Reduction of insulin resistance with effective clearance of hepatitis C infection: results from the HALT-C trial.
OBJECTIVE
Hepatitis C virus (HCV) infection is associated with an increased prevalence of diabetes and insulin resistance (IR); whether this is a causal relationship has not been established.


METHODS
We performed a longitudinal study within the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial to evaluate whether suppression of hepatitis C is associated with improvement in IR. Participants had advanced hepatic fibrosis and carried non-3 HCV genotypes (n = 96). Patients underwent 24 weeks of pegylated interferon and ribavirin therapy and were categorized into HCV clearance groups at week 20 on the basis of HCV RNA levels; null responders had <1 log(10) decline (n = 38), partial responders had >or=1 log(10) decline (n = 37) but detectable HCV RNA, and complete responders had no detectable HCV RNA (n = 21). The primary outcome was change (week 20 minus week 0) in IR by using the homeostasis model assessment (HOMA2-IR).


RESULTS
Adjusting only for baseline HOMA2-IR, mean HOMA2-IR differences were -2.23 (complete responders), -0.90 (partial responders), and +0.18 (null responders) (P = .036). The observed differences in mean HOMA2-IR scores were ordered in a linear fashion across response groups (P = .01). The association between HCV clearance and improvement in HOMA2-IR could not be accounted for by adiponectin or tumor necrosis factor-alpha and was independent of potential confounders including age, gender, ethnicity, body mass index, duration of infection, medications used, and fibrosis.


CONCLUSIONS
HCV suppression correlates with improvement in IR. These data provide further support for a role of HCV in the development of insulin resistance.
Department of Pediatrics, Batchelor Children's Research Institute, University of Miami, Miami, Florida, USA.
Aymin
A
Delgado-Borrego
Sergio H
SH
Jordan
Betania
B
Negre
David
D
Healey
Wenyu
W
Lin
Yoshitaka
Y
Kamegaya
Marielle
M
Christofi
David A
DA
Ludwig
Anna S F
AS
Lok
Raymond T
RT
Chung
D000328:Adult; D000368:Aged; D005260:Female; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a