CORRELATION BETWEEN HBSAG LEVEL AND VIRAL LOAD Belopolskaya M, Avrutin V, Firsov S, Yakovlev A.

Hepatitis B An important public health problem More than 350 million people worldwide have chronic hepatitis B Causes such severe liver diseases as cirrhosis and hepatocellular carcinoma Maria Belopolskaya, BIDH, SPb Vilnius 2014

Hepatitis B Surface Antigen First discovered by Blumberg The chief marker for the diagnosis of HBV infection HBsAg persistence in the serum for more than 6 months — chronic hepatitis Disappearance of HBsAg is the marker of convalescence from hepatitis B Maria Belopolskaya, BIDH, SPb Vilnius 2014

Pathway of HBsAg Production From: Tseng TC, Kao JH. J Gastroenterol. Jan 2013; 48(1): 13–21. Maria Belopolskaya, BIDH, SPb Vilnius 2014

HBsAg Level reflects the amount of cccDNA inside hepatocytes correlates with the transcriptional activity of cccDNA is considered a surrogate marker of infected cells Maria Belopolskaya, BIDH, SPb Vilnius 2014

HBsAg Levels in Different Phases of Chronic HBV Infection From: Tseng TC, Kao JH.J Gastroenterol. Jan 2013; 48(1): 13–21. Maria Belopolskaya, BIDH, SPb Vilnius 2014

Quantitative HBsAg: “a new trick of old dog”* To monitor the natural history To detect inactive carriers To predict the effect of antiviral therapy : Tseng TC, Kao JH.J Gastroenterol. Jan 2013; 48(1): 13–21 Maria Belopolskaya, BIDH, SPb Vilnius 2014

Potential Applications of HBsAg Level Monitoring During natural history Identification of: Benefit True inactive carriers Reassurance that treatment is not required Patients who need therapy now or whose disease is likely to be reactivated in the nearest future Identification of patients who need closer monitoring and possible identification of patients who need treatment Maria Belopolskaya, BIDH, SPb Vilnius 2014

Potential Applications of HBsAg Level Monitoring During therapy Early identification of: Benefit Patients who are unlikely to respond to PEG-IFN Early stopping rule for avoiding unnecessary and ineffective therapy Patients who are responding to PEG-IFN Motivation for patients to continue therapy Patients who experience a rapid decline in HBsAg levels during NA therapy Identification of patients who have a high chance of HBsAg clearance Maria Belopolskaya, BIDH, SPb Vilnius 2014

Inactive carriers of HBV Infection Genotype D HBV infection B / C HBsAg level HBsAg <1000 IU/ml <100 IU/ml Maria Belopolskaya, BIDH, SPb Vilnius 2014

HBV Viral load It is known that in most cases HBeAg positive patients have a high level of HBV DNA. The HBsAg level tends to be also higher in HBeAg positive patients. Numerous studies have shown that serum HBsAg levels of inactive HBV carriers are usually less than 1000 IU/ml* *Chan HL, Hepatology, 2010 Maria Belopolskaya, BIDH, SPb Vilnius 2014

Hepatitis B Immunoprophylaxis Infections in pregnancy, Vilnius 2014 Maria Belopolskaya, BIDH, SPb

Maternal HBV DNA level and immunoprophylaxis failure Zou H et al. J Viral Hepat, 2011 *Shi Z et al. Obstet Gynecol, 2010 Infections in pregnancy, Vilnius 2014 Maria Belopolskaya, BIDH, SPb

Criteria for excluding: patients with undetectable HBV DNA level patients co-infected with HCV, HIV or HDV patients with cirrhosis or hepatocellular carcinoma patients with autoimmune liver disease At the time of the measurement none of the patients was receiving any antiviral treatment Maria Belopolskaya, BIDH, SPb Vilnius 2014

Methods HBV DNA quantization HBsAg quantization COBAS TaqMan HBV test (Roche Diagnostics) Lower limit of detection — 150 IU/ml HBsAg quantization Architect HBsAg QT (Abbott Laboratories) HBsAg from 0.05 to 250 IU/ml (HBsAg level > 250 IU/ml — 1 : 500 dilution) Upper limit of detection — 125 000 IU/ml. Maria Belopolskaya, BIDH, SPb Vilnius 2014

Groups of patients 117,96 N Min Max (IU/ml) Men 28 37,8 73,82 16079,62 Mean age (year) Mean ALT (U/ml) Median HBsAg (IU/ml) Min Max (IU/ml) Men 28 37,8 73,82 16079,62 117,96  125 000 Non-pregnant women 26 37,6 51,09 17712,12 191,5 Pregnant women 31 29 22,47 7968,46 49 Maria Belopolskaya, BIDH, SPb Vilnius 2014

HBeAg status 2,9 × 108 8,19 × 108 9,1 × 108 N HBeAg positive Min Median HBV DNA (IU/ml) Min Max (IU/ml) Men 28 4 4090 <150 2,9 × 108  Non-pregnant women 26 6 7100 8,19 × 108  Pregnant women 31 2 350 9,1 × 108 Maria Belopolskaya, BIDH, SPb Vilnius 2014

Spearman rank correlation coefficient Shows how well the relationship between two variables can be described by a monotonic function. For data sets with no identical values: N – number of patients. di – difference of ranks of the HBV DNA level        and the HBsAg level for the i-th patient. For data sets with identical values: Maria Belopolskaya, BIDH, SPb Vilnius 2014

Results Spearman coefficient Reliability ρ ≈ 0.4812 P < 0.01 Group of patients N Spearman coefficient Reliability Men 28 ρ ≈ 0.4812 P < 0.01 Non-pregnant women 26 ρ ≈ 0.4728 Pregnant women 31 ρ ≈ 0.1871 P < 0.25 (without lower limit value) 18 ρ ≈ 0.4211 P < 0.05 All patients 85 ρ ≈ 0.3762 P < 0.0005 Maria Belopolskaya, BIDH, SPb Vilnius 2014

Correspondence between HBsAg and HBV DNA levels Maria Belopolskaya, BIDH, SPb Vilnius 2014

Conclusions The correlation between HBsAg and HBV DNA levels is significant in all groups. In the group of pregnant women a very low HBV DNA level (which is non-measurable) is observed more frequently than in other groups. This leads to a decrease of the Spearman rank correlation coefficient in this group. In almost all cases, a low level of HBsAg indicates a low HBV DNA level, whereas a high HBsAg level does not always correspond to a high viral load. Maria Belopolskaya, BIDH, SPb Vilnius 2014

Thank you for your attention Maria Belopolskaya, BIDH, SPb Vilnius 2014