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Erschienen in: Journal of Gastroenterology 5/2012

01.05.2012 | Original Article—Liver, Pancreas, and Biliary Tract

Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection

verfasst von: Mika Kurokawa, Naoki Hiramatsu, Tsugiko Oze, Takayuki Yakushijin, Masanori Miyazaki, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Hisashi Ishida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Sadaharu Iio, Yoshinori Doi, Akira Yamada, Masahide Oshita, Akira Kaneko, Kiyoshi Mochizuki, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Yoshiaki Inui, Kazuhiro Katayama, Harumasa Yoshihara, Yasuharu Imai, Eijirou Hayashi, Norio Hayashi, Tetsuo Takehara

Erschienen in: Journal of Gastroenterology | Ausgabe 5/2012

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Abstract

Background

Nucleotide analogues have recently been approved for the treatment of patients with hepatitis B virus (HBV) infection. However, it is still controversial whether the decrease of HBV-DNA amount induced by treatment with nucleotide analogues can reduce the risk of hepatocellular carcinoma (HCC) development in HBV patients.

Methods

A total of 293 HBV patients without HCC who were treated with lamivudine (LAM) were enrolled in a multicenter trial. The incidence of HCC was examined after the start of LAM therapy, and the risk factors for liver carcinogenesis were analyzed. The mean follow-up period was 67.6 ± 27.4 months.

Results

On multivariate analysis for HCC development in all patients, age ≥50 years, platelet count <14.0 × 104/mm3, cirrhosis, and median HBV-DNA levels of ≥4.0 log copies/ml during LAM treatment were significant risk factors. The cumulative carcinogenesis rate at 5 years was 3% in patients with chronic hepatitis and 30% in those with cirrhosis. For the chronic hepatitis patients, the log-rank test showed the significant risk factors related to HCC development to be age ≥50 years, platelet count <14.0 × 104/mm3, and hepatitis B e antigen negativity, but median HBV-DNA levels of <4.0 log copies/ml (maintained viral response, MVR) did not significantly suppress the development of HCC. In cirrhosis patients, however, the attainment of MVR during LAM treatment was revealed to reduce the risk of HCC development.

