Table 3.
Comparison of treatment indicators for chronic hepatitis B
| KASL | AASLD | EASL | APASL | |
|---|---|---|---|---|
| Immune tolerant CHB | 1) Monitor patients with very high HBV DNA (≥107 IU/mL) and normal ALT (male <34 IU/mL, female <30 IU/mL) | 1) Monitor patients with high HBV DNA (≥106 IU/mL) and normal ALT (male <35 IU/mL, female <25 IU/mL) | 1) Monitor patients with high HBV DNA (≥107 IU/mL) and normal ALT (<40 IU/L) if there are no signs of chronic hepatitis | 1) Monitor patients with high HBV DNA (e.g., >2×106–107 IU/mL) and normal ALT (<40 IU/L) if age <30 years |
| 1) Monitor | 2) Liver biopsy to determine treatment if there are risk factors (age ≥30–40 years, HBV DNA levels <107 IU/mL, noninvasive fibrosis tests suggesting significant hepatic fibrosis, or ALT is approaching the ULN) | 2) Antiviral therapy is suggested in selected patients (age >40 years with normal ALT and elevated HBV DNA [1,000,000 IU/mL], liver biopsy showing significant necroinflammation or fibrosis) | 2) Antiviral therapy may be indicated for patients >30 years of age, regardless of the severity of liver histological lesions | 2) Liver biopsy if indicated (age is >35 years or there is a family history of HCC or cirrhosis, noninvasive tests suggest evidence of significant fibrosis, persistently elevated ALT) Treat if ≥A2 or ≥F2 |
| 2) Consider | Patients with a family history of HCC or cirrhosis and extrahepatic manifestations can be treated | |||
| Immune active CHB | 1) Treat if HBV DNA ≥20,000 (for HBeAg-positive CHB) or ≥2,000 (for HBeAg-negative CHB) IU/mL and serum ALT level ≥2× ULN | 1) Treat if elevated HBV DNA (≥20,000 IU/mL for HBeAg-positive or ≥2,000 IU/mL for HBeAg-negative CHB) and ALT ≥2× ULN or there is evidence of significant histological disease | 1) Treat if HBV DNA >20,000 IU/mL and ALT >2× ULN, regardless of the degree of fibrosis | 1) Treat if HBV DNA >20,000 IU/mL for HBeAg-positive or >2,000 IU/mL for HBeAg-negative CHB and ALT levels are elevated >2× ULN |
| 1) Treat | 2) Consider liver biopsy if ALT is 1–2× ULN and treat if there is moderate to severe necroinflammation (≥A2) or significant fibrosis (≥F2) | 2) Consider the severity of liver disease to determine treatment for patients with ALT >1–2× ULN | 2) Treat all patients with HBeAg-positive or -negative CHB, defined by HBV DNA >2,000 IU/mL, ALT>ULN (40 IU/L), and/or at least moderate liver necroinflammation or fibrosis by biopsy | 2) Patients with high HBV DNA levels (>20,000 IU/mL for HBeAg-positive and >2,000 IU/mL for HBeAg-negative CHB) but ALT <2× ULN should depict a noninvasive fibrosis assessment |
| 2), 3) Consider | 3) In HBeAg-negative patients with HBV DNA ≥2,000 IU/mL and normal ALT levels, follow-up or liver biopsy/noninvasive fibrosis tests can be considered | Biopsy should be considered if indicated* | ||
| Antiviral therapy is recommended if ≥A2 or ≥F2 | ||||
| Immune inactive CHB | 1) Monitor | 1) Monitor | 1) Monitor | 1) Monitor |
| 1) Monitor | 2) Patients with HBeAg-negative chronic HBV infection, family history of HCC or cirrhosis, and extrahepatic manifestations can be treated even if typical treatment indications are not present | 2) HBeAg-negative patients with HBV DNA <2,000 IU/mL, should be evaluated for other causes if ALT is elevated and obtain a noninvasive fibrosis assessment | ||
| 2) Consider | Biopsy should be considered if indicated* | |||
| Antiviral therapy is recommended if ≥A2 or ≥F2 | ||||
| First-line agents | Entecavir, tenofovir DF, tenofovir AF, besifovir, peg-interferon | Entecavir, tenofovir DF, tenofovir AF, peg-interferon | Entecavir, tenofovir DF, tenofovir AF, peg-interferon | Entecavir, tenofovir DF, peg-interferon |
KASL, Korean Association for the Study of the Liver; AASLD, American Association for the Study of Liver Diseases; EASL, European Association for the Study of the Liver; APASL, Asian-Pacific Association for the Study of the Liver; CHB, chronic hepatitis B; HBV, hepatitis B virus; ALT, alanine aminotransferase; ULN, upper limit of normal; HCC, hepatocellular carcinoma; ≥A2, moderate to severe inflammation; ≥F2, significant fibrosis or more; HBeAg, hepatitis B e antigen; tenofovir DF, tenofovir disoproxil fumarate; tenofovir AF, tenofovir alafenamide fumarate; peg-interferon, pegylated interferon.
APASL recommends the consideration of liver biopsy if noninvasive tests suggest evidence of significant fibrosis, ALT becomes persistently elevated, age is >35 years, or there is a family history of HCC or cirrhosis.