Hepatitis B virus (HBV) is the most thoroughly characterized and complex hepatitis virus. The infective particle consists of a viral core plus an outer surface coat. The core contains circular double-stranded DNA and DNA polymerase, and it replicates within the nuclei of infected hepatocytes. A surface coat is added in the cytoplasm and, for unknown reasons, is produced in great excess.
HBV is the 2nd most common cause of acute viral hepatitis after hepatitis A. Prior unrecognized infection is common but is much less widespread than that with hepatitis A virus. In the US, 3218 cases of acute hepatitis B infection were reported in 2016—a decrease from the 25,000 annual cases reported before use of hepatitis B vaccine became widespread. However, because many cases are not recognized or not reported, the Centers for Disease Control and Prevention (CDC) estimates that the actual number of new infections was about 20,900 in 2016 (1).
HBV, for unknown reasons, is sometimes associated with several primarily extrahepatic disorders, including polyarteritis nodosa, other connective tissue diseases, membranous glomerulonephritis, and essential mixed cryoglobulinemia. The pathogenic role of HBV in these disorders is unclear, but autoimmune mechanisms are suggested.
HBV is often transmitted parenterally, typically by contaminated blood or blood products. Routine screening of donor blood for hepatitis B surface antigen (HBsAg) has nearly eliminated the previously common posttransfusion transmission, but transmission through needles shared by drug users remains common. Risk of HBV is increased for patients in renal dialysis and oncology units and for hospital personnel in contact with blood.
Infants born to infected mothers have a 70 to 90% risk of acquiring hepatitis B during delivery (see Neonatal Hepatitis B Virus Infection) unless they are treated with hepatitis B immune globulin (HBIG) and are vaccinated immediately after delivery. Earlier transplacental transmission can occur but is rare.
The virus may be spread through mucosal contact with other body fluids (eg, between sex partners, both heterosexual and homosexual; in closed institutions, such as mental health institutions and prisons), but infectivity is far lower than that of hepatitis A virus, and the means of transmission is often unknown.
The role of insect bites in transmission is unclear. Many cases of acute hepatitis B occur sporadically without a known source.
Chronic HBV carriers provide a worldwide reservoir of infection. Prevalence varies widely according to several factors, including geography (eg, < 0.5% in North America and northern Europe, > 10% in some regions of the Far East and Africa).
Hepatitis B infection causes a wide spectrum of liver diseases, from a subclinical carrier state to severe hepatitis or acute liver failure (fulminant hepatitis), particularly in the elderly, in whom mortality can reach 10 to 15%.
Most patients have typical manifestations of viral hepatitis, including anorexia, malaise, fever, nausea, and vomiting, followed by jaundice. Symptoms persist from a few weeks up to 6 months.
Five to 10% of all patients with acute HBV infection develop chronic hepatitis B or become inactive carriers. The younger the age when acute infection occurs, the higher the risk of developing chronic infection:
In the initial diagnosis of acute hepatitis, viral hepatitis should be differentiated from other disorders causing jaundice (see figure Simplified diagnostic approach to possible acute viral hepatitis).
If acute viral hepatitis is suspected, the following tests are done to screen for hepatitis viruses A, B, and C:
If any of the hepatitis B tests are positive, further serologic testing may be necessary to differentiate acute from past or chronic infection (see table Hepatitis B Serology). If serology suggests hepatitis B, testing for hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) is usually done to help determine the prognosis and to guide antiviral therapy. If serologically confirmed HBV infection is severe, antibody to hepatitis D virus (anti-HDV) is measured.
Hepatitis B has at least 3 distinct antigen-antibody systems that can be tested:
HBsAg characteristically appears during the incubation period, usually 1 to 6 weeks before clinical or biochemical illness develops, and implies infectivity of the blood. It disappears during convalescence. However, HBsAg is occasionally transient. The corresponding protective antibody (anti-HBs) appears weeks or months later, after clinical recovery, and usually persists for life; thus, its detection indicates past HBV infection and relative immunity. In 5 to 10% of patients, HBsAg persists and antibodies do not develop; these patients become asymptomatic carriers of the virus or develop chronic hepatitis.
HBcAg reflects the viral core. It is detectable in infected liver cells but not in serum except by special techniques. Antibody to HBcAg (anti-HBc) usually appears at the onset of clinical illness; thereafter, titers gradually diminish, usually over years or life. Its presence with anti-HBs indicates recovery from previous HBV infection. Anti-HBc is also present in chronic HBsAg carriers, who do not mount an anti-HBs response. In acute infection, anti-HBc is mainly of the IgM class, whereas in chronic infection, IgG anti-HBc predominates. IgM anti-HBc is a sensitive marker of acute HBV infection and occasionally is the only marker of recent infection, reflecting a window between disappearance of HBsAg and appearance of anti-HBs.
HBeAg is a protein derived from the viral core (not to be confused with hepatitis E virus). Present only in HBsAg-positive serum, HBeAg tends to suggest more active viral replication and greater infectivity. In contrast, presence of the corresponding antibody (anti-HBe) suggests lower infectivity. Thus, e antigen markers are more helpful in prognosis than in diagnosis. Chronic liver disease develops more often among patients with HBeAg and less often among patients with anti-HBe.
