Hepatitis B - Red Book 2018 PDF

HEPATITIS B 401 Hepatitis B...

HEPATITIS B 401 Hepatitis B CLINICAL MANIFESTATIONS: People acutely infected with hepatitis B virus (HBV) may be asymptomatic or symptomatic. The likelihood of developing symptoms of acute hepa- titis is age dependent: less than 1% of infants younger than 1 year, 5% to 15% of children 1 through 5 years of age, and 30% to 50% of people older than 5 years are symptomatic, although few data are available for adults older than 30 years. The spectrum of signs and symptoms is varied and includes subacute illness with nonspecific symptoms (eg, anorexia, nausea, or malaise), clinical hepatitis with jaundice, or fulminant hepatitis. Extrahepatic manifestations, such as arthralgia, arthritis, macular rashes, thrombocytopenia, polyarte- ritis nodosa, or glomerulonephritis, can occur early in the course of illness and may pre- cede jaundice. Papular acrodermatitis (Gianotti-Crosti syndrome) is an extrahepatic man- ifestation of infection attributable to a number of viral infections, including hepatitis B. However, since the advent of universal HBV immunization in infants, papular acroder- All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. matitis attributable to HBV is rare; it is more commonly caused by Epstein-Barr virus and less commonly by enteroviruses, cytomegalovirus, parvovirus B19, and others. Acute HBV infection cannot be distinguished from other forms of acute viral hepatitis on the basis of clinical signs and symptoms or nonspecific laboratory findings. Chronic HBV infection is defined as persistence in serum for at least 6 months of any one of the following: hepatitis B surface antigen (HBsAg), HBV DNA, or hepatitis B e an- tigen (HBeAg). Chronic HBV infection is likely in the presence of HBsAg, HBV DNA, or HBeAg in serum from a person who tests negative for antibody of the immunoglobulin (Ig) M subclass to hepatitis B core antigen (IgM anti-HBc). Age at the time of infection is the primary determinant of risk of progressing to chronic infection. Up to 90% of infants infected perinatally or in the first year of life will develop chronic HBV infection. Between 25% and 50% of children infected between 1 and 5 years of age become chronically infected, whereas 5% to 10% of infected older children and adults develop chronic HBV infection. Patients who become HBV infected while immunosuppressed or with an underlying chronic illness (eg, end-stage renal dis- ease) have an increased risk of developing chronic infection. In the absence of treatment, up to 25% of infants and children who acquire chronic HBV infection will die prema- turely from HBV-related hepatocellular carcinoma or cirrhosis. The clinical course of untreated chronic HBV infection varies according to the popu- lation studied, reflecting differences in age at acquisition, rate of loss of HBeAg, and possi- bly HBV genotype. Most children have asymptomatic infection. Perinatally infected chil- dren usually have normal or minimally elevated alanine transaminase (ALT) concentra- tions and minimal or mild liver histologic abnormalities, with detectable HBeAg and high HBV DNA concentrations (≥20 000 IU/mL) for years to decades after initial infection. Children with chronic HBV may exhibit growth impairment. Chronic HBV infection ac- Copyright 2018. American Academy of Pediatrics. quired during later childhood or adolescence usually is accompanied by more active liver disease and increased serum aminotransferase concentrations. Patients with detectable HBeAg (HBeAg-positive chronic hepatitis B) usually have high concentrations of HBV DNA and HBsAg in serum and are more likely to transmit infection. Because HBV-associated liver injury is thought to be immune mediated, in people coinfected with human immu- nodeficiency virus (HIV) and HBV, the return of immune competence with antiretroviral treatment of HIV infection may lead to a reactivation of HBV-related liver inflammation EBSCO Publishing : eBook Academic Collection (EBSCOhost) - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA AN: 1809323 ; Kimberlin, David W., Brady, Michael T., Jackson, Mary Anne, Long, Sarah S..; Red Book 2018 : Report of the Committee on Infectious Diseases Account: s4595122.main.emed  402 HEPATITIS B and damage. Over time (years to decades), HBeAg becomes undetectable in many chron- ically infected people. This transition often is accompanied by development of antibody to HBeAg (anti-HBe) and decreases in serum HBV DNA and serum aminotransferase concentrations and may be preceded by a temporary exacerbation of liver disease. These patients have inactive chronic infection but still may have exacerbations of hepatitis. Serologic reversion (reappearance of HBeAg) is more common if loss of HBeAg is not accompanied by development of anti-HBe; reversion with loss of anti-HBe also can occur. Some patients who lose HBeAg may continue