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Lymphoma Chemotherapy Can Cause Severe Hepatitis B Reactivation

Chronic hepatitis B patients are at risk for recurrence or relapse when they undergo chemotherapy for lymphoma, despite receiving prophylaxis with lamivudine (Epivir-HBV), according to an Italian study presented at the recent 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) in Boston. Investigators recommended that other potentially more effective antiviral drugs should be studied for this indication.

A majority of adults with hepatitis B virus (HBV) infection can naturally control the virus without treatment, but this control can be lost when people receive chemotherapy or immunotherapy for cancer. Chemotherapy drugs can damage bone marrow and the disease-fighting immune cells it produces, leaving the body susceptible to new infections and relapse of existing infections.

To help prevent relapse, people who carry hepatitis B are usually given antiviral drugs as prophylaxis. Hepatitis B surface antigen (HBsAg) positive patients typically receive nucleoside/nucleotide analogs for at least 1 year after completion of chemotherapy, but the optimal duration of prophylaxis is unknown. Lamivudine is one of the older HBV-fighting agents, and long-term therapy can be compromised by emergence of drug resistance. The risk of HBV reactivation during chemotherapy among HBsAg negative but hepatitis B core antibody (anti-HBc) positive patients remains to be determined. (See How to interpret HBV antigen and antibody tests.)

G. Genile from the University of Rome and colleagues retrospectively analyzed medical records from 630 lymphoma patients, identifying 13 people (2%) who were HBsAg positive and 59 (10%) who were HBsAg negative/anti-HBc positive. These patients underwent chemotherapy between January 2006 and September 2009.

All HBsAg positive patients received lamivudine prophylaxis to prevent HBV reactivation. In accordance with Italian guidelines, individuals who were HBsAg negative/anti-HBc positive after April 2007 also received lamivudine starting at the beginning of chemotherapy and lasting through 12-18 months after chemotherapy discontinuation. HBV reactivation was defined as detectable HBV DNA viral load and ALT liver enzyme elevation.

Results

• All 13 HBsAg positive patients received lamivudine prophylaxis, for a median duration of 16 months after competing chemotherapy (range 6-36 months).
• During lamivudine prophylaxis, 4 of these patients developed HBV reactivation hepatitis, occurring at 9, 12, 15, and 16 months after finishing chemotherapy.
• In 2 patients, HBV reactivation was associated with lamivudine-resistant HBV mutations.
• 1 person died of liver failure.
• Another patient experienced HBV reactivation 6 months after stopping lamivudine prophylaxis.
• Among the 59 HBsAg negative/anti-HBc positive participants, 47 received lamivudine prophylaxis.
• None of these treated patients experienced HBV reactivation.
• Among the remaining 12 patients who did not receive prophylaxis, 3 people (25%) experienced severe HBV reactivation.

Based on these findings, the researchers stated, "In HBsAg positive lymphoma patients receiving chemotherapy, severe HBV reactivation may occur after 1 year of prophylaxis with lamivudine."

In this setting, they continued, "the role of other [nucleoside/nucleotide analogs] should be evaluated.

HBV reactivation was also observed in HBsAg negative/anti-HBc positive people, they added, but "prophylaxis with lamivudine seems efficacious for this group of patients."

Investigator affiliation: Sapienza, Univ. of Rome, Rome, Italy.

9/28/10

Reference

G Gentile, E Russo, F De Angelis, and others. Hepatitis B Virus (HBV) Reactivation Following Chemoimmunotherapy: A Serious Complication in Both Hepatitis B Surface Antigen (HBsAg)-Positive and HBsAg-Negative Lymphoma Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract V-1786.