Somatostatin analog therapy in delaying progression of polycystic liver disease: A meta-analysis with trial sequential analysis

TL;DR

This study finds that somatostatin analogs reduce liver and kidney volume in polycystic liver disease but increase certain side effects.

Contribution

A meta-analysis and trial sequential analysis evaluating the efficacy and safety of somatostatin analogs in PLD.

Findings

Somatostatin analogs significantly reduced total liver volume and total kidney volume compared to placebo.

Adverse events like cholelithiasis and cholecystitis were more common with somatostatin analog therapy.

No significant effect on estimated glomerular filtration rate was observed.

Abstract

Polycystic liver disease (PLD) can occur independently or in association with autosomal dominant polycystic kidney disease and has no effective medical therapy. This meta-analysis evaluated whether somatostatin analog therapy slows progression of PLD.

The PubMed, Scopus, Web of Science, and Cochrane databases were searched through to May 1, 2025 to identify randomized controlled trials that evaluated somatostatin analogs in PLD. The primary endpoints were percentage change from baseline in total liver volume (TLV), total kidney volume (TKV), and estimated glomerular filtration rate (eGFR). Safety endpoints included cholelithiasis, cholecystitis, diarrhea, and abdominal pain. Effect sizes were estimated using mean differences (MDs) and odds ratios (ORs) within a random-effects framework. Trial sequential analysis was performed for TLV, TKV, and eGFR.

Seven randomized controlled trials with 640 participants were included. Somatostatin analog therapy led to a significant reduction in TLV (MD −6.73%, 95% CI −8.68 to −4.78; p ​< ​0.001; GRADE, low)]and TKV (MD −3.35%, 95% CI −4.97 to −1.74; p ​< ​0.001; GRADE, moderate) compared with placebo. No significant effect was observed for eGFR (MD 0.32, 95% CI −4.55 to 5.19; p ​= ​0.90; GRADE, low). Adverse events, including cholelithiasis and cholecystitis (OR 4.66, 95% CI 1.19–18.26; p ​= ​0.03; GRADE, moderate), diarrhea, and abdominal pain, were more frequent in the somatostatin group. Trial sequential analysis showed good evidence of benefit for TLV and TKV and inconclusive evidence for eGFR.

Based on low-to-moderate evidence, somatostatin analogs were significantly associated with reduced TLV and TKV, but not eGFR, in patients with PLD, and with higher adverse event rates. Long-term trials are warranted to define their role in clinical management.

Registration: PROSPERO, ID CRD420251045402.

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