Serological pattern of hepatitis C virus recurrence after liver transplantation.
BACKGROUND/AIMS: Hepatitis C infection is characterized by a high incidence of liver cirrhosis, frequently requiring liver transplantation. After orthotopic liver transplantation, recurrence of hepatitis C virus infection is common, but often difficult to differentiate from allograft rejection. In this context the role and diagnostic value of hepatitis C virus-associated markers like the anti-GOR response have not yet been determined. In this study we analyzed the time course of hepatitis C virus recurrence in hepatitis C virus-infected patients who underwent liver transplantation because of end-stage cirrhosis or acute liver failure. METHODS: We evaluated the serological pattern and diagnostic significance of anti-HCV, anti-HCV-IgM, anti-HCV-core, anti-HCV-core 5-27, anti-GOR, anti-GOR-IgM and HCV-RNA in serial serum samples during hepatitis C virus recurrence with or without allograft rejection up to 5-64 months after orthotopic liver transplantation. For comparison, we also studied these markers in serial serum samples from previously uninfected patients who acquired hepatitis C virus-infection during or shortly after orthotopic liver transplantation. Hepatitis C virus-infected patients who had undergone orthotopic liver transplantation were identified by screening pre-transplant sera from 235 patients for the presence of anti-HCV (2nd generation ELISA) and serum HCV-RNA (reverse transcription polymerase chain reaction). RESULTS: Of 218 patients transplanted for end-stage liver cirrhosis, 65 (30%) were anti-HCV positive and 33 (15%) were HCV-RNA positive, while only one of 17 patients (6%) transplanted for acute liver failure was found to be anti-HCV positive without detectable HCV-RNA. Fifty-two hepatitis C virus-infected patients were studied serially before and after liver transplantation: 46 patients (89%) showed recurrent anti-HCV antibodies within 3 months and 51 patients (98%) within 42 months after orthotopic liver transplantation. Serum HCV-RNA was detected in 39 patients (75%) within 3 months and in 44 patients (85%) within 42 months after orthotopic liver transplantation. In the patients studied serially during hepatitis C virus-recurrence, anti-GOR antibodies displayed the same serological profile as hepatitis C virus antibodies, i.e. a decrease after orthotopic liver transplantation and slowly rising titers when HCV-RNA became detectable again. De novo infection with hepatitis C virus as studied in four patients produced a significant peak of anti-HCV titers accompanied or followed by an increase in anti-GOR titers, indicating that the immune response to GOR-autoantigen is triggered by the hepatitis C virus. No significant diagnostic difference between anti-GOR and anti-HCV was noted during hepatitis C virus recurrence and allograft rejection.
Rehermann, B; Seifert, U; Tillmann, HL; Michel, G; Böker, KH; Pichlmayr, R; Manns, MP
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