Care of Patients With Hepatitis C and HIV Co-Infection

Vincent Soriano; Massimo Puoti; Mark Sulkowski; Stefan Mauss; Patrice Cacoub; Antonietta Cargnel; Douglas Dieterich; Angelos Hatzakis; Jurgen Rockstroh

Disclosures

AIDS. 2004;18(1) 

In This Article

Liver Transplantation in HIV-Co-Infected Patients

Background

HIV-infected patients with end-stage liver disease develop classic complications of decompensated cirrhosis, including ascites, jaundice, gastrointestinal bleeding, spontaneous peritonitis and encephalopathy. The only treatment available at this stage is orthotopic liver transplantation (OLT). Initial attempts before the introduction of highly active antiretroviral therapy (HAART) regimens provided very poor results.[106] Those reports showed that only a small percentage of transplanted HIV-positive recipients maintained good organ function, whereas most experienced an accelerated course to AIDS. Since the introduction of HAART, HIV-infected liver transplant recipients have improved their short and mid-term survival. Now, the outcome of transplantation is no longer compromised as long as HIV infection is controlled with HAART in the post-transplant period.

Table 5 summarizes the experience with OLT in HIV-infected patients during the HAART era.[106,107,108,109,110,111,112,113,114,115,116] Although cases came from different institutions, the criteria used for liver transplantation were quite similar. In general, candidates did not have prior history of opportunistic infections, CD4 cell counts greater than 100 cells/µl and undetectable plasma HIV-RNA on HAART. Alternatively, in subjects with detectable viremia, they had available drugs for successful treatment in the post-OLT period. There were at least 17 patients with end-stage liver disease due to chronic hepatitis C who underwent OLT and 12 (70%) remained alive, some of them up to 2 years. In one of the largest series, Roland et al.[114] in 18 cases of OLT in HIV-positives has reported a survival rate at 1 year similar to that found at the United Network for Organ Sharing (UNOS), 92% versus 87.9%, respectively. Similar rates were seen for graft survival, 83% versus 81.4%. These findings have been confirmed at 3 years in a more recent report.[116]

The information available so far may be summarized in the following points: (i) The risk of opportunistic infections in the post-transplant period is very low when HIV replication is well controlled with HAART, maintaining most cases with undetectable viral loads. Furthermore, CD4 cell counts remain stable or even increase with HAART. Therefore, the use of standard immunosuppressive therapy in patients with well-controlled HIV infection does not increase their susceptibility to opportunistic infections or malignant conditions. (ii) Cyclosporin and tacrolimus can inhibit HIV replication in vitro and mycophenolate mofetil may potentiate the antiviral efficacy of abacavir. The benefit of these interactions is currently being explored. (iii) There are important pharmacokinetic interactions between some antiretroviral drugs, protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors and immunosuppressive agents, mainly cyclosporin and tacrolimus. PI may increase the levels of cyclosporin and tacrolimus, whereas non-nucleoside reverse transcriptase inhibitors may reduce their levels, because of their opposing effects over the cytochrome p450. These interactions have caused some episodes of acute rejection in patients who stopped PI while taking calcineurin-inhibitors. Therapeutic drug monitoring of immunosuppressive agents is mandatory when taking antiretroviral drugs. (iv) Hepatotoxicity associated with a HAART regimen can also be observed in liver allografts, and liver function should be closely monitored. (v) HCV recurrence is very frequent after OLT, and leads to cirrhosis in nearly 20% of cases within 5 years. The rapid progression of HCV-related liver disease in HIV-infected recipients represents a major drawback and the main reason for a shorter life expectancy of these patients. Standard anti-HCV therapy must be prescribed as early as possible (1-3 months after OLT) following the recommendations stated in point 3. In addition, other approaches such as pre-emptive therapy (i.e. using IFN shortly before transplantation in the case of living donors) should be explored; and (vi) As survival in the waiting list seems to be much shorter in HIV-co-infected patients, strategies to make available liver transplantation sooner after a patient's assignment to this procedure should be underlined.

Panel Recommendation

All HIV-infected patients with end-stage liver disease as a result of HCV should be considered as candidates for liver transplantation as long as they do not have advanced HIV disease. In those with severe immunodeficiency (< 100 CD4 cells/µl), the control of HIV replication and immune restoration should be prioritized. The evaluation and the pre and postoperative medical management of HIV-positive candidates for OLT must include an interdisciplinary team composed of a hepatologist, infectologist, surgeons, psychologists, social workers and members of alcohol, heroine and cocaine detoxification programmes. HIV-positive candidates should have CD4 cell counts greater than 100 cells/µl and plasma HIV-RNA levels below 200 copies/ml, or the chance of becoming undetectable using optional drugs for successful treatment after transplantation. Moreover, they should have abstained from the consumption of alcohol and illegal drugs for at least 6 months. Patients with a good immunological response to HAART but a previous history of AIDS-related opportunistic infections or neoplasms (including Kaposi's sarcoma, cervical carcinomas and anal squamous carcinomas) deserve special attention, given the potentially higher risk of relapses of those conditions using immunosuppressors. SCORE: B2.

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