Hepatitis B: Laboratory Support of Diagnosis and Management 

Hepatitis B is a liver infection with potentially serious health consequences caused by the hepatitis B virus (HBV). Most cases of hepatitis B resolve after an acute infection. However, about 5% of infections progress to a chronic phase.1,2 Although most persons with chronic hepatitis B are asymptomatic, they remain infectious and are at increased risk of complications such as cirrhosis and hepatocellular carcinoma (HCC).1,2 Many professional organizations recommend screening people who are at increased risk of hepatitis B and its complications.1,3

This article discusses the epidemiology, disease course, and prevention of hepatitis B, as well as the laboratory’s role in screening, diagnosis, and management.
Hepatitis B Epidemiology
Of the 5 hepatitis viruses (see Sidebar), HBV is the second most common cause of chronic hepatitis infections in United States. In 2018, an estimated 21,600 people had new acute HBV infections4 and more than 860,000 were living with chronic hepatitis B,5 about two-thirds of whom did not know they had it.3 Globally, in 2015 an estimated 257 million people were living with chronic hepatitis B and 887,000 died from it; most chronic hepatitis B–related deaths were due to cirrhosis or HCC.6

HBV Infection and Transmission
HBV is transmitted through blood or other bodily fluids.1,2,6 Routes of transmission include needlestick injury, tattooing and piercing, needle sharing by persons who inject drugs, and sexual contact, including exposure to saliva, menstrual, vaginal, and seminal fluids.1,2,6 In highly endemic areas, perinatal transmission from mother to child is common.6 At-risk persons have been identified by various professional organizations and are listed in the Sidebar.1,3,7,8
Hepatitis B Disease Course
Most people who become newly infected with HBV do not experience any symptoms.1,2,6 However, some develop an acute illness that can last for 2 to 3 weeks or longer, with symptoms including jaundice, dark urine, extreme fatigue, nausea and vomiting, and abdominal pain.1,2,6

HBV infections usually resolve without any sequelae.1,2 However, around 5% of otherwise healthy adults will develop chronic hepatitis B.1,2,9 Importantly, 20% to 30% of persons with chronic hepatitis B will develop cirrhosis and/or HCC.1,2,9  

Children are more likely than adults to develop chronic hepatitis B, and younger children are the most susceptible: chronic hepatitis B develops in around 90% of children infected during the first year of life and 30% to 50% of those infected from 2 to 6 years of age.2,6 
Screening and Diagnosis of HBV Infection 
The Centers for Disease Control and Prevention (CDC), the American College of Physicians, and other professional organizations recommend testing at-risk persons (Sidebar)1,3,7,8 for serologic markers that can help evaluate HBV infection and immune status.1,3 These include
  • Hepatitis B surface antigen (HBsAg), a marker of HBV infection (acute and chronic) and infectiousness (>98% sensitive and specific for HBV)7,10
  • Hepatitis B surface antibody (HBsAb), a marker of past resolved HBV infection or an adequate response to vaccination; quantitative values ≥10 mIU/mL indicate immunity1,10
  • Total (IgG and IgM) hepatitis B core antibody (HBcAb), a marker of current or past infection; HBcAb IgM is present only during the acute phase of HBV infection10

Hepatitis B Prevention and Vaccination
Vaccination is the mainstay of hepatitis B prevention. The World Health Organization (WHO) recommends that all infants receive the hepatitis B vaccine as early as possible, preferably within 24 hours after birth.6 To complete the series, 2 or 3 doses of hepatitis B vaccine at least 4 weeks apart are recommended.6 The complete vaccine series induces protective antibody levels in more than 95% of infants, children, and young adults and prevents perinatal transmission.6

The CDC recommends that unvaccinated children <19 years old and persons at risk for HBV infection receive the hepatitis B vaccine series.9 Persons who should be vaccinated include healthcare workers, those at risk for infection by sexual exposure, persons with chronic liver disease, and individuals with hepatitis C.9 The complete list of CDC recommendations is available at CDC.gov/Hepatitis/HBV/HBVFAQ.htm#vaccFAQ.

Adult populations with risk factors for HBV transmission or HBV reactivation should receive complete serologic testing (HBsAg, anti-HBs, and anti-HBc) to rule out active infection prior to vaccination.1 Persons with positive HBsAg results should be referred to a specialist for evaluation; no additional testing is necessary for those who are negative.1 Vaccinating people who are immune to HBV infection because of current or previous infection or vaccination is not harmful and does not increase the risk for adverse events. Immunologic memory remains intact for at least 30 years among healthy people who received hepatitis B vaccination at >6 months of age.1

There is no general recommendation for a specific treatment for acute hepatitis B, which is managed by keeping the patient comfortable and replacing fluids lost from vomiting and diarrhea.1,2 In rare cases, acute liver failure may develop from a severe infection, and use of an oral anti-HBV agent may be appropriate.11

Chronic hepatitis B is primarily treated with oral antiviral agents, which slow the progression of cirrhosis, reduce incidence of HCC, and improve long-term survival.1,2,8 About 10% to 40% of persons with chronic hepatitis B will require antiviral therapy, depending on treatment criteria.1,2,6,8 In most people with chronic hepatitis B, treatment does not cure the HBV infection but only suppresses replication of the virus; thus, treatment must be continued for a prolonged period, and in some cases for life.1,2,6,10 As chronic hepatitis B is a serious condition, ongoing research is focused on developing therapies that will provide a functional cure.

