Alimentary Pharmacology & Therapeutics最新文献

Background and aims: The burden of metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis is rapidly rising globally. There are several therapeutic agents under clinical development for the treatment of cirrhosis due to MASH; however, their relative efficacy has not been systematically assessed. This systematic review and network meta-analysis was performed to compare the histological efficacy of available therapeutic agents for compensated MASH cirrhosis.

Methods: PubMed and Cochrane Library databases were searched from inception to May 25, 2025, for randomised controlled trials (RCTs) evaluating pharmacological treatments in patients with biopsy-proven compensated MASH cirrhosis (F4c). The primary endpoint was fibrosis regression of at least one stage without MASH worsening, and the secondary endpoint was MASH resolution. Treatment comparisons were conducted via network meta-analysis, and ranking probabilities were estimated using the surface under the cumulative ranking (SUCRA) curve analysis.

Results: Nine RCTs with 3266 participants met the eligibility criteria. Efruxifermin was the only intervention significantly superior to placebo for ≥ 1-stage fibrosis improvement without worsening of MASH. The highest-ranked interventions for fibrosis improvement were efruxifermin (SUCRA: 77.44), cilofexor + firsocostat (SUCRA: 72.38) and aldafermin (SUCRA: 71.27). For MASH resolution, efruxifermin, semaglutide + cilofexor + firsocostat and semaglutide were significantly superior to placebo. Efruxifermin (SUCRA: 81.38), semaglutide + cilofexor + firsocostat (SUCRA: 74.07) and semaglutide (SUCRA: 63.88) had the highest probability of ranking best for MASH resolution.

Conclusion: This network meta-analysis provides relative rank-order estimates of the histological efficacy of available pharmacological therapies for compensated MASH cirrhosis. These data may have implications for the design of future clinical trials.

Background: Immune checkpoint inhibitors (ICIs) have emerged as promising agents for the management of advanced HCC. By reducing tumour burden, ICIs may serve as a downstaging/bridging tool to improve transplant candidacy. The aim of this study was to assess the safety of patients receiving pre-LT ICIs.

Methods: Multicenter, retrospective cohort study from January 2018 to December 2024, including 48 patients who received ICIs prior to LT (ICI cohort). A control cohort (non-ICI cohort) was built (1:3) using propensity score matching including 144 patients who underwent LT for HCC without prior ICI.

Results: Within the ICI cohort (N = 48) rejection occurred in 9 patients (18.8%), all biopsy-proven, with a median onset of 31 days post-LT (12.0-182.0). The median washout period was 60 days (13-96). Patients experiencing rejection had shorter washout periods (p = 0.029). All rejection episodes were successfully managed; two were steroid-resistant, one requiring re-transplantation. There were no rejection-related deaths. Of the 5 patients with HCC recurrence, 60% received ICI for < 90 days (p = 0.027). Comparison between the ICI and non-ICI cohort revealed no significant differences in rejection rates (18.8% vs. 19.4%, p = 0.916), graft failure, HCC recurrence, or overall mortality. Overall survival (OS) did not differ between ICI and non-ICI patients (p = 0.625) or between those with and without rejection (p = 0.119). Rejection was not associated with increased mortality, with deaths primarily attributed to infection or HCC recurrence.

Conclusion: Our results demonstrate that rejection rates were similar in patients receiving ICIs pre-LT and it can be safely managed.

Background: Renal safety is an important consideration for treatment selection in chronic hepatitis B (CHB) because of the ageing population and increasing prevalence of medical comorbidities. However, the renal safety profiles of first-line nucleos(t)ide analogues (NUCs) for CHB-tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) have not been comprehensively reviewed.

Aims: To evaluate the renal safety of ETV, TDF, and TAF in general and special populations with CHB.

Methods: In this narrative review, relevant studies in PubMed were identified using a range of keywords, followed by manual screening of reference lists to capture additional sources.

Results: Based on current randomised and real-world evidence, TDF may cause more nephrotoxic effects than ETV in patients with pre-existing moderate-to-severe chronic kidney disease (CKD), but the two agents may have similar renal safety profiles among patients with no or mild baseline renal impairment. Randomised data showed that TAF is significantly less nephrotoxic than TDF in different clinical settings. Retrospective data from both treatment-naïve and -experienced patients, as well as special populations, including patients with renal impairment, kidney transplant, advanced age, and acute-on-chronic liver failure, indicated that TAF may be more likely to improve renal function compared to ETV.

Conclusions: Current first-line NUCs show comparable renal safety profiles in CHB patients with no or mild kidney dysfunction, with growing evidence that favours TAF. Future prospective studies are needed to validate these findings, and more research should focus on CHB patients with diabetes mellitus who are at risk of CKD.