P16 Transient elastography is underutilised in London hospitals and results in unnecessary endoscopic screening for oesophageal varices: a multi-site audit of practice

Abstract

Post-partum ALT increases are observed in 30% of HBsAg+ mothers and are also noticed in mothers administered nucleoside analogues (NA) to prevent mother-to-child transmission (MTCT). As such flares may be injurious we have studied the utility of novel and sensitive markers of cccDNA transcriptional activity [hepatitis B core-related antigen (HBcrAg) and pre-genomic (pg)RNA] to predict post-partum ALT flares in both NA treated and untreated HBsAg+ mothers.We aimed to evaluate the role of serum levels of HBcrAg and pgRNA in pregnancy to predict post-delivery ALT flares, their severity and by inference, a preference to continue on NA. Methods Plasma samples from 642 HBsAg-positive pregnant women were collected during 3rd trimester and at 6, 12, 24, 36 and 48 weeks post-partum. 103(16%) were HBeAg +; median age 31 years. Samples were tested for HBeAg, HBV DNA (Roche; IU/ml); quantitative HBsAg (Abbott Architect; log 10 IU/ml), HBcrAg levels (CLEIA Fujirebio; log 10 U/ml) and pgRNA concentrations (PCR assay Abbott Diagnostic; log 10 U/ml). 95/642(15%) mothers with HBV DNA concentrations >200,000 IU/ml started tenofovir prophylaxis from 28 weeks of gestation to prevent HBV MTCT. The ALT flares incidence and severe flares (defined as >10xULN) was correlated with HBcrAg and pgRNA in treated and untreated mothers. Results Untreated cohort: 106/547(19%) of untreated mothers developed a post-delivery flare, but none was severe. Higher pre-delivery HBV DNA, HBcrAg and pgRNA concentrations were observed in untreated mothers with postpartum ALT flares vs. mothers without a flare. Pregnancy ALT and HBsAg concentrations were similar in flare vs. no flare patients.NA treated cohort: Higher pre-delivery HBcrAg and pgRNA concentrations were observed in NA treated mothers with a post-partum flare. 80/95(84%) treated mothers stopped NA therapy post-partum (median 4 weeks). However no difference in flares incidence was observed in mothers discontinuing treatment vs. mothers who continued NA.[56/80(70%) vs 13/15(87%)]. Seven HBeAg-negative treated patients who stopped NA developed a severe ALT flare within 12 weeks post-delivery. High pre-delivery levels of HBcrAg (>7 log 10 U/ml) and pgRNA (>4 log 10 U/ml) were exclusive in mothers with severe flare, but no flares were associated with hepatic synthetic dysfunction and resolved after re-starting NA. 13/103(13%) mothers lost HBeAg and 6 (1%) lost HBsAg spontaneously within 1 year post-delivery (all mild flares). Conclusion Post-partum ALT flares are more common in pregnant women with higher pregnancy HBcrAg and pgRNA levels, in both NA treated and untreated mothers. High predelivery levels could suggest that NA therapy should be continued post-partum to avoid severe and injurious ALT flares.