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Outcome of recurrent hepatitis C virus after liver transplantation in a randomized trial of tacrolimus monotherapy versus triple therapy
Author(s) -
Manousou Pinelopi,
Samonakis Dimitrios,
Cholongitas Evangelos,
Patch David,
O'Beirne James,
Dhillon Amar P.,
Rolles Keith,
McCormick Aiden,
Hayes Peter,
Burroughs Andrew K.
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21907
Subject(s) - medicine , tacrolimus , gastroenterology , liver transplantation , immunosuppression , azathioprine , combination therapy , cirrhosis , hepatitis c , transplantation , regimen , surgery , randomized controlled trial , prednisolone , disease
Less potent immunosuppression is considered to reduce the severity of hepatitis C virus (HCV) recurrence after liver transplantation. An optimal regimen is unknown. We evaluated tacrolimus monotherapy versus triple therapy in a randomized trial of 103 first transplants for HCV cirrhosis. One hundred three patients who underwent transplantation for HCV were randomized to tacrolimus monotherapy (n = 54) or triple therapy with tacrolimus, azathioprine, and steroids (n = 49), which were tapered to zero by 3 to 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. The time to reach Ishak stage 4 was the predetermined endpoint. All factors documented in the literature as being associated with HCV recurrence and the allocated treatment were evaluated for reaching stage 4 and HVPG ≥ 10 mm Hg. No significant preoperative, perioperative, or postoperative differences, including the frequency of biopsies between groups, were found. During a mean follow‐up of 53.5 months, 9 monotherapy patients and 6 triple therapy patients died, and 5 monotherapy patients and 4 triple therapy patients underwent retransplantation. Stage 4 fibrosis was reached in 17 monotherapy patients and 10 triple therapy patients ( P = 0.04), with slower fibrosis progression in the triple therapy patients ( P = 0.048). Allocated therapy and histological acute hepatitis were independently associated with stage 4 fibrosis. HVPG increased to ≥10 mm Hg more rapidly in monotherapy patients versus triple therapy patients ( P = 0.038). In conclusion, long‐term maintenance immunosuppression with azathioprine and shorter term prednisolone with tacrolimus in HCV cirrhosis recipients resulted in a slower onset of histologically proven severe fibrosis and portal hypertension in comparison with tacrolimus alone, and this was independent of known factors affecting fibrosis. Liver Transpl 15:1783–1791, 2009. © 2009 AASLD.