Sanchuan Lai, Wei Wei, Tingting Su
Background/Objectives: The association between non-selective β-blocker (NSBB) use and portal vein thrombosis (PVT) in patients with cirrhosis remains controversial. Prior meta-analyses had notable methodological limitations and may have overestimated this relationship. This updated systematic review and meta-analysis aimed to comprehensively evaluate the association between NSBB therapy and PVT risk in cirrhotic populations. Methods: We systematically searched PubMed, Web of Science, the Cochrane Library, and EMBASE up to 24 January 2026. Observational clinical studies comparing PVT incidence between cirrhotic patients receiving NSBBs and those not receiving NSBB treatment were included. The Newcastle-Ottawa Scale (NOS) was used for methodological quality assessment. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated separately using random-effects models. Subgroup, sensitivity, and publication bias analyses were performed to explore heterogeneity and verify result robustness. Results: Eighteen observational studies enrolling 8104 cirrhotic patients were finally included. For binary PVT endpoints from 12 studies, NSBB use was significantly associated with elevated PVT risk (pooled OR = 1.89, 95% CI 1.29-2.78), with moderate-to-high between-study heterogeneity (I2 = 67.8%). For longitudinal incident PVT evaluated by HRs in 6 cohort studies, the overall pooled association did not reach statistical significance (HR = 1.61, 95% CI 0.99-2.63). Subgroup analyses demonstrated that the effect size was further attenuated after multivariable adjustment. Conclusions: Observational evidence reveals a correlation between NSBB exposure and higher PVT prevalence in cirrhotic patients. However, adjusted longitudinal data fail to confirm that NSBB therapy independently increases the risk of de novo PVT. Large-scale, well-adjusted prospective cohort studies are needed to verify the relationship between NSBB administration and incident PVT.