Histology of symptomatic acute hepatitis C infection in immunocompetent adults.
ABSTRACT Acute hepatitis C in immunocompetent individuals is rarely symptomatic and rarely biopsied. Thus, the histologic descriptions of acute hepatitis C remain limited. The histology of 5 cases of acute hepatitis C in adults were studied by selecting cases from the consult and surgical pathology files of a single institution. The 5 individuals, 3 males and 2 females, had an average age at biopsy of 50+/-17 years. They presented with jaundice and other nonspecific abdominal symptoms. The time interval from clinical presentation to biopsy ranged from 2 to 18 weeks. The average alanine aminotransferase/aspartate aminotransferase/alkaline phosphatase at the time of biopsy was 308/73/85 U/L. The average total bilirubin was 5.2 mg/dL. Each individual had a single liver biopsy. The histologic findings of the 2 cases biopsied in close temporal proximity to the initial clinical presentation showed similar histologic findings of mixed portal infiltrates with lymphocytes and neutrophils along with bile ductular proliferation that raised the possibility of down stream biliary tract disease. The lobules showed canalicular cholestasis and mild to moderate inflammation. In the third and fourth case, obtained 8 weeks after presentation, the biopsies showed mild to moderate portal and lobular lymphocytic inflammation, findings that were also present in the last case, obtained 18 weeks after presentation. In conclusion, early after acute hepatitis C viral infection, biopsies can have a cholestatic pattern whereas later biopsies tend to show mild nonspecific portal and lobular lymphocytic inflammation. Proper histologic diagnosis can be aided by an awareness of the various histologic findings, which vary depending on the time interval from clinical symptoms to biopsy.
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ABSTRACT: Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8⁺ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8⁺ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8⁺ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8⁺ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection.PLoS Pathogens 06/2012; 8(6):e1002759. DOI:10.1371/journal.ppat.1002759 · 8.06 Impact Factor
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ABSTRACT: The chimpanzee is the only animal model for investigating the pathogenesis of viral hepatitis types A through E in humans. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host responses to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), were compared in multiple experimentally infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. Respecting the limitations of microarray probes designed for human target transcripts to effectively assay chimpanzee transcripts, we conducted probe-level analysis of the microarray data in conjunction with a custom mapping of the probe sequences to the most recent human and chimpanzee genome sequences. Time points for statistical comparison were chosen based on independently measured viremia levels. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust in the magnitude and number of differentially expressed genes compared to HEV infection.Journal of Virology 11/2010; 84(21):11264-78. DOI:10.1128/JVI.01205-10 · 4.65 Impact Factor
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ABSTRACT: Chronic hepatitis C is the most common cause of cirrhosis in industrialized countries. Successful treatment of chronic hepatitis C in patients with advanced fibrosis or cirrhosis has significant benefits, including improvements in inflammation, fibrosis, and portal hypertension, with prevention of esophageal varices and clinical decompensation. In this report, we present two patients with well-compensated hepatitis C cirrhosis who achieved an end-of-treatment response on a direct-acting antiviral therapy-based triple regimen for hepatitis C virus, but subsequently presented with new-onset ascites associated with virologic relapse. We propose that the development of ascites in this setting is due to the adverse impact of inflammation of the virologic relapse on portal hypertension. Our observation that ascites formation can be a manifestation of virologic relapse has potentially important clinical implications, as it highlights not only the importance of close monitoring of cirrhotic patients after achieving end-of-treatment response but also the impact of active inflammation on the severity of portal hypertension.Hepatic Medicine: Evidence and Research 01/2014; 6:11-4. DOI:10.2147/HMER.S53604