The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients

J Gastroenterol. 2017 Mar;52(3):366-375. doi: 10.1007/s00535-016-1240-y. Epub 2016 Jul 15.

Abstract

Background: Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases.

Methods: Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed.

Results: Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325).

Conclusions: HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.

Keywords: HBV reinfection; HBcrAg; HBs gene mutations; Hepatitis B immune globulin; Liver transplantation.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / virology
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Hepatitis B Core Antigens / blood*
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / surgery*
  • Humans
  • Immunoglobulins / therapeutic use
  • Liver Neoplasms / surgery
  • Liver Neoplasms / virology
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local
  • Recurrence
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Immunoglobulins
  • hepatitis B hyperimmune globulin