Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C

Abstract

To elucidate the risk factors for liver carcinogenesis and to examine the incidence of hepatocellular carcinoma (HCC) after interferon therapy, 1,022 chronic hepatitis C patients treated with interferon were followed by ultrasonography for 13 to 97 months (median 36 months). Sustained response with prolonged alanine aminotransferase normalization was found in 313 patients, transient response with alanine aminotransferase relapse after therapy in 304, and no response in 405. Forty-six developed HCC, of whom 5 were sustained responders, 9 were transient responders, and 32 were nonresponders. The cumulative incidence of HCC in transient responders was almost equal to that in sustained responders, and it was significantly higher in nonresponders than in sustained and transient responders (P ‫؍‬ .0009). The seventh-year cumulative incidence rates of HCC in sustained responders, transient responders, and nonresponders were estimated to be 4.3%, 4.7%, and 26.1%, respectively. However, there was no significant difference in the cumulative incidence of HCC between patients with HCV subtype 1 and 2 (P ‫؍‬ .14). Cox regression analysis showed that the risk of HCC development was not elevated in transient responders compared with sustained responders, but that the risk was 7.90-fold higher in nonresponders than in sustained responders (P ‫؍‬ .008). Patients H55 years of age had a significantly higher risk ratio (4.65) than did those under 55 years of age (P ‫؍‬ .006). The risk of HCC development in men was 4.35 times higher than the risk in women (P ‫؍‬ .02). However, the degree of fibrosis was not a significant risk factor for the development of HCC (risk ratio, 3.16; P ‫؍‬ .052). These results suggest that patients in the high-risk group of HCC after interferon therapy were those who showed no response, those who were older, and those who were male, and that such patients should be carefully followed using ultrasonography.(HEPATOLOGY 1998;27:1394-1402.) Hepatocellular carcinoma (HCC) is one of the most common malignancies, especially in Southeast Asia. In Japan, its incidence has been increasing over the last 30 years, and epidemiological surveys have shown that as a causative agent, hepatitis C virus (HCV) is more common than hepatitis B virus. Chronic hepatitis C has been demonstrated to evolve to cirrhosis and HCC. 1,2 When blood transfusion is the cause, the intervals from its administration to the diagnosis of cirrhosis and HCC have been reported to be 20 to 25 years and 30 years, respectively. 2 The incidence of HCC has been shown to be higher in patients with chronic hepatitis C than in those with chronic hepatitis B. 3 Moreover, the HCC occurrence rate in cirrhotic patients with antibodies to HCV has been reported to increase steadily, with a yearly incidence of 1.4% to 7%. [4][5][6] Thus, a majority of cases with chronic HCV infection progress slowly to liver cirrhosis and HCC.In Japan, more than two hundred thousand patients with chronic hepatitis C have been treated with interferon. Many investigators have repo...

Impact of aging on the development of hepatocellular carcinoma in patients with posttransfusion chronic hepatitis C

“…7,20 Using multivariate Cox regression analyses, some previous studies demonstrated that fibrosis could be a dependent factor for the development of HCC. 19,21 The previous study confirmed that conclusion.…”

Sustained virological response to interferon-α is associated with improved outcome in HCV-related cirrhosis: A retrospective study

“…6,9,26 Cirrhosis is the main independent risk factor for HCC development, 9,27 and residual viremia, i.e., HCV-RNA not detected by the currently available commercial PCR assays, may explain the risk of HCC in these patients. 28 The finding that male subjects aged Ͼ54 years have a higher risk of developing HCC suggests that host-related factors and/or the duration of the disease might enhance the risk of HCC.…”

“…3 One prospective randomized trial 4 showed reduced HCC incidence in IFN-treated patients with chronic HCV irrespective of virological response, but these results have not been reproduced. A retrospective analysis of a large database in Japan 5 and other small studies [6][7][8] designed to assess the rate of SVR following IFN therapy have not provided conclusive evidence that the progression of liver disease underling HCV infection was halted in nonresponder patients.…”

Natural history of hepatitis C: Its impact on clinical management

“…21 Most of the studies to date have examined the effect of interferon at standard doses for 6 to 12 months. 23,24 The possible effects of prolonged therapy have not been studied nor has the combination of interferon and ribavirin. A National Institutes of Health-funded study that aims to address this question has been initiated (the HALT-C trial).…”