Quantitative analysis of IgM anti-HBc in chronic hepatitis B patients using a new “gray-zone” for the evaluation of “borderline” values

Colloredo, Guido; Bellati, G.; Leandro, Gioacchino; Colombatto, P.; Rho, Anna; Bissoli, Franco; Brunetto, Maurizia Rossana; Angeli, Giovanni; Idéo, G.; Bonino, Ferruccio

doi:10.1016/s0168-8278(96)80233-9

Cited by 38 publications

(40 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IgG anti-HBc can persist for many years and even for life, whilst IgM anti-HBc appears early in acute infection but its levels decline and become undetectable over time. However, in some cases these may fluctuate throughout the course of chronic HBV infection and follow the rise and fall of aminotransferase levels [Brunetto et al, 1993;Hadziyannis et al, 1993;Marinos et al, 1994;Colloredo et al, 1996]. The quantitative microparticle enzyme immunoassay for IgM anti-HBc (IMx CORE-M, Abbott Diagnostica, Wiesbaden-Delkenheim, Germany) has firstly been used for the diagnosis of acute hepatitis B [Kryger et al, 1982;Hoofnagle et al, 1985;Tassopoulos et al, 1997] but also for the monitoring of HBV activity during chronic infection [Hadziyannis et al, 1993;Marinos et al, 1994;Colloredo et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

“…However, in some cases these may fluctuate throughout the course of chronic HBV infection and follow the rise and fall of aminotransferase levels [Brunetto et al, 1993;Hadziyannis et al, 1993;Marinos et al, 1994;Colloredo et al, 1996]. The quantitative microparticle enzyme immunoassay for IgM anti-HBc (IMx CORE-M, Abbott Diagnostica, Wiesbaden-Delkenheim, Germany) has firstly been used for the diagnosis of acute hepatitis B [Kryger et al, 1982;Hoofnagle et al, 1985;Tassopoulos et al, 1997] but also for the monitoring of HBV activity during chronic infection [Hadziyannis et al, 1993;Marinos et al, 1994;Colloredo et al, 1996]. The IgM anti-HBc IMx index values in combination with aminotrasferase and HBV DNA levels have provided a very useful clinical tool in the follow-up of patients with chronic hepatitis B who are HBeAg-negative/anti-HBe-positive [Gerlich et al, 1986;Manesis et al, 2003], although its use has been questioned in patients with HBeAg-positive liver disease [Hayashi et al, 1996;Kumar et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

“…The IgM anti-HBc IMx index values in combination with aminotrasferase and HBV DNA levels have provided a very useful clinical tool in the follow-up of patients with chronic hepatitis B who are HBeAg-negative/anti-HBe-positive [Gerlich et al, 1986;Manesis et al, 2003], although its use has been questioned in patients with HBeAg-positive liver disease [Hayashi et al, 1996;Kumar et al, 2006]. IMx indexes are above 0.200 in all patients with HBeAgnegative chronic hepatitis B reactivations [Brunetto et al, 1993;Colloredo et al, 1996] and values persistently below 0.100 have been persistently recorded in patients with inactive chronic HBV infection [Brunetto et al, 1993;Colloredo et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Core mutations in patients with acute episodes of chronic HBV infection are associated with the emergence of new immune recognition sites and the development of high IgM anti‐HBc index values

Alexopoulou

Baltayiannis

Eroğlu

et al. 2008

Journal of Medical Virology

View full text Add to dashboard Cite

Acute exacerbations in HBeAg negative patients with chronic hepatitis B virus (HBV) infection are invariably associated with concurrent increases in the index of IgM class antibodies against the core protein (anti-HBc) of the virus. This study aimed to investigate whether this was related to the clearance of variants from the quasispecies pool and the appearance of new ones, with aminoacid substitutions in well recognized B-cell epitopes. In this study, 5 HBeAg negative patients (A to E) with 13 sequential serum samples (A1-A2, B1-B2-B3, C1-C2, D1-D2-D3, E1-E2-E3) were investigated after amplification of the entire core encoding region followed by cloning/sequencing studies. The sequences at different time points were compared with those from a single HBeAg positive patient with no apparent acute exacerbations. The results from sequence comparison showed that virus variants emerged in all (A2, B3, C2, D3, E2, and E3) but two (B2 and D2) subsequent sera with amino-acid substitutions affecting B-cell epitopes. It is concluded that the rise in the values of IgM anti-HBc may be attributed to the alteration of the antigenic epitopes leading to new antibody production in the majority of the cases. However, it appears that increases in IgM anti-HBc indexes in a few cases may relate to other possible mechanisms which are discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Core mutations in patients with acute episodes of chronic HBV infection are associated with the emergence of new immune recognition sites and the development of high IgM anti‐HBc index values

Alexopoulou

Baltayiannis

Eroğlu

et al. 2008

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Furthermore, we would like to emphasize that the presence of detectable anti-HBc IgM in two anti-HCV-positive patients was not associated with detectable HBV DNA. Other investigators have reported the finding of weakly positive anti-HBc IgM levels in chronic patients without current evidence of HBV replication (19).…”

mentioning

confidence: 98%

Absence of hepatitis B virus DNA in patients with hepatitis C and non-A-E hepatitis in the State of São Paulo, Brazil

