Survival after a liver transplant has improved significantly
in people with HIV and hepatitis C co-infection since the introduction of
direct-acting antiviral treatment for hepatitis C, US researchers report in the
journal Transplantation Direct.
Due to faster progression of liver damage in people
co-infected with HIV and hepatitis C, people with both viruses are especially
likely to develop end-stage liver disease and require a liver transplant. Prior to the introduction of direct-acting antiviral (DAA) therapy from 2013, people with HIV had worse outcomes after liver transplantation, irrespective of hepatitis C co-infection.
In co-infected people, liver transplantation may only offer a temporary respite from liver damage, as untreated hepatitis C begins to damage the transplanted organ. DAA treatment after transplantation results in a high cure rate but the extent to which transplant outcomes have improved since the introduction of DAAs has been unclear.
Glossary
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
- direct-acting antiviral (DAA)
A drug which prevents hepatitis C from reproducing by blocking certain steps in its lifecycle.
Another factor that remains unclear when assessing
transplant outcomes in people with HIV is the impact of receiving a liver from
an HIV-positive donor. The 2013 HOPE Act authorised the use of organs from
HIV-positive donors for transplants to people living with HIV, but the number
of transplants resulting from the HOPE Act in the United States has been low,
perhaps due to a lack of evidence on survival.
Researchers at major liver disease treatment centres in the
United States used data from the United Network for Organ Sharing / Organ
Procurement and Transplantation Network database to investigate whether transplant outcomes for people with HIV had improved since the introduction of DAA treatment.
They compared transplant outcomes in people with HIV with
and without hepatitis C co-infection to those in people infected with hepatitis
C alone and in people without either virus. They also compared outcomes in the
four groups between two periods: prior to the introduction of DAAs (2008-2012) and after the introduction of DAAs
(2014-2019). Transplants in 2013 were excluded because DAA
access was inconsistent and the less effective first generation of DAAs were used with pegylated interferon.
Between 2008 and 2019, 64,860 liver transplants were carried
out in people with a known HIV status. In the pre-DAA period, 24,238
transplants took place, 68 in co-infected people and 49 in people with HIV
alone. Transplant recipients with HIV were younger and had shorter waitlist
times than other recipients, while all transplant recipients without hepatitis
C had higher MELD scores, indicating more severe liver damage, and were more
likely to be on life support at the time of transplantation.
People with HIV and hepatitis had a significantly higher
risk of graft failure (hazard ratio 1.85, 95% CI 1.31-2.59) in the pre-DAA era
compared to people without either virus. This difference in risk disappeared in
the DAA era, so that by three years after transplant, 81% of recipients with
HIV and hepatitis C remained alive and had not suffered rejection of the donor
organ (graft failure), compared with 58% in the pre-DAA era (p = 0.006). Survival
was 100% over a median follow-up period of 656 days among graft recipients with
HIV who had chronic hepatitis C at the time of transplant.
Three-year graft survival in people who were not co-infected
with HIV and hepatitis C was similar; 80% of people with HIV alone, 83% of
people with hepatitis C alone and 84% of people with neither virus remained
alive without rejection of the donor organ.
Overall survival did not differ either; 84% of people with
HIV and hepatitis C remained alive after three years, compared to 81% in people
with HIV alone, 84% in people with hepatitis C alone and 86% in people without
either virus.
Survival in the 46 recipients of livers from HIV-positive donors did not differ from the overall survival; 82% of people with HIV who received a graft from an HIV-positive donor remained alive without rejection of the donor organ after three years.
The study authors say that the small number of transplants
from HIV-positive donors to other people with HIV suggests that the HOPE Act
provision is still underused. They speculate that transplant centres may be
reluctant to carry out transplants in people with HIV due to a lack of evidence
that prospects for graft survival have improved in people with HIV. Six
transplant centres accounted for 40% of transplants in people with HIV, again
suggesting lack of confidence or experience.
They also note that surgeons may over-estimate the risk of
HIV transmission from blood during transplant procedures.
“Our results should offer reassurance to transplant centers
and to encourage timely referral of HIV patients with decompensated cirrhosis
for transplantation evaluation, including patients coinfected with HCV,” the
authors conclude.