Clin Mol Hepatol > Accepted Articles
The long-term prognosis and the need for histologic assessment in chronic hepatitis B in serological immune-tolerant phase
Jeong-Ju Yoo1, Soo Young Park2, Ji Eun Moon3, Yu Rim Lee2, Han Ah Lee4, Jieun Lee5, Young Seok Kim1, Yeon Seok Seo6 , Sang Gyune Kim1
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
2Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
3Department of Biostatistics, Clinical Trial Center, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
4Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
5College of Medicine, Soonchunhyang University, Cheonan, Korea
6Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
Correspondence :  Yeon Seok Seo ,
Tel: +82-2-920-6608, Fax: +82-2-953-1943, Email:
Sang Gyune Kim ,
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Received: October 19, 2022  Revised: November 30, 2022   Accepted: January 3, 2023
The effect of histologic status of immune-tolerant (IT) phase of chronic hepatitis B on long-term outcomes is yet unclear. The aim of this study is to find out how well serological criteria currently used corresponds to the histologic criteria in determining IT phase and to suggest the indication for liver biopsy.
Patients in serological IT phase, defined by criteria of positive hepatitis B e antigen, HBV-DNA ≥ 106 IU/mL and normal or minimally elevated alanine aminotransferase (ALT) ≤ 60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation and death, were also analyzed.
Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to histologic IT phase. Age over 35, high AST and low albumin were useful for ruling out histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of histologic IT phase.
A significant number of patients who belonged to serological IT phase were not in histologic IT phase. Patients over 35 years and those with high AST, low albumin and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.
KeyWords: fibrosis; biopsy; hepatitis B virus

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