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Glucose Intolerance Associated with Advancing Liver Disease (Fibrosis)
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Insulin Resistance and Progression to Liver Fibrosis in HIV/HCV-co-infected Patients Participating to the Prospective ANRS Co13 French Cohort Study
Reported by Jules Levin
CROI 2007
Many studies have shown that diabetes, glucose intolerance can be associated with advancing liver disease (fibrosis). Which causes which? I think it can happen both ways, IÕm not sure if we know for sure.
Dominique Salmon*1, M A Loko2, S Dominguez3, P Bonnard4, P Morlat5, L Merchadou2, P Sogni1, L Alric6, F Dabis2, and Y Benhamou3
1Hosp Cochin, Paris, France; 2INSERM U593, Univ Victor Segalen, Bordeaux, France; 3Hosp Pitie Salpetriere, Paris, France; 4Hosp Tenon, Paris, France; 5Hosp St-Andre, Bordeaux, France; and 6Hosp Purpan, Toulouse, France
Background: Insulin resistance has been reported in patients with chronic hepatitis C virus (HCV). In HCV-mono-infected patients, insulin resistance has been associated with more rapid progression of liver fibrosis. However, the effect of insulin resistance on liver fibrosis in HIV/HCV co-infected is unknown. Our objective was to analyze the effect of insulin resistance as determined by HOMA score on liver fibrosis in HIV/HCV-co-infected patients.
Methods: HIV/HCV-co-infected patients, enrolled in a prospective French cohort study with available baseline blood measurements for fasted glycemia and insulinemia, and evaluation of fibrosis by either FibroTest or FibroScan were included in the current analysis. Univariate analysis was used to measure association between insulin resistance and severe liver fibrosis evaluated by FibroTest and FibroScan. (F³3, METAVIR). Thresholds used for the diagnosis of severe liver fibrosis are those reported in publications ie, FibroScan >9.5, FibroTest >0.68. For an accurate measurement of FibroTest that includes total serum bilirubin, patients receiving atazanavir were excluded. Insulin resistance was defined by a HOMA score (glycemia x insulinemia)/ 22.5) >4.
Results: We included 130 HIV/HCV-co-infected patients, whose mean was age 44 (range 31 to 70) years, and of whom 76.9% were male. HOMA score >4 was found in 26.9% of the patients. Patients with insulin resistance had a higher body mass index (p = 0.0002), higher aspartate aminotransferase (AST) (p = 0.004), higher alanine aminotransferase (ALT) (p = 0.02), higher g-glutamyl transferase (p = 0.003) than patients without insulin resistance. HCV genotype repartition did not differ between the 2 groups. When using FibroScan, the risk of severe liver fibrosis was significantly increased in patients with insulin resistance as compared to patients without insulin resistance (OR 4.2, 95%CI 1.4 to 12.7, p = 0.01). When using FibroTest, the same tendency was found but the relationship did not reach the significant level (OR 2.5, 95%CI 0.5 to 12, p = 0.28).
Conclusions: A high prevalence of insulin resistance was found in the studied population. This study suggests that insulin resistance may be associated with more severe liver fibrosis in HIV/HCV-co-infected patients. Further studies that include liver biopsies are needed to assess the role of insulin resistance on liver lesions and its effect on anti-HCV therapy.
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