , aberrant activation of innate immune signaling may trigger harmful inflammation, that contributes to tissue injury, fibrosis and carcinogenesis. Pathogen recognition receptors, such as toll-like receptors and nucleotide oligomerization domain-like receptors, are responsible for the recognition of immunogenic signals, and represent the major conduit for sensing hepatic and non-hepatic noxious stimuli. A pivotal role in liver inflammation is also played by cytokines, which can initiate or have a part in immune response, triggering hepatic intracellular signaling pathways. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic alteration traits: insulin resistance, obesity, diabetes, hyperlipidemia and their compounded combined effects. In this review we discuss the relevant role of innate immune cell activation in relation to non alcoholic fatty liver disease, the metabolic complications associated to this

  7. 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.

  8. Clinical Characteristics in Patients with Liver Cirrhosis Induced by HBV Infection and Combined with Mild Alcohol Intake

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To investigate the differences of clinical and biochemical characteristics between patients with liver cirrhosis induced by HBV infection combined with and without mild alcohol intake. Methods Data of patients with liver cirrhosis who were hospitalized in the First Hospital Afifliated to Xinjiang Medical University were retrospectively analyzed. Patients were divided into three groups: patients with liver cirrhosis induced by HBV infection and combined with mild alcohol intake, patients with HBV-related cirrhosis, and patients with alcohol-related cirrhosis. Biochemical detections including liver function, fasting lipid proifles, lipoprotein, kidney function, glucose, uric acid and regular blood tests were carried out and results were compared among three groups. Data were analyzed through STATA software and co-variant analysis. Results Total of 2 350 patients with liver cirrhosis were included, 732 patients had cirrhosis induced by HBV infection combined with mild alcohol intake, 1 316 patients had HBV-related liver cirrhosis, 302 patients had alcohol-related cirrhosis. The highest mean level of white cell count, mean corpuscular volume,γ-glutamyltranspeptidase and uric acid were observed in HBV infection combined with mild alcohol intake group. Multivariate regression analysis revealed that HBV infection, excessive alcohol intake, male and age were risk factors for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. Conclusions HBV infection combined with mild alcoholic-related liver cirrhosis group showed the highest oxidative stress compared with alcoholic liver cirrhosis group, which suggested that mild alcohol intake may increase the incidence of liver cirrhosis in HBV infected patients and may not increase the incidence of HCC.

  9. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-07-21

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

  10. 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

  11. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease.

    Science.gov (United States)

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia Del Giudice, Emanuele

    2015-06-07

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the possibility to both diagnose the NAFLD and evaluate its progression to fibrosis or cirrhosis with greater certainty than other techniques. The use of liver biopsy in clinical practice causes debate among health care providers. Most patients with NAFLD have a good prognosis and, therefore, the risks of a liver biopsy seem to outweigh the clinical benefits. It represents an impractical screening procedure because it is both expensive and invasive and, moreover, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies because histological lesions of non-alcoholic steatohepatitis are unevenly distributed throughout the liver parenchyma. The liver biopsy limitations have led the clinicians to use, also if highly imperfect, non-invasive methods to diagnose and stage NAFLD. In this editorial the main diagnostic controversies in pediatric NAFLD are examined.

  12. Molecular Structure of Human-Liver Glycogen.

    Directory of Open Access Journals (Sweden)

    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  13. Molecular Structure of Human-Liver Glycogen

    Science.gov (United States)

    Deng, Bin; Sullivan, Mitchell A.; Chen, Cheng; Li, Jialun; Powell, Prudence O.; Hu, Zhenxia; Gilbert, Robert G.

    2016-01-01

    Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets. PMID:26934359

  14. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Matteo Nicola Dario Di Minno; Anna Russolillo; Roberta Lupoli; Pasquale Ambrosino; Alessandro Di Minno; Giovanni Tarantino

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden.It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor.Lacking a definite treatment for NAFLD,a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches.In this review,major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described.n-3 PUFAs,besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension,hyperlipidemia,endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e.,peroxisome proliferator-activated receptor (PPAR)α,PPARγ,sterol regulatory element-binding protein-1,carbohydrate responsive element-binding protein],impacts both lipid metabolism and on insulin sensitivity.In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production,n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species.Further strengthening the results of the in vitro studies,both animal models and human intervention trials,showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements.Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans,well-designed randomized controlled trials of adequate size and duration,with histological endpoints,are needed to assess the long-term safety and efficacy of PUFA,as well as other therapies,for the treatment of NAFLD and non-alcoholic steatohepatitis patients.It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil,flaxseeds,olive oil) which are typical foods

  15. 内生性乙醇与非酒精性脂肪性肝病研究进展%Endogenous alcohol in non -alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    何崇信; 徐正婕(综述); 范建高(审校)

    2016-01-01

    非酒精性脂肪性肝病和酒精性肝病具有相似的病理学特征,使得内生性乙醇在非酒精性脂肪性肝病的进展中可能扮演的重要角色成为肝病学家们关注的新方向。内生性乙醇与肝脏、肠道和肠道细菌以及非酒精性脂肪性肝病的关系密切,给我们提供了解释非酒精性脂肪性肝病病因的新视角。%Similar pathologic characteristics between non-alcoholic fatty liver disease and alcoholic liver disease presents a new direction for the hepatologists worldwide that endogenous alcohol may play important role in the development of non-alcoholic fatty liver disease. The closed relationship among endogenous alcohol and liver,intestine,intestinal flora and non-alcoholic fatty liver disease provides a new sight to explain the pathogenesis of non-alcoholic fatty liver diseases.

  16. Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick;

    1983-01-01

    affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed......Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20......). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately...

  17. Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

    NARCIS (Netherlands)

    Portincasa, Piero; Grattagliano, Ignazio; Lauterburg, Bernhard H.; Palmieri, Vincenzo O.; Palasciano, Giuseppe; Stellaard, Frans

    2006-01-01

    Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic pati

  18. Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mishra, Alita; Younossi, Zobair M

    2012-06-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease burden across the world. By definition, although the histopathologic features of NAFLD are identical to that of alcoholic liver disease, its diagnosis requires absence of significant alcohol use and absence of other causes of chronic liver disease. We now know that NAFLD is not simply a disease of the Western world. It is manifested across the world, in varying rates, across gender, across varying ethnicities, and in its association with other host factors. In this review article, the definition of NAFLD, its spectrum, ranging from mild steatosis to hepatocellular injury and inflammation defined as non-alcoholic steatohepatitis (NASH) is discussed. Mild steatosis is generally a stable disease whereas NASH can be progressive. Based on current published literature, current incidence and prevalence of NAFLD and NASH are discussed. It is also accepted that these processes will continue to increase in prevalence with the rise of obesity, type II diabetes, and associated metabolic syndrome. Some of the risk factors have been well-established and are discussed. In addition, this review also presents emerging associations with other risk factors for NAFLD. Natural history of NAFLD is variable depending upon the histologic subtypes and other underlying comorbidities and is discussed in this review as well.

  19. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

    NARCIS (Netherlands)

    Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

    AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

  20. Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis

    NARCIS (Netherlands)

    Portincasa, Piero; Grattagliano, Ignazio; Lauterburg, Bernhard H.; Palmieri, Vincenzo O.; Palasciano, Giuseppe; Stellaard, Frans

    Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic

  1. Phenotyping the effect of diet on non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Wit, de N.J.W.; Afman, L.A.; Mensink, M.R.; Muller, M.R.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and progressi

  2. 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

  3. Variables predicting elevated portal pressure in alcoholic liver disease. Results of a multivariate analysis

    DEFF Research Database (Denmark)

    Krogsgaard, K; Christensen, E; Gluud, C

    1987-01-01

    In 46 alcoholic patients the association of wedged-to-free hepatic-vein pressure with other variables (clinical, histologic, hemodynamic, and liver function data) was studied by means of multiple regression analysis, taking the wedged-to-free hepatic-vein pressure as the dependent variable. Four ...

  4. Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Banasik, Karina; Justesen, Johanne M.; Hornbak, Malene

    2011-01-01

    Objective: Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. Research Design and Methods: By integrating public database text mining, trans-organism protein...

  5. Role of stellate cells in alcoholic liver fibrosis

    Directory of Open Access Journals (Sweden)

    Krzysztof Plewka

    2009-07-01

    Full Text Available Many different diseases and toxins can cause liver damage, which is diffi cult to treat and often leads to the development of liver fi brosis or even cirrhosis. The key event in this process is the activation of hepatic stellate cells (HSCs. During such activation, HSCs undergo a dramatic transformation in morphology and behavior, changing from a neuronal-like to a fi broblast-like morphology. After activation, HSCs increase their proliferation rate and extracellular matrix (ECM production. Overproduction of ECM, which contains mainly collagen type I, is a direct cause of liver disruption. HSCs also produce substances which inhibit protease activities, such as TIMPs, which enhance ECM deposition in the liver. On the molecular level, HSCs are activated by cytokines, growth factors, and oxidative stress, which are abundant in affl icted liver. These factors induce intracellular signals transmitted by many kinases, the most important of which are JNK, ERK1/2, p38, TAK-1, PKC, FAK, and P3IK. Signals transmitted via these pathways change the activities of transcription factors such as Smad, AP-1, and NF-κβ. This in turn causes changes In gene transcription and ultimately alters the whole cell’s behavior and morphology. The cell begins the production collagen type I, TIMP-1, and aSMA. Activated HSCs can sustain their own activation by producing growth factors such as PDGF and TGF-β. Despite the vast knowledge about the mechanisms causing liver fi brosis and cirrhosis, there is still no effective cure. Further studies are therefore needed to solve this problem.

  6. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Tong Zhou

    2017-01-01

    Full Text Available Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT, aspartate transaminase (AST, hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

  7. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice.

    Science.gov (United States)

    Zhou, Tong; Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-01-01

    Chronic excessive alcohol consumption (more than 40-80 g/day for males and more than 20-40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

  8. Nutritional status of patients with alcoholic cirrhosis undergoing liver transplantation: time trends and impact on survival.

