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Osasona OG, Oguntoye OO, Arowosaye AO, Abdulkareem LO, Adewumi MO, Happi C, Folarin O. Patterns of hepatitis b virus immune escape and pol/rt mutations across clinical cohorts of patients with genotypes a, e and occult hepatitis b infection in Nigeria: A multi-centre study. Virulence 2023; 14:2218076. [PMID: 37262110 DOI: 10.1080/21505594.2023.2218076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 03/27/2023] [Accepted: 05/20/2023] [Indexed: 06/03/2023] Open
Abstract
Hepatitis B virus (HBV) immune escape and Pol/RT mutations account for HBV immunoprophylactic, therapeutic, and diagnostic failure globally. Little is known about circulating HBV immune escape and Pol/RT mutants in Nigeria. This study focused on narrowing the knowledge gap of the pattern and prevalence of the HBV mutants across clinical cohorts of infected patients in southwestern Nigeria. Ninety-five enrollees were purposively recruited across clinical cohorts of HBV-infected patients with HBsAg or anti-HBc positive serological outcome and occult HBV infection. Total DNA was extracted from patients' sera. HBV S and Pol gene-specific nested PCR amplification was carried out. The amplicons were further sequenced for serotypic, genotypic, phylogenetic, and mutational analysis. HBV S and Pol genes were amplified in 60 (63.2%) and 19 (20%) of HBV isolates, respectively. All the sixty HBV S gene and 14 of 19 Pol gene sequences were exploitable. The ayw4 serotype was predominant (95%) while ayw1 serotype was identified in 5% of isolates. Genotype E predominates in 95% of sequences, while genotype A, sub-genotype A3 was observed in 5%. Prevalence of HBV IEMs in the "a" determinant region was 29%. Commonest HBV IEM was S113T followed by G145A and D144E. The Pol/RT mutations rtV214A and rtI163V among others were identified in this study. This study provided data on the occurrence of existing and new HBV IEMs and Pol gene mutations in Nigeria.
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Affiliation(s)
- Oluwadamilola G Osasona
- African Centre of Excellence for the Genomics of Infectious Diseases, Redeemers University, Ede, Nigeria
| | | | - Abiola O Arowosaye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Lukman O Abdulkareem
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
| | - Moses O Adewumi
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Christian Happi
- African Centre of Excellence for the Genomics of Infectious Diseases, Redeemers University, Ede, Nigeria
| | - Onikepe Folarin
- African Centre of Excellence for the Genomics of Infectious Diseases, Redeemers University, Ede, Nigeria
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Mahdy KA, Ahmed HH, Mannaa F, Abdel-Shaheed A. Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases. World J Gastroenterol 2007; 13:785-90. [PMID: 17278204 PMCID: PMC4066014 DOI: 10.3748/wjg.v13.i5.785] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between serum insulin-like growth factor 1 (IGF-1), osteocalcin, and parathyroid hormone (PTH) levels with the etiology and clinical condition of patients with chronic liver disease.
METHODS: Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection: bilharziasis (9 patients), hepatitis B virus (HBV, 12 patients) and hepatitis C virus (HCV, 29 patients). The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group. HBsAg, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). Anti-bilharzial antibodies were detected by indirect haem- agglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted.
RESULTS: Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin (14.7 ± 0.54 vs 3.6 ± 0.10, P < 0.05), while that for PTH was positively correlated with total protein (70.1 ± 2.17 vs 6.7 ± 0.10, P < 0.05) in patients with HCV infection.
CONCLUSION: Low serum IGF-1 level seems to play a critical role in the bone loss in patients with chronic liver disease. Elevated biochemical markers of bone remodeling suggest high-turnover in patients with viral infection and reflect severity of the clinical stage.
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Affiliation(s)
- Karam A Mahdy
- Medical Biochemistry Department, National Research Centre, Dokki 12311, Cairo, Egypt.
