Nucleos(t)ide analog(s) prophylaxis after hepatitis B immunoglobulin withdrawal against hepatitis B and D recurrence after liver transplantation

Transpl Infect Dis. 2016 Oct;18(5):667-673. doi: 10.1111/tid.12575. Epub 2016 Sep 7.

Abstract

Background/aims: Nucleos(t)ide analogs (NAs) have made a hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, this approach is considered controversial in patients transplanted for HBV and hepatitis D (HDV) co-infection.

Material/methods: All patients transplanted for HBV/HDV cirrhosis were evaluated. After LT, each patient received HBIG + NAs and then continued with NAs prophylaxis. All patients were followed up with HBV serum markers and HBV DNA, while anti-HDV/HDV RNA was performed in those with HBV recurrence.

Results: A total of 34 recipients were included (22 men, age: 46.7 ± 16 years). After HBIG discontinuation, NAs were received as monoprophylaxis (lamivudine [LAM]: 2, adefovir [AFV]: 1, entecavir: 9, tenofovir [TDF]: 12) or dual prophylaxis (LAM + AFV [or TDF]: 10 patients). Two (5.8%) of the 34 patients had HBV/HDV recurrence after HBIG withdrawal (median follow-up: 28 [range, 12-58] months). These 2 patients had undetectable HBV DNA at LT. Statistical analysis revealed that those with recurrence had received HBIG for shorter period, compared to those without recurrence (median: 9 vs. 28 months, P = 0.008).

Conclusions: We showed for the first time, to our knowledge, that maintenance therapy with NAs prophylaxis after HBIG discontinuation was effective against HBV/HDV recurrence, but it seems that a longer period of HBIG administration might be needed before it is withdrawn after LT.

Keywords: entecavir; glomerular filtration rate; hepatitis B and D co-infection; hepatitis B recurrence; hepatitis D; liver transplantation; renal function; tenofovir.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Coinfection / complications
  • Coinfection / prevention & control*
  • DNA, Viral / isolation & purification
  • Drug Therapy, Combination
  • Female
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / prevention & control*
  • Hepatitis D, Chronic / complications
  • Hepatitis D, Chronic / prevention & control*
  • Humans
  • Immunoglobulins / administration & dosage
  • Immunoglobulins / therapeutic use*
  • Lamivudine / administration & dosage
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / surgery
  • Liver Cirrhosis / therapy*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use
  • Secondary Prevention / methods*
  • Tenofovir / administration & dosage
  • Tenofovir / adverse effects
  • Tenofovir / therapeutic use
  • Treatment Outcome
  • Withholding Treatment
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Immunoglobulins
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Tenofovir
  • Adenine
  • hepatitis B hyperimmune globulin