Insulin resistance, serum adipokines and risk of fibrosis progression in patients transplanted for hepatitis C.
In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR 1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01-1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV.
Veldt
B J
BJ
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Poterucha
J J
JJ
Watt
K D S
KD
Wiesner
R H
RH
Hay
J E
JE
Rosen
C B
CB
Heimbach
J K
JK
Janssen
H L A
HL
Charlton
M R
MR
D054392:Adipokines / Q000097:blood*; D000328:Adult; D015331:Cohort Studies; D048909:Diabetes Complications; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007333:Insulin Resistance; D053208:Kaplan-Meier Estimate; D020738:Leptin / Q000097:blood; D008103:Liver Cirrhosis / Q000150:complications*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000503:physiopathology; D012044:Regression Analysis; D012306:Risk
D054392:Adipokines; D020738:Leptin