Intrahepatic and peripheral T-cell responses in genotype 1b hepatitis C virus-infected patients with persistently normal and elevated aminotransferase levels.

To evaluate whether the cytokine responses in liver and serum differ in chronic hepatitis C patients with normal and high alanine aminotransferase (ALT) levels. Thirty-three (16 with normal ALT level as group 1 and 17 with elevated ALT level as group 2) patients infected with genotype 1b hepatitis C virus (HCV) were examined. Liver infiltrating lymphomononuclear cells (LILMCs) were isolated from liver biopsy by collagenase type 1 and stimulated with phytohemagglutinin and interleukin 2 (IL-2). IL-10, IL-12, interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) were determined in serum and LILMCs by ELISA. Serum cytokine levels were similar in both groups (P>0.05). Stimulated IFN-gamma and TNF-alpha levels in LILMCs were increased in both groups. IL-12 and IL-10 levels stimulated with IL-2 were higher in group 1 than in group 2 (P = 0.023). Histological activity index (HAI) and stage had a negative correlation with TNF-alpha and IFN-gamma levels in group 2. Increased T-helper type 2 (Th2) cytokine response may regress inflammatory and biochemical activity. Progression of histological abnormalities in persons with elevated ALT probably depends on insufficient Th2 cytokine response, which does not balance Th1 cytokine response.