Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 16-03: Acute Hepatitis B + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Prodrome of anorexia, nausea, vomiting, malaise, aversion to smoking Fever, tender hepatomegaly, jaundice Markedly elevated serum aminotransferases early in the course Normal to low white blood cell count Liver biopsy shows hepatocellular necrosis and mononuclear infiltrate but is rarely indicated +++ General Considerations ++ Hepatitis B virus (HBV) contains an inner core protein (hepatitis B core antigen, HBcAg) and outer surface coat (hepatitis B surface antigen, HBsAg) The incubation period is 6 weeks to 6 months (average 3 months) The onset of HBV is more insidious and the aminotransferase levels higher on average than in hepatitis A virus (HAV) infection 10 genotypes of HBV (A–J) have been identified +++ Demographics ++ Incidence has decreased from 8.5 to 1.5 cases per 100,000 population since the 1990s HBV is usually transmitted by Infected blood or blood products Sexual contact It is also present in saliva, semen, and vaginal secretions About 7% of HIV-infected persons are coinfected with HBV HBsAg-positive mothers may transmit HBV to the neonate at delivery The risk of chronic infection in the infant approaches 90% if the mother is HBeAg positive HBV is prevalent in men who have sex with men and injection drug users, but most cases result from heterosexual transmission Other groups at high risk include Patients and staff at hemodialysis centers Physicians, dentists, and nurses Personnel working in clinical and pathology laboratories and blood banks The risk of HBV infection from a blood transfusion in the United States is no higher than 1 in 350,000 units transfused Screening for HBV infection is recommended for high-risk groups by the US Preventive Services Task Force + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Onset may be abrupt or insidious Malaise, myalgia, arthralgia, fatigability, upper respiratory symptoms, anorexia, and a distaste for smoking Nausea and vomiting, diarrhea or constipation Low-grade fever is generally present; serum sickness may be seen Abdominal pain is usually mild and constant in the right upper quadrant or epigastrium Defervescence and a fall in pulse rate coincide with the onset of jaundice Jaundice occurs after 5–10 days but may appear at the same time as the initial symptoms; it never develops in many patients Often worsening of the prodromal symptoms, followed by progressive clinical improvement Stools may be acholic The acute illness usually subsides over 2–3 weeks In most patients, there is complete clinical and laboratory recovery by 16 weeks In 5–10% of cases, the course may be more protracted, but acute liver failure will develop in < 1% Hepatitis B may become chronic +++ Differential Diagnosis ++ Acute and chronic hepatitis ACDE The TT virus (TTV) is found in up to 7.5% of blood donors and is readily transmitted by blood transfusions, but an association with liver disease is not established The SEN-V virus is found in 2% of US blood donors, is transmitted by transfusion, and may account for transfusion-associated non-ABCDE hepatitis Cytomegalovirus, Epstein-Barr virus, yellow fever virus, influenza virus, Middle East respiratory syndrome virus, herpes simplex virus, and Ebola virus + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ See Table 16–5 ++Table Graphic Jump LocationTable 16–5.Common serologic patterns in hepatitis B virus (HBV) infection and their interpretation.View Table||Download (.pdf) Table 16–5. Common serologic patterns in hepatitis B virus (HBV) infection and their interpretation. HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe Interpretation + – IgM + – Acute hepatitis B + – IgG1 + – Chronic hepatitis B with active viral replication + – IgG – + Inactive HBV carrier state (low HBV DNA level) or HBeAg-negative chronic hepatitis B with active viral replication (high HBV DNA level) + + IgG + or – + or – Chronic hepatitis B with heterotypic anti-HBs (about 10% of cases) – – IgM + or – – Acute hepatitis B – + IgG – + or – Recovery from hepatitis B (immunity) – + – – – Vaccination (immunity) – – IgG – – False-positive; less commonly, infection in remote past 1Low levels of IgM anti-HBc may also be detected. +++ HBsAg ++ Appears before biochemical evidence of liver disease, and persists throughout the clinical illness After the acute illness, it may be associated with chronic hepatitis +++ Anti-HBs ++ Appears after clearance of HBsAg and after successful vaccination against hepatitis B Signals recovery from HBV infection, noninfectivity, and immunity +++ Anti-HBc ++ IgM anti-HBc appears shortly after HBsAg is detected. (HBcAg alone does not appear in serum) Its presence in acute hepatitis indicates a diagnosis of acute hepatitis B It fills the rare serologic gap when HBsAg has cleared but anti-HBs is not yet detectable Can persist for 3–6 months or more and reappear during flares of chronic hepatitis B IgG anti-HBc also appears during acute hepatitis B but persists indefinitely In asymptomatic blood donors, an isolated anti-HBc with no other positive HBV serologic results may represent a falsely positive result or a latent infection +++ HBeAg ++ Found only in HBsAg-positive serum and indicates viral replication and infectivity Persistence beyond 3 months indicates an increased likelihood of chronic hepatitis B Its disappearance is often followed by the appearance of anti-HBe, generally signifying diminished viral replication and decreased infectivity +++ HBV DNA ++ Generally parallels the presence of HBeAg, though HBV DNA is a more sensitive and precise marker of viral replication and infectivity Very low levels of HBV DNA are detectable only by PCR May persist in serum after recovery from acute