Finding an effective therapy for the posttransplantation In this issue of HEPATOLOGY, Bizollon et al. present their population with recurrent HCV is a priority. Chronic hepatipreliminary results of an alternate form of therapy for recurtis C infection is now the most common indication for liver rent hepatitis C virus (HCV) infection following liver transtransplantation in the United States. 4 Over the last five years, plantation. 1 This nonrandomized pilot study assessed the the issues surrounding recurrent HCV post-liver transplantasafety and efficacy of interferon alfa (INF-a) in combination tion have rapidly evolved. Virological recurrence is almost with ribavirin. Twenty-one patients received a combination universal in patients posttransplantation. Rapid graft dysof INF and ribavirin for 6 months and then ribivarin alone function caused by HCV, although uncommon, is a well for an additional six months, as suggested by the authors for recognized, and often disastrous, complication. 5 Recent pro-''maintenance.'' The resulting response rates, as judged by spective data now indicate that recurrent hepatitis C associnormalization of liver enzymes, the disappearance of serum ated with histological damage is a common posttransplanta-HCV RNA, and the improvement in histology seem almost tion problem. Rates of moderate hepatitis and cirrhosis are too good to be true.
25% to 30% and 8% to 10%, respectively, at three and five All 21 patients developed normal alanine aminotransferase years posttransplantation, and patients with HCV genotype (ALT) values during the combination phase of the study, 1b seem to develop more severe graft injury (92% of patients accompanied by clearance of serum HCV RNA in almost onein the study by Bizollon et al. were HCV genotype 1b). 4,6 half of the patients (48% or 10 of 21). Histology improved Survival in this subgroup of patients with recurrent disease in all patients at the completion of this phase of the study. is not as favorable as previously thought. Two-and five-With ''maintenance'' ribavirin for a further 6 months, most year survival rates are decreased compared with patients with patients had continued improvement in histology and had auto-immune, cholestatic, and alcoholic liver diseases. 4 Depersistently normal liver tests (all but 1 patient), despite respite the observations that recurrent HCV has a high propenappearance of serum HCV RNA in 50% (5 of 10) who initially sity to recur histologically and virologically, the actual rate cleared HCV RNA. This led the authors to conclude that of graft loss and the need for retransplantation remain fairly such a period of ribavirin therapy was ''necessary.'' This aslow at approximately 2% to 5% in the early postoperative sumption is, however, yet to be proven and requires further years. 6,7 However, as we follow these patients in future years, assessment. Nevertheless, the results for viral RNA clearance, we suspect that long-term prospective studies will show a ALT normalization, and histological improvement are to date progressive diminution of graft survival, a more severe histothe best reported in this setting. logical recurrence, and an increased mortality. During combination therapy, the patients who did not It is thus reasonable and appropriate to offer patients with clear serum HCV RNA had a mean decrease in serum quantirecurrent hepatitis C posttransplantation an efficacious and tative HCV RNA levels of 0.5 log. Although this trend is tolerable form of therapy; unfortunately, no proven therapy reported as statistically significant, it is within the range obcurrently exists. In terms of either a transient or a sustained served in untreated and immunocompetent patients with biochemical or virological response, ribavirin monotherapy HCV infection. 2 The combination therapy was well tolerated has been ineffective in producing meaningful results. 8 To by the majority of patients as only 3 of 21 had to cease date, data on INF therapy alone for chronic HCV infection therapy because of ribavirin-induced hemolytic anemia, a posttransplantation have been disheartening. The majority well recognized dose-dependent and reversible side effect of of individuals treated with standard doses of type-1 INF fail this drug. 3 There was no observed increase in episodes of to clear serum HCV RNA, despite normalization of ALT valrejection throughout the twelve-month study and, imporues. Almost all patients who respond have relapsed virologitantly, immunosuppression was kept fairly constant in the cally after the cessation of therapy. 9 Likewise, posttreatment group throughout the study. Unfortunately, we have no folimprovement in hepatic histology is relatively uncommon low-up data on these 21 patients after cessation of ribavirin. with INF therapy alone. Of further concern and for unclear Did all patients relapse as we would expect from our experireasons, there has been an increased incidence of ductopenic ence with INF therapy in this immunosuppressed popularejection in these individuals, presumably secondary to INFtion, or were there continued biochemical and virological induced enhanced expression of human leukocyte antigenclass 1 molecules on hepatocytes. A recent study which utilized INF early after transplantation to prevent recurrent Abbreviations: HCV, hepatitis C virus; INF, interferon.
HCV and in which there was no observed increase in rejec-