Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.
Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C.
del Campo
José A
JA
Unit for Clinical Management of Digestive Diseases and CIBERehd, Valme University Hospital, Seville, Spain.
López
Reyes Aparcero
RA
Romero-Gómez
Manuel
M
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism / Q000821:virology; D015309:Glucose Clamp Technique; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use; D019562:Viral Load
D000998:Antiviral Agents; D007004:Hypoglycemic Agents; D008687:Metformin