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Chronic Hepatitis B

A brief review of chronic Hepatitis B. An analysis of cause and risk factors, staging and diagnosis, treatment and prevention.

Infectious Disease Term

hepatitis b

InBrief


Hepatitis B virus (HBV), a DNA virus, is the most common cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) worldwide, leading to 0.5- to 1.2-million deaths/year. Approximately 70% of patients infected with HBV have subclinical or anicteric (without jaundice) hepatitis; some 30% develop acute icteric (with jaundice) hepatitis. After symptomatic acute infection, about 90% of infected neonates, 30%-50% of children 1-4 years of age, and 1%-10% (generally < 5%) of adults develop persistent infection. Approximately 15%-40% of patients with persistent infection develop advanced liver disease, cirrhosis, and/or HCC. Overall, > 2-billion persons worldwide have serologic evidence of HBV infection; of these, 300 million are chronic carriers with some form of chronic infection. In the U.S. there are an estimated 1.6 million residents with chronic hepatitis B infections.


Foreign born U.S. residents (especially non-Hispanic Asians) have the highest prevalence. HBV infection is most prevalent in China, sub-Saharan Africa, and parts of the Middle East and Southeast Asia.


Causes and Risk Factors


causes of hepatitis b

HBV is transmitted via percutaneous or mucosal exposure to infected blood or bodily fluids (e.g., saliva, semen). Activities that increase risk of HBV transmission include sexual activity, intravenous drug use, and activities such as tattooing, piercings, acupuncture, medical and dental procedures, medical tourism. Risk of infection increases in unsafe settings or during travel to endemic regions. Other high-risk activity includes working in healthcare, living with any household contacts with HBV, and receiving chronic hemodialysis or blood transfusions. Coinfection with hepatitis-C virus or a history of alcohol abuse worsens the prognosis.


Diagnostic Evaluation


hepatitis b virus dsDNA-RT

The incubation period for HBV infection generally lasts 1-4 months, but may last as long as 6 months. The hallmark of HBV infection is the presence of hepatitis-B surface antigen (HBsAg), the first serologic marker that typically appears 1-10 weeks after an acute exposure. Persistently elevated HBsAg levels after 6 months indicates a chronic infection.


Total Hepatitis-B core antibody (HBcAb or anti-HBc) and hepatitis-B IgM core antibody(IgM anti-HBc) b both appear shortly after the appearance of HBsAg. Anti-HBc may be the only marker of a hepatitis B infection after HBsAg disappears and before hepatitis-B surface antibody (HBsAb or anti-HBs) appears in an improving patient. A positive total anti-HBc on its own is a nonspecific finding and can indicate an acute, chronic, or past resolved HBV infection. If total anti-HBc is the only positive marker, a IgM anti-HBc level should be checked and a negative result most commonly indicates a resolved HBV infection, A positive IgM anti-HBc indicates a recent infection of less than six months, as typically IgM anti-HBc disappears at that time.


In chronic hepatitis-B both the late phase marker hepatitis-B IgG core antibody (IgG anti-HBc), and HBsAg are typically present with no anti-ABs detectable.


In occult infections, low levels of antigen can result in a positive IgG anti-HBc with negative HBsAg levels. PCR for serum HBV DNA may be helpful in diagnosing an occult HBV infection. HBV DNA measures viral load and is detectable usually at one month after infection and disappears at disease resolution. It is detectable in chronic infection at varying levels.


Disappearance of HBsAg and the appearance of anti-HBs and IgG anti-HBc usually indicates recovery from an acute hepatitis B infection.


In patients who have acquired immunity from vaccination, only anti-HBs levels will be present.


Table 1 - Interpretation of Hepatitis B Serologic Test Results


hepatitis b table

Most patients with chronic HBV infection have mild-to-moderate elevation in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. A progression to cirrhosis is suspected when there is evidence of hypersplenism with decreased white blood cell and platelet counts and impaired hepatic function indicated by hypoalbuminemia, prolonged prothrombin time, and hyperbilirubinemia).