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Hellström UB, Sylvan SP, Decker RH, Sönnerborg A. Immunoglobulin M reactivity towards the immunologically active region sp75 of the core protein of hepatitis C virus (HCV) in chronic HCV infection. J Med Virol 1993; 39:325-32. [PMID: 8388029 DOI: 10.1002/jmv.1890390412] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Serum samples from a cohort of patients with chronic hepatitis C virus (HCV) infection were assayed for IgM anti-HCV/core reactivity with a "site-specific" ELISA, in which the solid phase was charged with the synthetic polypeptide analogue corresponding to the first 75 amino acids of the HCV core antigen (sp75). Thirteen of 24 (54%) patients exhibited IgM anti-sp75 reactivity. Both high-titered (1/16,000-1/32,000) and low-titered (1/1,000-1/4,000) IgM anti-sp75 reactive sera were found. IgM anti-sp75 antibodies persisted in the circulation over a long period in patients with fluctuating abnormal ALT levels. There was a striking association between detection of specific IgM anti-sp75 reactivity and the presence of HCV RNA in serum. Thus 11 of 15 (73%) sera containing HCV RNA also contained IgM anti-sp75 antibodies, while none of the HCV RNA-negative sera were IgM anti-sp75 reactive. Five of 11 patients without detectable levels of specific IgM anti-sp75 antibodies had their ALT levels returned to normal within 8 months to 3 years. Furthermore, a significant correlation was noted between the specific IgM anti-sp75 titers and the concentration of total plasma IgM, indicating that the immunological active region sp75 within the capsid of HCV has the capacity to induce an IgM secretion, which constitutes a substantial portion of the total plasma IgM, in patients with chronic HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- U B Hellström
- Department of Environmental, Health and Infectious Diseases Control, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden
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4
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Mortimer PP, Parry JV. Non-invasive virological diagnosis: Are saliva and urine specimens adequate substitutes for blood? Rev Med Virol 1991. [DOI: 10.1002/rmv.1980010204] [Citation(s) in RCA: 53] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Müller F, Müller KH. Detection of anti-HIV-1 immunoglobulin M antibodies in patients with serologically proved HIV-1 infection. Infection 1988; 16:115-8. [PMID: 3163678 DOI: 10.1007/bf01644317] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Serum samples from 247 patients with positive HIV-1 IgG serology were investigated for specific IgM antibodies. We found that 109 also reacted positively with a least one antigen in an HIV-1 IgM Western Blot and only 31 in an HIV-1 IgM enzyme-linked immunosorbent assay (ELISA). It was shown that in some of the persons, specific IgM antibodies against the gp160/120, p66, p55, gp41, p24, and p17 antigens of the virus are synthesized at some time after infection. IgM antibodies to the endonuclease-related p31 antigen were observed in one serum only. IgM antibodies against the gp160/120, p66, gp41, and p17 antigens seemed to disappear early after infection. Those against the p55 and the p24 antigens were found in 62% and 75% of investigated cases, respectively. A direct correlation between the Western Blot patterns and the IgM ELISA results was not found.