    Science.gov (United States)

    Singal, Ashwani K; Kamath, Patrick S; Francisco Ziller, Nickie; DiCecco, Sara; Shoreibah, M; Kremers, Walter; Charlton, Michael R; Heimbach, Julie K; Watt, Kymberly D; Shah, Vijay H

    2013-08-01

    Alcoholic cirrhotics evaluated for liver transplantation are frequently malnourished or obese. We analyzed alcoholic cirrhotics undergoing transplantation to examine time trends of nutrition/weight, transplant outcome, and effects of concomitant hepatitis C virus (HCV) and/or hepatocellular carcinoma (HCC). Nutrition and transplant outcomes were reviewed for alcoholic cirrhosis with/without HCV/HCC. Malnutrition was defined by subjective global assessment. Body mass index (BMI) classified obesity. A total of 261 patients receiving transplants were separated (1988-2000, 2001-2006, and 2007-2011) to generate similar size cohorts. Mean BMI for the whole cohort was 28 ± 6 with 68% classified as overweight/obese. Mean BMI did not vary among cohorts and was not affected by HCV/HCC. While prevalence of malnutrition did not vary among cohorts, it was lower in patients with HCV/HCC (P graft/patient survival was 90% and not impacted by time period, HCV/HCC, or malnutrition after adjusting for demographics and model end-stage liver disease (MELD). Alcoholic cirrhotics undergoing transplantation are malnourished yet frequently overweight/obese. Among patients selected for transplantation, 1-year post-transplant graft/patient survival is excellent, have not changed over time, and do not vary by nutrition/BMI. Our findings support feasibility of liver transplantation for alcoholic cirrhotics with obesity and malnutrition.

  9. Pathology and biopsy assessment of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Straub, Beate Katharina; Schirmacher, Peter

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters.

  10. Alcoholic Liver Disease in the Asian–Pacific Region with High Prevalence of Chronic Viral Hepatitis

    Directory of Open Access Journals (Sweden)

    Sien-Sing Yang

    2016-09-01

    Full Text Available The hospitalized cases and mortality from alcoholic liver disease (ALD are increasing in Taiwan and worldwide. Meanwhile, the Asia–Pacific region also has a high prevalence of hepatitis B virus (HBV and hepatocellular carcinoma (HCC. The Taiwanese have the highest percentage of aldehyde dehydrogenase 2 (ALDH2 deficiency and the lowest amount of alcohol consumption. Based on the histological changes, ALD is clinically classified as steatosis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatitis on cirrhosis. Patients with overt alcoholic hepatitis often develop marked hepatomegaly, audible hepatic arterial bruit, mild leukocytosis, and mild fever. Patients having alcoholic cirrhosis had much more serious complications and mortality. It is clinically important to identify hepatic fibrosis and cirrhosis earlier for early management. Active assessments for esophageal varices and ascites may help the diagnosis of cirrhosis. Sonography is helpful for exanimating features of cirrhosis including portal hypertension, ascites, increased hepatic portal flow, and collaterals. Synergistic damage of viral hepatitis on ALD patients lead to rapid progression to cirrhosis and HCC. Distinct from the Western population, 30% of Taiwanese alcoholics had concomitant chronic HBV regardless of the different histologic categories. Patient groups with combined alcoholics and HBV had fewer platelet counts and much more cirrhosis with Ishak Stage 5–6 fibrosis. The annual incidences of HCC were significantly higher in alcoholic cirrhotic patients having concomitant HBV infection than those with only HBV infection or alcoholism alone. Antiviral nucleotide and nucleoside analogs therapy reduces the prevalence of HCC to a similar level to those ALD patients without active HBV.

  11. Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations.

    Science.gov (United States)

    Solga, S F; Alkhuraishe, A; Cope, K; Tabesh, A; Clark, J M; Torbenson, M; Schwartz, P; Magnuson, T; Diehl, A M; Risby, T H

    2006-01-01

    Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liver disease (NAFLD). It was evaluated whether breath ethanol, ethane, sulfur compounds and acetone would be associated with hepatic histopathology amongst morbidly obese patients presenting for bariatric surgery. Breath samples were collected during a preoperative visit and compared with liver biopsies obtained during the surgery. A Student's two-tailed t-test was used to compare differences between the two groups. Linear regression was used to analyse associations between the concentrations of breath molecules and independent predictor variables. It was found that breath ethanol, ethane and acetone can be useful biomarkers in patients with NAFLD. In particular, breath ethanol can be associated with hepatic steatosis, and breath acetone can be associated with non-alcoholic steatohepatitis.

  12. Alteration in substrate specificity of horse liver alcohol dehydrogenase by an acyclic nicotinamide analog of NAD(+).

    Science.gov (United States)

    Malver, Olaf; Sebastian, Mina J; Oppenheimer, Norman J

    2014-11-01

    A new, acyclic NAD-analog, acycloNAD(+) has been synthesized where the nicotinamide ribosyl moiety has been replaced by the nicotinamide (2-hydroxyethoxy)methyl moiety. The chemical properties of this analog are comparable to those of β-NAD(+) with a redox potential of -324mV and a 341nm λmax for the reduced form. Both yeast alcohol dehydrogenase (YADH) and horse liver alcohol dehydrogenase (HLADH) catalyze the reduction of acycloNAD(+) by primary alcohols. With HLADH 1-butanol has the highest Vmax at 49% that of β-NAD(+). The primary deuterium kinetic isotope effect is greater than 3 indicating a significant contribution to the rate limiting step from cleavage of the carbon-hydrogen bond. The stereochemistry of the hydride transfer in the oxidation of stereospecifically deuterium labeled n-butanol is identical to that for the reaction with β-NAD(+). In contrast to the activity toward primary alcohols there is no detectable reduction of acycloNAD(+) by secondary alcohols with HLADH although these alcohols serve as competitive inhibitors. The net effect is that acycloNAD(+) has converted horse liver ADH from a broad spectrum alcohol dehydrogenase, capable of utilizing either primary or secondary alcohols, into an exclusively primary alcohol dehydrogenase. This is the first example of an NAD analog that alters the substrate specificity of a dehydrogenase and, like site-directed mutagenesis of proteins, establishes that modifications of the coenzyme distance from the active site can be used to alter enzyme function and substrate specificity. These and other results, including the activity with α-NADH, clearly demonstrate the promiscuity of the binding interactions between dehydrogenases and the riboside phosphate of the nicotinamide moiety, thus greatly expanding the possibilities for the design of analogs and inhibitors of specific dehydrogenases. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Transesterification of a series of 12 parabens by liver and small-intestinal microsomes of rats and humans.

    Science.gov (United States)

    Fujino, Chieri; Watanabe, Yoko; Uramaru, Naoto; Kitamura, Shigeyuki

    2014-02-01

    Hydrolytic transformation of parabens (4-hydroxybenzoic acid esters; used as antibacterial agents) to 4-hydroxybenzoic acid and alcohols by tissue microsomes is well-known both in vitro and in vivo. Here, we investigated transesterification reactions of parabens catalyzed by rat and human microsomes, using a series of 12 parabens with C1-C12 alcohol side chains. Transesterification of parabens by rat liver and small-intestinal microsomes occurred in the presence of alcohols in the microsomal incubation mixture. Among the 12 parabens, propylparaben was most effectively transesterified by rat liver microsomes with methanol or ethanol, followed by butylparaben. Relatively low activity was observed with longer-side-chain parabens. In contrast, small-intestinal microsomes exhibited higher activity towards moderately long side-chain parabens, and showed the highest activity toward octylparaben. When parabens were incubated with liver or small-intestinal microsomes in the presence of C1-C12 alcohols, ethanol and decanol were most effectively transferred to parabens by rat liver microsomes and small-intestinal microsomes, respectively. Human liver and small-intestinal microsomes also exhibited significant transesterification activities with different substrate specificities, like rat microsomes. Carboxylesterase isoforms, CES1b and CES1c, and CES2, exhibited significant transesterification activity toward parabens, and showed similar substrate specificity to human liver and small-intestinal microsomes, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. HFE MUTATIONS AND IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Luis COSTA-MATOS

    2013-03-01

    Full Text Available Context Alcoholic liver disease (ALD is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment and 52 healthy controls (during elective cholecystectomy. All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations. Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05, but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI: 2.09-142.34, P = 0.008. However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003. Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no

  15. EXPERIENCE OF ORNITHINE ASPARTATE (HEPA-MERZ) AND PROBIOTICS BIOFLORUM FORTE IN THE TREATMENT OF NON-SEVERE FORMS OF ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASE

    OpenAIRE

    2016-01-01

    Aim: to evaluate the efficacy and tolerability of ornithine aspartate, probiotic Bioflorum Forte and their combination with steatosis and steatohepatitis in patients  with alcohol and non-alcoholic  fatty  liver disease. Materials and methods.  An open, randomized,  comparative  clinical study, which included 30 outpatients and inpatients with a diagnosis of steatosis, steatohepatitis. We analyzed the clinical symptoms, functional state of the liver. With the help of questionnaires  (Grids Le...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Susceptibility of L-FABP-/- mice to oxidative stress in early-stage alcoholic liver.

    Science.gov (United States)

    Smathers, Rebecca L; Galligan, James J; Shearn, Colin T; Fritz, Kristofer S; Mercer, Kelly; Ronis, Martin; Orlicky, David J; Davidson, Nicholas O; Petersen, Dennis R

    2013-05-01

    Chronic ethanol consumption is a prominent cause of liver disease worldwide. Dysregulation of an important lipid uptake and trafficking gene, liver-fatty acid binding protein (L-FABP), may contribute to alterations in lipid homeostasis during early-stage alcoholic liver. We have reported the detrimental effects of ethanol on the expression of L-FABP and hypothesize this may deleteriously impact metabolic networks regulating fatty acids. Male wild-type (WT) and L-FABP(-/-) mice were fed a modified Lieber-DeCarli liquid diet for six weeks. To assess the response to chronic ethanol ingestion, standard biochemical indicators for alcoholic liver disease (ALD) and oxidative stress were measured. Ethanol ingestion resulted in attenuation of hepatic triglyceride accumulation and elevation of cholesterol in L-FABP(-/-) mice. Lipidomics analysis validated multiple alterations in hepatic lipids resulting from ethanol treatment. Increased immunohistochemical staining for the reactive aldehydes 4-hydroxynonenal and malondialdehyde were observed in WT mice ingesting ethanol; however, L-FABP(-/-) mice displayed prominent protein adducts in liver sections evaluated from pair-fed and ethanol-fed mice. Likewise, alterations in glutathione, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes, and protein carbonyl content all indicated L-FABP(-/-) mice exhibit high sustained oxidative stress in the liver. These data establish that L-FABP is an indirect antioxidant protein essential for sequestering FFA and that its impairment could contribute to in the pathogenesis of ALD.

  18. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

  19. No effect of long-term oral testosterone treatment on liver morphology in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Christoffersen, Pernille Yde; Eriksen, J

    1987-01-01

    duration of 30 months demonstrated a significant (p less than 0.01) increase in the prevalence of macronodular cirrhosis (from 6 to 51%) and a significant (p less than 0.01) decrease in the prevalence of alcoholic hepatitis (to 21%) and of fatty liver (to 52%). Testosterone treatment did not significantly...... Budd-Chiari's syndrome. The degree of fatty liver and of alcoholic hepatitis in follow-up liver specimens were significantly (p less than 0.002) higher among patients who consumed ethanol during follow-up than in patients who abstained (76 versus 22% and 30 versus 6%). In conclusion, this study does......The effect of oral testosterone treatment (200 mg tid) on liver morphology was examined in a double-blind, placebo controlled study including men with alcoholic cirrhosis (n = 126). Liver biopsies obtained before randomization showed micronodular cirrhosis in 119 patients (94%), alcoholic hepatitis...

