Hepatitis B

Includes non-perinatal acute hepatitis B, chronic hepatitis B, and delta hepatitis.

Reporting Information

Class B

Report a case, suspected case, and/or positive laboratory result to the local public health department in which the patient resides by the close of the next business day. If the patient residence is unknown, report to the local public health department in which the reporting healthcare provider or laboratory is located.

Reporting Form(s) and/or Mechanism

The Hepatitis B and C Case Collection Form (HEA 0201) is used for collecting information on persons testing positive for hepatitis B and C in Ohio. Do not send this form to ODH unless otherwise requested; information collected from the form should be entered into ODRS where fields are available.

The Ohio Disease Reporting System (ODRS) should be used to report cases and lab findings to the Ohio Department of Health (ODH). For healthcare providers without access to ODRS, the Ohio Confidential Reportable Disease Form (HEA 3334) may be used.

The Viral Hepatitis Case Report (CDC OMB 0920-0728) is available for use by the local public health department when following up with cases. Do not send this form to ODH unless otherwise requested; information collected from the form should be entered into ODRS where fields are available.

Key Fields for ODRS Reporting

• Patient demographics:
  • First and last name.
  • Date of birth or age (including age type).
  • Sex.
  • Race.
  • Pregnant: enter current pregnancy status for all females aged 12-50 years who have labs indicating active chronic infection.
• Laboratory information:
  • Test name (selected from drop down menu).
  • Result (qualitative).
  • Numeric results (quantitative).
  • Reference range for numeric results.
  • Organism does not need to be entered if the test is IgM anti-HBc, HBsAg, HBeAg, HBV DNA, or ALT (aminotransferase) as these tests do not identify the organism.
• Clinical information (for acute HBV):
  • Is patient symptomatic?
  • Symptom onset date.
  • Was patient jaundiced?
  • Jaundice onset date.
  • Elevated ALT (enter in Laboratory information).
  • Total Bilirubin (enter in Laboratory information).
  • Did condition resolve: if yes, as of date.
• Epidemiology information: pay special attention to questions related to healthcare-associated transmission (e.g., transfusion, dental work), drug use, tattooing and piercing, and incarceration.
• Vaccination information: complete for those receiving vaccine.
• Pregnancy information: this section is triggered by the Pregnant question in Person Demographics.
• Contact information: complete as appropriate to track contact status.
• Travel history: complete as appropriate to track patient travel history.

Agent

Hepatitis B is a 40-42 nanometer virus classified in the Hepadnaviridae family. It contains a circular, partially double-stranded DNA virus. Replication occurs primarily in the liver. There are ten HBV genotypes (A-J). Infection or immunization with one genotype generally confers immunity to all genotypes.

Hepatitis D (delta) virus is a defective single-stranded RNA virus that requires the helper function of the hepatitis B virus to replicate.

Case Definition

Hepatitis B, Acute

Clinical Criteria

In the absence of a more likely, alternative diagnosis*, acute onset or new detection of at least one of the following:

• Jaundice or
• Elevated serum alanine aminotransferase (ALT) levels >200 IU/L or
• Total bilirubin ≥3.0 mg/dL.

* Alternative diagnoses may include evidence of acute liver disease due to other causes or advanced liver disease due to hepatitis B reactivation, pre-existing chronic HBV infection, other causes including alcohol exposure, other viral hepatitis, hemochromatosis, or conditions known to produce false positives of hepatitis B surface antigen, etc.

Laboratory Criteria for Diagnosis

Confirmatory Laboratory Evidence

Tier 1:

• Detection of HBsAg AND detection of IgM anti-HBc, OR
• Detection of HBeAg AND detection of IgM anti-HBc, OR
• Detection of HBV DNA AND detection of IgM anti-HBc, OR
• Detection of HBsAg, HBeAg, or HBV DNA within 12 months (365 days) of a negative HBsAg test result. (i.e., HBsAg seroconversion).

Tier 2:

• Detection of HBV surface antigen (HBsAg) AND IgM antibody to HBV core antigen (IgM anti-HBc) test not done or result not available, OR
• Detection of HBV DNA AND IgM anti-HBc test not done or result not available.

Presumptive Laboratory Evidence

• Detection of IgM anti-HBc, AND
• Negative or not done for HBsAg, HBV DNA, or HBeAg.

Case Classification

Confirmed

• Meets Tier 1 confirmatory laboratory evidence of acute HBV infection, OR
• Meets clinical criteria AND Tier 2 confirmatory laboratory evidence of acute HBV infection.

Probable

• Meets clinical criteria AND presumptive laboratory evidence of acute HBV infection.

Hepatitis B, Chronic

Clinical Criteria

Persons with chronic hepatitis B virus (HBV) infection may have no evidence of liver disease or may have a spectrum of disease ranging from chronic hepatitis to cirrhosis or liver cancer.

Laboratory Criteria for Diagnosis

Confirmatory Laboratory Evidence

• Detection of HBsAg in two clinical specimens taken ≥6 months apart, OR
• Detection of HBeAg in two clinical specimens taken ≥6 months apart, OR
• Detection of (HBsAg OR HBeAg) AND total anti-HBc, OR
• Detection of HBsAg AND HBeAg, OR
• Detection of HBV DNA.

