Diagnosis of Hepatitis B Infection: A Comprehensive Guide

Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV). A significant challenge in combating hepatitis B is that over half of those infected are unaware they carry the virus. Furthermore, a large proportion, between 50% and 70%, of individuals with acute hepatitis B experience no noticeable symptoms. This lack of awareness and often asymptomatic nature underscores the critical importance of testing to identify and manage HBV infection, preventing its silent spread.

Chronic HBV infection, if left undetected and untreated, can lead to severe liver disease, including cirrhosis and liver cancer, and ultimately, death. However, reliable and cost-effective screening tests are available to detect chronic HBV infection long before these serious complications develop. Early diagnosis, coupled with routine monitoring and appropriate treatment, significantly reduces the risk of morbidity and mortality associated with chronic HBV infection. Beyond individual health benefits, effective management of chronic hepatitis B through prevention strategies is crucial to curtail further transmission within communities.

For individuals seeking general information about hepatitis B testing, resources are readily available online, such as dedicated hepatitis B testing information pages. These resources complement clinical guidance aimed at healthcare professionals to ensure broad access to vital information.

Deciding When to Test or Screen for Hepatitis B

It’s important to distinguish between hepatitis B screening and testing, although both involve serologic blood tests. Screening typically refers to testing asymptomatic individuals who are not known to be at high risk for HBV exposure. The goal of screening is to identify undiagnosed infections in the general population. Testing, on the other hand, is conducted on individuals who present with symptoms suggestive of hepatitis or who are known to be at increased risk of HBV exposure. Testing is diagnostic, aimed at confirming or ruling out HBV infection in those with clinical suspicion or risk factors.

Recommendations for Hepatitis B Screening and Testing:

Adults:

The Centers for Disease Control and Prevention (CDC) recommends universal hepatitis B screening for all adults aged 18 years and older at least once in their lifetime. This screening should be performed using a triple panel test (explained in detail later). To maximize testing accessibility, HBV testing should be offered to anyone who requests it, regardless of whether they disclose specific risk factors. This is crucial because many individuals may be hesitant to reveal stigmatizing risk behaviors.

Infants:

Universal infant testing is also recommended. All infants born to mothers who are positive for hepatitis B surface antigen (HBsAg) should be tested for both HBsAg and antibody to hepatitis B surface antigen (anti-HBs). This testing helps determine if the infant has acquired HBV infection and if they have developed protective antibodies, typically following vaccination.

Pregnant Women:

Screening pregnant women is a cornerstone of HBV prevention. The CDC recommends hepatitis B screening for all pregnant women during each pregnancy, ideally during the first trimester. This recommendation holds regardless of their vaccination status or prior testing history. For pregnant women with a documented history of appropriately timed triple panel screening and no new HBV exposure risks since that screening, only HBsAg screening is necessary.

Identifying People at Increased Risk for Hepatitis B

Beyond universal screening recommendations, targeted testing is essential for individuals at increased risk of HBV infection. These individuals should be tested periodically, regardless of age, as long as their risk factors persist. At-risk populations include:

• Individuals with a history of sexually transmitted infections (STIs) or multiple sexual partners: Unprotected sexual contact is a significant route of HBV transmission.
• People with a history of past or current hepatitis C virus (HCV) infection: Co-infection with HBV and HCV is not uncommon, and individuals with one viral hepatitis infection are at risk for others.
• People incarcerated or formerly incarcerated in correctional facilities: Prisons and jails can be settings with higher HBV transmission rates due to various factors.
• Infants born to HBsAg-positive mothers: Vertical transmission from mother to child is a major concern if not properly managed with infant vaccination and immunoglobin.
• People born in regions with high HBV prevalence (≥2%): Certain geographic regions have a higher endemicity of HBV, increasing risk for individuals born there. These regions include parts of Asia, Africa, Eastern Europe, and South America.
• US-born individuals not vaccinated as infants whose parents were born in high HBsAg prevalence regions (≥8%): This addresses the risk within families where HBV may be prevalent in the older generation from high-prevalence regions.
• People who inject drugs (PWID) or have a history of injection drug use: Sharing needles and injection equipment is a high-risk behavior for HBV transmission.
• People with human immunodeficiency virus (HIV) infection: HIV co-infection increases the risk of chronic HBV and liver disease progression.
• Men who have sex with men (MSM): MSM are at increased risk due to sexual transmission routes.
• Household contacts or former household contacts of individuals with known HBV infection: Close household contact can facilitate HBV transmission.
• People who have shared needles with or had sexual contact with individuals known to have HBV infection: Direct exposure to HBV through these routes necessitates testing.
• People on maintenance dialysis: Dialysis patients are at risk due to potential exposures in healthcare settings and the need for frequent vascular access procedures.
• People with elevated liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]): Unexplained elevated liver enzymes can be an indicator of underlying liver disease, including viral hepatitis.