to have ongoing histologic evidence of liver damage and moderate to high concentrations of HBV DNA (HBeAg-negative chronic hepatitis B). Patients with histologic evidence of chronic HBV infection, regardless of HBeAg status, remain at higher risk of death attributable to liver failure compared with HBV-infected people with no histologic evidence of liver inflammation and fibrosis. Resolved hepatitis B is defined as clearance of HBsAg, normalization of serum ami- notransferase concentrations, and development of antibody to HBsAg (anti-HBs). Chroni- cally infected adults clear HBsAg and develop anti-HBs at the rate of 1% to 2% annually; during childhood, the annual clearance rate is less than 1%. Reactivation of resolved chronic infection is possible if these patients become immunosuppressed and also is well reported among HBsAg-positive patients receiving anti-tumor necrosis factor agents or disease-modifying antirheumatic drugs (12% of patients). ETIOLOGY: HBV is a partially double-stranded DNA-containing 42-nm-diameter envel- oped virus in the family Hepadnaviridae. Important components of the viral particle include an outer lipoprotein envelope containing HBsAg and an inner nucleocapsid consisting of hepatitis B core antigen (HBcAg). EPIDEMIOLOGY: HBV is transmitted through infected blood or body fluids. Although HBsAg has been detected in multiple body fluids including human milk, saliva, and tears, the most potentially infectious include blood, serum, semen, vaginal secretions, and cere- brospinal, synovial, pleural, pericardial, peritoneal, and amniotic fluids. People with chronic HBV infection are the primary reservoirs for infection. Common modes of trans- mission include percutaneous and permucosal exposure to infectious body fluids; sharing or using nonsterilized needles, syringes, or glucose monitoring equipment or devices; sex- ual contact with an infected person; perinatal exposure to an infected mother; and house- hold exposure to a person with chronic HBV infection. The risk of HBV acquisition when a susceptible child bites a child who has chronic HBV infection is unknown. A theo- retical risk exists if HBsAg-positive blood enters the oral cavity of the biter, but transmis- sion by this route has not been reported. Transmission by transfusion of contaminated blood or blood products is rare in the United States because of routine screening of blood donors and viral inactivation of certain blood products before administration. Perinatal transmission of HBV is highly efficient and usually occurs from blood expo- sures during labor and delivery. In utero transmission accounts for less than 2% of all ver- tically transmitted HBV infections in most studies. Without postexposure prophylaxis, the risk of an infant acquiring HBV from an infected mother as a result of perinatal exposure is 70% to 90% for infants born to mothers who are HBsAg and HBeAg positive; the risk is 5% to 20% for infants born to HBsAg-positive but HBeAg-negative mothers. Person-to-person spread of HBV can occur in settings involving interpersonal contact over extended periods, such as in a household with a person with chronic HBV infection. In regions of the world with a high prevalence of chronic HBV infection, transmission EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HEPATITIS B 403 between children in household settings may account for a substantial amount of transmis- sion. The precise mechanisms of transmission from child-to-child are unknown; however, frequent interpersonal contact of nonintact skin or mucous membranes with blood-con- taining secretions, open skin lesions, or blood-containing saliva are potential means of transmission. Transmission from sharing inanimate objects, such as razors or tooth- brushes, also may occur. HBV can survive in the environment for 7 or more days but is inactivated by commonly used disinfectants, including household bleach diluted 1:10 with water. HBV is not transmitted by the fecal-oral route. Transmission among children born in the United States is unusual because of high coverage with hepatitis B (HepB) vaccine administered at birth. Screening mothers during pregnancy for HBV infection allows for additional immunoprophylaxis with Hepatitis B Immune Globulin (HBIG), which, when administered with the hepatitis B vaccine in the immediate newborn period, enhances prevention of mother-to-infant HBV transmission. The risk of HBV transmission is higher in children who have not completed a vaccine se- ries, children undergoing hemodialysis, institutionalized children with developmental dis- abilities, and children emigrating from regions and countries with endemic HBV (eg, Southeast Asia, China, Africa). Person-to-person transmission has been reported in child care settings, but risk of transmission in child care facilities in the United States has be- come negligible as a result of high infant hepatitis