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Histological characteristics predisposing to development of hepatocellular carcinoma in patients with chronic hepatitis B
  1. Sae Hwan Lee1,
  2. Young-Hwa Chung2,
  3. Jeong A Kim2,
  4. Young-Joo Jin2,
  5. Won Hyung Park2,
  6. Jong Gi Choi2,
  7. Danbi Lee2,
  8. Ju Hyun Shim2,
  9. Eunsil Yu3,
  10. Myoung Kuk Jang4
  1. 1Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, South Korea
  2. 2Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
  3. 3Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
  4. 4Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul, South Korea
  1. Correspondence to Young-Hwa Chung, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Republic of Korea; yhchung{at}


Aims Longstanding liver inflammation leads to hepatic regeneration and fibrosis, which subsequently progresses to cirrhosis in some patients with chronic hepatitis B virus (HBV) infection. It remains unclear, however, if the histological severity of chronic hepatitis B (CHB) may determine the development of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the effects of necroinflammation and fibrosis at presentation of CHB on the development of HCC.

Methods Medical records and radiographs of 796 biopsy-confirmed CHB patients were reviewed retrospectively for a median period of 107 months (6–218) (median age 34 years (18–64), male:female 636:160). Eighty-five per cent (680/796) of patients were treated with antiviral agents such as interferon alpha and/or lamivudine. All the patients were followed at a regular interval of 3–6 months with routine laboratory tests. Abdominal imagings together with serum alpha-fetoprotein were checked every 6–12 months to detect new HCC. Necroinflammation and fibrosis were assessed semiquantitatively. Univariate and multivariate analyses were performed to identify significant risk factors for HCC.

Results HCC developed in 3.4% (27/796) of patients during follow-up. The overall cumulative occurrence rates of HCC were 0.5% and 3.5% at 5 and 10 years, respectively. In multivariate analysis, age over 40 years (p<0.001), advanced fibrosis (p=0.006) and severe lobular activity (p=0.038) at presentation were independent risk factors for the development of HCC.

Conclusion Advanced fibrosis and severe lobular activity rather than porto–periportal activity on histology at presentation of CHB are independent predisposing risk factors for the development of HCC.

  • Colorectal cancer
  • fibrosis
  • gall bladder
  • haematology
  • hepatitis B
  • hepatocellular carcinoma
  • histopathology
  • liver
  • liver cancer
  • oncogenes
  • pancreas
  • p53
  • prognosis

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  • Funding This work was supported by a grant from Asan Institute for Life Science, Asan Medical Center, Republic of Korea (no AILS09-096).

  • Competing interests None.

  • Ethics approval The study was approved by the Investigation and Ethics Committee for Human Research at the Asan Medical Center, Seoul, Korea.

  • Provenance and peer review Not commissioned; externally peer reviewed.