Summary: Background: With the development of direct‐acting anti‐virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR).Aim: To evaluate the short‐term risk ofHCCamong patients withSVRbyDAAs, including those with cirrhosis or previousHCC.Methods: This large‐scale, multicentre cohort study included 1,675 consecutive patients who achievedSVRby treatment with interferon‐free sofosbuvir‐based regimens, divided into groups with (n = 152) or without previousHCC(n = 1,523). The Kaplan‐Meier method and Cox proportional hazard analysis were used to calculate the cumulativeHCCincidence and related factors ofHCC.Results: During the follow‐up period (median: 17 months), 46 (2.7%) patients developedHCC. The 1‐year cumulative rates of de novoHCCwere 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log‐rank test: P < 0.001). For cirrhotic patients, serum α‐fetoprotein level at the end of treatment (EOT‐AFP) was the strongest predictor of de novoHCC. The 1‐year cumulative de novoHCCrates were 1.4% and 13.1% in theEOT‐AFP< 9.0 ng/mLand ≥ 9.0 ng/mLgroups (cut‐off value) respectively (log‐rank test: P < 0.001). The 1‐year cumulative rates ofHCCrecurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log‐rank test: P = 0.023). For cirrhotic patients, previousHCCcharacteristics were significantly associated withHCCrecurrence. In contrast, sex, age and metabolic features did not influence de novoHCCor recurrence.Conclusions: For cirrhotic patients after elimination ofHCV, serumEOT‐AFPlevel and previousHCCcharacteristics would be useful markers for predicting de novoHCCor recurrence.

Aim: A nationwide survey in 2018 showed decreasing involvement of viral hepatitis and increasing involvement of nonviral liver diseases in the etiology of liver cirrhosis (LC) in Japan. An updated nationwide survey was undertaken in 2023.Methods: Cases of LC diagnosed between 2018 and 2021 were collected from 75 institutions, and the etiologies of LC were investigated. In addition, the data obtained were compared with the results of previous studies.Results: Among the 15 517 cases, alcohol‐related liver disease (ALD)‐associated LC was the most frequent cause (n = 5,487, 35.4%). Hepatitis C virus‐associated LC, nonalcoholic steatohepatitis (NASH)‐associated LC, and hepatitis B virus‐associated LC were ranked as second, third, and fourth, respectively. In comparison to the previous survey, the ratios of viral hepatitis‐associated LC decreased (HBV: from 11.5% to 8.1%; HCV: from 48.2% to 23.4%), while the ratios of ALD‐associated LC and NASH‐associated LC increased (from 19.9% to 35.4% and from 6.3% to 14.6%, respectively). Regarding cases of LC with hepatocellular carcinoma (n = 5906), HCV‐associated LC (1986 cases, 33.6%) was the most frequent cause. Alcohol‐related liver disease‐associated LC, NASH‐associated LC, and HBV‐associated LC were the second‐, third‐, and fourth‐ranked causes, respectively. In comparison to the previous survey, as the cause of hepatocellular carcinoma‐complicated LC, HCV‐associated LC decreased from 60.3% to 33.6%, while the ratios of ALD‐associated LC and NASH‐associated LC increased from 14.2% to 28.6% and from 4.2% to 14.0%, respectively.Conclusions: The major causes of LC in Japan are suggested to have been shifting from viral hepatitis to nonviral chronic liver diseases.

Summary: Background: Tenofovir alafenamide (TAF) may be preferable to other nucleos(t)ide analogues (NA) regarding outcomes against chronic hepatitis B virus (HBV) infection.Aims: To evaluate the longer term virological/biochemical effectiveness of TAF and the renal safety of sequential therapy to TAF in real‐world settingsMethods: This multi‐centre, retrospective cohort study included consecutive adult patients who were switched from other NAs to TAF. We assessed the virological and biochemical responses up to 144 weeks. We performed sensitivity analyses for a subgroup with chronic kidney disease (CKD) at baseline.Results: We analysed the data of 391 patients with chronic hepatitis B previously treated with entecavir (ETV) (n = 174), tenofovir disoproxil fumarate (TDF) (n = 116) or an NA combination (n = 101) for ≥ 24 months. HBV DNA <10 IU/ml at week 144 was found for 99% of patients, regardless of prior NA regimen or HBV DNA level at baseline. For patients who switched from TDF to TAF, total, low‐density lipoprotein, high‐density lipoprotein cholesterol and triglycerides were significantly increased after the switch. Patients who switched from a nucleotide analogue to TAF had an improved estimated glomerular filtration rate, although the rate of hypophosphataemia (<2.5 mg/dl) remained 9.7% at week 144. The virological and biochemical responses of patients with CKD were similar to the overall results.Conclusions: Switching to TAF remained effective and safe for up to 3 years. Given the increasing comorbidities related to ageing, it will be important to carefully follow the change in the lipid levels of patients with a prior TDF‐based regimen.