Monday, April 18, 2016


Hepatitis B Virus  (HBV) Is ubiquitous around the world. 1/3rd of the world population has been infected by it with 240 million people living with a chronic HBV infection. In the United States alone that number is 1.4 million and growing annually. HBV infection remains a serious world-wide healthcare issue.

Hepatitis B Virus (SM image)

While previously it was thought that only “high risk” individuals should be screened for the virus, the MSKCC (Memorial Sloan Kettering Cancer Center) experience teaches us that 50% of the infected individuals can be from the “low risk” category. (High Risk defined as country of birth, sexual history, blood transfusion etc. and Low Risk defined as no prior such risky behavior)

The HBV is a hepadnaviridae family of viruses. It has a partially double stranded DNA with up to 3320 nucleotides. The virus is encoded with three identified genes, The P gene or the Polymerase gene, The S gene or the Surface antigen gene and the X gene (function still debated). 

The mechanism of spread into the human body is quite simple and ingenious at the same time. After gaining entry, the viral core goes straight to the nucleus of the cell where it hijacks the cellular machinery for its own use to replicate producing a boatload of the viral cores. These cores are then shunted to the cytoplasm where the endoplasmic reticulum gives them the protein coating to move into the extracellular space to infect more cells. The process continues in perpetuity until the human body antibody defenses arrive to fight the virus colonies.

In most cases the diagnosis of past infection is established with anti-HBVs (surface antibody) or anti-HBVc (core antibody). A few people might harbor a small viral DNA load (via Polymerase Chain Reaction) but without symptoms or knowledge of the infection. 30% of the infected population does not know they ever had the infection.

In Oncology patients who undergo anti-neoplastic chemotherapy the risk of reactivation becomes a serious dilemma. Varying degree of reactivation risks are noted from 20-70% with an average of 49% associated with various immune suppressive agents.

Reactivation occurs as consequence of the suppression of the immune surveillance due to the chemotherapy, which leads to the viral cores liberation again in the liver causing the inflammation and the resultant 3x or more increase in the transaminases (the diagnostic criterion for reactivation). Although denovo infection and a reactivation can never be truly proven without a past history of the infection. The HBV reactivation can be sudden, dramatic and can occur up to 12 months after chemotherapy. The degree of inflammatory response in the liver can lead to liver failure and even death at times. Most times however it follows the traditional flare of the hepatitis with slow resolution. The derepression of the immune surveillance by the chemotherapeutic agents remains the causal key.

HBV reactivation has been noted in Breast Cancer patients following Cytoxan and Adriamycin chemotherapy, among Lymphoma patients undergoing CHOP regimens with and without the use of Rituxan an anti CD-20 drug, which on its own weight as a single agent can invoke the reactivation process and even patients taking TNFa inhibitors like Adilumumab used in Rheumatoid Arthritis and other chronic immune inflammatory diseases. 

The current recommendation is that history taking and considerations of the HBV risk must be taken into account for each individual. Screening with anti HBVs and anti HBVc should be done and if a positive Viral DNA Load is determined prior to initiation of any immunosuppressive therapy, those individuals are treated prophylactically with oral Entecavir daily through the entire course of chemotherapy. Lumividine (a cheaper drug) has been used extensively as well but Entecavir and Tenofovir are more potent HBV inhibitors to date.

It is incumbent upon the oncologist to elicit a history of potential risk and then screen for that risk prior to initiating the chemotherapeutic regimens. Prevention against reactivation, given the widespread nature of the infection worldwide, is an important tool for patient safety and good patient care.

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