- Email: [email protected]
241 REDUCING ALPHA-FETOPROTEIN WITH INTERFERON THERAPY SUPPRESSES HEPATOCARCINOGENESIS IN HEPATITIS C VIRUS-INFECTED PATIENTS WHO ARE VIROLOGICAL RESPONDERS AND NON-RESPONDERS
POSTERS (73.5%) were decompensated. Long-term cumulative survival was significantly better in presence of SVR respect to non-SVR (Fig.).
fibrosis, and steatosis, a multivariate analysis confirmed that posttreatment AFP level, age, gender, liver fibrosis, and steatosis were independent risk factors associated with HCC. Conclusion: AFP level after IFN treatment is an independent predictor for hepatocarcinogenesis. Suppressing AFP levels with IFN treatment significantly reduces the risk of HCC even in non-SVR. 242 EFFECT OF HIGH-DOSE RIBAVIRIN (RBV), ALINIA (NITAZOXANIDE) AND PEGYLATED INTERFERON (PEGIFN) ALFA-2A IN ATTAINING SUSTAINED VIROLOGIC RESPONSE (SVR) IN TREATMENT OF CHRONIC HEPATITIS C P. Basu1 , K. Rayapudi2 , N.J. Shah3 , T. Pacana3 , N. Krishnaswamy3 , R. Brown Jr.1 . 1 Columbia University Medical Center, Manhattan, 2 Vassar Brothers Hospital, Poughkeepsie, New York 12601, Poughkeepsie, 3 North Shore University Hospital at Forest Hills, Forest Hills, NY, USA E-mail: [email protected]
Our data suggest that, in front of low virological response and many life-treatening adverse events, viral eradication by PEG-IFN and RBV can significantly ameliorate prognosis in HCV-cirrhotics with PH, making the risk-to-benefit ratio of therapy more favorable in these patients. 241 REDUCING ALPHA-FETOPROTEIN WITH INTERFERON THERAPY SUPPRESSES HEPATOCARCINOGENESIS IN HEPATITIS C VIRUS-INFECTED PATIENTS WHO ARE VIROLOGICAL RESPONDERS AND NON-RESPONDERS Y. Asahina, K. Tsuchiya, N. Tamaki, M. Sato, T. Tanaka, I. Hirayama, Y. Yasui, K. Ueda, T. Kuzuya, H. Nakanishi, J. Itakura, M. Kurosaki, N. Izumi. Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan E-mail: [email protected] Background: Chronic hepatitis C (CH-C) patients without hepatocellular carcinoma (HCC) have occasionally elevated serum alpha-fetoprotein (AFP). The effects of interferon (IFN) on posttreatment AFP levels and hepatocarcinogenesis are unclear. Aims: To determine the change in AFP production after IFN treatment and the benefit of reducing AFP by IFN against hepatocarcinogenesis. Methods: Biopsy-proven 2,166 CH-C patients treated with IFN were studied. The absence of HCC before IFN treatment was carefully confirmed. The cumulative incidence of HCC after IFN treatment was analyzed by the Kaplan–Meier method for an average follow-up of 7.5 years. Factors associated with HCC risk were determined with Cox proportional hazard analysis. Serum AFP levels were measured every 1–2 months, and HCC was screened radiographically every 3–6 months. Patients in whom HCC developed within 1 year after IFN treatment were excluded. Results: HCC developed in 177 IFN-treated patients. Overall, the mean AFP level was significantly reduced from 13.7 to 6.9 ng/ml by IFN (p < 0.001). The cumulative incidence of HCC after IFN treatment depended on post-treatment AFP levels (15-year HCC rate: mean AFP < 5 ng/ml, 6%; 5–9, 15%; 10–19, 62%; 20–39, 85%; ≥40, 90%; logrank test, p < 0.001), and the risk ratio of HCC was 13-fold lower in patients with an AFP level less than 10 ng/ml as compared to that in other patients (95% CI: 9.1–16.9). Even in non-sustained virological responders (non-SVR), AFP levels were normalized in 58% of patients after IFN treatment, and the cumulative rate of HCC was equivalent to that observed in SVR (7.8% and 7.2% at 15 years, respectively). In contrast, cumulative rates of HCC were significantly higher in patients whose post-treatment AFP level was unchanged or increased (27% and 72% at 10 years, respectively). Although pretreatment AFP levels were significantly correlated with age, liver S102