Patients with chronic hepatitis B require frequent monitoring to determine suppression of viral replication and for the occurrence/progression of liver disease.8 Testing includes measurement of liver enzyme levels, HBV DNA, and HBV antigens.8 Determination of HBV genotype is also important, as genotype may play a role in the progression of HBV-related liver disease and the response to some therapies.8
Other Hepatitis Viruses 

In addition to HBV, four other hepatitis viruses have been well characterized: hepatitis A (HAV), C (HCV), D (HDV), and E (HEV), as described below:
  • HAV is the second most common cause of new viral hepatic infections in the United States (25,000; 2018 estimate).4 Hepatitis A is highly contagious via the fecal/oral route and usually manifests as acute infection in adults but is usually asymptomatic in children. It is a self-limiting disease, has no chronic carrier state, and seldom causes serious sequelae, although some patients may develop acute fulminant liver failure.13
  • HCV accounts for the most new viral hepatitis infections in the United States (50,300; 2018 estimate4) and the most chronic viral hepatitis infections as well (2.4 million; 2016 estimate).1,14 Similar to chronic hepatitis B, chronic hepatitis C can lead to cirrhosis and HCC.1,12
  • HDV infection is rare in the United States, except among HBV-infected individuals. HDV is considered a “defective” virus because it can only replicate in the presence of HBV. Acute HBV/HDV infection (coinfection) may be severe but tends to resolve spontaneously. On the other hand, chronic HBV/HDV infection (superinfection) can accelerate liver cirrhosis and failure and HCC.15,16
  • HEV infection is rare in the United States. The virus is transmitted by fouled water, undercooked meat, and blood and is primarily seen in underdeveloped countries.17,18
People at Increased Risk of Hepatitis B for Whom Screening Is Recommended

Professional organizations recommend hepatitis B screening for persons at increased risk of infection or complications from hepatitis B, including1,3,7,8
  • People born in highly (prevalence ≥8%) or moderately (prevalence ≥2%) endemic areas
  • Children of people born in highly endemic areas (if the child was not vaccinated as an infant)
  • People who have traveled to highly or moderately endemic areas
  • Pregnant women
  • Children born to women with HBV infection
  • People who use intravenous drugs (current or past)
  • Men who have sex with men
  • People who have a history of sexually transmitted infections or participate in high-risk sexual activities
  • Household and sexual contacts of people with HBV infection
  • Healthcare and public safety workers at risk of exposure to blood-borne pathogens
  • People living or working at facilities for developmentally disabled people
  • People living in correctional facilities
  • People requiring immunosuppressive therapy
  • People with end-stage renal disease (receiving dialysis)
  • People with HCV or HIV infection
  • People with diabetes, 19 to 59 years old, if not vaccinated
How the Laboratory Can Help

Quest Diagnostics offers tests for screening, diagnosis, and management of hepatitis B. Screening panels are available that meet the recommendations of the CDC and other professional organizations. Additional information about hepatitis B and other hepatitis viruses is available on the Quest Test Directory:

1.     Hepatitis B questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed July 28,2020. Accessed February 15, 2021. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm

2.     Nguyen MH, Wong G, Gane E, et al. Hepatitis B virus: advances in prevention, diagnosis, and therapy. Clin Microbiol Rev. 2020;33(2):e00046-19. doi:10.1128/CMR.00046-19

3.     Abara WE, Qaseem A, Schillie S, 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;167(11):794-804. doi:10.7326/M17-1106

4.     Viral Hepatitis Surveillance – United States, 2018. Centers for Disease Control and Prevention. Reviewed July 2020. Accessed May 10, 2021. https://www.cdc.gov/hepatitis/statistics/2018surveillance/index.htm

5.     Patel EU, Thio CL, Boon D, et al. Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011-2016. Clin Infect Dis. 2019;69(4):709-712. doi:10.1093/cid/ciz001

6.     Hepatitis B. World Health Organization. Published July 27, 2020. Accessed May 13, 2021. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b

7.     US Preventive Services Task Force; Krist AH, Davidson KW, et al. Screening for hepatitis B virus infection in adolescents and adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(23):2415-2422. doi:10.1001/jama.2020.22980

8.     Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800

9.     Hepatitis B vaccination. Centers for Disease Control and Prevention. Reviewed July 28, 2020. Accessed May 13, 2021. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm#vaccFAQ

10.  Roush SW, Beall B, McGee L, et al. Chapter 22: laboratory support for surveillance of vaccine-preventable diseases. In: Roush SW, Baldy LM, Kirkconnell MA, eds. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Reviewed May 29, 2019. Accessed May 15, 2021. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt22-lab-support.html

11.  Shiffman ML. Management of acute hepatitis B. Clin Liver Dis. 2010;14(1):75-91; viii-ix. doi:10.1016/j.cld.2009.11.013

12.  Hepatitis C questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed August 7, 2020. Accessed May 13, 2021. https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

13.  Hepatitis A questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed July 28, 2020. Accessed May 15, 2021. https://www.cdc.gov/hepatitis/hav/havfaq.htm

14.  Hofmeister MG, Rosenthal EM, Barker LK, et al. Estimating prevalence of hepatitis C virus infection in the United States, 2013-2016. Hepatology. 2019;69(3):1020-1031. doi:10.1002/hep.30297

15.  Hepatitis D questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed March 9, 2020. Accessed May 15, 2021. https://www.cdc.gov/hepatitis/hdv/hdvfaq.htm

16.  Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep. 2014;16(1):365. doi:10.1007/s11894-013-0365-x

17.  Hepatitis E questions and answers for health professionals. Centers for Disease Control and Prevention. Reviewed September 15, 2020. Accessed May 15, 2021. https://www.cdc.gov/hepatitis/hev/hevfaq.htm

18.  Khuroo MS, Khuroo MS, Khuroo NS. Hepatitis E: discovery, global impact, control and cure. World J Gastroenterol. 2016;22(31):7030-7045. doi:10.3748/wjg.v22.i31.7030

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Content reviewed 7/2021

Disclaimer: Images are used for illustrative purposes; those pictured are models.