  20. Safety of frozen liver for human consumption

    Directory of Open Access Journals (Sweden)

    Ghada A.K. Kirrella

    2017-07-01

    Full Text Available The objective of this study was to ensure and evaluate the safety of imported frozen beef liver traded in supermarkets of Kafr El-Sheikh Governorate, Egypt, through detection of Salmonella typhimurium, Salmonella enteritidies, Escherichia coli O157:H7, antibiotic residues, and aflatoxin B1 residue. Fifty samples of imported frozen liver were randomly collected from different shops at Kafr El-Sheikh Governorate for isolation of S. typhimurium, S. enteritidies, and E. coli O157:H7. The results revealed that for both microorganisms 4% of the examined samples presumed to contain Salmonella and E. coli O157:H7 organisms, according to the colonial character on Harlequin Salmonella ABC agar media and Harlequin SMAC-BCIG agar media. According to biochemical and serological identifications, both organisms could not be detected in the examined samples. A total of 29 (58% samples were positive for antibiotic residues, using the Premi test (a broad-spectrum screening test for the detection of antibiotic residues in meat at or below the maximum residue limits. In addition, aflatoxin B1 was detected in one (2% samples with a concentration of 1.1 μg/kg. The results reflect that there was good hygiene practice for handling and preparation of frozen liver while selling to consumers. However, a high percentage of antibiotic residues reflect ignorance of withdrawal time before slaughtering of animals as well as misuse of antibiotics in veterinary fields. Furthermore, aflatoxin B1 residue was detected in examined frozen liver samples at a concentration below the maximum residual level, which is not enough to cause threat to humans, but it is enough to cause problem if it is eaten regularly reflect contamination of animal feed with aflatoxins.

  1. EXPERIENCE OF ORNITHINE ASPARTATE (HEPA-MERZ AND PROBIOTICS BIOFLORUM FORTE IN THE TREATMENT OF NON-SEVERE FORMS OF ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    L. Yu. Ilchenko

    2016-01-01

    Full Text Available Aim: to evaluate the efficacy and tolerability of ornithine aspartate, probiotic Bioflorum Forte and their combination with steatosis and steatohepatitis in patients  with alcohol and non-alcoholic  fatty  liver disease. Materials and methods.  An open, randomized,  comparative  clinical study, which included 30 outpatients and inpatients with a diagnosis of steatosis, steatohepatitis. We analyzed the clinical symptoms, functional state of the liver. With the help of questionnaires  (Grids LeGo and post intoxication alcohol syndrome have established the presence of chronic alcohol intoxication. Test transmissions of numbers used to characterize the cognitive function, as well as detection  of minimal hepatic encephalopathy. Quality of life was assessed by questionnaire for patients with chronic liver disease — CLDQ (The chronic liver disease questionnaire. The duration of treatment was4 weeks. Results: all three treatment regimens have demonstrated therapeutic  efficacy: clinical improvement, recovery of liver function and results in cognitive function. When combined therapy also produced a significant improvement  in patients’ quality of life. It is shown that  the safety and tolerability of the means employed, adverse events were not reported. Conclusion: the results obtained allow us to recommend the use of ornithine aspartate (Hepa-Merz, both as monotherapy and as part of complex therapy of steatosis,  steatohepatitis with probiotic Bioflorum Forte in patients with alcoholic and non-alcoholic fatty liver disease.

  2. Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Gena, Patrizia; Mastrodonato, Maria; Portincasa, Piero; Fanelli, Elena; Mentino, Donatella; Rodríguez, Amaia; Marinelli, Raúl A; Brenner, Catherine; Frühbeck, Gema; Svelto, Maria; Calamita, Giuseppe

    2013-01-01

    One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.

  3. Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Patrizia Gena

    Full Text Available One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD, is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate of increased TG in hepatocytes. Obese leptin-deficient (ob/ob mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9, the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33% than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53% than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.

  4. 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.

  5. Reversibility of increased formation of catecholamines in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Reisenauer, C.; Biermann, J.;

    2004-01-01

    BACKGROUND: While chronic alcohol abuse has been shown to be associated with increased production of catecholamines, little is known about the reversibility of this increased sympathetic activity and the influence of severity of alcoholic liver disease (ALD). The aim of the present study...... was to investigate whether the increase in urinary excretion rates and plasma levels of catecholamines in alcohol-abusing patients are reversible during prolonged abstinence, especially with respect to the severity of ALD. METHODS: Urinary excretion rates and plasma levels of noradrenaline (NA), adrenaline (A......) and dopamine (DA) were determined in 15 subjects with mild to moderate ALD (ALD1) and in 7 alcoholic cirrhotics (ALD2) on admission and after 2 and 12 weeks of abstinence. Eight healthy males, age-matched to ALD1, served as controls (HC). RESULTS: Urinary excretion rates (24 h) and resting plasma...

  6. Optical Spectra of Hemoglobin Taken from Alcohol Dependent Humans

    OpenAIRE

    Dudok K.; Dudok T.; Vlokh I.; Vlokh R.

    2005-01-01

    Optical spectra of CNMetHb and CNMetHb-Coomassi G-250, taken from the blood of humans with alcohol dependence, are studied in the spectral range of 450–750nm. The shifts in the spectral absorption maxima of CNMetHb-Coomassi G-250 complexes are observed for the diseased persons with alcohol dependence. The obtained results show that the hemoglobin structure of alcohol dependent humans is changed.

  7. Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Farholt, S

    1991-01-01

    , elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione...

  8. Proinflammatory Cytokines (IL-1α, IL-6 and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Andrzej Prystupa

    2015-01-01

    Full Text Available Background. The aim of the study was to assess the activity of interleukin-1α, interleukin-6, and hepatocyte growth factor protein (HGF in serum of patients with alcoholic liver cirrhosis. Materials and Methods. Sixty patients with alcoholic liver cirrhosis treated in various hospitals were randomly enrolled. The stage of cirrhosis was assessed according to the Child-Turcotte-Pugh scoring system. The control group consisted of ten healthy persons without liver disease, who did not drink alcohol. Additionally, the group of alcoholics without liver cirrhosis was included in the study. The activity of interleukin-1α, interleukin-6, and HGF in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Results. Higher concentrations of HGF protein were demonstrated in patients with Child class B and Child class C liver cirrhosis, compared to controls and alcoholics without liver cirrhosis. Moreover, significantly higher concentrations of HGF protein were found in patients with Child class C liver cirrhosis compared to patients with Child class A liver cirrhosis p<0.05. The concentrations of interleukin-1α in patients with Child class B and Child class C liver cirrhosis were significantly higher in comparison with controls. Significantly higher concentrations of interleukin-6 were demonstrated in Child class C, compared to Child class A.

  9. Alanine Aminotransferase Elevation in Obese Infants and Children: A Marker of Early Onset Non Alcoholic Fatty Liver Disease

    OpenAIRE

    Engelmann, Guido; Hoffmann, Georg Friedrich; Grulich-Henn, Juergen; Teufel, Ulrike

    2014-01-01

    Background: Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. Objectives: We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. Patients and Methods: In a prospective study 224 h...

  10. Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Natalia A Osna; Paul G Thomes; Terrence M Donohue Jr

    2011-01-01

    This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.

  11. 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.

  12. 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.

  13. Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Kazushige Nirei

    2013-01-01

    Full Text Available This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient’s jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.

  14. [Non-alcoholic fatty liver disease in children: a new complication of obesity].

    Science.gov (United States)

    Bocca, G; Stolk, R P; Scheenstra, R; Sauer, P J J

    2008-11-08

    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 free fatty acids play a key role in the pathogenesis of NAFLD. NAFLD can therefore be seen as a metabolic complication of obesity. Since the prevalence of obesity in Dutch children is increasing, the prevalence of NAFLD in children is expected to increase as well. Prevention of obesity and identification of children with an increased risk of NAFLD are important steps in preventing irreversible liver damage. Lifestyle changes aimed at improving insulin sensitivity through healthy food and sufficient physical activity are essential in the treatment of NAFLD. Pharmacological treatment may have additional value.

  15. Heavy Alcohol Consumption with Alcoholic Liver Disease Accelerates Sarcopenia in Elderly Korean Males: The Korean National Health and Nutrition Examination Survey 2008-2010

    Science.gov (United States)

    Chang, U Im; Choi, Sooa; Jung, Yun Duk; Han, Kyungdo; Ko, Seung-Hyun

    2016-01-01

    Background and Aim Although a few studies have reported that sarcopenia is associated with alcoholic liver disease (ALD), no studies have investigated this association in a large sample representative of the elderly Korean population. Methods This was a cross-sectional study that used data from the Fourth and Fifth Korean National Health and Nutrition Examination Surveys (KNHANES) on subjects aged 65 years and older. Sarcopenia was defined as a skeletal muscle index (SMI) more than 1 SD below the gender-specific mean for young adults; SMI was calculated as the appendicular muscle mass divided by height squared (ASM/Ht2). Heavy alcohol consumption was defined as consuming at least 210 g/week, and elevated liver enzymes were defined as alanine aminotransferase levels of at least 32 U/L or aspartate aminotransferase levels of at least 34 U/L. ALD was defined as heavy alcohol consumption and elevated liver enzymes. Results The mean age of the 1,151 elderly males was 71.6 ± 0.2 years, and the prevalence of heavy alcohol consumption was 11.8% (136 subjects). SMI did not differ between the non-heavy and heavy alcohol consumer groups (7.1 ± 0.0 kg/m2 vs. 7.3 ± 0.1 kg/m2, respectively, P = 0.145). However, after stratifying by the presence of liver disease and heavy alcohol consumption and adjusting for other confounders in the multivariate logistic regression, SMI was significantly lower among heavy alcohol consumers with ALD (all P alcohol consumption and liver disease (P = 0.011). Conclusion Sarcopenia was accelerated in the elderly male ALD group, with a significant interaction between alcohol consumption and liver disease. PMID:27655344

  16. 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.

