icon-folder.gif   Conference Reports for NATAP  
 
  58th Annual Meeting of the American Association
for the Study of Liver Diseases
(AASLD)
November 2-6, 2007
Boston, MA
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Insulin Resistance Predicts HCV Progression in Genotype 1
 
 
  Reported by Jules Levin
AASLD, Nov 2-6, 2007, Boston, MA
 
Insulin resistance and severity of fibrosis in HCV genotype 1 chronic hepatitis
 
S. Petta1; C. Camma1; V. Di Marco1; N. Alessi1; F. Barbaria1; D. Cabibi2; R. Caldarella3; G. Tarantino1; F. Vitale3; A. Craxi1
1. Cattedra di Gastroenterologia, University of Palermo, Palermo, Italy.
2. Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy.
3. Cattedra di Igiene, University of Palermo, Palermo, Italy.
 
"In subjects infected by HCV genotype 1, a state of metabolic insulin resistance, regardless of the presence of clinically overt diabetes, and a high necroinflammatory activity are strongly linked to advanced fibrosis. Severity of IR may thus be used in nonfibrotic or mildly fibrotic HCV G1 patients as a predictor of a high risk of progression into more severe stages of fibrosis."
 
BACKGROUND AND AIMS
Patients with HCV G1 chronic hepatitis often have insulin resistance (IR), either due to metabolic causes and associated to visceral obesity or linked to virus-induced phenomena and non-metabolic. IR is central in the pathogenesis of steatosis, but contrasting data exist on its direct role in the progression of fibrosis. We aimed to assess whether the presence and degree of IR are linked to the stage of liver fibrosis in chronic hepatitis C genotype 1 patients.
 
Methods
Two hundred and one consecutive patients (11.04▒12.06) with HCV G1 chronic hepatitis, all na´ve to antiviral therapy and abstinent from alcohol, were evaluated by biopsy and by anthropometric and metabolic measurements including IR assessed by the homeostasis model assessment (HOMA) score. Non-diabetic patients were defined as insulin resistant if HOMA-IR>2.7. A single pathologist graded all liver biopsies (> 15 mm) by Scheuer's score. Steatosis was graded as absent (< 5% of hepatocytes) or present.
 
Results
Twenty-nine patients were diabetic (Group 1), 76 insulin resistant, non diabetic (Group 2), and 96 non diabetic, non insulin resistant (Group 3). Mean waist circumference was comparable among the three groups (Group 1, 96.5▒14.6 cm; Group 2, 94.2▒11.7 cm; Group 3, 90.8▒10.6 cm; p=0.08), while a significant difference was found in the mean age (Group 1, 60▒6 yrs; Group 2, 54▒11 yrs; Group 3, 49▒13 yrs; p=0.0003). Steatosis was present in 62% of patients in group 1, 63% in group 2 and 34% in group 3 (p=0.0006), and severe necroinflammatory activity (>1 by Scheuer) in 90%, 75% and 65% (p=0.034). Severe fibrosis (>2 by Scheuer) was found in 59%, 30% and 15% of patients (p=0.0001) in group 1, 2 and 3. At multivariate analysis severe fibrosis was independently linked to the degree of IR (OR 2.692; 95%CI 1.463-4.954), to a high necroinflammatory activity (OR 2.944; 95%CI 1.422-6.098), to platelet counts <140.000 mmc (OR 7.170 95%CI 3.000-16.700), to low cholesterol (OR 0.987; 95%CI 0.976-0.998) and to high ferritin (OR 1.002; 95%CI 1.000-1.003) .
 
Conclusions
In subjects infected by HCV genotype 1, a state of metabolic insulin resistance, regardless of the presence of clinically overt diabetes, and a high necroinflammatory activity are strongly linked to advanced fibrosis. Severity of IR may thus be used in nonfibrotic or mildly fibrotic HCV G1 patients as a predictor of a high risk of progression into more severe stages of fibrosis.