Analysis of Background Factors Influencing Long-Term Prognosis of Patients with Chronic Hepatitis C Treated with Interferon

Abstract

Objective: Interferon (IFN) therapy has been used as antiviral therapy for chronic hepatitis C (CH-C); however, complete response to the therapy is observed in only about 30% of patients in Japan. Background factors involved in the responsiveness to IFN therapy, and progression to liver cirrhosis (LC) and hepatocellular carcinoma (HCC) after IFN therapy have not yet been sufficiently investigated. Methods: One hundred twenty-one patients with CH-C who received IFN therapy at Showa University Hospital between 1984 and 1999 were analyzed. Results: At 6 months after the termination of IFN therapy, 53 patients achieved a complete response, 11 patients incomplete response, and 57 patients no response. During a mean follow-up of 52.7 months, 12 patients progressed to LC, and 10 patients developed HCC. Multivariate analysis showed that significant independent factors involved in progression to LC were platelet count and the efficacy of IFN therapy. The significant independent factor involved in the development of HCC was platelet count. The factor involved in the therapeutic effect at 6 months after the termination of IFN administration was the serum hepatitis C virus (HCV) RNA levels before IFN therapy. Conclusion: Patients with high HCV RNA levels and low platelet counts should be considered to be at high risk of progressing to LC and developing of HCC and should be carefully followed after IFN therapy using ultrasonography, CT scan and MRI.

Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon

“…This value was consistent with the results of previous studies of small numbers of sustained responders to IFN who developed HCC. 5,[11][12][13][14]20,[21][22][23][24][25] This rate was considerably lower than that in IFN-refractory patients or HCV-positive pa- tients who did not receive IFN therapy, which has been reported to be 1.4%-7% yearly, 4-7,10-13,21-24 and it was obvious that IFN therapy decreased the risk of HCC in sustained responders. However, the incidence of HCC gradually increased over a period of at least 9 years after the termination of IFN therapy (Fig.…”

“…These variables were chosen by considering possible factors involved in the development of HCC, as indicated by previous investigations, [1][2][3][4][5][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] or suggested from our own clinical experience. Each variable, which was classified as host-related or treatment-related, was divided into one of two subgroups on the basis of clinically meaningful values.…”

“…5,7,[10][11][12][13][14] However, HCC can still occur in patients who are treated successfully with IFN, i.e., those showing a sustained response to the therapy. 5,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The incidence and clinical features of HCC, and the risk factors for carcinogenesis, have not yet been investigated, although they have been documented in individuals and in small numbers of patients. 5,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] We investigated a large cohort of patients showing a sustained response to IFN therapy given for chronic hepatitis C. Our aims were to assess the incidence of HCC in these patients and to discover the clinical variables that may be associated with the development of HCC.…”

Hepatocellular carcinoma in sustained responders of interferon‐treated chronic hepatitis C

“…The risk factors for HCC development in patients with chronic HCV infection were reported to be male sex, excessive alcohol intake, older age, sporadic infection, advanced histological staging, and lower platelet counts 2–5 . In IFN‐treated chronic hepatitis C patients, advanced hepatic fibrosis and decreased platelet counts, reflecting the stage of liver disease, were the significant independent factors for HCC development 6,7 . Interestingly, higher hepatic expression of Fas protein before IFN therapy is also associated with HCC development 6 .…”

“…[2][3][4][5] In IFN-treated chronic hepatitis C patients, advanced hepatic fibrosis and decreased platelet counts, reflecting the stage of liver disease, were the significant independent factors for HCC development. 6,7 Interestingly, higher hepatic expression of Fas protein before IFN therapy is also associated with HCC development. 6 Ikeda et al .…”