tacrolimus and Hypertension--Portal

Early results of a randomised trial showed reduced fibrosis due to recurrent HCV hepatitis with tacrolimus triple therapy (TT) versus monotherapy (MT) following transplantation for HCV cirrhosis. We evaluated the clinical outcomes after a median 8 years of follow-up, including differences in fibrosis assessed by collagen proportionate area (CPA).. 103 consecutive liver transplant recipients with HCV cirrhosis receiving cadaveric grafts were randomised to tacrolimus MT (n=54) or TT (n=49) with daily tacrolimus (0.1 mg/kg divided dose), azathioprine (1 mg/kg) and prednisolone (20 mg), the last tailing off to zero by 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. Time to reach Ishak stage 4 was the predetermined endpoint. CPA was measured in all biopsies. Factors associated with HCV recurrence were evaluated. Clinical decompensation was the first occurrence of ascites/hydrothorax, variceal bleeding or encephalopathy.. No significant preoperative, peri-operative or postoperative differences between groups were found. During 96 months median follow-up, stage 4 fibrosis was reached in 19 MT/11 TT with slower fibrosis progression in TT (p=0.009). CPA at last biopsy was 12% in MT and 8% in TT patients (p=0.004). 14 MT/ three TT patients reached HVPG≥10 mm Hg (p=0.002); 10 MT/three TT patients, decompensated. Multivariately, allocated MT (p=0.047, OR 3.23, 95% CI 1.01 to 10.3) was independently associated with decompensation: 14 MT/ seven TT died, and five MT/ four TT were retransplanted.. Long term immunosuppression with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis assessed by Ishak stage and CPA, less portal hypertension and decompensation, compared with tacrolimus alone. ISRCTN94834276--Randomised study for immunosuppression regimen in liver transplantation.

Topics: Anti-Inflammatory Agents; Azathioprine; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Hypertension, Portal; Immunosuppressive Agents; Liver Cirrhosis; Liver Failure; Liver Transplantation; Male; Middle Aged; Prednisolone; Recurrence; Tacrolimus; Time Factors

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 >or= 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 >or=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.

Topics: Adolescent; Adult; Aged; Azathioprine; Biopsy; Child; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Hepatitis C; Humans; Hypertension, Portal; Immunosuppressive Agents; Kaplan-Meier Estimate; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Prednisolone; Proportional Hazards Models; Recurrence; Risk Assessment; Risk Factors; Severity of Illness Index; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

The present study was designed to elucidate the effectiveness of portal decompression and FK506 (FK) pretreatment in extended hepatectomy in dogs. In the first set of experiment the effect of portal decompression was evaluated in two groups of dogs which underwent extended hepatectomies (80%) with or without (control) a side-to-side portacaval shunt. The presence of the shunt significantly (p < 0.05) improved the 7-day survival of the animals (57.1%) when compared with those of the control group (28.6%) and eventually the portal pressure was significantly lower and mean arterial pressure was significantly higher in the shunt group (p < 0. 05). Moreover, the animals with lower portal pressure (

Topics: Animals; Carcinoma, Hepatocellular; Dogs; Female; Hepatectomy; Humans; Hypertension, Portal; Liver Neoplasms; Liver Regeneration; Male; Portacaval Shunt, Surgical; Tacrolimus