Changing faces—natural course and treatment of hepatitis C after liver transplantation

Abstract

Orthotopic liver transplantation (OLT) is an efficient treatment for patients with end-stage liver disease currently reaching 5-year survival rates of more than 70% (see www. eltr.org). However, the improved control of many of the short-term problems after OLT shifted the focus of interest to the long-term complications. Chronic hepatitis C represents the most abundant single diagnosis in patients undergoing OLT. Therefore, recurrence of hepatitis C after OLT has been and is a major issue in transplantation medicine. In this issue of the Journal Dumortier and co-workers present their experience using combination therapy with pegylated interferon alpha and ribavirin, thus opening a new round in the fight against recurrent hepatitis C after OLT [1]. In the immunocompetent host, chronic hepatitis C is a slowly advancing disease taking decades to progress to liver cirrhosis. After OLT, recurrence of the virus is nearly universal and viral load is considerably higher than prior to transplantation [2–5]. The impact of recurrent hepatitis C on the prognosis of patients after OLT has been a point of intensive discussion for many years. Early reports found that a small proportion of patients (approx. 5%) suffer from a rapidly progressing cholestatic hepatitis similar to fibrosing cholestatic hepatitis (FCH) which had been detected in immunosuppressed patients with hepatitis B [6–8]. However, the remaining patients appeared to have a favourable prognosis and progression to cirrhosis was rarely detected [2,8]. It was the landmark work of Berenguer and co-workers, who recently demonstrated that the rate of fibrosis progression might have increased depending on the date of OLT [9]. Their results suggested that posttransplant hepatitis C has changed from a snail to a cheetah with respect to the speed of disease progression. In other words, the median time interval between OLT and detection of liver cirrhosis shortened from more than 10 years in patients transplanted in the late 1980s to around 3 years in patients transplanted in the late 1990s. Meanwhile, these results have been confirmed by other centres [10,11]. Once cirrhosis is established, signs of decompensation develop quickly [12]. Additionally, recent data suggest an impaired survival of patients with hepatitis C after OLT which is not caused by recurrence of hepatocellular carcinoma [13,14]. Various explanations have been suggested for these findings including changes in the selection of patients and in postoperative care. However, the most important factor appears to be the recent acceptance of elderly donors since there is a strong correlation between donor age and the course of recurrent hepatitis C after OLT [10,11,15]. The lack of an efficient strategy to prevent reinfection of the graft and the increasingly aggressive course of hepatitis C after OLT indicate the need for an effective antiviral therapy. Several approaches have been proposed to prevent the progression of posttransplant hepatitis C to liver cirrhosis [16,17]. It was attempted to reduce viral load or eliminate HCV in patients on the waiting list for OLT using either standard interferon alpha monotherapy or standard interferon alpha/ribavirin combination therapy [18–20]. In treated patients, a virological response can be expected in up to one third of the patients, and 20% remain free of virus after OLT. However, many patients do not meet inclusion criteria, and serious adverse events occur frequently, mostly due to low platelet counts. Treatment may be initiated in the first weeks after liver transplantation prior to the onset of biochemical or histological signs of recurrent hepatitis (preemptive/prophylactic therapy) [21–24]. Although effective in some patients and apparently not associated with a grossly increased rate of acute rejections, data supporting this