Presumptive Laboratory Evidence

• Detection of ([HBsAg OR HBeAg) AND IgM anti-HBc test negative, not done, or result not available.

Case Classification

Confirmed

Meets confirmatory laboratory evidence of chronic HBV infection. Once person meets confirmed case definition, classification cannot be changed with new negative or undetectable HBV DNA test results.

Probable

Meets presumptive laboratory evidence of chronic HBV infection.

Criteria to Distinguish a New Case of Acute or Chronic Hepatitis B from Reports or Notifications which Should Not be Enumerated as a New Case for Surveillance

• A case of HBV infection classified under the Perinatal HBV position statement (16-ID-06) can be additionally enumerated as a confirmed case of chronic HBV infection if a positive HBV viral detection test (HBsAg, HBeAg, or HBV DNA) is obtained after the case is greater than 24 months of age.
• A confirmed acute case of HBV infection may be additionally enumerated as a new confirmed chronic case of HBV infection if a positive HBV viral detection test is reported 6 months or longer after acute case onset or, if asymptomatic, after the initial positive test result.
• An acute case of HBV infection should not have been previously enumerated as a case of either acute or chronic HBV infection.
• A chronic case of HBV infection should not have been previously enumerated as a case of chronic HBV infection.

Comments

Cases should be reported in the following manner:

• The serologic course of acute HBV infection lasts for under 6 months. Therefore, the clinical and laboratory criteria used to classify a case as acute HBV infection must have occurred or have been collected within a time period that is no longer than 6 months to meet classification requirements.
• If a positive test result has a specimen collection date greater than six months after an acute specimen collection date, create a new ODRS record with a reportable condition of chronic hepatitis B for the new laboratory result.
  • Example: If the first positive laboratory result was collected on October 1, 2021 and the new positive laboratory result was collected on May 12, 2022, create a new ODRS record with a reportable condition of chronic hepatitis B for the 2022 laboratory result.
• If a positive test result has a specimen collection date less than six months after an acute specimen collection date, update the existing acute hepatitis B case with the new laboratory result.
• Individuals born in the US, under or equal to the age of 24 months, and born to a mother with documented evidence of hepatitis B infection should be reporting using the Perinatal Hepatitis B Position Statement (16-ID-06), unless there is evidence that exposure occurred via a non-perinatal mechanism (e.g., healthcare-acquired).

Additional Information to Support the Operationalization of HBV Infection case Classifications and Case Notification

False positive HBsAg and HBeAg test results are possible. This can be due to multiple factors, including HBV vaccination in the prior 30 days (can be a longer time frame if the person is a hemodialysis patient) and certain health conditions. If a false positive result is suspected, jurisdictions should consider other test results that may be available that can help with interpretation. If results are determined to be false-positive, they should not be used to classify cases as confirmed or probable. Total anti-HBc is detectable, on average, approximately 5 weeks post-HBV exposure, remains detectable indefinitely following exposure, and indicates past or current infection. In the presence of total anti-HBc, a positive HBsAg, HBeAg, or anti-HBc IgM result is a more reliable indication of recent or current infection, while negative total anti-HBc results can be used to determine that a person is not a case. Jurisdictions that receive total anti-HBc laboratory results can use these results to clarify a person's HBV infection status and confirm chronic cases in conjunction with evidence of positive tests for HBsAg or HBeAg.

Multiple laboratory tests indicative of chronic HBV infection may be performed simultaneously on the same patient specimen as part of a "hepatitis panel." Testing performed in this manner may lead to seemingly discordant results (e.g., HBsAg-negative AND HBV DNA-positive). For the purposes of these case definitions, any positive result among the three laboratory tests mentioned above (HBsAg, HBeAg, or HBV DNA) is acceptable, regardless of other testing results. Negative HBeAg results and HBV DNA levels below positive cutoff level do not confirm the absence of HBV infection. HBV DNA results might be reported as below the lower limit of quantification (e.g., <12 IU/mL, <15 IU/mL, etc.) yet simultaneously indicate that HBV DNA was detected. HBV DNA results that are above the limit of detection but below the lower limit of quantification should be considered "detectable" or "positive" for surveillance classification purposes.

Individuals who have a history of hepatitis B infection - either inactive chronic hepatitis B or resolved acute hepatitis B - can experience hepatitis B reactivation. Hepatitis B reactivation is loss of hepatitis B immune control, which can be followed by a hepatitis flare characterized by alanine aminotransferase elevation (ALT increase to >3 times the baseline level and >100 U/L) with or without symptoms; illness can be severe and result in death. The following groups are at greatest risk of hepatitis B reactivation: patients undergoing cancer chemotherapy, patients taking immunosuppressive therapy, patients with HIV infection who have discontinued hepatitis B antiviral drugs, patients undergoing solid organ or bone marrow transplantation, and patients co-infected with hepatitis C who are undergoing direct acting antiviral treatment.

