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Interferon Can Block Telomere Erosion and in Rare Cases Result in Hepatocellular Carcinoma Development with Telomeric Repeat Binding Factor 1 Overexpression in Chronic Hepatitis C

Division of Gastroenterology and Hepatology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences [M. I., T. S., M. T., M. N., T. T., S. O., H. K., Y. M., N. W., Y. A.], and Division of Internal medicine, Shibata Prefectural Hospital [H. H.], Niigata, Japan

Purpose: The purpose of this study was to evaluate whether IFN therapy for chronic hepatitis C could overcome telomere reduction in the liver, a possible risk factor for hepatocellular carcinoma (HCC) development.

Experimental Design: Relative telomeric repeat content (RTC) in the liver was measured before and after IFN therapy in 21 chronic hepatitis C cases. Liver samples were obtained at average intervals of 12, 75, and 32 months in eight complete responders (CRs) and one biochemical responder (BR), four CRs in whom HCC developed after an eradication of hepatitis C virus, and eight nonresponders, respectively. Telomeric repeat binding factor 1 (TRF1) was immunostained in specimens from CRs and a BR.

Results: Although the average RTC of 0.96 ± 0.14 (mean ± SD) significantly decreased to 0.85 ± 0.12 after IFN therapy in nonresponders (P = 0.023), the value of 0.91 ± 0.14 before IFN therapy in CRs and a BR increased significantly to 1.0 ± 0.085 (P = 0.031). TRF1 expression was barely detectable and attenuated after IFN therapy, except in CRs developing HCC, in which frequent staining appeared, and the RTC evidently decreased from 0.97 ± 0.11 to 0.63 ± 0.0092 in corresponding noncancerous liver tissues.

Conclusions: It is strongly suggested that successful IFN therapy blocks telomere erosion, except in rare cases in which telomere reduction continues with overexpression of TRF1. Successive RTC evaluation in the liver may distinguish a risky case from a clinically cured one.

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