[Autoimmune chronic active hepatitis--early diagnosis is the best help].
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Biomedical subjects
Publications and source records attributed to O Weiland.
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The influence of age, origin, and region of domicile on the prevalence of hepatitis B virus markers was investigated in a cross-sectional sample of young Swedish adults. Sera and demographic data were prospectively collected from 2,000 male conscripts and 2,000 pregnant women from urban and rural parts of Sweden during 1988-1989. A total of 10 of 4,000 (0.25%) were found to be hepatitis B surface antigen carriers, and 62 (1.6%) were positive for both anti-hepatitis B core antigen and anti-hepatitis B surface antigen, indicating a present or prior hepatitis B virus infection. Origin from a country with high hepatitis B virus endemicity and increasing age were factors associated with serologic signs of a present or prior hepatitis B virus infection, whereas region of domicile was not. In addition, seven individuals positive only for anti-hepatitis B core antigen (blocking greater than 70% in the test) and 39 positive only for anti-hepatitis B surface antigen (with a titer of greater than or equal to 10 international units/liter) were believed to have been exposed to hepatitis B virus. Altogether, these results indicated that 3% of young Swedes had encountered hepatitis B virus and that origin from a country with high hepatitis B virus endemicity was the factor that most strongly was associated with a present or past hepatitis B virus infection.
The prevalence of hepatitis B virus (HBV) markers and exposure to risks possibly associated with HBV transmission were investigated in 797 health care workers (HCW) from Stockholm. Altogether, 31/797 (3.9%) persons were positive for at least one HBV marker, 8.0, 7.9 and 6.4% respectively of children's nurses, laboratory assistants and psychiatric assistant nurses. A history of exposure to needle-stick injuries from any patient, was more often obtained from HCW with HBV markers than from HCW without such markers. The prevalence of HBV markers increased with age and duration of occupation in health care. Most HCW had been exposed to at least one occupational risk for HBV transmission early in their professional careers. Although the risk of acquiring HBV at present is low, the virus constitutes a potential occupational hazard for non-vaccinated HCW in Stockholm, a risk which may increase in the future since the number of chronic HBsAg carriers is increasing in Sweden.
Serial serum samples from cardiac patients with a history of chronic or resolved post-transfusion non-A, non-B hepatitis were analyzed by a combination of cDNA synthesis and the polymerase chain reaction (cDNA/PCR) to amplify HCV RNA. Analysis of sera drawn after the acute hepatitis episode from 8 of the patients who had an acute, resolving HCV infection showed no detectable levels of HCV RNA when primers from the NS3 region were used. Evaluation of these sera with primers from the 5'-untranslated (5'-UT) region revealed that one patient was positive for HCV RNA. Further analysis of serial serum samples available from two of these patients indicated that a resolved infection was associated with a disappearance of detectable HCV RNA after a peak level during the acute phase of the disease. In contrast, post-acute samples from 4 of 6 patients with symptomatic acute HCV infection evolving to chronicity were positive for HCV RNA using primers from the NS3 region, however, upon retesting with primers from the 5'-UT region, all 6 patients were found to be positive. Analysis of serial serum samples from 2 of these patients showed the persistence of HCV RNA in 70% of the samples. These two patients were subsequently treated with interferon alpha-2b. One patient resolved his disease and normalized his aminotransferase level during treatment and thereafter, while the other relapsed upon cessation of treatment. In these two patients, normalization of ALT levels was consistent with the absence of HCV RNA while relapse of disease was confirmed by the reappearance of detectable levels of HCV RNA. These results indicate the utility of HCV RNA as a marker for persisting HCV viremia and in differentiating patients with ongoing active HCV infection from those with an acute resolving disease.
Thirty-three patients with chronic hepatitis C/non-A, non-B were included in a randomized controlled study of interferon-alpha 2b (IFN-alpha 2b) treatment, 3 x 10(6) U three times weekly for 36 weeks. Using an immunoperoxidase technique, frozen liver biopsy specimens were examined with MoAbs for the presence of T helper cells (CD4), T suppressor/cytotoxic cells (CD8), total T cells (CD2) and B cells (CD22) before and after treatment. beta 2-microglobulin (beta 2-MG) expression on hepatocytes was semiquantified using a scoring system on sections from paraffin-embedded biopsy specimens. Serum levels of beta 2-MG were analysed with a radioimmunoassay technique. Intralobular T helper and T suppressor/cytotoxic cells declined significantly in the treated patients but not in the controls. The portal CD4/CD8 ratio did not change. Before treatment, serum beta 2-MG levels and hepatocyte beta 2-MG expression were significantly higher in patients with chronic active hepatitis compared to patients with chronic persistent hepatitis. Serum beta 2-MG levels increased significantly in responders during IFN treatment, with a maximum after 12 weeks. However, in the liver, the hepatocyte beta 2-MG expression was significantly decreased after treatment. Thus, IFN-alpha treatment does not seem to induce an increased HLA class I antigen hepatocyte expression in chronic non-A, non-B hepatitis, which favours the hypothesis that its anti-viral effects are more important in modulating the disease activity.
