Scandinavian Journal of Infectious Diseases
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Acute Viral Hepatitis: A Comparative Study of Clinical, Biochemical, Morphological and Immunological Features in Patients with and without Australia Antigen Jens O. Nielsen, Viggo Faber, Hemming Poulsen, Per Christoffersen, Odd Dietrichson, Preben Elling, Kurt Iversen, Erik Juhl & Palle Petersen To cite this article: Jens O. Nielsen, Viggo Faber, Hemming Poulsen, Per Christoffersen, Odd Dietrichson, Preben Elling, Kurt Iversen, Erik Juhl & Palle Petersen (1975) Acute Viral Hepatitis: A Comparative Study of Clinical, Biochemical, Morphological and Immunological Features in Patients with and without Australia Antigen, Scandinavian Journal of Infectious Diseases, 7:3, 173-177, DOI: 10.3109/inf.1975.7.issue-3.04 To link to this article: http://dx.doi.org/10.3109/inf.1975.7.issue-3.04
Published online: 02 Jan 2015.
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Date: 25 April 2016, At: 16:59
Scand J Infect Dis 7: 173-177,1975
Acute Viral Hepatitis: A Comparative Study of Clinical, Biochemical, Morphological and Immunological Features in Patients with and without Australia Antigen JENS O. NIELSEN, VIGGO FABER, HEMMING POULSEN, PER CHRISTOFFERSEN, ODD D1ETRICHSON, PREBEN ELLING, KURT IVERSEN, ERIK JUHL and PALLE PETERSEN
Downloaded by [University of Leeds] at 16:59 25 April 2016
From the Copenhagen Hepatitis Acuta Programme (CHAP): Medical Department 2 and Department of Pathology, Kommunehospitalet, Copenhagen and University Clinic for Infectious Diseases, Blegdam Hospital, Copenhagen, Denmark
ABSTRACT. 500 consecutive patients with acute viral hepatitis verified by biopsy were divided into groups of 202 patients with detectable Australia (Au) antigen and 298 patients without antigenaemia at the time of admission to hospital. Comparison was made of the initially recorded clinical, biochemical, histological and serological variables in the two groups. Judged by both histological and biochemical criteria, the acute disease was more severe in the 202 patients with Au !lntigen than in the 298 patients without Au antigen. Evidence is presented that this difference is possibly due more to qualitative aetiological differences between the two groups than to the duration of antigenaemia or the time of hospitalization. Thus, the demonstration of Au antigenaemia provides not only epidemiological but also relevant clinical information.
INTRODUCTION
MATERIAL AND METHODS
Although at least two different forms of acute viral hepatitis were recognized 30 years ago (2, 9), the characterization in clinical routine of the individual patients as cases of infectious hepatitis (IH) and serum hepatitis (SH) has been very uncertain. The detection of Australia antigen (Au antigen) has offered a new serological basis for classifying patients with acute hepatitis. Though there seems to be increasing evidence to suggest that the Au antigen identifies the classical SH type of infection only (6, 15), Blumberg et al. (l, 7) emphasized recently that the relationship between Au antigen and SH-IH is still not fully clarified. It is this serological way of classifying patients with acute hepatitis as either "antigen-positive" or "antigen-negative" which inspired the present study. The aim of the study was to compare the initial phase of acute hepatitis in two groups-one with and one without Au antigen-according to clinical, biochemical, serological and histological features, in a consecutive series of 500 patients with acute viral hepatitis verified by biopsy.
The study group comprises 500 consecutive patients with acute viral hepatitis verified by biopsy admitted to two Medical Departments in Copenhagen during a 3!-year period. These patients form the basis of the Copenhagen Hepatitis Acuta Programme, and the patients with recorded variables have been described in a previous paper (13). At the time of admission to hospital, Au antigen was demonstrated in serum specimens from 202 of the 500 patients by immunoelectroosmophoresis according to Prince and Burke (14). By means of the Ouchterlony technique, the antigen was demonstrated in serum specimens from 200 of the 500 patients, all of whom were included in the 202 antigen-positive patients. Out of the initially recorded 112clinical, serological, biochemical and histological variables, the 43 included in Tables I-II were selected as being relevant for comparing the acute attack of hepatitis in the two groups. During the initial phase of acute hepatitis described in this report, none of the patients received corticosteroids or other immunosuppressive drugs. The non-parametric Mann-Whitney test was used in the statistical analysis. The quantitative variables are recorded by median and percentiles for 90% of the patients observed (values which omit 5 % of lowest and 5 % of highest range). Confidence limits for the binominal distribution are from Geigy Scientific Tables. Scand J Infect Dis 7
174 J. O. Nielsen et al.
Table I. Variables recorded at time of admission in 500 patients with acute viral hepatitis in relation to the presence of Australia (Au) antigen in serum NS=not significant, i.e. P>0.05. Normal values given in brackets after the laboratory tests.