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Affiliation(s)
- F Müller
- Department of Medical Microbiology, Institute of Hygiene, Hamburg
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6
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Czaja AJ, Shiels MT, Taswell HF, Wood JR, Ludwig J, Chase RC. Frequency and significance of immunoglobulin M antibody to hepatitis B core antigen in corticosteroid-treated severe chronic active hepatitis B. Mayo Clin Proc 1988; 63:119-25. [PMID: 3339905 DOI: 10.1016/s0025-6196(12)64944-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
To assess the frequency and significance of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc) in corticosteroid-treated severe chronic active hepatitis B, we tested 96 serum samples from 16 patients who were seropositive for hepatitis B surface antigen (HBsAg) (group 1) and 8 HBsAg-negative, anti-HBc-positive patients (group 2) by enzyme-linked immunoassay. Samples obtained in the presence and absence of disease activity before, during, and after long-term corticosteroid therapy (mean duration, 42 +/- 7 months) were evaluated. Seropositivity for IgM antibody was demonstrated in 12 group 1 patients, including 9 tested before corticosteroid therapy; no group 2 patients were seropositive. Seropositivity was more common in serum samples obtained during active than during inactive disease (51% versus 22%; P less than 0.05) and more frequent in serum samples that contained hepatitis B e antigen (46% versus 11%; P less than 0.02) and hepatitis B virus deoxyribonucleic acid (50% versus 24%; P less than 0.05) than in those without these markers. In some patients, seropositivity persisted or recurred intermittently during corticosteroid therapy for up to 57 months. We conclude that seropositivity for IgM antibody can be demonstrated frequently by enzyme-linked immunoassay in corticosteroid-treated patients with severe disease. Seropositivity reflects active virus replication, and it is commonly associated with inflammatory activity. The duration of seropositivity may be protracted during long-term corticosteroid therapy.
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Affiliation(s)
- A J Czaja
- Division of Gastroenterology and Internal Medicine, Mayo Clinic, Rochester, MN 55905
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Affiliation(s)
- S M Lemon
- University of North Carolina, Chapel Hill, NC 27599-7030
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Chu CM, Liaw YF, Yang CY, Sheen IS. Diagnosis of acute type B hepatitis by a solid phase u-antibody capture radioimmunoassay for IgM class antibody to hepatitis B core antigen: a diagnostic proposal based on a prospective study. LIVER 1987; 7:182-7. [PMID: 3613887 DOI: 10.1111/j.1600-0676.1987.tb00340.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The diagnostic and prognostic significance of IgM anti-HBc, studied by a solid phase u-antibody capture radioimmunoassay at a serum dilution of 1:4000, was prospectively evaluated in 73 adult patients with acute hepatitis seropositive for hepatitis B surface antigen (HBsAg). Of the 73 cases, 20 (27.4%) cleared their HBsAg within 6 months, while the remaining 53 (72.6%) did not. HBsAg seroconversion to its antibody occurred in 15 (93.8%) of the 16 patients positive for IgM anti-HBc with S/N ratios above 5.0, as did 5 (26.3%) of the 19 with S/N ratios between 2.1 to 5.0, and none (0%) of the 38 negative for IgM anti-HBc (S/N ratios less than 2.1). Therefore, a S/N ratio of IgM anti-HBc above 5.0 is diagnostic for acute type B hepatitis. However, low S/N ratios (2.1-5.0) of IgM anti-HBc were observed in the early stage of some patients with acute type B hepatitis, and would increase to a level greater than 5.0 when assayed again 1-2 weeks later. It was therefore suggested that repeated testing of anti-HBc IgM is mandatory for accurate diagnosis of acute type B hepatitis in patients whose initial serum specimens showed low S/N ratios of IgM anti-HBc. According to this criterion, only 22 (30.1%) of the 73 patients with acute hepatitis seropositive for HBsAg in Taiwan were true acute type B hepatitis, of whom 2 (9.1%) subsequently became chronic HBsAg carriers, while the remaining 51 (69.9%) were chronic HBsAg carriers with other superimposed forms of acute hepatic injury.
