Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection.
OBJECTIVE
Metabolic factors may affect the course of chronic hepatitis C (CHC). Insulin resistance (IR) determines steatosis, but its direct role in affecting progression of hepatic fibrosis is less clear. We aimed to assess whether increasing degrees of IR, up to overt diabetes, are linked to steatosis and higher stages of fibrosis in patients with CHC resulting from genotype 1 HCV (G1-HCV).


METHODS
Two hundred one consecutive patients with G1-HCV infection were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). Nondiabetic patients were defined as insulin resistant if HOMA-IR was >2.7. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis.


RESULTS
Ninety-six patients were noninsulin resistant (group 1), 76 were insulin resistant without diabetes (group 2), and 29 were diabetic (group 3). At multivariate analysis, fibrosis of >/=3 was independently associated with high necroinflammatory activity (odds ratio [OR] 2.994, 95% confidence interval [CI] 1.422-6.098), low platelets (OR 0.994, 95% CI 0.981-0.999), low cholesterol (OR 0.987, 95% CI 0.976-0.998), high ferritin (OR 1.002, 95% CI 1.001-1.004), and a high prevalence of IR (OR 2.692, 95% CI 1.463-4.954). Diabetic patients were twice as likely to have severe fibrosis (60%) than those with IR but no diabetes (30%) (P= 0.006). The degree of steatosis and that of fibrosis were weakly associated with each other (P= 0.42).


CONCLUSIONS
In subjects with CHC resulting from G1-HCV, IR and overt diabetes are major determinants of advanced fibrosis, regardless of the degree of steatosis, mainly in the presence of severe necroinflammation.
Petta
Salvatore
S
Cattedra ed Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy.
Cammà
Calogero
C
Di Marco
Vito
V
Alessi
Nicola
N
Cabibi
Daniela
D
Caldarella
Rosalia
R
Licata
Anna
A
Massenti
Fatima
F
Tarantino
Giuseppe
G
Marchesini
Giulio
G
Craxì
Antonio
A
D001706:Biopsy; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000473:pathology; D005234:Fatty Liver / Q000453:epidemiology / Q000473:pathology; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000473:pathology; D008111:Liver Function Tests; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors
D012367:RNA, Viral