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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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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Abbreviations

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

LAM:

Lamivudine

ADV:

Adefovir

ETV:

Entecavir

Hbs Ag:

Hepatitis B surface antigen

PCR:

Polymerase chain reaction

TMA:

Transcription-mediated amplification

IVR:

Initial viral response

MVR:

Maintained viral response

HBe Ag:

Hepatitis B e antigen

CT:

Computed tomography

MRI:

Magnetic resonance imaging

ALT:

Alanine aminotransferase

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Acknowledgments

This work was supported by Grants-in-Aid for Research on Hepatitis and BSE from the Ministry of Health Labour and Welfare of Japan and for Scientific Research from the Ministry of Education, Science, and Culture of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    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 & Tetsuo Takehara

  2. Higashiosaka City General Hospital, Higashiosaka, Japan

    Sadaharu Iio

  3. Otemae Hospital, Osaka, Japan

    Yoshinori Doi

  4. Sumitomo Hospital, Osaka, Japan

    Akira Yamada

  5. Osaka Police Hospital, Osaka, Japan

    Masahide Oshita

  6. NTT West Osaka Hospital, Osaka, Japan

    Akira Kaneko

  7. Kansai Rosai Hospital, Amagasaki, Japan

    Kiyoshi Mochizuki, Hideki Hagiwara & Norio Hayashi

  8. National Hospital Organization Osaka National Hospital, Osaka, Japan

    Eiji Mita

  9. Osaka Kouseinenkin Hospital, Osaka, Japan

    Toshifumi Ito

  10. Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan

    Yoshiaki Inui

  11. Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan

    Kazuhiro Katayama

  12. Osaka Rousai Hospital, Sakai, Japan

    Harumasa Yoshihara

  13. Ikeda Municipal Hospital, Ikeda, Japan

    Yasuharu Imai

  14. Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Japan

    Eijirou Hayashi

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  1. Mika Kurokawa
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  2. Naoki Hiramatsu
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Corresponding author

Correspondence to Naoki Hiramatsu.

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Kurokawa, M., Hiramatsu, N., Oze, T. et al. Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection. J Gastroenterol 47, 577–585 (2012). https://doi.org/10.1007/s00535-011-0522-7

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  • DOI: https://doi.org/10.1007/s00535-011-0522-7

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