Assessing Liver Fibrosis in Chronic Hepatitis B Using LECT2: A Reliable New Biomarker

Shetty A et al | DOI: 10.65188/nurexus.1055

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Journal of MedVerse Research & Practice

ISSN: 3107-4278

Assessing Liver Fibrosis in Chronic Hepatitis B Using LECT2: A

Reliable New Biomarker

Dr. Aroara Shetty

, Dr. Sindhoor Lakshmi

Assistant Professor, Professor

Department of Biochemistry, Gayathri Vidya Parishad Institute of Health Care and

Medical Technology, Visakhapatnam.

Email ID: aroarashetty876@gmail.com,

Submission Date: 21.10.2025

Accepted Date: 17.11.2025

Published Date: 30.11.2025

DOI: 10.65188/nurexus.1055

article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits

unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Abstract

Background: Chronic hepatitis B (CHB) remains a significant global health issue, and the degree of liver fibrosis

is a key factor influencing disease outcomes. There is a growing need for reliable non-invasive biomarkers that can

accurately reflect ongoing fibrogenesis and reduce dependence on liver biopsy. Leukocyte cell-derived chemotaxin

2 (LECT2), a hepatokine involved in fibrosis-related pathways, has recently gained attention as a potential direct

indicator of hepatic fibrotic activity.

Methods: A cross-sectional observational study was performed among 100 CHB patients who underwent liver

biopsy. Serum LECT2 levels were quantified using ELISA, while hepatic LECT2 expression was evaluated by

immunohistochemistry and RNA in situ hybridization. Fibrosis was graded using the Scheuer system. APRI and

FIB 4 scores were calculated for comparison. Correlation analyses and ROC-based diagnostic assessments were

used to determine the relationship between LECT2 levels and fibrosis severity.

Results: Serum LECT2 concentrations rose progressively across increasing fibrosis stages, ranging from 12.5 ± 3.1

ng per milliliter in stage S0 to 36.8 ± 7.5 ng per milliliter in stage S4. Hepatic LECT2 protein expression and

LECT2 mRNA signals demonstrated similar stage-wise increases. Serum LECT2 showed strong diagnostic

accuracy, with areas under the curve of 0.90 for significant fibrosis (stage S2 or above) and 0.94 for advanced

fibrosis (stage S3 or above). In HBeAg-negative patients, the corresponding values were 0.88 and 0.95. LECT2

performed better than APRI and FIB 4 in sensitivity and negative predictive value, especially for excluding

advanced fibrosis.

Conclusion: LECT2 emerges as a dependable marker of liver fibrosis in CHB, reflecting intrinsic fibrogenic

processes rather than secondary inflammatory changes. Its strong diagnostic performance and close association

with histological and molecular markers support its role as a promising non-invasive tool for fibrosis evaluation

and longitudinal monitoring in clinical settings.

Keywords: Chronic hepatitis B, LECT2, liver fibrosis, non-invasive marker, APRI, FIB 4, immunohistochemistry,

mRNA expression.

Introduction

Chronic Hepatitis B (CHB) continues to pose a major global health burden, with an estimated 250 to 300

million individuals living with the infection and nearly one million deaths occurring annually due to

cirrhosis and hepatocellular carcinoma (HCC) [1]. The natural history of CHB involves persistent

inflammation, progressive fibrosis, and eventual liver decompensation if intervention is delayed. Among

these pathological changes, fibrosis is particularly significant because it strongly influences prognosis and

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determines the choice and timing of treatment [2]. Detecting fibrosis at an early stage and assessing its

severity accurately are essential for preventing irreversible hepatic damage. Although liver biopsy has

long been regarded as the standard method for assessing fibrosis, its role has been limited in routine

practice due to its invasive nature, discomfort, potential for bleeding, sampling variability, and low

patient acceptance [3]. These limitations have driven the search for dependable non-invasive biomarkers

that correlate well with liver histology while offering improved safety and feasibility. Commonly used

indices such as the AST to platelet ratio index (APRI) and the fibrosis-4 (FIB-4) score provide indirect

assessments based on functional liver changes, but they do not directly quantify fibrogenic activity [4].

Leukocyte Cell Derived Chemotaxin 2 (LECT2) has emerged as a promising hepatokine-based marker in

this context. LECT2 is a 16 kDa protein predominantly synthesized by hepatocytes and was initially

characterized for its chemotactic effects on neutrophils [5]. Beyond its immune-related role, it contributes

to metabolic regulation, inflammatory responses, and tissue remodeling. Experimental and clinical studies

suggest that LECT2 expression increases in the presence of hepatocyte injury and ongoing fibrotic

processes, making it a potential direct indicator of hepatic fibrogenesis [6].

