Hepatitis B is a viral infection caused by the hepatitis B virus (HBV). It occurs worldwide and is transmitted sexually, parenterally, or vertically. After an incubation period of 1–6 months, most patients develop asymptomatic or mild inflammation of the liver, which usually resolves spontaneously within a few weeks or months. However, 5% of adult patients and 90% of infants infected perinatally develop chronic hepatitis B (CHB). Individuals with CHB may be asymptomatic carriers or develop ongoing hepatic inflammation with an increased risk of cirrhosis and hepatocellular carcinoma. Serologic testing initially includes measurement of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). A detectable serum anti‑HBs (indicating seroconversion) is a sign of recovery or successful immunization. CHB with persistent liver inflammation is characterized by detectable HBsAg and elevated HBV DNA and ALT. Treatment of acute hepatitis B consists of supportive measures. In patients with fulminant hepatitis, liver transplantation may be necessary. For chronic active hepatitis B, nucleoside or nucleotide analogs (e.g., tenofovir) are the preferred agents for reducing viral replication and infectivity. Prophylactic immunization with a recombinant vaccine is recommended for all age groups. Other preventive measures include postexposure prophylaxis for infants born to individuals with HBsAg positive or unknown status and for unvaccinated individuals with recent exposure to HBV.
See also “Acute liver failure.”
Prevalence: Following the introduction of the hepatitis B vaccine in 1991, rates of acute hepatitis B in the US have declined by approx. 82%. 
- In 2016 there were an estimated 862,000 cases (∼ 0.3% of US population) in the US. 
- In 2015, there were > 257 million cases worldwide (3.5% of the global population). 
- The Western Pacific is the most affected region worldwide (6.2% of its population). 
Epidemiological data refers to the US, unless otherwise specified.
- Hepatitis B virus (HBV)
- See “viral structure. ” for more information on
Frequency and patterns of transmission vary worldwide.
- Sexual: transmitted when bodily fluids come in contact with broken skin or mucous membranes (mouth, genitals, or rectum)
- Vertical transmission (mother-to-child transmission) 
- Common associations
Risk factors for HBV infection and groups at risk 
- Vertical transmission
Parenteral or sexual transmission
- Injection drug use (current or previous)
- History of sexually transmitted infections or multiple sexual partners
- Sex workers
- Men who have sex with men
- Household, sexual, or needle-sharing contacts of individuals with HBV
- Current or previously incarcerated individuals
- Health care personnel (e.g., needlestick injury)
- HIV infection
- HCV infection (current or past)
- Chronic liver disease
- End-stage renal disease
Replication cycle of HBV 
- After entering the host cell's nucleus, reverse transcriptase completes the positive strand of the virus's partially double-stranded relaxed circular DNA (rcDNA).
- The rcDNA is converted to covalently closed circular DNA (cccDNA) primarily by host enzymes in a process that is not entirely understood.
- The cccDNA is then transcribed into viral mRNA by host RNA polymerase.
- The viral mRNA leaves the nucleus and is translated into HBV core proteins and new reverse transcriptase in the cytoplasm.
- Viral mRNA and reverse transcriptase are packaged into a capsid, where viral mRNA is then reverse-transcribed into viral rcDNA.
- New viral DNA genomes are enveloped and leave the cell as progeny virions.
Acute infection 
- In acute infection, the cellular immune response causes damage to hepatocytes.
- Hepatitis B-infected hepatocytes express viral peptides ; on their surfaces → detection of the HBV-derived peptides by lymphocytes and the subsequent activation of CD8+ T cells that attack the infected hepatocytes → hepatic inflammation with destruction of hepatocytes 
Chronic infection 
Caused by viral persistence due to failing immune clearance, which promotes:
- Persistent hepatic inflammation → necrosis, mitosis, and regeneration processes → cirrhosis and cellular dysplasia → hepatocellular carcinoma (HCC)
- Integration of HBV DNA into the host genome → altered expression of endogenous genes, chromosomal instability →
- HBV proteins fulfill numerous immune-modulating functions that allow them to elude detection by the immune system and avoid clearance. 
