Serum HBV DNA level is crucial in the management of chronic hepatitis B (CHB); however, the assay is expensive and cannot be used widely. Therefore, we explored the possibility of hepatitis B surface antigen (HBsAg) quantification as a surrogate marker for HBV DNA level in CHB patients.
Methods
A total of 289 CHB patients were enrolled, 251 were evaluated at baseline and 75 of them were also evaluated during anti-HBV treatment. Another 38 on-treatment patients were used for validation. Serum HBsAg titre was quantified by an immunoassay and HBV DNA level by a PCR-based method. Baseline and on-treatment data were analysed.
Results
In parallel to log10 HBV DNA, the log10 HBsAg was high in both immune tolerance and immune clearance phases, and significantly decreased in the inactive carrier state and was again increased in the reactivation phase of the CHB infection. There was a positive correlation between log10 HBsAg and log10 HBV DNA, which was greater in patients with chronic hepatitis, hepatitis B e antigen- positivity, greater alanine aminotransferase or HBsAg levels at baseline and during pegylated interferon treatment. Log10 HBsAg could predict log10 HBV DNA independently. An HBsAg titre of >900 IU/ml at baseline or >1,500 IU/ml within the first year of treatment could predict an HBV DNA level of >20,000 IU/ml, especially in subgroups of chronic hepatitis with alanine aminotransferase levels >40 IU/l. The dynamics of HBsAg might also predict serial HBV DNA changes. In the validation group, 64% of patients with on-treatment HBV DNA levels >20,000 IU/ml could be correctly predicted.
Conclusions
Serum HBsAg concentration might serve as a surrogate marker of HBV DNA level in CHB patients.
References
1.
KaoJ.H., ChenD.S.Global control of hepatitis B virus infection.Lancet Infect Dis2002; 2: 395–403.
2.
KaoJ.H.Diagnosis of hepatitis B virus infection through serological and virological markers.Expert Rev Gastroenterol Hepatol2008; 2: 553–562.
GerlichW.H., GlebeD., SchuttlerC.G.Deficiencies in the standardization and sensitivity of diagnostic tests for hepatitis B virus.J Viral Hepat2007; 14 Suppl 1: 16–21.
5.
ChenD.S., LaiM.Y., LeeS.C., YangP.M., SheuJ.C., SungJ.L.Serum HBsAg, HBeAg, anti-HBe, and hepatitis B viral DNA in asymptomatic carriers in Taiwan.J Med Virol1986; 19: 87–94.
6.
SatoS., OhhashiW., IharaH., SakayaS., KatoT., IkedaH.Comparison of the sensitivity of NAT using pooled donor samples for HBV and that of a serologic HBsAg assay.Transfusion2001; 41: 1107–1113.
7.
DeguchiM., YamashitaN., KagitaM.Quantitation of hepatitis B surface antigen by an automated chemiluminescent microparticle immunoassay.J Virol Methods2004; 115: 217–222.
8.
KohmotoM., EnomotoM., TamoriA.Quantitative detection of hepatitis B surface antigen by chemiluminescent microparticle immunoassay during lamivudine treatment of chronic hepatitis B virus carriers.J Med Virol2005; 75: 235–239.
9.
ChenC.H., LeeC.M., WangJ.H., TungH.D., HungC.H., LuS.N.Correlation of quantitative assay of hepatitis B surface antigen and HBV DNA levels in asymptomatic hepatitis B virus carriers.Eur J Gastroenterol Hepatol2004; 16: 1213–1218.
10.
OzarasR., TabakF., TahanV.Correlation of quantitative assay of HBsAg and HBV DNA levels during chronic HBV treatment.Dig Dis Sci2008; 53: 2995–2998.
11.
KuhnsM.C., KleinmanS.H., McNamaraA.L., RawalB., GlynnS., BuschM.P.Lack of correlation between HBsAg and HBV DNA levels in blood donors who test positive for HBsAg and anti-HBc: implications for future HBV screening policy.Transfusion2004; 44: 1332–1339.
12.
WiegandJ., WedemeyerH., FingerA.A decline in hepatitis B virus surface antigen (HBsAg) predicts clearance, but does not correlate with quantitative HBeAg or HBV DNA levels.Antivir Ther2008; 13: 547–554.
13.
ManesisE.K., HadziyannisE.S., AngelopoulouO.P., HadziyannisS.J.Prediction of treatment-related HBsAg loss in HBeAg-negative chronic hepatitis B: a clue from serum HBsAg levels.Antivir Ther2007; 12: 73–82.
14.
YehS.H., TsaiC.Y., KaoJ.H.Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis.J Hepatol2004; 41: 659–666.
ChanH.L., WongV.W., TseA.M.Serum hepatitis B surface antigen quantitation can refect hepatitis B virus in the liver and predict treatment response.Clin Gastroenterol Hepatol2007; 5: 1462–1468.
17.
WursthornK., LutgehetmannM., DandriM.Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B.Hepatology2006; 44: 675–684.
18.
PawlotskyJ.M., DusheikoG., HatzakisA.Virologic monitoring of hepatitis B virus therapy in clinical trials and practice: recommendations for a standardized approach.Gastroenterology2008; 134: 405–415.
19.
Werle-LapostolleB., BowdenS., LocarniniS.Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy.Gastroenterology2004; 126: 1750–1758.
20.
BrunettoM., CavalloneD., MoriconiF.Kinetics of HBsAg decline during and following treatment of CHB: early and rapid HBsAg decline during peginterferon alfa-2a is predictive of HBsAg clearance.Hepatology2008; 48 Suppl 1: 717A–718A.
21.
MarcellinP., BrunettoM., BoninoF.In patients with HBeAg-negative chronic hepatitis B, HBsAg serum levels early during treatment with peginterferon alfa-2a predict HBsAg clearance 4 years post-treatment.Hepatology2008; 48 Suppl 1: 718A–719A.
22.
MoucariR., MackiewiczV., LadaO.Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients.Hepatology2009; 49: 1151–1157.
23.
LauG., MarcellinP., BrunettoM.On-treatment HBsAg decline during peginterferon alfa-2a (40kD) ± lamivudine in patients with HBeAg-positive CHB as a potential predictor of durable off-treatment response.Hepatology2008; 48 Suppl 1: 714A.
24.
BrunettoM.R., MoriconiF., BoninoF.Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B.Hepatology2009; 49: 1141–1150.
25.
WursthornK., JungM., MannsM., LopezP., WedemeyerH., NaoumoN.Different kinetics of serum HBsAg decline in HBeAg-positive vs HBeAg-negative patients during 3 years of telbivudine treatment in chronic hepatitis B (CHB).Hepatology2009; 50 Suppl 4: 536A.
26.
CabrerizoM., BartolomeJ., CarameloC., BarrilG., CarrenoV.Molecular analysis of hepatitis B virus DNA in serum and peripheral blood mononuclear cells from hepatitis B surface antigen-negative cases.Hepatology2000; 32: 116–123.
27.
ColemanP.F., ChenY.C., MushahwarI.K.Immunoassay detection of hepatitis B surface antigen mutants.J Med Virol1999; 59: 19–24.