hepatitis B However, HBV DNA is bound to IgG and is rarely infectious +++ Other laboratory tests ++ Normal to low white blood cell count and large atypical lymphocytes Mild proteinuria is common Bilirubinuria often precedes the appearance of jaundice Elevated serum aspartate or alanine aminotransferase occurs early, followed by elevations of serum bilirubin and alkaline phosphatase Marked prolongation of prothrombin time in severe hepatitis correlates with increased mortality + Treatment Download Section PDF Listen +++ +++ Medications ++ If nausea and vomiting are pronounced or oral intake is substantially decreased, give 10% glucose intravenously Small doses of oxazepam are safe, as metabolism is not hepatic; morphine sulfate should be avoided Antiviral therapy Generally unnecessary However, usually prescribed in cases of acute liver failure caused by HBV as well as in spontaneous reactivation of chronic hepatitis B presenting as acute-on-chronic liver failure Corticosteroids offer no benefit +++ Therapeutic Procedures ++ Bed rest only for severe symptoms Dietary management consists of palatable meals as tolerated, without overfeeding Strenuous physical exertion, alcohol, and hepatotoxic agents should be avoided + Outcome Download Section PDF Listen +++ +++ Complications ++ See Liver Failure, Acute See Hepatitis B, Chronic +++ Prognosis ++ Mortality rate is 0.1–1% but is higher with superimposed hepatitis D The risk of acute liver failure is < 1%, with a 60% mortality rate Following acute hepatitis B HBV infection persists in 1–2% of immunocompetent persons Risk is higher in immunocompromised persons Chronic hepatitis B, particularly when HBV infection is acquired early in life and viral replication persists Confers a substantial risk of cirrhosis and hepatocellular carcinoma (up to 25–40%) Men are at greater risk than women HBV may be associated with Glomerulonephritis Polyarteritis nodosa Universal vaccination of neonates in countries where HBV is endemic reduces the incidence of hepatocellular carcinoma +++ Prevention ++ Strict isolation of patients with HBV is not necessary Screening of donated blood for HBsAg and anti-HBc has reduced the risk of transfusion-associated hepatitis B markedly All pregnant women should be tested for HBsAg Immunoprophylaxis of the neonate reduces the risk of perinatal transmission of HBV infection When the mother's serum HBV DNA level is 200,000 international units/mL or higher (or the mother's serum HBsAg level is above 4–4.5 log10 international units/mL), antiviral treatment of the mother should also be initiated in the third trimester and is particularly important if the initial vaccine injection of the neonate may be delayed Counsel patients to use safer sex precautions Vaccinate against HAV (after prescreening for prior immunity) in those with chronic hepatitis B +++ Hepatitis B immune globulin (HBIG) ++ May be protective, or may at least attenuate the severity of illness, if given within 7 days after exposure (dose is 0.06 mL/kg body weight) followed by HBV vaccine Use this approach after exposure to HBsAg-contaminated material via mucous membranes or breaks in the skin, after sexual contact with an infected partner, and for infants born to HBsAg-positive mothers (in combination with the vaccine series) +++ Vaccination ++ The current vaccines are recombinant-derived CDC recommends universal vaccination of infants and children and all at-risk adults Over 90% of recipients mount protective antibody to hepatitis B Give 10–20 mcg (depending on the formulation), repeated again at 1 and 6 months, although alternative schedules are approved, including accelerated schedules of 0, 1, 2, and 12 months Check postimmunization anti-HBs titers if need to document seroconversion Protection appears to be excellent—at least for 20 years—even if the titer of anti-HBs wanes Booster reimmunization is not routinely recommended but is advised for immunocompromised persons in whom anti-HBs titers fall below 10 milli-international units/mL (see Table 30–7) Hepislav-B Uses a novel immune system-stimulating ingredient Requires only two injections Appears to be more effective than previous HBV vaccines For vaccine nonresponders, three additional vaccine doses may elicit seroprotective anti-HBs levels in 30–50% ++Table Graphic Jump LocationTable 30–7.Recommended adult immunization schedule—United States, 2020.View Table||Download (.pdf) Table 30–7. Recommended adult immunization schedule—United States, 2020. +++ When to Refer ++ Refer patients with acute hepatitis who require liver biopsy for diagnosis +++ When to Admit ++ Encephalopathy is present INR > 1.6 The patient is unable to maintain hydration + References Download Section PDF Listen +++ + +Abara WE et al. Hepatitis B vaccination, screening, and linkage to care: best practice advice from the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2017 Dec 5;167(11):794–804. [PubMed: 29159414] + +Anonymous. A two-dose hepatitis B vaccine for adults (Heplisav-B). Med Lett Drugs Ther. 2018 Jan 29;60(1539):17–8. [PubMed: 29364196] + +Hassanein TI. Hepatitis B virus update. Clin Liver Dis. 2019 Aug;23(3):383–572. [Full issue] + +Raimondo G et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol. 2019 Aug;71(2):397–408. [PubMed: 31004683] + +Schillie S et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018 Jan 12;67(1):1–31. [PubMed: 29939980] + +US Preventive Services Task Force; Owens DK et al. Screening for hepatitis B virus infection in pregnant women: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2019 Jul 23;322(4):349–54. [PubMed: 31334800] + +Yeo YH et al. Prevalence of undetectable vaccine-induced immunity against hepatitis B virus in US adults at high risk for infection. Hepatology. 2019 Apr;69(4):1385–97. [PubMed: 30246260]