- Email: [email protected]
P824 SOLUBLE CD163, A MACROPHAGE ACTIVATION MARKER, IS INDEPENDENTLY ASSOCIATED WITH STEATOHEPATITIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE
POSTERS with either inflammation or fibrosis. In the 31 biopsy patients, the histological NAFLD Activity Score (NAS) determined patients with NAFLD (NAS < 5) from those with NASH (NAS ≥ 5). Results: Increasing BMI in adults and children was associated with increasing hepatic steatosis (Figure 1). Obese boys had markedly higher liver fat compared to lean boys (median 2.79 v 0.46; p = 0.04).
support coffee’s protective role in NAFLD is lacking. We tested the association between coffee consumption and NAFLD in a prospective general population cohort. Methods: The analysis was performed both in a cross sectional manner (n = 347, 31% NAFLD) and in a prospective manner in a subcohort without NAFLD at baseline followed for 7 years (n = 147, 19% incident NAFLD). NAFLD was diagnosed with abdominal ultrasound and SteatoTest. FibroTest was used to assess fibrosis. A detailed structured questionnaire on coffee consumption was administrated during a face-to-face interview. Results: NAFLD patients did not differ from controls in their coffee consumption. Subjects with high coffee consumption (of ≥3 cups/day) did not differ from those with lower consumption in steatosis assessed by Hepato-Renal index and SteatoTest, or fibrosis assessed by FibroTest or liver enzymes. In a multivariate analysis, adjusting for age, gender, smoking, sugar consumption and physical activity no association was demonstrated between high coffee consumption and NAFLD (OR = 0.95, 0.60–1.52, 95% CI). In the prospective analysis, no association was demonstrated between high coffee consumption and new onset of NAFLD (OR = 1.02, 0.45–2.35). High coffee consumption was significantly associated with a lower rate of advanced fibrosis (10.4% vs. 26.3%, P = 0.047). Adjusting for the variables mentioned above the association become borderline significant (OR = 0.54, 0.27–1.08, P = 0.083). Conclusions: No association was demonstrated between coffee consumption and NAFLD, but a protective affect from fibrosis is suggested. P824 SOLUBLE CD163, A MACROPHAGE ACTIVATION MARKER, IS INDEPENDENTLY ASSOCIATED WITH STEATOHEPATITIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE K. Kazankov1 , F. Barrera2 , H.J. Møller3 , H. Vilstrup1 , J. George2 , H. Grønbæk1 . 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2 The Storr Liver Unit, Westmead Millenium Institute, University of Sydney and Westmead Hospital, Westmead, NSW, Australia; 3 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected]
Figure 1. Hepatic lipid content in children, adults, and patients with biopsyproven NAFLD.
Patients with NASH had higher cT1 than those with NAFLD (971±89 ms versus 879±139 ms; p = 0.03). The three obese boys with greatest steatosis also had cT1 ≥970 ms, compared to 783±25 ms in lean boys, suggesting they had steatohepatitis similar to adult NASH. Conclusions: Multiparametric MR can quantify hepatic steatosis, which increases with obesity, in adults and children, and may be used to differentiate NASH from NAFLD. P823 COFFEE DOES NOT PREVENT DEVELOPMENT OF NAFLD BUT MAY DELAY FIBROSIS PROGRESSION: A PROSPECTIVE COHORT STUDY IN THE GENERAL POPULATION S. Zelber-Sagi1,2 , F. Salomone3 , M. Webb1 , H. Yeshua1 , Z. Halpern1,4 , O. Shibolet1,4 . 1 Liver Unit Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, 2 School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; 3 U.O.C. di Gastroenterologia, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy; 4 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel E-mail: [email protected] Background and Aims: Studies suggest that coffee consumption reduces the risk for type 2 diabetes, cirrhosis, hepatocellular carcinoma and possibly of NAFLD. However, conclusive data to
