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

Table 1 Summary of treatment criteria for chronic hepatitis B

	HBeAg+; HBV DNA (IU/mL)	HBeAg+; ALT (IU/L)	HBeAg–; HBV DNA (IU/mL)	HBeAg–; ALT (IU/L)	Cirrhosis
EASL[15]	≥ 2000	> ULN and/or at least moderate liver necro-inflammation or fibrosis	≥ 2000	> × ULN or significant histological disease	HBV-DNA detectable
	≥ 20000	> 2 × ULN or irrespective of fibrosis	≥ 20,000	> 2 × ULN irrespective of fibrosis
APASL[16]	≥ 20000	> 2 × ULN or significant histological disease	≥ 2000	> 2 × ULN or significant histological disease	HBV-DNA detectable
AASLD[17]	> 20000	> 2 × ULN or significant histological disease	≥ 2000	> 2 × ULN or significant histological disease	HBV-DNA detectable
JSG[18]	≥ 2000	> ULN	≥ 2000	> ULN	HBV-DNA detectable

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; HBeAg: Hepatitis B e-antigen; HBV: Hepatitis B virus; JSG: Japanese Society of Hepatology; ULN: Upper limit of normal.

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.

Table 3 Treatment indications for patients in the hepatitis B e-antigen-negative immune-inactive phase

	Monitor criteria	Consideration for anti-viral therapy
EASL[15]	Normal ALT (< 40 IU/L) and HBV DNA (< 2000 IU/mL) levels. Monitor ALT and HBV DNA levels (< 2000 IU/mL)every 6-12 mo, (≥ 2000 IU/mL)every 3-6 mo	Age > 30 yr, family history of HCC or cirrhosis and extrahepatic manifestations
APASL[16]	Normal ALT (< 40 IU/L) and HBV DNA (< 2000 IU/mL) levels. Monitor ALT and HBV DNA levels every 3-6 mo	Age > 35 yr, liver biopsy showing F2 or 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 HBV DNA (< 2000 IU/mL) levels. Monitor ALT and HBV DNA levels every 3 mo for 1 yr, then every 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 level (≤ 30 IU/L) and HBV DNA (< 2000 IU/mL) levels	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.