HBV-DNA can be detected in the serum of patients with active HBV infection.
Hepatitis B Serology*
Liver tests are needed if not previously done; they include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin.
Other tests should be done to evaluate liver function; they include serum albumin, platelet count, and prothrombin time/international normalized ratio (PT/INR).
No treatments attenuate acute viral hepatitis, including hepatitis B. Alcohol should be avoided because it can increase liver damage. Restrictions on diet or activity, including commonly prescribed bed rest, have no scientific basis.
If fulminant hepatitis occurs, treatment with oral nucleoside or nucleotide analogs can increase the likelihood of survival. However, emergency liver transplantation provides the best hope for survival. Survival in adults is uncommon without transplantation; children tend to do better.
For cholestatic hepatitis, cholestyramine 8 g orally once or twice a day can relieve itching.
Viral hepatitis should be reported to the local or state health department.
Patients should be advised to avoid high-risk behavior (eg, sharing needles to inject drugs, having multiple sex partners).
Blood and other body fluids (eg, saliva, semen) are considered infectious. Spills should be cleaned up using dilute bleach. Barrier protection is recommended, but isolation of patients is of no value.
Posttransfusion infection is minimized by avoiding unnecessary transfusions and screening all donors for hepatitis B and C. Screening has decreased the incidence of posttransfusion hepatitis B and hepatitis C, which are now extremely rare in the US.
Hepatitis B vaccination in endemic areas has dramatically reduced local prevalence.
Preexposure immunization has long been recommended for people at high risk. However, selective vaccination of high-risk groups in the US and other nonendemic areas has not substantially decreased the incidence of HBV infection; thus, vaccination is now recommended for all US residents ≤ 18 years old beginning at birth (see table Recommended Immunization Schedule for Ages 0–6 years). Universal worldwide vaccination is desirable but is too expensive to be feasible.
Adults at high risk of HBV infection should be screened and vaccinated if they are not already immune or infected (see Adult Immunization Schedule). These high-risk groups include
Men who have sex with men
People with a sexually transmitted disease
People who have had > 1 sex partner during the previous 6 months
Health care and public safety workers potentially exposed to blood or other infectious body fluids
People who have diabetes and are < 60 years old (or ≥ 60 years if their risk of acquiring HBV is considered increased)
People with end-stage renal disease, HIV, or chronic liver disease
Household contacts and sex partners of people who are HBsAg-positive
Clients and staff members of institutions and nonresidential day care facilities for people with developmental disabilities
People in correctional facilities or facilities providing drug abuse treatment and prevention services
International travelers to regions with high or intermediate HBV endemicity
Two recombinant vaccines are available; both are safe, even during pregnancy. Three IM deltoid injections are given: at baseline, at 1 month, and at 6 months. Children are given lower doses, and immunosuppressed patients and patients receiving hemodialysis are given higher doses. Also, a formulation that combines hepatitis A and hepatitis B vaccines (Twinrix®) is available. A newer recombinant vaccine, HepB-CpG (Heplisav-B®), uses the immune-stimulating adjuvant, cytidine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) and requires only 2 doses, but there are insufficient data to recommend use during pregnancy.
After vaccination, levels of anti-HBs remain protective for 5 years in 80 to 90% of immunocompetent recipients and for 10 years in 60 to 80%. Booster doses of vaccine are recommended for patients receiving hemodialysis and immunosuppressed patients whose anti-HBs is < 10 mIU/mL.
Hepatitis B postexposure immunoprophylaxis combines vaccination with hepatitis B immune globulin (HBIG), a product with high titers of anti-HBs. Efficacy of postexposure HBIG is about 75%.
For infants born to HBsAg-positive mothers, an initial dose of vaccine plus 0.5 mL of HBIG is given IM in the thigh immediately after birth.
For anyone having sexual contact with an HBsAg-positive person or percutaneous or mucous membrane exposure to HBsAg-positive blood, 0.06 mL/kg of HBIG is given IM within days, along with vaccine.
Any previously vaccinated patient sustaining a percutaneous HBsAg-positive exposure is tested for anti-HBs; if titers are < 10 mIU/mL, a booster dose of vaccine is given.
Hepatitis B is often transmitted by parenteral contact with contaminated blood but can result from mucosal contact with other body fluids.
Infants born to mothers with hepatitis B have a 70 to 90% risk of acquiring infection during delivery unless the infants are treated with hepatitis B immune globulin (HBIG) and are vaccinated after delivery.
Chronic infection develops in 5 to 10% of patients with acute hepatitis B and often leads to cirrhosis and/or hepatocellular carcinoma.
Diagnose by testing for hepatitis B surface antigen and other serologic markers.
Routine vaccination beginning at birth is recommended for all.
Postexposure prophylaxis consists of HBIG and vaccine; HBIG probably does not prevent infection but may prevent or attenuate clinical hepatitis.