Viral Hepatitis

Overview

For hepatitis B

• Clinicians should screen all untested newly arriving refugees for hepatitis B virus (HBV).
• Specifically screen adults 18 and older, pregnant women during every pregnancy, and children.
• To evaluate immune status, clinicians should test for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and total antibody to hepatitis B core antigen (total anti-HBc)

For hepatitis D

• CDC does not recommend routine screening for hepatitis D virus (HDV), but clinicians should test for HDV in patients who are HBsAg-positive.

For hepatitis C

• Clinicians should screen all untested newly arriving adult refugees 18 and older, all pregnant women during every pregnancy, and children with risk factors for hepatitis C virus (HCV) infection.

For hepatitis A or hepatitis E

• CDC does not recommend routine screening for hepatitis A virus (HAV) or hepatitis E virus (HEV) infection. Clinicians should test only in those who have symptoms of acute hepatitis.

Background

Hepatitis is inflammation of the liver. It can result from infectious or noninfectious causes. Many viral infections can cause liver inflammation, but the term viral hepatitis usually refers to infections with one of the five hepatotropic viruses that target the human liver: HAV, HBV, HCV, HDV, and HEV.

Infections caused by these viruses can have different incubation periods, routes of transmission, geographic and demographic distribution, patterns of clinical presentation, and propensity for becoming chronic disease. As a result, prevention strategies and approaches to clinical management vary.

All types of viral hepatitis can cause illness during acute infection (2 weeks to 6 months following exposure). HAV and HEV infection predominantly cause acute hepatitis; but HBV and HCV infection can also cause chronic hepatitis. Although acute viral hepatitis can be severe or fatal, acute HBV and HCV infections are often asymptomatic and silently damage the liver. Untreated HBV and HCV infections result in a high disease burden and are leading causes of cirrhosis (late-stage scarring of the liver) and hepatocellular carcinoma (HCC) (liver cancer) in the United States and globally1. Because chronic HBV and HCV infections are often asymptomatic and many refugees come from settings where these viruses are endemic, clinicians should consider these infections during domestic medical screening for newly arrived refugees.

For additional information on viral hepatitis, see the CDC Viral Hepatitis webpage. For information on hepatitis A and hepatitis B vaccination, see the CDC Refugee Health Domestic Guidance: Immunizations webpage.

This guidance adapts CDC's viral hepatitis guidance for healthcare providers in the United States who conduct the initial medical screening for refugees.

Overseas Pre-Departure Screening and Vaccination

Refugees from participating overseas locations may be eligible to receive up to two doses of hepatitis B vaccine before resettlement in the United States through the Vaccination Program for US-bound Refugees. Prior to administering hepatitis B vaccine to eligible refugees who choose to participate in the pre-departure vaccination program, clinicians screen these refugees for hepatitis B infection using a test for hepatitis B surface antigen (HBsAg). Refugees who test positive for HBsAg do not receive hepatitis B vaccination overseas. Instead, they are counseled on infection and methods to prevent transmission. Refugees who test negative for HBsAg may receive up to two doses of hepatitis B vaccine to initiate or continue the series. HBsAg results are documented on the DS-3026 (Medical History and Physical Examination Worksheet). Vaccines received through this program are documented on the DS-3025 (Vaccination Documentation Worksheet). These records are available to state health departments through the Electronic Disease Notification (EDN) system.

Household contacts of HBsAg-positive people who test negative for HBsAg may receive a third hepatitis B vaccine dose overseas to complete the series, if time allows. Clinicians should be aware that the dose may be given close to departure time, and HBsAg testing results may be falsely positive during the first month after vaccination. Clinicians should consider waiting at least 30 days after vaccination before testing for HBsAg in these refugees.

Domestic Testing and Clinical Management

Hepatitis B Virus (HBV)

Chronic HBV infection is defined as having HBsAg positivity for at least 6 months and is a major cause of preventable morbidity and mortality2. In 2024, an estimated 240 million people were living with chronic HBV infection worldwide and the disease caused nearly 1.1 million deaths globally, mostly from cirrhosis and HCC3.

Background

HBV infection prevalence and transmission patterns vary across countries and populations. Many refugees arrive from countries in which the prevalence of HBV infection is high. Currently, the burden of HBV infection is concentrated in two regions: the Western Pacific Region and the African Region which together accounted for 70% of the global number of people living with a chronic HBV infection in 20243.

