Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B
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Background/Aims: The clinical effects of clevudine have been reported in patients with chronic hepatitis B virus infections (CHIs). In this investigation, we assessed whether clevudine induced biochemical and virological improvements in hepatocellular carcinoma (HCC) patients with CHI. Methods:Fifty-four patients who received 30 mg clevudine for more than 24 weeks between 2007 and 2009 at the National Cancer Center Hospital, Korea, were enrolled. Among these cases, 39 had HCC (CHI/HCC group) and 15 did not (CHI group). Results: In relation to the CHI group, the CHI/HCC group was older (55.5 years.) and had a higher liver cirrhosis rate (79.5%) (p<0.05). Median changes in serum hepatitis B virus (HBV) DNA levels from baseline at weeks 12, 24, and 36 of treatment in the CHI/HCC group were not signifi cantly different from those of the CHI group (-2.3, -2.7, -2.6 vs -1.7,-1.8, -2.4, respectively). HBV DNA <2,000 copies/mL was achieved in 76.5% of the CHI/HCC group at 24 weeks. Rates of ALT normalization in the CHI/HCC and CHI groups were 62.5% and 66.7%, respectively (p>0.05). Liver function was preserved with clevudine treatment in patients displaying response or stable disease under anti-cancer therapy. Four patients (7.4%) developed viral resistance during clevudine therapy. Among these, one was naïve, and three had previously received antiviral therapy. One CHI/HCC patient (1.9%)discontinued clevudine treatment due to symptomatic myopathy. Conclusions: Our findings clearly indicate that clevudine has comparable antiviral and biochemical effects in patients with CHI and with CHI/HCC and preserves the underlying liver function in HBV-related HCC patients.
Abstract
Background/Aims: The clinical effects of clevudine have been reported in patients with chronic hepatitis B virus infections (CHIs). In this investigation, we assessed whether clevudine induced biochemical and virological improvements in hepatocellular carcinoma (HCC) patients with CHI. Methods:Fifty-four patients who received 30 mg clevudine for more than 24 weeks between 2007 and 2009 at the National Cancer Center Hospital, Korea, were enrolled. Among these cases, 39 had HCC (CHI/HCC group) and 15 did not (CHI group). Results: In relation to the CHI group, the CHI/HCC group was older (55.5 years.) and had a higher liver cirrhosis rate (79.5%) (p<0.05). Median changes in serum hepatitis B virus (HBV) DNA levels from baseline at weeks 12, 24, and 36 of treatment in the CHI/HCC group were not signifi cantly different from those of the CHI group (-2.3, -2.7, -2.6 vs -1.7,-1.8, -2.4, respectively). HBV DNA <2,000 copies/mL was achieved in 76.5% of the CHI/HCC group at 24 weeks. Rates of ALT normalization in the CHI/HCC and CHI groups were 62.5% and 66.7%, respectively (p>0.05). Liver function was preserved with clevudine treatment in patients displaying response or stable disease under anti-cancer therapy. Four patients (7.4%) developed viral resistance during clevudine therapy. Among these, one was naïve, and three had previously received antiviral therapy. One CHI/HCC patient (1.9%)discontinued clevudine treatment due to symptomatic myopathy. Conclusions: Our findings clearly indicate that clevudine has comparable antiviral and biochemical effects in patients with CHI and with CHI/HCC and preserves the underlying liver function in HBV-related HCC patients.
참고문헌 (27)
- Parkin DM, "Global cancer statistics, 2002", CA Cancer J Clin, 55, pp.74~108 (2005)
- Lok AS, "Hepatitis B virus infection in Chinese families in Hong Kong", Am J Epidemiol, 126, pp.492~499 (1987)
- Park KW, "Survival analysis of 904 patients with hepatocellular carcinoma in a hepatitis B virus-endemic area", J Gastroenterol Hepatol, 23, pp.467~473 (2008)
- 김지훈, "Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus-related hepatocellular carcinoma", Liver Int., 29, pp.203~207
- Yeo W, "Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy", Hepatology, 43, pp.209~220 (2006)
- Kim JH, "Hepatitis B virus reactivation after three-dimensional conformal radiotherapy in patients with hepatitis B virus-related hepatocellular carcinoma", Int J Radiat Oncol Biol Phys, 69, pp.813~819 (2007)
- Kubo S, "Reactivation of viral replication after liver resection in patients infected with hepatitis B virus", Ann Surg, 233, pp.139~145 (2001)
- Yeo W, "Hepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy", Hepatology, 45, pp.1382~1389 (2007)
- Lee HS, "A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B", HEPATOLOGY, 43, pp.982~988, JOHN WILEY & SONS INC
- Hui CK, "Clevudine for the treatment of chronic hepatitis B virus infection", Expert Opin Investig Drugs, 14, pp.1277~1284 (2005)
- Korba BE, "Clevudine therapy with vaccine inhibits progression of chronic hepatitis and delays onset of hepatocellular carcinoma in chronic woodchuck hepatitis virus infection", Antivir Ther, 9, pp.937~952 (2004)
- Yoo BC, "Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B", HEPATOLOGY, 45, pp.1172~1178, JOHN WILEY & SONS INC
- Yoo BC, "Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression", HEPATOLOGY, 46(4), pp.1041~1048, JOHN WILEY SONS INC
- Park JW, "Practice guideline for diagnosis and treatment of hepatocellular carcinoma", Korean J Hepatol, 10, pp.88~98 (2004)
- Park JW, "Accuracy of clinical criteria for the diagnosis of hepatocellular carcinoma without biopsy in a Hepatitis B virus-endemic area", J Cancer Res Clin Oncol, 133, pp.937~943 (2007)
- Schafer DF, "Hepatocellular carcinoma", Lancet, 355, pp.1253~1257 (1999)
- Martins A, "Treatment and prognostic factors in patients with hepatocellular carcinoma", Liver Int, 26, pp.680~687 (2006)
- Llovet JM, "Hepatocellular carcinoma", Lancet, 362, pp.1907~1917 (2003)
- Lok AS, "Chronic hepatitis B", Hepatology, 45, pp.507~539 (2007)
- Kim YS, "Earlydevelopment of clevudine resistance during clevudine therapy in a patient with chronic hepatitis B who received prior lamivudine therapy", Liver Int, 29, pp.950~951 (2009)
- 고경현, "라미부딘 치료 후 클레부딘으로 전환한 만성 B형간염 환자에서 발생된 클레부딘 내성 1예: 연관 염기서열 분석", 대한소화기학회지, 52(5), pp.325~328 (2008), 대한소화기학회
- 이헌주, "만성 B형간질환에서 핵산유사체 치료경험이 없는 환자와 라미부딘 경험자에서의 클레부딘 치료", Clinical and Molecular Hepatology, 15(2), pp.179~192 (2009), 대한간학회
- Sharon A, "Understanding the molecular basis of HBV drug resistance by molecular modeling", Antiviral Res, 80, pp.339~353 (2008)
- Marcellin P, "A phase II doseescalating trial of clevudine in patients with chronic hepatitis B", Hepatology, 40, pp.140~148 (2004)
- Lee KS, "Clevudine therapy for 24 weeks further reduced serum hepatitis B virus DNA levels and increased ALT normalization rates without emergence of viral breakthrough than 12 weeks of clevudine therapy", INTERVIROLOGY, 50, pp.296~302, KARGER
- Seok JI, "Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA", Hepatology, 49, pp.2080~2086 (2009)
- Kim BK, "Clevudine myopathy in patients with chronic hepatitis B", J Hepatol, 51, pp.829~834 (2009)