Liver transplantation for hepatitis D virus/hepatitis B virus coinfection in Italy: An intention-to-treat analysis of long-term outcomes

Am J Transplant. 2025 Jul;25(7):1502-1514. doi: 10.1016/j.ajt.2025.03.003. Epub 2025 Mar 7.

Abstract

Patients with hepatitis D virus (HDV)/hepatitis B virus (HBV)-related end-stage liver disease candidates for liver transplantation (LT) have traditionally been regarded as a special population, although their outcomes are controversial. An intention-to-treat (ITT) analysis of long-term outcomes of HDV/HBV-coinfected patients waitlisted for LT in Italy, between 2011 and 2020, was performed and compared with HBV-monoinfected LT candidates. Of 1731 HBV-infected LT candidates, 1237 (71.5%) had HBV monoinfection and 494 (28.5%) HDV/HBV coinfection. At listing, HDV/HBV-coinfected patients were significantly younger, listed mainly for decompensated cirrhosis, and with fewer hepatocellular carcinoma (HCC) cases; (26% vs 65.8%; P <.0001) compared with HBV-monoinfected patients. HDV/HBV-coinfected patients showed better 5-year ITT survival (83.2%; 95% CI: 79.4%-83.4%, vs 71.6%; 95% CI: 68.8%-74.2%; P < .0001). ITT-multivariable analysis identified the presence of HCC, advanced recipient age, and high model for end-stage liver disease-Na scores as mortality risk factors. Five years after LT, 99.1% of HDV/HBV-coinfected patients received oral nucleos(t)ide analogs, with immunoglobulins against antigen of the hepatitis B virus in 91.8% of cases. HBV and HDV viral recurrences were 1.1% and 0.2%, respectively, whereas recurrent or de novo HCC were 8.9% and 0.3%, respectively. In Italy, HDV/HBV-coinfected patients waitlisted for LT showed more favorable outcomes compared with HBV-monoinfected patients, both before and after LT. These excellent results, from the largest cohort reported so far, suggest that HDV/HBV-coinfected LT recipients do not represent a risky population and may be considered for simpler long-term antiviral prophylactic strategies.

Keywords: chirrosis; hepatitis B infection; hepatitis D infection; hepatocellularcarcinoma; liver transplantation; outcomes; viral prophylaxis.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / virology
  • Coinfection* / mortality
  • Coinfection* / surgery
  • Coinfection* / virology
  • End Stage Liver Disease* / mortality
  • End Stage Liver Disease* / surgery
  • End Stage Liver Disease* / virology
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Hepatitis B virus* / isolation & purification
  • Hepatitis B* / complications
  • Hepatitis B* / surgery
  • Hepatitis B* / virology
  • Hepatitis D* / complications
  • Hepatitis D* / mortality
  • Hepatitis D* / surgery
  • Hepatitis D* / virology
  • Hepatitis Delta Virus* / isolation & purification
  • Humans
  • Italy / epidemiology
  • Liver Neoplasms / surgery
  • Liver Transplantation* / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Waiting Lists / mortality