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Abstract Recurrent HCV infection after liver transplantation (LT) is the most frequent cause of death and represents two-thirds of graft failures and associated with significant morbidity. This study was a descriptive retrospective study aimed to estimate the frequency of recurrent HCV disease after LT and its response to different treatments regimens and was conducted on 124 chronic HCV liver transplanted patients with positive serum HCV RNA by PCR technique following LT. Patients were selected from the International Medical Center (IMC), Cairo, Egypt during the period from September 2005 till January 2016. The studied patients were classified into two groups based on the approved treatment protocols of HCV therapy following LT (Interferon based therapy from September 2005 till January 2014 Vs DAA based therapy from January 2014 till January 2016): GI: Included 106 patients who were underwent LT before January 2014. According to the histopathological interpretation of liver biopsy following LT, they were sub classified into two subgroups;G IA[included 41 liver transplanted patients with histopathological evidence of recurrent HCV disease on liver biopsy. They were 32 males (78%) and 9 females (22%), their ages ranged from 45 year to 58 years with the mean age of 49.8±4.6 years. These patients were candidate for interferon based therapy] and G IB [included 65 liver transplanted patients without histopathological evidence of recurrent HCV disease on liver biopsy. They were 52 males (80%) and 13 females (20%), their ages ranged from 42 year to 59 years with the mean age of 50.0±5.6years. These patients received DAA after their approval]. G II: Included18 patients who were underwent LT from January 2014 till January 2016 and they were candidate for DAA therapy based on recurrent HCV viremia following LT. They were 14 males (77.8%) and 4 females (22.2%), their ages ranged from 51 year to 62 years with the mean age of 54.8±4.6 years. All studied patients were subjected to preoperative evaluation for LT including full history tacking and clinical examination followed by laboratory and radiological work up. All of them received adequate immunosuppression after LT, G 1 patients under went annual liver biopsy to assess the recurrent HCV disease in their grafts and sub sequent initiation of anti-viral therapy which based on interferon /ribavirin(IFN/RIB) combination therapy. After availability of DAA drugs, treatment of recurrent HCV infection was recommended as early as possible after stabilization of the patient condition (generally after 3 months of LT) based on the presence of post LT HCV viremia. In the present study, various regimens of DAA combination therapies was initiated in 101 recipients [GI recipients who had no evidence of recurrent HCV disease in their liver biopsies(65), GI recipients with previous IFN/RIB failure (18) and GII recipients (18)]. Statistical analysis of the presenting data was done using SPSS method and revealed the following: Child A, Child B and Child C liver cirrhosis were present in 0.8%, 23.4% and 75.8% in all recipients respectively. Indication for LT was ESLD in 92.8% in all recipients (115 patients) combined with HCC in 57.3% of them (71 patients), while HCC alone was the indication for LT in 7.2% of all recipients (9 patients). Non of the HCC patients outside the Milan criteria for LT. None of the studied donors had Steatosis <25 % in their liver biopsy and graft recipient weight ratio (GRWR) in all studied patients was < 0.8 and the overall male to female ratio was about 6.75:1 (5.63:1 in GI and 18:1 in GII donors). Steroid used for induction therapy in all patients and it was combined with basiliximab in 3 patients only. Ninety-four recipients (75.8%) received TAC while 30 recipients (24.2%) received cyclosporine A during induction and maintainace therapy with or without MMF, MFA or sirolimus. All GI and GII recipients were positive for serum PCR of HCV RNA following LT. In G I recipients, histopathological study of liver biopsy after LT revealed presence of necroinflamatory activity in 61 (57.6%) recipients and various grades of fibrosis in 41(38.7%) recipients. None of the recipients had fibrosing chestatic hepatitis in their liver biopsy. Forty eight weeks IFN/RIB combination therapy was initiated in 41 out of 106 recipients who had histopathological evidence of recurrent HCV disease. Twenty three of these patients (56.1 %) had achieved SVR-6 months following end of treatment, while 18 patients (43.9%) failed to achieve SVR; primary non response (5 patients), relapsers (11 patients) and treatment discontinuation due to complications (2 patients). Various regimens of DAA combination therapies were initiated in 101 recipients [GI recipients who had no evidence of recurrent HCV disease in their liver biopsies (65 patients), GI recipients with previous IFN/RIB failure (18 patients) and GII recipients (18 patients)]. Six IFN/RIB experienced recipients received 12 weeks SOF/RIB/IFN combination therapy and the SVR was achieved in 5 of them (83.3%) while 60 recipients received 24 weeks SOF/RIB combination therapy (48 naive and 12 IFN/RIB experienced) and the SVR was achieved in 44 of them (73.3%). Eight naïve recipients received 12 weeks SOF/SIM combination therapy with SVR 12 weeks following end of treatment 100% while two naïve recipients received 12 weeks SOF/LED combination therapy with 100% SVR 12 weeks following end of treatment. Forty two recipients received 12 weeks SOF/DAC combination therapy [25 naïve and 17 experienced recipients (14 SOF/RIB failure, 2 IFN/RIB failure then SOF/RIB failure and 1 IFN/RIB failure then SOF/RIB/IFN failure)]. SVR 12 weeks following end of treatment was 100% in all of these patients. Finally, the overall response rate was 100% in regimens containing SOF/SIM, SOF/LED and SOF/DAC, while it was 83.3% in SOF/RIB/IFN regimen, 70.3% in SOF/RIB regimen and 56.1% in IFN/RIB regimen. |