Management of hepatitis C virus infection in the setting of liver transplantation

Abstract

C hronic hepatitis C virus (HCV) infection is common and affects a significant proportion of the world population, with an estimated 170 million people infected and 3 to 4 million new cases per year. 1,2 HCV-related cirrhosis is the most common indication for liver transplantation (LT) in the United States and most European countries. [3][4][5][6][7] In the United States, over one-third of available liver allografts are transplanted into recipients with chronic HCV infection. In fact, despite a decline in the incidence of new HCV cases, the prevalence of infection will not peak until the year 2040. 5 As the duration of infection increases, the number of new patients with cirrhosis will double by the year 2020 in an untreated patient population. 5 If this model is correct, the projected increase in the need for LT secondary to chronic HCV infection will place a burden that may be impossible to meet on an already limited supply of organ donors.In this article, we review the natural history of HCV in the transplantation population, risk factors associated with severity of recurrence, histological changes associated with recurrence of disease, treatment strategies, and the role of retransplantation. Natural History of Recurrent HCV Infection Virological RecurrenceThe clinical history of recurrent HCV infection as defined by detectable HCV RNA in serum is almost a universal phenomenon. 4,[8][9][10][11][12] Reinfection of the liver allograft has been recognized at the virological level by either an increasing level of serum HCV RNA or detection of HCV RNA in the allograft itself. 13 In fact, while the interval between LT and clinical allograft infection varies, the presence of negative-strand HCV RNA, the sine qua non of HCV replication, in serum has been recorded as early as 48 hours after LT and hepatocyte expression of HCV antigens as early as 10 days after LT (25% of patients). 11,12,14,15 A recent study of post-LT hepatitis C viral kinetics showed that the first round of infection likely occurs during reperfusion of the graft. In this study, serum viral levels reached pre-LT titers by postoperative day 4 in a significant number of patients. Viral load then tended to increase over the ensuing weeks, reaching a plateau at approximately 1 month after LT. 16 Serum levels of HCV RNA peak at 1 to 3 months, achieving 1-year post-LT levels that are 10-to 100-fold greater than the mean pre-LT levels. 11,17 Viral titers at 1 year after LT usually plateau at 1 to 2 logs higher than pre-LT levels.

Survival of Liver Transplant Patients Coinfected with HIV and HCV Is Adversely Impacted by Recurrent Hepatitis C

“…Our current experience does indicate that HCV recurrence is a significant cause of graft loss and patient mortality in these patients. This finding is not completely unexpected since progression of fibrosis and cirrhosis has been shown to be faster than expected in HIV/HCV positive patients in the nontransplant setting (21,22), recurrence of hepatitis C is nearly universal after LTx (26), and HCV infection is known to adversely affect patient and graft de Vera et al…”

Rezidiv der Grunderkrankung nach Lebertransplantation

“…Dabei stellt die rekurrierende HCV-Infektion im Transplantat die häufigste Ursache für das Organversagen bei diesem Patientenkollektiv dar. Serologische Untersuchungen der Viruskinetik zeigten, dass die Viruslast in der Regel in den ersten 1-3 Monaten deutlich ansteigt und 1 Jahr nach Transplantation etwa 1-2 Logstufen höher ist als präoperativ [3].…”

“…Gegen eine präemptive Interferon-(IFN-)Therapie werden ein erhöhtes Abstoßungsrisiko, eine schlechtere Tolerabilität, die perioperativ oft erhebliche Gewichtsabnahme und Zytopenie, ein erhöhtes Infektionsrisiko sowie ein schlechteres Ansprechen Beckebaum S, et [25]. Etwa 30-60% der Patienten benötigen im Verlauf der Erkrankung eine Dosisreduktion des Ribavirins, und bei etwa 20-30% der Patienten wird die Behandlung aufgrund von Nebenwirkungen frühzeitig abgesetzt [3,25,30]. Bisher gibt es keine einheitlichen Empfehlungen bezüglich des optimalen Therapiebeginns, der Dauer der Behandlung und der Dosierung.…”

“…Bisher gibt es keine einheitlichen Empfehlungen bezüglich des optimalen Therapiebeginns, der Dauer der Behandlung und der Dosierung. Während in den meisten Studien eine 12-monatige Therapie durchgeführt wurde, schlagen einige Autoren bei Patienten mit fibrosierender cholestatischer Hepatitis eine langfristige antivirale Behandlung vor [3,31]. Bei Auftreten einer Anämie mit Hämoglobinwerten, welche um mehr als 3 g/dl vom Ausgangswert abfallen, oder bei Symptomatik kann eine Behandlung mit Erythropoetin erfolgen.…”

Treatment of hepatitis C in the potential liver transplant recipient

“…The number of patients with HCV cirrhosis who develop decompensated liver disease or HCC is expected to increase over the next decade [1]. Improved response rates with pegylated interferon used in combination with ribavirin, the availability of hemopoietic growth factor support, and the need to clear the virus before transplant have contributed to an interest in treating the HCV patient with cirrhosis [3][4][5].…”