Downloaded by [University of Leeds] at 16:59 25 April 2016
Variable
Clinical Mean age in years Males Less than I week from onset of symptoms to icterus Less than 2 weeks from icterus to admission to the study Blood transfusions within 6 months Hepatitis contact within 6 months Visit to endemic areas Previous hepatitis Drug addicts, intravenous
Au-negative (N =298)
Au-positive (N=202)
% (95% confidence limits)
% (95% confidence limits)
Histological Many focal centrilobular liver cell necrosis Piecemeal necrosis Partial or total destruction of limiting plate Moderate or marked variation in size of liver cells Moderate or marked variation in size of nuclei Many acidophilic bodies Subrnassive necrosis Moderate or marked Kupffer cell proliferation Diffuse cholestasis Centrilobular cholestasis Focal infiltration of the parenchyma with lymphocytes Focal infiltration of the parenchyma with plasma cells Scand J lnfect Dis 7
Median (90 % observed range)
Differences
65 (60-70)
68 (61-75)
P70%) Total protein (>5.9 g/lOO rnl) Albumin (4.4-5.9 g/lOO ml) Immunological Antistreptolysin 0 (titre > 200) Antistreptococcal hyaluronidase (;;.8000 Vlml) Antinuclear antibodies Mitochondrial antibodies Smooth muscle antibodies Latex F II test IgG (7.2-15.1 g/l) IgA (0.74-3.06 gil) IgM (0.23-1.33 gIl)
Median (90 % observed range)
NS
64 (57-71) 17 (12-23) 5 (2-9) 53 (45-57)
203 (32-2 006) 2.7 (0.5-11.8) 124 (47-282) 73 (44-120) 7.5 (6.5-8.3) 4.3 (3.4-5.1)
P
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Acute Viral Hepatitis: A Comparative Study of Clinical, Biochemical, Morphological and Immunological Features in Patients with and without Australia Antigen Jens O. Nielsen, Viggo Faber, Hemming Poulsen, Per Christoffersen, Odd Dietrichson, Preben Elling, Kurt Iversen, Erik Juhl & Palle Petersen To cite this article: Jens O. Nielsen, Viggo Faber, Hemming Poulsen, Per Christoffersen, Odd Dietrichson, Preben Elling, Kurt Iversen, Erik Juhl & Palle Petersen (1975) Acute Viral Hepatitis: A Comparative Study of Clinical, Biochemical, Morphological and Immunological Features in Patients with and without Australia Antigen, Scandinavian Journal of Infectious Diseases, 7:3, 173-177, DOI: 10.3109/inf.1975.7.issue-3.04 To link to this article: http://dx.doi.org/10.3109/inf.1975.7.issue-3.04
Published online: 02 Jan 2015.
Submit your article to this journal
Article views: 4
View related articles
Citing articles: 5 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [University of Leeds]
Date: 25 April 2016, At: 16:59
Scand J Infect Dis 7: 173-177,1975
Acute Viral Hepatitis: A Comparative Study of Clinical, Biochemical, Morphological and Immunological Features in Patients with and without Australia Antigen JENS O. NIELSEN, VIGGO FABER, HEMMING POULSEN, PER CHRISTOFFERSEN, ODD D1ETRICHSON, PREBEN ELLING, KURT IVERSEN, ERIK JUHL and PALLE PETERSEN
Downloaded by [University of Leeds] at 16:59 25 April 2016
From the Copenhagen Hepatitis Acuta Programme (CHAP): Medical Department 2 and Department of Pathology, Kommunehospitalet, Copenhagen and University Clinic for Infectious Diseases, Blegdam Hospital, Copenhagen, Denmark
ABSTRACT. 500 consecutive patients with acute viral hepatitis verified by biopsy were divided into groups of 202 patients with detectable Australia (Au) antigen and 298 patients without antigenaemia at the time of admission to hospital. Comparison was made of the initially recorded clinical, biochemical, histological and serological variables in the two groups. Judged by both histological and biochemical criteria, the acute disease was more severe in the 202 patients with Au !lntigen than in the 298 patients without Au antigen. Evidence is presented that this difference is possibly due more to qualitative aetiological differences between the two groups than to the duration of antigenaemia or the time of hospitalization. Thus, the demonstration of Au antigenaemia provides not only epidemiological but also relevant clinical information.
