Inhibition of hepatocarcinogenesis is a crucial issue in treating chronic hepatitis C patients, especially those who do not respond completely to interferon therapy. Interferon has been reported to reduce the incidence of hepatocellular carcinoma (HCC) not only in sustained virological responders but also in transient biochemical responders. However, the incidence of HCC increases in 5 years or more after interferon therapy in transient biochemical responders. The aim of this study is to assess whether interferon retreatment reduces the incidence of HCC in chronic hepatitis C patients in whom hepatitis C virus was not eradicated during initial interferon therapy. We enrolled 309 patients who were not sustained virological responders after initial interferon treatment consisting of a total dose of more than 250 megaunits of interferon and were followed for more than 2 years after treatment. Ninety-nine patients received interferon retreatment and 210 did not. Two courses of interferon therapy were administered in 84, three courses in 14 and five courses in one. The incidence of HCC was compared between patients with retreatment and those without. In the clinical characteristics, retreated patients were younger and followed up for a longer time period. The cumulative incidence of HCC was significantly lower in retreated patients. In multivariate analysis, patients' age (P=0.018) and the number of courses of interferon therapy (P=0.022) were independently associated with HCC incidence. These results suggest that interferon retreatment reduces or delays the incidence of HCC in chronic hepatitis C patients who did not completely respond to initial therapy.
Simultaneous commencement of treatment with interferon and a nucleoside analog may be worthy as a treatment option to augment the early virologic response and prevent drug resistance in difficult-to-treat patients. Combination treatment was also shown to enhance reversion of the precore mutation. Further studies are warranted to clarify the therapeutic implications of this phenomenon.
The clinical progression of chronic hepatitis C is not uniform throughout the entire period of infection and is more rapid in patients with advanced histologic disease. Our study was designed to identify factors contributing to progression to cirrhosis and hepatocellular carcinoma by taking the entire period of infection into consideration. Two hundred thirteen patients with transfusion-associated hepatitis type C chronic liver disease were included in this study. They did not have either a history of antiviral therapy or any other potential causes of chronic liver disease except for transfusion. Hepatitis C virus genotype 1b was detected in 144 (68%) patients, followed by 2a in 51 (24%), 2b in 11 (5%), 1a in 4 (2%), and coinfection with 1b and 2a in 3 (1%). The log-rank test in the Kaplan-Meier method revealed that the cumulative percentage of cirrhosis-free or hepatocellular carcinoma-free patients became significantly lower as the transfusion age went up. Patient age at the time of transfusion was the only independent factor related to disease progression in multivariate analysis using Cox's proportional hazards model. Thus age at transfusion should be taken into consideration in designing the optimal follow-up schedule and therapy in patients with posttransfusion-associated chronic hepatitis C.
Although estrogen replacement therapy (ERT) has been established as an effective treatment for postmenopausal bone loss, the clinical features which predict the effects of ERT have not been well investigated in Japanese postmenopausal women. We analyzed the role of physical factors influencing the effect of ERT on vertebral bone mineral density (BMD) in 94 Japanese postmenopausal women treated for 2 years or longer. The increase in BMD with ERT is 17.6 ± 27.6 mg/cm2/year (mean ± SD) during the first 2 years. Rates of BMD change were negatively correlated with the estimated initial BMD, and positively correlated with age and years since menopause, while no correlation was noted with the body mass index by a simple correlation analysis. The relationships between BMD change and estimated initial BMD or age also held in a multiple regression analysis. The estimated initial BMD and age together accounted for 34.4% of the BMD change during ERT. Furthermore, there were very few (2.4%) nonresponders with a negative linear regression slope of BMD in the osteoporosis and osteopenia group, although 32.7% of the normal initial BMD group were nonresponders. These results suggest that the initial BMD and age are potent predictive factors of the ERT effect on BMD change in Japanese postmenopausal women.
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