In Japan, hepatitis B or C virus infection has been a major health issue. For the prevention of liver‐related deaths, multifaceted strategies have been taken against hepatitis virus. In fiscal year (FY) 2002, nationwide screening for hepatitis was started as a part of health examinations provided by municipal governments. From FY2007, the hepatitis treatment network has been strengthened by the nationwide establishment of regional government‐based hepatitis treatment systems, comprising linked regional core centers, specialized institutions for hepatitis treatment, primary care physicians, and regional governments. Special subsidy program for patients with viral hepatitis was started at FY2008. The range of coverage has been expanding from patients treated with interferon to those on nucleotide analogs or interferon‐free therapies, including drug prices and examination expenses. The Basic Act on Hepatitis Measures was established in 2009. The Basic Guidelines for Promotion of Control Measures for hepatitis was issued in 2011, comprising nine principles in order to promote measures for hepatitis B and C. The Hepatitis Information Center was established in 2008. Its mission is to provide up‐to‐date hepatitis‐related information, supporting collaboration between regional core centers, and training medical personnel. The revision of the above‐mentioned Basic Guidelines in 2016 set the target as the reduction of patients progressing to cirrhosis and/or liver cancer. Achieving this goal definitely requires active collaboration among the national and local governments, regional core centers, and the Hepatitis Information Center, and participation by medical personnel, patients, and people with awareness.

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, −0.41%, P < 0.01; BMI, −1.06 kg/m 2 , P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18) of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects. (Hepatology Communications 2021;0:1-13).

Background Our previous studies have indicated a close association between visceral fat accumulation and hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). This study investigated whether visceral fat accumulation was related to the pathogenesis and disease progression of nonalcoholic steatohepatitis (NASH)/NAFLD. Methods First, a total of 550 subjects who underwent a health checkup and measurement of visceral fat accumulation, done with a bioelectrical impedance analyzer (X-SCAN; Owa Medical, Fukuoka, Japan), were included. The relationship between visceral fat accumulation and biochemical parameters was examined. Second, a total of 74 patients with NASH/NAFLD who underwent liver biopsy were reviewed. Visceral fat accumulation was determined by abdominal computed tomography. The association between visceral fat accumulation and the histopathological grade/stage determined by the NAFLD activity score and Brunt's classification was evaluated. Results There was a significant relationship between visceral fat accumulation and glucose, triglyceride, and alanine aminotransferase (ALT; r = 0.423, P \ 0.01). In stepwise regression analysis, visceral fat area (VFA), serum triglyceride level, and serum low-density lipoprotein (LDL)-cholesterol level were selected as predictor variables for serum ALT level, in a continuous manner (serum ALT level = -1.359 ? 0.143 9 VFA ? 0.046 9 triglyceride ? 0.059 9 LDL, R 2 = 0.217, P \ 0.001). In patients with NASH, there was no correlation between histological grade and the visceral fat volume. Visceral fat accumulation in patients with stage 3/4 advanced NASH was greater than that in patients with stage 1/2 early NASH (P \ 0.05). Conclusions These results suggest that visceral fat accumulation plays a role in steatosis and fibrosis in the pathogenesis and prognosis of NAFLD.

Aim The Enhanced Liver Fibrosis (ELF) test comprises a logarithmic algorithm combining three serum markers of hepatic extracellular matrix metabolism. We aimed to evaluate the performance of ELF for the diagnosis of liver fibrosis and to compare it with that of liver stiffness measurement (LSM) by FibroScan in non‐alcoholic fatty liver disease. Methods ELF cut‐off values for the diagnosis of advanced fibrosis were obtained using receiver operating characteristic analysis in patients with biopsy‐confirmed non‐alcoholic fatty liver disease (training set; n = 200). Diagnostic performance was analyzed in the training set and in a validation set (n = 166), and compared with that of LSM in the FibroScan cohort (n = 224). Results The area under receiver operating characteristic curve was 0.81 for the diagnosis of advanced fibrosis, and the ELF cut‐off values were 9.34 with 90.4% sensitivity and 10.83 with 90.6% specificity in the training set, and 89.8% sensitivity and 85.5% specificity in the validation set. There was no significant difference in the area under the receiver operating characteristic curve between ELF and LSM (0.812 and 0.839). A combination of ELF (cut‐off 10.83) and LSM (cut‐off 11.45) increased the specificity to 97.9% and the positive predictive value, versus ELF alone. Sequential use of the Fibrosis‐4 index (cut‐off 2.67) and ELF (cut‐off 9.34) increased the sensitivity to 95.9%. Conclusions ELF can identify advanced liver fibrosis in non‐alcoholic fatty liver disease, and its diagnostic accuracy is comparable to that of FibroScan. According to the clinical setting, combinations or sequential procedures using other non‐invasive tests complement the diagnostic performance of ELF for the identification of advanced fibrosis.

Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients.