Treatment of chronic hepatitis B infection in infants and young children: A systematic review

Table 2 Indications to treat according to different scientific societies

	Adults	Children
ESPGHAN[15]	N/A	CHB patients presenting with elevated serum ALT levels for at least 6 months if HBeAg-positive, or for at least 12 months if HBeAg-negative, and either moderate necroinflammation or fibrosis, or mild inflammation or fibrosis with a family history of HCC
WHO[1]	In the presence of significant fibrosis or cirrhosis regardless of HBV DNA and ALT levels, or HBV DNA > 2000 IU/mL and an ALT level above the upper limit of normal (for adolescents in at least two measurements 6-12 months apart), or in the presence of other factors, such as co-infections, family history of HCC or cirrhosis, immune-suppression, comorbidities or extra-hepatic manifestations	For adolescents (12 years and older) the indications for adults are applicable. For children < 12 years, WHO states that current evidence is insufficient to give recommendations on when to start treatment
AASLD[16,17]	ALT elevation > 2 × ULN (30 U/L for men and 19 U/L for women) or evidence of significant histological disease, plus HBV DNA > 2000 IU/mL (HBeAg-negative) or > 20000 IU/mL (HBeAg-positive); adults > 40 years old with immune-tolerant CHB and normal ALT, elevated HBV DNA (> 1000000 IU/mL), and liver biopsy showing substantial necroinflammation or fibrosis; adults with compensated cirrhosis and low viraemia (< 2000 IU/mL); HBsAg-positive adults with decompensated cirrhosis regardless of HBV DNA concentration, HBeAg status, or ALT concentration (these patients should be treated with antiviral therapy indefinitely); HBsAg-positive pregnant women with HBV DNA > 200000 IU/mL	HBeAg-positive children (aged 2-17 years) with elevated ALT and measurable HBV DNA concentrations
EASL[18]	CHB (HBeAg-positive or -negative), with HBV DNA > 2000 IU/mL, ALT > ULN and/or at least moderate liver necroinflammation or fibrosis; adults with compensated or decompensated cirrhosis and detectable HBV DNA, regardless of ALT levels. Patients with HBV DNA > 20000 IU/mL and ALT > 2 × ULN, regardless of the degree of fibrosis. HBeAg-positive chronic HBV infection, (persistently normal ALT and high HBV DNA levels) if 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, even if typical treatment indications are not fulfilled	Refer to the joint EASL-ESPGHAN guidelines
APASL[19]	Decompensated cirrhosis, and detectable HBV DNA or severe reactivation of chronic infection; compensated cirrhosis and HBV DNA > 2000 IU/mL; persistently elevated (≥ 1 month between observations) ALT concentration more than two times ULN and HBV DNA > 20000 IU/mL if HBeAg-positive or > 2000 IU/mL if HBeAg-negative (liver biopsy or a non-invasive method to estimate the extent of fibrosis might provide further useful information); pronounced fibrosis, and normal or slightly elevated ALT concentration or HBV DNA < 20 000 IU/mL if HBeAg-positive or < 2000 IU/mL if HBeAg-negative	In the presence of cirrhosis (compensated or decompensated); children with severe reactivation of chronic HBV (detectable HBV DNA and elevated ALT); non-cirrhotic, HBeAg-positive chronic HBV infection, HBV DNA > 20000 IU/mL, and ALT more than two times ULN for > 12 months; non-cirrhotic, HBeAg-positive chronic HBV infection and either HBV DNA > 20000 IU/mL and ALT less than two times ULN for more than 12 months, or a family history of hepatocellular carcinoma or cirrhosis and moderate-to-severe inflammation or pronounced fibrosis; non-cirrhotic, HBeAg-positive chronic HBV infection, HBV DNA < 20000 IU/mL, and moderate to severe inflammation or pronounced fibrosis; non-cirrhotic, HBeAg-negative chronic HBV infection, HBV DNA > 2000 IU/mL, and ALT more than two times ULN; non-cirrhotic, HBeAg-negative chronic HBV infection and moderate to severe inflammation or pronounced fibrosis, regardless of HBV DNA concentration

AASLD: American Association for the Study of Liver Diseases; APASL: Asian-Pacific Association for the Study of the Liver; CHB: Chronic hepatitis B; EASL: European Association for the Study of the Liver; ESPGHAN: European Society for Paediatric Gastroenterology Hepatology and Nutrition; HBeAg: Hepatitis B envelope antigen; HCC: Hepatocarcinoma; N/A: Not applicable; WHO: World Health Organization; ULN: Upper limit of normal; HBV: Hepatitis B virus; ALT: Alanine aminotransferase.