Deciding on the Best Treatment in Patients With Various Types of Hepatitis B

Rowen K. Zetterman, MD


April 19, 2016

In This Article

The Impact of Hepatitis B

There are an estimated 350 million hepatitis B virus (HBV) carriers worldwide,[1] resulting in 600,000 deaths annually due to complications of chronic hepatitis B.[2] Up to 560,000 new cases of hepatocellular carcinoma develop annually,[3] many associated with HBV. Overall, one half of all liver cancer mortality globally is a consequence of HBV.[4]

Approximately 0.3% of persons living in the United States (850,000 persons) have chronic HBV infection. HBV is two- to threefold greater among non-Hispanic black persons than in the general population, and it is present in 3.1% of non-Hispanic Asian persons.[5] Some estimates of disease prevalence suggest that when recent immigrants to the United States are included, there may be 2.2 million persons domestically with chronic hepatitis B.[6]

Roughly one half of all US ambulatory care visits for chronic liver disease care are due to either HBV or hepatitis C virus (HCV)-related disease.[7] Studies indicate that the identification and treatment of patients with chronic hepatitis B can reduce such complications as cirrhosis and hepatocellular carcinoma, and suggest that screening of at-risk persons must be considered. It is recommended that the following groups undergo screening for HBV[8]:

  • Persons born in high-risk areas for HBV infection;

  • Persons with multiple sexual partners;

  • Persons with current or past intravenous drug use;

  • Persons infected with HIV or HCV;

  • Spouses and household contacts of HBV-infected persons;

  • Persons who have had sexual contact with HBV-infected persons; and

  • High-risk persons who will require chemotherapy or immunosuppression.

Once adult patients with HBV are identified, use of the latest recommendations to guide treatment decisions is necessary. This review in particular will discuss the recommendations from the American Association for the Study of Liver Diseases (AASLD)[9] and the World Health Organization (WHO).[10] However, review of the treatment algorithms for adults from the Asian Pacific Association for the Study of the Liver[11] and for children from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition[12] is also recommended.

Pathology and Transmission

HBV is a double-stranded DNA hepadnavirus with a high mutation rate. The precore mutation is most common and results in hepatitis B envelope antigen (HBeAg)-negative disease with continued viral replication. Basal core promoter mutations also occur. Ten or more genotypes of HBV are known to exist.[13]

HBV is parenterally transmitted through contact of the newborn with his or her HBV-carrier mother and by sexual or blood-borne contact, such as sharing of needles, dialysis, and transfusion. Whether a person infected by HBV becomes a carrier of the virus depends in part on their age at acquisition.[14] Among those infected as a neonate, up to 95% will become HBV carriers. The risk for virus transmission from mother to child depends on the maternal level of circulating HBV and is more likely when it is > 107 copies/mL.[15] Thirty percent of children who become infected between 1 and 5 years of age with HBV become carriers, compared with 5% of infected adults.

Many adults with untreated immune-active chronic hepatitis B and elevated alanine aminotransferase (ALT) and circulating HBV DNA levels will develop cirrhosis.[16] Hepatocellular carcinoma is more likely in persons with continued elevation of the HBV DNA level (>2000 IU/mL) who are also HBeAg-positive and have associated cirrhosis.[17] Other factors that increase the risk for hepatocellular carcinoma in chronic hepatitis B include cigarette smoking, obesity, and alcohol use. Of adults with inactive chronic hepatitis B, 0.5% will lose hepatitis B surface antigen (HBsAg) annually.[9]

Vaccination Strategies

Vaccination for HBV reduces the risk for infection.[18] HBV vaccines have been available since 1981, and the number of Americans with evidence of prior vaccination continues to increase.[5] The routine vaccination of neonates, other unvaccinated children, and those at high risk for HBV infection is a crucial step to reduce infection and carrier rates.

HBV vaccination is recommended for the following[14]:

  • Newborns of mothers with chronic hepatitis B

  • All children

  • Those at high risk:

    • Healthcare workers

    • Those with contact with HBV carriers

    • Those with multiple sexual partners

    • Men who have sex with men

    • Injection-drug users

    • Dialysis patients

    • Institutionalized persons

Up to 95% of vaccinated adults will have an adequate antibody response to the vaccine.

The current WHO guidelines[10] do not recommend vaccine boosters for previously vaccinated adults. Rather, vaccinated patients who lack antibody to HBV after a high-risk HBV exposure should receive a dose each of vaccine and high-titer antibody to hepatitis B surface antigen (anti-HBs).

Evaluation of Newly Recognized Patients

A thorough history should be obtained that includes sexual practices, prior transfusions and operations, occupation, such habits as smoking and alcohol use, and determination of any family history of liver disease. A physical examination is also needed.

Laboratory studies should include hepatitis B testing (HBsAg, HBV DNA, HBeAg, antibody to hepatitis B core antigen [anti-HBc], and antibody to hepatitis B e antigen [anti-HBe]), HCV antibody, HIV antibody, liver enzymes, albumin, complete blood count, platelet count, and international normalized ratio. Identification of isolated immunoglobulin G (IgG) anti-HBc may be indicative of prior HBV infection. This finding may also identify a patient at risk for chronic hepatitis B reactivation after immunosuppression or chemotherapy. Some IgG anti-HBc–positive persons may have detectable HBV DNA in their liver or serum.[19]

Ultrasound of the liver can screen for hepatocellular carcinoma; identify complications of cirrhosis, such as ascites; and provide an initial assessment of possible hepatic fibrosis or cirrhosis.

Stages of Infection

HBV is not directly cytopathic, and liver injury is a consequence of the immune response to the virus by infected hepatocytes. An immune response to the virus may be the cause of fulminant hepatitis B, and a suboptimal T-cell response the cause of chronic B infection.[20] Whether the infected person can clear the virus depends in part on their age (and thus their immune status) when they became infected. The majority of adults will have anicteric hepatitis and clear the virus.

Three phases of chronic HBV infection are observed: immune-tolerant, immune-active, and inactive chronic hepatitis B. Patients may progress from one stage to the next or revert back to a former stage. Perinatal infection often results in immune-tolerant chronic hepatitis B, with progression to immune-active disease at a point later in life. Adults who fail to clear HBV may develop immune-tolerant or immune-active hepatitis B, eventually ending up with inactive chronic hepatitis. Those with inactive disease may return to an immune-active phase after immunosuppression, chemotherapy, or a spontaneous flare.


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