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Hepatitis B can sleep in the liver for years and wake up when cancer treatment weakens the immune system, sometimes damaging the liver badly. A blood test before treatment finds people at risk. Those who have it, or have had it and get high-risk treatment such as rituximab or a stem cell transplant, take an antiviral tablet during and for at least a year after treatment, or are checked closely.
ASCO's 2020 Provisional Clinical Opinion moved from risk-based to universal testing: everyone anticipating systemic anticancer therapy has HBsAg, anti-HBc (total Ig or IgG) and anti-HBs before or at the start of treatment, without delaying it (strong). Chronic HBV (HBsAg-positive) on any systemic anticancer therapy gets antiviral prophylaxis for the whole of treatment and at least 12 months after, with ALT and HBV DNA at baseline and every 6 months, monthly ALT for 3 months after stopping antivirals, and a clinician experienced in HBV (strong). Past HBV (HBsAg-negative, anti-HBc-positive) with anti-CD20 antibodies or stem cell transplant gets prophylaxis from the start and for at least 12 months after (strong), or, where follow-up can be relied on, HBsAg and HBV DNA every 3 months with antivirals at the first sign of reactivation (HBsAg appears or HBV DNA above 1,000 IU/mL). Past HBV with other regimens is monitored with HBsAg and ALT every 3 months. Hormonal therapy alone follows non-cancer HBV guidance (moderate).
APASL 2021 stratifies by the risk of the immunosuppressive therapy and by liver fibrosis, prefers entecavir, tenofovir or TAF (evidence I, recommendation 1), and considers stopping nucleos(t)ide analogues 6 months after immunosuppression ends in selected patients, where ASCO says at least 12 months. Anti-HBc can be falsely positive after intravenous immunoglobulin, so testing before IVIG is simpler to read.
Why: Asking about risk factors misses many carriers; testing everyone finds all the people whose virus could reactivate.
“All patients with cancer anticipating systemic anticancer therapy should be tested for hepatitis B virus (HBV) by three tests--hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to, or at the beginning of, systemic anticancer therapy.”
ASCO, Journal of Clinical Oncology 2020 · Strength of recommendation: strong
Why: The cancer is the more urgent problem, and prophylaxis can start alongside treatment.
“Anticancer therapy should not be delayed for the results of these screening tests.”
Why: IgM is a test for a new infection; immunoglobulin infusions can carry anti-HBc and give a false positive.
“anti-HBc testing after IVIG should be interpreted with caution.”
Why: Without it the virus can flare during or after treatment and damage the liver.
“Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy for the duration of anticancer therapy, as well as for at least 12 months after receipt of the last anticancer therapy.”
ASCO, Journal of Clinical Oncology 2020 · Strength of recommendation: strong
Why: Older drugs such as lamivudine let resistant virus emerge during long courses.
“4.3 Preferred NUCs include entecavir, tenofovir and TAF”
Asian Pacific Association for the Study of the Liver, Hepatology International 2021 · evidence I, recommendation 1
Why: Hepatitis can flare when the antiviral is withdrawn, so the months after stopping need closer checks.
“As such, ALT levels should be monitored frequently, at least monthly for the first 3 months after the cessation of antiviral therapy and every 3 months thereafter.”
Why: They decide how long antivirals continue and check for cirrhosis and liver cancer.
“Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy.”
Why: These treatments carry the highest risk of waking a resolved infection.
“Patients with past HBV receiving anticancer therapies associated with an established high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should be started on antiviral prophylaxis at the beginning of anticancer therapy and continued on antiviral therapy for at least 12 months after the cessation of anticancer therapy.”
ASCO, Journal of Clinical Oncology 2020 · Strength of recommendation: strong
Why: The reactivation risk with most other cancer drugs is unclear and probably low, so watching is enough.
“Patients with past HBV undergoing anticancer therapies that are not clearly associated with a high risk of HBV reactivation (eg, regimens that do not include anti-CD20 monoclonal antibodies or stem-cell transplantation) should be followed carefully during cancer treatment, with HBsAg and ALT testing every 3 months (with subsequent HBV DNA testing if a hepatitis flare develops), with initiation of antiviral therapy only if HBsAg becomes positive or HBV DNA exceeds 1,000 IU/mL in the setting of a hepatitis flare.”
