Question 1 · Hard
A 63-year-old man with diffuse large B-cell lymphoma was screened before six cycles of rituximab-based chemotherapy: HBsAg nonreactive, total anti-HBc reactive, anti-HBs 24 mIU/mL and HBV DNA not detected. He declined antiviral prophylaxis and then missed his monitoring visits. Seven months after the last cycle he is jaundiced, with ALT 940 U/L (reference below 40) and bilirubin 86 µmol/L (5.0 mg/dL). Results: HBsAg reactive (confirmed by neutralization); IgM anti-HBc weakly reactive; anti-HBs below 2 mIU/mL; HBeAg reactive; HBV DNA 3.8 × 10^7 IU/mL. Markers of hepatitis A, C and E are negative, and he reports no new sexual or blood exposure. The most likely diagnosis is:
- AChronic hepatitis B missed at screening
- BA new acute hepatitis B infection
- CDrug-induced liver injury
- DReactivation of a resolved HBV infection
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Answer: D · Reactivation of a resolved HBV infection
Before treatment he had anti-HBc and anti-HBs without HBsAg, the profile of a resolved infection; HBV still persists in his liver as cccDNA, held in check by the immune system. Rituximab removes B cells, anti-HBs falls, and the virus can replicate again, so HBsAg reappears ('reverse seroconversion') with a high viral load and a hepatitis flare. IgM anti-HBc can return at a low level during reactivation, so it does not prove a new infection, and he had no new exposure. Drug injury would not produce HBsAg and 10^7 IU/mL of HBV DNA, and chronic infection was excluded at screening by a nonreactive HBsAg and undetectable DNA. Guidelines advise antiviral prophylaxis for anti-HBc-positive patients who receive rituximab, continued for many months after the last dose.
- A: HBsAg was nonreactive and HBV DNA undetectable before treatment.
- B: IgM anti-HBc can reappear in reactivation; his pre-treatment anti-HBc shows earlier infection.
- C: Drug injury does not make HBsAg appear or produce a high HBV DNA.