Combined liver-kidney transplantation in an HIV–HCV-coinfected patient with haemophiliaписьмо
Аннотация: Prior to the development of viral inactivation procedures in the mid-1980s, virtually all haemophilic patients who had previously received large pool plasma-derived clotting factor concentrates were infected with hepatitis C virus (HCV). A considerable number of these patients were also infected with HIV [1,2]. We describe for the first time a case of combined liver and kidney transplantation (liver-KTx) in an HCV/HIV-coinfected patient with severe haemophilia A. The patient was a 38-year-old Caucasian man with HCV cirrhosis. He was diagnosed with haemophilia A at age 1 year. He was infected with HCV and HIV due to repeated haemotransfusions and factor-VIII administrations. His coagulation disorder was responsible for clipping arthropathy. The antiretroviral therapy was based on lamivudine, abacavir, and atazanavir. Laboratory studies (7 months before transplant) revealed alanine transaminase 44 IU/l [normal (nl) range < 40], aspartate transaminase 71 IU/l (nl < 37), total serum bilirubin 1.55 mg/dl (nl 0.2–1.2 mg/dl), prothrombin time 38% (nl 70–100%), activated partial thromboplastin time 116 s (nl 26–38 s), platelets 62.000/μl, factor-II 82%, factor-V 103%, factor-VII 102%, factor-VIII 0.4%, factor-VIII-inhibitor 0.1 IU/ml, and factor-X 72%. The patient's liver disease was classified as Child-Pugh C, Model for End-Stage Liver Disease score 21, United Network for Organ Sharing 2A. Estimate of glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) formula was 43 ml/min/1.73 m2 (stage 3 of chronic kidney disease). Anti-hepatitis Bs, anti-hepatitis Be, anti-HCV, and cytomegalovirus (CMV) immunoglobulin G were positive, and HbsAg and CMV immunoglobulin M were negative. Serum HCV-RNA was 8.19 × 105 IU/ml (genotype of 1b), CD4 cell count was 205/μl (44.6%) and plasma HIV-RNA was less than 50 copies/ml. Computerized tomography showed abundant ascites, splenomegaly, and cirrhosis. The patient remained well until March 2007, when fever, arterial hypertension, macroscopic haematuria, and oliguria occurred with swelling of the limbs, ascites, and right pleural effusion; eGFR by MDRD formula was 18 ml/min/1.73 m2 (stages 4–5 of chronic kidney disease). Progressive impairment of renal function occurred and the patient underwent haemodialysis. Given the deteriorated liver function and lack of improvement in kidney function, a combined liver-KTx work-up was started. In April 2007, the patient underwent successful surgery. The donor was a 58-year-old man deceased due to cerebral haemorrhage. Liver transplantation was performed by standard piggy-back placement. The kidney was transplanted extraperitoneally in the right iliac fossa. A total of 8 U of packed red cells and 2 U of fresh frozen plasma were infused during the 13-h procedure. Heat-treated and purified factor-VIII concentrates were administrated (in four parts) preoperatively, intraoperatively, and postoperatively (for 48 h only) at doses of 60, 30, and 60 U/kg/ day, respectively. The first measurement of native factor-VIII level (without substitution) on day 5 was normal (92%). Histological examination of the explanted liver revealed portal fibrosis with septa and nodular regeneration. No evidence of hepatic tumour was found. The immunosuppressive regimen was based on i.v. induction with 2 mg/kg of basiliximab and 1 g methylprednisolone and subsequent oral administration of cyclosporine and prednisolone 20 mg od. A second dose with basiliximab (1 mg/kg) was administered on day 7. The cyclosporine was suspended 15 days after surgery and replaced with sirolimus (trough level of 8–12 ng/ml). Steroid therapy was gradually stopped 3 months post-liver-KTx. The same pretransplantation antiretroviral therapy association was introduced after 20 days when the CD4 cell count was 307/μl (43%) and HIV-RNA was less than 50 copies/ml. The postoperative course was complicated by a biliary fistula treated successfully by positioning a biliary stent through endoscopic retrograde cholangiopancreatography. The patient was seen 1 year after combined liver-KTx. He underwent routine liver biopsy and histological findings were normal, as were the liver and renal function test results. Before the introduction of highly active antiretroviral treatment (HAART) in the mid-1990s, HIV-related complications were considered to be the leading cause of morbidity and mortality in HIV/HCV-coinfected patients and the importance of HCV infection was underplayed [2]. However, as the widespread use of HAART has dramatically improved both survival and progression to AIDS, previously insignificant comorbidities, such as hepatitis C infection and HIV-associated nephropathy, have assumed increasing prominence [2–7]. We believe that HCV-related end-stage liver disease together with irreversible renal failure, in the context of HIV co-infection, does not close the door on a combined liver-KTx opportunity. However, common posttransplant management criteria could be inadequate in this population, and further investigations into other immunosuppressant properties are instead needed. In this setting, due to its features, such as anti-HIV property [8–12], lower nephrotoxicity, and the recently suggested effect on HCV replication [13], sirolimus could play a leading role. Acknowledgements R.B. wrote the manuscript; F.D.B. and M. S. and G.E.G. participated in writing the manuscript; M.M., N.D.R., R.M. and A.R. were patient physicians (Transplant Center); and S.C. and G.G. were patient physicians (Clinic of Infectious Diseases). All the authors were involved in the clinical management of the case and the writing of the article. There are no conflicts of interest.
Год издания: 2008
Авторы: Roberto Ballarin, Fabrizio Di Benedetto, Michele Masetti, Mario Spaggiari, Nicola De Ruvo, Roberto Montalti, Antonio Romano, Stefania Cocchi, Giovanni Guaraldi, Giorgio Enrico Gerunda
Издательство: Lippincott Williams & Wilkins
Источник: AIDS
Ключевые слова: Hepatitis C virus research, HIV/AIDS drug development and treatment, Pneumocystis jirovecii pneumonia detection and treatment
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Открытый доступ: bronze
Том: 22
Выпуск: 15
Страницы: 2047–2049