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Background: The incidence of liver-related events, cardiovascular events and type 2 diabetes mellitus in patients with histopathologically confirmed NAFLD remains unclear.Methods: We retrospectively investigated the incidence of liver events, cardiovascular events, malignancy, and type 2 diabetes mellitus in 402 Japanese patients with histopathologically confirmed NAFLD for a median follow-up of 4.2 years. We also investigated predictors of the development of hepatocellular carcinoma and type 2 diabetes mellitus in these patients.Results: The rate of liver-related events per 1000 person years was 4.17 (hepatocellular carcinoma, 3.67; hepatic encephalopathy, 1.60; esophago-gastric varices, 2.43; ascites, 0.80; and jaundice, 0.40). The rate of cardiovascular events and type 2 diabetes mellitus was 5.73 and 9.95, respectively. Overall mortality was 3.33 (liver-related events, 1.25; cardiovascular events, 0.42; and malignancies other than hepatocellular carcinoma, 0.83), in patients free of previous or current malignancies. Multivariate analyses identified old age (≥70 years) and advanced fibrosis stage 4 as significant determinants of hepatocellular carcinoma development, and hepatocyte steatosis (> 33%), female sex, and serum ferritin (≤80 μg/l) as significant determinants of type 2 diabetes mellitus development in these patients.Conclusions: Our results highlighted the importance of cardiovascular and liver-related events in Japanese patients with histopathologically-confirmed NAFLD. Hepatocellular carcinoma was the most common liver-related event, and the incidence of hepatocellular carcinoma was more than half of that of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Portal vein thrombosis (PVT) is a serious complication in liver cirrhosis with portal hypertension. We examined the treatment, recurrence and prognosis of PVT in cirrhotic patients., Methods: The study subjects were all 90 cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department between July 2007 and September 2016. The mean age was 68 years and mean Child-Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and repeated in those who developed PVT recurrence after the initial therapy., Results: Complete response was noted in 49% (n = 44), partial response (shrinkage ≥70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the patients after the initial course of treatment. DS treatment neither caused adverse events, particularly bleeding or thrombocytopenia, nor induced significant changes in serum albumin, total bilirubin, prothrombin time, and residual liver function. Re-treatment was required in 44 patients who showed PVT recurrence and 61% of these responded to the treatment. The cumulative recurrence rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The recurrence rates were significantly lower in patients with acute type, compared to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years after treatment (including maintenance therapy with warfarin) were 83 and 60%, respectively, and were significantly higher in patients with acute type than chronic type (p = 0.0053)., Conclusion: We can expect prognostic improvement of liver cirrhosis by warfarin following two-week DS therapy for the treatment of PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis of PVT along with the evaluation of the volume of PVT on CT and an early intervention would contribute to the higher efficacy of the treatment.

Background: The association between circulating microRNA-122 (miR-122) and histopathological features of nonalcoholic fatty liver disease (NAFLD) remains unclear., Methods: The association of serum miR-122 levels with histopathological features of NAFLD (steatosis, ballooning, lobular inflammation, and stage, as histological components of nonalcoholic steatohepatitis) was examined in serial liver biopsies from 36 hepatocellular carcinoma (HCC)-free Japanese patients with histopathologically-proven NAFLD. The median interval between first and second liver biopsies was 4.6 years., Results: In patients who showed improvement of histopathological scores (steatosis, ballooning, and stage), serum miR-122 levels were significantly lower at second biopsy than first biopsy. In patients who showed no improvement, the changes at second biopsy were not different from those at first biopsy. There were significant and strong associations between serum miR-122 ratio (ratio of level at second biopsy to that at first biopsy) and changes in histopathological scores (of steatosis, lobular inflammation, and stage). There were also significant and strong associations between serum miR-122 ratio and changes in other clinical parameters, including aspartate aminotransferase and alanine aminotransferase., Conclusions: Longitudinal examination of serial liver biopsies showed the association of serum miR-122 with histopathological features of HCC-free NAFLD patients.

Background: There is no information on the long-term effects of peginterferon (PEG-IFN) alfa-2a therapy for chronic hepatitis B (CHB) in Japan. This double-blind, randomized trial investigated the efficacy of PEG-IFN therapy., Methods: We analyzed 22 Japanese patients with CHB (hepatitis B e antigen [HBeAg]-positive: 17, HBeAg-negative: 5) treated with PEG-IFN alfa-2a and followed-up posttreatment for 5 years. Responders represented patients who showed persistent normalization of alanine transferase (ALT) levels, HBeAg clearance, and low hepatitis B virus (HBV) DNA levels (HBeAg-positive patient; <5 log copies/mL, HBeAg-negative patient; <4.3 log copies/mL) at end of treatment, and at 1, 2, 3, 4 and 5 years posttreatment. In addition, baseline HBeAg-positive patients who showed sustained normalization of ALT level, HBeAg clearance, and low HBV DNA level for more than 6 months until at 1, 2, 3, 4, and 5 years after completion of PEG-IFN were also classified as "triple responders" and the proportion of triple responders relative to all patients was termed the "triple response rate"., Results: The response rates among HBeAg-positive patients were 13%, 25%, 14%, 21% and 21% at end of treatment, and at 1, 2, 3, 4, and 5 years, respectively. The response rate tended to be higher in patients treated for 48 than 24 weeks. The respective response rates among HBeAg-negative patients were 0%, 20%, 20%, 20% and 25%. During the treatment period, hepatitis B surface antigen (HBsAg) clearance at 3.5 years was noted in one patient, who was 37-year-old, male, had genotype C and received PEG-IFN alfa-2a at 90 μg for 48 weeks., Conclusion: At 5 years after completion of PEG-IFN, the triple response rate in HBeAg-positive patients and combined response rate in HBeAg-negative patients were 21% (3/14) and 25% (1/4), respectively. The triple response was seen in three patients who had all been treated with PEG-IFN for 48 weeks.