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Abstract
Title | THE SIGNIFICANCE OF VIRAL AND SEROLOGICAL MARKERS IN PREDICTING LIVER DISEASE SEVERITY IN e-AG NEGATIVE HEPATITIS B VIRUS INFECTION | Speaker: | Vinod Audimoolam | Author: | V.K. Audimoolam*, I. Carey, A. Suddle, M. Bruce, M. Horner, K. Agarwal, P.M. Harrison | Affiliation: | King's College Hospital, London, UK. *[email protected] | Background and aims: In hepatitis B virus (HBV)infection, seroconversion to HBeAg negative/eAb positive accompanied by low serumHBV-DNA (persistently ≤2000 IU/mL) and low quantitative HBsAg (qHBsAg)signifies transition to an inactive carrier (IC) state. However, in patientswith raised serum HBVDNA differentiating those with inactive disease (ID) fromeAg negative chronic HBV (eAg-CHB) currently relies on liver biopsy. This studyinvestigated whether serological (qHBsAg) and virological markers (serumHBV-DNA) can predict disease severity in patients with eAg negative HBV acrossa range of HBV genotypes.
Methods: Liver biopsy was performed in 364 consecutiveeAg negative patients (median age 38 years, 212 males) who had HBVDNA >1000IU/ml on at least 2 clinic visits over 6-18 months. ALT [IU/l], qHBsAg [Abbott ARCHTECT®], HBVgenotype [direct sequencing] and HBV-DNA [real-time TaqMan PCR] were evaluated at the time of liver biopsy.
Results: Based on the liver histologyfindings, 217 had ID (an Ishak fibrosis score of F0-1) and 147 had eAg-CHB(≥F2). HBV genotype-E predominated (50%) followed by D (16%), A (15%), B (10%)and C (9%). Overall qHBsAg levels were higher in ID than eAg-CHB patients (median3.84 vs. 3.7 log10IU/ml;p=0.02). Assessment by individual genotype demonstrated that qHBsAg levels remainedhigher in ID than eAg-CHB in genotypes A and E (4.01 vs. 3.73 and 3.95 vs. 3.8 log10IU/ml; both p< 0.05).However, in genotype B qHBsAg levels correlated with the severity of fibrosis [2.81in F0-1 vs. 3.34 in F≥2; p< 0.01]. The qHBsAg levels were similar in ID andeAg-CHB in genotypes C and D. HBV genotype had no impact on the severity ofliver fibrosis (p=0.16). Patients with eAg-CHB compared to those with ID hadraised ALT [81% vs. 65 %; p< 0.01], higher HBV-DNA (3.99 vs. 3.6 log10IU/ml; p< 0.01), olderage (39 vs. 36 years; p< 0.01) and more were males (68% vs. 51%; p< 0.01).
Conclusion: In eAg negative patients with HBVDNA >1000 IU/ml, the relationship between qHBsAg levels and liver fibrosiswas genotype specific. Even allowing for HBV genotype, the absolute qHBsAg levelwas a poor discriminator of clinically significant liver fibrosis. |
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