  17. Serum inflammatory markers in overweight children and adolescents with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Neuman, Gal; Sagi, Rami; Shalitin, Shlomit; Reif, Shimon

    2010-07-01

    Obesity, a worldwide pandemia, is associated with a large variety of comorbidities, among which is non-alcoholic fatty liver disease. NAFLD is a complex disease that may eventually lead to cirrhosis, posing a high risk for the patient and thus necessitating early diagnosis and treatment. To evaluate the association between ultrasonographically diagnosed non-alcoholic fatty liver disease and the levels of serum inflammatory markers in obese children and adolescents. This prospective cohort study was conducted in children and adolescents attending the endocrine obesity clinic in a tertiary care children's hospital in 2001-2003. Blood tests and ultrasound were performed to detect the presence of fatty liver. The severity of fatty liver was determined by measuring the liver/kidney echogenicity ratio (hepatorenal index). Blood tests included complete blood count, liver enzymes, lipid profile, erythrocyte sedimentation rate, high sensitivity C-reactive protein, serum amyloid A, and the degree of erythrocyte adhesiveness/aggregation as measured in peripheral blood slides. The 30 boys and 34 girls, age 9-21 years, who participated in the study were divided into those who evidenced NAFLD on ultrasound (Group 1, n=37) and those whose liver appeared normal on ultrasound (Group 2, n=24). ESR, hs-CRP, SAA and the degree of erythrocyte adhesiveness/aggregation were compared between the groups. There was no significant association between elevated ESR, the levels of CRP, SAA and/or the degree of erythrocyte adhesiveness/aggregation and the hepatorenal index and NAFLD. The degree of erythrocyte adhesiveness/ aggregation correlated with body mass index-standard deviation score in both genders (P Fatty liver itself may not be a cofactor in stimulating inflammatory markers in obese patients. Obese children diagnosed with NAFLD may have simple steatosis and their increased inflammatory markers are therefore compatible with those expected in obesity.

  18. Observation on Effect of Treatment of Alcoholic Fatty Liver by Traditional Medical Therapy of Liver-Clearing, Dampness-Removing and Collaterals-Dredging

    Institute of Scientific and Technical Information of China (English)

    张诗军; 陈泽雄; 劳绍贤; 黄必军

    2002-01-01

    @@ Spirits of wine is one of the pathogenetic factors of liver damage which is merely secondary to hepatitis virus. The incidence of fatty liver in Chinese adults is 5%-9% now. It is reported that interleukin-8 (IL-8) and lipid peroxidation play an important role in development of alcoholic fatty liver and liver damage(1-3). The authors have observed the therapeutic effect in 30 patients of alcoholic fatty liver treated with Chinese herbal drugs for Liver-clearing, Dampness-removing and Collaterals-dredging (abbre. as CHD) from Aug. 1999 to June 2001 and explored the relationship between the effects of treatment and some indices, including IL-8, malonyldialdehyde (MDA) and superoxide dismutase (SOD).

  19. Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year.

    Science.gov (United States)

    Grąt, Michał; Lewandowski, Zbigniew; Grąt, Karolina; Wronka, Karolina Maria; Krasnodębski, Maciej; Barski, Krzysztof; Zborowska, Hanna; Patkowski, Waldemar; Zieniewicz, Krzysztof; Krawczyk, Marek

    2014-10-01

    Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism.

  20. Nonspecific Erysipelothrix rhusiopathiae Bacteremia in a Patient with Subclinical Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Asim Ahmed Kichloo

    2013-01-01

    Full Text Available Erysipelothrix rhusiopathiae, a pleomorphic gram-positive bacillus, is found widely in nature or as a commensal pathogen. It infects domestic animals such as swine, which may be the major reservoir of the organism. E. rhusiopathiae is primarily an occupational illness; 89% of the cases are linked to high-risk epidemiological situations. Humans that are infected by this bacillus typically present with one or a combination of the following symptoms: localized skin lesion (erysipeloid, diffuse cutaneous eruptions with systemic symptoms, or bacteremia, which is often followed by endocarditis. We report a case of E. rhusiopathiae bacteremia that was present without severe clinical illness such as endocarditis, arthritis, or skin lesions. The patient was a 64-year-old male with a complicated past medical history including subclinical alcoholic liver disease. Penicillin-G therapy completely resolved the patients bacteremia. The case presented has exceptional clinical merit due to 2 key factors: the patient does not fit the occupational demographic typically affected by this bacterium, and the patient presented with subclinical septicemia, which has a high correlation with fatal endocarditis. This case brings a new prospective to E. rhusiopathiae bacteremia.

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

    Science.gov (United States)

    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.

  2. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    Science.gov (United States)

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.

  3. Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological abnormalities

    Institute of Scientific and Technical Information of China (English)

    Hui Dong; Fu'er Lu; Nan Wang; Xin Zou; Jingjing Rao

    2011-01-01

    Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease (NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unknown.The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes.The serum biochemical markers,such as fasting plasma glucose (FPG),haemoglobin A1c (HbA1c),liver enzymes,lipid profiles,and haemorheological properties,were examined.IHLC was quantified using proton magnetic resonance spectroscopy (1H-MRS) scanning of the liver.A significant correlation was observed between IHLC and whole blood viscosity at high,middle,and low shear rates.IHLC also positively correlated with haematocrit,the reduced whole blood viscosity at low and middle shear rates,and the erythrocyte aggregation index.Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD.In summary,haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

  4. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  5. [Psychosocial indication of liver transplantation for alcohol-related liver failure: current controversies and imminent issues in Japanese society].

    Science.gov (United States)

    Kiuchi, Tetsuya

    2012-10-01

    Organ transplant therapy is becoming a usual practice also in Japan, which dramatically improves the length and quality of life in patients with end-stage organ disease. Liver transplantation was resumed in Japan much later than that in the West and is continued now under unique circumstances where more than 90% of grafts come from living donors. Nevertheless the number of liver transplantation for alcohol-related liver failure shows a sharp rise to the level comparable to the West, and not a few physical and/or psychosocial problems caused by recidivism after transplantation are coming up. To find appropriate solutions to how to predict recidivism and define psychosocial indication of liver transplantation in our society, and to how to monitor and support sobriety after transplantation, there is an urgent need for multidisciplinary management by hepatologist, transplant surgeon, psychiatrist, and dependence specialist. Life-saving therapy and dependence management are expected to work closely together from the viewpoints of transparency, equity, utility, and autonomy requested in transplant therapy, protection of living donors, and consideration for donor family and public emotion.

  6. GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jinmi Lee

    2012-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.

  7. Noninvasive assessment of alcoholic liver disease using unidimensional transient elastography (Fibroscan(®)).

    Science.gov (United States)

    Lupsor-Platon, Monica; Badea, Radu

    2015-11-14

    Unidimensional transient elastography (TE) is a noninvasive technique, which has been increasingly used in the assessment of diffuse liver diseases. This paper focuses on reviewing the existing data on the use of TE in the diagnosis of fibrosis and in monitoring disease progression in alcoholic liver disease, on the factors that may influence the result of fibrosis prediction, and last but not least, on its potential use in assessing the steatosis degree. Therefore, this field is far from being exhausted and deserves more attention. Further studies are required, on large groups of biopsied patients, in order to find answers to all the remaining questions in this field.

  8. The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

    Directory of Open Access Journals (Sweden)

    Anna Di Sessa

    2017-07-01

    Full Text Available The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

  9. [Non-alcoholic fatty liver disease in obese children and adolescents].

    Science.gov (United States)

    Denzer, C

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents in industrialized countries. Recent studies have demonstrated a prevalence rate of NAFLD in overweight and obese children and adolescents in Germany of up to 30%. The spectrum of NAFLD ranges from pure fatty infiltration (simple steatosis) to inflammation (steatohepatitis, synonymous NASH) to fibrosis and cirrhosis. Age, gender, ethnicity, insulin resistance, and sex steroids are implicated in the pathogenesis of NAFLD in childhood and adolescence. Moreover, NAFLD in the pediatric age group is associated with marked cardiovascular comorbidities. This review focuses on current data regarding epidemiology, pathophysiology, comorbidities, and treatment of NAFLD in children and adolescents.

  10. The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children.

    Science.gov (United States)

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele

    2017-07-07

    The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

  11. Noninvasive assessment of alcoholic liver disease using unidimensional transient elastography (Fibroscan®)

    Science.gov (United States)

    Lupsor-Platon, Monica; Badea, Radu

    2015-01-01

    Unidimensional transient elastography (TE) is a noninvasive technique, which has been increasingly used in the assessment of diffuse liver diseases. This paper focuses on reviewing the existing data on the use of TE in the diagnosis of fibrosis and in monitoring disease progression in alcoholic liver disease, on the factors that may influence the result of fibrosis prediction, and last but not least, on its potential use in assessing the steatosis degree. Therefore, this field is far from being exhausted and deserves more attention. Further studies are required, on large groups of biopsied patients, in order to find answers to all the remaining questions in this field. PMID:26576080

  12. Pathogenesis of Alcoholic Liver Disease: Interactions between parenchymal and non-parenchymal cells

    Science.gov (United States)

    Cohen, Jessica I.; Nagy, Laura E.

    2016-01-01

    The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. The impact of ethanol on hepatocytes can be characterized as a condition of “organelle stress” with multi-factorial changes in hepatocellular function accumulating during ethanol exposure. These changes include oxidative stress, mitochondrial dysfunction, decreased methylation capacity, endoplasmic reticulum stress, impaired vesicular trafficking and altered proteosome function. Injury to hepatocytes is attributed, in part, to ethanol metabolism by the hepatocytes. Changes in the structural integrety of hepatic sinusoidal endotheial cells, as well as enhanced inflammation in the liver during ethanol exposure are also important contributors to injury. Activation of hepatic stellate cells initiates the deposition of extracellular matrix proteins characteristic of fibrosis. Kupffer cells, the resident macrophages in liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharide via toll-like receptor 4. This sensitization enhances production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species, that contribute to hepatocyte dysfunction, necrosis and apoptosis of hepatocytes and generation of extracellular matrix proteins leading to fibrosis. In this review, we provide an overview of the complex interactions between parenchymal and non-parenchymal cells in the liver during the progression of ethanol-induced liver injury. PMID:21091930

  13. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  14. Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Wei-Xing Chen; You-Ming Li; Chao-Hui Yu; Wei-Min Cai; Min Zheng; Feng Chen

    2002-01-01

    AIM: To investigate the expression of the transforminggrowth factor beta 1 (TGF- beta 1 ) mRNA in different stagesof alcoholic liver disease (ALD) and its clinical value.METHODS: One hundred and seven male alcoholics weregrouped by clinical findings into four groups: alcoholabusers without liver impairment (n=22 ), alcoholicsteatosis ( n = 30 ); alcoholic hepatitis ( n = 31 ); andalcoholic cirrhosis ( n = 24 ) Using peripheral bloodmononuclear cells(PBMC) as samples the gene expressionof TGF-beta 1 was examined quantitatively by reversetranscription polymerase chain reaction (RT-PCR) and dotblot. There are 34 healthy subjects served as control.RESULTS: The expression of TGF-beta 1 from all ALDpatients was significantly greater than that in controls ( 1. 320± 1.162 vs 0.808±0.276, P<0.001). The differences of theexpressions were significant between the patients from eachgroups ( alcoholic steatosis, alcoholic hepatitis andalcoholic cirrhosis) and the controls ( 1. 168 ± 0.852, 1.462 ±1.657, 1.329± 0.610 vs 0.808 ± 0.276, P< 0.050). Nosignificant differences of TGF -beta 1 mRNA expression wereobserved between alcohol abusers without liver impairmentand controls. The expressions in patients with alcoholichepatitis and alcoholic cirrhosis were significantly greaterthan that in alcohol abusers respectively (1.462 ± 1. 657, 1.329 ± 0. 610 vs 0. 841 ± 0. 706, P < 0. 050). No significantdifferences of TGF -beta 1 mRNA expression were observedbetween alcoholic fatty liver men and alcohol abusers.CONCLUSION: TGF-beta 1 expression level can be a riskfactor for alcoholic liver disease and might be related to theinflammatory activity and fibrosis of the liver in patients .

