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Alcoholic liver disease and hepatitis C:A frequently underestimated combination

World Journal of Gastroenterology 2009年第28期15卷 3462-3471页

作者： Sebastian Mueller Gunda Millonig helmut k seitz Department of Medicine and Center for Alcohol Research Live Disease and Nutrition Salem Medical Center University of Heidelberg Zeppelinstraβe 11-33 69121 Heidelberg Germany

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 *** review discusses the epidemiology and combined impact of ALD and HCV on the progres sion of liver *** and HCV affect the progres sion of liver disease to liver cirrhosis and hepatocellular carcinoma(HCC) in a synergistic ***, the risk for HCC increases f ive times with a daily alcohol con sumption of 80 g;in the presence of HCV it is increased 20fold, and a combination of both risk factors leads to a more than 100fold risk for HCC *** consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV *** molecu lar mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease *** include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of ***, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liversecreted systemic iron hormone hepcidin.A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the *** now, it can be generally concluded that HCVinfect ed patients should abstain from alcohol and alcoholicsshould be encouraged to participate in detoxification programs.

关键词：丙型肝炎酒精性肝病

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Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M

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World Journal of Hepatology 2016年第35期8卷 1547-1556页

作者： Vanessa Rausch Teresa Peccerella Carolin Lackner Eray Yagmur helmut-karl seitz Thomas Longerich Sebastian Mueller Salem Medical Center and Center for Alcohol Research University of Heidelberg Institute for Pathology Medical University Graz Laboratory Diagnostics Center RWTH-University Hospital Aachen Aachen and Medical Care Center Institute of Pathology RWTH-University Hospital Aachen

AIM To investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness(LS) during alcohol withdrawal and its association with *** Caucasian heavy drinkers(n = 521) with a mean alcohol consumption of 192.1 g/d(median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography(Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease(steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the kleiner score was obtained in 80 *** The PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis(r = 0.404, P k Pa) as compared to CG and GG carriers(17.6 and 17.2 kPa). Notably, LS primarily correlated with fibrosis stage(r = 0.828, P kPa but to a lesser extent in GG carriers from 17.6 to 14.5 kPa. This was due to prolonged resolution of inflammation with significantly elevated aspartate transaminase levels after alcohol withdrawal in GG carriers. Non-invasive fibrosis assessment by LS in all patients showed a significantly higher F0 rate as compared to the biopsy cohort(47% vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to

关键词：肝僵硬含酒精的肝疾病 Adiponutrin PNPLA3 短暂 elastography 白酒退却发炎

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

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World Journal of Gastroenterology 2010年第8期16卷 966-972页

作者： Sebastian Mueller Gunda Millonig Lucie Sarovska Stefanie Friedrich Frank M Reimann Maria Pritsch Silke Eisele Felix Stickel Thomas Longerich Peter Schirmacher helmut karl seitz Department of Medicine and Center for Alcohol Research Salem Medical Center University of Heidelberg Institute of Medical Biometry and Informatics University of Heidelberg Institute of Clinical Pharmacology University of Bern Department of Pa-thology University of Heidelberg

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 misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT kedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

关键词： Alcoholic liver disease Alcoholic steatohep-atitis Liver cirrhosis Bilirubin Tissue elasticity imaging FibroScan

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Non-invasive diagnosis of alcoholic liver disease

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World Journal of Gastroenterology 2014年第40期20卷 14626-14641页

作者： Sebastian Mueller helmut karl seitz Vanessa Rausch Department of Internal Medicine Salem Medical Center University of Heidelberg 69121 Heidelberg Germany Center for Alcohol Research University of Heidelberg 69121 Heidelberg Germany

Alcoholic liver disease(ALD)is the most common liver disease in the Western *** many reasons,it isunderestimated and *** early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular *** two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging *** is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver ***-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of *** algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of *** correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase *** non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these *** biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.

关键词： Alcoholic hepatitis Alcoholic steatohepatitis Alco

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