If reactivation is identified in a previously reported probable or confirmed acute hepatitis B case in a prior reporting year, and the person meets chronic case classification criteria with the latest report, this case should be submitted as a new chronic hepatitis B case. If reactivation is identified in a previously reported probable or confirmed chronic hepatitis B case, this case should not be counted again; however, reactivation may be noted in the jurisdiction's hepatitis B surveillance database if the jurisdiction chooses to do so.

Laboratory evidence of reactivation includes the following:

• Meets any of the following laboratory criteria after having HBsAg positive and total anti-HBc positive tests at baseline testing that occurred before experiencing at least one risk factor for hepatitis B reactivation.
  • A ≥100-fold increase in HBV DNA compared to baseline HBV DNA testing, OR
  • HBV DNA ≥1,000 IU/mL in a patient with previously undetectable level, OR
  • HBV DNA ≥10,000 IU/mL if the baseline level is not available.
• Meets either of the following criteria after having HBsAg negative and total anti-HBc positive tests at baseline testing that occurred baseline before experiencing at least one risk factor for hepatitis B reactivation:
  • HBV DNA is detectable, OR
  • HBsAg seroconversion occurs (HBsAg negative to HBsAg positive).

HBV reactivation can lead to a positive IgM anti-HBc test result. If it is determined that the case under investigation has test results known to be due to reactivation (e.g., a prior history of acute or chronic HBV), the IgM anti-HBc test result should not be used for case classification purposes. History of acute or chronic HBV infection includes those that were previously reported to and documented in a jurisdictions surveillance system, were reported by a separate jurisdiction as having such a history, or a provider report of prior infection.

Hepatitis D (Delta Hepatitis)

Clinical Description

Hepatitis D, also known as "delta hepatitis," is a serious liver disease caused by infection with the hepatitis D virus (HDV), which is an RNA virus structurally unrelated to hepatitis A, B, or C viruses. Hepatitis D, which can be acute or chronic, is uncommon in the United States. HDV is an incomplete virus that requires the helper function of HBV to replicate and only occurs among people who are infected with HBV. HDV is transmitted through percutaneous or mucosal contact with infectious blood and can be acquired either as a coinfection with HBV or as superinfection in a person who is already infected with HBV.

Laboratory Criteria for Diagnosis

Meets the case definition for either acute or chronic hepatitis B AND one of the following tests positive for hepatitis D:

• Total Anti-HDV positive OR
• IgM anti-HDV positive OR
• HDV RNA OR
• HDsAg.

Case Classification

Probable or Confirmed

Case classification for a hepatitis D virus case that is laboratory confirmed will follow the case classification designated for the associated hepatitis B virus case.

Signs and Symptoms

The onset of acute hepatitis B is generally insidious. Clinical signs and symptoms include various combinations of fever, fatigue, anorexia, malaise, nausea, vomiting, abdominal pain, dark urine, clay-colored stools, and jaundice. Skin rashes, arthralgia, and arthritis can also occur. Symptoms of acute hepatitis B vary by age. Most children less than 5 years of age and newly infected, immunosuppressed adults are asymptomatic. In adults, approximately half of newly acquired HBV infections are symptomatic. Symptoms begin an average of 90 days (range: 60-150 days) after exposure to the virus. Disease is more severe among persons older than 60 years of age. Approximately one percent of reported cases result in acute liver failure and death.

Persons with chronic HBV infection might be asymptomatic, have no evidence of liver disease, or have a spectrum of disease ranging from chronic hepatitis to cirrhosis or hepatocellular carcinoma (a type of liver cancer). Most chronic hepatitis B virus carriers are asymptomatic. Approximately 25% of those who become chronically infected during childhood and 15% of those who become chronically infected after childhood die prematurely from cirrhosis or liver cancer, and the majority remain asymptomatic until onset of cirrhosis or end-stage liver disease. In the United States, chronic HBV infection results in an estimated 2,000-4,000 deaths per year.

Diagnosis

Test Name Abbreviations

Hepatitis B

Hepatitis B is distinguished from other forms of hepatitis through laboratory testing.

Serologic Diagnosis

Hepatitis B virus antigens and antibodies typically appear and disappear in serum in a predictable sequence over time. Different combinations of these markers are detected in a single serum sample, depending on when during the illness testing is done. The serologic profile contributes to the diagnosis of hepatitis B virus infection and indicates the stage of illness, degree of infectivity, carrier state, or state of immunity.

Serologic Markers

HBsAg: HBsAg (hepatitis B surface antigen) is a protein on the surface of the virus and is the antigen used to make the hepatitis B vaccine. It is the first serologic marker to appear and can be detected in an infected person's blood an average of four weeks (range: 1-9 weeks) after exposure to the virus. About one of two patients will no longer be infectious by seven weeks after onset of symptoms, and all patients who do not remain chronically infected will be HBsAg-negative by 15 weeks after onset of symptoms. Its presence is indicative of active infection.

When HBsAg is positive in patients with apparent acute hepatitis, acute hepatitis B is suggested; however, superimposed hepatitis caused by another agent may give similar symptoms in a patient chronically infected with the hepatitis B virus. To differentiate an acute from a chronic infection in a person who is HBsAg-positive, it is necessary to test for IgM anti-HBc. If the IgM anti-HBc is positive, acute hepatitis B infection is suspected.