  15. Does an association exist between chronic pancreatitis and liver cirrhosis in alcoholic subjects?

    Institute of Scientific and Technical Information of China (English)

    Luis Aparisi; Luis Sabater; Juan Del-Olmo; Juan Sastre; MigueI-Angel Serra; Ricardo Campello; Daniel Bautista; Abdalla Wassel; José-Manuel Rodrigo

    2008-01-01

    AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (η = 53), LC (η = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and fecal pancreatic elastase-1 test were assessed. RESULTS: In patients with cirrhosis, major clinical manifestations of CP such as pancreatic pain and steatorrhea, as well as imaging alterations of CP such as calcifications, duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases, and elastase-1 test was altered in only 7%, and severely altered in none. In patients with CP, clinical characteristics of cirrhosis such as ascites, encephalopathy and gastrointestinal hemorrhage were present in one case, Child-Pugh grade > A in 5.7%, and altered indocyanine green test in 1.9% cases. In asymptomatic alcoholism, there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%, respectively, but other characteristics of cirrhosis or CP were absent. An inverse correlation (r=-0.746) between elastase-1 test and indocyanine test was found in alcoholic patients. CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology, but an inverse correlation between pancreatic and liver function tests. These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis.

  16. Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α in alcoholic liver disease

    OpenAIRE

    Fisher, N; Neil, D.; Williams, A.; Adams, D.

    1999-01-01

    BACKGROUND—Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1α (MIP-1α).
AIMS—To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease.
PATIENTS—Fifty one patients with alcoholic liver disease and 12 healthy co...

  17. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Non-alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans;

    2016-01-01

    CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting and hyperin......CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting...... and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD-). DESIGN: 27 non-diabetic, upper-body obese (WHR >0.9, BMI >28 kg/m(2)) men, 18 NAFLD+ and 9 NAFLD- determined by magnetic resonance spectroscopy, were enrolled.(14)C-labeled VLDL-TG and (3)H-labeled glucose and palmitate tracers were applied...... metabolic abnormalities associated with NAFLD and presumably diabetes....

  18. Is there any progress in the treatment of non-alcoholic fatty liver disease?

    Institute of Scientific and Technical Information of China (English)

    Emmanuel; A; Tsochatzis; George; V; Papatheodoridis

    2011-01-01

    Despite the fact that non-alcoholic fatty liver disease(NAFLD) and its severe clinical form,non-alcoholic steatohepatitis,are becoming increasingly prevalent in the industrialised countries,there are no licensed pharmacological treatments for them.Weight loss and life modifications,antioxidant therapies and insulin-sensitising agents are the current treatment strategies and have all been tested with inconclusive results.Low sample numbers,inadequate treatment duration and invalid surrogate markers for treatment response might all account for these results.As NAFLD is a systemic rather than a liver disease,future trials should address the patient as a whole and also address cardiovascular risk factors.

  19. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig (Germany)

    2014-08-15

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.

  20. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  1. Calculations of hydrogen tunnelling and enzyme catalysis: a comparison of liver alcohol dehydrogenase, methylamine dehydrogenase and soybean lipoxygenase

    Science.gov (United States)

    Tresadern, Gary; McNamara, Jonathan P.; Mohr, Matthias; Wang, Hong; Burton, Neil A.; Hillier, Ian H.

    2002-06-01

    Although the potential energy barrier for hydrogen transfer is similar for the enzymes liver alcohol dehydrogenase, methylamine dehydrogenase and soybean lipoxygenase, the degree of tunnelling is predicted to differ greatly, and is reflected by their primary kinetic isotope effects.

  2. 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.

  3. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended

  4. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

    Science.gov (United States)

    Milić, Sandra; Lulić, Davorka; Štimac, Davor

    2014-07-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

  5. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-09-28

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle

  6. Genetical genomic determinants of alcohol consumption in rats and humans

    Directory of Open Access Journals (Sweden)

    Mangion Jonathan

    2009-10-01

    Full Text Available Abstract Background We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs. Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results In the HXB/BXH recombinant inbred (RI rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume

  7. YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Bojesen, Stig E; Nordestgaard, Børge G

    2014-01-01

    .1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7...... was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1...

  8. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice

    OpenAIRE

    Le Roy, Tiphaine; Llopis, Marta; Lepage, Patricia; Bruneau, Aurelia; Rabot, Sylvie; Bevilacqua, Claudia; Martin, Patrice; Philippe, Catherine; Walker, Francine; Bado, Andre; Perlemuter, Gabriel; Cassard-Doulcier, Anne-Marie

    2013-01-01

    Objective: Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese people and is considered the hepatic manifestation of metabolic syndrome. However, not all obese individuals develop NAFLD. Our objective was to demonstrate the role of the gut microbiota in NAFLD development using transplantation experiments in mice. [br/] Design: Two donor C57BL/6J mice were selected on the basis of their responses to a high-fat diet (HFD). Although both mice displayed similar body weight gain, on...

  9. An unusual cause of spontaneous bacterial peritonitis due to Campylobacter fetus with alcoholic liver cirrhosis

    OpenAIRE

    Hadano, Yoshiro; Iwata, Hiroyoshi

    2013-01-01

    A 40-year-old man with severe alcoholic liver cirrhosis with a 2-day history of fatigue and abdominal pain was admitted. He reported eating sushi and sliced raw chicken a few days previously. His abdomen was distended, with shifting dullness. Based on the patient's history, physical examination and the results of abdominocentesis, he was diagnosed as having spontaneous bacterial peritonitis; blood and ascitic fluid cultures were positive for Campylobacter fetus. The patient was started on tre...

  10. Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

    Institute of Scientific and Technical Information of China (English)

    H; Joe; Wang; Samir; Zakhari; M; Katherine; Jung

    2010-01-01

    Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous syst...

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  12. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Mônica Rodrigues de Araújo Souza

    2012-03-01

    Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

  13. WJH 6th Anniversary Special Issues(7): Nonalcoholic fatty liver disease Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Hye-jin; Yoon; Bong; Soo; Cha

    2014-01-01

    Non-alcoholic fatty liver disease affects approximately one-third of the population worldwide, and its incidence continues to increase with the increasing prevalence of other metabolic disorders such as type 2 diabetes. As non-alcoholic fatty liver disease can progress to liver cirrhosis, its treatment is attracting greater attention. The pathogenesis of non-alcoholic fatty liver disease is closely associated with insulin resistance and dyslipidemia, especially hypertriglyceridemia. Increased serum levels of free fatty acid and glucose can cause oxidative stress in the liver and peripheral tissue, leading to ectopic fat accumulation, especially in the liver. In this review, we summarize the mechanism underlying the progression of hepatic steatosis to steatohepatitis and cirrhosis. We also discuss established drugs that are already being used to treat non-alcoholic fatty liver disease, in addition to newly discovered agents, with respect to their mechanisms of drug action, focusing mainly on hepatic insulin resistance. As well, we review clinical data that demonstrate the efficacy of these drugs, together with improvements in biochemical or histological parameters.

  14. Presence of fatty liver and the relationship between alcohol consumption and markers of inflammation.

    Science.gov (United States)

    Kächele, Martin; Wolff, Stefan; Kratzer, Wolfgang; Haenle, Mark; Homann, Jörg; Trischler, Gerlinde; Koenig, Wolfgang; Imhof, Armin

    2015-01-01

    Background and Aims. Local and systemic inflammation represent a major feature of atherosclerotic cardiovascular disease (CVD) and are also linked to nonalcoholic fatty liver disease (NAFLD). Studies indicate that NAFLD might be a risk factor for CVD whereas low-to-moderate alcohol consumption is associated with lower cardiovascular morbidity and mortality compared to abstainers and heavy drinkers. We hypothesize that FLD interacts with the effect of alcohol intake on markers of inflammation, and thus potentially on cardiovascular risk. Methods and Results. We evaluated alcohol consumption, markers of inflammation and sonographic criteria of FLD in 515 subjects, representing a subsample of a cross-sectional population based study (Echinococcus multilocularis and Internal Diseases in Leutkirch (EMIL) Study). Presence of FLD was markedly reduced in subjects drinking 0-20 g alcohol/d (19%), compared to nondrinkers (35%) and heavy drinkers (34-44.9%). Serum concentrations of inflammatory markers were substantially higher in subjects with FLD. However, presence of FLD showed no effect on the association between alcohol consumption and inflammatory biomarkers. Conclusions. Based on data from a population-based sample, there is no evidence for a link between FLD, alcohol consumption, and inflammatory cardiovascular risk markers. However, larger prospective studies are needed to confirm this.

  15. Presence of Fatty Liver and the Relationship between Alcohol Consumption and Markers of Inflammation

    Directory of Open Access Journals (Sweden)

    Martin Kächele

    2015-01-01

    Full Text Available Background and Aims. Local and systemic inflammation represent a major feature of atherosclerotic cardiovascular disease (CVD and are also linked to nonalcoholic fatty liver disease (NAFLD. Studies indicate that NAFLD might be a risk factor for CVD whereas low-to-moderate alcohol consumption is associated with lower cardiovascular morbidity and mortality compared to abstainers and heavy drinkers. We hypothesize that FLD interacts with the effect of alcohol intake on markers of inflammation, and thus potentially on cardiovascular risk. Methods and Results. We evaluated alcohol consumption, markers of inflammation and sonographic criteria of FLD in 515 subjects, representing a subsample of a cross-sectional population based study (Echinococcus multilocularis and Internal Diseases in Leutkirch (EMIL Study. Presence of FLD was markedly reduced in subjects drinking 0–20 g alcohol/d (19%, compared to nondrinkers (35% and heavy drinkers (34–44.9%. Serum concentrations of inflammatory markers were substantially higher in subjects with FLD. However, presence of FLD showed no effect on the association between alcohol consumption and inflammatory biomarkers. Conclusions. Based on data from a population-based sample, there is no evidence for a link between FLD, alcohol consumption, and inflammatory cardiovascular risk markers. However, larger prospective studies are needed to confirm this.

