Original Contribution
The American Journal of Gastroenterology (2008) 103, 1136–1144; doi:10.1111/j.1572-0241.2008.01813.x
Insulin Resistance and Diabetes Increase Fibrosis in the Liver of Patients With Genotype 1 HCV Infection
Salvatore Petta MD1, Calogero Cammà MD1, Vito Di Marco MD1, Nicola Alessi MD1, Daniela Cabibi MD2, Rosalia Caldarella MD3, Anna Licata MD1, Fatima Massenti MD3, Giuseppe Tarantino MD1, Giulio Marchesini MD4 and Antonio Craxì MD1
- 1Cattedra ed Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy
- 2Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy
- 3Dipartimento di Igiene e Microbiologia—Sezione Igiene, University of Palermo, Palermo, Italy
- 4Dipartimento di Medicina e Gastroenterologia, "Alma Mater Studiorum," University of Bologna, Bologna, Italy
Correspondence: Salvatore Petta, Dipartimento di Gastroenterologia e Epatologia, Piazza delle Cliniche, 2, 90127 Palermo, Italy.
Received 28 August 2007; Accepted 21 November 2007.
Abstract
OBJECTIVES:
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.
