Recurrent hepatitis C: Worse outcomes established, interventions still inadequate

Significant improvements have been made in recent years in the treatment of hepatitis C in the immunecompetent population. More than half of currently treatment-naı̈ve patients can be cured with the combination of long-acting pegylated interferon and ribavirin. Demonstration that these advances improve survival is however lacking. In the HCV-infected transplant population, antiviral therapy has historically yielded poor results. Fortunately, results have also improved in this setting, such that sustained viral response can currently be achieved in more than 35% of treated patients. However, toxicity remains a substantial limiting factor, and about one-third of patients discontinue therapy due to severe side effects, limiting the population that might benefit from peginterferon plus ribavirin. In light of the reduced response and increased side effects, one strategy would be to treat only patients at high risk of severe HCV recurrence. Such a strategy requires a detailed understanding not only of the natural history of HCV after transplantation, but also of the variables associated with disease progression as well as of treatment response. Despite early reports that recurrent HCV infection did not compromise patient or graft survival, numerous studies show that histological progression of HCV is accelerated following liver transplantation resulting in the rapid development (within 5 years) of cirrhosis in 30% of transplant patients with HCV. This rapidly progressing disease ultimately results in reduced graft and patient survival. At 5 and 10 years after transplantation, survival reaches 61%-75% and 68% compared with 76%-85% and 78%, respectively, in other indications. In a recent U.S. study of 11,036 patients, transplantation in HCV-positive recipients was associated with an increased rate of death of 1.23 (95% confidence interval, 1.12-1.35) as compared with transplantation in recipients without HCV. With the clear understanding that HCV infection of the graft impairs both graft and patient survival, there has been intensive investigation into variables associated with these poor outcomes, particularly those variables that may be modified in order to improve outcome. An important variable that was investigated in the studies of Belli et al. and Thuluvath et al. in this issue of Liver Transplantation is “year of transplantation”. Recent observations suggest that the speed at which fibrosis progresses has increased in patients undergoing transplantation in recent years, so that the proportion of patients developing advanced disease in the first 3-5 years after transplantation is higher among patients who underwent transplantation in the late 1990s compared with those who underwent transplantation in the late 1980s to early 1990s. In 2000, using data from La Fe Hospital in Spain and the University of California San Francisco in the United States, we showed for the first time an accelerated rate of posttransplant fibrosis progression among HCV-positive patients who had more recently undergone liver transplantation. The cumulative probability of developing stage 4 fibrosis at 5 years increased from 0% in patients who underwent transplantation in 1988-1989, to 7% and 18% in those who underwent transplantation in 1990-1991 and 1992-1993, respectively. In addition, we showed that Spanish patients had a higher rate of posttransplant fibrosis progression than U.S. patients despite similar progression rates prior to transplantation. Two years later, we provided further insight into these results through the analysis of 522 patients with cirrhosis who underwent transplantation between