 |
|
|
| |
Insulin Resistance in 424 HCV+ Patients: association with HCV replication and advanced fibrosis
|
| |
| |
Reported by Jules Levin
EASL, Barcelona, Spain
....Management of insulin resistance should become part of the assessment of CHC patients....
R. Moucari 1, T. Asselah 1, V. Paradis 2, H. Voitot 3, R. Sobesky 1, M. Martinot-Peignoux 1, S. Maylin 4, M-H. Nicolas-Chanoine 4, M. Vidaud 3, D. Valla 1, P. Bedossa 2, P. Marcellin 1
1 Hepatology Department And INSERM CRB3, Beaujon Hospital, Clichy, France; 2 Pathology Department, Beaujon Hospital, Clichy, France; 3 Biochemistry Department, Beaujon Hospital, Clichy, France; 4 Microbiology Department, Beaujon Hospital, Clichy, France
Aim:
To assess the impact of metabolic and viral factors on insulin resistance (IR) development in a large cohort of chronic hepatitis C patients.
Patients and Methods:
466 consecutive adult patients with chronic hepatitis C (n=424), or B (n=42) and adequate liver biopsy were evaluated. Presence of metabolic syndrome and its five components was assessed in all patients on the day of liver biopsy. Overweight was defined as BMI>25 kg/m2, and IR as HOMA>3. Serum HCV RNA (Bayer's VERSANT(r) HCV RNA 3.0 Assay) and genotype (sequencing) were determined for all patients. Necroinflammation and fibrosis were evaluated using METAVIR score. Moderate-severe fibrosis was F2-F4, and severe necroinflammation A2-A3. Steatosis was graded as absent, moderate (<30%) or severe (>30%).
Results:
Characteristics of CHC Patients were: male sex (56%), mean age (47 years), mean BMI (24.8). Metabolic syndrome and IR were present in 11% and 35% of patients. Genotype distribution was: 1(56%), 2(7%), 3(16%), 4(19%), 5(2%). Mean serum HCV RNA was 1.08 106 IU/ml, and 48% of patients had high viral load (>600000 IU/ml). Histological features were: severe steatosis (32%), and F2-F4 fibrosis (54%).
In multivariate analysis, IR was associated with: overweight (p<0.001, OR=4.8), F2-F4 fibrosis (p<0.001, OR=2.4), severe steatosis (p=0.01, OR=1.8) and high viral load (p=0.03, OR=1.6). In subjects with BMI<25 (n=252), HOMA was significantly higher in patients with high viral load (2.8 vs. 1.9, p=0.01). IR was present in 21% of these patients, and was associated in multivariate analysis with high viral load (p=0.009, OR=2.4), A2-A3 necroinflammation (p=0.04, OR= 2), and F2-F4 fibrosis (p=0.04, OR=2).
In CHB non Asiatic patients (n=42), IR was significantly less frequent than in CHC patients (n=238) matched for sex, age, BMI, ALT levels, necroinflammation and fibrosis (1/42 vs. 53/238, p=0.003). IR parameters were significantly lower: HOMA (1.5 vs. 2.5, p=0.02), insulin (7 vs. 10.5 ľU/ml, p=0.02), C peptide (1.7 vs. 2.4 ng/ml, p=0.002).
Conclusion:
Insulin resistance is specifically associated with HCV infection. HCV replication may be directly responsible of IR in the absence of metabolic factors. IR is significantly associated with high fibrosis stages. Management of IR should become part of the assessment of CHC patients.
|
| |
|
|
|
|
|
