- •The definition of immune-tolerant phase of chronic hepatitis B and their prognosis is controversial.
- •Some studies suggest that early antiviral treatment are required for patients with immune-tolerant phase, but not others.
- •In this multi-center study from the East Asia, we used stringent criteria to define the genuine immune-tolerant phase with both age < 40 years and HBV DNA > 6 log10 IU/mL.
- •The risk of hepatocellular carcinoma development during the untreated immune-tolerant phase is negligible.
Abbreviations:CHB (chronic hepatitis B), HBV (hepatitis B virus), NUCs (nucleos(t)ide analogues), IT phase (immune-tolerant phase), EASL (European Association for the Study of Liver Diseases), ALT (alanine aminotransferase), AVT (antiviral therapy), HBeAg (hepatitis B e antigen), HCC (hepatocellular carcinoma), PT INR (prothrombin time international normalized ratio), CDARS (Clinical Data Analysis and Reporting System), ULN (upper limit of normal), HBsAg (hepatitis B surface antigen), HRs (hazard ratios), 95% CIs (95% confidence intervals), AASLD (American Association for the Study of Liver Diseases)
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to European Journal of Internal Medicine
- Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.JAMA. 2006; 295: 65-73
- Predicting cirrhosis risk based on the level of circulating hepatitis B viral load.Gastroenterology. 2006; 130: 678-686
- The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B.Clin Mol Hepatol. 2019; 25: 93-159
- Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance.Hepatology. 2018; 67: 1560-1599
- European Association for the Study of the Liver (EASL). EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection.J Hepatol. 2017; 67: 370-398
- AASLD guidelines for treatment of chronic hepatitis B.Hepatology. 2016; 63: 261-283
- Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT.Gastroenterology. 2008; 134: 1376-1384
- HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant.Gastroenterology. 2016; 151 (e4): 986-998
- The clinical significance of persistently normal ALT in chronic hepatitis B infection.J Hepatol. 2007; 47: 760-767
- High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B.Gut. 2018; 67: 945-952
- Nucleos(t)ide analogue treatment for patients with hepatitis B virus (HBV) e antigen-positive chronic HBV genotype c infection: a nationwide, multicenter, retrospective study.J Infect Dis. 2017; 216: 1407-1414
- Prognosis of immune-tolerant phase chronic hepatitis B.Gut. 2018; 67: 988
- Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.Hepatol Int. 2016; 10: 1-98
- Unresolved issues of immune tolerance in chronic hepatitis B.J Gastroenterol. 2020; 55: 383-389
- Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update.Clin Mol Hepatol. 2019; 25: 245-263
- Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022
- European Association for the Study of Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943
- Prognosis of untreated minimally active chronic hepatitis B patients in comparison with virological responders by antivirals.Clin Transl Gastroenterol. 2019; 10: e00036
- Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease.Gut. 2014; 63: 1943-1950
- HBV genotypes: relevance to natural history, pathogenesis and treatment of chronic hepatitis B.Antivir Ther. 2011; 16: 1169-1186
- Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend.Clin Mol Hepatol. 2018; 24: 108-113
- Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals..Sci Rep. 2019; 9: 2508
- Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase.Aliment Pharmacol Ther. 2020; 52: 196-204
- Letter: risk of hepatocellular carcinoma in immune-tolerant phase of chronic hepatitis B-authors' reply.Aliment Pharmacol Ther. 2020; 52: 913-914
- Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase.Hepatology. 2007; 46: 395-401
- Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma.Gastroenterology. 2011; 141 (1248 e1-2): 1240-1248
- Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study.BMJ. 2004; 328: 983