Souza

Pinho

Carrilho

et al. 2004

Braz J Med Biol Res

View full text Add to dashboard Cite

Occult hepatitis B virus (HBV) infection has been reported as cases in which HBV DNA was detected despite the absence of any HBV serological markers or in cases in which anti-HBc antibody was the sole marker. The aim of the present study was to determine, using the polymerase chain reaction (PCR), whether HBV infection occurs in hepatitis C and non-A-E hepatitis patients without serological evidence of hepatitis B infection in São Paulo State. Two different populations were analyzed: 1) non-A-E hepatitis patients, including 12 patients with acute and 50 patients with chronic hepatic disorders without serological evidence of infection with known hepatitis viruses; 2) 43 patients previously diagnosed as hepatitis C with positive results for anti-HCV and HCV RNA. Among hepatitis C patients, antiHBc was detected in 18.6% of the subjects. Three different sets of primers were employed for HBV DNA detection by nested PCR, covering different HBV genes: C, S and X. HBV-DNA was not detected in any sample, whereas the positive controls did produce signals. The lack of HBV DNA detection with these pairs of primers could be due to a very low viral load or to the presence of mutations in their annealing sites. The latter is unlikely as these primers were screened against an extensive dataset of HBV sequences. The development of more sensitive methods, such as real time PCR, to detect circular covalent closed DNA is necessary in order to evaluate this question since previous studies have shown that cryptic hepatitis B might occur. (1) studied patients with chronic liver disease and detected HBV-DNA sequences in 52 (59%) of 88 liver samples and in 10 (9.5%) of 105 serum samples (6 of which

show abstract

“…Most anti-HBc IgM values for patients with HBeAg-negative chronic HBV infection are below the cutoff limit for a diagnosis of acute hepatitis B, either in the negative or in the "gray" zone. When determined by a classic enzyme-linked immunosorbent assay, they range from 20 to 600 U/ml (10), and when tested with a MEIA (the IMx system), the results range from index values of 0.2 to 2.0, approximately 10 to 300 U/ml (1,7).…”

mentioning

confidence: 99%

Performance Characteristics of Microparticle Enzyme and Chemiluminescence Immunoassays for Measurement of Anti-HBc Immunoglobulin M in Sera of Patients with HBeAg-Negative Chronic Hepatitis B Virus Infection

Hadziyannis

Manesis

Vassilopoulos

et al. 2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

The IMx, AxSym, and Architect immunoglobulin M anti-HBc assay systems for detecting hepatitis B virus e antigen-negative chronic hepatitis B virus infection were compared. Despite good intra-and interassay coefficients of variation, significantly different values and low correlation (overestimation by AxSym and underestimation by Architect) were observed. Association and cutoff values for distinguishing patients with viral replication should be established for all methods.In patients with hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, absolute levels and changing titers of immunoglobulin M antibodies against the HBV core protein (anti-HBc IgM) are considered markers of viral replication (11,13,17). The measurement of anti-HBc IgM is an easily performed and inexpensive alternative to frequent serum HBV DNA measurements for monitoring untreated patients, as well as patients treated with alpha interferon or antiviral agents (1, 5, 11-13, 15-18, 20).Most experience in the detection of anti-HBc IgM in patients with chronic hepatitis B (CHB) is based on microparticle enzyme immunoassays (MEIA) using the IMx analyzer. Most anti-HBc IgM values for patients with HBeAg-negative chronic HBV infection are below the cutoff limit for a diagnosis of acute hepatitis B, either in the negative or in the "gray" zone. When determined by a classic enzyme-linked immunosorbent assay, they range from 20 to 600 U/ml (10), and when tested with a MEIA (the IMx system), the results range from index values of 0.2 to 2.0, approximately 10 to 300 U/ml (1, 7).In most laboratories, the IMx analyzer has been replaced by the AxSym analyzer (MEIA), and newer analyzers with chemiluminescent assays (CMIA) are gradually being instituted (4, 6, 21). We compared the anti-HBc IgM measurements by the three analyzers for patients with HBeAg-negative chronic HBV infection.The IMx (MEIA), AxSym (MEIA), and Architect (CMIA) analyzers (Abbott Laboratories, Abbott Park, IL) were used for anti-HBc IgM quantification. The results of the MEIA are expressed as index values (ratio of sample to calibrator) (9), and the results of the CMIA are in relative light units divided by the cutoff value determined in the preceding calibration (21).For the evaluation of the inter-and intra-assay variation (coefficient of variation [CV]), we used multiple aliquots of sera from three patients with HBeAg-negative CHB (patients P1 to P3). Each serum sample was tested five times in the same assay and five times over five days with each of the three analyzers. Anti-HBc IgM measurements for 53 consecutive patients with HBeAg-negative chronic HBV infection were compared. The influence of rheumatoid factor (RF) measured by nephelometry (Immage immunochemistry systems; Beckman Coulter, Inc., Fullerton, CA) was assessed.For data entry, frequencies, and comparisons, SPSS version 14.0 (SPSS, Inc., Chicago, IL) was used. The t test and the Mann-Whitney test were applied for parametric and nonparametric data comparisons, respectively. For paired compa...

show abstract

Quantitative analysis of IgM anti-HBc in chronic hepatitis B patients using a new “gray-zone” for the evaluation of “borderline” values

Cited by 38 publications

References 15 publications

Core mutations in patients with acute episodes of chronic HBV infection are associated with the emergence of new immune recognition sites and the development of high IgM anti‐HBc index values

Core mutations in patients with acute episodes of chronic HBV infection are associated with the emergence of new immune recognition sites and the development of high IgM anti‐HBc index values

Absence of hepatitis B virus DNA in patients with hepatitis C and non-A-E hepatitis in the State of São Paulo, Brazil

Performance Characteristics of Microparticle Enzyme and Chemiluminescence Immunoassays for Measurement of Anti-HBc Immunoglobulin M in Sera of Patients with HBeAg-Negative Chronic Hepatitis B Virus Infection

Contact Info

Product

Resources

About