Protective Effects of Statin Therapy in Cirrhosis Are Limited by a Common SLCO1B1 Transporter Variant

Hepatol Commun. 2021 Oct;5(10):1755-1766. doi: 10.1002/hep4.1753. Epub 2021 Aug 28.

Abstract

Complications of cirrhosis and portal hypertension (PH) can be reduced by statin therapy. The common loss-of-function variant p.V174A in the solute carrier organic anion transporter gene 1B1 (SLCO1B1) gene encoding the organic anion transporting polypeptide 1B1 results in decreased hepatic uptake of statins. Our specific aim was to assess the impact of this variant in patients with cirrhosis and statin treatment while controlling for the stage of cirrhosis and other potential confounders with propensity score matching (PSM), availing of a large cohort of genotyped study patients. In total, from 1,088 patients with cirrhosis in two German academic medical centers, PSM yielded 154 patients taking statins and 154 matched controls. The effect on PH was assessed by the liver stiffness-spleen size-to-platelet score (LSPS), and complications of cirrhosis were retrospectively recorded applying consensus criteria. As hypothesized, patients on statin treatment presented less frequently with signs of PH: Esophageal varices (41% vs. 62%; P < 0.001) were less common, and LSPS (4.8 ± 11.5 vs. 5.6 ± 6.4; P = 0.01) was reduced. Correspondingly, decompensation events were also reduced in patients on statins (odds ratio [OR] = 0.54, 95% confidence interval [CI] 0.32-0.90; P = 0.02). When the variant in SLCO1B1 was present in patients on statins, esophageal varices (OR = 2.68, 95% CI 1.24-5.81; P = 0.01) and bacterial infections (OR = 2.50, 95% CI 1.14-5.47; P = 0.02) were more common as compared with wild type carriers on statins. Conclusion: In this cohort, signs and complications of PH were reduced in patients with cirrhosis treated with statins. Notably, this effect was diminished by the common loss-of-function variant in SLCO1B1. Further prospective studies in independent cohorts are warranted to confirm these genotype-specific observations.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bacterial Infections / chemically induced
  • Bacterial Infections / genetics
  • Esophageal and Gastric Varices / chemically induced
  • Esophageal and Gastric Varices / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Predisposition to Disease / prevention & control
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypertension, Portal / genetics*
  • Hypertension, Portal / prevention & control
  • Liver / drug effects
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / genetics*
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Loss of Function Mutation
  • Male
  • Middle Aged
  • Odds Ratio
  • Propensity Score
  • Protective Agents / therapeutic use*
  • Retrospective Studies

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Protective Agents
  • SLCO1B1 protein, human