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• W1971696411 abstract "To C or Not To C: These Are the Questions in Renal Transplantation With the development of specific tests to diagnose hepatitis C virus (HCV) in the beginning of this decade and since the segregation of hepatitis B-positive patients within hemodialysis units, it has become apparent that most liver disease in renal transplant (RT) recipients is related to HCV (1). The prevalence of HCV infection in hemodialysis (HD) patients averages 10–20%, more than 5 times higher than in the general population, and some HD units (2) have reported rates greater than 60%. Although considerable data have emerged regarding outcome after renal transplantation, many of the results are conflicting. In part, this is a result of the fact that many earlier studies were confounded by an underestimation of the true incidence of infection (serologic tests instead of HCV RNA assessment), multiple immunosuppressive protocols, retrospective nature, and short-term follow-up. A recent case control analysis (3), which matched for variables including year of transplantation and immunosuppressive regimen, found that HCV-infected RT recipients had significantly diminished survival as compared to their noninfected counterparts. On the other hand, RT may actually improve the long-term survival of HCV-infected patients with end-stage renal disease as compared to infected patients maintained on HD (4). Within the subset of HCV-infected patients, there are likely important pretransplant variables which predict outcome. If one assumes that the requisite immunosuppression of solid organ transplantation accelerates the natural history of HCV in terms of histological injury and progression to cirrhosis, then it would follow that the extent of pretransplant liver injury would be an important predictor of outcome. Surprisingly, however, there is a paucity of data regarding underlying liver disease in RT candidates. In an early study of patients with hepatitis B or non-A, non-B hepatitis, Rao and co-workers (5) reported that approximately one-third of RT recipients with early chronic active hepatitis on a pretransplant biopsy and nearly two-thirds with advanced chronic active hepatitis experienced clinical deterioration with the development of cirrhosis and death as a result of liver failure. The study by Martin and colleagues (6) published in this issue of Transplantation is an important contribution to the literature, as it identifies the severity of histological liver abnormalities in HCV-seropositive end-stage renal disease patients. Eighty-one (30/37) percent of the patients demonstrated some degree of fibrosis, and cirrhosis was present in almost one quarter of the specimens. It is sobering to realize these histological lesions would have been overlooked if biopsies were indicated solely on the basis of level of aminotransferase elevation, still a common practice in the nephrology community. Previous work has suggested that the upper normal limits of aspartate aminotransferase and alanine aminotransferase serum levels in patients undergoing dialysis should be reduced considerably, and these levels should be interpreted with caution in the diagnosis of liver disease. Indeed, among the patients maintained on HD in the current series, the mean levels for aspartate aminotransferase and alanine aminotransferase were 22.5 and 21.1 U/L, respectively. Martin et al. found no correlation between serum aminotransferase levels, viral levels and liver histological changes, further underscoring the need for a liver biopsy as the most reliable assessment of underlying liver disease before renal transplantation. Still, a number of important questions remained unanswered. Why do patients on dialysis have milder liver findings on histopathological assessment than patients not maintained on renal replacement therapy? As few of us us would subscribe to the hypothesis that dialysis is somehow “protective” against progression of liver disease in HCV, the next possible explanation for these findings would be selection bias. One could speculate that patients with severe liver damage associated with HCV might die from liver disease before dialysis is necessary, as suggested by the finding that no patient in the current analysis had grade IV histological lesions. Alternatively, it is possible patients with HCV and advanced liver disease might be referred for organ replacement therapy sooner than patients with milder disease. In fact, the rate of referral for liver-kidney transplant and prevalence of cirrhosis was different between groups, although no “statistical difference” was found. In addition, the authors implicate dialysis as the possible source of HCV infection; thus, patients on dialysis would have a shorter duration of disease and possibly less advanced histological damage. Should we treat HCV-positive patients with antiviral medications before renal transplantation? A number of studies have demonstrated that recombinant interferon-α has virological efficacy in a proportion of HD patients (7), but emerging data suggest this effect will likely not be maintained after RT. Rates of sustained virologic response in non-renal patients have been dramatically increased with the addition of ribavirin (8), which causes mild hemolytic anemia in a significant percentage of patients. Moreover, in renal failure patients, the increased absolute bioavailability, reduced volume of distribution, depressed bone marrow responsiveness, and shortened red cell longevity preclude the use of ribavirin. A recent pharmacokinetics analysis demonstrated that ribavirin is not cleared by HD and should be avoided in patients with a creatinine clearance less than 50 ml/min (9). How do we monitor the natural history of HCV after RT? Should we adopt a “preemptive” protocol for liver biopsies? How soon (and how frequently) after starting immunosuppressive therapy should we advise liver biopsy? Perhaps more importantly, what would we do with this information? Interferon treatment after RT has been associated with unacceptably high rates of rejection and graft loss, even in patients with stable graft function (1). Would different immunosuppressive regimens (10) have different impacts on the progression of HCV disease? How should immunosuppression be modified in patients who show interval worsening in histological severity? These are all critical questions that await further investigation. For now, however, it is prudent to obtain as much information as possible before offering RT to an HCV-positive patient with end-stage renal disease, and this starts with a liver biopsy." @default.
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• W1971696411 date "2000-04-01" @default.
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• W1971696411 title "Histopathological Features of Hepatitis C in Renal Transplant Candidates. Transplantation 2000; 69: 1479." @default.
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