Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients.

The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic liver transplantation (OLT) is not precisely determined. The aim of this analysis is to study the progression of disease recurrence and its impact on patient and graft survival. Data for 300 patients who underwent OLT for hepatitis C were analyzed regarding the incidence of histological recurrence, risk factors, immunosuppressive regimen, rejection episodes, and survival. For patients with histological recurrence, the timing and risks for disease progression were analyzed. Data for 30 patients who underwent retransplantation were studied. Histological recurrence occurred in 40.3% of patients, 27.2% of whom progressed to bridging fibrosis or cirrhosis. Eighty-seven percent of the patients experienced recurrence of disease within 24 months of OLT. Patients with histological recurrence within 6 months of OLT had an increased risk for progression to cirrhosis compared with patients with recurrence later than 6 months (risk ratio, 2.3). Recurrence within 1 year was associated with decreased patient and graft survival rates at 1 and 5 years (65.1% and 56.4% versus 80.6% and 78.4%; P =.004 and P =.0008, respectively). Patients with histological recurrence had a greater incidence of acute cellular rejection, as well as multiple episodes of rejection, steroid-resistant rejections, and greater cumulative doses of corticosteroids. Histological recurrence after OLT for hepatitis C is common and usually occurs within 2 years of OLT. Early recurrence negatively affects patient and graft survival. Host factors impacting on recurrence need further study. A relation between the hepatitis C virus, allograft rejection, and immunosuppression exists and needs investigation.

Long-term outcome of patients transplanted with livers from hepatitis C-positive donors.

BACKGROUND: The use of hepatitis C serology-positive donors has become an option in patients affected by hepatitis C (Hep C) end-stage liver disease. Previous studies with less than 1 year of follow-up have suggested that there is no difference in early patient and graft survival. The aim of our review is to confirm with a longer follow-up (a minimum of 1 year) that the use of these organs is safe and that patient and graft survival are comparable to those of patients with Hep C who received Hep C-negative grafts. METHODS: Between 1985 and 1995, 213 patients were transplanted with a diagnosis of Hep C. Seventy-six patients were excluded from the study, 47 for insufficient follow-up and 29 because the diagnosis of recurrence was not certain. Twenty-two patients received Hep C+ donor grafts and 115 patients received Hep C-donor grafts. These two groups were evaluated to assess the rate and severity of recurrence by serial biopsies and to assess patient and graft survival. RESULTS: Recurrent Hep C was documented by biopsy in 12 of 22 patients who received Hep C+ donor grafts. Of these 12 patients, 9 had mild chronic hepatitis, 2 had fibrosis, and 1 had cirrhosis. Ten of the 22 patients had normal biopsies. Of the patients who received Hep C- grafts, 48 of 115 had recurrent disease. Of these 48 patients, 23 had mild chronic hepatitis, 15 had fibrosis, and 10 had cirrhosis. Sixty-seven of 115 had normal biopsies. The recurrence rate was 54.55% in the Hep C+ donor grafts and 41.74% in the Hep C- donor grafts (P=NS). Patient and graft survival at 4 years after transplant were 83.9% and 71.9% in the Hep C+ donor grafts and 79.1% and 76.2% in the Hep C- donor grafts, respectively (P=NS). CONCLUSIONS: Our study suggests that Hep C+ donors can be used with excellent long-term results and that the progression of the recurrent disease does not seem to be affected by the pre-existence of the Hep C virus in the donor.

Conversion from Sandimmune to Neoral in organ transplant recipients.

The pharmacokinetic profiles of Sandimmune and Neoral vary considerably among transplant recipients. Cyclosporine exposure is far more consistent with Neoral than it is with Sandimmune. Because intrapatient variability of drug exposure has been demonstrated to be a risk factor for chronic rejection, this difference becomes important. Neoral also has a linear dose response and a stronger correlation between trough level and drug exposure. Dose linearity greatly facilitates accurate dose titration. Results of controlled studies in which kidney, liver, and heart transplant recipients were converted from Sandimmune to Neoral have shown that conversion on a 1:1 mg basis results in more predictable bioavailability and often in reductions in cyclosporine dose. Carefully monitored conversion has not been associated with increased side effects, and any side effects that do emerge can usually be managed by taking Neoral with food, changing the dose from every 12 hours to every 8 hours, or through dose reduction.

Influence of donor and recipient gender on the outcome of liver transplantation.

BACKGROUND: Gender is currently not a criterion in the allocation of scarce donor organs. The purpose of this study was to determine the effects of gender on patient and graft survival, incidence of rejection, and postoperative complications after orthotopic liver transplantation. METHODS: During a 10-year period, 1138 liver transplants were performed on 1010 adult patients at Baylor University Medical Center. In this study, 994 patients with at least 6 months of posttransplant follow-up were reviewed. The four combinations of gender match and mismatch included: group 1, donor female to recipient female (n=229); group 2, donor female to recipient male (n= 126); group 3, donor male to recipient female (n=247); and group 4, donor male to recipient male (n=392). These groups were evaluated for patient survival, graft survival, episodes of rejection, incidence of chronic rejection, and postoperative complications. RESULTS: All groups were similar with respect to recipient age, underlying medical condition, incidence of bacterial and viral infections, postoperative biliary complications, and the incidence of chronic rejection. Female recipients had the highest incidence of early rejection (0-6 months, 70%) compared with male recipients (60%, P<0.039). Postoperative vascular complication (10%) was highest in group 3 (P<0.01). The two-year graft survival rate for groups 1, 3, and 4 was 76.2%, 75.6%, and 73.5%, respectively. Group 2, donor female to recipient male, had a 2-year graft survival rate of 55.9% (P<0.0001). This finding is not explained by the incidence of early rejection. Chronic rejection does not appear to be contributory. The mean donor age for groups 1, 3, and 4 was 35.7, 25.8, and 30.4 years, respectively. The mean donor age for group 2 was slightly older, at 41.6 years (P<0.0001). This difference, while statistically significant, is of unknown clinical relevance. A multivariate analysis controlling for donor age confirmed the decreased graft and patient survival rates in the donor female to recipient male group. CONCLUSIONS: The decreased graft survival rate in male recipients of female livers warrants further study and may argue for modifying the current management of adult male liver transplant recipients.