Hepatology International最新文献

Background: The effects of genetic predispositions and steatotic liver disease (SLD) on the outcomes of chronic hepatitis C (CHC) patients with sustained virological responses (SVRs) remain unknown.

Methods: A 15-year prospective study of CHC patients with SVRs was conducted.

Results: Among 965 SVR patients, the baseline and 24-week post-HCV therapy SLD rates were 64% and 54%, respectively; the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M-rs738409 G allele was negatively correlated with the methylenetetrahydrofolate reductase (MTHFR) C677T Ala222Val-rs1801133 T allele (Pearson's correlation: -0.078, p = 0.025). At baseline, body mass index (BMI) (OR: 1.18; 95% CI: 1.12-1.25), cirrhosis (0.34; 0.20-0.56) and the PNPLA3 G allele (1.28; 1.03-1.60) were associated with SLD. At 24 weeks posttherapy, BMI (1.16; 1.09-1.24), the fibrosis-4 index (0.86; 0.75-0.99), cirrhosis (0.23; 0.14-0.40), HOMA-IR (1.16; 1.04-1.30), the ALT level (1.01; 1.00-1.03) and the MTHFR T allele (0.66; 0.48-0.91) were associated with 24-week SLD in SVR patients. Longitudinally, compared with sex- and age-matched patients without 24-week SLD, patients with 24-week SLD had higher BMIs and ALT levels, poorer metabolic profiles, and greater cumulative incidences of cardiovascular events (70.9% vs. 63.7%, p = 0.026) but lower fibrosis-4 indices and cumulative incidences of cirrhosis (12.7% vs. 31.5%, p < 0.001) and HCC (4.6% vs. 12.1%, p < 0.001). A 24-week SLD was negatively associated with the cumulative incidences of cirrhosis (HR: 0.548; 95% CI HR: 0.281 ~ 0.894) and HCC (0.637; 0.32 ~ 0.99).

Conclusions: Poorer metabolic profiles and greater cardiovascular but lower hepatic event cumulative incidences were noted in patients with than in those without 24-week SLD. The paradoxical association between SLD and hepatic events might stem from the negative correlation between the PNPLA3 G allele and the MTHFR T allele, which are HCV-specific SLD factors.

Background and aim: To identify predictive factors for rapid hepatitis B surface antigen (HBsAg) seroclearance at week 24 in inactive HBsAg carriers (IHC) receiving pegylated interferon alpha-2b (Peg-IFN) therapy, and to develop a machine learning-based model to optimize individualized treatment strategies.

Methods: This retrospective analysis was based on a multicenter, prospective cohort study involving 2882 IHC patients treated with Peg-IFN and followed for at least 24 weeks. Predictive variables for week 24 HBsAg seroclearance were selected using both LASSO regression and the Boruta algorithm. Nine machine learning models were developed, including logistic regression (LR), decision tree (DT), and random forest (RF), with performance assessed via tenfold cross-validation. External validation was conducted in an independent cohort (n = 167) from three medical centers in Beijing. SHapley Additive Explanations (SHAP) were used to interpret model predictions and feature importance.

Results: The overall HBsAg seroclearance rate at week 24 was 18.7% (541/2,882). Key predictive factors included baseline HBsAg level, ≥ 1 log IU/mL decline in HBsAg at week 12, the ratio of alanine aminotransferase (ALT) to HBsAg at week 12, the ratio of week 12 ALT to baseline HBsAg, week 12 hepatitis B virus (HBV) DNA level, and week 12 hepatitis B surface antibody (HBsAb) level. The Light Gradient Boosting Machine (Light GBM) model demonstrated the best performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.902 (95% CI 0.881-0.923) and a sensitivity of 0.889 in the training cohort, and an AUC of 0.917 (95% CI 0.850-0.983) with a sensitivity of 0.879 in the external validation cohort. SHAP analysis revealed that the week 12 ALT/ HBsAg ratio was the most impactful feature.

Conclusions: We developed a LightGBM-based machine learning model that accurately predicts rapid HBsAg seroclearance at week 24 among IHC patients receiving Peg-IFN therapy. This model offers a valuable tool for early identification of rapid responders, personalized treatment planning, and potential discontinuation strategies. The individualized stopping rules derived from model-predicted probabilities provide an evidence-based approach to precision therapy in IHC patients.

Objective: This study aimed to comprehensively evaluate the efficacy and safety of targeted therapy and immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic biliary tract cancer (BTC).

Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science databases through October 2024. The outcomes assessed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CIs) were used to quantify each outcome.

