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- Title
The correlation of the hepatic expression of SOCS3 with the response to PegInterferon in patients with chronic hepatitis C and obesity induced insulin resistance.
- Authors
Mota, Maria; Dinu, Ilie-Robert; Popa, Simona Georgiana; Diaconescu, Iulian; Vladu, Mihaela Ionela; Bicu, Mihaela Larisa; Mota, Eugen
- Abstract
The infection with the hepatitis virus C (HVC) represents one of the major medical problems, because of its frequency, the limited therapy resources, and the severe chronic complications. The response rate depends on the viral and host's factors and many patients stillfail to eradicate the virus. Three are the mechanisms proposed to explain the interference between obesity and treatment response. The first is based on the premise that obesity is an inflammatory condition which causes an abnormal immune response. Leptin, adiponectin, TNF-α have been proposed as heavily influencing non-responsiveness to the Peglnterferon-α (PegIFN-α) in patients with CHC and obesity. The second mechanism connects obesity with IR, fact which leads to fibrosis and the alteration of treatment response. It has been observed that HVC "core" proteins inhibit the phosphorylation induced by insulin upon the fostatidilinositol-3 kinase and of Akt which are downstream components of the insulin receptor substrate path in the liver. HVC mediates the dysfunction of insulin signaling paths by increasing the expression of the suppressor of cytokine signaling 3 (SOCS-3). Through SOCS3, HVC reduces the response to treatment, operating at the level of PegIFN-α action path by blocking the Jak/STAT path. From three SOCS3 genetic polymorphisms (8464 A/C, -4874 A/G, -1383 A/C), the lowest response rate to antiviral therapy was observe, in those with SOCS3 -4874 AA genotype. The third mechanism explains the low response rate in obese patients on the basis of the diminution of PegIFN-α biodisponibility. The treatment of patients that have IR associated to obesity could induce higher rates of the sustained virologic response. The therapeutic option is represented by the supervised losing weight and physical exercise, adequate medication to sustain insulin sensibility, omega 3 fatty acids, and branched-chain aminoacids; in the future one can try to use drugs, which help to reduce SOCS3 expression, influence the adipokines secretor profile induced by obesity.
- Subjects
NUTRITION disorders; OBESITY; HEPATITIS C; VIRAL hepatitis; FLAVIVIRAL diseases; GENETIC research; THERAPEUTICS; INSULIN; HYPOGLYCEMIC agents
- Publication
Maedica - a Journal of Clinical Medicine, 2008, Vol 3, Issue 2, p100
- ISSN
1841-9038
- Publication type
Article