Background and Aims: Macrophages play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the development of steatohepatitis (NASH). Soluble (s)CD163 is a specific marker of activated macrophages. Methods: In a cross-sectional study we investigated associations between sCD163 and biochemical and histological parameters of liver inflammation and fibrosis in 171 NAFLD patients. Demographic, clinical and biochemical parameters were recorded at the time of the liver biopsy. sCD163 was measured by ELISA. Results: We observed increased sCD163 levels in close association with the severity of liver injury, histologically assessed by the NAFLD Activity Score (NAS) and the fibrosis score. Patients with a histological diagnosis of NASH (NAS ≥ 5) had higher sCD163 compared with those with NAS < 5 [3.8 mg/L (IQR 2.8–5.3) vs. 2.5 mg/L (IQR 1.9–3.4), p < 0.001). sCD163 was associated with biochemical parameters of liver injury and insulin resistance, and showed distinct independent associations with NAS (p = 0.03) and fibrosis stage (p = 0.007) in multivariate regression analyses. Moreover, sCD163 was a predictor of NASH (NAS ≥ 5) independent of other biochemical parameters, and we computed a novel sCD163based predictive score (CD163-NASH) with an area under the Receiver Operating Characteristics curve (AUROC) of 0.83 (95% CI: 0.75–0.91) for the diagnosis of NASH. Conclusions: Levels of sCD163 are increased in association with the severity of liver disease, reflecting macrophage activation in NAFLD and NASH. Soluble sCD163 is associated with NASH independently
Journal of Hepatology 2014 vol. 60 | S215–S359
S345
POSTERS of other parameters, and a novel sCD163-based NASH score shows excellent predictive capability of NASH. P825 NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH REDUCED SERUM CHOLESTEROL-ADJUSTED VITAMIN E LEVELS D. Pastori1 , M. Del Ben1 , L. Polimeni2 , R. Carnevale1 , C. Nocella1 , C. Calabrese1 , F. Baratta1 , G. Labbadia2 , P. Pignatelli1 , F. Violi1 , F. Angelico2 . 1 Internal Medicine and Medical Specialties, 2 Sapienza University of Rome, Rome, Italy E-mail: [email protected] Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide. No data regarding serum cholesterol-adjusted vitamin E levels in patients with NAFLD are available. Aim of this study was to investigate serum levels of cholesterol-adjusted vitamin E in a large cohort of patients with NAFLD. Methods: We enrolled 310 consecutive patients in which liver steatosis was evaluated with a liver ultrasonographic scanning (US). Severity of NAFLD was defined according to Hamaguchi’s criteria. In 18 patients a biopsy-proven diagnosis of NASH was made. Serum levels of vitamin E were measured and adjusted for serum cholesterol (vit E/chol). Results: Mean age was 53.9 years. NAFLD was found in 81.9% of patients at ultrasonography (US). Subjects with NAFLD (3.4±2.1 mmol/mmol chol) and those with NASH (3.3.±1.8 mmol/mmol chol) showed significantly lower mean values of serum vit E/chol than controls (4.8±2.0 mmol/mmol chol, p < 0.001). After dividing our cohort according to median value of vit E/chol, we found a significant inverse association between US-NAFLD and serum vit E/chol (OR = 0.819 [95% CI 0.727–0.922] p = 0.001 for each point of Hamaguchi score). No significant differences in vitamin E intake was found. In a multivariable logistic regression analysis metabolic syndrome predicted NAFLD (OR = 5,812 [95% CI 2,638–12,805] p < 0.001) whilst vit E/chol was negatively associated (OR = 0.769 [95% CI 0.655–0.904] p = 0.001). Conclusions: Subjects with NAFLD, and not only those with NASH, have significantly reduced serum levels of vit E/chol. Low serum levels of vit E/chol are associated to NAFLD independently from the presence of metabolic syndrome and dietary vitamin E intake. P826 HEPCIDIN LEVELS IN PATIENTS WITH NAFLD WITH OR WITHOUT HYPERFERRITINEMIA AND/OR DYSMETABOLIC IRON OVERLOAD J. Marmur1 , S. Beshara2 , G. Eggertsen2 , N. Albiin3 , O. Danielsson4 , R. Hultcrantz1 , P. Stal ˚ 1 . 