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

• Published in: PloS one 2013-06, Vol.8 (6), p.e66457
• Main Authors: Su, Chien-Wei, Chiou, Yu-Wei, Tsai, Yi-Hsuan, Teng, Ruei-Dun, Chau, Gar-Yang, Lei, Hao-Jan, Hung, Hung-Hsu, Huo, Teh-Ia, Wu, Jaw-Ching
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens; Antiviral agents; Antiviral Agents - administration & dosage; Biology; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - virology; Care and treatment; Cell differentiation; Cirrhosis; Clinical medicine; Clonal deletion; Deletion mutant; Deoxyribonucleic acid; DNA; DNA, Viral - blood; DNA, Viral - genetics; Female; Follow-Up Studies; Gastroenterology; Gene deletion; Gene mapping; Genetic aspects; Genotypes; Hepatitis; Hepatitis B; Hepatitis B - blood; Hepatitis B - genetics; Hepatitis B - therapy; Hepatitis B Surface Antigens - blood; Hepatitis B Surface Antigens - genetics; Hepatitis B virus - genetics; Hepatocellular carcinoma; Hospitals; Humans; Liver; Liver cancer; Liver cirrhosis; Liver Neoplasms - blood; Liver Neoplasms - genetics; Liver Neoplasms - surgery; Liver Neoplasms - virology; Male; Medical prognosis; Medical research; Medicine; Middle Aged; Mortality; Multivariate analysis; Mutants; Mutation; Patients; Prognosis; Risk analysis; Risk factors; Sequence Deletion; Studies; Surgery; Survival; Therapy; Tumor removal; Ultrasonic imaging; Viral Load; Viruses; γ-Glutamyltransferase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066457

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