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10
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Gerlich WH, Uy A, Lambrecht F, Thomssen R. Cutoff levels of immunoglobulin M antibody against viral core antigen for differentiation of acute, chronic, and past hepatitis B virus infections. J Clin Microbiol 1986; 24:288-93. [PMID: 3745425 PMCID: PMC268891 DOI: 10.1128/jcm.24.2.288-293.1986] [Citation(s) in RCA: 69] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The titer of antibody against core antigen of hepatitis B virus in the immunoglobulin M class (IgM anti-HBc) was determined by an IgM capture assay of reduced sensitivity (30 arbitrary units). The distribution of titers among 235 acute hepatitis patients who were hepatitis B surface antigen (HBsAg) positive suggested that 600 U forms a lower cutoff value for acute hepatitis B. Clinically apparent cases of acute hepatitis with high IgM anti-HBc and without HBsAg were rare (2.6%). Acute, non-B hepatitis in HBsAg carriers was more frequent (9.4%). In chronic hepatitis B, 39% of 174 biopsy-proven cases had moderate titers of 30 to 600 U, whereas healthy HBsAg carriers were rarely (4/84) positive. In mild or inapparent infections without HBsAg, titers were between 50 and 400 U. Thus, sufficiently accurate and sensitive quantitation of IgM anti-HBc allows for differentiation of acute and nonacute hepatitis B virus infection in acute hepatitis, partial differentiation between clinically symptomatic and asymptomatic chronic infections, and identification of recent subclinical infections.
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11
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Lindenschmidt EG. Follow-up studies on IgM anti-HBc during chronic hepatitis B. ZENTRALBLATT FUR BAKTERIOLOGIE, MIKROBIOLOGIE, UND HYGIENE. SERIES A, MEDICAL MICROBIOLOGY, INFECTIOUS DISEASES, VIROLOGY, PARASITOLOGY 1986; 261:461-70. [PMID: 3765952 DOI: 10.1016/s0176-6724(86)80078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Sera of 190 HBsAg positive chronic hepatitis B patients were followed up for IgM class antibodies to hepatitis B virus core antigen (IgM-anti-HBc) by a commercial ELISA (Abbott) as well as a 19S(IgM) RIA until these antibodies were no longer detectable. IgM anti-HBc was detected only up to two of five years after onset of acute disease. The periods of detectable IgM anti-HBc in 34 chronic persistent and 36 chronic active hepatitis B (CPH, CAH) patients did not differ significantly on the basis of chi 2-test. 56% of the CPH and 47% of the CAH patients showed markers of infectivity in the sera recently cleared of IgM anti-HBc. Sera of both the IgM anti-HBc positive CPH and CAH patients had on the average fivefold elevated aminotransferase (SGPT) activity. In sera recently cleared of IgM anti-HBc, mean SGPT activity was detected twofold the normal value in CPH and threefold in CAH patients. Inflammatory activity in the liver biopsies was seen highly increased both in the IgM anti-HBc positive CPH and CAH patients. Fibrosis was most progressed and cirrhosis observed mainly in the liver biopsies of the IgM anti-HBc cleared CAH patients. In 3 IgM anti-HBc cleared chronic hepatitis B patients (CPH n = 1, CAH n = 2) converted to anti-HBe, IgM anti-HBc was detectable anew after a HBV superinfection with other HBsAg subtypes.
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12
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Vilja P, Turunen HJ, Leinikki PO. Determination of immunoglobulin M antibodies for hepatitis B core antigen with a capture enzyme immunoassay and biotin-labeled core antigen produced in Escherichia coli. J Clin Microbiol 1985; 22:637-40. [PMID: 3908476 PMCID: PMC268482 DOI: 10.1128/jcm.22.4.637-640.1985] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
A new capture enzyme immunoassay for the determination of immunoglobulin M (IgM) antibodies against hepatitis B core antigen (HBcAg) is described. Core antigen produced in Escherichia coli was labeled with biotin and subsequently detected by an avidin-biotin-peroxidase complex. The biotin-labeled core antigen was effective at concentrations as low as 20 ng/ml. Of 561 serum samples from different groups of patients that were tested, 465 samples were negative for other hepatitis B virus markers and also for anti-HBcAg IgM. Sera from the early stages of hepatitis B infection had high levels of anti-HBcAg IgM, and a clear correlation with the acuteness of the disease was observed in 45 follow-up sera from 23 patients with acute or recent hepatitis B. Sera from 21 patients with past hepatitis B were all negative for anti-HBcAg IgM. Twenty serum samples from chronic carriers of hepatitis B surface antigen showed slightly elevated antibody levels for anti-HBcAg IgM. Ten sera which were positive for anti-HBcAg IgG antibodies and had high levels of rheumatoid factor were negative for anti-HBcAg IgM.
