Sustained biochemical remission after interferon treatment may closely be related to the end of treatment biochemical response and associated with a lower incidence of hepatocarcinogenesis

Abstract

Clinical background and incidence of hepatocellular carcinoma (HCC) of patients with chronic hepatitis C who obtained biochemical remission without eradication of virus (biochemical response) after interferon (IFN) treatment was retrospectively analyzed for 755 patients. Annual incidence of HCC was significantly lower in the patients with biochemical response and sustained response than that of the patients that did not show these responses. Logistic regression analysis showed that only the normalization of alanine aminotransferase (ALT) value at the end of IFN treatment was a significant factor for biochemical response. Annual incidence of HCC was significantly lower in the patients who obtained normalization of ALT values at the end of treatment than those who did not. Patients who were younger, who had a lower level of activity and fibrosis indices in histology, higher platelet count, and who were given more higher total dose of IFN were more likely to attain normalization of ALT levels at the end of treatment, and this was related to biochemical response. Low incidence of HCC in patients who obtained normalization of ALT values at the end of treatment was likely because they were in the earlier stage of chronic hepatitis. Active treatment of chronic hepatitis C with interferon in the early phase of the disease may bring about a biochemical response in some patients, even if sustained virological response is not obtained.

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.…”

Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study

“…Thus, our current findings identify AFP integration value as a useful predictive marker of HCC development in non-SVR patients. Data from several previous studies suggest that the continuous normalization of alanine aminotransferase (ALT) levels by interferon therapy can reduce the risk of HCC development [36][37][38][39]. In addition, one recent study suggested that the ALT integration value is a predictive factor for HCC [35].…”

Angiogenesis in hepatocellular carcinoma: the retrospectives and perspectives

“…Interferon a (IFNa) has been used in the treatment of HBV and HCV for many years, and a decreased incidence of HCC in patients with chronic HCV infection after long-term treatment with IFNa has been reported (Suzuki et al 2003). In patients with HBV, however, the benefit of long-term IFNa treatment is still controversial (Ikeda et al 1998).…”