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Hepatitis B

Hepatitis B

  • Hepatitis B is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
  • Transmission of hepatitis B in the United States occurs predominantly through contact with infected blood products or body secretions (saliva, vaginal fluids, and semen) or sharing of needles by intravenous drug abusers.
  • The incubation period for hepatitis B is 1 to 6 months. This is followed by a symptomatic prodromal phase consisting of malaise, fatigue, weakness, anorexia, myalgias, and arthralgias. Jaundice occurs in about one-third of patients and may persist for several weeks.
  • The sequence of serologic markers for hepatitis B are given in Table Interpretation of the Laboratory Profile in Hepatitis B Virus (hepatitis B) Infection.
  • Clinical manifestations of acute hepatitis B infection are age dependent. Infants infected with hepatitis B are generally asymptomatic, while about 85% to 95% of children aged 1 -to 5 years are asymptomatic.
TABLE. Recommended Dosing of Havrix and Vaqta
Vaccine Vaccinee’s Age (years) Dose Volume (mL) Number Doses Schedule (months)b
Havrix 2 to 18 720 ELISA unitsa 0.5 2 0, 6– 12
>18 1440 ELISA units 1 2 0, 6– 12
Vaqta 2 to 17 25 units 0.5 2 0, 6– 18
>17 50 units 1 2 0, 6
aHavrix previously was also available as 360 ELISA units per dose. This formulation was administered as a three-dose schedule for persons 2 to 18 years of age. It is no longer available.
b0 months represents the timing of the initial dose; subsequent numbers represent months after the initial dose.
From Centers for Disease Control.2
TABLE. Interpretation of the Laboratory Profile in Hepatitis B Virus (hepatitis B) Infection
Pattern Is Patient Infectious? HBsAg HBeAg Anti-HBc Total Anti-HBs Anti-HBe
Not infected/early incubation No
Early acute hepatitis B infection Yes +
Acute hepatitis B infection Yes + + +
Chronic hepatitis B infectionsa Yes + +/- +
Resolved infection No + +
«Window» period following acute hepatitis B infection No + +
 
TABLE. Clinical Presentation of Chronic Hepatitis Ba
Signs and symptoms

  • Easy fatigability, anxiety, anorexia, and malaise
  • Ascites, jaundice, variceal bleeding, and hepatic encephalopathy can manifest with liver decompensation
  • Hepatic encephalopathy is associated with hyperexcitability, impaired mentation, confusion, obtundation, and eventually coma
  • Vomiting and seizures

Physical examination

  • Icteric sclera, skin, and secretions
  • Decreased bowel sounds, increased abdominal girth, and detectable fluid wave
  • Asterixis
  • Spider angiomata

Laboratory tests

  • Presence of hepatitis B surface antigen for at least 6 months
  • Intermittent elevations of hepatic transaminase (alanine transaminase  and aspartate transaminase) and hepatitis B virus DNA greater than 105 copies/mL
  • Liver biopsies for pathologic classification as chronic persistent hepatitis, chronic active hepatitis, or cirrhosis
aChronic hepatitis B can be present even without all the signs, symptoms, and physical examination findings listed being apparent.

Acute symptomatic infections vary in severity and include fever, anorexia, nausea, vomiting, jaundice, dark urine, clay-colored or pale stools, and abdominal pain.

  • Approximately 90% of infants but 10% of adolescents or adults develop chronic hepatitis B. Chronic hepatitis B predisposes patients to chronic liver disease, cirrhosis, and hepatocellular carcinoma.

Treatment

  • The key goal of therapy is to eradicate or permanently suppress hepatitis B. The short-term goal is to limit hepatic inflammation and to reduce the risk of fibrosis and/or decompensation. The long-term goal is to prevent transaminase flares and the development of complications, and to prolong survival.
  • No specific therapy is available for the management of acute hepatitis B infection.
  • Interferon alpha2b (IFN-alpha2B), lamivudine, and adefovir dipivoxil are approved in the US for treatment of hepatitis B.
  • Drug therapy is not recommended for patients with normal alanine transaminase values.
  • Patients with persistent alanine transaminase levels greater than twice the upper limit of normal should be considered for treatment.
  • Patients with alanine transaminase levels greater than 5 times the upper limit of normal are experiencing an exacerbation and should receive lamivudine.
  • Patients considered for treatment are those who are HBsAg-positive for greater than 6 months with persistent elevations in serum aminotransferases, detectable markers of viral replication (HBeAg and hepatitis B DNA) in serum and signs of chronic hepatitis on liver biopsy. Patients should not have decompensated liver disease.
  • In patients with chronic hepatitis B who are HBeAg-positive and have intermittent or persistent elevation of alanine transaminase, either interferon or lamivudine may be used as first-line therapy.
  • Patients with HBeAg-positive chronic hepatitis B
    • alanine transaminase greater than 2 times the upper limit of normal or moderate/severe hepatitis on biopsy: Treatment may be initiated with either lamivudine or interferon-О±
    • alanine transaminase less than 2 times upper limit of normal: Treatment with lamivudine or interferon-О± should be limited to patients with significant necroinflammation on liver biopsy. Patients should have their alanine transaminase assessed every 3 to 6 months.
  • Patients with HBeAg-negative chronic hepatitis B: Only patients with alanine transaminase greater than 2 times upper limit of normal, hepatitis B DNA greater than 105 copies/mL, or moderate/severe hepatitis on biopsy should be considered for treatment with lamivudine or interferon-О±.
  • Patients who fail to respond to a course of interferon-О± and have alanine transaminase greater than 2 times upper limit of normal, hepatitis B DNA greater than 105 copies/mL, or moderate/severe hepatitis on biopsy may be treated with a course of lamivudine.
  • Patients with decompensated cirrhosis: Interferon-О± should not be used and lamivudine may be considered in these patients.
  • Patients in an inactive HBsAg carrier state: No treatment is indicated.

