HEPATOLOGY Changes of soluble CD26 and CD30 levels correlate with response to interferon plus ribavirin therapy in patients with chronic hepatitis C Sheng-Shun Yang,* ,† Lin-Shien Fu, ‡ Chi-Sen Chang,* Hong-Zen Yeh,* Gran-Hum Chen* and Jia-Horng Kao § *Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, † Department of Life Science, National Chung-Hsin University, ‡ Department of Pediatrics, Taichung Veterans General Hospital, Taichung and § Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Abstract Background: Clearance of hepatitis C virus (HCV) is attributed to host cellular immune responses, in which T helper cells play a critical role. The purpose of the present paper was therefore to study the serial changes of serum soluble markers released from T helper 1 (Th1) and 2 (Th2) and their correlations with treatment responses in chronic hepatitis C patients receiving interferon-a plus ribavirin for 24 weeks. Methods: Serum markers (soluble CD26 and CD30 levels) of T helper cells were quan- tified before and 6 months after combination therapy in 33 chronic hepatitis C patients and in 20 healthy controls. Results: Compared to healthy controls, chronic hepatitis C patients had significantly lower serum soluble CD26 levels before (140.4  63.9 ng/mL vs 200.6  60.3 ng/mL, P < 0.0001) and after (115.9  32.9 ng/mL vs 200.6  60.3 ng/mL, P < 0.0001) combina- tion therapy. The level was even lower in those with non-sustained virologic response (non-SVR; 139.0  50.9 ng/mL vs 117.7  40.3 ng/mL, P = 0.039). In contrast, soluble CD30 levels at 6 months after combination therapy were significantly lower in patients with SVR than those with non-SVR (6.4  3.5 U/mL vs 10.4  5.4 U/mL, P = 0.021). Conclusion: Chronic hepatitis C patients have a weak Th1 response as reflected by lower soluble CD26 levels and the levels are even lower in non-sustained responders. In sharp contrast, downregulation of Th2 response with serial changes of soluble CD30 level is associated with successful treatment of HCV infection. Key words chronic hepatitis, hepatitis C virus, interferon, lymphocytes, ribavirin, sCD26, sCD30, Th1/Th2 response. Accepted for publication 28 October 2005. Correspondence Dr Jia-Horng Kao, Hepatitis Research Center and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan. Email: kjh@ha.mc.ntu.edu.tw Introduction Hepatitis C virus (HCV) infection causes a wide spectrum of liver disease ranging from acute and chronic hepatitis, liver cirrhosis, hepatocellular carcinoma and several extrahepatic manifestations. 1 The viral and host factors responsible for clinical outcomes of HCV infection have not yet been clarified. However, it is conceiv- able that dysregulation of specific immunoregulatory cells includ- ing imbalance of different T helper cells may play an important role in the pathogenesis of persistent HCV infection. The human T helper cell system has two different modes of function based on the types of invading microorganism. The first is T helper 1 (Th1) cells that preferentially develop during infec- tion by intracellular pathogens and trigger cell-mediated immu- nity. The second is T helper 2 (Th2) cells that attack extracellular pathogens or organisms found outside the cells (e.g. helminth infection or environmental allergens) by inducing humoral or antibody-mediated immune reactions. The Th1 and Th2 cells have not only different functional properties but also bear distinct surface markers. CD26 is a cell surface glycoprotein with dipep- tidyl peptidase IV (DPP IV) enzyme activity in the extracellular domain, affecting T-cell activation through selective modification of chemokines. 2 A previous study suggested that regulation of CD26 surface markers correlates with production of Th1-like cytokine. 3 After T-cell activation, the soluble form of CD26 (sCD26) is released into the bloodstream. In addition, CD30 is a member of the tumor necrosis factor (TNF)/nerve growth recep- tor superfamily, 4 and appears to be preferentially expressed and released by human CD4+ and CD8+ T cells producing predomi- nantly Th2 cytokines. 5 The soluble form of CD30 (sCD30) is also released into the bloodstream after cellular activation. A cytokine- mediated immune dysregulation or so-called ‘Th1/Th2 imbal- ance’ has been implicated in several immune responses involved in infections, allergy and autoimmune diseases. 6 Analysis of serum sCD26 and sCD30 level has been used as an indicator of Th1/Th2 imbalance during pregnancy and anti-neutrophil doi:10.1111/j.1440-1746.2006.04677.x 1789 Journal of Gastroenterology and Hepatology 21 (2006) 1789–1793 © 2006 The Authors Journal compilation © 2006 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd