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”
Article information
Dear Editor,
We read with great interest the article by Kim et al., who investigated the presence of liver fibrosis in chronic hepatitis B (CHB) patients with different hepatitis B virus (HBV) DNA levels [1]. They demonstrated that patients with moderate HBV DNA levels (6–7 log10 IU/mL) had the highest aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores and an increased risk of hepatocellular carcinoma development [1]. These findings suggest that moderate serum HBV DNA level is a significant factor associated with disease progression, providing important insights for the management of patients with CHB. However, the assessment of liver fibrosis was based on noninvasive tests, including APRI and FIB-4, which only have moderate sensitivity and accuracy in identifying hepatitis Brelated fibrosis [2,3]. Currently, liver biopsy remains the gold standard method for assessing liver fibrosis. We analyzed data from a large multicenter cohort of patients with CHB who underwent liver biopsy to assess the presence of liver fibrosis in patients with different serum HBV DNA levels.
A total of 1,058 treatment-naïve patients with CHB who underwent liver biopsy and had alanine aminotransferase (ALT) levels <80 IU/L were recruited from four medical institutions (Nanjing Drum Tower Hospital, The Fifth People’s Hospital of Suzhou, The Fifth People’s Hospital of Wuxi, and The Fourth People’s Hospital of Huai’an). The patients were divided into seven groups according to their serum HBV DNA levels. Liver fibrosis was staged using the Scheuer scoring system, with stages (S) ≥2, S ≥3, and S4 defined as significant fibrosis, advanced fibrosis, and cirrhosis, respectively [4].
The median age of the patients was 40 years and 64.6% were male. The median levels of platelets, ALT, hepatitis B surface antigen (HBsAg), and HBV DNA were 170×109/L, 33.0 IU/L, 3.0 log10 IU/mL, and 4.2 log10 IU/mL, respectively. Of these, 36.1% were hepatitis B e antigen (HBeAg) positive. A comparison of the clinical features among the patients with different serum HBV DNA levels is shown in Supplementary Table 1. Overall, patients with HBV DNA levels >7 log10 IU/mL were younger, whereas patients in the HBV DNA 5–6 log10 IU/mL and 6–7 log10 IU/mL groups had lower platelet counts and higher ALT levels. Most patients with HBV DNA >7 log10 IU/mL were HBeAg positive, while all patients with HBV DNA ≤3 log10 IU/mL were HBeAg negative. Serum HBsAg levels were positively associated with HBV DNA levels.
In the overall cohort, the proportion of significant fibrosis was highest in patients with HBV DNA 6–7 log10 IU/mL (78.7%), followed by patients with HBV DNA 5–6 log10 IU/mL (76.4%), ≤3 log10 IU/mL (55.7%), 4–5 log10 IU/mL (55.6%), 3–4 log10 IU/mL (50.7%), 7–8 log10 IU/mL group (43.1%), and >8 log10 IU/mL (38.2%) (Fig. 1A). Patients with moderate HBV DNA levels (6–7 log10 IU/mL) also had the highest proportion of advanced fibrosis (51.7%) and cirrhosis (28.1%) (Fig. 1B, 1C). We further conducted a subgroup analysis based on HBeAg status. Notably, although 75.4% of patients with HBV DNA 6–7 log10 IU/mL had significant fibrosis, the proportion was lower than in patients with HBV DNA 3–4 log10 IU/mL (100%) and 5–6 log10 IU/mL (81.8%) among HBeAg-positive patients (Fig. 1D). Similar results were observed in the proportion of patients with advanced fibrosis and cirrhosis (Fig. 1E, 1F). In the HBeAg-negative subgroup, patients with HBV DNA levels of 6–7 log10 IU/mL had the highest proportions of significant fibrosis (90.0%), advanced fibrosis (55.0%), and cirrhosis (35.0%) compared to the other groups (P=0.002, P=0.019, and P=0.071; Fig. 1G–1I).
The proportions of significant fibrosis, advanced fibrosis, and cirrhosis in chronic hepatitis B patients with different serum HBV DNA levels. HBV, hepatitis B virus; HBeAg, hepatitis B e antigen.
Using a large multicenter cohort of patients with CHB, where liver biopsy served as the gold standard method to evaluate liver fibrosis stages, our results suggest that moderate serum HBV DNA levels (6–7 log10 IU/mL) are associated with a higher risk of liver fibrosis, particularly in HBeAg-negative patients. These findings are consistent with those of Kim et al. Thus, early initiation of antiviral treatment should be considered for CHB patients with moderate serum HBV DNA levels, even in the absence of liver cirrhosis. However, our study was limited by the lack of adjustment for confounding factors in patients with different HBV DNA levels and included only Chinese patients with CHB. Further prospective studies are required to validate these findings.
Notes
Authors’ contribution
Dr. Rui Huang had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Rui Huang, Jian Wang, Chao Wu. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Jian Wang, Rui Huang. Critical review of the manuscript for important intellectual content: Rui Huang. Statistical analysis: Jian Wang, Shaoqiu Zhang. Administrative, technical, or material support: Jian Wang, Chuanwu Zhu, Yuanwang Qiu. Supervision: Rui Huang.
Conflicts of Interest
The authors have no conflicts to disclose.
Acknowledgements
This work was supported by grants of Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2022-LCYJ-MS-07 and 2021-LCYJPY-43).
SUPPLEMENTAL MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (http://www.e-cmh.org).
Clinical features of study population
Abbreviations
ALT
alanine aminotransferase
APRI
aspartate aminotransferase to platelet ratio index
CHB
chronic hepatitis B
FIB-4
fibrosis-4
HBeAg
hepatitis B e antigen
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus