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. 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. 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. 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.

Background/Objectives: Long-term treatment options for fibromyalgia syndrome (FMS) remain limited and there is a lack of real-world data on the extended use of nutraceutical formulations containing palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC). This study describes a cohort treated for 12 months with a fixed multicomponent formulation containing PEA and ALC, followed by an additional visit three months post-treatment. Methods: This retrospective, uncontrolled single-cohort study involved 150 consecutive adults diagnosed with fibromyalgia syndrome (FMS). Participants received a fixed oral formulation comprising palmitoylethanolamide (PEA) 600 mg, acetyl-L-carnitine (ALC) 500 mg, Boswellia serrata 100 mg, vitamin B6 and vitamin E, administered twice daily as an adjunct to stable background therapy. Pain levels were assessed using the Visual Analogue Scale (VAS), and the impact of the disease was evaluated with the revised Fibromyalgia Impact Questionnaire (FIQR) over a period of up to 15 months. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) for up to 6 months. Missing data were addressed through various methods, including a mixed model, last observation carried forward, delta-adjusted and baseline-carried-forward scenarios, as well as non-responder imputation. Results: Sixty-four patients completed the 12-month course, 45 discontinued (36 for perceived lack of efficacy) and 41 were lost to follow-up. Estimated mean VAS fell from 76.3 to 52.3 at 12 months and FIQR from 73.6 to 56.1; under the worst-case assumption that every non-completer returned to baseline, the mean 12-month change in VAS was −13.0 points (95% CI −15.9 to −10.2). At 6 months, 78.1% of completers reached the FIQR minimal clinically important difference and 59.4% the IMMPACT 30% pain threshold, corresponding to 37.3% and 28.7% of all 150 patients with non-responder imputation; only 20.3% of completers (10.0% of all patients) improved by ≥3 PSQI points. Recorded adverse events occurred in 10.0% of patients. Retention at 12 months was 60.6% (42.7% if patients lost to follow-up were counted as discontinuations). In completers, pain and FIQR three months after the end of treatment were within one point of the 12-month values. Conclusions: In this uncontrolled cohort, 12 months of add-on treatment with a multicomponent formulation containing PEA and ALC was associated with reductions in pain and disease impact, whereas sleep outcomes changed minimally. However, attrition was substantial and partially response-dependent; therefore, the observed changes cannot be attributed to the formulation or its individual components. These descriptive findings support the need for a controlled trial with a duration of at least 12 months.