Conclusions

These results suggest that the incidence of HCC in HBV patients with cirrhosis can be reduced in those with an MVR induced by consecutive LAM treatment.
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Literatur
2.
Zurück zum Zitat Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.PubMedCrossRef Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.PubMedCrossRef
4.
Zurück zum Zitat Beasley RP. Hepatitis B virus: the major etiology of hepatocellular carcinoma. Cancer. 1988;61:1942–56.PubMedCrossRef Beasley RP. Hepatitis B virus: the major etiology of hepatocellular carcinoma. Cancer. 1988;61:1942–56.PubMedCrossRef
6.
Zurück zum Zitat Tang B, Kruger WD, Chen G, Shen F, Lin WY, Mboup S, et al. Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic careers. J Med Virol. 2004;72:35–40.PubMedCrossRef Tang B, Kruger WD, Chen G, Shen F, Lin WY, Mboup S, et al. Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic careers. J Med Virol. 2004;72:35–40.PubMedCrossRef
7.
Zurück zum Zitat Kim SR, Kudo M, Hino O, Han KH, Chung YH, Lee HS. Epidemiology of hepatocellular carcinoma in Japan and Korea. A review. Oncology. 2008;75:13–6.PubMedCrossRef Kim SR, Kudo M, Hino O, Han KH, Chung YH, Lee HS. Epidemiology of hepatocellular carcinoma in Japan and Korea. A review. Oncology. 2008;75:13–6.PubMedCrossRef
8.
Zurück zum Zitat Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808–16.PubMedCrossRef Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808–16.PubMedCrossRef
9.
Zurück zum Zitat Taura K, Ikai I, Hatano E, Fujii H, Uyama N, Shimahara Y. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old. Ann Surg. 2006;244:265–73.PubMedCrossRef Taura K, Ikai I, Hatano E, Fujii H, Uyama N, Shimahara Y. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old. Ann Surg. 2006;244:265–73.PubMedCrossRef
10.
Zurück zum Zitat Shimada K, Sano T, Sakamoto Y, Kosuge T. A long-term follow-up and management study of hepatocellular carcinoma patients surviving for 10 years or longer after curative hepatectomy. Cancer. 2005;104:1939–47.PubMedCrossRef Shimada K, Sano T, Sakamoto Y, Kosuge T. A long-term follow-up and management study of hepatocellular carcinoma patients surviving for 10 years or longer after curative hepatectomy. Cancer. 2005;104:1939–47.PubMedCrossRef
11.
Zurück zum Zitat Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131:461–9.PubMedCrossRef Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131:461–9.PubMedCrossRef
12.
Zurück zum Zitat Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995;333:1657–61.PubMedCrossRef Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995;333:1657–61.PubMedCrossRef
13.
Zurück zum Zitat Nevens F, Main J, Honkoop P, Tyrrell DL, Barber J, Sullivan MT, et al. Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study. Gastroenterology. 1997;113:1258–63.PubMedCrossRef Nevens F, Main J, Honkoop P, Tyrrell DL, Barber J, Sullivan MT, et al. Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study. Gastroenterology. 1997;113:1258–63.PubMedCrossRef
14.
Zurück zum Zitat Rapti I, Dimou E, Mitsouka P, Hadziyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBVAg-negative chronic hepatitis B. Hepatology. 2007;45:307–13.PubMedCrossRef Rapti I, Dimou E, Mitsouka P, Hadziyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBVAg-negative chronic hepatitis B. Hepatology. 2007;45:307–13.PubMedCrossRef
15.
Zurück zum Zitat Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carriho FJ, et al. Entecavir treatment for 5 years in patients with hepatitis Be antigen-positive chronic hepatitis B. Hepatology. 2010;51:422–30.PubMedCrossRef Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carriho FJ, et al. Entecavir treatment for 5 years in patients with hepatitis Be antigen-positive chronic hepatitis B. Hepatology. 2010;51:422–30.PubMedCrossRef
16.
Zurück zum Zitat Kiyosawa K, Tanaka E, Sodeyama T. Hepatitis C virus and hepatocellular carcinoma. Curr Stud Hematol Blood Transfus. 1998;62:161–80.PubMedCrossRef Kiyosawa K, Tanaka E, Sodeyama T. Hepatitis C virus and hepatocellular carcinoma. Curr Stud Hematol Blood Transfus. 1998;62:161–80.PubMedCrossRef
17.
Zurück zum Zitat Ohkoshi S, Norio O, Ichida T. The long-term clinical outcome of 1-year treatment of chronic hepatitis B with lamivudine-5 years observation. Hepatol Res. 2003;27:13–7.PubMedCrossRef Ohkoshi S, Norio O, Ichida T. The long-term clinical outcome of 1-year treatment of chronic hepatitis B with lamivudine-5 years observation. Hepatol Res. 2003;27:13–7.PubMedCrossRef
18.
Zurück zum Zitat Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: natural history and treatment. Semin Liver Dis. 2006;26:142–52.PubMedCrossRef Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: natural history and treatment. Semin Liver Dis. 2006;26:142–52.PubMedCrossRef
19.
Zurück zum Zitat Matsumoto A, Tanaka E, Rokuhara A, Kiyosawa K, Kumada H, Omata M, et al. Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: a multicenter retrospective study of 2795 patients. Hepatol Res. 2005;32:173–84.PubMedCrossRef Matsumoto A, Tanaka E, Rokuhara A, Kiyosawa K, Kumada H, Omata M, et al. Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: a multicenter retrospective study of 2795 patients. Hepatol Res. 2005;32:173–84.PubMedCrossRef
20.
Zurück zum Zitat Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, et al. Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference. Ann Intern Med. 2009;150(2):111–24.PubMed Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, et al. Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference. Ann Intern Med. 2009;150(2):111–24.PubMed
21.
Zurück zum Zitat Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31.PubMedCrossRef Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31.PubMedCrossRef
22.
Zurück zum Zitat Perrillo R, Hann HW, Mutimer D, Willems B, Leung N, Lee WM, et al. Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Gastroenterology. 2004;126:81–90.PubMedCrossRef Perrillo R, Hann HW, Mutimer D, Willems B, Leung N, Lee WM, et al. Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Gastroenterology. 2004;126:81–90.PubMedCrossRef
23.
Zurück zum Zitat Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.PubMedCrossRef Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.PubMedCrossRef
24.
Zurück zum Zitat Chan HL, Hui AY, Wong ML, Tse AM, Hung LC, Wong VW, et al. Genotype C hepatitis B virus infection is associated with increased risk of hepatocellular carcinoma. Gut. 2004;53:1494–8.PubMedCrossRef Chan HL, Hui AY, Wong ML, Tse AM, Hung LC, Wong VW, et al. Genotype C hepatitis B virus infection is associated with increased risk of hepatocellular carcinoma. Gut. 2004;53:1494–8.PubMedCrossRef
25.
Zurück zum Zitat Chan HL, Tse CH, Koh FM, Wong VW, Wong GL, Chan SL, et al. High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008;26:177–82.PubMedCrossRef Chan HL, Tse CH, Koh FM, Wong VW, Wong GL, Chan SL, et al. High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008;26:177–82.PubMedCrossRef
26.
Zurück zum Zitat Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL, et al. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology. 2004;40:883–91.PubMedCrossRef Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL, et al. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology. 2004;40:883–91.PubMedCrossRef
27.
Zurück zum Zitat Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808–16.PubMedCrossRef Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003;348:808–16.PubMedCrossRef
28.
Zurück zum Zitat Kurashige N, Hiramatsu N, Ohkawa K, Yakushijin T, Kiso S, Kanto T, et al. Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis B. J Gastroenterol. 2009;44(6):601–7.PubMedCrossRef Kurashige N, Hiramatsu N, Ohkawa K, Yakushijin T, Kiso S, Kanto T, et al. Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis B. J Gastroenterol. 2009;44(6):601–7.PubMedCrossRef
29.
Zurück zum Zitat Chen CJ, Yu MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12:5294–308. Chen CJ, Yu MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12:5294–308.
30.
Zurück zum Zitat Yun LF. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int. 2009;29:100–7.CrossRef Yun LF. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int. 2009;29:100–7.CrossRef
31.
Zurück zum Zitat Sung JJ, Tsoi KK, Wong VW, Li KC, Chan LL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067–77.PubMedCrossRef Sung JJ, Tsoi KK, Wong VW, Li KC, Chan LL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067–77.PubMedCrossRef
Metadaten
Titel
Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection
verfasst von
Mika Kurokawa
Naoki Hiramatsu
Tsugiko Oze
Takayuki Yakushijin
Masanori Miyazaki
Atsushi Hosui
Takuya Miyagi
Yuichi Yoshida
Hisashi Ishida
Tomohide Tatsumi
Shinichi Kiso
Tatsuya Kanto
Akinori Kasahara
Sadaharu Iio
Yoshinori Doi
Akira Yamada
Masahide Oshita
Akira Kaneko
Kiyoshi Mochizuki
Hideki Hagiwara
Eiji Mita
Toshifumi Ito
Yoshiaki Inui
Kazuhiro Katayama
Harumasa Yoshihara
Yasuharu Imai
Eijirou Hayashi
Norio Hayashi
Tetsuo Takehara
Publikationsdatum
01.05.2012
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 5/2012
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-011-0522-7

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