Hepatitis B virus reactivation in seronegative occult hepatitis B patient receiving ibrutinib therapy

A 61-year-old woman presented in November 2000 with chronic lymphocytic leukaemia (CLL). She was treated with fludarabine, mitoxantrone and dexamethasone, followed by chlorambucil from February 2001 to June 2002.

She remained well until 2021, when she presented with a tonsillar mass that on biopsy showed small lymphocytic lymphoma (SLL). She received the anti-CD20 antibody rituximab, but with the first infusion could only tolerate less than 10% of the intended dose before a serious infusion reaction aborted the treatment. The treatment was then changed to ibrutinib (420 mg/day). Prior to initiation of rituximab, she was negative for HBsAg and anti-HBc. Serum HBV-DNA was not tested.

Investigations / diagnosis / treatment

Four months after ibrutinib treatment, her alanine aminotransferase (ALT) level suddenly increased to 350 U/L. HBsAg became positive, with HBV DNA quantified at 1.92 × 108 IU/ml, confirming HBV-related hepatitis. She had not received any blood product in the prior months, and there was no known HBsAg + household contacts. Antibodies against hepatitis A, hepatitis C and hepatitis E viruses were negative. Ultrasonography did not show any liver pathology. With no prior clinical or serological evidence of HBV exposure in recent years, a diagnosis of HBV reactivation from seronegative occult hepatitis B infection was made. Entecavir 0.5 mg/day was commenced.

Outcome and follow up

With entecavir treatment, her liver function improved and HBV DNA level declined from 1.92 × 108 IU/ml to 33,900 IU/ml over 4 months. The clinical course was complicated by an intentional overdose of paracetamol (exact dose ingested unknown). ALT rose to 1956 U/L, and aspartate aminotransferase increased to 1324 U/L. There was improvement with N-acetylcysteine. However, her serum HBV DNA was still high at 33,900 IU/ml. Tenofovir alafenamide 25 mg/day was added for better HBV control. At the latest follow-up 6 months after the initial episode of HBV reactivation, she had remained asymptomatic, with ALT at 180 U/L and HBV DNA at 2450 IU/ml (Fig. 1). Her blood values obtained before, during, and after HBV reactivation were shown in Table 1.

Fig. 1
figure 1

Summarized course of the haematological disease and HBV reactivation

Table 1 Blood values obtained before, during, and after reactivation

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