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13
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Liaw YF, Chu CM, Lin LH, Ling CM, Huang MJ. Serodiagnosis of acute B hepatitis: comparison between a competitive binding radioimmunoassay and an enzyme linked immunosorbent assay for IgM antibody to hepatitis B core antigen. SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES 1985; 17:251-7. [PMID: 4059865 DOI: 10.3109/inf.1985.17.issue-3.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The standard radioimmunoassay for anti-HBc (CORAB) was modified for the differential detection of anti-HBc IgM by incorporation of a step in which anti-HBc IgG was preferentially absorbed by Staphylococcus aureus cells (Protein A). The ratio (R) of anti-HBc IgM to total anti-HBc was evaluated by computing the ratio of sample cpm's after and before protein A absorption. The R values of acute B hepatitis ranged from 0.9 to 2.1 (mean 1.3 +/- 0.3) while those of chronic HBsAg carriers ranged from 3.1 to 8.3 (mean 4.9 +/- 1.1). Adopting 2.1 as the upper limit of R value for acute B infection, this modified CORAB was shown to have excellent correlation with enzyme immunoassay, and to be capable of differentiating acute from persistent HBV infection in HBsAg positive patients, and discriminating acute B hepatitis from non-A, non-B hepatitis in HBsAg negative but anti-HBc positive acute hepatitis.
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Chen DS, Sung JL, Lai MY, Sheu JC, Yang PM, Lee SC, Chen SH, Chang MH, Ko TM, Lee TY. Inadequacy of immunoglobulin M hepatitis B core antibody in detecting acute hepatitis B virus infection in infants of HBsAg carrier mothers. J Med Virol 1985; 16:309-14. [PMID: 4031828 DOI: 10.1002/jmv.1890160402] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
To study the usefulness of IgM hepatitis B core antibody (anti-HBc IgM) for detecting hepatitis B virus infections in infants of hepatitis B surface antigen (HBsAg) carrier mothers, serial serum samples from 86 infants of carrier mothers were tested for anti-HBc IgM with a highly specific enzyme immunoassay. Asymptomatic hepatitis B infection occurred frequently in infants under 12 mo of age. Anti-HBc IgM never became positive in 25 infants infected under 9 mo old. It was positive in only 1 of 6 infected at 9 mo and 4 of 13 infected at 12 mo of age. The IgM antibody lasted for less than 6 mo. Although the infection was delayed in 28 infants receiving hepatitis B immune globulin, the poor anti-HBc IgM response did not seem to be due to the immune prophylaxis. Our study clearly indicates the limitation of anti-HBc IgM for detecting acute hepatitis B infection in infants born to HBsAg carrier mothers.
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Abstract
IgM antibody to hepatitis B core antigen (anti-HBc IgM) as determined by IgM capture immunoassay is generally present in high titer during acute hepatitis B infection. A strong positive reaction for anti-HBc IgM during acute hepatitis is indicative of an acute HBV infection even in hepatitis B surface antigens (HBsAg)-negative patients. With the help of anti-HBc IgM otherwise unidentified HBV infection can be diagnosed in HBsAg-negative patients and an optimal combination of diagnostic tests for acute hepatitis B infection would therefore include assays for both HBsAg and anti-HBc IgM. In the HBsAg carrier with or without chronic liver disease the presence and meaning of anti-HBc IgM is still a matter for discussion. Detection of a weak positive result for anti-HBc IgM in HBsAg-positive patients without a recent history of acute hepatitis cannot always be regarded as a definite marker of recent hepatitis B infection. However, quantitation of the anti-HBc IgM results seems to improve the clinical value of the test. Comparison of the available anti-HBc IgM assays is needed and may well establish a reliable cut-off level that would differentiate acute from chronic hepatitis B and ongoing from resolving hepatitis B in HBsAg-positive patients.
