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Liver transplants for liver cancer in HIV infection

Co-infection with hepatitis B and C viruses can rapidly degrade the liver in the setting of HIV infection. Furthermore, both of these hepatitis viruses can eventually cause liver failure, liver cancer and death. Several studies have found that about 25% of liver-related deaths in HIV-positive people in high-income countries are due to complications from liver cancer. In selected HIV-negative people with liver cancer, transplant with a new liver can be life saving.

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Researchers in France conducted a study to assess the risks and benefits of liver transplantation for HIV-positive people with liver cancer who were also co-infected with hepatitis B (HBV) or C (HCV). Their results found a high rate of successful transplant outcomes.

Study details

Between 2003 and April 2008, 147 patients (124 men and 23 women) were referred for treatment at Hôpital Paul Brousse in Villejuif, France, because of liver cancer. This diagnosis was based on results from CAT scans or biopsy.

Meetings with a large team of the following specialists were convened to review the results of medical assessments and make decisions about which patients would get a liver transplant:

  • liver surgeons
  • hepatologists
  • virologists
  • oncologists
  • radiologists

People who were not placed on the waiting list for a transplant had these complications:

  • spontaneous bleeding in blood vessels near the tumour(s)
  • tumours outside the liver
  • history of other cancers in the past five years

Of the 147 patients, assessments found that 86 had severely damaged livers. Specifically, these 86 people had cirrhosis, as their healthy liver tissue had been replaced with useless scar tissue, and 21 of these 86 were HIV positive.

Grafts of new livers or parts of livers were transplanted. After transplantation, immunosuppression was provided by cyclosporine- or tacrolimus-based regimens. All patients received corticosteroids; these were gradually withdrawn between three and six months after transplantation. Patients were given comprehensive medical monitoring and also received ultrasound liver scans.

The basic profile of 21 HIV-positive participants who were placed on the waiting list for a liver transplant was as follows:

  • 85% men, 15% women
  • age – 48 years
  • HBV co-infection – 9%
  • HCV co-infection – 80%
  • HBV and HCV co-infection – 9%

Using a scoring system called MELD (the model for end-stage liver disease) that is useful for predicting survival, overall most HIV-positive patients on the transplant list had a low risk of death in the next three months.

Results—On the waiting list

While on the waiting list for a transplant, 61% of HIV-positive patients received TACE, or transarterial chemoembolization. In this procedure, doctors, guided by X-ray or other scans use a thin flexible tube to penetrate the artery that supplies fresh blood to the liver and any tumours there. Small doses of chemotherapy are then piped through the tube and this bathes the tumour(s), damaging them. After chemotherapy is applied, the smaller blood vessels that supply blood to the tumour(s) are blocked. Both of these actions help to slow down the growth of tumours and can extend the survival time of people on the waiting list.

AFP

Assessment of alpha-fetoprotein (AFP) is an important part of liver cancer care. AFP has no known function in healthy adults. However, in certain conditions, including testicular cancer, liver cancer and tumours from other parts of the body that have spread to the liver, AFP levels rise.

Disappearing from the waiting list

Researchers found this trend: HIV-positive patients were more likely to leave the waiting list without a liver transplant. Usually this departure from the waiting list happened within six months after being listed. This greater dropout rate was likely due to worsening health because medical records showed that AFP levels rose more quickly among HIV-positive patients, suggesting the spread of cancer within the liver. This likely resulted in the appearance of complications. All of the people, both HIV negative and HIV positive, who prematurely left the waiting list subsequently died. None of the HIV-positive people who prematurely left the waiting list had a CD4+ cell count below 100 cells.

Transplantation

In total, 16 HIV-positive and 58 HIV-negative people who were on the waiting list received a transplant. In the first two months after transplant, three people died as follows:

  • one HIV-negative and one HIV-positive person – complications from a burst artery to the liver
  • one HIV-negative person – complications from multiple organ failure

Overall survival rates

At one year

  • HIV-positive people – 81%
  • HIV-negative people – 74%

Recurrence of liver cancer occurred in 31% of HIV-positive people given a transplant and in 15% of HIV-negative people. This difference was not statistically significant, likely because the number of people used for comparison was relatively small. Four of the HIV-positive people whose liver cancer recurred died. Moreover, when liver cancer recurred, HIV-positive people appeared to die twice as fast as HIV-negative people. According to the researchers, increases in AFP of more than 15 g/uL per month while on the waiting list were highly predictive of a recurrence of cancer after transplantation.

The French researchers noted that their study raises several important issues:

  • Monitoring AFP levels while patients are on the waiting list is very useful for predicting (1) survival before transplantation and (2) the risk of liver cancer recurring after transplant.
  • As none of the HIV-positive patients on the waiting list dropped out because of low CD4+ cell counts, therapy for liver cancer may help HIV-positive people on the waiting list survive until a new liver is ready.

The present study was based on a small number of HIV-positive patients with a relatively short period of monitoring after transplantation. So these findings need to be interpreted with caution. However, the study does provide valuable information that may save the lives of other HIV-positive people on the waiting list for a liver transplant.

REFERENCES:

  1. Lanoy E, Spano JP, Bonnet F, et al. The spectrum of malignancies in HIV-infected patients in 2006 in France: The ONCOVIH study. International Journal of Cancer. 2011 Jan 4. [Epub ahead of print].
  2. Simard EP, Pfeiffer RM, Engels EA. Cumulative incidence of cancer among individuals with acquired immunodeficiency syndrome in the United States. Cancer. 2011 Mar 1;117(5):1089-96.
  3. Vibert E, Duclos-Vallée JC, Ghigna MR, et al. Liver transplantation for hepatocellular carcinoma: the impact of human immunodeficiency virus infection. Hepatology. 2011 Feb;53(2):475-82.