Correlation of histology, viral load, and in situ viral 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 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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ABSTRACT: Fourteen hepatitis C virus (HCV) chronically infected patients were submitted to routine liver biopsy for histological evaluation. Liver samples were assayed to HCV-RNA by in situ hybridization, using digoxigenin labeled probe. HCV genotypes were found to be predominantly type 1 (71.4%), followed by genotype 3 (21.4%), and genotype 2 (7.2%). Alanine-aminotransferase levels were raised in 10 patients. The histopathological scores were minimal (21.4%), mild (57.2%), and moderate (21.4%). Viral RNA was detected in liver cells from nine patients (64.3%). ISH method provides localization and poor confirmation of HCV RNA in the liver tissue of HCV chronic patients.Memórias do Instituto Oswaldo Cruz 06/2005; 100(3):269-72. DOI:10.1590/S0074-02762005000300009 · 1.59 Impact Factor
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