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1 Department of Gastrointestinal and Liver Diseases, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
2 Department of Pathology
3 Department of Clinical Virology
4 Department of Epidemiology
5 Department of Experimental Internal Medicine
6 Department of Infectious Diseases Control, Municipal Public Health Service, 1018 WT Amsterdam, The Netherlands
7 Department of Viral Serology, Central Laboratory of the Dutch Red Cross Blood Transfusion Services, 1066 CX Amsterdam, The Netherlands
8 Department of Hepatogastroenterology, Erasmus University Hospital, 3015 GD Rotterdam, The Netherlands
9 Department of Gastrointestinal and Liver Diseases, University Hospital, 3589 Utrecht, The Netherlands
Dr ter Borg, Department of Internal Medicine, Deventer Ziekenhuis, Fesevurstraat 7, PO Box 5001, 7400 GC Deventer, The Netherlandsemail: borgtf{at}dz.nl Aims—To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile.
Methods—The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data.
Results—Sampling error seemed to be a constant feature, even for biopsies 
20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III–IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression.
Conclusions—The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10–20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.
Key Words: liver pathology • chronic hepatitis B virus infection • anti-hepatitis B antigen e positive • core antigen expression • serum hepatitis B virus DNA • hepatitis grading • sampling error
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| Journal of Clinical Pathology | Molecular Pathology |