1 Unit of Gastroenterology and Hepatology, Dept of Medicine, 2 Unit of Clinical Chemistry, Dept of Laboratory Medicine, 3 Dept of Radiology, 4 Unit of Pathology, Dept of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden E-mail: [email protected] Background and Aims: Patients with NAFLD often display dysmetabolic iron overload (DIO) or increased serum ferritin without iron overload. In the present study we evaluated serum hepcidin and iron parameters in NAFLD patients having normal or elevated ferritin, with or without DIO, and compared values to those of patients with other chronic liver diseases and healthy controls. Methods: Serum hepcidin was analyzed in 83 patients with chronic liver disease (38 of which had NAFLD) and 39 healthy controls. NAFLD patients were divided into those with normal serum ferritin (NAFLD-N, n = 16), elevated ferritin but normal liver iron (NAFLDFERR, n = 7), or DIO (NAFLD-DIO, n = 15). Liver biopsy was performed in 75/84 patients and hepcidin mRNA in liver was determined with rt-qPCR. S346
Results: Hepcidin levels were increased in HFE-negative hemochromatosis and NAFLD-DIO, and correlated to liver iron stores. In NAFLD, hepcidin correlated to serum ferritin (r2 = 0.20, p < 0.01) and liver iron (r2 = 0.21, p < 0.01) but not to BMI, CRP, NAS-score or steatosis. Patients with NAFLD-DIO had significantly higher transferrin saturation (40±8%) than NAFLD-FERR (25±10%), p < 0.05. There was a good correlation between hepcidin mRNA and serum hepcidin (r2 = 0.46, p < 0.01). Conclusions: In NAFLD, serum hepcidin correlates to iron parameters such as serum ferritin and liver iron in patients either with or without DIO, but not to NAS-score, steatosis or BMI. Transferrin saturation may discriminate between hyperferritinemic NAFLD patients with or without DIO. Apart from genetic hemochromatosis, hepcidin regulation was similar in NAFLD compared to other chronic liver diseases with various degrees of hepatic iron overload. P827 INSULIN SECRETORY FUNCTION AND HBa1c ARE RELATED TO LIVER FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE Y. Eguchi1 , Y. Kitajima1,2 , H. Takahashi1 , M. Ono3 , M. Okada1 , H. Hyogo4 , Y. Sumida5 , N. Araki2 , N. Ono2 , T. Eguchi2 , R. Iwakiri1 , K. Anzai1 , JSG-NAFLD. 1 Internal Medicine, Div of Hepatology, Saga, 2 Eguchi Hospital, Ogi, 3 Kochi Medical School, Nangoku, 4 Hiroshima University, Hiroshima, 5 Kyoto Prefectual University of Medicine, Kyoto, Japan E-mail: [email protected] Background and Aims: The relationship between the pathogenesis of diabetes and liver fibrosis (LF) in nonalcoholic fatty liver disease (NAFLD) should be assessed. We conducted a multicenter study to analyze the relationship between LF and HBA1c/insulin secretory function (ISF). Methods: We performed general health check-ups on 10,574 HBsAg and HCV-Ab negative subjects (cohort 1). The relationship between HbA1c and LF evaluated by the Fib4-index was analyzed. Liver biopsies showed 155 NAFLD subjects (cohort 2). HOMA-b was indicatively used for the evaluation of ISF and categorized into 3 groups (Low HOMA-b: <1.85; Intermediate HOMA-b: 1.85– 2.24; High HOMA-b: 2.25≤). The relationship between HOMA-b and pathological LF was analyzed. Results: In cohort 1, the prevalence of Fib4-index ≥1.3 was significantly increased in relation to the increase of HbA1c. In addition, HbA1c was an independent risk for Fib4-index ≥1.3 (Odds = 1.46). In cohort 2, low ISF showed significantly higher Fib-4 index and more progressive pathological fibrosis than in other subjects. HOMA-b was an independent risk for fibrosis stage ≥2 (Odds = 2.82). BMI of the low HOMA-bgroup was significantly lower than the other groups at entry (27.7±3.8), at 20 years old (21.3±2.3) and at their previous maximum BMI (27.5±3.8). Conclusions: HbA1c and decreased ISF are related to LF. Lower ISF without severe obesity could be one of the pathogenic phenotypes of NAFLD in Japan. P828 THE COMMON PNPLA3 VARIANT IS ASSOCIATED WITH HEPATIC STEATOSIS QUANTIFIED BY CONTROLLED ATTENUATION PARAMETER AND DETERMINES THE FATE OF PATIENTS WITH CHRONIC LIVER DISEASES A. Arslanow, C.S. Stokes, S.N. Weber, F. Grunhage, ¨ F. Lammert, M. Krawczyk. Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany E-mail: [email protected] Background and Aims: The common variant p.I148M of the PNPLA3 gene encoding the enzyme adiponutrin represents a genetic driver of severe hepatic phenotypes (Anstee/Day Nat Rev Gastroenterol Hepatol 2013). Here we present the results in patients with chronic
