TREATMENT WITH PEGYLATED INTERFERON BEFORE TRANSPLANTATION IMPROVES POSTTRANSPLANT OUTCOME IN DIALYSIS PATIENTS INFECTED WITH HCV

Uvod: Dijalizni bolesnici infi cirani HCV kandidati su za transplantacijsko liječenje, no dugoročno preživljenje ovih bolesnika i transplantiranog bubrega lošije je no u neinfi ciranih bolesnika. Primarni cilj ovog rada je usporedba jednogodišnjeg i trogodišnjeg preživljenja transplantata i bolesnika koji su u predtransplantacijskom razdoblju liječeni pegiliranim interferonom alfa 2 a (PEG-INF) (PEG DA skupina) i onih kod kojih ovo liječenje nije provedeno (PEG NE skupina). Sekundarni cilj je praćenje posttransplantacijskih komplikacija i to odgođene funkcije transplantata, odbacivanja transplantata, uroloških komplikacija (infekcije rane, urinom, limfokela, krvarenja), učestalost virusnih infekcija (infekcije polioma virusima -BK virusom, JS virusom, citomegalovirusom - CMV, te varicela-zoster virusom - VZV), te pojavnost neoplazmi. Bolesnici i metode: Retrospektivna analiza učinjena je pregledom medicinske dokumentacije 28 bolesnika s kroničnom HCV infekcijom koji su liječeni transplantacijom bubrega u KBC Zagreb (2007.-2010.). Devet od 28 bolesnika liječeno je pegiliranim interferonom alfa 2a (PEG-INF)-135 ug s.c. tjedno tijekom 48 tjedana, jednu do četiri godine prije transplantacije. Prosječna životna dob u trenutku transplantacije bila je 48,8 (17-61) godina, prosječno liječenje dijalizom 14 (5-23) godina. Šest od devet bolesnika liječenih PEG-INF postigli su SVR te su bili HCV RNA negativni, a kod troje bolesnika nije postignut SVR. U svih bolesnika učinjena je kadaverična transplantacija bubrega, imunosupresivni protokol uključivao je indukciju basiliksimabom ili daclizumabom, inhibitor kalcineurina (ciklosporin ili tacrolimus), mikofenolat mofetil i steroide. Rezultati: Trogodišnje preživljenje transplantata iznosilo je 78 % u PEG NE skupini, 88 % u PEG DA skupini, preživljenje bolesnika 89 % u PEG NE skupini, a 100 % u PEG DA skupini. Posttransplantacijske komplikacije bile su rjeđe u PEG DA skupini. Odgođena funkcija transplantiranog bubrega zabilježena je u 44,4 % bolesnika u PEG DA skupini, a u PEG NE skupini u 57,8 %. Akutno odbacivanje transplantiranog bubrega imalo je ukupno 25 % naših bolesnika, 31,58 % u skupini PEG NE, a značajno manje - 11,11 % u skupini PEG DA; samo jedan bolesnik u PEG DA skupini (11,1 %) imao je akutno odbacivanje transplantata, naprama 6 bolesnika (32 %) u PEG NE skupini. Virusne infekcije bile su nešto učestalije u PEG NE skupini. Nije zabilježena značajnija razlika u učestalosti infekcije polioma virusima BK/JS (26,3 %/33,3 %) i infekcije VZV (10,5 %/11,1 %), dok je CMV infekcija bila manje učestala u PEG DA skupini (22 % naprama 42,1 %). Zabilježen je samo jedan malignom i to planocelularni karcinom kože u bolesnika PEG DA skupine. Zaključak: Kod dijaliziranih bolesnika s kroničnom HCV infekcijom potrebno je provesti liječenje pegiliranim interferonom ili DAA lijekovima prije transplantacije bubrega, jer se eradikacijom HCV smanjuje rizik, a poboljšava transplantacijski ishod. Naši rezultati pokazuju da je uspješno liječenje HCV infekcije pegiliranim interferonom reduciralo rizik akutnog odbacivanja transplantiranog bubrega.Introduction: Dialysis patients with hepatitis C virus (HCV) infection are candidates for transplantation, but long-term patient and graft survival is less favorable than in non-infected patients. The primary objective of this study was to compare three-year graft and patient survival in patients treated with pegylated interferon alfa 2 (PEG-IFN) before transplantation (PEG YES group) and patients without specifi c anti-HCV treatment (PEG NO group). The secondary target was tracking of the following post-transplant complications: delayed graft function, graft rejection, urologic complications (wound infection, urinoma, lymphocele, bleeding), viral infections (polyoma BK/JC virus infection, varicella-zoster (VZV) infection, cytomegalovirus (CMV) infection), and incidence of neoplasia. Subjects and Methods: A retrospective analysis was done by reviewing medical charts of 28 patients with chronic HCV infection that received renal allograft at Zagreb UHC (2007-2010). Nine of 28 patients received 135 μg of PEG-IFN 2a weekly for 48 weeks, 1-4 years before transplantation. The mean age at the time of transplantation was 48.8 (17-61) years, dialysis vintage 14 (5-23) years. Six (66.7%) patients achieved sustained virological response (SVR) and were HCV-RNA negative before transplantation, while three patients did not achieve SVR. All patients received kidney allograft from deceased donors, immunosuppressive protocol included basiliximab or daclizumab, calcineurin inhibitor cyclosporine or tacrolimus, mycophenolate mofetil, and steroids. Results: Three-year graft survival was 78% in the PEG NO group and 88% in the PEG YES group, with patient survival of 89% and 100%, respectively.Post-transplant complications were less frequent in the PEG YES group. Delayed graft function was observed in 44.4%, while in the PEG NO group it occurred in 57.8%. Acute rejection was recorded in 25% of our patients, 31.58% in the PEG NO group and signifi cantly less (11.11%) in the PEG YES group; only one (11.1 %) patient treated with PEG-IFN developed acute allograft rejection, as opposed to six (32%) patients in the PEG NO group. Viral infections were more frequent in the PEG NO group; there was no difference in polyoma BK/JC virus infection (26.3%/33.3%) and VZV infection (10.5%/11.1%), but CMV infection was less common in the PEG YES group (42.1 %/22.2%). Only one case of malignancy (squamous cell carcinoma) was observed in a patient from the PEG YES group. Conclusion: HCV positive patients should be treated with pegylated interferon before transplantation in order to eradicate HCV, thus eliminating one of the risk factors for adverse outcome after transplantation. Our results demonstrated that treatment with pegylated interferon reduced the risk of acute allograft rejection after kidney transplantation