Hepatitis C After Orthotopic Liver Transplantation

HCV in their population. At the University of PittsS burgh, 25% of patients on the waiting list have HCV ince the hepatitis C virus (HCV) was cloned and sequenced in 1989, it has became apparent that infection as at least one of their pretransplantation diagHCV is one of the most important health problems in the noses. United States. Orthotopic liver transplantation (OLT) Knowledge of HCV after liver transplantation is incaused by HCV costs the U.S. health care system between creasing both at the molecular and at the clinical level, $150 and $300 million annually. Because HCV is the partly because of the ability to detect HCV recurrence most common etiology of posttransfusion hepatitis, our with increasingly sensitive assays. The first-generation current assumptions of its natural history are essentially enzyme-linked immunosorbent assay (ELISA), patented an extrapolation of the clinical course that has been obin 1990 by the Chiron Corp. (Emeryville, CA), had an served in patients with non-A, non-B posttransfusion unacceptable rate of false negatives. This problem has hepatitis. Hence, the natural history of HCV from the been partially solved with the introduction of the secondacute infection to end-stage liver disease is believed to generation ELISA, although all serological assays lack be slow and measured in decades. Moreover, current insensitivity in immunosuppressed patients. With the terferon (IFN) therapy for chronic HCV has been disapavailability of reverse-transcription polymerase chain repointing with a maximum of 20% sustained response action (RT-PCR) assay to detect HCV RNA, HCV recurrate. HCV has also become an important cause of morrence has been well defined, which has improved our bidity and mortality in patients undergoing solid organ understanding of the natural history of HCV infection and bone marrow transplantation, and transmission from after transplantation. Clinical manifestations of HCV rethe donor to the recipient of these organs has been well currence range from asymptomatic infection to severe documented. For example, in the bone marrow transdisease. Unfortunately, whereas knowledge of the natural plantation setting, the morbidity can be variable but history of HCV infection both in immunocompetent and there has been one report of fulminant HCV infection. immunocompromised patients has improved signifiAfter cadaveric renal transplantation, the morbidity is cantly, ability to effectively treat recurrent disease is still also variable, with reports ranging from minimal morlimited. bidity to acute renal failure caused by cryoglobulinemia. Because of the demonstrated epidemiological and fiIn patients undergoing heart transplantation, the danger nancial importance of HCV, this review will focus on of HCV transmission from the graft has been highlighted recent published observations relevant to diagnosis, natuby a case report from the University of Florida in which ral history, pathogenesis, and treatment of HCV infection a recipient developed cholestatic hepatitis and hepatic in patients undergoing liver transplantation. failure within 6 months of transplantation. Therefore, HCV can cause significant morbidity and mortality Detection of Recurrence among infected patients undergoing solid organ and bone HCV RNA measurement by RT-PCR has become marrow transplantation. a reliable way of detecting early disease recurrence (Table The impact of HCV on our health care resources is 1). When this tool was not generally available, several and will remain significant. By 1993, it became evident studies underestimated recurrence rates because of their in the United Network for Organ Sharing transplant registry that HCV had surpassed alcoholic cirrhosis as