Prevention

  • Two products are available for prevention of hepatitis B infection: hepatitis B vaccine, which provides active immunity, and hepatitis B immune globulin, which provides temporary passive immunity.
TABLE. Recommended Schedule of Immunoprophylaxis to Prevent Perinatal or Sexual Transmission of hepatitis B Infection
Vaccine Recipient Immunoprophylaxis Timing
Infant born to
HBsAg-positive mother
Vaccine dose 1
HBlg (0.5 mL intramuscularly at a site different from that used for the vaccine)
Within 12 h of birth
Within 12 h of birth
Vaccine doses 2 and 3 Usual schedule
Infant born to mother not screened for HBsAg Vaccine dose 1a
HBlg (0.5 mL intramuscularly at a site different from that used for the vaccine)
Within 12 h of birth
If mother is found to be
HBsAg-positive, administer dose to infant as soon as possible, but no later than 1 wk after birth
Vaccine doses 2 and 3a Usual schedule
Sexual exposure HBlg (0.06 mL/kg intramuscularly at a site different from that used for the vaccine) Single dose within 14 days of sexual contact
Vaccine dose 1 At time of HBlg treatment
Vaccine doses 2 and 3 Usual schedule
aThe first dose of vaccine is the same as that for the infant of an HBsAg-positive mother. If the mother is found to be HBsAg-positive, that dose is continued. If the mother is found to be HBsAg-negative, the remaining vaccine doses are those appropriate for other infants and children.
HBlg, hepatitis B immunoglobulin; HBsAg: hepatitis B surface antigen. From Centers for Disease Control and Prevention. Protection against viral hepatitis: Recommendations of the Immunization Practices Advisory Committee (ACIP). Morb Mortal Wkly Rep 1990;39:1– 26; Centers for Disease Control and Prevention.
TABLE. Recommendations for Hepatitis B Prophylaxis Following Percutaneous or Permucosal Exposure
  Treatment According to HBsAg Status of Source
Vaccination Status of Exposed Person HBsAg-Positive HBsAg-Negative Source Not Tested or Unknown
Unvaccinated HBlg (one dose of 0.06 mL/kg intramuscularly), plus initiate vaccinea Initiative vaccinea Initiate vaccinea
Previously vaccinated, known responder Test exposed person for anti-HBs level
If adequate,b no treatment
If inadequate or titer unknown, I vaccine booster dose
No treatment No treatment
Previously vaccinated, known nonresponder HBlg (two doses 1 month apart) or HBlg one dose, plus dose of vaccine No treatment If known high-risk source, may treat as if source were HBsAg-positive
Previously vaccinated, response unknown Test exposed person for anti-HBs level
If inadequate,b HBlg one dose, plus one vaccine booster dose
If adequate, no treatment
If titer unknown, one vaccine booster dose
No treatment Test exposed for anti-HBs level
If inadequate,b vaccine booster dose
If adequate, no treatment
aVaccine dosage is given in Table 40-8.
bAdequate anti-HBs is ≥10 milli-international units per milliliter by radioimmunoassay or enzyme immunoassay.
anti-HBs, antibody to HBsAg; HBlg, hepatitis B immunoglobulin; HBsAg, hepatitis B surface antigen.
  • The goals of immunization against viral hepatitis include prevention of the short-term viremia that can lead to transmission of infection, clinical disease, and chronic hepatitis B infection.
TABLE. Groups Recommended for Preexposure Hepatitis B Vaccination
All infants via routine infant vaccination
Unvaccinated 11- to 12-year-old children
Unvaccinated children ages <11 years of age who are Pacific Islanders of who reside in households of first-generation immigrants from countries where hepatitis B is of high or intermediate endemicity
Health care and public safety workers who have occupational exposure to blood
HIV-infected individuals
Injection drug users
Heterosexual individuals who have had more than one sexual partner in the previous 6 months and/or those with a recent episode of a sexually transmitted disease
Sexually active homosexual or bisexual males
Hemodialysis patients
Recipients of certain blood products (i.e., patients with hemophilia and other clotting disorders)
Clients and staff of institutions for the developmentally disabled
Household, sexual, and blood exposure contacts of either HBsAg-positive persons or those with acute hepatitis B infection
Household contacts of adoptees from countries where hepatitis B is highly endemic
Populations where hepatitis B is highly endemic (e.g., Alaskan Eskimos)