INTRODUCTION
MATERIAL AND METHODS
Although at least two different forms of acute viral hepatitis were recognized 30 years ago (2, 9), the characterization in clinical routine of the individual patients as cases of infectious hepatitis (IH) and serum hepatitis (SH) has been very uncertain. The detection of Australia antigen (Au antigen) has offered a new serological basis for classifying patients with acute hepatitis. Though there seems to be increasing evidence to suggest that the Au antigen identifies the classical SH type of infection only (6, 15), Blumberg et al. (l, 7) emphasized recently that the relationship between Au antigen and SH-IH is still not fully clarified. It is this serological way of classifying patients with acute hepatitis as either "antigen-positive" or "antigen-negative" which inspired the present study. The aim of the study was to compare the initial phase of acute hepatitis in two groups-one with and one without Au antigen-according to clinical, biochemical, serological and histological features, in a consecutive series of 500 patients with acute viral hepatitis verified by biopsy.
The study group comprises 500 consecutive patients with acute viral hepatitis verified by biopsy admitted to two Medical Departments in Copenhagen during a 3!-year period. These patients form the basis of the Copenhagen Hepatitis Acuta Programme, and the patients with recorded variables have been described in a previous paper (13). At the time of admission to hospital, Au antigen was demonstrated in serum specimens from 202 of the 500 patients by immunoelectroosmophoresis according to Prince and Burke (14). By means of the Ouchterlony technique, the antigen was demonstrated in serum specimens from 200 of the 500 patients, all of whom were included in the 202 antigen-positive patients. Out of the initially recorded 112clinical, serological, biochemical and histological variables, the 43 included in Tables I-II were selected as being relevant for comparing the acute attack of hepatitis in the two groups. During the initial phase of acute hepatitis described in this report, none of the patients received corticosteroids or other immunosuppressive drugs. The non-parametric Mann-Whitney test was used in the statistical analysis. The quantitative variables are recorded by median and percentiles for 90% of the patients observed (values which omit 5 % of lowest and 5 % of highest range). Confidence limits for the binominal distribution are from Geigy Scientific Tables. Scand J Infect Dis 7
174 J. O. Nielsen et al.
Table I. Variables recorded at time of admission in 500 patients with acute viral hepatitis in relation to the presence of Australia (Au) antigen in serum NS=not significant, i.e. P>0.05. Normal values given in brackets after the laboratory tests.
Downloaded by [University of Leeds] at 16:59 25 April 2016
Variable
Clinical Mean age in years Males Less than I week from onset of symptoms to icterus Less than 2 weeks from icterus to admission to the study Blood transfusions within 6 months Hepatitis contact within 6 months Visit to endemic areas Previous hepatitis Drug addicts, intravenous
Au-negative (N =298)
Au-positive (N=202)
% (95% confidence limits)
% (95% confidence limits)
Histological Many focal centrilobular liver cell necrosis Piecemeal necrosis Partial or total destruction of limiting plate Moderate or marked variation in size of liver cells Moderate or marked variation in size of nuclei Many acidophilic bodies Subrnassive necrosis Moderate or marked Kupffer cell proliferation Diffuse cholestasis Centrilobular cholestasis Focal infiltration of the parenchyma with lymphocytes Focal infiltration of the parenchyma with plasma cells Scand J lnfect Dis 7
Median (90 % observed range)
Differences
65 (60-70)
68 (61-75)
P70%) Total protein (>5.9 g/lOO rnl) Albumin (4.4-5.9 g/lOO ml) Immunological Antistreptolysin 0 (titre > 200) Antistreptococcal hyaluronidase (;;.8000 Vlml) Antinuclear antibodies Mitochondrial antibodies Smooth muscle antibodies Latex F II test IgG (7.2-15.1 g/l) IgA (0.74-3.06 gil) IgM (0.23-1.33 gIl)
Median (90 % observed range)
NS
64 (57-71) 17 (12-23) 5 (2-9) 53 (45-57)
203 (32-2 006) 2.7 (0.5-11.8) 124 (47-282) 73 (44-120) 7.5 (6.5-8.3) 4.3 (3.4-5.1)
P
