Journal of Gastroenterology

, Volume 47, Issue 5, pp 577–585 | Cite as

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

  • 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
Original Article—Liver, Pancreas, and Biliary Tract

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.

Keywords

Lamivudine Chronic hepatitis B Cirrhosis Hepatocellular carcinoma HBV-DNA level 

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

Supplementary material

535_2011_522_MOESM1_ESM.pptx (238 kb)
Supplementary material 1 (PPTX 237 kb)

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Copyright information

© Springer 2011

Authors and Affiliations

  • Mika Kurokawa
    • 1
  • Naoki Hiramatsu
    • 1
  • Tsugiko Oze
    • 1
  • Takayuki Yakushijin
    • 1
  • Masanori Miyazaki
    • 1
  • Atsushi Hosui
    • 1
  • Takuya Miyagi
    • 1
  • Yuichi Yoshida
    • 1
  • Hisashi Ishida
    • 1
  • Tomohide Tatsumi
    • 1
  • Shinichi Kiso
    • 1
  • Tatsuya Kanto
    • 1
  • Akinori Kasahara
    • 1
  • Sadaharu Iio
    • 2
  • Yoshinori Doi
    • 3
  • Akira Yamada
    • 4
  • Masahide Oshita
    • 5
  • Akira Kaneko
    • 6
  • Kiyoshi Mochizuki
    • 7
  • Hideki Hagiwara
    • 7
  • Eiji Mita
    • 8
  • Toshifumi Ito
    • 9
  • Yoshiaki Inui
    • 10
  • Kazuhiro Katayama
    • 11
  • Harumasa Yoshihara
    • 12
  • Yasuharu Imai
    • 13
  • Eijirou Hayashi
    • 14
  • Norio Hayashi
    • 7
  • Tetsuo Takehara
    • 1
  1. 1.Department of Gastroenterology and HepatologyOsaka University Graduate School of Medicine 2-2, YamadaokaSuitaJapan
  2. 2.Higashiosaka City General HospitalHigashiosakaJapan
  3. 3.Otemae HospitalOsakaJapan
  4. 4.Sumitomo HospitalOsakaJapan
  5. 5.Osaka Police HospitalOsakaJapan
  6. 6.NTT West Osaka HospitalOsakaJapan
  7. 7.Kansai Rosai HospitalAmagasakiJapan
  8. 8.National Hospital Organization Osaka National HospitalOsakaJapan
  9. 9.Osaka Kouseinenkin HospitalOsakaJapan
  10. 10.Hyogo Prefectural Nishinomiya HospitalNishinomiyaJapan
  11. 11.Osaka Medical Center for Cancer and Cardiovascular DiseaseOsakaJapan
  12. 12.Osaka Rousai HospitalSakaiJapan
  13. 13.Ikeda Municipal HospitalIkedaJapan
  14. 14.Kinki Central Hospital of Mutual Aid Association of Public School TeachersItamiJapan

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