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Biomedical subjects

L R Mathiesen

Publications and source records attributed to L R Mathiesen.

At least 55 records · Page 3Linked to original sources

Delta infection and hepatitis B virus replication in Danish patients with fulminant hepatitis B.

The presence of hepatitis B virus and delta agent markers was investigated in 41 patients referred during the years 1970-1985 with fulminant hepatitis classified as type B or non-A non-B and compared to findings in patients with uncomplicated hepatitis B and chronic hepatitis B infection. 13 patients had no markers of hepatitis B and delta infection and were classified as non-A non-B hepatitis. The remaining 28 patients were all HBsAg and IgM anti-HBc positive and 14 (50%) had evidence of delta infection. In contrast, only 13/71 patients (18%) with acute benign hepatitis B had evidence of delta coinfection (p less than 0.005). This corresponds to an odds ratio of 4.5 for development of fulminant hepatitis among patients with hepatitis B and delta coinfection. In 100 chronic HBsAg carriers 29% were positive for delta markers. 12 of the delta infected patients with fulminant hepatitis were positive for total antibody to the delta antigen, and 2 were delta antigen positive. Three were HBeAg positive/anti-HBe negative. None had hepatitis B virus DNA. Among the 14 patients without delta infection, hepatitis B virus DNA was found in 2/4 HBeAg positive/anti-HBe negative patients and in 1/8 patients negative for both markers. The present data indicate that a high proportion of Danish patients with fulminant hepatitis B have hepatitis B and delta agent coinfection. Further, the findings suggest that hepatitis B and delta coinfection may be associated with an increased risk of development of fulminant hepatitis as compared to that of hepatitis B alone.

Adolescent↗

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients.

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.

Acquired Immunodeficiency Syndrome↗

Serological diagnosis of acute viral hepatitis.

Fifty cases of symptomatic acute viral hepatitis presenting at the Washington, D.C., Veterans Administration Medical Center between 1976 and 1978 were tested for serological markers of hepatitis virus infection. The etiology of the acute hepatitis appeared to be hepatitis A virus in 20%, hepatitis B virus in 52%, non-A, non-B agents in 22%, delta hepatitis in 4%, and infectious mononucleosis in 2%. The diagnosis of type B hepatitis was difficult to verify because 10% of cases were seronegative for HBsAg and another 10% were seronegative by conventional testing for IgM antibody to hepatitis B core antigen (a putative marker of acute hepatitis B virus infection). Accurate serodiagnosis of acute viral hepatitis depends upon the correct application of testing for IgM antibody to hepatitis A virus, IgM antibody to hepatitis B core antigen, HBsAg, and tests for syphilis and mononucleosis.

Adult↗

Methods for localization of hepatitis B surface antigen in liver tissue. An evaluation of different staining- and tissue preparation methods.

To investigate different staining techniques for demonstration of hepatitis B-surface antigen a series of 250 liver biopsies were stained with direct immunofluorescence (I.F.) on frozen tissue and indirect immunoperoxidase (I.P.), direct I.F., orcein and haema toxylin-eosin (H.E.) on paraffin embedded tissue. Examination of different fixatives and various fixation times of formalin fixed tissue on the demonstration of HBsAg was performed on liver tissue from one case with large amounts of HBsAg in the tissue. Among 70 HBsAg sero-positive cases only 27 were tissue positive. In 51 sero-positive AVH cases, 11 were positive with I.F., 3 with I.P., one with orcein and none with H.E. In the remaining 19 sero-positive cases, representing 9 cases with chronic hepatitis, 6 cases with cirrhosis, 3 cases with non-specific reactive changes and one case without pathological changes, 15 cases were positive with I.F. as well as with I.P., 9 with orcein and 5 with H.E. Membrane related staining reaction was best preserved when using Bouin's and Clarke's fixative. No difference was observed between different fixatives as regards intracytoplasmic staining reaction. Formalin fixation for more than 7 hours duration caused a decrease in the amount of demonstrable HBsAg, which only to a limited extent could be restored by pre-treatment with proteolytic enzyme.

Acute Disease↗

The long-term prognosis of non-transfusion-associated non-A, non-B hepatitis. A clinical, epidemiological, and histological investigation.

