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Hepatitis B

Afsha Rais Kaisani, MD, FAAFP and Niyomi DeSilva, MD Reviewed 05/2023



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Hepatitis B infection(HBV), caused by a DNA virus, is often transmitted by body fluids (blood, semen and vaginal secretions). HBV is a serious global healthcare concern due to the spectrum of liver disease it can cause ranging from acute hepatitis to cirrhosis and/or hepatocellular carcinoma (HCC). 



  • Infects patients of all ages; 80% of cases are in persons aged 30-59 (1)

  • Predominant sex: fulminant HBV: male > female (2:1)

  • ~60,000 new cases annually in the U.S.  (2)

  • Lower incidence in the U.S. compared to Asia and Africa due to: better access to healthcare, use of vaccinations and preventive measure.


  • In the U.S., 1.59 million persons (range 1.25-2.49 million) with chronic HBV (3)

  • Asia, the Pacific Islands, and people born in Africa have the largest populations at risk

  • Chronic HBV worldwide: 350 to 400 million persons

    • Second most important carcinogen (behind tobacco)

    • Of chronic carriers with active disease, 25% die due to complications of cirrhosis or HCC


HBV is a DNA virus of the Hepadnaviridae family. Two modes of transmission: 
  • Horizontal: mucosal surface contact with infectious bodily fluids

  • Vertical: maternal-to-newborn perinatal


Family history of HBV and/or HCC 


Screen the following high-risk groups for HBV with HBsAg. If positive, test for antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc) to distinguish between infection and immunity. Vaccinate if seronegative (4
  • Household or sexual contacts with hepatitis B. Persons born in regions with increase prevalence (Asia, Africa, Eastern Europe). HIV- and HCV-positive patients

  • Persons born in the U.S. who were not vaccinated as infants or whose parents are from regions of high prevalence

  • Individuals with chronic liver disease. Pregnant women. Residents in carceral facilities

Additional risk factors: 
  • Donors and recipients of blood/products. Persons on hemodialysis or immunosuppressive therapy. Needle stick/occupational exposure. Intranasal drug use; body piercing/tattoos. Survivors of sexual assault. Infants born to mothers positive for Hepatitis B surface antigen

Pediatric Considerations
  • Shorter acute course; fewer complications

  • 90% of vertical/perinatal infections become chronic.

Pregnancy Considerations
  • Screen for HBsAg at first prenatal visit (4)[A].

  • If HBsAg (+), obtain HBV DNA.

  • Consider treating patients with high viral load at 28 weeks or history of previous HBV (+) infant with oral nucleos(t)ide medication beginning at 32 weeks to reduce perinatal transmission . Infants born to HBV-infected mothers require hepatitis B immune globulin (HBIG) and HBV vaccine within 12 hours of birth, completing the vaccine series and serologic testing for infection and immunity by 9 to 12 months.

  • Breastfeeding is safe if HBIG and HBV vaccines are administered and the areolar complex is without fissures or open sores. Avoid oral nucleos(t)ide medications during lactation.

  • HIV increases risk of vertical transmission. Continue medications if pregnancy occurs while on an oral antiviral therapy to prevent acute flare.



  • Three IM injections at 0, 1, and 6 months in infants or healthy adults

  • Indicated for: all medically stable infant weighing 2,000 g (4 lb, 6 oz) or more within 24 hours of birth, unvaccinated infants and children and adults, all at-risk patients, healthcare and public safety workers, sexual contacts and household contacts of HBsAg carriers

  • CDC does not recommend administration of more than 2 complete hepatitis B series except for certain cases related to patients on hemodialysis

Other preventive measures 
  • Proper hygiene/sanitation by health care workers, IVDUs, and tattoo/piercing artists. Barrier precautions, needle disposal, sterilize equipment, cover open cuts. Do not share personal items exposed to blood (e.g., nail clipper, razor, toothbrush).

  • Safe sexual practices (condoms)

  • HBsAg carriers cannot donate blood or tissue.

  • Postexposure (e.g., needle stick):

    • HBIG 0.06 mL/kg in <24 hours in addition to vaccination (no more than 7 days after exposure)

    • Second dose of HBIG should be administered 30 days after exposure


  • HIV, hepatitis C coinfection

  • Extrahepatic manifestations include:

    • Serum sickness-like syndrome (fever, erythematous rash, myalgias, arthralgias, fatigue). Glomerulonephritis (membranous or membranoproliferative glomerulonephritis, IgA-mediated nephropathy)

    • Polyarteritis nodosa (Primary systemic necrotizing vasculitis, high fever, weakness, malaise, loss of weight and appetite). Dermatologic conditions (bullous pemphigoid, lichen planus, Gianotti-Crosti syndrome). Cryoglobulinemia (Raynaud phenomenon, arthritis, sicca syndrome)

    • Neurologic/psychological condition (Guillain-Barré syndrome, altered mental status, depression/psychosis)



Exposure: detailed family history, such as HBV infection and liver disease, vaccinations status and social history including alcohol use, drug use, and sexual history 
  • Acute HBV

    • Fever, fatigue, arthralgias, myalgias, anorexia, nausea, vomiting, right upper quadrant (RUQ) abdominal pain

    • Jaundice/scleral icterus, dark urine, pale stools

  • Chronic HBV: typically asymptomatic


Evaluate for stigmata of chronic liver disease: jaundice/scleral icterus, RUQ tenderness, hepatomegaly, palmar erythema, ascites, spider nevi, hepatic encephalopathy. 