In highly endemic regions where routine immunization has not been implemented, most new infections occur in infants and young children, usually due to perinatal or household transmission.

The sequelae of chronic HBV vary by age at time of infection. Infection during infancy or childhood is associated with a higher likelihood of progression to chronic infection. Without early diagnosis and management, chronic HBV infection can progress to chronic liver disease, including cirrhosis, HCC, and extrahepatic manifestations, such as glomerulonephritis.

Chronic HBV infection is often asymptomatic, but people with chronic infection can still transmit HBV to others. Common modes of HBV transmission include perinatal exposure, sexual contact, and needle sharing. Transmission can also occur within households.

The domestic medical examination (DME) is an opportunity to identify HBV infection in resettling refugees, decreasing the risk of morbidity and mortality and preventing transmission to family members and other close contacts.

CDC's Division of Viral Hepatitis provides more details on HBV prevention and screening.

Testing for HBV Infection

Most refugees resettling to the United States come from or have lived in countries with intermediate or high hepatitis B endemicity. The serologic patterns of HBV infection are complex, and a full discussion is beyond the scope of this document. For detailed information on HBV infection and interpretation of hepatitis B serologic markers, please refer to the CDC Clinical Testing and Diagnosis for Hepatitis B webpage.

The serologic markers most widely used in diagnosis of acute, chronic, and resolved HBV infection include HBV surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and total antibody to hepatitis B core antigen (total anti-HBc)45. Table 1 outlines the typical interpretation of hepatitis B serology.

Table 1. Hepatitis B Serologic Marker Interpretation and Initial Management

Screening Recommendations for Chronic HBV Infection in Refugees

In accordance with national screening recommendations, clinicians should screen all newly arriving refugees, if not previously tested4Most refugees receive HBsAg testing before departure for the United States. Review overseas records for pre-departure testing for infection and vaccination and to determine if further management is needed.

Adults

• If the refugee was not tested for HBV infection overseas, test for HBsAg, total anti-HBc, and anti-HBs
• If the refugee was tested for HBV infection overseas, follow the guidance (below) for management:
  • If positive for HBV infection (HBsAg-positive), then conduct additional evaluation and offer treatment options or refer to a specialist for evaluation and treatment.
  • If negative for HBV infection (HBsAg-negative), and the refugee has documentation of completion of hepatitis B vaccinations at appropriate intervals before arrival, no further testing or vaccination is necessary. *
  • If negative for HBV infection (HBsAg-negative), and the refugee has received no previous (documented) doses of vaccine, then test the refugee for immunity by serology with total anti-HBc, and anti-HBs. Vaccination with the hepatitis B vaccine series can be started while awaiting serologic test results. If serologic testing is negative, complete the vaccination series. If serology for both anti-HBc and anti-HBs are positive, then no further vaccine doses are needed.

*In refugees with high risk of exposure since the initial screen or high risk of future exposure, consider serology to confirm immunity.

Pregnant Women

Screen all pregnant women during each pregnancy, preferably in the first trimester. Screen regardless of vaccination status or prior testing history.

Pregnant women with a history of appropriately timed triple panel screening (HBsAg, total anti-HBc, and anti-HBs) and no subsequent HBV exposure risk only need HBsAg screening.

Children and Adolescents

• If the refugee was not tested for HBV infection overseas, test for HBsAg, total anti-HBc, and anti-HBs
• If the refugee was tested for HBV infection overseas, follow the guidance (below) for management:
  • If positive for HBV infection (HBsAg-reactive), then conduct additional evaluation and offer treatment options or refer to a specialist for evaluation and treatment
  • If negative for HBV infection (HBsAg-negative), and the overseas health records confirm completion of hepatitis B vaccinations at appropriate intervals before arrival, no further testing or vaccination is necessary. *
  • If negative for HBV infection (HBsAg-negative), and the vaccination series has been initiated, complete the series according to the Advisory Committee on Immunization Practices schedule.
  • Infants and children born to women with HBV infection or whose HBsAg status is unknown, should receive postvaccination serologic testing (hepatitis B surface antigen and antibody to hepatitis B surface antigen) at 9–12 months of age, at least 1-2 months after vaccine series completion. If the vaccine series is delayed, postvaccination serologic testing should be performed 1–2 months after vaccine series completion. Serologic testing identifies whether the child has developed an adequate immune response to the hepatitis B vaccine series or has been infected with HBV.