In a prospective study of the natural course of acute hepatitis, 157 of 1020 patients with biopsy-verified acute hepatitis could be classified as having hepatitis type non-A, non-B. We here report on the long-term prognosis for these 157 patients. The main type of exposure was drug addiction (40%), whereas 40% had no known hepatitis exposure. Only two patients had received blood products (blood transfusion and factor VIII). Follow-up liver biopsy (mean histological follow-up, 22 months) in 94 of the 157 patients showed chronic liver disease in 15-that is, cirrhosis in 6, suspicion of cirrhosis in 2, chronic aggressive hepatitis in 5, and chronic persistent hepatitis in 2. There was a striking predominance of elderly women with no known hepatitis exposure and with a high frequency of autoantibodies in serum among the patients with progression to chronicity, whereas chronic non-A, non-B hepatitis in drug addicts or after blood transfusions seems to be a limited problem. A comparison of histological features in the initial biopsies from patients with progression to chronicity or complete resolution showed piecemeal necrosis and abnormal bile duct epithelium to be of prognostic value.

Adolescent↗

Azathioprine versus prednisone in non-alcoholic chronic liver disease (CLD). Relation to a serological classification.

One hundred and forty-eight patients with non-alcoholic cirrhosis or chronic aggressive hepatitis entered a prospective, unblinded, randomized trial on the effect of azathioprine versus prednisone. For all 148 patients, there were no differences in survival related to the two drugs. In 99 patients the disease was classified as autoimmune, in 23 as posthepatitic, and in 26 as cryptogenic. No significant differences were seen in survival between these three groups of patients and no differences in survival related to the two drugs were registered within any of the groups. The autoimmune group included the patients with the biochemically most active disease, and a statistically significant reduction in activity was obtained with prednisone as well as azathioprine. Most remarkably, the frequencies of the autoantibodies were reduced parallel to the biochemical improvement in these patients. Immunosuppressive treatment was found to be rather ineffective in posthepatic chronic liver disease of type B; however, no signs of activation of the hepatitis B virus were seen.

Adult↗

Acute hepatitis A, B and non-A, non-B in a Swedish community studied over a ten-year period.

985 episodes of hepatitis representing 98% of all acute hepatitis episodes found in a Swedish city during a 10-year period were analyzed for anti-hepatitis A IgM antibodies and hepatitis B surface antigen. Hepatitis A was diagnosed in 311 episodes (32%), hepatitis B in 494 (50%), simultaneous acute hepatitis A and B in 12 (1.2%), and 168 episodes (17%) were classified as hepatitis non-A, non-B. The majority of the hepatitis A cases were drug addicts (58%), and all were concentrated in 3 outbreaks of 1-2 years duration. 16% of all hepatitis A cases were probably imported. Hepatitis B cases decreased significantly (p less than 0.001) between the first and second half of the study period. 47% were drug addicts. Hepatitis non-A, non-B was also dominated by drug addicts (61%). Approximately 20% of the cases in all 3 types of hepatitis had no identifiable source.

Cross Infection↗

Enzyme-linked immunosorbent assay for detection of immunoglobulin M antibody to hepatitis B core antigen.

An enzyme-linked immunosorbent assay for detection of specific immunoglobulin M (IgM) antibodies against the core antigen of the hepatitis B virus (anti-HBc IgM) is described. The interference of IgM rheumatoid factor was evaluated quantitatively. In the anti-HBc IgM test, the rheumatoid factor gave false-positive results when the concentration exceeded 20 IU/ml. The rheumatoid-positive sera were disclosed by a control and retested for anti-HBc IgM after absorption of rheumatoid factor with latex particles aggregated with human IgG. In five of seven selected patients with acute hepatitis B followed to biochemical and clinical recovery, anti-HBc IgM was present transiently until antibodies against hepatitis B surface antigen (anti-HBs) appeared. Two patients had persistent anti-HBc IgM during the follow-up period. Four patients with hepatitis B surface antigenemia and progression to chronic liver disease did not clear their anti-HBc IgM in the period of observation (11 to 24 months). Anti-HBc IgM could not be demonstrated in 223 of 225 Danish blood donors. The two donors found positive for anti-HBc IgM also had anti-HBs. Twenty patients with acute A or non-A non-B hepatitis were negative for anti-HBc IgM. The enzyme-linked immunosorbent assay for anti-HBc IgM described here has a high specificity and sensitivity. The diagnostic relevance needs further evaluation, including quantitation of anti-HBc IgM, but the results presented indicate that anti-HBc IgM may be helpful in differentiating between prior and recent or ongoing hepatitis B infection.

