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Hepatitis B


Hepatitis B virus (HBV) was the first human hepatitis virus to be identified. HBV can establish acute infections, sometimes very severe (fulminant hepatitis), and chronic infections in humans. Approximately two billion people have been in contact with HBV and 250 million are chronic carriers worldwide. Each year, there are approximately one million deaths due to the complications of chronic HBV infection (cirrhosis and hepatocellular carcinoma or primary liver cancer, of which HBV is now the main cause).

Modes of transmission and epidemiology

HBV is transmitted by blood or other body fluids (sperm and vaginal secretions). There are three main modes of transmission: percutaneous, sexual, and mother-to-child (vertical transmission).

  • Percutaneous exposure that causes HBV transmission includes the transfusion of blood or blood products that have not been tested for the absence of the virus, the use of contaminated medical equipment during care, injectable drug use, tattooing, and piercing.
  • Sexual transmission is common in unvaccinated adults and is favored by risky sexual behavior. Men who have sex with men (MSM) are a high-risk group.
  • Vertical transmission from mother to child at the time of birth or during the following weeks has been documented, as has the high risk of progression to chronic HBV infection in children.

Approximately 250 million people are chronic carriers of HBV worldwide, despite the existence of an effective hepatitis B vaccine and powerful, well-tolerated drugs. Although the prevalence (number of cases at a given time or over a given period) of HBV has tended to decrease in Europe since the 2000s, it remains high in some countries elsewhere, particularly sub-Saharan Africa and the Western Pacific (Mongolia, China, Southeast Asia). In France, approximately 3.1 million people have been infected with HBV during their lifetime and 280,000 are chronic HBV carriers. Between 2004 and 2007, the incidence (number of new cases over a given period) of symptomatic acute hepatitis B was estimated to be 1.1 per 100,000 inhabitants, or 675 new cases per year. The latest survey estimated that there were 291 cases of acute hepatitis B diagnosed in 2013, an incidence of 0.44 cases per 100,000 inhabitants.

Natural history of HBV infection

Acute hepatitis

There are no clinical symptoms in more than 60% of cases of acute hepatitis B. Acute hepatitis B is more frequently symptomatic (nausea, asthenia, anorexia, fever, arthralgia, sometimes jaundice) in adolescents and young adults than other groups. Acute hepatitis B is always characterized by an abnormally high serum activity of alanine aminotransferase (ALT), an enzyme produced by the liver; its activity may be more than 10 times the upper normal limit. The time between infection and the appearance of clinical signs (incubation period) varies from one to three months (10 weeks on average).

The HBV surface antigen (HBs antigen) is a specific biological marker for HBV infection. It can be detected approximately three weeks after the onset of clinical signs and usually disappears during the month after. Other biological markers are also present. Anti-HBc antibodies (antibodies to the capsid, a structure that surrounds the viral genome) appear at the onset of clinical signs. IgM anti-HBc antibodies are present during the acute stage of infection and disappear within a few weeks, whereas anti-HBc antibodies persist for life, regardless of the course of the disease. More than 99% of adults able to develop an immune response spontaneously clear the virus and recover after acute infection. In contrast, most children infected at birth are unable to eliminate the virus and develop a chronic infection.

Fulminant hepatitis

Approximately 1/1,000 to 1/100 cases of HBV-related acute hepatitis are severe, due to the destruction of hepatocytes in large numbers by the immune response to the virus, resulting in the loss of vital liver functions. Hepatitis may be sub-fulminant or fulminant, characterized by liver failure with a poor short-term vital prognosis, requiring urgent liver transplantation. The risk of developing fulminant hepatitis is a strong argument in favor of vaccination against hepatitis B.

Chronic hepatitis

Chronic hepatitis B is defined as the persistence of the HBs antigen in the patient's blood beyond six months. Chronic HBV infection is a complex dynamic process that reflects the interaction between virus multiplication and the host's immune response. Chronic hepatitis B involves HBs antigen carriage with persistent viral multiplication (viral replication), permanent or intermittent elevation of serum ALT activity, and inflammation of the liver. The level of viral replication in a chronic HBV carrier should be systematically measured: it is a major determinant of progression from liver disease to cirrhosis or hepatocellular carcinoma (HCC) and a very important factor for the choice of therapy.


It is not possible to distinguish hepatitis B from hepatitis caused by other viral agents clinically. Thus, it is essential to confirm the diagnosis in the laboratory. Several blood tests are available to diagnose and monitor people with hepatitis B. They can also be used to differentiate between acute and chronic infections.

Laboratory diagnosis of HBV infection is based on the detection of HBs antigen and other markers (anti-HBc and anti-HBs, HBV DNA) using a blood sample taken from the arm at the bend of the elbow. Only two markers are recommended for the diagnosis of acute hepatitis: HBs antigen and IgM anti-HBc antibodies. The simultaneous presence of HBs antigen and anti-HBc IgM in a patient with acute hepatitis allows the diagnosis of acute hepatitis B. Chronic carriage of HBV is defined by the persistence of HBs antigen for more than six months, the therapeutic indication depending on the level of viral replication (determined by measuring the amount of HBV DNA in the blood) and serum ALT activity.


Acute hepatitis B does not require specific antiviral treatment. Care consists of ensuring the comfort of the patient and balanced nutrition.

Chronic hepatitis B requires medication. Two treatment strategies are available, one based on oral antivirals for life, the other on weekly injections of interferon alpha for one year. The goal of treatment is to improve the quality of life and the survival of patients by preventing progression of the disease to one of its complications (cirrhosis, decompensation of cirrhosis, terminal hepatic failure, hepatocellular carcinoma, death).

Three oral antivirals are now available for the treatment of chronic hepatitis B: entecavir, and two forms of tenofovir (tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF)). These medications must be given for life when started and have the distinction of being very well-tolerated over long periods of administration. The long-term administration of these drugs can stop viral replication, resulting in undetectable HBV DNA, or considerably slow it down, keeping the DNA level very low and preventing hepatic inflammation and progression of the disease with its associated complications. Treatment failure is rare, and mainly involves patients who do not take the drugs on a regular basis.

The rationale for using interferon alpha is to induce long-term immunological control of the infection after 48 weeks of treatment. However, this goal is only achieved in approximately 25 to 30% of cases and this is among those subjects with an indication for this type of treatment and who can tolerate it.


The prevention of HBV infection is essentially based on vaccination. The classic vaccination schedule includes three injections. No boost is necessary. The vaccination policy against hepatitis B in France is two-pronged: a) identification and vaccination of people at high risk of infection; (b) the vaccination of infants (now recommended), and the vaccination of previously unvaccinated children and adolescents up to the age of 15 years during a medical consultation, with the goal of long-term control of hepatitis B. An anti-HBs antibody titer ≥ 10 mIU/mL is considered protective.

There is a particular recommendation for health professionals. Article L. 3111-4 of the French Public Health Code (CSP) makes immunization against hepatitis B mandatory for people who are engaged in work activities that expose them to risks of contamination and for pupils or students preparing to exercise certain health professions, to protect them from this infection. Immunization of professionals also aims to protect patients from the transmission of this virus by a caregiver. Personnel are considered immune if the anti-HBs titer is > 100 mIU/mL.