  16. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study

    Directory of Open Access Journals (Sweden)

    Jang Eun

    2012-10-01

    Full Text Available Abstract Background Liver function tests (LFTs can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. Methods We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Results Coffee consumption was closely related to male gender, high body mass index (BMI, alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST. On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Conclusions Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

  17. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study.

    Science.gov (United States)

    Jang, Eun Sun; Jeong, Sook-Hyang; Hwang, Sung Ho; Kim, Hyun Young; Ahn, So Yeon; Lee, Jaebong; Lee, Sang Hyub; Park, Young Soo; Hwang, Jin Hyeok; Kim, Jin-Wook; Kim, Nayoung; Lee, Dong Ho

    2012-10-18

    Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

  18. Applying the nursing theory of human relatedness to alcoholism and recovery in alcoholics anonymous.

    Science.gov (United States)

    Strobbe, Stephen; Hagerty, Bonnie; Boyd, Carol

    2012-12-01

    Alcohol misuse is a global health risk, and Alcoholics Anonymous (AA) is the largest and most popular mutual-help program for individuals with alcohol-related problems. In recent years, researchers and clinicians have become increasingly interested in specific mechanisms of action that may contribute to positive outcomes through involvement with this 12-step program for recovery, yet few have applied a theoretical framework to these efforts. We examined the phenomena of alcoholism and recovery in AA, using the nursing Theory of Human Relatedness (THR). THR addresses a pervasive human concern: "establishing and maintaining relatedness to others, objects, environments, society and self." The theory describes four states of relatedness (connectedness, disconnectedness, parallelism, and enmeshment) and four relatedness competencies (sense of belonging, reciprocity, mutuality, and synchrony). Both alcoholism and recovery in AA can be viewed primarily in terms of relatedness. In active alcoholism, an individual's involvement with alcohol (enmeshment) can limit, impair, or preclude healthy or adaptive relatedness toward virtually all other referents, including self. As a program of recovery, each of the 12 Steps of Alcoholics Anonymous addresses an individual's relatedness to one or more identified referents while simultaneously enhancing and expanding each of the four relatedness competencies. THR provides a theoretical framework to help direct patient care, research, and education and has the potential to serve as a unifying theory in the study of alcoholism and recovery in AA.

  19. Metabolic danger signals, uric acid and ATP, mediate inflammatory cross-talk between hepatocytes and immune cells in alcoholic liver disease.

    Science.gov (United States)

    Petrasek, Jan; Iracheta-Vellve, Arvin; Saha, Banishree; Satishchandran, Abhishek; Kodys, Karen; Fitzgerald, Katherine A; Kurt-Jones, Evelyn A; Szabo, Gyongyi

    2015-08-01

    Inflammation defines the progression of ALD from reversible to advanced stages. Translocation of bacterial LPS to the liver from the gut is necessary for alcohol-induced liver inflammation. However, it is not known whether endogenous, metabolic danger signals are required for inflammation in ALD. Uric acid and ATP, 2 major proinflammatory danger signals, were evaluated in the serum of human volunteers exposed to a single dose of ethanol or in supernatants of primary human hepatocytes exposed to ethanol. In vitro studies were used to evaluate the role of uric acid and ATP in inflammatory cross-talk between hepatocytes and immune cells. The significance of signaling downstream of uric acid and ATP in the liver was evaluated in NLRP3-deficient mice fed a Lieber-DeCarli ethanol diet. Exposure of healthy human volunteers to a single dose of ethanol resulted in increased serum levels of uric acid and ATP. In vitro, we identified hepatocytes as a significant source of these endogenous inflammatory signals. Uric acid and ATP mediated a paracrine inflammatory cross-talk between damaged hepatocytes and immune cells and significantly increased the expression of LPS-inducible cytokines, IL-1β and TNF-α, by immune cells. Deficiency of NLRP3, a ligand-sensing component of the inflammasome recognizing uric acid and ATP, prevented the development of alcohol-induced liver inflammation in mice and significantly ameliorated liver damage and steatosis. Endogenous metabolic danger signals, uric acid, and ATP are involved in inflammatory cross-talk between hepatocytes and immune cells and play a crucial role in alcohol-induced liver inflammation.

  20. Role of Innate Immune Response in Non-Alcoholic Fatty Liver Disease: Metabolic Complications and Therapeutic Tools

    OpenAIRE

    Rosaria eMeli; Giuseppina eMattace Raso; Antonio eCalignano

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, both in adults and children. It is characterized by an aberrant lipid storage in hepatocytes, named hepatic steatosis. Simple steatosis remains a benign process in most affected patients, while some of them develop superimposed necroinflammatory activity with a non-specific inflammatory infiltrate and a progression to non-alcoholic steatohepatitis with or without fibrosis. Deep similarity and inter...

  1. Intima-media thickness and liver histology in obese children and adolescents with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Manco, Melania; Bedogni, Giorgio; Monti, Lidia; Morino, Giuseppe; Natali, Gianluigi; Nobili, Valerio

    2010-04-01

    To evaluate the relationship between biopsy-proven non-alcoholic fatty liver disease (NAFLD) and carotid artery intima-media thickness (CIMT) in children and adolescents. A case-control study was performed. Cases were 31 mostly obese children and adolescents, with NAFLD detected at ultrasonography, and confirmed by liver biopsy. Controls were 49 mostly obese children matched for gender, age and BMI without NAFLD at ultrasonography and with normal levels of aminotransferases. Besides standard laboratory measurements, subjects underwent an oral glucose tolerance test to evaluate glucose tolerance and to estimate whole body insulin sensitivity (ISI). CIMT was similar in cases and controls on the right side but higher in cases on the left side. Although statistically significant, this difference is unlikely to be clinically relevant because of substantial overlap of CIMT values between cases and controls. Moreover, there was no association between CIMT and the severity of steatosis, ballooning, fibrosis, and the non-alcoholic steato-hepatitis score in cases. At multivariable analysis in the pooled sample (n=80), age and the z-score of BMI but not NAFLD, gender, blood pressure and triglycerides, were associated with CIMT. We found no association between CIMT and NAFLD in children and adolescents. More importantly, there was no association between histological severity and CIMT in children with NAFLD. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  2. Kerusakan Hati Akibat Keracunan Alkohol Berulang pada Tikus Wistar (LIVER DAMAGE DUE TO ALCOHOL INTOXICATION REPEAT IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Ni Made Suaniti

    2014-08-01

    Full Text Available The aims of this study was to determine the liver damage from alcohol intoxication in Wistar rats.The design used in this study was a randomized true experimental post test only control group design. Thestudy used 15 rats divided into 3 treatment groups each of which consists of 5 rats. The first group wasgiven distill water. The second group was given 5% alcohol, and the third group was given 20% alcohol. Ratswere treated with alcohol daily for six weeks. Biochemical markers were detected the levels of aldehydedehydrogenase (ALDH in serum and histological changes in liver tissue. ALDH is a biochemical markerof a sensitive and specific ethanol after chronic alcohol administration. Blood sample was collected at 6and 24 hours after the last peroral administration of repeated alcohol treatment, and serum levels ofALDH was tested by enzyme linked immunosorbent assay (ELISA. The results showed that the levels ofALDH in the blood of alcohol treated Wistar rats significantly higher as compared to those of control rats.ALDH levels increased by 83.11% after administration of 5% alcohol and 112.05% after administration of20% taken after 6 hours of alcohol for 6 weeks. On samples taken after 24 hours, ALDH levels by 95.11%after administration of 5% alcohol and 86.79% after administration of 20% alcohol. Oral treatment with20% alcohol chronically was led to changes in the microscopic structure (necrosis of liver tissue in Wistarrats. Liver tissue damage occured due to repeated use of alcohol is accompanied by increasing serum levelsof ALDH in Wistar rats.

  3. Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

    Directory of Open Access Journals (Sweden)

    Joo Ho Lee

    2014-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is defined as a pathologic accumulation of fat in the form of triglycerides (TG in the liver (steatosis that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis, which is referred to as non-alcoholic steatohepatitis (NASH. Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC. NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.

  4. Assessment of alcohol consumption in liver transplant candidates and recipients: the best combination of the tools available.

    Science.gov (United States)

    Piano, Salvatore; Marchioro, Lucio; Gola, Elisabetta; Rosi, Silvia; Morando, Filippo; Cavallin, Marta; Sticca, Antonietta; Fasolato, Silvano; Forza, Giovanni; Chiara Frigo, Anna; Plebani, Mario; Zanus, Giacomo; Cillo, Umberto; Gatta, Angelo; Angeli, Paolo

    2014-07-01

    The detection of alcohol consumption in liver transplant candidates (LTCs) and liver transplant recipients (LTRs) is required to enable a proper assessment of transplant eligibility and early management of alcohol relapse, respectively. In this clinical setting, urinary ethyl glucuronide (uEtG), the Alcohol Use Disorders Identification Test for Alcohol Consumption (AUDIT-c), serum ethanol, urinary ethanol, carbohydrate-deficient transferrin (CDT), and other indirect markers of alcohol consumption were evaluated and compared prospectively in 121 LTCs and LTRs. Alcohol consumption was diagnosed when AUDIT-c results were positive or it was confirmed by a patient's history in response to abnormal results. Alcohol consumption was found in 30.6% of the patients. uEtG was found to be the strongest marker of alcohol consumption (odds ratio = 414.5, P alcohol consumption [area under receiving operating characteristic (ROC) curve = 0.94] than CDT (area under ROC curve = 0.63, P alcohol consumption in comparison with the combination of CDT and AUDIT-c (area under ROC curve = 0.98 versus 0.80, P alcohol consumption in patients with negative AUDIT-c results. In conclusion, the combination of AUDIT-c and uEtG improves the detection of alcohol consumption in LTCs and LTRs. Therefore, they should be used routinely for these patients.

  5. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Silvia Sookoian

    Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

  6. Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.

    Directory of Open Access Journals (Sweden)

    Elizabeth Osterndorff-Kahanek

    Full Text Available Chronically available alcohol escalates drinking in mice and a single injection of the immune activator lipopolysaccharide can mimic this effect and result in a persistent increase in alcohol consumption. We hypothesized that chronic alcohol drinking and lipopolysaccharide injections will produce some similar molecular changes that play a role in regulation of alcohol intake. We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes among four groups of animals, three consuming alcohol (vs water in different consumption tests and one injected with lipopolysaccharide (vs. vehicle. The three tests of alcohol consumption are the continuous chronic two bottle choice (Chronic, two bottle choice available every other day (Chronic Intermittent and limited access to one bottle of ethanol (Drinking in the Dark. Gene expression changes were more numerous and marked in liver than in prefrontal cortex for the alcohol treatments and similar in the two tissues for lipopolysaccharide. Many of the changes were unique to each treatment, but there was significant overlap in prefrontal cortex for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide and in liver all pairs showed overlap. In silico cell-type analysis indicated that lipopolysaccharide had strongest effects on brain microglia and liver Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine-related (PPP1R1B, DRD1, DRD2, FOSB, PDNY network that was highly over-represented in the Chronic Intermittent group, with several genes from the network being also regulated in the Chronic and lipopolysaccharide (but not Drinking in the Dark groups. Liver showed a CYP and GST centered metabolic network shared in part by all four treatments. We demonstrate common consequences of chronic alcohol

  7. Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?

