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Excerpt
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.
