The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy

PLoS One. 2013 Jun 21;8(6):e66457. doi: 10.1371/journal.pone.0066457. Print 2013.

Abstract

Background: Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.

Aims: To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.

Methods: A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.

Results: After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10(6) copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.

Conclusions: Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / surgery
  • Carcinoma, Hepatocellular* / virology
  • DNA, Viral* / blood
  • DNA, Viral* / genetics
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens* / blood
  • Hepatitis B Surface Antigens* / genetics
  • Hepatitis B virus / genetics*
  • Hepatitis B* / blood
  • Hepatitis B* / genetics
  • Hepatitis B* / therapy
  • Humans
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / surgery
  • Liver Neoplasms* / virology
  • Male
  • Middle Aged
  • Sequence Deletion*
  • Viral Load*

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens

Grants and funding

This work was supported by grants from the National Science Council of Taiwan (NSC 101-2314-B-075-013-MY2), Taipei Veterans General Hospital (V95C1-014, VGHUST100-G7-2-1), Yang-Ming University (101AC-T501, Ministry of Education, Aim for the Top University Plan), and the Center of Excellence for Cancer Research at TVGH (DOH101-TD-C-111-007), Taipei, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.