INTRODUCTION: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases. RESULTS: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26–0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42–1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences ( P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41–1.92; P = 0.77). DISCUSSION: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.

Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35–24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03–6.54, P < 0.001), male gender (HR/CI 2.69/1.29–5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03–1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04–19.09, P = 0.04) and BMI (HR/CI 1.11/1.03–1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.

Transfusion dependent subjects are at a great risk of viral hepatitis infection. We aimed to evaluate the prevalence and factors associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among transfusion-dependent patients in Taiwan. A total of 140 patients (67 thalassemic patients, 70 hemophilic patients, two patients with hereditary spherocytosis and one patient with von Willebrand disease) were prospectively enrolled to evaluate the prevalence and factors associated with viral hepatitis and spontaneous HCV clearance. All patients were tested for HBV and HCV serology and virology. Two consecutive serum samples, at least 1 year apart, were collected to clarify HCV seroclearance. The seropositivity rate of hepatitis B surface antigen (HBsAg), HCV antibody (anti-HCV), and both HBsAg/anti-HCV were 6.4%, 45.7% and 5%, respectively. Logistic regression analysis of factors associated with anti-HCV seropositivity included age (odds ratio/95% confidence interval [OR/CI]: 1.12/1.07–1.18, P<0.001), serum alanine aminotransferase (ALT) (OR/CI: 1.04/1.02–1.06, P<0.001) and platelet counts (OR/CI: 0.995/0.991–0.998, P = 0.002). Age was the only factor independently associated with HBsAg seropositivity (OR/CI: 1.08/1.02–1.14.4, P = 0.007). Compared to patients born before 1992, the seroprevalence of HCV among thalassemic patients decreased dramatically in those born after 1992 (46.0% vs. 11.8%, p = 0.012). The seroprevalence of HCV among hemophilic patients also decreased significantly when comparing patients born before 1987 to those born after 1987 (79.5% vs. 11.5%, p<0.001). Similarly, the seroprevalence of HBV decreased significantly in the post-vaccination cohort compared to its counterpart (13.1%, vs. 1.3%, p = 0.005). The spontaneous clearance of HCV was observed in 25.4% (15/59) of patients, and ALT was the only factor associated with it (OR/CI 0.98/0.96–1.00, P = 0.02). Both HBV and HCV infections are prevalent among transfusion-dependent thalassemic and hemophilic patients in Taiwan. Nevertheless, seroprevalence decreased significantly and dramatically for HCV after universal blood screening and for HBV after implementation of a universal mass vaccination program.

We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti‐HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter [PM_2.5], nitrogen dioxide [NO₂], ozone [O₃] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05–4.77; p < 0.001), smoking (OR, 1.79; 95% CI, 1.16–2.74; p = 0.01), age (OR, 1.04; 95% CI, 1.02–1.05; p < 0.001) and PM_2.5 (OR, 1.10; 95% CI, 1.05–1.16; p < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM_2.5 (β: 0.134; 95% CI: 0.025, 0.243; p = 0.02). There was a dose‐dependent relationship between different fibrotic stages and the PM_2.5 level (the PM_2.5 level in patients with fibrotic stages 0, 1–2 and 3–4: 27.9, 28.4, and 29.3 μg/m³, respectively; trend p < 0.001). Exposure to PM_2.5, as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dose‐dependent correlation between PM_2.5 levels and the severity of hepatic fibrosis.