Staging

There are four phases of chronic HBV infection:

  1. The immune tolerant high replication phase is characterized by the findings of high HBV DNA serum levels, positive hepatitis B e antigen (HBeAg), and normal ALT levels. In this initial stage there is no evidence of active liver disease. The presence of HBeAg indicates active replication of virus and is associated with a more virulent HBV infection.

  2. In the immune clearance phase, persistence of HBeAg would be associated with chronic liver disease.

  3. In the inactive carrier state, patients are HBeAg-negative and hepatitis B e antibody-postive(HBeAb) and have normal ALT and low serum HBV DNA levels.

  4. In some cases, patients have a reactivation phase, in which they are still HBeAg-negative but have elevated ALT and HBV serum DNA levels, with continued HBV replication and active liver disease.

Some patients do eventually go on to become HBsAg-negative with undetectable HBV DNA levels, indicating complete recovery after chronic infection.


Treatment of Hepatitis B

Medications approved by the FDA for the treatment of chronic hepatitis B include two formulations of interferon (interferon alpha and pegylated interferon) and five nucleoside or nucleotide analogs (lamuvidine, telbivudine, abacavir, entecavir, and tenofovir).


Prevention of Hepatitis B

For prevention of HBV infection, recombinant HBV vaccine (thimerosal-free Engerix-B and Recombivax-HB) is usually given at 0, 1, and 6 months. One dose may be given just before a short travel; the second dose may be given at 1 month upon return. Alternatively, an accelerated schedule involving immunization on days 0, 7, and 21 (with a booster at 12 months) is recommended for higher risk travel necessitating more rapid and confident protection. Some 5%-10% of people do not respond to currently available vaccines. In 2008, the estimated global coverage rate of HBV vaccination in infants was 69%. In 2020, the estimated global coverage with three doses of hepatitis B vaccine was 83%, but only 42% of infants received their first dose at birth.

 

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References:

Johnson DF, Leder K, Torresi J. Hepatitis B and C infection in international travelers. J Travel Med. 2013;20:194-202.


Williamson MA, Snyder LA, eds. Wallach's Interpretation of Diagnostic Tests. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.


Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Medical; 2009.


Lim JK, Nguyen M, Kim W, Gish R, Perumalswami P, Jacobson I. Prevalence of Chronic Hepatitis B Virus Infection in the United States. The American Journal of Gastroenterology. 2020; 115,9:1429-1438. doi: 10.14309/ajg.0000000000000651


Heiberg IL, Hoegh M, Ladelund S, Niesters H, Hogh B. Hepatitis B Virus DNA in Saliva from Children with Chronic Hepatitis B Infection. Implications for Saliva as a Potential Mode of Horizontal Transmission. The Pediatric Infectious Disease Journal. 2010; 29,5:465-467. doi: 10.1097/INF.0b013e3181d8e009


Song JE, Kim DY. Diagnosis of Hepatitis B. Ann. Transl. Med. 2016;4(18):338. Doi. 10.21037/atm.2016.09.11


Global Viral Hepatitis: Millions of People are Affected | CDC Page last reviewed: July 19, 2021 Content source: Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention https://www.cdc.gov › hepatitis › global


Pockros P, Mulgaonkar A. Cessation of Nucleoside/Nucleotide Analogue Therapy in Chronic Hepatitis B HBeAg-Negative Patients. Gastroenterology & Hepatology. 2022;18,(6).


Updated CDC Recommendations for the Management of Hepatitis B Virus–Infected Health-Care Providers and Students. MMWR Morbidity and Mortality Weekly Report. July 6, 2012. Retrieved from: https://www.cdc.gov/mmwr/pdf/rr/rr6103.pdf


[Table 1] Interpretation of Hepatitis B Serologic Test Results, CDC, 2005. Retrieved from: https://www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf


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