    Science.gov (United States)

    Fu, Jun-Fen; Shi, Hong-Bo; Liu, Li-Rui; Jiang, Ping; Liang, Li; Wang, Chun-Lin; Liu, Xi-Yong

    2011-02-14

    To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and if liver B-ultrasound can be used for its diagnosis. We classified 861 obese children (6-16 years old) into three subgroups: group 0 (normal liver in ultrasound and normal transaminases); group 1 (fatty liver in ultrasound and normal transaminases); and group 2 (fatty liver in ultrasound and elevated transaminases). We measured the body mass index, waist and hip circumference, blood pressure, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), lipid profile and transaminases in all the participants. The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination. Among the 861 obese children, 587 (68.18%) were classified as having NAFLD, and 221 (25.67%) as having MS. The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587), which was much higher than that in non-NAFLD group (group 0, 12.04%) (P liver fatty infiltration carried a high risk of hypertension [odds ratio (OR): 2.18, 95% confidence interval (95% CI): 1.27-3.75], dyslipidemia (OR: 7.99, 95% CI: 4.34-14.73), impaired fasting glucose (OR: 3.65, 95% CI: 1.04-12.85), and whole MS (OR: 3.77; 95% CI: 1.90-7.47, P fatty infiltration increased. NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and liver B-ultrasound can be a useful tool for MS screening.

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

    DEFF Research Database (Denmark)

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

    1987-01-01

    The fenestration of hepatic sinusoidal endothelial cells in 15 needle biopsies obtained from chronic alcoholics without cirrhosis was studied by scanning electron microscopy. As compared to nonalcoholics, a significant reduction in the number of fenestrae and porosity of the sinusoidal lining wall...

  9. Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.

    Directory of Open Access Journals (Sweden)

    Andrea Baiocchini

    Full Text Available Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis. Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

  10. [Interrupted alcohol treatment and liver: free radical homeostasis, nitric oxide, adaptive mechanisms].

    Science.gov (United States)

    Miskevich, D A; Borodinskiĭ, A N; Petushok, N E; Konovalenko, O V; Lelevich, V V

    2006-01-01

    Alcohol administration can result in liver damage. Reactive oxygen species (ROS), nitric oxide (NO) and their interaction are crucial factors in this process. The aim of work was to investigate, free radical state and mechanisms of adaptation of the antioxidant system (AOS) to stress, caused by interrupted alcohol intake. Repeated cycles of alcoholization caused an imbalance between production and utilization of various ROS. This imbalance was due to impairments in the system superoxide dismutase/catalase. Nevertheless, in most experimental groups there was clear reduction of lipid peroxidation (LPO) products evaluated by thiobarbituric acid reactive substances. This might be attributed to the antioxidant effect of NO. However, there was an increased level of transaminases in blood plasma. After 28 days of this experimental scheme all the parameters studied normalized.

  11. Non-Alcoholic Fatty Liver Disease: Lipids and Insulin Resistance

    Science.gov (United States)

    Berk, Paul D; Verna, Elizabeth C

    2016-01-01

    Abstract/Synopsis Obesity and its major co-morbidities, including type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), obesity cardiomyopathy, and certain cancers, are major public health problems worldwide. They are responsible for substantial morbidity and mortality, to a degree that life expectancy in the United States has actually declined in recent years because of it. Obesity is the increased accumulation of fat, i.e. triglycerides (TG), which are synthesized from glycerol and long chain fatty acids (LCFA), throughout the body. Although long believed to enter cells solely by passive diffusion, it has been established over the past 30 years that LCFA enter adipocytes, hepatocytes and cardiomyocytes via specific, facilitated transport processes, and that these processes are hormonally up-regulated in obesity. Metabolism of increased cellular TG content in obesity may lead to cell-specific lipotoxicity, contributing to co-morbidities such as NAFLD and cardiomyopathy. In contrast to the popular perception, dietary control and bariatric surgery can each achieve major initial weight loss in many patients. However several mechanisms, including persistent up-regulation of LCFA transport, contribute to weight regain in the large majority of patients. Better understanding of these transport processes and their regulation may be a key to successful future strategies to treat obesity and NAFLD. PMID:27063267

  12. 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.

  13. 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.

  14. Alcohol consumption and risk of fatty liver disease: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Guoli Cao

    2016-10-01

    Full Text Available Background Observational studies have shown inconsistent results regarding alcohol consumption and risk of fatty liver. We performed a meta-analysis of published literature to investigate the association between alcohol consumption and fatty liver disease (FLD. Methods We searched Medline, Embase, Web of Science, and several Chinese databases, identifying studies that reported an association between alcohol consumption and the risk of FLD. Results A total of 16 studies with 76,608 participants including 13 cross-sectional studies, two cross-sectional following longitudinal studies, and one cohort study met the inclusion criteria. For light to moderate alcohol consumption (LMAC, there was a 22.6% reduction in risk of FLD (odds ratio [OR] = 0.774, 95% confidence interval CI [0.695–0.862], P <0.001, and subgroup analysis showed that a greater reduction in risk of FLD was found in the female drinkers (30.2% and the drinkers with BMI ≥25 kg/m2(31.3% compared with the male drinkers (22.6% and the drinkers with BMI <25 kg/m2(21.3%, respectively. For heavy alcohol consumption, there was no significant influence on risk of FLD (OR = 0.869, 95% CI [0.553–1.364], P = 0.541 in Japanese women, but there was a 33.7% reduction in risk of FLD (OR = 0.663, 95% CI [0.574–0.765], P < 0.001 in Japanese men and a significant increased risk of FLD (OR = 1.785, 95% CI [1.064–2.996], P = 0.028 in Germans. Conclusion LMAC is associated with a significant protective effect on FLD in the studied population, especially in the women and obese population. However, the effect of heavy alcohol consumption on FLD remains unclear due to limited studies and small sample sizes.

  15. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Rahimi

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α, interleukin 1 (IL-1, IL-6, IL-8, adhesion molecules (ICAM, VCAM and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.

  16. Proteomic and genomic studies of non-alcoholic fatty liver disease--clues in the pathogenesis.

    Science.gov (United States)

    Lim, Jun Wei; Dillon, John; Miller, Michael

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production.

  17. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kawano, Yuki; Cohen, David E

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.

  18. Nutritional deficiencies in German middle-class male alcohol consumers: relation to dietary intake and severity of liver disease

    DEFF Research Database (Denmark)

    Bergheim, I.; Parlesak, Alexandr; Dierks, C.

    2003-01-01

    OBJECTIVE: The purpose of the present study was to compare the nutrient intake and the nutritional status between German middle-class alcohol consumers and non-drinkers. DESIGN: Cross-sectional study using patients with different stages of alcoholic liver disease (ALD) and healthy volunteers....... SETTING: Southern Germany. SUBJECTS: Seventy-six hospitalized German middle-class alcohol consumers with different stages of alcoholic liver disease (ALD) and 22 healthy control subjects. METHODS: Subjects and controls were nutritionally assessed and mineral and vitamin content was measured in blood...... than those of non-drinkers. CONCLUSION: From the results of this study it is concluded that in German middle-class male alcohol consumers the status of several micronutrients is disturbed, although dietary intake hardly differs from that in non-alcoholic controls....

  19. Nutritional deficiencies in German middle-class male alcohol consumers: relation to dietary intake and severity of liver disease

    DEFF Research Database (Denmark)

    Bergheim, I.; Parlesak, Alexandr; Dierks, C.;

    2003-01-01

    OBJECTIVE: The purpose of the present study was to compare the nutrient intake and the nutritional status between German middle-class alcohol consumers and non-drinkers. DESIGN: Cross-sectional study using patients with different stages of alcoholic liver disease (ALD) and healthy volunteers....... SETTING: Southern Germany. SUBJECTS: Seventy-six hospitalized German middle-class alcohol consumers with different stages of alcoholic liver disease (ALD) and 22 healthy control subjects. METHODS: Subjects and controls were nutritionally assessed and mineral and vitamin content was measured in blood...... and urine. RESULTS: When compared with controls, alcohol consumers had significantly higher intakes of total calories, but intake of non-alcoholic calories did not differ between groups (P

  20. Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Salvatore Petta

    Full Text Available BACKGROUND AND AIMS: Variant in glucokinase regulatory protein (GCKR, associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C→T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype. METHODS: In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy, we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed. RESULTS: At multivariate logistic regression analysis in the entire NAFLD cohort, the presence of significant liver fibrosis (>F1 was independently linked to high HOMA (OR 1.12, 95% CI 1.01-1.23, p = 0.02, NAFLD activity score ≥ 5 (OR 4.09, 95% CI 2.45-6.81, pT SNP (OR 2.06, 95% CI 1.43-2.98, pT SNP was also associated with higher serum triglycerides (ANOVA, p = 0.02 in the entire cohort. CONCLUSIONS: In patients with NAFLD, GCKR rs780094 C>T is associated with the severity of liver fibrosis and with higher serum triglyceride levels.

  1. 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.

  2. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

    Directory of Open Access Journals (Sweden)

    Claudia Sanna

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  3. What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

    Science.gov (United States)

    Finelli, Carmine; Tarantino, Giovanni

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries. Insulin resistance is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of insulin resistance or obesity. Adiponectin is the most abundant adipose-specific adipokine. There is evidence that adiponectin decreases hepatic and systematic insulin resistance, and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and the severity of NAFLD; however, to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically. PMID:23430039

  4. C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Anty, Rodolphe; Tordjman, Joan

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH...

  5. Mental disorders in alcoholic liver disease%酒精性肝病与精神障碍

    Institute of Scientific and Technical Information of China (English)

    胡伟(综述); 韩涛; 刘华(审校)

    2014-01-01

    酒精性肝病是由于长期大量饮酒所导致的慢性肝脏疾病。酗酒会导致机体多系统受损,其中包括神经损害和精神障碍。临床上,酒精所致的神经精神损害表现复杂多样,常导致诊断困难甚至出现误诊。本文将对酒精所致的精神障碍的机制、5种常见的酒精性精神障碍疾病的识别要点及酒精性相关精神障碍的治疗进行综述。多学科有效协作、社会和家庭各方面相互合作对此类疾病的诊治和预防具有重要意义。%Alcoholic liver disease is caused by long-term heavy alcohol drinking. Alcoholism may lead to the multiple systems injury of human body,including neuropsychiatric injury. The manifestations of neuropsychiatric injury caused by alco-holism are complex and varied,which often make clinical diagnosis difficult. In this paper,we will review the mechanisms of alco-hol-induced mental disorders,the clinical features and treatment of five kinds of common alcoholic mental disorders. Effective multi-disciplinary collaboration and the help of society and family members are great significance for diagnosis,treatment and pre-vention of these diseases.