Results: Fifteen studies met the inclusion criteria. Pooled analyses revealed that targeted and immune therapy significantly improved OS and PFS compared to control. Subgroup analyses identified significant OS benefits with PD-L1 inhibitors, IDH1 inhibitors, and PD-1 inhibitors. In contrast, anti-EGFR agents, MET inhibitors, and anti-VEGF agents did not significantly prolong OS. PFS was improved with IDH1 inhibitors, PD-L1 inhibitors, and PD-1 inhibitors, while anti-VEGF agents showed no significant PFS benefit. Targeted and immune therapy significantly improved ORR and DCR, as confirmed by trial sequential analysis (TSA). Incidences of all-grade, serious, and grade 3/4 AEs were comparable between the targeted and immune therapy and control groups. Meta-regression analysis revealed no significant influence of sample size, treatment duration, or publication year on OS and PFS outcomes.

Conclusion: This meta-analysis demonstrates that targeted and immune therapy significantly improves survival outcomes and overall response in patients with advanced or metastatic BTC. Considering the potential limitations, further large-scale studies are warranted to validate these findings.

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality. Although the atezolizumab/bevacizumab regimen demonstrated impressive efficacy in the IMbrave150 clinical trial, long-term outcomes, particularly 3-year overall survival (OS), remain unestablished because of limited follow-up. Long-term outcomes have been reported for the tremelimumab/durvalumab combination, highlighting the need for comparable data on atezolizumab/bevacizumab. We aimed to elucidate the 3-year OS in patients with unresectable HCC (uHCC) treated with atezolizumab plus bevacizumab.

Methods: This retrospective multicenter study included patients with uHCC who received atezolizumab/bevacizumab. Among the 506 patients treated at the participating institutions, only those who initiated therapy between October 2020 and January 2022 were included. Comprehensive clinical, laboratory, and imaging data were collected, and the patients were followed up until March 2025.

Results: A total of 257 patients were analyzed, with a median follow-up of 48.23 months (range, 36.23-53.60 months). The 2- and 3-year OS rates were 39.2% and 25.3%, respectively. Among patients meeting the IMbrave150 criteria, the 3-year OS rate was 31.6%. Multivariate regression analysis identified baseline alpha-fetoprotein level > 116 ng/mL (odds ratio [OR] 0.41; 95% confidence interval [CI] 0.20-0.84; p = 0.015) and modified albumin-bilirubin grade 1-2a (OR 2.50; 95% CI 1.18-5.32; p = 0.017) as significant factors associated with 3-year OS.

Conclusions: In a real-world setting, the 3-year OS for uHCC patients treated with atezolizumab/bevacizumab was 25.3%, rising to 31.6% among those meeting the IMbrave150 criteria. Survival outcomes underscore the clinical value of atezolizumab/bevacizumab in improving long-term prognosis and guiding first-line treatment decisions for patients with unresectable HCC.

Background and aims: The impact of clinically significant portal hypertension (CSPH) on patients with hepatocellular carcinoma (HCC) after liver resection remains controversial. This study evaluated the effect of CSPH on postoperative outcomes in very-early, early, and intermediate-stage HCC.

Methods: In total, 857 patients with HCC undergoing liver resection were identified from a single-institution database. Patients were stratified using the Japan integrated staging (JIS) score, which combines Child-Pugh grade (A: 0, B: 1, C: 2) and TNM stage (I: 0, II: 1, III: 2, IV: 3). Patients were categorized as very-early (JIS 0, n = 198), early (JIS 1, n = 272), and intermediate (JIS 2-4, n = 287). Multivariable Cox regression assessed overall survival (OS).

Results: Risk-adjusted hazard ratios [95% confidence intervals] for OS in CSPH versus non-CSPH patients were 2.18 [1.14-4.18] (very-early), 0.67 [0.40-1.11] (early), and 1.67 [1.10-2.56] (intermediate). In early stage HCC, CSPH had no significant impact on OS, liver failure (19% vs. 19%, p = 0.925), 90-day mortality (2.6% vs. 2.9%, p = 1.000), or liver decompensation-related death (12% vs. 15%, p = 0.758). However, CSPH patients in very-early and intermediate stages had significantly higher liver failure (0.7% vs. 6.9%, p = 0.027; 6.0% vs. 19%, p = 0.001) and decompensation-related deaths (3.3% vs. 18%, p = 0.027; 9.0% vs. 34%, p < 0.001).

Conclusions: CSPH's impact varied by stage. In early stage HCC, CSPH had minimal effect on survival. However, in very-early and intermediate stages, CSPH was associated with worse outcomes. Refining surgical criteria for patients who have HCC with CSPH is essential to balance oncological benefits and hepatic risks.