Impact of host insulin resistance on fibrosis and response to interferon in chronic hepatitis C.
Chronic hepatitis C and obesity inflict significant health and economic burdens on the world. Insulin resistance associated to obesity is the key factor in this disease, mainly because it has been related to fibrosis extension and non-response to antiviral therapy. The mechanism underlying this correlation is not fully explained yet. Leptin, adiponectin, TNF alfa, the hepatic expression of suppressor of cytokine signalling 3 (SOCS3), and hyperinsulinemia have been considered as heavily influencing fibrosis extension and nonresponsiveness to the IFN-alpha. The adipokines increased hepatic expression of SOCS3, and hyperinsulinemia has been proposed as heavily influencing non-responsiveness to the IFN-alpha and fibrosis extension by maintaining the hepatic stellate cells activated phenotype in patients with chronic hepatitis C and insulin resistance-related obesity. We shall review the mechanisms by which obesity-related insulin resistance may be associated with fibrosis extension and decreased efficacy of IFN-alpha based therapies in obese individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies. Consequently, being aware of the role of obesity-related insulin resistance in chronic hepatitis C, it will be possible to elaborate new therapeutic strategies for chronic hepatitis C obese patients. Also, it will be possible to elaborate new criteria for the initiation of antiviral therapy by including parameters such as body weight, abdominal circumference, HOMA-IR, the dosage of adipokines in order to more accurately define the groups of patients with a higher risk of non-responsiveness to antiviral therapy, thus lowering long-term costs.
Moţa
Maria
M
Department of Diabetes, Nutrition and Metabolic Disease, University of Medicine and Pharmacy, Craiova, Romania. mota@rdslink.ro
Popa
Simona
S
Mota
E
E
Diaconescu
I
I
Gheorghiţoiu
I
I
Panduru
M
M
D000998:Antiviral Agents / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007372:Interferons / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D000998:Antiviral Agents; D007372:Interferons