ASCO, Journal of Clinical Oncology 2020 · Strength of recommendation: strong
Why: Hormone treatment on its own is unlikely to reactivate the virus.
“Hormonal therapy without systemic anticancer therapy is unlikely to increase the risk of HBV reactivation in patients with chronic or past HBV.”
ASCO, Journal of Clinical Oncology 2020 · Strength of recommendation: moderate
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
Test everyone before systemic anticancer therapy with HBsAg, anti-HBc and anti-HBs, without delaying treatment (ASCO 2020, strong; APASL 2021 also screens all patients planned for immunosuppressive therapy, evidence II-2, recommendation 1). Give a high-barrier antiviral (entecavir, tenofovir or TAF) to everyone with chronic hepatitis B on systemic therapy and to people with past infection on anti-CD20 antibodies or stem cell transplant. Where they differ: ASCO continues prophylaxis for at least 12 months after the last anticancer treatment, while APASL considers stopping 6 months after immunosuppression ends for HBsAg-positive patients without advanced fibrosis or with low HBV DNA, and for those who remain HBsAg negative; APASL also asks for a hepatologist's fibrosis assessment in every positive patient and treats anyone with advanced fibrosis or cirrhosis whatever the drug risk. ASCO allows close monitoring every 3 months in place of prophylaxis for past infection on high-risk therapy where follow-up is reliable.
ASCO, Journal of Clinical Oncology 2020 · Asian Pacific Association for the Study of the Liver, Hepatology International 2021
Where it differs: Grades each immunosuppressive therapy as high, moderate or low risk, gives pre-emptive antivirals to all HBsAg-positive or anti-HBc-positive patients in the high-risk group and to those with advanced fibrosis or cirrhosis in the others, monitors liver tests every 12 weeks in the rest, and considers stopping antivirals 6 months after immunosuppression ends.
Evidence: Graded on a modified GRADE scale; pre-emptive antivirals in the high-risk group are evidence I, recommendation 1; stopping at 6 months is evidence II-2, recommendation 1.
Asian Pacific Association for the Study of the Liver, Hepatology International 2021
Where it differs: HBsAg and HBV DNA every 3 months during and up to 12 months after treatment, with antivirals started immediately if HBsAg appears or HBV DNA exceeds 1,000 IU/mL.
Evidence: Offered by ASCO only where patients and clinicians can keep to frequent, consistent follow-up; part of a strong, informal-consensus recommendation.
Where it differs: Tests only people with risk factors for hepatitis B or those due to receive anti-CD20 antibodies or a stem cell transplant.
Evidence: ASCO replaced this with universal testing in 2020 on the basis of large prospective cohorts in which risk-factor questions missed infected patients; no randomised trial compares the two, and ASCO calls one unethical. Cost-effectiveness of universal testing in solid tumours is inconsistent across six analyses.
Hepatitis B can lie quiet for decades and flare when cancer treatment weakens the immune system, sometimes fatally. An American Society of Clinical Oncology opinion says everyone starting systemic cancer treatment should be tested first, and antiviral tablets prevent most flares. Across 29 studies, 57 per cent of patients were tested before chemotherapy.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Universal three-test HBV screening before systemic anticancer therapy | Type: evidence-based; benefits outweigh harms; Strength of recommendation: strong | ASCO, Journal of Clinical Oncology 2020 |
| Antiviral prophylaxis for chronic HBV throughout and 12 months after anticancer therapy | Type of recommendation: informal consensus, benefits outweigh harms; Strength of recommendation: strong | ASCO, Journal of Clinical Oncology 2020 |
| Hormonal therapy alone follows non-cancer HBV guidance | Type: informal consensus; benefits outweigh harms; Strength of recommendation: moderate | ASCO, Journal of Clinical Oncology 2020 |
| Screen all patients planned to receive immunosuppressive therapy “All patients planned to receive immunosuppressive therapy should be screened.” | evidence II-2, recommendation 1 | Asian Pacific Association for the Study of the Liver, Hepatology International 2021 |
| Pre-emptive nucleos(t)ide analogues for all HBsAg-positive or anti-HBc-positive patients in the high-risk group | evidence I, recommendation 1 | Asian Pacific Association for the Study of the Liver, Hepatology International 2021 |
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