NICE guidance on management of chronic hepatitis B infection

NICE guidance on management of chronic hepatitis B infection

Treatment sequence in adults with HBeAg-positive chronic hepatitis B and compensated liver disease

• a 48-week course of peginterferon alfa-2a should be offered as first-line treatment in adults with HBeAgpositive chronic hepatitis B and compensated liver disease
• tenofovir disoproxil should be offered as second-line treatment to people who do not undergo HBeAg seroconversion or who relapse (revert to being HBeAg positive following seroconversion) after first-line treatment with peginterferon alfa-2a
• entecavir should be offered as an alternative second-line treatment to people who cannot tolerate tenofovir disoproxil or if it is contraindicated

Treatment sequence in adults with HBeAg-negative chronic hepatitis B and compensated liver disease

• a 48-week course of peginterferon alfa-2a should be offered as first-line treatment in adults with HBeAgnegative chronic hepatitis B and compensated liver disease
• Offer entecavir or tenofovir disoproxil should be offered as second-line treatment to people with detectable HBV DNA after first-line treatment with peginterferon alfa-2a

Women who are pregnant or breastfeeding

• tenofovir disoproxil should be offered to women with HBV DNA greater than 10^7 IU/ml in the third trimester to reduce the risk of transmission of HBV to the baby

Prophylactic treatment during immunosuppressive therapy

In people who are HBsAg positive and have HBV DNA greater than 2000 IU/ml, offer prophylaxis with entecavir or tenofovir disoproxil

• start prophylaxis before beginning immunosuppressive therapy and continue for a minimum of 6 months after HBeAg seroconversion and HBV DNA is undetectable.

In people who are HBsAg positive and have HBV DNA less than 2000 IU/ml, offer prophylaxis:

• consider lamivudine if immunosuppressive therapy is expected to last less than 6 months
  • monitor HBV DNA monthly in people treated with lamivudine and change to tenofovir disoproxil if HBV DNA remains detectable after 3 months
• consider entecavir or tenofovir disoproxil if immunosuppressive therapy is expected to last longer than 6 months
• start prophylaxis before beginning immunosuppressive therapy and continue for a minimum of 6 months after stopping immunosuppressive therapy

Liver transplantation may be considered in some patients.

Notes:

• avoid use of peginterferon alfa-2a in pregnancy unless the potential benefit outweighs risk. Women of childbearing potential must use effective contraception throughout therapy
• at the time of publication (October 2017), tenofovir disoproxil did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented
• at the time of publication (October 2017), entecavir, lamivudine and tenofovir disoproxil did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented
• entecavir and tenofovir are oral nucleoside analogues
  • inhibits the viral DNA polymerase responsible for hepatitis B virus replication
    • entecavir and tenofovir have a marketing authorisation in the UK for the treatment of chronic HBV infection in adults with compensated liver disease and evidence of active viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis
    • adverse events associated with the use of nucleoside analogues include lactic acidosis and severe hepatomegaly with steatosis. Additional adverse events reported for entecavir include headache, fatigue, dizziness and nausea. Additional adverse events reported for tenofovir disoproxil include headache, fatigue and gastrointestinal disorder
• patients who are HBeAg positive, generally associated with high HBV DNA levels, and those with chronic active hepatitis (with a persistently raised ALT) are at most risk of sequelae from chronic infection
• not currently known what level of HBV DNA is associated with chronic liver disease - however treatment is generally considered in patients with a level of >105 copies per ml. A patient may be treated at lower HBV DNA levels if he has histological evidence of disease
• there is a small group of patients who have no detectable HBeAg in the serum but despite this do have a high HBV viral load
  • generally these have an HBV mutation that prevents the production of HBeAg (known as pre-core mutant virus), and they may be either HBeAb positive or negative - in comparison with nonmutant hepatitis B virus, this variant has been associated with a higher incidence of fulminant hepatitis B
• reduction in risk of hepatocellular carcinoma (HCC)
  • interferon or nucleoside analogue treatment significantly reduces risk of HCC (2)
    • this study revealed that while interferon benefited patients with cirrhosis, nucleoside analogue therapy benefited patients with no cirrhosis and HBeAg-positive CHB infection

Reference:

• 1) NICE (October 2017). Hepatitis B (chronic) Diagnosis and management of chronic hepatitis B in children, young people and adults
• 2) Sung JJ et al. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008 Nov 1;28(9):1067-77.
• 3) Prescriber 2005; 16(6):66-75.