Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis.
Aged
Carcinoma, Hepatocellular
/ complications
Diabetes Mellitus, Type 2
/ complications
Female
Follow-Up Studies
Humans
Liver Cirrhosis
/ complications
Liver Neoplasms
/ complications
Male
Metformin
/ therapeutic use
Middle Aged
Non-alcoholic Fatty Liver Disease
/ complications
Prognosis
Retrospective Studies
Survival Analysis
Time Factors
Treatment Outcome
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
07
02
2019
revised:
18
03
2019
accepted:
10
05
2019
pubmed:
4
6
2019
medline:
15
5
2020
entrez:
4
6
2019
Statut:
ppublish
Résumé
Metformin may protect against hepatocellular carcinoma and mortality among patients with type 2 diabetes. To investigate whether long-term use of metformin improves survival and reduces liver-related outcomes among patients with type 2 diabetes and non-alcoholic steatohepatitis. A total of 191 diabetic patients with biopsy-proven non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis were retrospectively identified at Indiana University Medical Center between October 2004 and January 2016. Of them, 110 were users and 81 never-users of metformin. Primary outcomes were transplant-free survival, development of hepatocellular carcinoma or a first event of hepatic decompensation. Cirrhosis was present in 85% of metformin users and 88% of nonusers. Metformin dose was greater than or equal to 1 g/d in 104 out of 110 users and its median duration of use was 6 (95% CI: 4.4-7.9) years. The mean follow-up was 6.92 and 6.80 years for metformin users and non-users, respectively. During follow-up, 28 patients developed hepatocellular carcinoma (metformin users: 7, nonusers: 21), and 52 died (metformin users: 7, nonusers: 24) or were transplanted (metformin users: 13, non-users: 13). Metformin use was associated with lower risk of overall mortality or transplant (HR: 0.42; 95% CI: 0.24-0.74, P = 0.003) and hepatocellular carcinoma (sHR: 0.25; 95% CI: 0.11-0.58, P = 0.001), and remained independently associated with both outcomes after propensity-score and covariate-adjusted analyses. No instances of hepatotoxicity or lactic acidosis were observed. Our study demonstrated an association between long-term metformin use and reduced the risk of all-cause mortality/transplant and hepatocellular carcinoma in diabetics with non-alcoholic steatohepatitis and advanced fibrosis.
Sections du résumé
BACKGROUND
Metformin may protect against hepatocellular carcinoma and mortality among patients with type 2 diabetes.
AIM
To investigate whether long-term use of metformin improves survival and reduces liver-related outcomes among patients with type 2 diabetes and non-alcoholic steatohepatitis.
METHODS
A total of 191 diabetic patients with biopsy-proven non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis were retrospectively identified at Indiana University Medical Center between October 2004 and January 2016. Of them, 110 were users and 81 never-users of metformin. Primary outcomes were transplant-free survival, development of hepatocellular carcinoma or a first event of hepatic decompensation.
RESULTS
Cirrhosis was present in 85% of metformin users and 88% of nonusers. Metformin dose was greater than or equal to 1 g/d in 104 out of 110 users and its median duration of use was 6 (95% CI: 4.4-7.9) years. The mean follow-up was 6.92 and 6.80 years for metformin users and non-users, respectively. During follow-up, 28 patients developed hepatocellular carcinoma (metformin users: 7, nonusers: 21), and 52 died (metformin users: 7, nonusers: 24) or were transplanted (metformin users: 13, non-users: 13). Metformin use was associated with lower risk of overall mortality or transplant (HR: 0.42; 95% CI: 0.24-0.74, P = 0.003) and hepatocellular carcinoma (sHR: 0.25; 95% CI: 0.11-0.58, P = 0.001), and remained independently associated with both outcomes after propensity-score and covariate-adjusted analyses. No instances of hepatotoxicity or lactic acidosis were observed.
CONCLUSION
Our study demonstrated an association between long-term metformin use and reduced the risk of all-cause mortality/transplant and hepatocellular carcinoma in diabetics with non-alcoholic steatohepatitis and advanced fibrosis.
Substances chimiques
Metformin
9100L32L2N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-328Commentaires et corrections
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Informations de copyright
© 2019 John Wiley & Sons Ltd.