HBsAg positivity persisting beyond six months is indicative of chronic hepatitis B. The risk for chronic infection varies according to the age at infection and is greatest among young children. Approximately 90% of infants and 25-50% of children aged 1-5 years will remain chronically infected with HBV. By contrast, approximately 95% of adults recover completely from HBV infection and do not become chronically infected. Chronic hepatitis B virus carriers are likely to remain HBsAg positive indefinitely. All HBsAg positive persons are potentially infectious, regardless of the presence or absence of any other serologic markers and the duration of infection. Undetectable levels of HBsAg are present in many patients with subclinical hepatitis.

Note regarding bilirubin levels: Jaundice appears four weeks (range of 1-7 weeks) after the appearance of HBsAg. The severity of the hepatitis, as measured by bilirubin levels, correlates with the duration of HBsAg positivity. As bilirubin clears, HBsAg titers fall, and generally become undetectable within several weeks.

IgM Anti-HBc: IgM anti-HBc (IgM antibody to hepatitis B core antigen) is often detectable at the time of clinical onset and declines to sub-detectable levels within six months. It is a diagnostic marker for acute hepatitis B virus infection, useful clinically for differentiating acute or recent infection from chronic carrier state or resolved hepatitis B virus infection. It is also useful in the "window" period, when HBsAg has become negative, but the patient has not yet developed the antibody to HBsAg (anti-HBs). A negative test for IgM anti-HBc in association with a positive test for HBsAg, a positive test for total anti-HBc, and a negative anti-HBs test usually indicates that an individual has chronic hepatitis B virus infection.

Total anti-HBc: Total (combination of IgM and IgG) anti-HBc (hepatitis B core antibody) is generally detectable in serum by the onset of clinical illness. Total anti-HBc persists for many years, both in persons who have cleared the hepatitis B virus and in those who become chronic carriers. In patients with chronic hepatitis B virus infection, both HBsAg and total anti-HBc usually remain detectable for life.

Anti-HBs: Anti-HBs (hepatitis B surface antibody) titers rise slowly during convalescence, after the disappearance of HBsAg in patients who do not progress to chronic infection. Presence of anti-HBs generally indicates recovery and immunity from infection. Anti-HBs also develops in those who have been successfully vaccinated against hepatitis B. In approximately 50% of patients with self-limited hepatitis B virus infection, there is a time interval of up to several months between the disappearance of detectable HBsAg and the appearance of anti-HBs. During this time, only the total anti-HBc is detectable; this period is referred to as the "core window" or "window period." Approximately 5% of patients with self-limited hepatitis B virus infection will have cleared the HBsAg by the time they are seen by a clinician. Therefore, the initial diagnostic tests performed on patients presenting with a recent history of symptoms of viral hepatitis should include an IgM anti-HBc, as well as an HBsAg.

A positive IgM anti-HBc in the absence of HBsAg is indicative of a recently resolved hepatitis B virus infection. Low titers of total anti-HBc and IgM anti-HBc, and high titers of anti-HBs may be present; their presence in conjunction with liver function abnormalities, appearing in a time frame consistent with the hepatitis B virus incubation period, suggests that hepatitis B virus infection has occurred and is probably resolving. Some persons who are HBsAg-positive will develop detectable anti-HBs; however, these persons are still considered infectious due to the presence of HBsAg. Since seroconversion to anti-HBs indicates immunity, anti-HBs is generally not detected in chronic infections. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B.

HBeAg: HBeAg (hepatitis B e antigen) is a secreted product of the nucleocapsid gene of HBV that is found in serum during acute and chronic hepatitis B. It appears a few days after HBsAg becomes detectable and typically disappears before HBsAg is gone, although it might persist for years in a chronic carrier of hepatitis B virus. HBeAg is variably present in patients with chronic hepatitis B virus infection with 25-50% of patients having detectable HBeAg. The presence of HBeAg correlates with higher titers of circulating hepatitis B virus and increased infectivity. It is not generally necessary to test for HBeAg or its antibody (anti-HBe), unless it is of importance that the patient's relative infectivity be determined. The HBeAg or anti-HBe status should not alter the general recommendations given to patients and their contacts, since all HBsAg-positive individuals are at risk of transmitting hepatitis B. Testing for HBeAg, if done at all, should be reserved for persons who have already been shown to be HBsAg-positive, as HBeAg is not found in the absence of HBsAg.

Anti-HBe: Anti-HBe (hepatitis B e antibody) is produced by the immune system temporarily during acute HBV infection or consistently during or after a burst in viral replication. It appears at about the time that HBeAg disappears. Spontaneous conversion from e antigen to e antibody (a change known as seroconversion) is a predictor of long-term clearance of HBV in patients undergoing antiviral therapy and indicates lower levels of HBV. Failure of an HBeAg-positive patient to seroconvert to anti-HBe is associated with disease activity and probable chronicity. Anti-HBe is present in 50-75% of patients with chronic hepatitis B virus infection.

