Definition and epidemiology
Hepatitis B is inflammation of the liver caused by the hepatitis B virus, a partially double-stranded DNA virus of the Hepadnaviridae family. Infection can be acute (self-limited in most adults) or chronic (persistent HBsAg for more than 6 months).
- Estimated 250-300 million people live with chronic HBV infection worldwide
- Highest prevalence in sub-Saharan Africa and East/Southeast Asia
- Universal infant vaccination has sharply reduced incidence in many countries since the 1990s
- Leading cause of hepatocellular carcinoma (HCC) globally
- Risk of chronicity is highest with perinatal/early childhood infection, lowest with adult infection
- IgM anti-HBc marks acute infection; IgG anti-HBc marks past or chronic infection
- HBsAg present for more than 6 months defines chronic hepatitis B
- Isolated anti-HBs positivity (no anti-HBc) indicates vaccination, not natural infection
- Tenofovir and entecavir are first-line oral antivirals for chronic hepatitis B
- HBV is a major cause of hepatocellular carcinoma even without cirrhosis
- Pregnant women with high viral load should receive tenofovir in the third trimester to prevent transmission
- Reactivation can occur during chemotherapy or immunosuppression even in inactive carriers
Etiology and risk factors
HBV is transmitted through percutaneous or mucosal exposure to infected blood or body fluids.
Routes of transmission
- Perinatal (mother to child) — most common route in endemic regions
- Sexual contact (unprotected intercourse)
- Parenteral (shared needles, unscreened blood products, needlestick injury)
- Household/horizontal spread in childhood (close contact in endemic areas)
Risk factors
- Birth to an HBsAg-positive mother without immunoprophylaxis
- Injection drug use
- Multiple sexual partners, men who have sex with men
- Healthcare workers with needlestick exposure
- Hemodialysis patients
- Unvaccinated travelers to endemic regions
Pathophysiology
HBV is not directly cytopathic; liver injury results mainly from the host's cytotoxic T-cell response against infected hepatocytes expressing viral antigens. The outcome depends heavily on the host immune response at the time of exposure.
- Neonates and young children have immature immune responses, leading to immune tolerance and high rates of chronicity
- Adults mount a vigorous cytotoxic response, which clears the virus in most cases but causes the acute hepatitis symptoms
- Chronic infection progresses through immune-tolerant, immune-active (clearance), inactive carrier, and reactivation phases
- Ongoing immune-mediated inflammation drives fibrosis, cirrhosis, and increases HCC risk, partly through direct viral DNA integration into the host genome
Clinical features
Many infections, especially in children, are asymptomatic.
Acute hepatitis B
- Prodrome of fatigue, nausea, anorexia, low-grade fever, right upper quadrant discomfort
- Jaundice, dark urine, pale stools in symptomatic cases
- Rarely, serum sickness-like syndrome (arthralgia, urticarial rash) in the prodrome
- Fulminant hepatic failure occurs in less than 1% of acute cases
Chronic hepatitis B
- Often asymptomatic for years, detected incidentally on screening
- Nonspecific fatigue; symptoms of cirrhosis once advanced fibrosis develops
- Extrahepatic manifestations: polyarteritis nodosa, membranous nephropathy
Diagnosis
Diagnosis relies on serologic markers plus HBV DNA quantification and liver tests.
| Marker | Meaning |
|---|---|
| HBsAg | Current infection (acute or chronic) |
| Anti-HBs | Immunity (vaccination or resolved infection) |
| IgM anti-HBc | Acute/recent infection |
| IgG anti-HBc | Past or chronic infection |
| HBeAg | Active viral replication, high infectivity |
| Anti-HBe | Seroconversion, often lower replication |
| HBV DNA | Viral load, guides treatment decisions |
Workup
- Liver function tests (ALT/AST, bilirubin, albumin, INR)
- HBV DNA level and HBeAg status to assess replication phase
- Screen for coinfection with hepatitis D, C, and HIV in at-risk patients
- Non-invasive fibrosis assessment (elastography) or liver biopsy to stage disease
- Alpha-fetoprotein and liver ultrasound for HCC surveillance in chronic carriers
Differential diagnosis
- Hepatitis A, C, D, and E — distinguished by serology and exposure history
- Autoimmune hepatitis — autoantibodies, hypergammaglobulinemia
- Drug-induced liver injury — temporal relation to a hepatotoxic agent
- Alcoholic hepatitis — history of heavy alcohol use, AST:ALT ratio often greater than 2
- Wilson disease or hemochromatosis in younger patients with unexplained liver disease
- Hepatitis D superinfection in a known HBsAg carrier with sudden worsening
Management
Acute hepatitis B is managed supportively in most patients; antivirals are reserved for severe or fulminant cases. Chronic hepatitis B management depends on viral load, ALT, HBeAg status, and fibrosis stage.