  • Epstein-Barr virus (EBV); cytomegalovirus (CMV); hepatitis A, C, Dor E

  • Drug-induced, alcoholic, or autoimmune hepatitis

  • Wilson's disease; Hemochromatosis; HIV


Initial Tests (lab, imaging)

  • AST/ALT: Markedly elevated in acute HBV, ALT typically higher than AST

    • Transaminases may be normal or mildly elevated in chronic HBV; may increase before bilirubin

  • Bilirubin (conjugated/unconjugated): normal to markedly elevated in acute HBV; last test to normalize as acute infection resolves

  • Alkaline phosphatase: mild elevation

  • HBcAb IgM may be the only early finding (“window period” before HBsAg is positive).

  • For acute hepatitis:

    • PT/INR, albumin, electrolytes, glucose, CBC. If severe acute HBV, check for superinfection with hepatitis D (HDV Ag and HDV Ab). Hepatitis B serologic markers

  • Hepatitis B e-antigen (HBeAg+) indicates high replication/infectivity; confirmed with high HBV DNA (≥105 copies/mL); benefit from medical therapy

  • Screen for HDV, HIV, HCV, and immunity to hepatitis A virus (HAV Ab total/IgG).

    • Acute HBV and HDV coinfection tends to be more severe than acute HBV infection alone.

    • 10% of patients with HIV have co-infection/chronic HBV, making treatment of each more complex

  • Ultrasound to document ascites, organomegaly, signs of portal hypertension, hepatic or portal obstruction, and screen for HCC

Follow-Up Tests & Special Considerations

Chronic HBV: HBsAg+ persistence >6 months; has five distinct phases based on HBsAg, HBeAg, HBV DNA, ALT, liver inflammation: immune tolerant, immune reactive HBeAg positive, inactive carrier, HBeAg negative and Occult hepatitis B. 
  • Measure HBV DNA level and ALT q3–6 mo.

  • If age >40 years and ALT borderline or mildly elevated, consider liver biopsy.

  • Measure baseline AFP.

  • Follow HBeAg for elimination every 6–12 mo.

Screening for HCC (4
  • HCC surveillance recommended for all patients with viral load >100,000 copies/mL

  • Abdominal ultrasound and alpha fetoprotein testing every 6 months as screening for HCC; if ultrasound is abnormal, CT or MRI of the liver is recommended.

  • Continue surveillance even after treatment.

Diagnostic Procedures/Other

  • Liver biopsy is diagnostic

  • Noninvasive tests (Hepascore™, FibroTest™) or elastography (FibroScan™) can be used to assess fibrosis

Test Interpretation

Liver biopsy in chronic HBV may show interface hepatitis and inflammation, necrosis, cholestasis, fibrosis, cirrhosis, or chronic active hepatitis. 



  • Vaccinate for HBV if seronegative.

  • Monitor CBC, coagulation, electrolytes, glucose, renal function. Monitor ALT and HBV DNA; increased ALT and reduced DNA imply response to therapy. Screen for HCC if HBsAg+.

  • High risk for developing HCC with chronic HBV infection—needs routine monitoring


Goals of therapy: loss of HBsAg with sustained HBV DNA suppression, improvement in patient-oriented outcomes, HBeAg loss/seroconversion and ALT normalization. 

First Line

  • Acute HBV

    • Supportive care; spontaneously resolves in 95% of immunocompetent adults

    • Antiviral therapy not indicated except: fulminant liver failure or immunosuppressed

    • Treat patients with severe or protracted course and those with acute liver failure.

    • Treatment options include monotherapy with tenofovir or entecavir.

    MarkerAcute InfectionChronic InfectionInactive CarrierResolved InfectionSusceptible to InfectionVaccinated
    Anti-HBc+IgM−IgM; +total/IgG++
    HBV DNAPresentPresentLow negative
    ALTMarked elevationNormal to mildly elevatedNormalNormalNormalNormal
  • Chronic HBV: treatment per HBeAg status.

    • FDA-approved drugs: lamivudine 100 mg, adefovir 10 mg, entecavir* 0.5 to 1 mg, telbivudine 600 mg, or tenofovir alafenamide* 25 mg, all given PO every day (dose based on renal function and age); pegylated interferon (peg-IFN) α2a (Pegasys)*, α2b SC weekly for 48 weeks (4)[A]

    • *Recommended as first-line treatment options for chronic hepatitis B

  • Extended oral regimens are indicated (4)[A]

    • HBeAg+, treat 6 to 12 months post disappearance of antigen and gain of antibody.