HBV DNA: HBV DNA appears soon after HBsAg. It rises to high concentrations during the late incubation period and falls with the onset of clinical disease. Most chronic carriers have high titers of infectious hepatitis B virus in the serum. Detectable hepatitis B virus DNA in the serum is associated with a highly contagious state, and undetectable hepatitis B virus DNA indicates that the patient has no detectable infectious virus but does not mean that the patient has resolved the infection.

The table below summarizes interpretation of laboratory findings:

¹ IgM anti-HBc also might be positive in persons with chronic infection during severe HBV infection flares or reactivation.

² Immune if anti-HBs concentration is >10 mIU/mL after vaccine series completion.

³ Anti-HBs concentrations might wane over time among vaccine responders. People with a documented, complete HepB vaccine series typically do not need to be revaccinated, except for special populations like patients on hemodialysis or healthcare personnel.

Hepatitis D (Delta Hepatitis)

Serologic Markers

The serologic course of hepatitis D virus infection varies depending on whether the virus is acquired as a coinfection with hepatitis B virus or as a superinfection of a person with chronic hepatitis B virus infection. In most persons with HBV/HDV coinfection, both IgM anti-HDV and IgG anti-HDV are detectable during infection. However, in about 15% of patients, the only evidence of hepatitis D virus infection may be the detection of either IgM anti-HDV alone during the early acute period of illness or IgG anti-HDV alone during convalescence. Total anti-HDV generally declines to undetectable levels after the infection resolves. There is no serologic marker that persists to indicate that the patient was ever infected with the hepatitis D virus.

Hepatitis delta antigen (HDAg) can be detected in serum in only about 25% of patients with HBV/HDV coinfection. When HDAg is detectable, it generally disappears as HBsAg disappears and most patients do not develop chronic infection.

In patients with chronic hepatitis B virus infection who are superinfected with hepatitis D virus, several characteristic serologic features generally occur, including:

• Concentration of HBsAg declines at the time HDAg appears in the serum.
• HDAg and HDV RNA remain detectable in the serum because chronic hepatitis D virus infection occurs in most patients with hepatitis D virus superinfection, unlike the case with coinfection.
• High concentration of both IgM and IgG anti-HDV are detectable, which persist indefinitely.

Epidemiology

Source

Hepatitis B

Hepatitis B virus is found in highest concentrations in blood and lower concentrations in other body fluids (e.g., semen, vaginal secretions, and wound exudates). It is highly infectious and can be transmitted in the absence of visible blood. The virus can survive outside the body for at least seven days and still can cause infection.

Hepatitis D (Delta Hepatitis)

Hepatitis D virus is found in human blood and blood products, semen, vaginal secretions, and serous fluids.

Occurrence

Hepatitis B

Hepatitis B virus infection is a major cause of acute and chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma. Every year, over four million acute cases of HBV occur. More than 2 billion people alive today have been infected with HBV at some time in their lives, and, of these, about 350 million remain infected chronically and become carriers of the virus. Three quarters of the world's population live in areas where there are high levels of infection. Approximately one million people a year die from cirrhosis or primary liver cancer due to chronic infection.

The prevalence of hepatitis B virus infection varies markedly in different parts of the world. In North America, Western Europe, Australia, and some part of South America, it is a disease of low endemicity, where <2% of the population are carriers and infection occurs primarily during adulthood and <20% of the population is infected with the virus. In contrast, hepatitis B virus infection is highly endemic (>8% prevalence) in Southeast Asia and the Pacific Basin (excluding Japan, Australia, and New Zealand), sub-Saharan Africa, the Amazon Basin, parts of the Middle East, the central Asian Republics, and some countries in Eastern Europe. In these areas, most persons acquire infection at birth or during childhood, with 70-90% of the population becoming HBV-infected before the age of 40, and 8-20% of people are carriers. In other parts of the world, hepatitis B virus is a disease of intermediate endemicity, where 2-8% of persons are hepatitis B virus carriers.

The rate of new HBV infections has declined by approximately 82% since 1991 in the United States, when a national strategy to eliminate HBV infection was implemented. The decline has been greatest among children born since 1991, when routine vaccination of children was first recommended. After a decade of stable rates, the rate of acute hepatitis B abruptly decreased by 32% after 2019. This decrease may be related to fewer people seeking healthcare and being tested for hepatitis B during the COVID-19 pandemic. In 2020, 2,157 cases of acute hepatitis B in the United States were reported to the Centers for Disease Control and Prevention (CDC), which resulted in a rate of 0.7 cases per 100,000 population. CDC estimates the actual number of new acute infections to be an estimated 14,000 persons, due to many infections being either asymptomatic or not reported. During 2020, a total of 11,635 newly identified cases of chronic hepatitis B were reported to CDC, corresponding to a rate of 5.0 cases per 100,000 people. Rates of disease are highest among adults, particularly males, aged 25-44 years. Acute infection ranges from asymptomatic or mild disease to, rarely, fulminant hepatitis. Disease is more severe in older adults (>60 years). The fatality rate among acute cases reported to CDC is 0.5-1.0%.

