Will chemotherapy cause my “hepatitis B” to come back? What can I do?

by Specialist

What is HBV reactivation?

We are a major hepatitis B country.

China is a “hepatitis B country” with a 9.72% hepatitis B virus (HBsAg) positivity rate in the population, and cancer patients are at significantly higher risk of hepatitis B virus (HBV) infection than healthy people. When lung cancer patients with “hepatitis B” or HBV receive chemotherapy, the drugs suppress immune function, making the virus replicate more actively and causing liver damage, which is known professionally as “HBV reactivation. This is known as “HBV reactivation”. 20% to 50% of HBsAg-positive patients may experience varying degrees of reactivation during or after the application of immunosuppressive or “cytotoxic” chemotherapy drugs.

HBV reactivation can cause liver damage, fulminant hepatitis, and even liver failure, affecting antitumor outcomes and patient outcomes.  

How do you determine if HBV reactivation has occurred?

How is HBV reactivation determined? There is no consensus in the profession. Most scholars believe that HBV reactivation occurs after one of the following three criteria is met and other viral infections are ruled out:

    Hepatitis during or immediately after chemotherapy with a 10-fold or greater increase in blood HBV viral load (expressed as HBV-DNA) compared to pre-chemotherapy;

  1. HBV-DNA absolute values greater than 20,000 IU/ml;

  2. HBV-DNA serology changed from negative to positive.

How does the occurrence of HBV reactivation affect me?

This impact is mainly in the liver injury itself and in the oncology treatment.

After HBV reactivation, in mild cases there are no symptoms, only elevated ALT (alanine aminotransferase) on blood tests, or typical hepatitis symptoms such as fatigue, jaundice (yellowing of skin and mucous membranes and sclera), ascites, and hepatic encephalopathy (coma and unconsciousness due to liver failure); in severe cases, “fulminant hepatitis” and progressive liver failure can occur. In severe cases, “fulminant hepatitis” and progressive liver failure may occur, leading to death. The incidence of fulminant hepatitis is higher and more likely to be life-threatening when compared to regular acute hepatitis B due to HBV reactivation caused by chemotherapy.

The occurrence of reactivation requires interruption of chemotherapy, which clearly compromises the anti-tumor effect.

Patients with hepatitis B, assess risk of HBV reactivation before chemotherapy

Our 2015 professional guidelines call for routine screening of hepatitis B surface antigen (HBsAg), core antibody (HBcAb), and viral load (HBV-DNA) levels in all patients receiving chemotherapy or immunosuppressive therapy before treatment initiation to assess the risk of liver injury from HBV reactivation and to plan for management.

The United States has similar requirements. Immunosuppressants are classified as high, medium, or low risk according to their potential to cause HBV reactivation. The American Gastroenterological Association (AGA) recommends screening for HBsAg and HBcAb before using “medium- and high-risk” immunosuppressants, with further HBV-DNA testing for those who are positive. Based on the test results and treatment plan, physicians stratify patients by risk of liver injury and consider prophylactic antiviral therapy.

Chemotherapy for HBsAg-positive patients, early initiation of anti-HBV therapy

There are three times to initiate anti-HBV therapy in HBsAg-positive patients receiving chemotherapy:

    Preventive dosing: start NAs 1 to 2 weeks before, or concurrently with, chemotherapy and continue treatment after chemotherapy, regardless of ALT (glutamate transaminase, a blood indicator of liver function) and HBV-DNA levels, as long as HBsAg is positive;

  1. Early treatment: test HBV-DNA and ALT every 2 weeks during chemotherapy, and if HBV-DNA is found to be elevated or changed from “undetectable” to “detectable”, take NAs immediately before ALT is elevated;

  2. Delayed intervention: receive antiviral therapy after HBV reactivation has clearly occurred.

Studies have found that delayed intervention is less effective in controlling viral reactivation and has poorer patient outcomes than prophylaxis and early treatment. Therefore, existing guidelines recommend prophylactic anti-HBV therapy.

Our 2015 expert consensus recommends:

    For HBsAg-positive chemotherapy patients, prophylactic antiviral therapy, such as entecavir or tenofovir, should be used 2 to 4 weeks before chemotherapy, even if HBV-DNA is below the lower limit of detection and ALT is normal.

  1. If HBV-DNA is less than 20,000 IU/ml before chemotherapy, consider discontinuing prophylaxis 6 months after the end of immunosuppression or chemotherapy; if HBV-DNA is not less than 20,000  IU/ml before chemotherapy, continue treatment as chronic hepatitis B after chemotherapy and let the hepatologist or infectious disease physician decide when to discontinue the drug.

  2. For HBsAg-negative, HBcAb-positive patients, prophylactic antiviral therapy may be administered if the chemotherapy agent is anti-CD20 (e.g., rituximab), anti-tumor necrosis factor, or high-dose glucocorticoids, as appropriate; otherwise, the physician will monitor closely and add antiviral agents as soon as changes in HBV-DNA levels and HBsAg positivity occur, and after chemotherapy is completed, NAs therapy should be continued for at least 6 months after chemotherapy.

    3. How to choose anti-HBV drugs during chemotherapy

    There are two main classes of anti-HBV drugs: interferons and nucleoside analogues (NAs). Interferons are limited by the potential for increased liver injury and bone marrow suppression when used with chemotherapy drugs.

    There are 5 NAs approved for clinical use: lamivudine, adefovir, entecavir, tipifovir, and tenofovir. Of these, HBV is most likely to be “resistant” to lamivudine, with resistance rates increasing over time. The newer antivirals (entecavir, adefovir, tenofovir) have the advantage of high efficiency and low resistance.

    Our guidelines recommend lamivudine or telbivudine for expected duration of therapy up to 12 months, and prefer entecavir or adefovir for longer duration of therapy.

    Extended reading

    What conditions predispose to HBV reactivation?

    Experts generally agree that HBV reactivation is not a problem.

    Experts generally agree that HBV reactivation is primarily related to viral infection status, tumor type and treatment regimen, and patient physical status.

    1.

    1. Viral infection status

    HBV carrier status and pretreatment viral load are associated with “reactivation”.

    Patients with surface antigen HBsAg (+), E antigen HBeAg (+), and core antibody HBcAb (+) (also known as “major triplets”) are usually more likely to have them. A high viral load is an independent risk factor.

    In addition, low HBsAb levels and negative serum HBsAg with measurable viral load are also important risk factors.

    2. Tumor type and treatment options

    Cancer type and chemotherapy drugs also have an impact. The incidence of hematologic malignancies in general (especially lymphomas) is high (24% to 67%). Among solid tumors, the incidence of breast cancer is 41% to 56%, and the incidence of lung, colon, and gastric cancers is lower at 14% to 21%.

    Among the “cytotoxic drugs,” corticosteroids (e.g., glucocorticoids, dexamethasone) and anthracyclines (e.g., adriamycin, epi-amycin) are the most common “culprits” for “reactivation. “. In biologics, monoclonal antibody drugs such as etanercept, tuximab, and alemtuzumab can deplete immune cells and thus cause HBV reactivation.

    Co-authors: Dr. Yue-Li Sun, Guangdong Provincial People’s Hospital, Guangdong Lung Cancer Institute, Dr. Ming-Feng Zhang