Treatment of chronic hepatitis B hepatitis

The main aim of chronic HBV therapy is to improve survival and quality of life by preventing disease progression, and consequently HCC development. In addition, anti retroviral therapy is used to prevent mother to child transmission, hepatitis B reactivation and the prevention and treatment of HBV-associated extrahepatic manifestations (1)

The World Health Organization (WHO) recommends initiating antiviral therapy in all adults (including pregnant women) and adolescents ≥12 years of age with: (2)

• Evidence of significant fibrosis or cirrhosis (based on transient elastography or aspartate aminotransferase-to-platelet ratio index scores), regardless of HBV DNA or ALT levels; OR
• HBV DNA level >2000 IU/mL and an ALT level above the upper limit of normal (ULN). For adolescents this should be based on ALT level > ULN on at least two occasions in a 6-12-month period; OR
• Presence of: coinfections (e.g., HIV, hepatitis C, hepatitis D); family history of liver cancer or cirrhosis; immunosuppression (e.g., solid organ or stem cell transplant, long-term corticosteroid use); comorbidities (e.g., diabetes, metabolic dysfunction-associated steatotic liver disease); or extrahepatic manifestations (e.g., vasculitis, glomerulonephritis) - regardless of aminotransferase-to-platelet ratio index score, HBV DNA, or ALT levels; OR
• Persistently abnormal ALT levels (i.e., two ALT values above the ULN at unspecified intervals during a 6-12 month period) in the absence of access to an HBV DNA assay, and regardless of aminotransferase-to-platelet ratio index score.

General measures include:

• counselling regarding chronic HBV infection and treatment
  • dynamic clinical course of the disease
  • need for absolute compliance and the possibility of long term therapy
• possible transmission to contacts
  • family and contacts need HBV screening and vaccination of those who are not immune to HBV
  • referral for clinical evaluation of those who are HBsAg-positive.
• importance of alcohol abstinence
• hepatitis A vaccine for those who are not immune the infection (3)

Specific measures:

• managed by a clinician with expertise in the management of viral hepatitis
• aim of antiviral therapy is to alter the natural history of the disease by reducing HBV DNA levels, facilitating conversion to 'e' antibody (HBeAb) positive, and clearing HBsAg
• measures are required to control infectivity, eradicate the virus and prevent complications of cirrhosis and hepatocellular carcinoma
• markers of therapeutic success include the loss of HBeAg, seroconversion to anti-HBe positive and a reduction in circulating viral load (although HBeAg-negative chronic hepatitis B may occur - see linked item)

Currently, there are two main treatment options for chronic HBV:

• oral nucleoside/nucleotide analogues -
  • lamivudine (LAM)
  • adefovir dipivoxil (ADV)
  • entecavir (ETV)
  • telbivudine (TBV)
  • tenofovir disoproxil fumarate (TDF)
  • tenofovir alafenamide (TAF)
• interferon injections (IFNα)
  • standard or pegylated interferon- PegIFNa)

Indications for treatment are generally same for both HBeAg-positive and HBeAg-negative and are based on the combination of - serum HBV DNA levels, serum ALT levels, severity of liver disease:

• all patients with HBeAg-positive or -negative chronic hepatitis B, defined by HBV DNA >2,000 IU/ml, ALT > upper limit of normal (ULN) and/or at least moderate liver necroinflammation or fibrosis, should be treated
• patients with compensated or decompensated cirrhosis need treatment, with any detectable HBV DNA level and regardless of ALT levels
• patients with HBV DNA>20,000 IU/ml and ALT>2xULN should start treatment regardless of the degree of fibrosis
• patients with HBeAg-positive chronic HBV infection, defined by persistently normal ALT and high HBV DNA levels, may be treated if they are older than 30 years regardless of the severity of liver histological lesions
• patients with HBeAg-positive or HBeAg-negative chronic HBV infection and family history of HCC or cirrhosis and extrahepatic manifestations can be treated even if typical treatment indications are not fulfilled (1)

Reference:

1. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398
2. World Health Organization. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. Mar 2024 [internet publication].
3. World Gastroenterology Organization (WGO) 2015. World Gastroenterology Organisation Practice Guideline. Hepatitis B