Protective Effects of Statin Therapy in Cirrhosis Are Limited by a Common SLCO1B1 Transporter Variant.
Aged
Bacterial Infections
/ chemically induced
Esophageal and Gastric Varices
/ chemically induced
Female
Genetic Predisposition to Disease
/ genetics
Genotype
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Hypertension, Portal
/ genetics
Liver
/ drug effects
Liver Cirrhosis
/ complications
Liver-Specific Organic Anion Transporter 1
/ genetics
Loss of Function Mutation
Male
Middle Aged
Odds Ratio
Propensity Score
Protective Agents
/ therapeutic use
Retrospective Studies
Journal
Hepatology communications
ISSN: 2471-254X
Titre abrégé: Hepatol Commun
Pays: United States
ID NLM: 101695860
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
30
04
2021
received:
05
01
2021
accepted:
06
05
2021
pubmed:
25
9
2021
medline:
13
1
2022
entrez:
24
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34558822
doi: 10.1002/hep4.1753
pmc: PMC8485882
pii: 02009842-202110000-00011
doi:
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Liver-Specific Organic Anion Transporter 1
0
Protective Agents
0
SLCO1B1 protein, human
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1755-1766Informations de copyright
© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.
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