  6. 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.

  7. Elderly Alcoholism: Implications for Human Service Education

    Science.gov (United States)

    Beechem, Michael

    2004-01-01

    Incumbent upon those faculty who teach substance abuse courses is the need to integrate elderly alcoholism-related course content to encourage and adequately prepare university students to serve this "hidden" population. Course content would ideally include theories specific to loss-grief, aging, and alcoholism. In addition, field placement…

  8. Effects of Alcohol on Human Aggression.

    Science.gov (United States)

    Parrott, Dominic J; Eckhardt, Christopher I

    2018-02-01

    There is little debate that alcohol is a contributing cause of aggressive behavior. The extreme complexity of this relation, however, has been the focus of extensive theory and research. And, likely due to this complexity, evidence-based programs to prevent or reduce alcohol-facilitated aggression are quite limited. We integrate I(3) Theory and Alcohol Myopia Theory to provide a framework that (1) organizes the myriad instigatory and inhibitory factors that moderate the effect of alcohol on aggression, and (2) highlights the mechanisms by which alcohol facilitates aggression among at-risk individuals. This integrative framework provides the basis for understanding the appropriate targets for prevention and intervention efforts and may serve as a catalyst for future research that seeks to inform intervention development.

  9. Free triiodothyronine as determinant of non-alcoholic fatty liver disease in euthyroid subjects: The lifelines cohort study

    NARCIS (Netherlands)

    Van Den Berg, Eline; van Tienhoven-Wind, Lynnda; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, H.; Dullaart, Robin P.F.

    2016-01-01

    Background: Non-alcoholic fatty live disease (NAFLD) is becoming the leading cause of chronic liver disease in de Western world. The liver plays a crucial role in the metabolism of cholesterol and triglycerides and thyroid hormones interact on hepatic lipid homeostasis. Given the importance of

  10. Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects : The Lifelines Cohort Study

    NARCIS (Netherlands)

    van den Berg, Eline H.; van Tienhoven-Wind, Lynnda J. N.; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.

    Objective. Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a

  11. Effect of alcohol on blood glucose and antioxidant enzymes in the liver and kidney of diabetic rats

    Directory of Open Access Journals (Sweden)

    K R Shanmugam

    2011-01-01

    Full Text Available Objective: Diabetes mellitus affects every organ in the man including eyes, kidney, heart, and nervous system. Alcohol consumption is a widespread practice. As the effects of chronic alcohol consumption on diabetic state have been little studied, this study was conducted with the objective of evaluating the effect of alcohol in diabetic rats. Materials and Methods: For this study, the rats were divided into five groups (n = 6 in each group: normal control (NC, alcohol treatment (At, diabetic control (DC, diabetic plus alcohol treatment (D + At, diabetic plus glibenclamide treatment (D + Gli. Alcohol treatment was given to the diabetic rats for 30 days. During the period the blood glucose levels, and body weight changes were observed at regular intervals. The antioxidant enzymes like superoxide dismutase (SOD, catalase (CAT, and malondialdehyde (MDA levels were assayed in the liver and kidney tissues. Results: The blood glucose levels were significantly (P < 0.001 elevated and body weight significantly (P < 0.001 decreased in alcohol-treated diabetic rats. SOD and CAT activities were decreased and the MDA level increased significantly (P < 0.001 in alcohol-treated diabetic rats. Histopathological studies showed that alcohol damages the liver and kidney tissues in diabetic rats. Conclusion: These finddings concluded that the consumption of alcohol in diabetic rats worsens the condition. So the consumption of alcohol by diabetic subjects may be potentially harmful.

  12. Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

    Science.gov (United States)

    McKee, Chad; Sigala, Barbara; Soeda, Junpei; Mouralidarane, Angelina; Morgan, Maelle; Mazzoccoli, Gianluigi; Rappa, Francesca; Cappello, Francesco; Cabibi, Daniela; Pazienza, Valerio; Selden, Claire; Roskams, Tania; Vinciguerra, Manlio; Oben, Jude A.

    2015-01-01

    Amphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-α converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also assessed in a mouse model of NASH and in humans with NASH. hHSC time dependently expressed AR and TACE. AR increased hHSC proliferation through several mitogenic signaling pathways such as EGFR, PI3K and p38. AR also induced marked upregulation of hHSC fibrogenic markers and reduced hHSC death. AR expression was enhanced in the HSC of a murine model of NASH and of severe human NASH. In conclusion, AR induces hHSC fibrogenic activity via multiple mitogenic signaling pathways, and is upregulated in murine and human NASH, suggesting that AR antagonists may be clinically useful anti-fibrotics in NAFLD. PMID:25744849

  13. Non-alcoholic fatty liver disease and metabolic syndrome in obese children.

    Science.gov (United States)

    Atabek, Mehmet Emre

    2011-10-21

    I read with great interest the article of Fu et al who investigated whether non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and whether liver B-ultrasound could be used for its diagnosis, in a study involving 861 obese children (6-16 years old). In this study, it was reported that NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and that liver B-ultrasound can be a useful tool for metabolic syndrome (MS) screening. The authors reported that NAFLD and MS were present in 68.18% and 25.67% of obese children, respectively. Moreover, they observed that the prevalence of MS in NAFLD children was 37.64%, which was much higher than that in the non-NAFLD group. Criteria analogous to those of the Adult Treatment Panel Ⅲ definition for MS were used for children in this study. The reported prevalence data on MS in the young has varied markedly, in large part because of disagreement among the variously proposed definitions of MS. Therefore, in my opinion, a study aiming to assess the association between MS components and NAFLD in obese children has to take into account a simple, easy-to-apply clinical definition proposed by the international diabetes federation for MS. Interpretation of the results of the Fu et al study are limited by another major caveat: that the diagnosis or exclusion of NAFLD was based on liver enzymes and ultrasound imaging, but was not confirmed by liver biopsy. Indeed, it is known that liver enzymes may be within the reference interval in up to 70% of patients with diagnosed NAFLD and that the full histopathological spectrum of NAFLD may be present in patients with normal liver enzymes, which therefore cannot be reliably used to exclude the presence of NAFLD.

  14. Non-alcoholic fatty liver disease and metabolic syndrome in obese children

    Institute of Scientific and Technical Information of China (English)

    Mehmet Emre Atabek

    2011-01-01

    I read with great interest the article of Fu et al who investigated whether non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and whether liver B-ultrasound could be used for its diagnosis, in a study involving 861 obese children (6-16 years old). In this study, it was reported that NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and that liver B-ultrasound can be a useful tool for metabolic syndrome (MS) screening.Theauthorsreportedthat The authorsreportedthat reported that NAFLD and MS were present in 68.18% and 25.67% of obese children, respectively. Moreover, they observed that the prevalence of MS in NAFLD children was 37.64%, which was much higher than that in the non-NAFLD group. Criteria analogous to those of the Adult Treatment Panel Ⅲ definition for MS were used for children in this study. The reported prevalence data on MS in the young has varied markedly, in large part because of disagreement among the variously proposed definitions of MS. Therefore, in my opinion, a study aiming to assess the association between MS components and NAFLD in obese children has to take into account a simple, easy-to-apply clinical definition proposed by the international diabetes federation for MS. Interpretation of the results of the Fu et al study are limited by another major caveat: that the diagnosis or exclusion of NAFLD was based on liver enzymes and ultrasound imaging, but was not confirmed by liver biopsy. Indeed, it is known that liver enzymes may be within the reference interval in up to 70% of patients with diagnosed NAFLD and that the full histopathological spectrum of NAFLD may be present in patients with normal liver enzymes, which therefore cannot be reliably used to exclude the presence of NAFLD.

  15. Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration

    Institute of Scientific and Technical Information of China (English)

    Yan Sun; Dong Xiao; Hong-An Li; Jin-Fang Jiang; Qing Li; Ruo-Shuang Zhang; Xi-Gu Chen

    2009-01-01

    AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cells during liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alupositive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)+, CD34+ and CD45+ cells were observed in the chimeric liver on day 10 after PHxinduced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.

  16. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espfrito Santo

    Directory of Open Access Journals (Sweden)

    Patricia Lofego Goncalves

    2013-01-01

    Full Text Available OBJECTIVES: To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. METHODS: The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively were pursued in all cases. RESULTS: The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2±12.6 years. The following main etiological factors were observed: chronic alcoholism alone (39.7%, chronic alcoholism in association with HBV or HCV (16.1 %, HCV alone (14.5% and in association with alcoholism (8.6% (total, 23.1 %, and HBV alone (13.1% and in association with alcoholism (7.5%, total 20.6%. The remaining etiologies included cryptogenic cases (9.8% and other causes (6.0%. The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001 with reduced age (at the time of cirrhosis diagnosis and increased prevalence of hepatocellular carcinoma (p = 0.052. CONCLUSION: Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis.

  17. Protective effect of Cordyceps militaris polypeptide against acute alcoholic liver injury in rats

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    CAI Qi

    2016-04-01

    Full Text Available ObjectiveTo investigate the protective effect of Cordyceps militaris polypeptide against acute alcoholic liver injury in rats and related mechanism. MethodsA total of 60 Wistar rats were randomly divided into blank control group, model group, and low-, medium-, and high-dose Cordyceps militaris polypeptide groups. All rats except those in the blank control group were given 10 ml/kg 56° liquor by gavage once a day; the rats in the blank control group were given distilled water of the same dose by gavage once a day. At 1 hour after gavage with liquor, the rats in the model group and low-, medium-, and high-dose Cordyceps militaris polypeptide groups were given distilled water or Cordyceps militaris polypeptide solution (6 ml/kg by gavage. Blood samples were collected from the orbit 4 weeks later. The serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST and the activity of superoxide dismutase (SOD and level of malondialdehyde (MDA in the liver were measured for each group, and the pathological changes in the liver were observed under a light microscope. Analysis of variance was applied for comparison between multiple groups, and the SNK-q test was applied for comparison between any two groups. ResultsCompared with the model group, the low-, medium-, and high-dose Cordyceps militaris polypeptide groups showed significant reductions in the serum levels of ALT and AST and the level of MDA in the liver (all P<0.05, as well as a significant increase in the activity of SOD in the liver (all P<0.05, while these indices showed significant differences between the low-, medium-, and high-dose Cordyceps militaris polypeptide groups (all P<0.05. The liver pathological sections from the low-, medium-, and high-dose Cordyceps militaris polypeptide groups showed alleviated hepatocyte fatty degeneration and necrosis induced by alcohol under a light microscope. ConclusionCordyceps militaris polypeptide has a protective effect