Indications to treat chronic HBV (general consensus, criteria vary slightly by society)
- Elevated ALT with high HBV DNA (immune-active phase)
- Compensated or decompensated cirrhosis with detectable HBV DNA, regardless of ALT
- Reactivation during immunosuppression or chemotherapy (prophylactic treatment)
- Pregnant women with high viral loads to prevent perinatal transmission (commonly tenofovir in the third trimester)
First-line agents
- Tenofovir disoproxil fumarate or tenofovir alafenamide — preferred nucleos(t)ide analogs, high potency, low resistance
- Entecavir — alternative first-line agent, especially if renal or bone concerns favor it over tenofovir
- Pegylated interferon alfa — finite-duration option in selected patients, particularly younger patients wanting a defined treatment course
Prevention
- Universal infant vaccination (birth dose plus completion series)
- Hepatitis B immune globulin plus vaccine for neonates of HBsAg-positive mothers
- Postexposure prophylaxis after needlestick or sexual exposure in unvaccinated individuals
- Screening of blood products and safe injection practices
Treatment is typically long-term or lifelong for most chronic patients since cure (HBsAg loss) is uncommon with current therapy; nucleos(t)ide analogs suppress replication rather than eradicate the virus.
Complications and prognosis
- Progression to cirrhosis occurs in a significant minority of untreated chronic carriers over decades
- Hepatocellular carcinoma risk is markedly increased, even without cirrhosis, due to viral DNA integration
- Decompensated cirrhosis: ascites, variceal bleeding, hepatic encephalopathy
- Hepatitis D superinfection accelerates liver damage
- Reactivation can occur with immunosuppression, sometimes causing severe flares
- Acute infection in adults resolves in roughly 95% of cases; chronic infection is rarely cured but is well controlled with antivirals, and long-term suppression reduces cirrhosis and HCC risk
Remember HBV serology by matching each marker to its letter: HBsAg = Surface antigen, meaning current infection is present. HBeAg = rEplication, meaning the virus is actively replicating and highly infectious. IgM anti-HBc = Core antibody of a reCent infection, meaning exposure was within the last few months. Together: Surface = infected, E = replicating, IgM Core = recent.
Practice questions
1. A 32-year-old man undergoes a routine health screening. Serology shows: HBsAg negative, anti-HBs positive, anti-HBc negative, IgM anti-HBc negative. He reports completing the hepatitis B vaccine series five years ago and denies any prior liver disease. What does this pattern indicate?
2. A 28-year-old woman who is 32 weeks pregnant is found to be HBsAg positive with an HBV DNA level of 1,200,000 IU/mL and HBeAg positive. She has normal liver enzymes and no evidence of cirrhosis. Which intervention most effectively reduces the risk of perinatal HBV transmission to her infant?
3. A 45-year-old man with known chronic hepatitis B on no treatment presents for follow-up. Labs show HBsAg positive, HBeAg negative, anti-HBe positive, ALT normal, and HBV DNA undetectable. Liver ultrasound and elastography are normal. Which phase of chronic HBV infection does this represent?
Frequently asked questions
What causes hepatitis B?
Hepatitis B is caused by the hepatitis B virus (HBV), a DNA virus spread through contact with infected blood or body fluids. Common routes include perinatal transmission from mother to child, unprotected sexual contact, and exposure to contaminated needles or blood products. Household and childhood close-contact transmission also occurs in endemic regions. The outcome, whether the infection clears or becomes chronic, depends heavily on the age and immune status at the time of exposure.
What are the first symptoms of hepatitis B?
The earliest symptoms are often nonspecific: fatigue, nausea, loss of appetite, low-grade fever, and mild right upper quadrant discomfort. Jaundice, dark urine, and pale stools typically follow a few days to weeks later in symptomatic acute cases. Many infections, particularly in children, cause no symptoms at all. A minority of patients develop a serum sickness-like prodrome with joint pain and rash before jaundice appears.
How is hepatitis B diagnosed?
Hepatitis B is diagnosed with blood tests for viral serologic markers, primarily HBsAg, anti-HBc (IgM and IgG), anti-HBs, and HBeAg/anti-HBe, combined with HBV DNA quantification. Liver function tests assess the degree of liver injury. HBsAg positive for over 6 months confirms chronic infection, while IgM anti-HBc indicates a recent acute infection. Fibrosis staging with elastography or biopsy helps guide treatment decisions in chronic cases.
Is hepatitis B curable?
Acute hepatitis B resolves on its own in about 95% of immunocompetent adults, with lasting immunity afterward. Chronic hepatitis B, however, is rarely cured with current therapy; antivirals like tenofovir and entecavir suppress viral replication and reduce complications but usually require long-term or lifelong use rather than achieving a complete cure. Loss of HBsAg, considered the closest thing to a functional cure, is uncommon but does occur in some patients, especially after years of effective suppression.
Hepatitis B vs hepatitis C — what is the difference?
Hepatitis B is caused by a DNA virus and is preventable by vaccination, while hepatitis C is caused by an RNA virus with no vaccine currently available. Hepatitis B more often causes chronic infection when acquired perinatally or in early childhood, whereas hepatitis C frequently becomes chronic regardless of age at infection. Hepatitis C is now curable with short courses of direct-acting antivirals, while hepatitis B treatment is typically long-term viral suppression rather than cure.
Key drugs
Related conditions and differentials
Sources and further reading
StatPearls (NCBI Bookshelf)MedlinePlusWHO ICD-10: B16
Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.