Hepatitis B Virus

HBV consists of a core antigen surrounded by a surface antigen. It has eight distinct genotypes (A to H) which vary in geographical distribution. The different genotypes differ in severity and respond differently to treatment

HBV can be acute or chronic. Actue HBV is characteristic by inflammation in the liver and is self-limiting disease. Chronic HBV occurs when there is failure of the immune system to clear the HBV virus. This means the hepatitis B surface antigen (HBsAg) is in circulation for more than 6 months. HBV infected hepatocytes become inflamed and necrotic due to a cytolytic T-cell response of the host. The resultant liver damage may eventually lead to cirrhosis and hepatocellular cancer

Presentation

Patients can be asymptomatic, in which case they should be tested for HBV if they are at a high risk of HBV (see below)

Symptomatic patients

  • Fever
  • arthralgia
  • Rash (may appear about 2 weeks before the onset of jaundice, then resolves in acute hepatitis B)
  • Fatigue
  • Nausea
  • Poor appetite
  • Right upper quadrant abdominal pain
  • Jaundice (with dark urine and/or pale stools if cholestasis is present)
  • Extrahepatic manifestations such as glomerulonephritis, vasculitis, and polyarteritis
  • Signs of chronic liver disease (in advanced chronic hepatitis B)

History

  • Assess risk factors for HBV
  • Injecting drug users
  • People who change sexual partners frequently, particularly men who have sex with men.
  • Travellers or people from a country with a high prevalence of HBV
  • Sex workers and their clients.
  • Household contacts of people with HBV
  • Families adopting a child from a country with a high prevalence of hepatitis B.
  • People receiving regular blood or blood products (such as people with haemophilia) and their carers.
  • People with chronic renal failure or chronic liver disease.
  • People with an occupational risk (e.g healthcare workers, laboratory staff, and morticians).
  • Infants born to women with hepatitis B infection.

Assess risk of transmission

  • Sharing of needles and injecting equipment
  • Occupational hazards e.g needlestick injury
  • Blood transfusions
  • Sexual transmission
  • Tattoos and piercings
  • Mother to baby

Differential diagnoses

  • Alcoholic liver disease.
  • Non-alcoholic fatty liver disease.
  • Autoimmune hepatitis.
  • Metabolic and genetic disorders (e.g Wilson's disease, hereditary haemochromatosis, alpha1 antitrypsin deficiency).
  • Drug-induced liver disease.
  • Hepatitis A, C, or D (acute hepatitis B cannot easily be distinguished from other forms of acute hepatitis)

Laboratory investigations

Patients at high risk of HBV infection, symptomatic patients and patients with abnormal LFTs should be considered for HBV serology testing

HBsAg (hepatitis B surface antigen)

  • This is the first biochemical marker to rise in people with hepatitis B
  • Detectable in the blood if there is a current hepatitis B infection
  • This indicates active HBV disease in acute or chronic patients. This is present for 1-6 months in acute disease. Persistence of HBsAg for >6 months indicates chronic infection

Anti-HBs (Anti-surface antigen antibodies).

  • This indicates immunity to HBV, either from past infection or immunisation.
  • Absent in chronic HBV infections

Anti-HBc (Anti-core antigen antibodies)

  • Indicates previous or current HBV infection

Immunoglobulin M (IgM) antibody against hepatitis B core antigen (anti-HBc)

  • First antibody to rise after infection
  • IgM anti-HBc indicates infection within the last 6 months (acute/current infection)
  • If IgM anti-HBc is negative, but Anti-HBc is positive, this indicates chronic infection

Hepatitis B e-antigen (HBeAg) and hepatitis B virus-DNA (HBV-DNA)

  • Disappearance of HBeAg, development of antibodies to HBeAg (anti-HBe), and a decline in HBV-DNA, indicates control of viral replication and predicts resolution of acute hepatitis B
  • Persistence of HBsAg, HBeAg, and HBV-DNA indicates possible progression to chronic hepatitis B
  • High levels of HBV-DNA is associated with a greater risk of progression to cirrhosis and hepatocellular cancer

IgG

  • IgG anti-HBc generally persists for life even after acute infection
  • Indicative of past infection.