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Sjogren MH, Lemon SM, Chung WK, Sun HS, Hoofnagle JH. IgM antibody to hepatitis B core antigen in Korean patients with hepatocellular carcinoma. Hepatology 1984; 4:615-8. [PMID: 6204916 DOI: 10.1002/hep.1840040407] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Primary hepatocellular carcinoma (PHC) has been linked etiologically to persistent hepatitis B virus (HBV) infections by epidemiologic, serologic and molecular lines of evidence. To evaluate the frequency of IgM antibody to the viral core antigen (IgM anti-HBc) detected by a highly sensitive radioimmunoassay, we compared 110 Korean patients with PHC to a group of 63 age- and sex-matched control patients with other tumors. Results were correlated with those of commercially available HBV assays. IgM anti-HBc was found in 74 of 110 PHC patients (67%), but only 1 of 63 (1.6%) control patients. Although HBsAg was found in a larger percentage of PHC patients (81%), it was also present in more control patients (14%). Thus, IgM anti-HBc was more specifically associated with PHC than was the presence of HBsAg. IgM anti-HBc was found in 91% of PHC patients with detectable HBeAg and 74% of PHC patients with positive anti-HBe tests (p less than 0.04). The frequency of IgM anti-HBc was similar among HBsAg-positive PHC patients with and without anti-HBs, or those with low or high levels of serum alpha-fetoprotein. In 18 patients with PHC, IgM anti-HBc was further characterized by rate-zonal centrifugation of sera, all were found to have 19S IgM anti-HBc although 6 also had greater or equal IgM anti-HBc reactivity in the low molecular weight region. The presence of IgM anti-HBc in adult Korean HBsAg carriers may indicate an especially high risk for the development of PHC, and this should be evaluated in prospective studies.
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Lavarini C, Farci P, Chiaberge E, Veglio V, Giacobbi D, Bedarida G, Susani G, Toti M, Almi P, Caporaso N. IgM antibody against hepatitis B core antigen (IgM anti-HBc): diagnostic and prognostic significance in acute HBsAg positive hepatitis. BMJ 1983; 287:1254-6. [PMID: 6416354 PMCID: PMC1549741 DOI: 10.1136/bmj.287.6401.1254] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
IgM antibody against hepatitis B core antigen (IgM anti-HBc), a marker of recent hepatitis B virus infection, was sought by radioimmunoassay in sera diluted 1/4000 from 376 patients presenting to four centres in Italy with acute, apparently type B hepatitis (hepatitis B surface antigen (HBsAg) positive). In 320 patients (85%) a positive IgM anti-HBc test result confirmed that hepatitis was due to primary infection with hepatitis B virus. In the remaining 56 patients absence of the IgM marker indicated that they were previously unrecognised long term carriers of HBsAg. Further serum analysis often showed delta infection and occasionally hepatitis A or cytomegalovirus infection as the true cause of their illness. After six to eight months circulating HBsAg persisted in 38 of 45 patients (84%) without IgM anti-HBc but in only six of 150 patients (4%) with the IgM antibody (p less than 0.0001). A negative IgM anti-HBc test result in patients with acute HBsAg positive hepatitis points to a factor other than hepatitis B virus as the cause of the liver damage and predicts the carriage of HBsAg.