Journal of Hepatology 2014 vol. 60 | S215–S359
support coffee’s protective role in NAFLD is lacking. We tested the association between coffee consumption and NAFLD in a prospective general population cohort. Methods: The analysis was performed both in a cross sectional manner (n = 347, 31% NAFLD) and in a prospective manner in a subcohort without NAFLD at baseline followed for 7 years (n = 147, 19% incident NAFLD). NAFLD was diagnosed with abdominal ultrasound and SteatoTest. FibroTest was used to assess fibrosis. A detailed structured questionnaire on coffee consumption was administrated during a face-to-face interview. Results: NAFLD patients did not differ from controls in their coffee consumption. Subjects with high coffee consumption (of ≥3 cups/day) did not differ from those with lower consumption in steatosis assessed by Hepato-Renal index and SteatoTest, or fibrosis assessed by FibroTest or liver enzymes. In a multivariate analysis, adjusting for age, gender, smoking, sugar consumption and physical activity no association was demonstrated between high coffee consumption and NAFLD (OR = 0.95, 0.60–1.52, 95% CI). In the prospective analysis, no association was demonstrated between high coffee consumption and new onset of NAFLD (OR = 1.02, 0.45–2.35). High coffee consumption was significantly associated with a lower rate of advanced fibrosis (10.4% vs. 26.3%, P = 0.047). Adjusting for the variables mentioned above the association become borderline significant (OR = 0.54, 0.27–1.08, P = 0.083). Conclusions: No association was demonstrated between coffee consumption and NAFLD, but a protective affect from fibrosis is suggested. P824 SOLUBLE CD163, A MACROPHAGE ACTIVATION MARKER, IS INDEPENDENTLY ASSOCIATED WITH STEATOHEPATITIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE K. Kazankov1 , F. Barrera2 , H.J. Møller3 , H. Vilstrup1 , J. George2 , H. Grønbæk1 . 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2 The Storr Liver Unit, Westmead Millenium Institute, University of Sydney and Westmead Hospital, Westmead, NSW, Australia; 3 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected]
Figure 1. Hepatic lipid content in children, adults, and patients with biopsyproven NAFLD.
Patients with NASH had higher cT1 than those with NAFLD (971±89 ms versus 879±139 ms; p = 0.03). The three obese boys with greatest steatosis also had cT1 ≥970 ms, compared to 783±25 ms in lean boys, suggesting they had steatohepatitis similar to adult NASH. Conclusions: Multiparametric MR can quantify hepatic steatosis, which increases with obesity, in adults and children, and may be used to differentiate NASH from NAFLD. P823 COFFEE DOES NOT PREVENT DEVELOPMENT OF NAFLD BUT MAY DELAY FIBROSIS PROGRESSION: A PROSPECTIVE COHORT STUDY IN THE GENERAL POPULATION S. Zelber-Sagi1,2 , F. Salomone3 , M. Webb1 , H. Yeshua1 , Z. Halpern1,4 , O. Shibolet1,4 . 1 Liver Unit Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, 2 School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; 3 U.O.C. di Gastroenterologia, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy; 4 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel E-mail: [email protected] Background and Aims: Studies suggest that coffee consumption reduces the risk for type 2 diabetes, cirrhosis, hepatocellular carcinoma and possibly of NAFLD. However, conclusive data to