An estimated 580,000 to 1.17 million persons in the United States have chronic HBV infection. Risk for chronic infection is inversely related to age at infection with approximately 90% of infected infants and 30% of infected children aged <5 years becoming chronically infected, compared with two to six percent of adults. Approximately 25% of those who become chronically infected during childhood and 15% of those who become chronically infected after childhood die prematurely from cirrhosis or liver cancer, and the majority remain asymptomatic until onset of cirrhosis or end-stage liver disease. Among persons with chronic HBV infection, the risk for premature death from cirrhosis or hepatocellular carcinoma is 15-25%. In 2020, the mortality rate for hepatitis B in the United States was 0.45 deaths per 100,000 population (n=1,752).

Hepatitis B virus infection in a pregnant woman poses a serious risk to her infant at birth. Without post-exposure immunoprophylaxis, approximately 40% of infants born to HBV-infected mothers in the United States will develop chronic HBV infection, with approximately one out of four dying from chronic liver disease.

Hepatitis D (Delta Hepatitis)

In general, in countries with a low prevalence of chronic hepatitis B virus infection, such as the United States, hepatitis D virus prevalence is generally low among both asymptomatic hepatitis B virus carriers (<10%) and patients with chronic hepatitis B virus-related liver disease (<25%). Hepatitis D virus infection in these countries occurs most commonly among injecting drug users and persons with hemophilia.

Hepatitis D virus infection is acquired as either a coinfection with HBV or a superinfection in persons with chronic HBV infection. Persons with HBV/HDV coinfection may have more severe acute disease and a higher risk of hepatitis with rapid liver failure (2-20%) compared to those infected with HBV alone; however, chronic HBV infection appears to occur less frequently in persons with coinfection. Chronic HBV carriers who acquire hepatitis D virus superinfection usually develop chronic HDV infection (80%). Superinfection is associated with a higher occurrence of fulminant disease (2-20%), cirrhosis, (60-70%), and may progress to hepatocellular carcinoma.

Mode of Transmission

Hepatitis B

Hepatitis B virus is transmitted by percutaneous or mucosal exposure to HBsAg-positive blood and/or body fluids from persons who have acute or chronic HBV infection.

Modes of transmission include the following:

• Sex with an infected partner.
• Injection drug use that involves sharing needles, syringes, or drug-preparation equipment.
• Birth to an infected mother.
• Contact with blood or open sores of an infected person.
• Needle sticks or sharp instrument exposures.
• Sharing items such as razors or toothbrushes with an infected person.

HBV is not spread through food or water, sharing eating utensils, breastfeeding, hugging, kissing, hand holding, coughing, or sneezing. Infection can occur in settings of continuous close personal contact, such as in households or among residents via inapparent or unnoticed contact of infectious secretions with skin lesions or mucosal surfaces. The virus is stable on environmental surfaces for at least seven days. While minimal amounts of virus can be found in saliva, it is not an effective vehicle for transmission of disease unless it also contains blood. Any blood spills – including dried blood, which can still be infectious – should be cleaned using 1:10 dilution of one part household bleach to 10 parts of water for disinfecting the area. Gloves should be used when cleaning up any blood spills.

Hepatitis D (Delta Hepatitis)

The modes of hepatitis D virus transmission are like those for hepatitis B virus, with percutaneous exposures the most common. Sexual transmission of hepatitis D virus is less efficient than with hepatitis B virus. Perinatal hepatitis D virus transmission is rare. There is no vaccine for hepatitis D, but it can be prevented in persons who are not already HBV- infected by hepatitis B vaccination.

Screening and Testing Recommendations

In 2023, the CDC published updated recommendations to screening and testing guidelines for hepatitis B. The updated recommendations advise hepatitis B screening for all adults at least once in their lifetime. Full implementation of the recommendations will substantially improve timely diagnosis and facilitate linkage to care for persons with hepatitis B.

At Risk Groups

CDC recommends testing susceptible people periodically, regardless of age with ongoing risk for exposures, while risk for exposures persists, including:

• People with a history of sexually transmitted infections or multiple sex partners.
• People with hepatitis C infection or a history of hepatitis C virus infection.
• People incarcerated or formerly incarcerated in a jail, prison, or other detention setting.
• Infants born to HBsAg-positive people.
• People born in regions with HBV infection prevalence of ≥2%.
• US born people not vaccinated as infants whose parents were born in geographic regions with HBsAg prevalence of >8%.
• People who inject drugs or have a history of injection drug use.
• People with HIV infection.
• Men who have sex with men.
• Household contact or former household contacts of people with known HBV infection.
• Needle-sharing or sexual contacts of people with known HBV infection.
• People on maintenance dialysis, including in-center or home hemodialysis and peritoneal dialysis.
• People with elevated liver enzymes.

Susceptible people include those who have never been infected with HBV and either did not complete an HBV vaccine series per ACIP recommendations or who are known to be vaccine non-responders.

Period of Communicability

The role of the hepatitis B virus carrier is central in the epidemiology of hepatitis B virus transmission. A person who is HBsAg positive and IgM anti-HBc negative or whose HBsAg positivity persists for six months or more is considered a carrier. Although the degree of infectivity is best correlated with HBeAg-positivity, any person positive for HBsAg is potentially infectious. The likelihood of developing the carrier state varies inversely with the age at which infection occurs. Approximately 90% of infected infants and 25-50% of children aged 1-5 years will remain chronically infected with hepatitis B, while in adults only 5% will remain chronically infected.