Thirty-three patients with chronic hepatitis non-A, non-B/C were included in a randomized controlled study of recombinant alpha-2b interferon treatment 3 MU three times weekly for 36 weeks. In lysed whole blood, lymphocyte subpopulations were enumerated by flow cytometry detecting fluorescein or phycoerytrin conjugated monoclonal antibodies directed against seven different epitopes. Patients with chronic active hepatitis were significantly older than patients with chronic persistent hepatitis (p less than 0.05). Before treatment, the proportions of different subsets of lymphocytes were within the normal reference values and the CD4/CD8 ratio was also normal. No increased activation of T-cells was noticed. Patients over 50 years of age, however, had a significantly increased (p less than 0.01) proportion of HLA-DR+ lymphocytes, mainly B-cells. Treatment decreased the absolute number of peripheral blood leukocytes and lymphocytes. There was also a significant decline in the proportion of CD8+ lymphocytes and NK-cells, and a significant increase in the proportion HLA-DR+ cells and of the CD4/CD8 ratio. The increased proportion of HLA-DR+ cells, however, did not reflect peripheral T-cell activation; instead, it was due to increasing B lymphocyte numbers.
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Sulfur amino acid metabolism was studied in patients with mild to severe forms of liver dysfunction and compared with that of healthy controls. Patients with mild liver dysfunction (for example, Gilbert's syndrome) had a normal sulfur amino acid metabolism. With increased inflammatory activity and cirrhosis (for example, chronic active hepatitis, alcohol-induced cirrhosis, and hepatic coma) a decreased ability to metabolize methionine (to cysteine, with cystathionine accumulation) and cysteine (to inorganic sulfate, with thiosulfate and N-acetylcysteine accumulation) was found. In contrast, transaminative metabolism of sulfur amino acids was preserved in patients with advanced forms of liver dysfunction, suggesting that transamination of sulfur amino acids is performed not only in the liver but also in extrahepatic tissues. Some implications of these findings are discussed.
28 patients with posttransfusion non-A, non-B (NANB) hepatitis in Stockholm, Sweden, were studied for seroconversion to hepatitis C virus antibodies (anti-HCV) and time lag to seroconversion by first and second generation tests. 15/28 patients (54%) seroconverted to anti-HCV with a first generation anti-HCV ELISA using C100-3 from the nonstructural (NS) region 4 of the HCV genome and 23 (82%) with a second generation anti-HCV ELISA including also antigens from the core and NS3 regions of the HCV genome. The mean time from onset of hepatitis to seroconversion was 6.1 weeks (0-18 weeks) with the first generation test and 2.3 weeks (0-7 weeks) with the second generation test. Development of chronic hepatitis was noticed in 14/23 (61%) patients who seroconverted to anti-HCV with the second generation ELISA and in none of 5 patients with posttransfusion NANB hepatitis who did not seroconvert. The inclusion of antigens from the core and NS3 regions of the HCV genome has increased the sensitivity of the second generation anti-HCV ELISA as compared to the first generation ELISA and also shortened the time lag to seroconversion in patients with posttransfusion hepatitis C. Patients with posttransfusion NANB hepatitis seroconverting seem more prone to develop chronic disease than patients not seroconverting.
In an open controlled study 286 health care workers in Stockholm, Sweden, received 20 micrograms of a recombinant hepatitis B vaccine (Engerix B) by the intramuscular route, and 383 2 micrograms by the intradermal route. Seroconversion to protective anti-HBs levels (anti-HBs titre greater than or equal to 10 IU/l) was achieved in 94% of the i.m. and 89% of the i.d. vaccinees. Female sex, intramuscular vaccination, young age, and being a non-smoker were associated with a higher response rate and a higher geometric mean anti-HBs titre than male sex, intradermal vaccination, old age and being a smoker. If an acceptable response rate to protective anti-HBs levels of 85% is chosen, intradermal vaccination can be used as a cost reducing strategy for all women and for non-smoking men less than 30 years of age, as estimated in a logistic regression model. Due to the variable antibody response in different individuals, post vaccination testing for anti-HBs titres is recommended in health care workers, regardless of vaccination route.