“Susceptible people” in this context are those who have never been infected with HBV and have either not completed a full hepatitis B vaccine series or are known to be non-responders to the vaccine.

Recommended Hepatitis B Tests: The Triple Panel

The CDC now recommends the triple panel test as the preferred initial screening and diagnostic test for hepatitis B. This comprehensive panel includes testing for three key serologic markers:

1. Hepatitis B surface antigen (HBsAg): HBsAg is a protein found on the surface of the HBV virus. Its presence indicates current HBV infection, whether acute or chronic.
2. Antibody to hepatitis B surface antigen (anti-HBs): Anti-HBs is an antibody produced by the body in response to HBV surface antigen. Its presence usually indicates immunity to HBV, either from prior infection and recovery or from successful vaccination.
3. Total antibody to hepatitis B core antigen (total anti-HBc): Anti-HBc is an antibody to the hepatitis B core antigen. Its presence indicates past or present HBV infection. Unlike anti-HBs which can be vaccine-induced, anti-HBc only develops following actual HBV infection.

For any follow-up testing after the initial triple panel, the specific tests used will depend on the initial results and the clinical situation. Previously, guidance recommended a single test for HBsAg, but the triple panel provides a more complete picture of a person’s HBV status.

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Alt text: Flowchart depicting the integration of Hepatitis B Virus (HBV) screening and testing into typical clinic workflows, starting with patient encounters and branching through screening, testing, result interpretation, and appropriate clinical actions such as vaccination, care linkage, and reporting.

Interpreting Hepatitis B Test Results: Serologic Markers and Their Meaning

Different combinations of hepatitis B serologic markers are used to differentiate between various stages of HBV infection, determine immunity status, and identify susceptibility to infection. Understanding these markers is crucial for accurate diagnosis and clinical management.

• Hepatitis B surface antigen (HBsAg): As mentioned, HBsAg indicates current infection. It is detectable in the blood during both acute and chronic HBV infection. A positive HBsAg test means the person is infectious and can transmit the virus to others. However, it’s important to note that HBsAg can be transiently positive within 30 days after hepatitis B vaccination. HBsAg is also the antigen used in the hepatitis B vaccine to stimulate antibody production.

• Antibody to hepatitis B surface antigen (anti-HBs): The presence of anti-HBs generally signifies recovery from HBV infection and subsequent immunity. It also develops after successful hepatitis B vaccination, indicating vaccine-induced immunity. While anti-HBs levels may decline over time in vaccine responders, most individuals retain long-term immunity and will mount an immune response upon HBV exposure.

• Total antibody to hepatitis B core antigen (total anti-HBc): Anti-HBc appears at the onset of symptoms in acute hepatitis B and persists for life. It detects both IgM and IgG antibodies to the core antigen. Total anti-HBc indicates past or present HBV infection but does not differentiate between resolved, chronic, or acute infection. Importantly, anti-HBc is not produced in response to hepatitis B vaccination; its presence always indicates exposure to the virus itself.

• IgM antibody to hepatitis B core antigen (IgM anti-HBc): IgM anti-HBc is specifically indicative of recent, acute HBV infection, typically within the last six months. It is ordered when acute HBV infection is suspected. IgM anti-HBc positivity points to acute infection. However, it’s worth noting that IgM anti-HBc can sometimes be positive in chronic HBV infection during flares or reactivation episodes.

Hepatitis B Serologic Test Result Interpretation and Actions:

| Test outcome | Interpretation | Action