Clinical and Molecular Hepatology最新文献

Background/aims: Besifovir (BSV) showed comparable antiviral activity superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment.

Methods: In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks.

Results: The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% CI -0.01 to 0.04; P=1.000), with a predefined margin of -0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (-1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group.

Conclusions: In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF. ClinicalTrials.gov Identifier: NCT04202536.

Background/aims: Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.

Methods: We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.

Results: In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC: 0.59%, 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC: -0.71%, 95% CI -0.75 to -0.67%) and AUD (APC: -0.90%, 95% CI -0.94 to -0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019-2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.

Conclusions: Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.

Background/aims: Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV). This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC).

Methods: This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) were defined as >200 mg/dL.

Results: The median age of the study population was 59.6 years, with a predominance of male patients (n = 4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30-12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4.

Conclusions: Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.