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We evaluated oral ribavirin as therapy for chronic hepatitis C infection in a pilot study including 10 patients. Patients (7 men, 3 women; mean age 40 years, range 23-54) all had biopsy-proven chronic non-A, non-B hepatitis and were repeatedly positive for antibodies to hepatitis C virus. Treatment was with oral ribavirin 1000-1200 mg per day in two divided doses for 12 weeks. The median serum alanine aminotransferase concentration for all patients at enrollment was 3.15 mu kat/l (range 1.22-7.79) and decreased significantly (p less than 0.005) to 1.25 mu kat/l (0.78-2.04) after 12 weeks of treatment. Within 6 weeks of the end of treatment the median serum alanine aminotransferase concentration was not significantly different from that before treatment. Side-effects were mild and fully reversible after cessation of therapy. We conclude that ribavirin is the first drug to offer a potentially effective oral treatment for chronic hepatitis C. It should be further evaluated in controlled trials, possibly in combination with interferon alpha.
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A specific IgM solid-phase enzyme-linked immunoassay for the diagnosis of a recent infection by hepatitis C virus (HCV) was developed. The assay utilizes a structural antigen encoded by sequences at the 5' end of HCV (core region) and non-structural (NS) antigens encoded by the NS-3 (33c) and NS-4 (c100-3) regions of the HCV genome. Serial serum samples from several clinically diagnosed post-transfusion non-A, non-B hepatitis patients were analyzed for anti-HCV IgM. This antibody was frequently but transiently detected. Anti-HCV core IgM was more frequently detected than anti-c100-3 or anti-33c IgM. In individuals who resolved their HCV infection or progressed to chronicity, anti-HCV IgM was produced transiently at or near the onset of clinically diagnosed acute hepatitis.
The histological outcome in liver biopsies following 9 months of interferon alpha-2b treatment was assessed in detail in 19 patients with chronic posttransfusion non-A, non-B hepatitis (PTH-NANB) and compared with 12 untreated PTH-NANB patients. Fourteen (74%) treated and 7 (58%) control patients were reactive for antibodies against hepatitis C virus (anti-HCV). Liver biopsies taken before and after the 9-month period were scored numerically for portal inflammation, piecemeal necrosis (PMN) and fibrosis, without knowledge of whether the specimens came from control or treated patients. There were no score differences in the initial biopsies between the treated and control group. In the follow-up biopsies the treated group showed significantly less portal inflammation, PMN and fibrosis than the control group (p less than 0.05-0.01). When paired samples from the treated group were compared, significantly regressed portal inflammation, PMN and fibrosis were noted in the follow-up biopsies (p less than 0.05-0.001). The presence or not of anti-HCV antibodies in serum had no impact on the histological response to interferon treatment. We conclude that a 9-month course of interferon alpha-2b treatment significantly diminishes not only inflammation but also fibrosis in the liver of patients with PTH-NANB whether they are anti-HCV reactive or not.
Eight of 13 Swedish patients (62%), studied prospectively, who developed posttransfusion non-A, non-B hepatitis (PT-NANBH) had earlier been found to seroconvert for antibodies to hepatitis C virus (anti-HCV) c100-3 in the first-generation anti-HCV enzyme-linked immunosorbent assay 1-18 (mean, 8) weeks after onset of hepatitis. By using a second-generation test utilizing antigens encoded by the core NS3 and NS4 region of HCV, a further four patients non-reactive to c100-3 (NS4) were found to seroconvert. Thus 12 of 13 (92%) Swedish patients with PT-NANBH were shown to have HCV infection. In addition, the serologic reactivity for several individual synthetic peptides and/or recombinant HCV proteins was studied in seven anti-HCV c100-3 seroconverts studied long-term after onset of acute PT-HCV infection. No special patterns were found that could differentiate patients who recovered from those who developed chronic HCV infection. It was concluded that the addition of new recombinant antigens derived from the core and NS3 region to c100-3 (NS4) both improved the sensitivity of the anti-HCV test and shortened the window phase to seroconversion.
The transmission of non-A, non-B hepatitis (NANB)/hepatitis C virus (HCV) was studied in patients undergoing open-heart surgery and related to the reception of blood products and hospitalization and surgery per se. Posttransfusion hepatitis NANB was noticed in 17/390 (4.4%) patients receiving heterologous blood and 8/16 tested became positive for anti-HCV (Ortho HCV ELISA), all within 5 months after onset of hepatitis. Among patients with normal ALAT before surgery and during follow-up, who had received heterologous blood, 1/50 seroconverted after 6 months. This patient probably had a subclinical HCV infection, or possibly a temporary non-specific anti-HCV reactivity with a maximum optical density/cut-off ratio (OD/CO) of 1.2, whereas all posttransfusion hepatitis C cases had OD/CO ratios greater than 4. No hepatitis occurred among the 92 non-transfused patients and no seroconversion was found in any of 62 non-transfused patients tested 6 months after the operation. It was concluded that (1) hospitalization and surgery per se does not seem to offer a risk of hepatitis NANB/C, and (2) seroconversion to for HCV occurs in only 50% of Swedish patients with acute posttransfusion NANB hepatitis.
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