Antibodies, Viral↗

Persistence of viral hepatitis A and B in an isolated Caucasian population.

The persistence of viral hepatitis A (HAV) and hepatitis B (HBV) in the Faroe Islands, a Caucasian, high sanitary standard, isolated area, was studied by means of notified clinical cases of hepatitis and by specific antibody testing of population samples. Large epidemics of hepatitis occurred on the Faroe Islands in 1928-1930 and 1955-1958, although sporadic cases have been continuously recorded. Presence of antibody to HAV (anti-HAV) was confined to age groups exposed to the epidemics, while antibody to HBV surface antigen (anti-HBs) was demonstrated in all age groups, including children. This study provides further evidence for the concept of HAV as a self-limited infection, unable to maintain itself by chronic virus carriers. HBV, by contrast, again is shown to survive even in small populations with high sanitary conditions and to have no recognizable risk factors.

Adolescent↗

Hepatitis A virus in the liver and intestine of marmosets after oral inoculation.

A total of 12 seronegative marmosets (Saguinus mystax) were inoculated orally with hepatitis A virus (HAV) and sacrificed at 3- to 4-day intervals. Tissues from the livers, intestines, mesenteric lymph nodes, and spleens were obtained for immunofluorescence studies, and bile and intestinal contents were obtained for enzyme-linked immunosorbent assay studies. Two marmosets sacrificed on days 34 and 41 after inoculation developed antibody to HAV and demonstrated HAV in their livers but not in any part of their intestinal tissues. None of the remaining marmosets sacrificed from days -3 to 31 survived long enough to develop antibody to HAV, but an additional two marmosets, which were sacrificed on days 21 and 31, demonstrated HAV in their livers and also in bile but not in the intestinal tissues or their contents. The mesenteric lymph nodes and spleens were negative for HAV by immunofluorescence in all the marmosets. No evidence of HAV replication was demonstrated in any part of the intestine at any time during the incubation period or during acute illness in the marmosets inoculated orally with HAV. The shedding of HAV in stools in the late incubation period can be explained by excretion of HAV from the livers with the bile.

Alanine Transaminase↗

Etiological characterization of hepatitis B surface antigen-negative hepatitis among adult patients in Athens, Greece.

In a 4-month period, 216 cases of acute viral hepatitis were diagnosed in adults at the Infectious Diseases Hospital, Athens, Greece. Twenty-six percent of these were hepatitis B surface antigen negative. A full set of clinical specimens was obtained from 19 of these patients, who were studied in depth for the etiology of their hepatitis. A total of 7 of the 19 patients had serological evidence of hepatitis A virus infection, and 2 had evidence of recent hepatitis B virus infection. The remaining 10 patients lacked evidence of hepatitis A virus, hepatitis B virus, cytomegalovirus, or Epstein-Barr virus infection related to their illness and were classified as having type non-A, non-B hepatitis. Types A and non-A, non-B hepatitis were clinically similar in these adults patients. However, patients with type non-a, non-B hepatitis were, on the average, older and more likely to have received parenteral inoculations during the 6 months before contracting hepatitis. Approximately 76% of the 216 consecutive cases of acute viral hepatitis were probably type B, approximately 10% were probably type A, and approximately 14% were probably type non-A, non-B, although the latter two types may be underestimated because of the possibility of superinfection with these viruses in asymptomatic hepatitis B surface antigen carriers. Thus, all three types of viral hepatitis appear to be important in the etiology of liver disease in Athens, Greece.

Acute Disease↗

Hepatitis type A, B, and non-A non-B in fulminant hepatitis.

Serological investigations for hepatitis B surface and e antigen, antibody to hepatitis B surface, core and e antigen and antibody to hepatitis A virus were carried out in 22 patients with fulminant hepatitis admitted to Medical Department A, Rigshospitalet, Copenhagen, in 1970-77. Nine patients had hepatitis type B and four type A. One patient had evidence of both type A and B infection, whereas the remaining eight patients showed no evidence of type A or B infection. Two of these had been treated with disulfiram and a drug aetiology could not be excluded, but in six patients no known cause of fulminant hepatitis could be determined and these patients were classified as having hepatitis type non-A non-B. The survival rate was not statistically different for patients having type A, B, or non-A non-B hepatitis.