High-Risk Groups

High-risk groups for exposure to HBV include5:

• People who use injection drugs
• Men who have sex with men
• People who need immunosuppressive therapy, including chemotherapy, immunosuppression related to organ transplantation, or immunosuppression for rheumatologic or gastroenterological disorders
• People with elevated liver enzymes (alanine aminotransferase [ALT] ≥19 IU/L for women and ≥30 IU/L for men or abnormal aspartate aminotransferase [AST]) of unknown etiology
• People who need hemodialysis
• Household members, people who share needles with or are sexual contacts of people who are HBsAg positive
• People who are at risk for exposure to blood or body fluids and may require postexposure prophylaxis (e.g., needlestick, sexual assault)
• People who have a history of sexual exploitation, including child marriage
• People with human immunodeficiency virus (HIV) infection
• People infected with hepatitis C virus
• People who are or have been incarcerated (although unlikely among newly arrived refugees)
• Children whose mothers have a history of HBV infection or cleared infection

Note: Tattooing is common in some refugee groups. Tattooing in non-commercial or unlicensed facilities may increase risk for exposure to HBV. However, definitive data are lacking.

Clinical and Public Health Management of People with HBV Infection

Clinicians should refer all refugees who are HBsAg-positive to a gastroenterologist and/or hepatologist for assessment of disease stage, screening for sequelae of chronic HBV infection (including HCC), and development of a long-term management plan. The initial follow-up evaluation usually includes testing for HBV DNA, hepatitis B e antigen (HBeAg), ALT levels, and liver fibrosis stage.

Clinicians typically provide supportive care for acute HBV infection. For patients with chronic HBV infection, several antiviral medications are available, but not every person with chronic HBV infection will need medication. For detailed management, clinicians should refer to the American Association for the Study of Liver Diseases (AASLD))6.

Refugees who are HBsAg-positive should be considered infectious. Hepatitis B is a reportable disease; therefore, cases should be reported to the state or local health department, according to state reporting requirements.

Clinicians should provide HBsAg-positive refugees with counseling about the infection and ways to reduce transmission. They should also discuss lifestyle modifications and provide culturally sensitive education materials in the refugee's primary language. Translated resources are available from the CDC Division of Viral Hepatitis. Educational materials for HBV infection developed by other agencies may be found at:

• The Refugee Patient Education Project of CNY

• Minnesota Center of Excellence in Newcomer Health - MN Dept. of Health

Clinicians should counsel patients on the need for lifelong HCC screening. Hepatic ultrasound and labs are generally recommended every 6 months, consistent with the AASLD guidelines.

Hepatitis D Virus (HDV)

Hepatitis D virus (HDV) is a deficient virus that requires HBsAg protein to establish infection. Therefore, HDV infection only occurs in HBsAg-positive people. HDV may be acquired as a co-infection with HBV or as a superinfection after HBV infection. Hepatitis B vaccination is a primary preventive measure that protects against HDV infection.

Background

Data on the epidemiology of HDV are limited789. Studies show high HDV infection prevalence in several geographical areas, including Mongolia, the Republic of Moldova, and countries in western and central Africa8.

People with chronic HBV infection who have superinfection with HDV typically develop chronic HDV infection. Chronic HDV infection is associated with severe hepatitis, and frequently leads to rapid cirrhosis progression, hepatic decompensation, and HCC78. For more information, review:

• Pathogenesis of and new therapies for hepatitis D (Koh C, Heller T, Glenn JS. Gastroenterology. 2019;156(2):461–476.e1)
• Hepatitis D: a review (Negro F, Lok AS. JAMA. 2023;330(24):2376-2387)

Screening Recommendations for HDV Infection in Refugees

• CDC does not recommend routine HDV screening for all new arrivals.
• Clinicians should test all HBsAg-positive new arrivals for HDV infection, regardless of the presence of risk factors (i.e., HIV infection, intravenous drug use, men who have sex with men)10.
• Clinicians should test for HDV infection with a serological assay to detect total antibody to HDV (anti-HDV) with reflex to nucleic acid testing for HDV RNA (if available)10.
• Clinicians should refer refugees who test positive for HDV RNA to a specialist for further evaluation, including grading and staging of liver disease, surveillance for HCC, and antiviral treatment.
• Chronic HDV infection is challenging to treat, and detailed management is beyond the scope of this document. For guidance refer to the AASLD/IDSA Practice Guideline on Treatment of Chronic Hepatitis B.