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Kryger P. Non-A, non-B hepatitis. Serological, clinical, morphological and prognostic aspects. LIVER 1983; 3:176-98. [PMID: 6413805 DOI: 10.1111/j.1600-0676.1983.tb00866.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Chau KH, Hargie MP, Decker RH, Mushahwar IK, Overby LR. Serodiagnosis of recent hepatitis B infection by IgM class anti-HBc. Hepatology 1983; 3:142-9. [PMID: 6832706 DOI: 10.1002/hep.1840030202] [Citation(s) in RCA: 101] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
The time sequence, relative reactivity, and persistence of anti-HBc IgM were assessed in patients with HBsAg-positive viral hepatitis. A solid-phase immunoassay was developed using the IgM capture procedure with anti-mu-coated polystyrene beads. HBcAg was purified from serum Dane particles and used as a probe with 125I-labeled anti-HBc IgG. This immunoassay exhibited a pronounced prozoning phenomenon, and relative titers of sera differed widely depending upon the dilution of serum tested. When all sera were tested at 1:5,000 dilution, results were comparable in different patient groups. Anti-HBc IgM persisted at detectable levels for up to 2 years, and it was necessary to establish relative titers to discriminate current from remote infections. A cut-off assay value was established, and in 12 cases of acute hepatitis B virus (HBV) infection, antibody exceeded this value for about 6 months after onset of HBs antigenemia. A similar profile of anti-HBc IgM persistence was observed in seven patients who developed an HBsAg chronic carrier state. Long-term viral replication did not sustain elevated IgM class-specific antibody levels. The studies suggest that anti-HBc IgM analyses may be useful for differentiating recent and current HBV infections from remote infections, eliminating HBV as the agent for non-A, non-B hepatitis in asymptomatic HBsAg carriers, and detecting HBV as the etiologic agent during silent (HBsAg negative) infections.
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Sutherland S, Briggs JD. The detection of antibodies to cytomegalovirus in the sera of renal transplant patients by an IgM antibody capture assay. J Med Virol 1983; 11:147-59. [PMID: 6302219 DOI: 10.1002/jmv.1890110209] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
An IgM antibody capture assay for detection of cytomegalovirus (CMV) IgM antibody (MACRIA) was developed. It was shown to be of similar sensitivity to the indirect immunofluorescence test but has the advantage that rheumatoid factor does not react in it and pretest fractionation of serum is not required. It does, however, give false results with some Paul Bunnell-positive sera. The assay was used to measure the IgM response in 28 renal transplant patients followed prospectively. Seven patients (100%) with primary infections and six of 13 (46%) patients with secondary infections developed IgM by MACRIA. Nine of 13 (69%) patients with CMV IgM-positive sera had symptoms other than pyrexia associated with CMV infections, while only one of seven (14%) IgM-negative infections were symptomatic. Four of seven irreversible rejection episodes were associated with CMV IgM. The possible significance of CMV IgM production is discussed.
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Feinman SV, Overby LR, Berris B, Chau K, Schable CA, Maynard JE. The significance of IgM antibodies to hepatitis B core antigen in hepatitis B carriers and hepatitis B-associated chronic liver disease. Hepatology 1982; 2:795-9. [PMID: 7141390 DOI: 10.1002/hep.1840020609] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Smedile A, Farci P, Verme G, Caredda F, Cargnel A, Caporaso N, Dentico P, Trepo C, Opolon P, Gimson A, Vergani D, Williams R, Rizzetto M. Influence of delta infection on severity of hepatitis B. Lancet 1982; 2:945-7. [PMID: 6127458 DOI: 10.1016/s0140-6736(82)90156-8] [Citation(s) in RCA: 258] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The prevalence of serum markers of primary delta infection was determined in 532 patients with acute benign hepatitis B seen in Italy, and in 111 patients with fulminant hepatitis B seen in Italy, France and England. Patients with fulminant hepatitis had significantly higher prevalence of delta markers (43/111, 39%) than did those with benign hepatitis (101/532, 19%). In 25 of the 43 patients with delta-positive fulminant hepatitis, serum markers indicated a primary hepatitis B infection while in the remaining 18, IgM antibody to hepatitis B core antigen was absent, indicating that hepatitis B preceded superinfection with the delta agent. The increased morbidity of HBsAg hepatitis with delta infection may result from the cumulative simultaneous exposure to hepatitis B virus and delta, or from superinfection of HBsAg carriers with delta.
