Hepatitis B in Pregnancy, Prophylaxis, and HDV Coinfection

Educational Objectives

The goal of this program is to improve management of hepatitis B in special populations. After hearing and assimilating this program, the clinician will be better able to:

1. Maximize the value of prophylaxis in patients with hepatitis B who are at high risk for reactivation.
2. Implement targeted strategies to prevent maternal-fetal transmission of the hepatitis B virus.
3. Provide optimal treatment in patients with hepatitis B and hepatitis D virus coinfection.

Summary

Background: >240 million persons worldwide affected by hepatitis B virus (HBV) infection; majority of HBV infections in United States in immigrant populations; first-line agents include entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide; treatments suppress HBV viral load, and barrier to resistance high; pegylated interferon given to select individuals (eg, use not safe in patients with cirrhosis)

American Association for the Study of Liver Diseases (AASLD) guidelines: treat patients with HBV infection who are viremic and have signs of liver inflammation or elevated alanine aminotransferase (ALT) levels; criteria include HBV DNA >20,000 for hepatitis B e-antigen (HBeAg) — positive patients; HBV DNA >2,000 and ALT level 2 times the upper limit of normal for HBeAg-negative patients; data to support early treatment in immune-tolerant patients lacking (those with high viral load but who do not meet cutoff for ALT level); consider treatment in immune-tolerant patients aged >30 yr; tenofovir alafenamide not approved for use in pregnancy; tenofovir disoproxil fumarate most appropriate in women of childbearing age and pregnancy; consider discontinuing therapy in patient with loss of e-antigen after consolidation

HBV prophylaxis: reactivation of HBV — defined by increases in replication of HBV DNA during immunosuppressive therapy; may or may not be associated with hepatitis (viral load may increase, but ALT level may not); patients at high risk — hepatitis B surface antigen (HBsAg) — positive; hepatitis B core antibody (HBcAb) — positive (but HBsAg — negative); patients who take immunosuppressive agents (eg, disease-modifying antirheumatic drugs, corticosteroids [high doses, prolonged use], tumor necrosis factor [TNF]-α inhibitors, direct-acting antiviral [DAA] agents)

American Gastroenterological Association guidelines (Reddy et al 2015): high-risk group — risk for HBV reactivation >10%; includes isolated HBcAb-positive (HBsAg — negative) patients, patients who take B cell — depleting agents (eg, rituximab), and HBsAg-positive patients who take anthracycline derivatives or moderate- to high-dose corticosteroids for ≥4 wk; medium-risk group — includes isolated HBcAb-positive patients who take TNF inhibitors or moderate- to high-dose corticosteroids for ≥4 wk; recommendations — start antiviral therapy in patients in medium- and high-risk groups; monitor low-risk group

AASLD guidelines: test for HBsAg and HBcAb before starting immunosuppressive or immunomodulating therapy; start HBV prophylaxis for HBsAg-positive patients (regardless of viral load) and isolated HBcAb-positive patients who take rituximab or are undergoing stem cell transplantation; continue treatment 6 to 12 mo after completion of immunosuppressive therapy; prescribe entecavir or either form of tenofovir; in patients not receiving prophylaxis, monitor HBV DNA levels every 1 to 3 mo during treatment and ≤1 yr after end of therapy

Hepatitis C and reactivation of HBV infection: reactivation of hepatitis B may occur in patients with hepatitis C virus (HCV) infection who take DAAs; Mücke et al (2018) found pooled rate for HBV reactivation 8%; measure HBsAg and HBcAb before starting DAAs for HCV; European Association for the Study of the Liver (EASL) guidelines — give HBV prophylaxis for HBsAg-positive patients who are starting DAA therapy for HCV infection (even if criteria for HBV prophylaxis not met); in patients with HCV infection and isolated HBcAb-positive status, monitor ALT levels; if ALT level increases, measure HBsAg and viral load, and start prophylaxis if indicated; AASLD guidelines — monitor patients with HBsAg- and HBcAb-positive status; start prophylaxis if ALT level increases or signs of active hepatitis present

HBV infection in pregnancy: background — perinatal transmission accounts for >50% of the global burden of HBV infection and is the most prevalent route of transmission; US Preventive Services Task Force gives grade A recommendation for HBsAg screening in all pregnant women; 90% of infants who acquire HBV through maternal-fetal transmission develop chronic HBV infection; prevention — effectiveness of administration of HBV vaccine and hepatitis B immune globulin (HBIG) ≈95%; in infants born to mothers with HBV infection, administer first dose of HBV vaccine and HBIG ≤12 hr after birth; Pan et al (2016) reported risk for maternal-fetal transmission of HBV significantly higher when tenofovir was not prescribed in the third trimester to mothers with HBeAg-positive status and viral load >200,000; recommendations — treat pregnant women with viral load >200,000 during third trimester to reduce risk for maternal-fetal transmission

Management: screen all pregnant women for HBsAg; test level of HBV activity; start treatment with tenofovir if needed (even during first trimester); in women not qualifying for treatment at baseline, recheck viral load at 26 to 28 wk; if viral load >200,000 (even with normal ALT level), give tenofovir in the third trimester; stop treatment at delivery or within 1 mo of birth; monitor for flare of HBV infection after cessation of treatment

Hepatitis D virus (HDV) infection (δ hepatitis): virus has 1.7-kilobase single-stranded circular RNA genome; most severe form of human viral hepatitis; rate of development of cirrhosis within 5 to 10 yr ≤80%; HDV acts as satellite virus and requires HBV for replication

Studies: Kushner et al (2015) — studied >25,000 patients with HBV infection within US Department of Veterans Affairs medical system; found rate of testing for HDV ≈9% (rate of positive tests ≈3.4); incidence of liver cancer significantly higher in patients with HDV infection compared with patients without HDV infection; Patel et al (2019) — National Health and Nutrition Examination Survey (2011-2016) found prevalence of HDV among HBsAg-positive patients 42%; among intravenous drug users very high; testing for HDV in all patients with HBV infection recommended

Treatment: AASLD recommends pegylated interferon for 12 mo in patients with elevated HDV RNA and ALT levels; EASL recommends pegylated interferon for ≥48 wk in patients with HDV coinfection; effectiveness of treatment low (response rate ≤33%); adverse effects significant; late relapse possible

Readings

Kushner T et al: Delta hepatitis within the Veterans Affairs medical system in the United States: Prevalence, risk factors, and outcomes. J Hepatol, 2015 Sep;63(3):586-92; Mücke MM et al: Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol, 2018 Mar;3(3):172-80; Pan CQ et al: Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med, 2016 Jun;374(24):2324-34; Patel EU et al: Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011-2016. Clin Infect Dis, 2019 Aug;69(4):709-12; Reddy KR et al: American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology, 2015 Jan;148(1):215-9; Screening for hepatitis B virus infection in pregnant women: Recommendation statement. Am Fam Physician, 2020 Jan;101(2):112-4; Terrault NA et al: Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology, 2018 Apr;67(4):1560-99.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Kushner was recorded at the 14th Annual Science in the City: Review of Treatments for Viral Hepatitis and an Update on Evolving Therapies for Chronic Liver Diseases, held November 23, 2019, in New York, NY, and presented by the Icahn School of Medicine at Mount Sinai. For more information about upcoming CME activities sponsored by the Icahn School of Medicine at Mount Sinai, please visit icahn.mssm.edu/education/cme. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

GE341802

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.