Hepatitis C Virus (HCV)

Hepatitis C virus (HCV) infection can progress to chronic viral hepatitis that can eventually result in cirrhosis and HCC. The prevalence of HCV infection varies between regions and countries, and it is estimated that 50 million people worldwide have chronic HCV infection11.

Background

Data on HCV prevalence among newcomers to the United States are limited. A study of 64,703 newcomers to the United States (2010–2017) found that 1.6% of all newcomers and 2% of adult newcomers (18 and older) screened positive for HCV antibodies (have been exposed to HCV) during initial domestic medical screening12. Similarly, a study of new arrivals to the U.S. (2014–2016) reported that 2.3% of adults (18 and older) and 0.7% of children (younger than 18) screened positive for HCV antibodies13.

Without treatment, approximately 30% (range 15-45%) of HCV-infected people spontaneously clear the virus within 6 months of infection. However, 70% (range 55-85%) of HCV-infected people will develop chronic infection11.

HCV is transmitted through exposure to infected blood or other body fluids that contain blood. In developed countries, infection primarily results from injection drug use. In developing countries or lower-resource settings, HCV is predominantly transmitted in medical settings during reuse of needles or surgical equipment or through transfusions with infected blood products. Sexual contact is considered a less common route of transmission14. Perinatal transmission occurs in 6% - 7% of pregnancies in which the mother is HCV infected15, but there is no evidence that breastfeeding spreads HCV16.

Screening Recommendations for Chronic HCV Infection in Refugees

In accordance with national screening recommendations, all newly arriving adult refugees age ≥18 years should be screened for hepatitis C, if not previously tested14. All pregnant women should be screened for HCV infection during every pregnancy.

Adults

• Clinicians should screen all adult (18 and older) refugees for HCV infection with a test for antibody to HCV (anti-HCV) with reflex to nucleic acid testing (NAT) for detection of HCV ribonucleic acid (RNA) when the antibody test is positive17.
• Clinicians should refer refugees who test positive for HCV RNA to a specialist for further evaluation, including grading and staging of liver disease, surveillance for HCC, and curative treatment.

For additional guidance on the screening and management of HCV infection, refer to the CDC's webpage: Clinical Overview of Hepatitis C.

Pregnant Women

• Clinicians should test all pregnant women for HCV infection during each pregnancy. Testing should occur during an early prenatal visit.
• Clinicians can consider repeat testing later in pregnancy for pregnant women with ongoing risk factors (e.g., injection-drug use) (see CDC: Screening and Testing for HIV, Viral Hepatitis, STD & Tuberculosis in Pregnancy | Pregnancy and HIV, Viral Hepatitis, STDs, & Tuberculosis Prevention | CDC.

Children and Adolescents

CDC does not recommend universal HCV screening for refugee children less than 18 years of age during the DME unless they are members of high-risk groups, which include:

• Perinatally exposed infants and children: Infants and children born to women with known or probable HCV infection or whose HCV infection status is unknown.
  • Infants should receive a NAT for HCV RNA at 2- 6 months to identify those in whom chronic HCV infection might develop if not treated.
  • Infants and children aged 7–17 months who have not previously been tested should receive a NAT for HCV RNA.
  • Children aged ≥18 months who have not previously been tested should receive an anti-HCV test with reflex to NAT for HCV RNA.
  • Infants with detectable HCV RNA should be managed in consultation with a health care provider with expertise in pediatric hepatitis C management.
  • Infants with an undetectable HCV RNA result do not require further follow-up unless clinically warranted. (see CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children — United States, 2023)15.
• Unaccompanied refugee minors
• Children with risk factors including but not limited to:
  • Injection or intranasal drug use (current or former)
  • Chronic hemodialysis
  • HIV infection
  • Signs or symptoms of liver disease (e.g., abnormal liver enzyme tests, jaundice, abdominal pain or swelling, fatigue)
  • Household contacts with HCV infection
  • History of female genital mutilation or cutting (FGM/C). Data on the association between FGM/C and hepatitis C virus infection are limited. In surveys of Egyptian men and women aged 15-59 (n=12,780), researchers found that FGM/C was an independent risk factor for HCV infection1819.

