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Surface antigen negative hepatitis B infection: the importance of screening before B cell‐depleting therapy

Sanjivan Mudaliar, Ken Liu and Simone I Strasser
Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50165
Published online: 3 June 2019

A 68‐year old man who was a migrant from Greece underwent 6 months of treatment with the anti‐CD20 B cell‐depleting agent obinutuzumab and chlorambucil for chronic lymphocytic leukaemia. Over this period, his widespread lymphadenopathy regressed, and his lymphocyte count normalised from a peak of 29 × 109/L (reference interval [RI], 4–10× 109/L). He was negative for hepatitis B virus (HBV) surface antigen (HBsAg) on HBV screening performed before treatment. HBV core antibody (anti‐HBc) was not tested. Routine monitoring during and after treatment demonstrated a progressive elevation of liver enzymes from a normal baseline (Box). When the alanine aminotransferase (ALT) level reached 420 U/L (RI, 5–55 U/L) at 6 months after treatment completion, a full serological panel along with HBV DNA revealed anti‐HBc and HBV e antigen (HBeAg) positivity, with a HBV DNA level of 26 700 000 IU/mL (7.4 log10), but persistently negative HBsAg despite this clear reactivation flare. Testing for hepatitis C virus revealed no evidence of infection. There were no features of hepatic decompensation. He was immediately commenced on entecavir 0.5 mg daily. However, because the effect of entecavir on stopping active liver inflammation by suppressing viral replication is not immediate, his ALT level continued to climb to a peak of 1488 U/L after 4 weeks of treatment. At this time, he underwent HBeAg seroconversion, becoming HBeAg negative with progressive reduction in HBV DNA and normalisation of ALT level over the next 4 months. Of particular note, he remained persistently HBsAg negative throughout follow‐up. Subsequent testing revealed multiple mutations in the gene encoding HBsAg protein, which prevented epitope binding by commercially available HBsAg assays.

  • Sanjivan Mudaliar1,2
  • Ken Liu1,2
  • Simone I Strasser1,2

  • 1 A W Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
  • 2 University of Sydney, Sydney, NSW


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