Correspondence on Letter regarding “Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune tolerant phase”

Article information

Clin Mol Hepatol. 2023;29(2):513-515

Publication date (electronic) : 2023 February 15

doi : https://doi.org/10.3350/cmh.2023.0044

Jeong-Ju Yoo, Sang Gyune Kim

Department of Internal Medicine, Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Bucheon, Korea

Corresponding author : Sang Gyune Kim Department of Gastroenterology and Hepatology, Digestive Research Center and Liver Clinic Soonchunhyang University Bucheon Hospital, 170 Jomaruro, Wonmi-gu, Bucheon 14584, Korea Tel: +82-32-621-5215, Fax: +82-32-621-6079, E-mail: mcnulty@schmc.ac.kr

Editor: Seung Up Kim, Yonsei University College of Medicine, Korea

Received 2023 February 6; Revised 2023 February 9; Accepted 2023 February 9.

Dear Editor,

We would like to thank Chu and Liaw [1] for their interest in our paper [2] and for providing valuable insights into the immune tolerant (IT) phase. We acknowledge the potential for selection bias in our study due to the relatively high average age of the patients included. We included all patients with the current IT criteria to highlight the wide range of the IT phase. If limited to patients younger than 30 years of age, four out of 51 patients had advanced fibrosis. Out of those four patients, hepatocellular carcinoma occurred in only one patient with severe fatty liver. Likewise, many IT phase patients who meet the current guidelines’ criteria often require treatment in real practice.

There is a general agreement that IT phase patients with significant fibrosis should receive treatment [3,4]. Although our study included a large number of such patients, we do not believe that a liver biopsy is necessary for all IT phase patients. The challenge is to accurately identify those with significant fibrosis without a biopsy. There are many diagnostic tools for non-invasive fibrosis, such as transient elastography (TE) or magnetic resonance elastography, and these can be used as secondary tools for accurate diagnosis of the IT phase and excluding significant liver fibrosis [5,6].

Although seroconversion can be delayed in genotype C patients (commonly found in South Korea), it is usually accompanied by significant fibrosis in patients over 35 years of age [7]. However, the current IT phase diagnosis guidelines only use serological criteria. Our data showed that serum alanine aminotransferase (ALT) levels alone do not fully reflect the histological activity of IT phase. In the same vein, previous studies [8-10] have found that ALT levels do not indicate the actual inflammation in the liver due to the following reasons: i) ALT elevation is associated with the location of inflammation [11], and ii) the changes in ALT levels occur faster than the changes in histology [12]. One of the alternatives, as mentioned1 by the authors, is that different standards for normal ALT levels might be applied according to age.

Nevertheless, we completely agree with the authors’ view of the IT phase patients, and we also believe that ALT levels should be monitored every 3–6 months to detect transitions from the IT phase to the immune active phase. Although there are many diagnostic tools for fibrosis and steatosis with the recent development of technology, there is no powerful diagnostic tool for inflammation other than a liver biopsy [13,14]. In this case, TE can provide information about inflammation as well as fibrosis, but the measured stiffness value should be used with caution. Our research team has found that the liver stiffness value is related to both histologic inflammation and fibrosis in patients with ALT levels less than 200 U/L [15].

In conclusion, our study highlights the concern that the current IT phase guidelines may delay treatment for actually non-IT phase patients with hepatitis B. As mentioned by Chu and Liaw [1], we fully support the opinion that the HBV DNA cut-off value in the IT phase should be set very high, similar to the EASL guideline, and that the ALT criteria should be adjusted according to age. We hope that future IT phase guidelines will include age criteria and non-invasive diagnostic technologies for accurate fibrosis and/or inflammation diagnosis.