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Discriminant value of serum HBV DNA levels as predictors of liver fibrosis in chronic hepatitis B


Dr. Faisal Sanai, Department of Hepatobiliary Science, King Abdulaziz Medical City, PO Box 22490 (1440), Riyadh 11426, KSA. E-mail:


Summary.  Current guidelines recommend antiviral therapy in chronic hepatitis B (HBV) patients with significant histological disease. We aimed to compare histological fibrosis (METAVIR, ≥F2) in patients with HBV DNA ≥20 000 IU/mL vs≥2000 IU/mL and identify predictors of fibrosis. We performed prospective liver biopsies on 203 HBeAg-negative patients in four groups: Group I (n = 55): HBV DNA ≥20 000 IU/mL and persistently elevated alanine aminotransferase (ALT) levels (PEALT; >40 U/L); Group II (n = 34): HBV DNA ≥20 000 IU/mL and persistently normal ALT (PNALT); Group III (n = 40): HBV DNA <20 000 IU/mL and PEALT; and Group IV (n = 74): HBV DNA <20 000 IU/mL, and PNALT. We reanalysed all groups in relation to updated cut-off for treatable viremia (2000 IU/mL). Genotype D was detected in 86% of patients. Hepatic fibrosis ≥F2 was detected in 72.7%, 52.9%, 57.5% and 18.9% in Groups I–IV, respectively (< 0.0001). Except in Group II with a trend for lower ≥F2 fibrosis (= 0.067), there was no significant difference by using HBV DNA cut-off 20 000 vs 2000 IU/mL. Multivariate logistic regression analysis identified study Group IV (OR, 0.0276; CI: 0.088–0.868; = 0.0276) and milder (A0–1) necroinflammatory grade (OR, 0.135; CI: 0.063–0.287; < 0.0001) as independent predictors of ≥F2 fibrosis. The specificity, positive and negative predictive values for PEALT in detection of ≥F2 fibrosis for viremia ≥2000 IU/mL (80%, 69% and 65%, respectively) or ≥20 000 IU/mL (86%, 73% and 63%, respectively) were similar, with a marginal gain in sensitivity (51%vs 42%, respectively). Significant fibrosis is prevalent in a large proportion of HBeAg-negative patients with high viremia and persistently normal ALT. Lower HBV DNA cut-offs could be adopted with marginal gains in fibrosis detection and without loss of diagnostic accuracy.