Natural history of hepatitis C virus infection in adult renal graft recipients

Aim. To study the natural history of hepatitis C virus infection in renal transplantation, 464 HbsAg negative patients were prospectively studied from 1989. Methods. AntiHCV was tested by ELISA II and HCVRNA by Amplicor HCV RNA tests. Results. Two hundred nine patients were antiHCV positive (C+). HCVRNA was confirmed in 89% of C+ patients. Compared with the 255 anti-HCV negative (C-), C+ had undergone longer periods of dialysis (P = .0001), were more transfused (P = .01), and included more retransplants (P = .002). Immunosuppression was azathioprine (AZA) plus steroids in 133 and cyclosporine (CsA) in 331 patients. Liver biopsy showed chronic active hepatitis in 50, cirrhosis in 8, and fibrosing cholestatic hepatitis in 2 patients. Histologic progression of liver disease was confirmed in 18 of 26 patients. The causes of death in 84 patients (51 C+ vs 33 C-) were cardiovascular disease in 49%, sepsis in 13%, liver failure in 14%, neoplasia in 21%, and hepatocarcinoma in 2%. The 14-year patient survival was 75% in C+ and 86% in C- (P = .002). By multivariate analysis, age (>40) (P = .001) and C+ (P = .019) correlated with a worse patient survival. If patients were stratified according to age (<40 vs <40), younger C+ patients had a lower survival probability (P = .03). The 14-year graft survival was 44% in C+ vs 60% in C- patients (P = .001) but pure graft survival was similar (68% in C+ vs 72% in C-) (P = .13). Conclusion. The presence of C+ significantly reduced both patient and graft survival in the long-term with liver failure being the second most frequent cause of death

Natural history of hepatitis B and C in renal allograft recipients

Background. In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available. Methods. In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation. Results. At enrollment in 1989 (5.5\ub14 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+,C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8), B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival. Conclusions. In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival. Copyrigh

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results

BACKGROUND: The European tacrolimus versus ciclosporin A microemulsion (CsA-ME) renal transplantation study showed that tacrolimus was significantly more effective in preventing acute rejection and had a superior cardiovascular risk profile at 6 months. METHODS: The endpoints of this investigator-initiated, observational, 36-month follow-up were acute rejection incidence rates, rates of patient and graft survival and renal function. An additional analysis was performed using the combined endpoints BPAR, graft loss and patient death. Data available from the original ITT population (557 patients; 286 tacrolimus and 271 CsA-ME) were analysed. RESULTS: A total of 231 tacrolimus and 217 CsA-ME patients participated. At 36 months, Kaplan-Meier-estimated BPAR-free survival rates were 78.8% in the tacrolimus group and 60.6% in the CsA-ME group, graft survival rates were 88.0% and 86.9% and patient survival rates were 96.6% and 96.7%, respectively. The estimated combined endpoint-free survival rate was 71.4% with tacrolimus and 55.4% with CsA-ME (P 6 mmol/L (26.3% versus 12.6%, P <or= 0.0003, chi-square test). CONCLUSIONS: Patients treated with tacrolimus had significantly higher combined endpoint-free survival rates and lower acute rejection rates with less immunosuppressive medication at 36 months