# Detecting early kidney injury due to host–virus interaction response in treatment-naive CHB—a pilot study

**Authors:** Puneet Gandhi, Kavita Peter, Subodh Varshney, Mahendra Kumar Atlani, Kewal Krishan Maudar

PMC · DOI: 10.3389/fcimb.2025.1601678 · Frontiers in Cellular and Infection Microbiology · 2025-07-29

## TL;DR

This pilot study identifies protein biomarkers that can detect early kidney injury in patients with chronic hepatitis B before changes in creatinine levels.

## Contribution

A novel noninvasive panel of protein biomarkers is proposed for early detection of kidney injury in treatment-naive CHB patients.

## Key findings

- sCys-C, sNGAL, and uIL-18BP were significantly elevated in CHB patients compared to controls.
- Combining four biomarkers achieved 97.1% sensitivity and 91.3% specificity in detecting kidney injury.
- sCys-C and sNGAL varied significantly across CHB infection phases.

## Abstract

Clinical evidence suggests that patients with chronic hepatitis B (CHB) have an increased risk of renal impairment due to inflammation induced by virus–host interaction. We aimed to evaluate and validate a set of protein biomarkers singularly and in combination for the early detection of subclinical kidney injury in patients with CHB naive to antiretroviral therapy.

This work is part of a prospective cross-sectional study for which 69 HBsAg-positive, treatment-naive patients with CHB with an equal number of age-matched healthy volunteers were considered. At diagnosis, serum creatinine (sCr), urea, alanine transaminase, aspartate transaminase, serum cystatin-C (sCys-C), serum neutrophil gelatinase-associated lipocalin (sNGAL), serum Fetuin-A (sFet-A), urinary interleukin-18 binding protein (uIL-18BP), and urinary kidney injury molecule-1 (uKIM-1) levels were determined.

There was a significant elevation in the concentrations of three proteins in our CHB cohort (sCys-C, sNGAL, and uIL-18BP; p < 0.0001) while sFet-A was down-regulated (p<0.01) as compared to the control group. A receiver operating characteristic curve analysis revealed an Area under the curve of 0.935 for sCys-C and 0.811 for sNGAL, which improved to 0.984 when all four indicators were combined in a panel to discriminate the onset of renal injury incited by inflammatory response in CHB with 97.1% sensitivity at 91.3% specificity. Additionally, only sCys-C and sNGAL differed significantly among the phases of CHB infection (p<0.05).

This novel noninvasive diagnostic screen is expedient in detecting inflammation and early kidney injury before a rise in sCr and can aid in predicting renal outcomes in patients with CHB.

## Linked entities

- **Proteins:** CYSTATIN-C (cystatin-C), AHSG (alpha 2-HS glycoprotein)
- **Diseases:** chronic hepatitis B (MONDO:0005344)

## Full-text entities

- **Genes:** AHSG (alpha 2-HS glycoprotein) [NCBI Gene 197] {aka A2HS, AHS, APMR1, FETUA, HSGA}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}, HAVCR1 (hepatitis A virus cellular receptor 1) [NCBI Gene 26762] {aka CD365, HAVCR, HAVCR-1, KIM-1, KIM1, TIM}, IL18BP (interleukin 18 binding protein) [NCBI Gene 10068] {aka FVH, IL18BPa}
- **Diseases:** kidney injury (MESH:D007674), CHB (MESH:D019694), inflammation (MESH:D007249)
- **Chemicals:** creatinine (MESH:D003404), sCr (-), urea (MESH:D014508)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12339531/full.md

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Source: https://tomesphere.com/paper/PMC12339531