Acute hepatitis B virus infection
Acute HBV infection is defined as infection acquired in the past 6 months.
- Incubation period: 1–6 months 
Clinical course: varies significantly 
- Serum sickness-like syndrome can develop during the prodromal (preicteric) period 1–2 weeks after infection: rash, arthralgias, myalgias, fever 
- Subclinical hepatitis (∼ 70% of cases) 
- Symptomatic hepatitis (∼ 30% of cases; see also acute viral hepatitis)
- Symptoms usually resolve after a few weeks, but can last up to 6 months. 
- May develop into fulminant hepatitis (∼ 0.5% of cases)
Chronic hepatitis B virus infection 
- Most patients are inactive, noncontagious carriers. 
- Potential reactivation of chronic inactive hepatitis can manifest variably in the following ways:
The younger when infected, the more likely a patient develops chronic HBV 
- 90% of infants
- ∼ 50% of children between 1 and 5 years
- Only 5% of adults
Overview of HBV serology
|Overview of HBV antigens and their corresponding antibodies |
|HBV antigen/DNA||Description||Corresponding antibodies|
Hepatitis B surface antigen (HBsAg)
Hepatitis B core antigen (HBcAg)
Hepatitis B e antigen (HBeAg) 
| || |
Indications for HBV screening 
Obtain initialfor the following individuals (see “Diagnostics” for interpretation of results):
- All individuals aged ≥ 18 years: at least once per lifetime
- Pregnant individuals: once per pregnancy, preferably in the first trimester (see “Perinatal hepatitis B”) 
- Individuals with 
- Patients with elevated transaminases of unknown etiology
- Blood and tissue donors 
- Individuals who require immunosuppression 
- Any individual who requests screening
Suspected acute HBV infection
- Obtain to confirm the diagnosis.
- Consider routine laboratory studies to assess liver damage and function.
- Perform a clinical evaluation to assess for:
- Assess for liver fibrosis using, e.g.: 
- Screen for other infections, including HCV, HDV, and HIV.
- Consider abdominal ultrasound and/or liver biopsy in certain patients.
HBV serology 
- Screening for HBV infection
- Patients with symptoms of or
- Initial tests ; 
- Further disease markers: indicated to assess disease activity if initial tests are positive
Interpretation of hepatitis B serology
|Interpretation of hepatitis B serology |
|Acute infection||↑||Undetectable||↑ IgM||↑||Undetectable||Undetectable or ↑||↑ (ALT > AST)|
|Undetectable||Undetectable||↑ IgM → ↑ IgG||Undetectable||Undetectable or ↑||Undetectable or ↑||↑ (ALT > AST)|
Active (high transmissibility)
|↑||Undetectable||↑ IgG||↑||Undetectable||Normal or ↑|
Inactive (low transmissibility)
|↑||Undetectable||↑ IgG|| |
|↑||HBV DNA ≤ 2000 IU/mL||Normal|
|Immunity||Resolved infection||Undetectable||↑||↑ IgG||Undetectable||↑||Undetectable||Undetectable|
HBeAg: BEware! Extremely infEctious.
Additional laboratory studies 
- Liver chemistries: elevated in acute infection, normal or elevated in chronic infection
- Evaluation of coinfection
Abdominal ultrasound 
- Indication: to evaluate liver parenchyma and biliary tract and screen for fibrosis and/or HCC
- Findings in acute hepatitis
- Findings in chronic hepatitis
Liver biopsy 
Active viral hepatitis 
Chronic viral hepatitis 
- Formation of lymphoid follicles and mononuclear infiltrates
- Interface hepatitis (piecemeal necrosis)
- Fibrous septa 
- Ground glass hepatocytes ; 
|Differential diagnosis of viral hepatitis|
|Pathogen||Hepatitis A virus (HAV) ||Hepatitis B virus (HBV) ||Hepatitis C virus (HCV) ||Hepatitis D virus (HDV) ||Hepatitis E virus (HEV) |
|Route of transmission|| || || || |
|Incubation period|| || || || |
|Clinical course|| || || || |
|Risk of chronification|| || || || |
|Extrahepatic manifestations || || || |
|Treatment|| || |
|Immunization|| || |
|Prognosis|| || || || || |
Vowels (A and E) are bowels (transmitted fecal-orally) and usually only cause AcutE hepatitis.
