Patients with chronic hepatitis-B-virus (HVB) infection may exhibit significant liver pathology despite alanine aminotransferase (ALT) and HBV-DNA levels below current treatment guideline's cut-off values. This study evaluated the
candidacy for HBV therapy if baseline histopathological changes were considered. Clinical, biochemical, serological, virological, and histopathological (Metavir Score) data of a cohort of 161 consecutive patients [129 (80.1 %) males, mean ± SD age 35.2 ±11.2 years, 130 (80.7% HBeAgnegative, 149 (90.1 %) genotype D] were collected and analyzed. Our results showed that significant pathology (F≥2 and/or A≥2) and significant fibrosis (F≥2 ± A≥2) were found in 98/161(60.9 %) and 81/161(50.3 %) patients respectively. Based on HBV-DNA (>2000 iu/mL or >20000 iu/mL according
to HBeAg status) and ALT level >2x40 u/L (the standard cut-off value), only 36/161(22.4 %) patients were candidate for therapy. This increased to 71/161(44.1 %) patients when the new ALT cut-off values (30 u/L for males, and 19 u/L for females) were applied. Relying on either (F≥2 and/or A≥2) or (F≥2±A≥2) increases the treatment candidacy by 62/161(38.5 %) or 45/161(28 %), and further increases the candidacy for treatment by 27/161(16.8 %) or 10/161(6.2 %) patients when standard and new ALT cut-off values are applied respectively. Finally, liver histopathology is more reliable than ALT and HBV-DNA levels in the decision to treat patients with chronic HBV infection.