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Management of children and adults with immune-tolerant hepatitis B virus infection

Management of children and adults with immune-tolerant hepatitis B virus infection
  Children Adults (AASLD guidance)[1]
Definition of immune-tolerant phase

HBV DNA >20,000 IU/mL*

ALT <1.5 times ULN

HBV DNA very elevated (typically >1 million IU/mL)*

ALT <2 times ULN
ALT cutoff (ULN)

Males: 35 IU/L

Females: 25 IU/L

Males: 30 IU/L

Females: 25 IU/L
Monitoring

Monitor every 6 to 12 months

Monitoring includes blood testing (ALT, HBeAg, HBeAb) and surveillance for HCC		 Monitor every 6 months
Fibrosis assessment Transient elastography (Fibroscan)Δ  
Liver biopsy If needed to confirm cirrhosis, or guided biopsy for a suspicious lesion

Liver biopsy in selected patients to assess for inflammation and cirrhosis that might be an indication for treatment (refer below)

Candidates include:
  • Age >40 years of age and infected since a young age
  • Suspicious lesion
Treatment

Treatment in immune-tolerant phase is generally not recommended

Uncommon exceptions are:
  • Severe liver disease for other reasons (eg, cirrhosis)
  • Comorbidity that increases risk for HBV progression (eg, another condition requiring immunosuppression such as organ transplantation)

Treat in immune-tolerant phase is generally not recommended

Exceptions are:
  • Age >40 years with HBV DNA ≥1 million IU/mL*, normal ALT, and liver biopsy showing significant necroinflammation or fibrosis
  • Pregnant patients (treat those with HBV DNA >20,000 IU/mL*, using antiviral agents during the third trimester to prevent transmission to the offspring)

AASLD: American Association for the Study of Liver Diseases; AFP: alpha-fetoprotein; ALT: alanine aminotransferase; DNA: deoxyribonucleic acid; HBV: hepatitis B virus; HBeAb: hepatitis B antibody; HBeAg: hepatitis B antigen; HCC: hepatocellular carcinoma; IU: international units; ULN: upper limit of normal.

* For HBV DNA, IU/mL = 5 × copies/mL (ie, 20,000 IU/mL = 106 copies/mL).

¶ Surveillance for HCC consists of ultrasonography approximately every 6 months, with serum AFP if practical, but this depends on age and phase of HBV infection. Because the risk for HCC increases with age, we monitor somewhat less frequently (eg, every 2 to 3 years) for young patients in the immune-tolerant phase, provided that the baseline AFP and ultrasound are normal.

Δ Transient elastography is a useful tool for monitoring hepatic fibrosis, but availability and monitoring protocols vary. In our practice, we perform transient elastography at diagnosis and approximately once annually, including during the immune-tolerant phase. More frequent monitoring and/or liver biopsy is appropriate for children with abnormal results.
Reference:
  1. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560.

Adapted from: Lee HW, Chan HL. Unresolved issues of immune tolerance in chronic hepatitis B. J Gastroenterol 2020; 55:383.

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