Recovery rates of hepatitis B infection in adults are very good, with less than 5% of cases progressing to chronic infection. In contrast, the risk of developing chronic hepatitis is considerably higher in infants infected perinatally (90%) and young children (20–50%).
The differential diagnoses listed here are not exhaustive.
- All patients
Acute hepatitis B
- Antiviral therapy is generally not indicated.
- In rare cases, patients may require .
- Chronic hepatitis B
Antiviral therapy for chronic hepatitis B 
Treatment decisions should be made by a specialist and based on the risk of liver-related morbidity and mortality. The following information applies to nonpregnant individuals; for pregnant individuals, see “Management of hepatitis B in pregnancy.”
Indications for antiviral therapy for HBV infection include:
- Cirrhosis or advanced fibrosis
- Acute liver failure
- Immune active phase: ALT ≥ 2× ULN plus significantly elevated HBV DNA levels with or without HBeAg 
- HBV reactivation: an increase in HBV DNA or change from HBsAg negative to HBsAg positive in anti-HBc-positive patients
- Immunosuppression in HBV-positive patients
- Coinfection with HCV or HIV
- Family history of HCC
- Agents: For details on mechanisms of action and adverse effects, see “ ” and “ .”
- Treatment regimens
Supportive care and patient education
- Avoid hepatotoxic medications.
- Advise alcohol cessation.
- Provide and/or as indicated.
- Provide to encourage weight loss as indicated. 
- Educate patients on measures to prevent HBV transmission, including: 
- Vaccinating household and sexual contacts
- Abstaining from blood and tissue donation
- Practicing safer sex (e.g., using condoms)
- Covering open wounds
- Cleaning up blood spills with diluted bleach
- Avoiding IV drug use or practicing strategies if injecting drugs
- Avoiding sharing of personal care items, such as razors, toothbrushes, glucometers, and injection equipment
HBV can survive outside the body (e.g., in dried blood on a surface) for at least 7 days, and remains infectious during that time. 
Hepatitis D virus infection 
- Epidemiology: 5% of all chronically infected HBV patients are carriers of the hepatitis D virus.
- Etiology: Hepatitis D virus (HDV)
- Transmission: : sexual, parenteral, perinatal
- Incubation period
- Clinical features: similar to acute HBV infection
- Treatment: Pegylated interferon alfa (PEG-IFN-α)
- Complications: identical to those of hepatitis B (see below)
- Epidemiology: Affects ∼ 1% of acute HBV infections 
- Diagnosis: evidence of hepatic injury (e.g., ↑ transaminases, ↑ bilirubin), hepatic encephalopathy, and coagulopathy (INR > 1.5).
- Management: See “Acute liver failure.”
Long-term complications of hepatitis B 
- (HCC) 
- Extrahepatic manifestations (10–20% of cases) 
- Reactivation of previous HBV infection due to immunosuppression
- Post‑hepatitis syndrome
We list the most important complications. The selection is not exhaustive.
- The hepatitis B vaccine (HBV vaccine) is an inactivated recombinant vaccine that contains a subunit of the hepatitis B virus. 
- The first dose of a 3-dose HBV vaccine series should be administered to all infants at birth
- Catch-up vaccination
- See “ACIP immunization schedule” for details.
Hepatitis B postvaccination serology 
- Individuals at risk of occupational exposure (e.g., health care workers)
- Immunocompromised individuals
- Patients receiving hemodialysis
- Sexual partners of HBsAg-positive persons
- Infants born to individuals with HBsAg positive or unknown status
- Infants 
- Anti-HBS ≥ 10 IU/mL: immune, and no further management is required
Anti-HBS < 10 IU/mL: non-immune
- Additional dose(s) and repeat postvaccination serology are required. Choose one of the following options:
- If repeat anti-HBs titers remain < 10 IU/mL after two complete series of HBV vaccine, the individual is considered an HBV vaccine nonresponder.