Antibody to HBsAg (anti-HBs)

  • Indicates recover from HBV infection
  • Develops during recovery following the disappearance of HBsAg
  • Persists for life
  • Anti-HBs without anti-HBc is a marker of immunisation

Further investigations

  • LFTs (ALT, AST, GGT, serum albumin, total bilirubin, total globulins)
  • FBC
  • Prothrombin time
  • Serum alpha fetoprotein and liver ultrasound scan to assess for hepatocellular carcinoma

Management - Acute HBV

Notify the Health Protection Unit to facilitate appropriate surveillance and contact tracing.

Acute HBV does not usually need specific treatment, but may require treatment to relieve the symptoms

  • Paracetamol for pain relief
  • Metoclopramide or cyclizine for nausea
  • Chlorphenamine at night for itching (as well as maintaining a cool, well-ventilated environment, wearing loose clothing, and avoiding hot baths or showers)

Perform serology tests after 6 months to determine if chronic HBC infection has developed

Management - Chronic HBV

Ensure people with confirmed chronic hepatitis B have been vaccinated against hepatitis A if they are not already immune

Assessment of degree of liver disease

+++++Transient elastography (FibroScan)

  • Non-invasive test to quantify liver fibrosis

Transient elastography score <6 kPa

  • Unlikely to have significant fibrosis
  • Offer liver biopsy to adults younger than 30 years and have HBV DNA greater than 2000 IU/ml and abnormal ALT on 2 consecutive tests conducted 3 months apart to assess liver disease

Transient elastography score of 6-10 kPa

  • Consider liver biopsy to confirm the level of fibrosis in adults with a transient elastography score between 6 and 10 kPa

Transient elastography score of 11 kPa or more

  • Offer antiviral treatment without a liver biopsy
  • Very likely to have cirrhosis and confirmation by liver biopsy is not needed before starting anti-viral treatment

Anti-viral treatment

  1. Offer antiviral treatment to adults aged 30 years and older who have HBV DNA greater than 2000 IU/ml and abnormal ALT (greater than or equal to 30 IU/ml in males and greater than or equal to 19 IU/ml in females) on 2 consecutive tests conducted 3 months apart.
  2. Offer antiviral treatment to adults younger than 30 years who have HBV DNA greater than 2000 IU/ml and abnormal ALT on 2 consecutive tests conducted 3 months apart if there is evidence of necroinflammation or fibrosis on liver biopsy or a transient elastography score >6 kPa

1st line treatment for compensated liver disease

  • 48-week course of peginterferon alfa-2a

1st line treatment for decompensated liver disease

  • Offer entecavir
  • DO NOT offer peginterferon alfa-2a

Monitoring

Monitor serology

  • Monitor full blood count, liver function (including bilirubin, albumin and ALT), renal function (including urea and electrolyte levels) and thyroid function (and in children, weight and height) before starting peginterferon alfa-2a and 2, 4, 12, 24, 36 and 48 weeks after starting treatment
  • Monitor HBV DNA and quantitative HBsAg levels and HBeAg status before starting peginterferon alfa-2a at 12, 24 and 48 weeks after starting treatment to determine treatment response

Six-monthly surveillance testing for hepatocellular carcinoma

  • Perform surveillance for hepatocellular carcinoma by hepatic ultrasound and alpha-fetoprotein testing in people with significant fibrosis

Prognosis

  • Symptoms and jaundice generally last for 1–3 months
  • Hepatitis B surface antigen (HBsAg) is cleared in 95% of immunocompetent adults
  • Most people with chronic hepatitis B infection are inactive carriers of HBsAg and are asymptomatic and healthy, however 25% will undergo reactivation of the disease

Complications

  • 15–20% of adults with chronic hepatitis B will develop cirrhosis
  • Risk of extrahepatic manifestations e.g glomerulonephritis, vasculitis, and polyarteritis in both acute and chronic HBV
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-ShareAlike 3.0 License