Incubation Period

Hepatitis B

The average incubation period is 60 days (range: 40-90 days) to onset of abnormal serum ALT levels and 90 days (range: 60-150 days) to onset of jaundice.

Hepatitis D (Delta Hepatitis)

The incubation period for hepatitis D ranges from 6 to 26 weeks.

Public Health Management

Case

Investigation

Determine through the patient's physician if the patient is/was acutely ill and meets the case definition. If the patient is pregnant, follow the detailed guidance in the Perinatal Hepatitis B chapter.

Treatment

For persons with acute infection, treatment at this time is only supportive as no medication is available to treat the infection. There are several antiviral drugs available to treat chronic infection. Persons with chronic HBV infection require medical evaluation and regular monitoring to determine whether disease is progressing and to identify liver damage or hepatocellular cancer.

Isolation

Because hepatitis B is transmitted only through percutaneous or permucosal inoculation of hepatitis B virus, isolation of infected persons is unnecessary and inappropriate. Hospitalized patients should be placed on Standard Precautions. Physicians, nurses, dentists, and others who draw blood or perform surgical procedures should be informed of the patient’s status, but Standard Precautions should always be followed.

Hepatitis B has been transmitted in healthcare settings by HBsAg-positive healthcare workers (HCWs), but such cases are rare, and patient contacts of infected HCWs are generally not at risk.

There is no evidence that HBsAg-positive food handlers pose a health risk in an occupational setting. Hepatitis B has never been documented as being foodborne; nevertheless, it is reasonable to educate infected food handlers about the sources of hepatitis B virus and routes of transmission and the importance of good personal hygiene, frequent handwashing, and avoidance of hand injuries. Food handlers who are HBsAg-positive should not be restricted from work.

In the community setting, it is important to avoid placing unreasonable restrictions on persons who are HBsAg-positive. Instructions to the patient should include a thorough explanation of the modes of transmission of hepatitis B virus. Personal toiletry items (e.g., toothbrushes, razors) and tools (e.g., nail scissors, nail files) which may potentially cause cutting injuries should not be shared with susceptible individuals. The patient should avoid sexual contact with susceptible individuals and should not donate blood or blood products.

Contacts

Post-Exposure Prophylaxis

Hepatitis B vaccine is used as prophylaxis when someone has been exposed to the hepatitis B virus. The vaccine, when given as soon as possible but preferably within 24 hours, can effectively prevent infection. The mainstay of post-exposure prophylaxis is hepatitis B vaccine, but in certain circumstances the addition of hepatitis B immune globulin (HBIG) will provide increased protection.

The following factors and considerations are important in an assessment for post-exposure prophylaxis:

• Perinatal exposure.
• Maternal screening.
• Acute exposure to blood that contains (or might contain) HBsAg.
  • Exposed person not previously vaccinated:
    • Source known, HBsAg-positive.
    • Source known, HBsAg status unknown.
    • Source unknown.
  • Exposed person previously vaccinated against hepatitis B:
    • Source known, HBsAg-positive.
    • Source known, HBsAg status unknown.
    • Source unknown.
• Sexual contacts of persons with acute hepatitis B virus infection.
• Household contacts of persons with acute hepatitis B virus infection.

Prevention and Control

Vaccination

High vaccination coverage rates, with subsequent declines in acute hepatitis B incidence, have been achieved among infants and adolescents. In contrast, vaccination coverage among most high-risk adult groups (e.g., persons with more than one sex partner in the previous six months, men who have sex with men, and injection drug users) have remained low, and most new infections occur in these high-risk groups.

Two single-antigen vaccines and three combination vaccines are currently licensed in the United States for prevention of hepatitis B infection.

The Advisory Committee on Immunization Practices (ACIP) recommends that the following persons be vaccinated against hepatitis B:

• All infants.
• Persons aged <19 years.
• Adults aged 19-59 years.
• Adults aged ≥60 years with risk factors for hepatitis B:
  • Persons at risk for infection by sexual exposure.
  • Sex partners of persons testing positive for HBsAg.
  • Sexually active persons who are not in a long-term, mutually monogamous relationship (e.g., persons with more than one sex partner during the previous 6 months).
  • Persons seeking evaluation or treatment for a sexually transmitted infection.
  • Men who have sex with men.
• Persons at risk for infection by percutaneous or mucosal exposure to blood.
  • Persons with current or recent injection drug use.
  • Household contacts of persons testing positive for HBsAg.
  • Residents and staff members of facilities for persons with developmental disabilities.
  • Healthcare and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids.
  • Persons on maintenance dialysis, including incenter or home hemodialysis and peritoneal dialysis, and persons who are predialysis.
  • Persons with diabetes at the discretion of the treating clinician.
• Others.
  • International travelers to countries with high or intermediate levels of endemic hepatitis B virus infection (HBsAg prevalence of ≥2%).
  • Persons with hepatitis C virus infection.
  • Persons with chronic liver disease (including, but not limited to, persons with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase or aspartate aminotransferase level greater than twice the upper limit of normal).
  • Persons with HIV infection.
  • Persons who are incarcerated.
• Adults aged ≥60 years without known risk factors for hepatitis B may receive hepatitis B vaccines.