Purpose: Sustained virologic response (SVR) in Hepatitis C is ~50% globally in all genotypes. Alinia (nitazoxanide [NTZ]) is an interferon inducer that may increase SVR in combination with PegIFN and RBV. Very rapid virologic response (VRVR) (undetectable HCV RNA 14 days after initiation of combination therapy) may predict higher SVR rates. We assessed NTZ with high-dose RBV and PegIFN alfa2a in achieving VRVR, RVR, early virologic response (EVR), End Treatment Response (ETR) and Sustained Viral response (SVR) in naïve patients with chronic hepatitis C genotype 1 (GT1). Methods: A prospective, open-label, pilot study of naïve chronic hepatitis C GT1 patients. All received NTZ 500 mg bid – first 2 weeks; RBV 800 mg(AM) + 600 mg(night) added to NTZ for next 2 weeks; subcutaneous PegIFN alfa-2a 180 mcg weekly added to RBV and NTZ at the same dose for next 12 weeks. Those with EVR continued PegIFN alfa-2a and RBV for the next 36 weeks at the same dose. VRVR, RVR, EVR, ETR, and SVR were assessed. Results: 23 Patients: Caucasian (n = 9, 39%), Hispanic (n = 4, 17%), African-American (n = 5, 21%) and Asian (n = 5, 21%). Mean BMI of 27.9; mean HCV RNA – 600,000 IU/ml; fibrosis score – F2 (57%). Growth factors were used to minimize dose reductions. Adverse effects (AE): skin rash (39%); neutropenia (47.8%); thrombocytopenia (43.4%); anemia (52%); Alopecia (30%); 8.7% discontinued treatment due to AE.None had dose reductions. Virologic response (interim results) VRVR Nonresponder RVR Complete EVR Partial EVR Week 24 Week 48 SVR
9/23 (39%) 2/23 (8.6%) 11/23 (47.8%) 14/23 (60.8%) 7/23 (30.4%) 15/23 (65.2%) 13/23 (56.5%) 13/23 (56.5%)
Conclusion: This regimen of NTZ, high-dose RBV and PegIFN alfa2a enhances RVR over historical controls and offers an improved SVR rate of 56.5% compare to the standard global 46% with GT1.
Journal of Hepatology 2010 vol. 52 | S59–S182
fibrosis, and steatosis, a multivariate analysis confirmed that posttreatment AFP level, age, gender, liver fibrosis, and steatosis were independent risk factors associated with HCC. Conclusion: AFP level after IFN treatment is an independent predictor for hepatocarcinogenesis. Suppressing AFP levels with IFN treatment significantly reduces the risk of HCC even in non-SVR. 242 EFFECT OF HIGH-DOSE RIBAVIRIN (RBV), ALINIA (NITAZOXANIDE) AND PEGYLATED INTERFERON (PEGIFN) ALFA-2A IN ATTAINING SUSTAINED VIROLOGIC RESPONSE (SVR) IN TREATMENT OF CHRONIC HEPATITIS C P. Basu1 , K. Rayapudi2 , N.J. Shah3 , T. Pacana3 , N. Krishnaswamy3 , R. Brown Jr.1 . 1 Columbia University Medical Center, Manhattan, 2 Vassar Brothers Hospital, Poughkeepsie, New York 12601, Poughkeepsie, 3 North Shore University Hospital at Forest Hills, Forest Hills, NY, USA E-mail: [email protected]
Our data suggest that, in front of low virological response and many life-treatening adverse events, viral eradication by PEG-IFN and RBV can significantly ameliorate prognosis in HCV-cirrhotics with PH, making the risk-to-benefit ratio of therapy more favorable in these patients. 241 REDUCING ALPHA-FETOPROTEIN WITH INTERFERON THERAPY SUPPRESSES HEPATOCARCINOGENESIS IN HEPATITIS C VIRUS-INFECTED PATIENTS WHO ARE VIROLOGICAL RESPONDERS AND NON-RESPONDERS Y. Asahina, K. Tsuchiya, N. Tamaki, M. Sato, T. Tanaka, I. Hirayama, Y. Yasui, K. Ueda, T. Kuzuya, H. Nakanishi, J. Itakura, M. Kurosaki, N. Izumi. Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan E-mail: [email protected] Background: Chronic hepatitis C (CH-C) patients without hepatocellular carcinoma (HCC) have occasionally elevated serum alpha-fetoprotein (AFP). The effects of interferon (IFN) on posttreatment AFP levels and hepatocarcinogenesis are unclear. Aims: To determine the change in AFP production after IFN treatment and the benefit of reducing AFP by IFN against hepatocarcinogenesis. Methods: Biopsy-proven 2,166 CH-C patients treated with IFN were studied. The absence of HCC before IFN treatment was carefully confirmed. The cumulative incidence of HCC after IFN treatment was analyzed by the Kaplan–Meier method for an average follow-up of 7.5 years. Factors associated with HCC risk were determined with Cox proportional hazard analysis. Serum AFP levels were measured every 1–2 months, and HCC was screened radiographically every 3–6 months. Patients in whom HCC developed within 1 year after IFN treatment were excluded. Results: HCC developed in 177 IFN-treated patients. Overall, the mean AFP level was significantly reduced from 13.7 to 6.9 ng/ml by IFN (p < 0.001). The cumulative incidence of HCC after IFN treatment depended on post-treatment AFP levels (15-year HCC rate: mean AFP < 5 ng/ml, 6%; 5–9, 15%; 10–19, 62%; 20–39, 85%; ≥40, 90%; logrank test, p < 0.001), and the risk ratio of HCC was 13-fold lower in patients with an AFP level less than 10 ng/ml as compared to that in other patients (95% CI: 9.1–16.9). Even in non-sustained virological responders (non-SVR), AFP levels were normalized in 58% of patients after IFN treatment, and the cumulative rate of HCC was equivalent to that observed in SVR (7.8% and 7.2% at 15 years, respectively). In contrast, cumulative rates of HCC were significantly higher in patients whose post-treatment AFP level was unchanged or increased (27% and 72% at 10 years, respectively). Although pretreatment AFP levels were significantly correlated with age, liver S102
Purpose: Sustained virologic response (SVR) in Hepatitis C is ~50% globally in all genotypes. Alinia (nitazoxanide [NTZ]) is an interferon inducer that may increase SVR in combination with PegIFN and RBV. Very rapid virologic response (VRVR) (undetectable HCV RNA 14 days after initiation of combination therapy) may predict higher SVR rates. We assessed NTZ with high-dose RBV and PegIFN alfa2a in achieving VRVR, RVR, early virologic response (EVR), End Treatment Response (ETR) and Sustained Viral response (SVR) in naïve patients with chronic hepatitis C genotype 1 (GT1). Methods: A prospective, open-label, pilot study of naïve chronic hepatitis C GT1 patients. All received NTZ 500 mg bid – first 2 weeks; RBV 800 mg(AM) + 600 mg(night) added to NTZ for next 2 weeks; subcutaneous PegIFN alfa-2a 180 mcg weekly added to RBV and NTZ at the same dose for next 12 weeks. Those with EVR continued PegIFN alfa-2a and RBV for the next 36 weeks at the same dose. VRVR, RVR, EVR, ETR, and SVR were assessed. Results: 23 Patients: Caucasian (n = 9, 39%), Hispanic (n = 4, 17%), African-American (n = 5, 21%) and Asian (n = 5, 21%). Mean BMI of 27.9; mean HCV RNA – 600,000 IU/ml; fibrosis score – F2 (57%). Growth factors were used to minimize dose reductions. Adverse effects (AE): skin rash (39%); neutropenia (47.8%); thrombocytopenia (43.4%); anemia (52%); Alopecia (30%); 8.7% discontinued treatment due to AE.None had dose reductions. Virologic response (interim results) VRVR Nonresponder RVR Complete EVR Partial EVR Week 24 Week 48 SVR
9/23 (39%) 2/23 (8.6%) 11/23 (47.8%) 14/23 (60.8%) 7/23 (30.4%) 15/23 (65.2%) 13/23 (56.5%) 13/23 (56.5%)
Conclusion: This regimen of NTZ, high-dose RBV and PegIFN alfa2a enhances RVR over historical controls and offers an improved SVR rate of 56.5% compare to the standard global 46% with GT1.
Journal of Hepatology 2010 vol. 52 | S59–S182