Background and Aims: Macrophages play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the development of steatohepatitis (NASH). Soluble (s)CD163 is a specific marker of activated macrophages. Methods: In a cross-sectional study we investigated associations between sCD163 and biochemical and histological parameters of liver inflammation and fibrosis in 171 NAFLD patients. Demographic, clinical and biochemical parameters were recorded at the time of the liver biopsy. sCD163 was measured by ELISA. Results: We observed increased sCD163 levels in close association with the severity of liver injury, histologically assessed by the NAFLD Activity Score (NAS) and the fibrosis score. Patients with a histological diagnosis of NASH (NAS ≥ 5) had higher sCD163 compared with those with NAS < 5 [3.8 mg/L (IQR 2.8–5.3) vs. 2.5 mg/L (IQR 1.9–3.4), p < 0.001). sCD163 was associated with biochemical parameters of liver injury and insulin resistance, and showed distinct independent associations with NAS (p = 0.03) and fibrosis stage (p = 0.007) in multivariate regression analyses. Moreover, sCD163 was a predictor of NASH (NAS ≥ 5) independent of other biochemical parameters, and we computed a novel sCD163based predictive score (CD163-NASH) with an area under the Receiver Operating Characteristics curve (AUROC) of 0.83 (95% CI: 0.75–0.91) for the diagnosis of NASH. Conclusions: Levels of sCD163 are increased in association with the severity of liver disease, reflecting macrophage activation in NAFLD and NASH. Soluble sCD163 is associated with NASH independently
Journal of Hepatology 2014 vol. 60 | S215–S359
S345
POSTERS of other parameters, and a novel sCD163-based NASH score shows excellent predictive capability of NASH. P825 NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH REDUCED SERUM CHOLESTEROL-ADJUSTED VITAMIN E LEVELS D. Pastori1 , M. Del Ben1 , L. Polimeni2 , R. Carnevale1 , C. Nocella1 , C. Calabrese1 , F. Baratta1 , G. Labbadia2 , P. Pignatelli1 , F. Violi1 , F. Angelico2 . 1 Internal Medicine and Medical Specialties, 2 Sapienza University of Rome, Rome, Italy E-mail: [email protected] Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide. No data regarding serum cholesterol-adjusted vitamin E levels in patients with NAFLD are available. Aim of this study was to investigate serum levels of cholesterol-adjusted vitamin E in a large cohort of patients with NAFLD. Methods: We enrolled 310 consecutive patients in which liver steatosis was evaluated with a liver ultrasonographic scanning (US). Severity of NAFLD was defined according to Hamaguchi’s criteria. In 18 patients a biopsy-proven diagnosis of NASH was made. Serum levels of vitamin E were measured and adjusted for serum cholesterol (vit E/chol). Results: Mean age was 53.9 years. NAFLD was found in 81.9% of patients at ultrasonography (US). Subjects with NAFLD (3.4±2.1 mmol/mmol chol) and those with NASH (3.3.±1.8 mmol/mmol chol) showed significantly lower mean values of serum vit E/chol than controls (4.8±2.0 mmol/mmol chol, p < 0.001). After dividing our cohort according to median value of vit E/chol, we found a significant inverse association between US-NAFLD and serum vit E/chol (OR = 0.819 [95% CI 0.727–0.922] p = 0.001 for each point of Hamaguchi score). No significant differences in vitamin E intake was found. In a multivariable logistic regression analysis metabolic syndrome predicted NAFLD (OR = 5,812 [95% CI 2,638–12,805] p < 0.001) whilst vit E/chol was negatively associated (OR = 0.769 [95% CI 0.655–0.904] p = 0.001). Conclusions: Subjects with NAFLD, and not only those with NASH, have significantly reduced serum levels of vit E/chol. Low serum levels of vit E/chol are associated to NAFLD independently from the presence of metabolic syndrome and dietary vitamin E intake. P826 HEPCIDIN LEVELS IN PATIENTS WITH NAFLD WITH OR WITHOUT HYPERFERRITINEMIA AND/OR DYSMETABOLIC IRON OVERLOAD J. Marmur1 , S. Beshara2 , G. Eggertsen2 , N. Albiin3 , O. Danielsson4 , R. Hultcrantz1 , P. Stal ˚ 1 . 1 Unit of Gastroenterology and Hepatology, Dept of Medicine, 2 Unit of Clinical Chemistry, Dept of Laboratory Medicine, 3 Dept of Radiology, 4 Unit of Pathology, Dept of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden E-mail: [email protected] Background and Aims: Patients with NAFLD often display dysmetabolic iron overload (DIO) or increased serum ferritin without iron overload. In the present study we evaluated serum hepcidin and iron parameters in NAFLD patients having normal or elevated ferritin, with or without DIO, and compared values to those of patients with other chronic liver diseases and healthy controls. Methods: Serum hepcidin was analyzed in 83 patients with chronic liver disease (38 of which had NAFLD) and 39 healthy controls. NAFLD patients were divided into those with normal serum ferritin (NAFLD-N, n = 16), elevated ferritin but normal liver iron (NAFLDFERR, n = 7), or DIO (NAFLD-DIO, n = 15). Liver biopsy was performed in 75/84 patients and hepcidin mRNA in liver was determined with rt-qPCR. S346