Refugee populations may have other risk factors, including traditional tattooing.

Clinical and Public Health Management of Chronic HCV Infection

In accordance with AASLD/IDSA clinical practice guidelines for simplified treatment, clinicians should refer refugees who are currently infected (HCV RNA-positive) to a healthcare primary care provider or specialist experienced in the management of chronic liver disease. Clinicians should counsel refugees with HCV infection on preventing HCV transmission, using culturally appropriate methods and educational materials in the refugee's primary language, when possible.

Refugees with HCV infection benefit from evaluation and education about liver disease, including HCC. Patients at higher risk for HCC include those with cirrhosis; hepatic steatosis (fatty liver); heavy alcohol consumption (>7 drinks/week for women or >14 drinks/week for men); and HBV, HDV, or HIV co-infections. In addition, patients should be offered vaccination for hepatitis A and hepatitis B (if appropriate) and treatment with antiviral therapy. Treatment and ongoing care recommendations are beyond the scope of this document. Clinicians should refer to the current AASLD guidelines for additional information.

See the CDC Clinical Screening and Diagnosis for Hepatitis C webpage for additional information on testing and clinical management of HCV infection.

Hepatitis A Virus

HAV infection is common in low- and middle-income countries with poor sanitary conditions and hygiene20. HAV is primarily transmitted via the fecal-oral route, and the average incubation period for HAV is 28 days (range: 15–50 days)21.

Background

In regions with high HAV endemicity, people are often infected as children, and adults may have immunity due to prior infection. Infection provides lifelong protection and does not lead to chronic disease. Hepatitis A prevalence is decreasing in the U.S. and globally, especially in areas with improved hygiene, sanitation, and routine vaccination2223.

Acute HAV infection in adults usually presents with fatigue, anorexia (poor appetite), abdominal pain, nausea, and jaundice. For most adults, signs and symptoms resolve within 2 months. However, fulminant hepatitis can cause severe illness and death. Severe disease can occur commonly in people with underlying chronic liver disease.

Young children infected with HAV typically have sub-clinical infection, but they can remain infectious for several months and can be a major source of sustained transmission within communities. Additional information on HAV infection is available from the CDC Division of Viral Hepatitis.

Screening Recommendations for HAV Infection in Refugees

• CDC does not recommend routine HAV screening for new arrivals.
• Clinicians should evaluate refugees with signs or symptoms of acute HAV infection by testing serum for IgM antibodies to HAV (anti-HAV IgM) or HAV RNA in serum or stool (see CDC's Clinical Screening and Diagnosis for Hepatitis A).
• Clinicians should also test refugees with signs or symptoms of acute HAV infection for HBV, HCV, and HEV infection because these infections can present similarly to HAV infection. It is rare to encounter a refugee with clinically active HAV infection on arrival.

Hepatitis E Virus (HEV)

HEV infection can be found in all parts of the world. HEV infection causes acute viral hepatitis and is transmitted by the fecal-oral route, primarily through contaminated water. The average incubation period ranges from 2 to 10 weeks, with an average of 5 to 6 weeks.

Background

HEV infection causes significant global burden of acute hepatitis, with an estimated 20 million cases and 4,431 deaths in 202324. It occurs most commonly in sub-Saharan Africa and east and south Asia. Most infections are self-limited, but some can progress to fulminant hepatitis.

Acute HEV infection in adults usually presents with mild fever, anorexia, nausea, and vomiting. Abdominal pain and jaundice are also common symptoms. HEV infection is typically a self-limited disease, but fatalities associated with infection can occur. HEV infection is particularly virulent in pregnant women, especially those infected during the third trimester, and maternal mortality rates may exceed 20%24.

Acute HEV infection in children is typically asymptomatic, but some children experience mild illness, usually without jaundice. Additional information on HEV infection is available from the CDC Division of Viral Hepatitis.

Screening Recommendations for HEV Infection in Refugees

• CDC does not recommend routine HEV screening for new arrivals.
• Clinicians should evaluate refugees with signs or symptoms of acute HEV infection by testing serum for IgM antibodies to HEV (anti-HEV IgM) or HEV RNA in serum or stool. Additional information on HEV infection is available on the World Health Organization Hepatitis E webpage.
• Clinicians should also test refugees with signs or symptoms of acute HEV infection for HAV, HBV, and HCV infection because these infections can present similarly to HEV infection.