- HBsAg positive (in infants): Provide treatment for hepatitis B infection.
Hepatitis B postexposure prophylaxis 
- Exposure is defined as percutaneous or mucosal contact with blood or body fluids.
- Irrigate exposed tissue. 
- HBV PEP recommendations differ for exposures in occupational and nonoccupational settings.
- Depending on immunization status, affected individuals will receive one of the following:
Occupational exposure (i.e., )
- Verify vaccination status and immune response in the exposed health care provider ( ).
- If series is complete and ≥ 10 mIU/mL is already documented, source patient is not required.
- If series is complete and immune response is unknown, measure exposed and source patient .
- If unvaccinated or series is incomplete, measure source patient only.
- See “needlestick injuries. ” for additional information, e.g., on
|HBV PEP for occupational exposure |
|HCP vaccination status||Source patient|
|HBsAg negative||HBsAg positive or unknown|
|Complete series||≥ 10 mIU/mL|| |
|< 10 mIU/mL|| || |
Unvaccinated or incomplete series
Modification of work duties and sexual practices of HCPs following exposure to a patient with a positive or unknown HBsAg status is unnecessary during the 6-month follow-up period. Pregnancy and breastfeeding are safe during this time. 
- Exposure types include needle sharing and high-risk sexual contact.
- Obtain vaccination history and measure HBsAg, anti-HBs, and anti-HBc in unvaccinated exposed patients.
- Do not withhold or delay vaccination for prevaccination testing.
|HBV PEP following nonoccupational exposure |
|Patient vaccination status||Source individual|
|HBsAg unknown||HBsAg positive|
|Complete series||≥ 10 mIU/mL|| |
|< 10 mIU/mL or unknown|| || |
|Unvaccinated or incomplete series|
- Perform universal first trimester. , preferably in
- If anti-HBs < 10 mIU/mL in a pregnant individual, initiate a 3-dose HBV vaccine series.
- If HBV serology indicates infection, , including:
- Provide appropriate immunoprophylaxis to .
Hepatitis B in pregnancy 
Screening for HBV infection in pregnancy 
- During each pregnancy, as part of initial during the first trimester
When admitted for delivery, screen individuals if either:
- Screening was not done in prenatal period
- Or ongoing are present
- Anti-HBs < 10 mIU/mL: Administer a 3-dose hepatitis B vaccine series.
- HBV serology indicating infection: See “Management of hepatitis B in pregnancy.”
Management of HBV infection in pregnancy 
- For patients with newly positive HBsAg on prenatal screening, obtain additional , including:
- Refer to infectious disease and/or hepatology specialists.
- Report case to state and local perinatal hepatitis B prevention programs (see “Tips and Links”). 
- Monitor HBV DNA and ALT every 3 months.
- Evaluate the need for antiviral therapy with tenofovir disoproxil fumarate (preferred drug) ; 
- Breastfeeding may be started immediately if there are no contraindications (e.g., cracked or bleeding nipples), regardless of whether individuals:
- Continue close monitoring (e.g., of HBV DNA and ALT levels) for at least 6 months postpartum. 
Hepatitis B in infants 
Management of infants born to individuals with HBsAg positive or unknown status
- Administer the birth dose of HBV vaccine to all infants within 12 hours of life.
- If the birthing parent's HBsAg status is unknown, obtain test immediately.
- Determine the need for HBIG.
- Report case to state and local perinatal hepatitis B prevention programs (see “Tips and Links”).
|Management of infants born to HBsAg-positive and HBsAg-unknown individuals |
|Status of birthing parent at delivery||HBIG ||HBV vaccine|
|HBsAg-positive or other evidence of HBV infection|| |
|HBsAg-unknown||< 2000 g birth weight|
|≥ 2000 g birth weight|