Statins in chronic liver disease and its complications: An umbrella review and meta-analysis of systematic reviews
STATINE IN MALATTIA CRONICA DEL FEGATO. ABBATTONO IL RISCHIO DI HCC E DI SCOMPENSO? UNA MAGNIFICA UMBRELLA META-ANALISI ITALIANA DI REVISIONI SISTEMICHE. DA “DIG &LIVER DISEASE” (FREE!)
_______________________________________________________________________
KEY POINTS FROM IA
Questo articolo è particolarmente interessante perché non aggiunge semplicemente un’altra meta-analisi, ma riordina criticamente un’intera area della letteratura. Questa umbrella review rappresenta la sintesi più completa delle evidenze disponibili sul ruolo delle statine nelle epatopatie croniche. La principale novità è la distinzione tra associazioni robuste osservate negli studi osservazionali e l’assenza di conferme definitive dagli studi randomizzati, offrendo una lettura più critica e metodologicamente rigorosa della letteratura. Il messaggio clinico è chiaro: le statine non devono essere evitate nei pazienti con epatopatia cronica quando indicate per la prevenzione cardiovascolare, mentre il loro potenziale effetto epatoprotettivo richiede ancora conferme da trial dedicati.
_______________________________________________________________________
Abstract
Abstract
Background and aims
Statins have been proposed as hepatoprotective agents in chronic liver disease (CLD); however, evidence from existing systematic reviews—including observational studies and clinical trials—is inconsistent and affected by substantial overlap. We conducted an umbrella review to synthesize the available evidence on the associations between statin use and hepatological outcomes in CLD patients, while addressing study overlap.
Design
PubMed, EMBASE, and Cochrane Library were searched up to September 2025 for systematic reviews of statin therapy in CLD. Methodological quality was evaluated using AMSTAR-2. Study overlap was assessed using corrected covered area (CCA) and minimized via hierarchical exclusion prioritizing methodological quality, comprehensiveness, and recency. Random-effects meta-analyses with bias assessments were conducted.
Results
Of 850 records screened, 17 systematic reviews (229 unique studies; 10,515,877 participants from 34 countries) were included after overlap adjustment (CCA = 5.79%). Statin therapy was associated with 46% reduction in hepatocellular carcinoma (HCC) risk (HR 0.54, 95% CI 0.48–0.59; I² = 46.7%) and 46% reduction in hepatic decompensation (HR 0.54, 95% CI 0.49–0.59; I² = 0.1%); these estimates derive predominantly from observational studies and should be interpreted as associations rather than causal effects. Geographic heterogeneity was observed: Asian populations showed stronger benefits (HCC HR 0.49, 95% CI 0.45–0.53; I² = 0%) compared with Western populations (HCC HR 0.71, 95% CI 0.52–0.96; I² = 95.7%; p = 0.003). Statin use also associated with reduced all-cause mortality (HR 0.65, 95% CI 0.52–0.81), though with substantial heterogeneity (I² = 80%). In contrast, available RCT-based evidence does not consistently confirm these associations for decompensation or mortality outcomes.
Conclusions
Statin use is consistently associated with reduced HCC risk and hepatic decompensation in CLD patients, particularly in Asian populations, though these findings derive predominantly from observational evidence subject to potential confounding. These associations support the continued use of statins in patients with CLD and cardiovascular indications where these are otherwise indicated, with potential additive hepatoprotective effects. These results underscore the urgent need for adequately powered randomized trials to clarify the boundaries of safety and efficacy in this high-risk population.
Fig. 2 Forest plot HCC prevention.