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Goldwater PN, Woodfield DG, Anderson RA, Gill MB, Carpenter S. Acute sporadic non-A and non-B hepatitis in an urban community in New Zealand. AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE 1982; 12:268-71. [PMID: 6287989 DOI: 10.1111/j.1445-5994.1982.tb02475.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Acute sporadic non-A, non-B hepatitis is reported for the first time in New Zealand. Examination of sera from 94 patients with biochemical evidence of hepatitis showed that 26 (27%) had acute hepatitis B (HB), 22 (23%) had acute hepatitis A (HA) and 25 (26%) had acute non-A, non-B hepatitis (NANBH). Nine (10%) patients had Epstein-Barr virus (EBV) associated hepatitis and one (1%) had cytomegalovirus (CMV) hepatitis. There were 11 (13%) patients with mixed infections; eight with HA plus HB, one with HB plus EBV, one with HA plus EBV and one with HB plus CMV. Thus NANBH and EBV associated hepatitis must be considered in the differential diagnosis of patients presenting with clinical hepatitis with no history of possible percutaneous infection.
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Anderson MJ, Davis LR, Jones SE, Pattison JR, Serjeant GR. The development and use of an antibody capture radioimmunoassay for specific IgM to a human parvovirus-like agent. J Hyg (Lond) 1982; 88:309-24. [PMID: 7061840 PMCID: PMC2133843 DOI: 10.1017/s0022172400070169] [Citation(s) in RCA: 62] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
An IgM-antibody capture radioimmunoassay (MACRIA) was developed for the detection of IgM antibody specific for the human parvovirus-like agent B19. Diagnosis of infection with this agent by either antigen detection or antibody seroconversion had been made by counter-current immunoelectrophoresis (CIE) in 18 cases of aplastic crisis occurring in children with homozygous sickle-cell disease. The MACRIA described here gave positive results in 17 of these 18 cases; in the remaining case only an acute specimen taken from the patient during viraemia and late convalescent specimens taken 184 and 247 days after onset of illness were available. The test was used to investigate 20 further cases of aplastic crisis in which neither viral antigen nor antibody seroconversion could be detected by CIE. Detection of virus-specific IgM permitted diagnosis of infection with this parvovirus-like agent in 17 of these cases. In the remaining three cases only single serum specimens taken late in convalescence, 82 days or more after the onset of symptoms, were available. In addition to these 34 cases of aplastic crisis in which primary infection with this agent was diagnosed by MACRIA, seven cases of apparent 'silent' infection detected by CIE were investigated. The test permitted the discrimination between primary infection and re-exposure to the virus in six of these patients. The use of this assay has added a considerable weight of evidence implicating primary infection with this parvovirus-like agent as an important cause of aplastic crisis in children with sickle-cell disease. Furthermore, MACRIA permits diagnosis of infection when only single serum specimens taken up to ten weeks after infection are available. Thus the use of this test will significantly facilitate the investigation of other clinical syndromes of presumptive infectious aetiology.
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Tedder RS, Wilson-Croome R. Detection by radioimmunoassay of IgM class antibody to hepatitis B core antigen: a comparison of two methods. J Med Virol 1980; 6:235-47. [PMID: 7229628 DOI: 10.1002/jmv.1890060307] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
A solid-phase radioimmunoassay (RIA) for IgM anti-HBc is described. The assay (anti-mu RIA) is based on the adsorption of IgM to a tube coated with sheep antibody to the human IgM mu-chain. The adsorbed immunoglobulin is assayed for anti-HBc activity. Positive reactions in the test are shown to be due to IgM antibody, and a confirmation blocking test is described. Reactivity of test sera can be quantitated by comparison with standard sera containing known levels of IgM anti-HBc. Sera assayed for IgM anti-HBc by both the anti-mu RIA and a method employing serum fractionation and competitive RIA gave similar results. Rheumatoid factor (RF) alone did not react in the anti-mu RIA, but reactivity could be generated in the presence of RF and preformed aggregates of IgG anti-HBc.
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