Hepatitis B: Who should be treated?-managing patients with chronic hepatitis B during the immune-tolerant and immunoactive phases

Table 2 Treatment indications for patients with hepatitis B e-antigen positive, alanine aminotransferase < upper limit of normal for chronic hepatitis B

	Monitor criteria	Consideration for anti-viral therapy
EASL[15]	Normal ALT (< 40 IU/L) and high HBV DNA (≥ 2000 IU/mL) levels. Monitor ALT and HBV DNA levels every 3-6 mo	Age > 30 yr, family history of HCC or cirrhosis and extrahepatic manifestations. Consider liver biopsy or non-invasive test if: ALT level is elevated; excluding other causes
APASL[16]	Normal ALT (< 40 IU/L) and high HBV DNA (≥ 20000 IU/mL) levels Monitor ALT and HBV DNA levels every 3 mo	Age > 35 yr, liver biopsy showing F2/A2, significant fibrosis by non-invasive tests, stiffness ≥ 8 kPa, persistently elevated ALT, family history of HCC/cirrhosis
AASLD[17]	Normal ALT [< 35 IU/L (male), < 25 IU/L (female)] and high HBV DNA (≥ 20000 IU/mL) levels. Monitor ALT and HBV DNA levels every 3-6 mo	Liver biopsy or non-invasive test shows ≥ F2 or F3, persistently elevated ALT level; exclude other causes, especially age > 40 yr
JSG[18]	Normal ALT (≤ 30 IU/L) level	Consider liver biopsy or non-invasive test if Age > 40 yr, high HBV DNA or platelet counts < 15 × 104/uL, family history of HCC

A2: Activity score 2; AASLD: American Association for the Study of Liver Disease; ALT: Alanine aminotransferase; APASL: Asian-Pacific Association for the Study of the Liver; EASL: European Association for the Study of Liver Disease; F2/3: Fibrosis score 2/3; HBeAg: Hepatitis B e-antigen; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; JSG: Japanese Society of Hepatology.