# Clinical and histopathological features of chronic hepatitis B with normal alanine aminotransferase levels with or without concomitant non-alcoholic fatty liver disease

**Authors:** Wencong Li, Shiheng Liu, Weiguang Ren, Xiaoxiao Zhang, Lingdi Liu, Fang Han, Ying Zhang, Yuemin Nan, Suxian Zhao

PMC · DOI: 10.3389/fmed.2026.1626154 · Frontiers in Medicine · 2026-02-12

## TL;DR

This study examines liver damage in hepatitis B patients with normal enzyme levels, finding that those with fatty liver disease have more severe damage.

## Contribution

The study reveals that combining non-alcoholic fatty liver disease with chronic hepatitis B increases liver injury risk, particularly in specific subgroups.

## Key findings

- Patients with CHB and NAFLD had higher rates of significant liver injury compared to CHB alone.
- HBcAg expression was linked to higher HBV DNA levels and more severe liver damage.
- AAR was better for diagnosing fibrosis in CHB+NAFLD, while FIB-4 worked better for CHB alone.

## Abstract

To analyze the clinical and hepatic pathological characteristics of patients with chronic hepatitis B (CHB) alone or with non-alcoholic fatty liver disease (NAFLD), who have normal alanine aminotransferase (ALT) levels.

The patients with normal ALT levels and pathologically diagnosed CHB alone or in combination with NAFLD were enrolled, the demographic, laboratory, and pathological data were collected and analyzed.

Among 391 enrolled CHB patients with normal ALT levels, 107 individuals combined with NAFLD. The incidence of significant liver injury (G and/or S ≥ 2) in patients with CHB alone was lower significantly than that of patients with CHB and NAFLD (64.08% vs. 78.50%, P < 0.05), especially by the subgroup analyses in HBeAg positive, male, age > 30 years (P < 0.05). In all patients, who with negative HBcAg expression had lower HBV DNA levels than those with positive HBcAg expression (P < 0.001). Patients with G and/or S ≥ 2 had a higher proportion of HBcAg cytoplasm/cytoplasmic nucleus expression type compared to patients with liver tissue G and S < 2 (32.42% vs. 16.67% in CHB alone, 36.91% vs. 21.74% in CHB + NAFLD, all P < 0.001). Aspartate aminotransferase to ALT ratio index (AAR) demonstrated relatively superior efficacy in diagnosing significant liver fibrosis among patients with CHB and NAFLD, while fibrosis-4 (FIB-4) exhibited superior performance in patients with CHB alone.

Patients with normal ALT can still demonstrate significant liver tissue damage. The combination of NAFLD will significantly increase the incidence of significant liver injury in patients with CHB, especially in those who are HBeAg positive, male, over 30 years old.

## Linked entities

- **Diseases:** chronic hepatitis B (MONDO:0005344), non-alcoholic fatty liver disease (MONDO:0013209)

## Full-text entities

- **Genes:** LOC102724197 (inactive glutathione hydrolase 2) [NCBI Gene 102724197] {aka GGT2}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, GGTLC4P (gamma-glutamyltransferase light chain 4 pseudogene) [NCBI Gene 729838] {aka GGT}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** Liver tissue lesions (MESH:D008107), hepatic inflammation (MESH:D007249), fatty degeneration (MESH:D008067), cirrhosis (MESH:D005355), NAFLD (MESH:D065626), liver cirrhosis (MESH:D008103), hepatitis C (MESH:D019698), HBV infection (MESH:D006509), fatty liver disease (MESH:D005234), metabolic dysfunction (MESH:D008659), death (MESH:D003643), lipidosis (MESH:D008064), infection (MESH:D007239), alcoholic hepatitis (MESH:D006519), cholestatic hepatitis (MESH:D002779), insulin resistance (MESH:D007333), CHB (MESH:D019694), liver tissue damage (MESH:D056486), Liver injury (MESH:D017093), HCC (MESH:D006528), lipid toxicity (MESH:D011017), tissue (MESH:D017695), chronic (MESH:D002908)
- **Chemicals:** TBil (MESH:D001663), S (MESH:D013455), lipid (MESH:D008055), alcohol (MESH:D000438), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935996/full.md

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Source: https://tomesphere.com/paper/PMC12935996