Correlation of histology, viral load, and in situ detection in hepatic biopsies from patients with liver transplants secondary to hepatitis C infection
Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.Human Pathlogy (Impact Factor: 2.77). 04/2002; 33(3):277-84. DOI: 10.1053/hupa.2002.32211
The diagnosis of hepatitis C infection in the setting of liver transplantation in based on several variables, including histopathologic changes and the presence of viral RNA in the serum. It may be difficult to differentiate acute rejection from recurrent viral hepatitis in liver biopsies from patients who received liver transplants for end-stage hepatitis C infection. The purpose of this study was to analyzed the histologic features, viral load, and in situ viral detection in 37 biopsies taken from 25 people who underwent liver transplant for end-stage hepatitis C infection. Hepatitis C antigen was detected in 9 of 37 (24%) biopsies using immunohistochemistry; the detection rate increased to 19 of 37 (51%) using reverse transcriptase in situ polymerase chain reaction for viral cDNA. Hepatitis E cDNA was detected in 4 of 37 (11%) cases, hepatitis G cDNA in 3 of 37 (8%) cases and in 1 case cytomegalovirus was noted; with several cases of dual infection, 22 of 37 (59%) of tissues were positive for at least 1 virus. Histologic parameters that significantly correlated with in situ viral detection included single-cell hepatocyte necrosis (P = 0.02), bile duct damage (P = 0.03), lymphoid aggregates (P = 0.02), and cholestasis (P = 0.01). Further, a serum viral load exceeding 1,250,000 viral equivalents/ml was strongly correlated with in situ viral detection in the liver (P = 0.01). We conclude that certain histologic features and an increased viral load are highly correlated with the in situ detection of viral RNA in the liver, which is consistent with recurrent viral infection.
- Transplantation Proceedings 06/2003; 35(3):1030-1. DOI:10.1016/S0041-1345(03)00256-2 · 0.98 Impact Factor
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ABSTRACT: The accumulation of individual hepatitis C virus (HCV) proteins in the liver cells of patients with acute hepatitis C (AHC) and their association with the course and outcome of the disease were studied. AHC protein expression in the cryostat liver sections from 20 patients with AHC was estimated by immunohistochemical assay using original monoclonal antibodies to 5 HCV proteins (core, NS3, NS4A, NS4B, and NS5A). The results of HCV detection in the patients were compared with their biochemical, clinical, and morphological findings. HCV proteins were totally revealed in the livers of all the patients, individual proteins were identified with a frequency of 89-95%, which is significantly more than those in patients with chronic hepatitis C. The hepatic expression of core protein was shown to inversely correlate with the duration of an acute period. There was a direct relationship between the accumulation of core, NS3, and NS5A proteins and the liver tissue damage caused by stepwise necrosis rather than intralobular necrosis. The presumed convalescence was ascertained to be associated with the larger count of hepatocytes containing the proteins NS4A and NS3 early after AHC manifestation.Voprosy virusologii 01/2005; 50(4):18-23.
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ABSTRACT: The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P = .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed.Hepatology 03/2005; 41(3):617-25. DOI:10.1002/hep.20581 · 11.06 Impact Factor
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