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Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis

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World Journal of Gastroenterology 2018年第13期24卷 1440-1450页

作者： Takefumi Kimura Naoki Tanaka Naoyuki Fujimori Ayumi Sugiura Tomoo Yamazaki satoru joshita Michiharu Komatsu Takeji Umemura Akihiro Matsumoto Eiji Tanaka Department of Internal Medicine Division of Gastroenterology Shinshu University School of Medicine Department of Metabolic Regulation Shinshu University Graduate School of Medicine Research Center for Agricultural Food Industry Shinshu University

AIM The impact of mild drinking habit(less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease(NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD. METHODS A total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with nonalcoholic steatohepatitis, 26% with advanced fibrosis(F3-4)] were divided into the mild drinking group withe thanol consumption of less than 20 g/d(mild drinking group, n = 93) and the non-drinking group(n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma(HCC) occurrence were compared between the *** We observed significant differences in male prevalence(P = 0.01), platelet count(P = 0.04), and gammaglutamyl transpeptidase(P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group(6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox's regression model revealed that hepatic advanced fibrosis(F3-4)(P < 0.01, risk ratio: 11.60), diabetes mellitus(P < 0.01, risk ratio: 89.50), and serum triglyceride(P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal(P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis(F3-4), however, a drinking habit(P = 0.04, risk ratio: 4.83), alpha-fetoprotein(P = 0.01, risk ratio: 1.23), and diabetes mellitus(P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence. CONCLUSION A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.

关键词： Non-alcoholic fatty liver disease Ethanol Hepatocellular carcinoma Risk factor

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Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2018年第11期24卷 1239-1249页

作者： Naoyuki Fujimori Takeji Umemura Takefumi Kimura Naoki Tanaka Ayumi Sugiura Tomoo Yamazaki satoru joshita Michiharu Komatsu Yoko Usami Kenji Sano Koji Igarashi Akihiro Matsumoto Eiji Tanaka Department of Internal Medicine Division of GastroenterologyShinshu University School of MedicineMatsumoto 390-8621Japan Department of Metabolic Regulation Shinshu University Graduate School of MedicineMatsumotoJapanand Research Center for Agricultural Food IndustryShinshu UniversityMatsumoto390-8621Japan Department of Laboratory Medicine Shinshu University HospitalMatsumoto 390-8621Japan Bioscience Division TOSOH CorporationKanagawa 252-1123Japan

AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) *** One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively *** samples were collected at the time of biopsy and ATX was measured by enzyme *** obtained from 160 healthy,nonobese individuals were used as *** findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's *** accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical *** Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female *** were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis *** AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective *** Serum ATX levels may at least partially reflect histological severity in NAFLD.

关键词： Autotaxin Non-alcoholic fatty liver disease Fibrosis Ballooning

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Association between endotoxemia and histological features of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2017年第4期23卷 712-722页

作者： Hiroyuki Kitabatake Naoki Tanaka Naoyuki Fujimori Michiharu Komatsu Ayaka Okubo Kyogo Kakegawa Takefumi Kimura Ayumi Sugiura Tomoo Yamazaki Soichiro Shibata Yuki Ichikawa satoru joshita Takeji Umemura Akihiro Matsumoto Masayoshi Koinuma Kenji Sano Toshifumi Aoyama Eiji Tanaka Department of Metabolic Regulation Shinshu University Graduate School of Medicine Department of Internal Medicine Division of GastroenterologyShinshu University School of Medicine Center for Clinical Research Shinshu University Hospital Faculity of Pharmaceutical Sciences Teikyo Heisei University Department of Laboratory Medicine Shinshu University Hospital

AIMTo assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD).METHODSOne hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological *** LBP concentration was significantly increased in nonalcoholic steatohepatitis (NASH) patients as compared with nonalcoholic fatty liver (NAFL) subjects and was correlated with steatosis (r = 0.38, P < 0.0001) and ballooning scores (r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum EndoCab IgG concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between EndoCab IgG and histological ***/EndoCab IgG were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.

关键词： Nonalcoholic steatohepatitis Endotoxemia Lipopolysaccharide-binding protein EndoCab IgG Fibrosis Steatosis

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