Hepatitis B vaccination is recommended in certain settings with a high proportion of clients who have known risk factors for HBV infection. The ACIP recommends universal vaccination of adults who receive care in those settings, including:

• Sexually transmitted disease treatment facilities.
• HIV testing and treatment facilities.
• Facilities providing drug-abuse treatment and prevention services.
• Healthcare settings targeting services to injection drug users.
• Correctional facilities.
• Healthcare settings targeting services to men who have sex with men.
• Chronic hemodialysis facilities and end-stage renal disease programs.
• Institutions and nonresidential day care facilities for developmentally disabled persons.

The vaccination schedule most often used for children and adults is three intramuscular injections, the second and third doses administered one to six months, respectively, after the first dose. Alternate schedules have been approved for certain vaccines and/or populations. For more information on vaccination schedules, refer to the following resources:

• Child and Adolescent Immunization Schedules.
• Adult Immunization Schedule.

Anyone who has had a serious allergic reaction to a prior dose of hepatitis B vaccine, a component of the hepatitis B vaccine, or yeast should not receive hepatitis B vaccine.

Historically, routine pre-vaccination testing has not been recommended because it has not generally been found to be cost-effective with regard to vaccination. However, with the availability of antiviral agents to treat chronic HBV infection, new recommendations for identifying persons with chronic HBV infection are being developed. CDC currently recommends that certain populations undergo testing for HBV infection, with serologic assays for HBsAg and anti-HBs, to determine infection or immunity prior to vaccination. The groups include:

• Hemodialysis patients.
• Pregnant women.
• Persons with known or suspected exposure to HBV including:
  • Infants born to HBV-infected mothers.
  • Household contacts of HBV-infected person.
  • Persons with known occupational or other exposures to infectious blood or body fluids.
• Foreign-born persons from countries of high HBV endemicity.
• HIV-positive persons.

Post-vaccination testing or testing for immunity is advised only for person whose subsequent clinical management depends on knowledge of their immune status. This testing should be performed one to two months after completion of the vaccine series and test for anti-HBs. The groups recommended to receive post-vaccination testing include:

• Infants born to HBsAg-positive mothers.
• Healthcare and public safety workers at high risk for continued percutaneous or mucosal exposure to blood or body fluids.
• Chronic hemodialysis patients, HIV-infected persons, and other immunocompromised persons (e.g., hematopoietic stem-cell transplant recipients or person receiving chemotherapy).
• Sex partners of persons with chronic HBV infection.

Studies indicate that immunologic memory remains intact for at least 20 years among healthy vaccinated individuals who initiated hepatitis B vaccination after six months of age. The vaccine confers long-term protection against clinical illness and chronic hepatitis B virus infection. Cellular immunity appears to persist even though antibody levels might become low or decline below detectable levels. Among vaccinated cohorts who initiated hepatitis B vaccination at birth, long-term follow-up studies are ongoing to determine the duration of vaccine-induced immunity. Booster doses of hepatitis B vaccine are not recommended for persons with normal immune status who have been vaccinated. Booster doses are recommended in certain circumstances:

• Hemodialysis patients: the need for booster doses should be assessed by annual testing for anti-HBs. A booster dose should be administered when anti-HBs levels decline to <10 IU/mL.
• Other immunocompromised persons (e.g., HIV-infected persons, hematopoietic stem-cell transplant recipients, and persons receiving chemotherapy): the need for booster doses has not been determined. When anti-HBs levels decline to <10 IU/mL, annual anti-HBs testing and booster doses should be considered for those with an ongoing risk for exposures.

Please refer to the most current Advisory Committee on Immunization Practices (ACIP) recommendations for hepatitis B vaccination.

Comment

Because hepatitis D virus is dependent on hepatitis B virus for replication, hepatitis B virus-hepatitis D virus coinfection can be prevented with either pre- or post-exposure prophylaxis for hepatitis B virus. However, no products exist to prevent hepatitis D virus superinfection of persons with chronic hepatitis B virus infection. Thus, prevention of hepatitis D virus superinfection depends primarily on education to reduce risk behaviors.

Special Information

Questions about reporting, surveillance, and epidemiology for non-perinatal hepatitis B or requests for data should be directed to the ODH Viral Hepatitis Surveillance Program at Hepatitis@odh.ohio.gov or (614) 995-5599.

Questions about the testing, prevention, and control of non-perinatal hepatitis B should be directed to the ODH Viral Hepatitis Prevention Program at Hepatitis@odh.ohio.gov or (614) 995-5599.

Questions about perinatal hepatitis B should be directed to the ODH Perinatal Hepatitis B Prevention Program at (614) 995-5599.

Questions about immunization for hepatitis B should be directed to the ODH Immunization Program at (614) 466-4643 or (800) 282-0546.

The Division of Viral Hepatitis at the Centers for Disease Control and Prevention (CDC) has comprehensive information about viral hepatitis available on their website.