Infections are a major well-known cause of complications in CLL and the risk of hepatitis B virus (HBV) reactivation is also higher, especially among patient treated with chemotherapy and immunosuppressive drug.
We report here the case of an 86-year-old woman diagnosed with CLL in 1998. Chlorambucil was started in February 2017 because of increasing lymphocytosis (>100 000/µL).
Her hepatitis B serology was positive four years before treatment with Chlorambucil for an occult hepatitis B infection with the presence of anti-hepatitis B core antigen antibodies (HBcAb). The detection of the hepatitis B surface antigen (HBsAg) and anti-hepatitis B surface antigen antibodies (HBsAb) were negative.  She was considered as an occult HBV carrier and had received no treatment at that time. 
Chlorambucil was stopped in February 2018. Five months after discontinuation, the patient suddenly developed a symptomatic acute hepatitis with jaundice and asthenia. 
The lab results showed a major hyperbilirubinemia with levels of ALAT and ASAT 10x higher than normal value. At that time, the lymphocytosis was < 10 000/µL and IgM were below normal value (<0.25g/L). 
The control of the HBV serology was positive for the surface antigen (HBsAg) and 3796 copies of the virus were identified by PCR, showing a reactivation of hepatitis B. 
Acute hepatitis with Metavir F3 score was proven by liver trans-jugular biopsy. 
We started an antiretroviral agent, Tenofovir, with progressive clinical and biological improvement.
It is very uncommon to have a reactivation of hepatitis B with an alkylating agent alone without additional immunosuppression.  The immunosuppressive role of Chlorambucil is probably underestimated. 
This case highlights the importance of considering a pre-emptive therapy for inactive and occult HBV carrier and not only for HBsAg positive patient.  It also shows the significant immunosuppressive role of an alkylating agent in monotherapy in CLL patients.

Acute hepatitis after chlorambucil alone for chronic lymphocytic leukemia (CLL).