HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection

Table 1 Epidemiology of precore and basal core promoter variants and their correlation with hepatitis B virus genotype distribution[15-18,30]

Genotype	Region	Precore variant	Basal core promoter variant
B, C	East and South East Asia	Yes	Yes
A	Northern Europe, North America, Central Africa	No	Yes
D	Southern Europe, Middle East, Indian subcontinent	Yes	No
E	West and Sub-Saharan Africa	Yes	No
F	Indian Population of Central and South America	No	No

Table 2 Clinical importance of hepatitis B surface antigen quantification in hepatitis B surface antigen negative patients in either predicting hepatitis B surface antigen seroclearance or differentiating inactive carriers from chronic hepatitis patients

Ref.	Studies predicting HBsAg seroclearance
	Study design	HBsAg levels	Reliability of prediction
Chan et al[68]	Genotype B/C, longitudinal study for 11 yr	HBsAg < 100 IU/mL	75% sensitivity and 91% specificity
Chan et al[85]	Longitudinal study for 99 ± 16 mo	HBsAg levels < 1000 IU/mL and HBV DNA < 2000 IU/mL	Cumulative probability of 9% and 21% at 5 and 8 yr respectively
Tseng et al[86]	Follow-up at 1 yr after spontaneous HBeAg seroclearance	HBsAg < 100 IU/mL vs 100-999 IU/mL	Hazard ratio 24.3 vs 4.4 for HBsAg seroclearance
Tseng et al[87]	Genotype B/C follow-up of 11.6 yr	HBV DNA < 2000 IU/mL and HBsAg < 10 IU/mL	Adjusted hazard ratio of HBsAg loss was 13.2
Martinot-Peignoux et al[70]	Follow-up of 1 yr	HBsAg < 1000 IU/mL, annual decrease > 0.3 log IU/mL	95%NPV and 89% PPV
	Differentiation of inactive disease from chronic hepatitis
Brunetto et al[69]	Genotype D, Follow-up for 34.5 mo	HBsAg levels < 1000 IU/mL and HBV DNA < 2000 IU/mL	88% NPV and 97% PPV to identify inactive carriers
Martinot-Peignoux et al[70]	Follow-up of 1 yr	HBsAg levels > 1000 IU/mL and HBV DNA > 200 IU/mL	96% NPV and 92% sensitivity to identify reactivation
Larsson et al[88]	Single time point evaluation of ALT, histological score	HBsAg levels < 1000 IU/mL and HBV DNA < 10000 IU/mL	96% PV to identify inactive carriers
Park et al[89]	Genotype C follow-up > 48 mo	HBsAg levels > 850 IU/mL and HBV DNA > 850 IU/mL	85% diagnostic accuracy to identify reactivation

HBV: Hepatitis B virus; NPV: Negative predictive value; HBsAg: Hepatitis B surface antigen; PPV: Positive predictive value.