    • HBeAg−, treat indefinitely or until clearance of antigen with antibody development.

  • Change/add drug based on resistance; confirm medication adherence prior to assuming drug resistance.

  • Precautions:

    • Oral drugs: renal insufficiency

    • Peg-IFN: coagulopathy, myelosuppression, depression/suicidal ideation


Referral to hepatology and transplant for all persistent HBsAg+, fulminant acute hepatitis, end-stage liver disease or HCC. 
Chronic Hepatitis B Therapy (4
HBeAgHBV DNA Viral LoadALT*Recommend
+≥20,000 IU/mLElevatedTreat with antiviral or interferon.
+≥20,000 IU/mLElevated but <2x ULNMonitor every 3–6 months; treat if biopsy shows moderate fibrosis
+≥20,000 IU/mLNormalObserve every 6 months, consider treatment if ALT elevated. Biopsy if age >40 years or ALT is high normal to mild elevation.
≥2,000 IU/mLElevatedTreatment indicated
≥2,000 IU/mLElevated but <2x ULNConsider biopsy or serum fibrosis marker, treatment if findings concerning.
≥2,000 IU/mLNormalMonitor every 3 months
≤2,000 IU/mLNormalMonitor every 3–6 months.
CirrhosisAnyAnyTreat with mono or combination treatment.
Liver failureAnyAnyTreat and refer for transplant.
*ALT elevated if >2 X ULN; ULN for male = 30 IU/mL and for female = 19 IU/mL


Liver transplantation, operative resection, radiofrequency ablation for HCC 


Worsening course (marked increase in bilirubin, transaminases, or symptoms); Hepatic failure (high PT, encephalopathy) 



Patient Monitoring

  • Serial ALT and HBV DNA: High ALT + low HBV DNA associated with favorable therapy response.

  • WBC and platelets if on interferon therapy

  • Monitor HBV DNA q3–6mo during therapy:

    • Undetectable DNA at week 24 of oral therapy associated with low resistance at year 2

  • Monitor for complications (ascites, encephalopathy, variceal bleed) in cirrhosis.

  • Vaccination status.

  • Ultrasound q6–12mo to screen for HCC starting at age 40 years in men and 50 in women (4)[B]


Alcohol increases risk of cirrhosis or HCC. 


  • Acute HBV: Review transmission precautions.

  • Chronic HBV, alcohol and tobacco use accelerate progression. Emphasize medication compliance to prevent flare.

  • Counsel chronic HBV carriers regarding risk of transmission to others.

  • Immunizations, especially against hepatitis A



Chronic hepatitis B  
  • Once HBV diagnosed, the 5-year cumulative incidence of developing cirrhosis is ~8-20% in those with untreated chronic HBV. Of patients with chronic HBV, 2-5% will progress to HCC with or without presence of cirrhosis.


  • Hepatic necrosis; cirrhosis; hepatic failure. HCC (all chronic HBV are at risk)

  • Severe flare of chronic HBV with corticosteroids and other immunosuppressants

  • Reactivation of infection if immunosuppressed. Premedicate prophylactically if HBsAg+ or if HBcAb+ and receiving systemic chemotherapy.


Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67(No. RR-1):1–31.
Centers for Disease Control and Prevention. 2019 Viral Hepatitis Surveillance Report. Accessed November 4, 2021.
Lim JK, Nguyen MH, Kim WR, et al. Prevalence of Chronic Hepatitis B Virus Infection in the United States. Am J Gastroenterol. 2020;115(9):1429-1438. 
Wilkins T, Sams R, Carpenter M. Hepatitis B: Screening, Prevention, Diagnosis, and Treatment. Am Fam Physician. 2019;99(5):314-323.


Cirrhosis of the Liver; Hepatitis A; Hepatitis C 



  • B19.10 Unspecified viral hepatitis B without hepatic coma

  • B16.9 Acute hepatitis B w/o delta-agent and without hepatic coma

  • B18.1 Chronic viral hepatitis B without delta-agent

  • Z22.51 Carrier of viral hepatitis B


  • 66071002 Type B viral hepatitis (disorder)

  • 76795007 acute type B viral hepatitis (disorder)

  • 61977001 chronic type B viral hepatitis (disorder)

  • 235871004 hepatitis B carrier (finding)


  • Screen all patients born in countries with endemic disease for HBV infection using HBsAg.

  • Chronic HBV is present if HBsAg persists > 6 months. Patients with chronic HBV need lifetime monitoring for disease progression and HCC.

  • Acute HBV is diagnosed with HBsAg and IgM anti-HBc; treatment is supportive.

  • Antiviral therapy is based on the presence or absence of cirrhosis, the ALT level and HBV DNA levels.