Inmates of long-term correctional facilities
International travelers to highly endemic hepatitis B regions for >6 months and who have close contact with the local population; also short-term travelers who have contact with blood, or sexual contact with residents in high- or intermediate-risk areas
Unvaccinated infants under 12 months of age exposed to acute hepatitis B infection through primary caregiver
HBsAg, hepatitis B surface antigen; hepatitis B, hepatitis B virus; HIV, human immunodeficiency virus.
From Centers for Disease Control and Prevention. Protection against viral hepatitis: Recommendations of the Immunization Practices Advisory Committee (ACIP). Morb Mortal Wkly Rep 1990;39:1– 26 and Centers for Disease Control and Prevention. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Morb Mortal Wkly Rep 1999;48(RR-10):1– 66.
TABLE. Recommended Doses and Schedules of Currently Licensed Hepatitis B Vaccines
  Vaccine
Group Recombivax HBa dose, mcg (mL) Engerix-Ba,bdose, mcg (mL) Comvaxc dose, mcg (mL)
Infants of HBsAg-positive mothers 5 (0.5) 10 (0.5) Not indicated
All other infants, children and adolescents ≤19 years of age 5 (0.5)d 10 (0.5) 5 (0.5)e
Adults age 20 years and older 10 (1) 20 (1) Not indicated
Dialysis patients and other immunocompromised persons 40 (1)f 40 (2)g,h Not indicated
aUsual schedules: Infants: Three doses given at birth, at 1 to 2 months, and at 6 to 18 months of age; or, for infants, with other routine immunizations at 1 to 2 months, 4 months, and 6 to 18 months of age. Older children and adults: Three doses given at 0-, 2-, and 6-month or, at 0-, 2-, and 4-month intervals. Higher titers of HBsAg are achieved with the last two doses of vaccine being spaced at least 4 months apart.
bAlternative approved schedule: Four doses, one given at 0, then one each given at 1-, 2-, and 12-month intervals.
HBsAg, hepatitis B surface antigen.
cContains 5 mcg 0.5 mL HBsAg and 7.5 mcg Haemophilus influenzae type B purified capsular polysaccharide fragments conjugated to 125 mcg Neisseria meningitidis outer membrane protein complex. dAn alternate two-dose schedule can be used for adolescents aged 11 to 15 years. If the two-dose schedule is used, the adult dose (1 mL containing 10 mcg of HBsAg) is administered with the second dose given 4 to 6 months after the first dose. eUsually given at 2, 4 and 12 to 15 months of age. Comvax is not used when immunizing older children or adolescents. fSpecial formulation for dialysis patients. gTwo 1-mL doses given at different sites. hFour-dose schedule recommended at 0 then at 1-, 2-, 6-month intervals.
TABLE. Side Effects of Interferon-О±
Early (in First 2 Weeks of Therapy) Hematologic Neuropsychiatric Autoimmune Miscellaneous
Fever Neutropenia Irritability Development of autoantibodies Chronic fatigue
Chills Thrombocytopenia Mood lability Infections
Myalgias Anemia Depression Hepatitis Increased sleep requirement
Fatigue   Tearfulness Thyroid dysfunction
Malaise Delirium Thyroiditis Anorexia
Nausea Paresthesias Arthropathy Weight loss
Sleep disturbance Seizures Type I diabetes mellitus Myalgias
Abdominal pain Psychosis Exacerbation of psoriasis or lichen planus Low-grade fevers
Diarrhea Exacerbation of other autoimmune phenomena Decreased libido
Headache Alopecia
Appetite changes Hypertriglyceridemia
Irritability
Anxiety
Depression
Attention span deficits
Absolute contraindications to use of interferon include current or past psychosis or severe depression, neutropenia or thrombocytopenia, organ transplant (except liver), symptomatic heart disease, decompensated cirrhosis, and uncontrolled seizures. Relative contraindications to interferon include uncontrolled diabetes and autoimmune disorders.

Hepatitis B Immune Globulin

  • HBIg is used only for postexposure prophylaxis for hepatitis B for perinatal exposure of infants of hepatitis B-carrier mothers, sexual exposure to HBsAg-positive persons, percutaneous or permucosal exposure to HBsAg-positive blood, and exposure of an infant to a caregiver who has acute hepatitis B.
  • The recommended dose is 0.06 mL/kg administered intramuscularly.

Hepatitis B Vaccine

  • The most effective measure for prevention of hepatitis B is universal precaution.
  • Side effects of the vaccines are soreness at the injection site, headache, fatigue, irritability, and fever.

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