Correspondence to letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”

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Clin Mol Hepatol. 2025;31(1):e108-e109
Publication date (electronic) : 2024 August 5
doi : https://doi.org/10.3350/cmh.2024.0619
1Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
2University of Ulsan College of Medicine, Seoul, Korea
3Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Corresponding author : Young-Suk Lim Department of Gastroenterology, Asan Medical Centre, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-5933, Fax: +82-2-485-5782, E-mail: limys@amc.seoul.kr
*GA Kim and SW Choi contributed equally to this work and deserve co-first authorship.
Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea
Received 2024 August 1; Accepted 2024 August 4.

Dear Editor,

We appreciate the letter from Wang et al. [1] in response to our article [2]. The letter explored liver fibrosis by serum HBV DNA levels in treatment-naïve chronic hepatitis B (CHB) patients without significant alanine aminotransferase (ALT) elevation. It is a large, multi-center cohort study using liver biopsy results, and its findings support our previous study involving non-invasive liver fibrosis scores.

The study can find its significance in the use of biopsy results. They showed that patients with moderate HBV DNA of 6–7 log10 IU/mL had the highest proportion of significant fibrosis, advanced fibrosis, and cirrhosis compared to the other viral load groups. The tendency was more prominent in hepatitis B e antigen-negative patients. It is in line with our study that showed a non-linear parabolic association between viral load and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores [2]. Moderate viral loads of 6–7 log10 IU/mL corresponded to the highest APRI and FIB-4 scores. It is very encouraging that the study using liver biopsy produced comparable findings to this study.

The risk of moderate HBV DNA levels in CHB patients without ALT elevation has been underappreciated, but recently many studies have demonstrated their association with unfavorable outcomes [3,4]. Recent studies involving liver biopsy showed moderate HBV viral load of 5–7 log10 IU/mL was independently associated with significant liver inflammation and fibrosis [5-7]. Moderate viral loads were also associated with an increased risk of developing hepatocellular carcinoma (HCC) [3,4]. With the underlying mechanisms not being elucidated yet, there is great anticipation for related research.

Taken together, valuable insights are being offered regarding the moderate HBV viral load and its significance. The established knowledge regarding the association of HBV viral load with liver fibrosis and HCC risk is expected to enhance the strategy for antiviral treatment for non-cirrhotic CHB patients.

Notes

Authors’ contribution

Drafting the article: GAK, SWC, and YSL; final approval of the version of the article to be published: GAK, SWC, and YSL.

Conflicts of Interest

Y-SL is an advisory board member of Gilead Sciences and receives investigator-initiated research funding from Gilead Sciences. All the other authors have no conflict of interest to declare.

Abbreviations

ALT

alanine aminotransferase

APRI

aspartate aminotransferase to platelet ratio index

CHB

chronic hepatitis B

FIB-4

fibrosis-4

HCC

hepatocellular carcinoma

References

1. Wang J, Zhang S, Zhu C, Qiu Y, Wu C, Huang R. Presence of liver fibrosis in chronic hepatitis B patients with varying serum hepatitis B virus DNA levels: Letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”. Clin Mol Hepatol 2025;31:e27–e30.
2. Kim GA, Choi SW, Han S, Lim YS. Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B. Clin Mol Hepatol 2024;30:793–806.
3. Kim GA, Han S, Choi GH, Choi J, Lim YS. Moderate levels of serum hepatitis B virus DNA are associated with the highest risk of hepatocellular carcinoma in chronic hepatitis B patients. Aliment Pharmacol Ther 2020;51:1169–1179.
4. Choi WM, Kim GA, Choi J, Choi GH, Lee YB, Sinn DH, et al. Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B. Gut 2024;73:649–658.
5. Liu J, Wang J, Yan X, Xue R, Zhan J, Jiang S, et al. Presence of liver inflammation in asian patients with chronic hepatitis B with normal ALT and detectable HBV DNA in absence of liver fibrosis. Hepatol Commun 2022;6:855–866.
6. Wang J, Yan X, Zhu L, Liu J, Qiu Y, Li Y, et al. Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone. Aliment Pharmacol Ther 2023;57:464–474.
7. Huang R, Liu J, Wang J, Qiu Y, Zhu L, Li Y, et al. Histological features of chronic hepatitis B patients with normal alanine aminotransferase according to different criteria. Hepatol Commun 2024;8:e0357.

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