HIV-HBV Coinfected Liver Transplant Recipients Have Outcomes Similar to Those of HIV Negative Patients

People with HIV were routinely excluded from liver and other organ transplantation until studies began to show that HIV positive individuals with well controlled HIV disease and relatively high CD4 cell counts could achieve outcomes similar to those of HIV negative transplant recipients.

Nevertheless, although liver transplantation is the acknowledged treatment of choice for HBV-infected individuals with end-stage liver disease, outcomes in HIV-HBV coinfected patients may be complicated by HIV disease progression or recurrent liver disease after transplantation.

As reported at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007), researchers conducted a study to evaluate the safety and effectiveness of liver transplantation for HBV-HIV coinfected patients. The Solid Organ Transplantation in HIV Study followed 16 coinfected individuals receiving liver transplants at several U.S. centers from 2003 through 2007. In addition, 60 HBV monoinfected liver transplant recipients with a median follow-up period of 21 months served as controls for the survival analysis.

HIV-specific criteria for transplantation included:

• Undetectable HIV viral load if on antiretroviral therapy, or prediction of full HIV suppression once treatment was started post-transplantation (since some individuals with advanced liver disease must discontinue HAART due to intolerance);
  
  
• A CD4 count above 100 cells/mm³ (or above 200 cells/mm³ if the patient had a history of opportunistic infections or cancers).

Standardized post-transplant prophylaxis to prevent HBV recurrence included hepatitis B immunoglobulin (HBIG) and the antiviral drugs tenofovir (Viread) plus lamivudine (Epivir-HBV) or emtricitabine (Emtriva), all of which are active against both HBV and HIV.

Serum samples were collected pre-transplant and at 12, 26, and 52 weeks and 2 years after transplantation. The investigators assessed patient and graft survival and HBV recurrence, defined as positive serum HBV DNA and hepatitis B surface antigen (HBsAg). Ultra-sensitive real-time PCR was used to detect HBV genomes using S-gene specific primers and fluorescent-labeled Taq-man based DNA probes.

• All 16 HIV-HBV coinfected transplant recipients were Caucasian males, with a median age of 46 years.
  
  
• The median pre-transplant CD4 count was 362 cells/mm³ (range 128-1070 cells/mm³).
  
  
• 1 patient had hepatocellular carcinoma and 2 were also infected with hepatitis C virus (HCV).
  
  
• HIV positive patients were followed for a median 8.5 months (range 0.46 to 36) after liver transplantation.
  
  
• At the time of transplantation, 68% were on anti-HBV drugs active against lamivudine-resistant HBV, and 50% had HBV DNA > 20 IU/mL.
  
  
• All patients remained HBsAg negative after transplantation on combination prophylaxis.
  
  
• However, 44% had low-level HBV viremia (mean 26 IU/mL; range 9-79 IU/mL), of whom 31% had detectable pre-transplant HBV DNA.
  
  
• The cumulative 1-year survival rate was 86% for the HIV-HBV coinfected patients compared with 93% for the HBV monoinfected individuals (P = 0.58; not a statistically significant difference).
  
  
• No patient died due to recurrent HBV infection in either group.

“Short-term outcomes in this cohort of HBV-HIV coinfected patients undergoing liver transplantation are comparable to HBV monoinfected patients,” the researchers concluded.

“Combination HBIG and antivirals effectively prevents serologically evident HBV infection in all patients, however, low-level viremia is intermittently detected in up to 44%,” they added. “The clinical significance of low-level viremia in the absence of HBsAg is unknown, but suggests long-term combination prophylaxis will be essential to prevent recurrence.”

University of California San Francisco, CA; University of Virginia, Charlottesville, VA; Columbia University, New York, NY; Cedars-Sinai, Los Angeles, CA; Harvard School of Medicine, Boston, MA; Tulane University, New Orleans, LA; University of Cincinnati, Cincinnati, OH.

11/13/07

Reference
CS Coffin, CL Berg, LM Dove. Survival and Risk of Hepatitis B Virus (HBV) Recurrence in HIV-HBV Coinfected Liver Transplant Recipients: Preliminary Findings from the HIV-TR Study. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston. November 2-6, 2007. Abstract 28.