Pharmacological Intervention for Hepatorenal Syndrome: A Systematic Review and Meta-analysis

Abstract

Introduction: Hepatorenal syndrome (HRS) is a devastating complication of advanced chronic liver disease. Various medical therapies have been studied with variable efficacy. Terlipressin, the most effective and safe medication is unavailable in the US. We performed a systematic review and meta-analysis to compare the effectiveness of various drugs in the treatment of HRS. Methods: Out of 508 articles searched from Pubmed and Embase, randomized controlled trials (RCT) comparing active drug with placebo or comparing two different drugs were included in this analysis. Study outcomes were reversal of HRS (decrease in serum creatinine by more than 50% from pre-treatment value or below 1.5 mg/dL), relapse of HRS, and patient survival. The data was pooled in the comprehensive meta-analysis software using a random effects model. Effect size on outcome is reported as odds ratio with 95% confidence interval.Table 1: Comparison of drugsResults: 11 RCT were analyzed comparing various to pool on the pre-defined outcomes (Table). Heterogeneity assessed (using I2 statistics) with ≥2 studies in the analysis showed homogeneous data for all the analyses. Publication bias assessed with ≥3 studies in the analysis showed no publication bias. Conclusion: Intravenous infusion of terlipressin (T) is the most effective medical therapy for treatment of HRS. With unavailability of this agent in the US, intra-venous infusion of nor-adrenaline (NE) is an acceptable alternative therapy. Oral midodrine (M) and subcutaneous octreotide (O) combination works as effectively as NE but is inferior to T. Multicenter larger studies are needed as a basis of examining efficacy of M+O combination in the treatment of HRS. Studies are also suggested to develop maintenance regimen to prevent relapse of HRS as basis of bridging patients to liver transplantation and improve patient survival.