Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C
- 1Service d’Hépatologie, Hôpital Saint-Antoine, Paris, France, and Inserm U680, Universite Pierre et Marie Curie, Paris, France
- 2Service d’Hépatologie, Hôpital Saint-Antoine, Paris, France
- 3Service de Biochimie, Hôpital Saint-Antoine, Paris, France
- 4Service d’Anatomo-pathologie, Hôpital Saint-Antoine, Paris, France
- Correspondence to:
Dr L Serfaty
Service d’Hépatologie, Hopital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France; lawrence.serfatysat.ap-hop-paris.fr
- Accepted 26 October 2004
- Revised 1 October 2004
Abstract
Background: Insulin resistance is a frequent feature of chronic hepatitis C. Whether insulin resistance could be the cause or consequence of steatosis and fibrosis is unknown. The ability of HCV genotype 3 to promote steatosis by itself provides an unique opportunity to answer this question.
Aims: The aim of the present study was to assess the relationships between insulin resistance, steatosis, and fibrosis according to genotype in 141 non-diabetic patients with biopsy proven non-cirrhotic chronic hepatitis C.
Methods: All patients had fasting serum glycaemia and insulinaemia measurements. Insulin resistance was evaluated using the homeostasis model assessment (HOMA IR) method. Liver steatosis was determined according to hepatitis C virus genotype (1 or 3). Logistic regression and multivariate regression analysis were used to identify variables independently associated with insulin resistance, fatty liver, and fibrosis.
Results: Although steatosis and fibrosis were more severe in genotype 3 patients, median HOMA IR was significantly higher in patients with genotype 1 related steatosis than in those with genotype 3 related steatosis (2.1 v 1; p = 0.001). Independent risk factors for steatosis were insulin resistance in genotype 1 patients (p = 0.001) and viral load in genotype 3 patients (p = 0.003). Among genotype 1 patients, independent parameters associated with insulin resistance were age (p = 0.04) and steatosis (p = 0.004). Steatosis was associated with more severe fibrosis whatever the genotype (p = 0.002). Among genotype 1 patients, although there was a significant relationship between circulating insulin level and fibrosis stage (p = 0.006), only steatosis and inflammatory score were independently associated with fibrosis.
Conclusion: This study shows that insulin resistance is the cause rather than the consequence of steatosis and fibrosis in genotype 1 patients and that increased circulating insulin is a risk factor for fibrosis through insulin resistance induced steatosis.
- HCV, hepatitis C virus
- RT-PCR, reverse transcription-polymerase chain reaction
- BMI, body mass index
- ALT, alanine aminotransferase
- HOMA, homeostasis model assessment
- IRS-1, insulin receptor substrate 1
Footnotes
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Conflict of interest: None declared.