B immunization rates. Acute HBV infection is reported most commonly among adults 30 through 49 years of age in the United States. Since 1990, the incidence of acute HBV infection has decreased in all age categories, with a 98% decline in children younger than 19 years and a 93% decline in young adults 20 through 29 years of age, with most of the de- crease among people 20 through 24 years of age. Current statistics on hepatitis B case numbers and incidence rates can be found at www.cdc.gov/hepatitis/statistics/ 2015surveillance/index.htm. People at high risk for acute hepatitis B virus infection include people who inject drugs, people with multiple sexual partners, men who have sex with men, and those who reported surgery during the 6 weeks to 6 months before onset of symptoms. Others at increased risk include people with occupational exposure to blood or body fluids, staff of institutions and nonresidential child care programs for children with developmental disabilities, patients undergoing hemodialysis, and sexual or house- hold contacts of people with an acute or chronic infection. Approximately 62% of case reports in 2014 with risk exposure or behavior information did not have a readily identifi- able risk characteristic. HBV infection in adolescents and adults is associated with other sexually transmitted infections, including syphilis and HIV infection. Investigations have indicated an increased risk of HBV infection among adults with diabetes mellitus. Out- breaks in nonhospital health care settings, including assisted-living facilities and nursing homes, highlight the increased risk among people with diabetes mellitus undergoing as- sisted blood glucose monitoring. 1 The prevalence of HBV infection and patterns of transmission vary markedly throughout the world (see Table 3.19). Approximately 45% of people worldwide live in regions of high HBV endemicity, where the prevalence of chronic HBV infection is 8% or greater. Historically in these regions, most new HBV infections occurred as a result of 1Centers for Disease Control and Prevention. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60(50):1709–1711 EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  404 HEPATITIS B perinatal or early childhood infections. In regions of intermediate HBV endemicity, where the prevalence of HBV infection is 2% to 7%, multiple modes of transmission (ie, perinatal, household, sexual, injection drug use, and health care associated) contribute to the burden of infection. In countries with low endemicity, where chronic HBV infection prevalence is less than 2% (including the United States) and where routine immunization has been adopted, new infections increasingly occur among unimmunized age groups. Many people born in countries with high endemicity live in the United States. Infant im- munization programs in some of these countries have, in recent years, greatly reduced the seroprevalence of HBsAg, but many other countries with endemic HBV have yet to im- plement widespread routine childhood hepatitis B immunization programs. The incubation period for acute HBV infection is 45 to 160 days, with an average of 90 days. DIAGNOSTIC TESTS: Serologic protein antigen tests are available commercially to detect HBsAg and HBeAg. Serologic antibody assays also are available for detection of anti- HBs, total anti-HBc, IgM anti-HBc, and anti-HBe (see Table 3.20, p 405, Fig 3.2, p 406, and Fig 3.3, p 407). In addition, nucleic acid amplification testing (NAAT), polymerase chain reaction (PCR) assay, and branched DNA methods as well as hybridization assays are available to detect and quantify HBV DNA in plasma or serum. At least 2 PCR as- says for quantitative detection of HBV DNA are cleared by the US Food and Drug Ad- ministration (FDA). These assays are used to monitor patients with chronic HBV infec- tion and to evaluate their response to treatment regimens. The assays differ in their limits of detection, dynamic range, and target gene sequences detected. Because of variability in the different assays, it is best to use the same manufacturer’s assay performed in the same laboratory to monitor an individual’s patient’s HBV load. Tests to quantify HBsAg and HBeAg currently are being developed but are not yet available commercially. Table 3.19. Estimated International HBsAg Prevalencea Region Estimated HBsAg Prevalenceb North America 0.1% Mexico and Central America 0.3% South America 0.7% Western Europe 0.7% Australia and New Zealand 0.9% Caribbean (except Haiti) 1.0% Eastern Europe and North Asia 2.8% South Asia 2.8% Middle East 3.2% Haiti 5.6% East Asia 7.4% Southeast Asia 9.1% Africa 9.3% Pacific Islands 12.0% HBsAg indicates hepatitis B surface antigen. a Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization of adults. MMWR Recomm Rep. 2006;55(RR-16):1–33 b Level of HBV endemicity defined as high (≥8%), intermediate (2%–7%), and low (