Results: Hepcidin levels were increased in HFE-negative hemochromatosis and NAFLD-DIO, and correlated to liver iron stores. In NAFLD, hepcidin correlated to serum ferritin (r2 = 0.20, p < 0.01) and liver iron (r2 = 0.21, p < 0.01) but not to BMI, CRP, NAS-score or steatosis. Patients with NAFLD-DIO had significantly higher transferrin saturation (40±8%) than NAFLD-FERR (25±10%), p < 0.05. There was a good correlation between hepcidin mRNA and serum hepcidin (r2 = 0.46, p < 0.01). Conclusions: In NAFLD, serum hepcidin correlates to iron parameters such as serum ferritin and liver iron in patients either with or without DIO, but not to NAS-score, steatosis or BMI. Transferrin saturation may discriminate between hyperferritinemic NAFLD patients with or without DIO. Apart from genetic hemochromatosis, hepcidin regulation was similar in NAFLD compared to other chronic liver diseases with various degrees of hepatic iron overload. P827 INSULIN SECRETORY FUNCTION AND HBa1c ARE RELATED TO LIVER FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE Y. Eguchi1 , Y. Kitajima1,2 , H. Takahashi1 , M. Ono3 , M. Okada1 , H. Hyogo4 , Y. Sumida5 , N. Araki2 , N. Ono2 , T. Eguchi2 , R. Iwakiri1 , K. Anzai1 , JSG-NAFLD. 1 Internal Medicine, Div of Hepatology, Saga, 2 Eguchi Hospital, Ogi, 3 Kochi Medical School, Nangoku, 4 Hiroshima University, Hiroshima, 5 Kyoto Prefectual University of Medicine, Kyoto, Japan E-mail: [email protected] Background and Aims: The relationship between the pathogenesis of diabetes and liver fibrosis (LF) in nonalcoholic fatty liver disease (NAFLD) should be assessed. We conducted a multicenter study to analyze the relationship between LF and HBA1c/insulin secretory function (ISF). Methods: We performed general health check-ups on 10,574 HBsAg and HCV-Ab negative subjects (cohort 1). The relationship between HbA1c and LF evaluated by the Fib4-index was analyzed. Liver biopsies showed 155 NAFLD subjects (cohort 2). HOMA-b was indicatively used for the evaluation of ISF and categorized into 3 groups (Low HOMA-b: <1.85; Intermediate HOMA-b: 1.85– 2.24; High HOMA-b: 2.25≤). The relationship between HOMA-b and pathological LF was analyzed. Results: In cohort 1, the prevalence of Fib4-index ≥1.3 was significantly increased in relation to the increase of HbA1c. In addition, HbA1c was an independent risk for Fib4-index ≥1.3 (Odds = 1.46). In cohort 2, low ISF showed significantly higher Fib-4 index and more progressive pathological fibrosis than in other subjects. HOMA-b was an independent risk for fibrosis stage ≥2 (Odds = 2.82). BMI of the low HOMA-bgroup was significantly lower than the other groups at entry (27.7±3.8), at 20 years old (21.3±2.3) and at their previous maximum BMI (27.5±3.8). Conclusions: HbA1c and decreased ISF are related to LF. Lower ISF without severe obesity could be one of the pathogenic phenotypes of NAFLD in Japan. P828 THE COMMON PNPLA3 VARIANT IS ASSOCIATED WITH HEPATIC STEATOSIS QUANTIFIED BY CONTROLLED ATTENUATION PARAMETER AND DETERMINES THE FATE OF PATIENTS WITH CHRONIC LIVER DISEASES A. Arslanow, C.S. Stokes, S.N. Weber, F. Grunhage, ¨ F. Lammert, M. Krawczyk. Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany E-mail: [email protected] Background and Aims: The common variant p.I148M of the PNPLA3 gene encoding the enzyme adiponutrin represents a genetic driver of severe hepatic phenotypes (Anstee/Day Nat Rev Gastroenterol Hepatol 2013). Here we present the results in patients with chronic
Journal of Hepatology 2014 vol. 60 | S215–S359