Acute Disease↗

The role of acute hepatitis type A, B, and non-A non-B in the development of chronic active liver disease.

In 19 patients followed from biopsy-verified acute viral hepatitis to chronic active liver disease and 74 patients followed to complete resolution verified by a normal liver biopsy, sera from the acute phase were studied for serologic evidence of hepatitis type A and B. Eleven of the 19 patients who developed chronic active liver disease progressed from acute hepatitis type B and 7 from acute hepatitis type non-A non-B. One patient could not be classified because the sera were exhausted. None had serological markers of actual hepatitis type A infection. Of the 74 patients with a histologically complete resolution, the acute episode could be classified as type B hepatitis in 47 and type A hepatitis in 13 patients. The remaining 14 patients were classified as having acute viral hepatitis type non-A non-B. Our findings confirm that type B and non-A non-B hepatitis may give rise to chronic liver disease, whereas type A hepatitis so far has not been demonstrated to initiate a chronic liver disease.

Age Factors↗

Circulating autoantibodies in patients with acute viral hepatitis. Relation to etiology and clinical course.

The prevalences of liver-cell-membrane antibody (LMA), smooth-muscle antibodies, antinuclear antibodies and antimitochondrial antibodies were evaluated in 63 selected patients with acute viral hepatitis of types A, B, and non-A non-B. Twenty patients had a complete, uneventful recovery, 19 patients had fulminant hepatitis, and 24 progressed to a chronic liver disease. Acute-phase and follow-up sera from all patients were tested for antibodies of IgA, IgM, and IgG class. The prevalences of the IgM autoantibodies in the acute-phase sera were not significantly different in the three groups irrespective of clinical outcome. Similar prevalences were found with respect to IgG class; however, antinuclear antibodies of IgG class were predominantly found in acute-phase sera from patients who later progressed to a chronic liver disease. The diagnostic significance of these autoantibodies was stressed by the fact that 85% of the sera with LMA of IgG class and 100% of the follow-up sera with smooth-muscle antibodies of IgG class at a titer at or above 1:128 originated from patients with chronic liver disease. A similar pattern was found for antinuclear antibodies, and testing for all these antibodies of IgA anad IgM class did not yield any further information. In some serum samples LMA could be found independently of smooth-muscle antibody and vice versa, indicating the essential difference between these two autoantibodies.

Acute Disease↗

Antibody to hepatitis A virus in plasma of Danish blood donors and in immune serum globulin produced in Denmark.

Antibody to hepatitis A virus (anti-HAV) was studied in 225 Danish blood donors. The prevalence was found to be 3% in individuals younger than 30 years but then rising with age to 78% in individuals older than 55 years. The titer of anti-HAV in 51 lots of Danish immune serum globulin (ISG) produced from June 1969 to June 1977 was found to vary between 2300 and 5900 except for 2 with titers of 14000 and 28000. The titers did not change during the period and compared well to 3 lots of ISG produced in the USA and selected by the manufacturer because of a high anti-HAV titer.

Adolescent↗

Acute non-A, non-B hepatitis--clinical, epidemiological and histological characteristics.

Among 73 consecutive patients with biopsy documented acute non-toxic hepatitis, half of the patients (49%) had acute type B hepatitis, while 27 patients (37%) had acute type A infection. One patient had a significant rise in antibodies against cytomegalovirus. The remaining 10 patients (14%) fulfilled the criteria of hepatitis type non-A, non-B. The main type of exposure for hepatitis A was visit to endemic hepatitis areas (41%), and for type B it was drug addiction (46%). Half of the patients with hepatitis non-A, non-B had no known hepatitis exposure while some had visited endemic hepatitis areas or were drug addicts. The patients with non-A, non-B hepatitis had significantly less biochemical changes as compared to the patients with hepatitis B. In contrast, the histological findings showed the greatest activity in the biopsies from patients with hepatitis B and non-A, non-B. Follow-up liver biopsies in half of the patients with non-A, non-B hepatitis showed no signs of chronic active liver disease. It is concluded that hepatitis type non-A, non-B is a significant problem in Denmark.

Acute Disease↗