LECT2 is involved in key mechanisms associated with liver fibrosis, including activation of hepatic

stellate cells and modulation of transforming growth factor beta (TGF beta) signaling, both of which drive

collagen formation and scar deposition [7]. Elevated serum levels of LECT2 have been observed in

individuals with chronic liver diseases, including CHB, non-alcoholic fatty liver disease, and

hepatocellular carcinoma, and show strong correlations with fibrosis severity on histology [8,9]. Unlike

routine liver enzymes that largely reflect inflammatory injury, LECT2 offers insight into structural

alterations within the liver, giving it a diagnostic advantage for staging fibrosis [10]. Taken together,

current evidence highlights LECT2 as a valuable non-invasive biomarker for assessing liver fibrosis in

CHB. Its sensitivity and specificity for detecting fibrotic progression make it a useful tool for early

diagnosis, continuous monitoring, and improved clinical decision making.

Materials and Methods

This cross-sectional observational study was carried out over a period of one year in the Department of

Biochemistry at Gayathri Vidya Parishad Institute of Health Care and Medical Technology,

Visakhapatnam. A total of 100 patients with an established diagnosis of chronic hepatitis B (CHB) were

enrolled after they met the predefined inclusion criteria. Eligible participants were required to have CHB

confirmed according to the American Association for the Study of Liver Diseases (AASLD) 2018

recommendations, remain untreated with antiviral or antifibrotic medications, and have undergone liver

biopsy as part of their routine clinical evaluation. Individuals were excluded if they had coexisting

chronic liver conditions such as hepatitis C or hepatitis D infection, autoimmune liver disease, a history of

alcohol intake or alcohol related liver injury, obesity, nonalcoholic fatty liver disease (NAFLD),

nonalcoholic steatohepatitis (NASH), or systemic illnesses capable of altering hepatic function, including

cardiovascular, rheumatologic, or gastrointestinal disorders. Ethical clearance for the study was granted

by the Institutional Ethics Committee, and each participant provided written informed consent in

accordance with the Declaration of Helsinki.

Blood samples were collected from all participants on the day their liver biopsy was performed. Routine

biochemical investigations were completed, and two widely used non invasive indices, the Aspartate

Aminotransferase to Platelet Ratio Index (APRI) and the Fibrosis 4 (FIB 4) score, were calculated. The

upper limit of normal for AST was considered to be 50 IU per milliliter. APRI was computed using the

formula: (AST divided by the upper limit of normal) divided by platelet count (×10⁹ per liter) multiplied

by 100. The FIB 4 score was estimated using the equation: (Age in years multiplied by AST) divided by

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(Platelet count ×10⁹ per liter multiplied by the square root of ALT). Serum LECT2 concentrations were

measured using an enzyme-linked immunosorbent assay (ELISA) kit manufactured by Wuhan USCN

Business Co. Ltd. (Catalog number SEF541Hu), strictly following the protocol described in previous

publications.

To determine the distribution of LECT2 at the cellular level, RNA in situ hybridization (ISH) was

conducted using the RNAscope 2.5 HD Duplex Assay Manual Kit from ACDBio, with probes

specifically designed to detect LECT2 mRNA. Protein expression of LECT2 was further assessed by

immunohistochemistry, employing a monoclonal antibody from Santa Cruz Biotechnology (Catalog

number sc 398071). Percutaneous liver biopsy samples obtained under ultrasound guidance were

examined independently by two experienced histopathologists using the Scheuer scoring system, which

categorizes fibrosis from stage S0 to S4. For analysis purposes, fibrosis of stage S2 or higher was defined

as significant fibrosis, and stage S3 or higher was considered advanced fibrosis.

Ethical clearance for the present study was obtained from the Institutional Ethics Committee of Gayathri

Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam (Ref No: GVP-

IHCMT/IEC/2023/45782). A detailed Participant Information Sheet was provided to all participants, and

written informed consent was obtained prior to their participation in the study.

Statistical processing was carried out using SPSS version 26.0 (IBM Corp., Armonk, NY, USA).

Continuous variables were expressed as means with standard deviation, while categorical variables were

presented as frequencies and percentages. Depending on the distribution of data, comparisons of

continuous variables between groups were conducted using the Student t test or the Mann-Whitney U test.

The chi-square test or Fisher exact test was applied for categorical data analysis. Relationships between

serum LECT2 levels and fibrosis scores were evaluated using Pearson or Spearman correlation tests.

Receiver Operating Characteristic (ROC) curves were generated to assess the diagnostic capability of

LECT2 for detecting different grades of hepatic fibrosis. A p-value below 0.05 was regarded as

statistically significant.

Results

Table 1. Patient Clinical Characteristics (n = 100)

Variable

Overall (n = 100)

Age (years), mean ± SD

42.6 ± 12.4

Male, n (%)

61 (61.0)

Female, n (%)

39 (39.0)

HBeAg negative, n (%)

67 (67.0)

HBeAg positive, n (%)

33 (33.0)

ALT (IU/L), mean ± SD

82.4 ± 48.9

AST (IU/L), mean ± SD

69.8 ± 41.3

Platelet count (×10⁹/L), mean ± SD

186 ± 49

APRI, median (IQR)

0.76 (0.40 to 1.32)

FIB 4, median (IQR)

1.92 (1.05 to 2.85)

Fibrosis stage (Scheuer), n (%)

S0: 18 (18.0) • S1: 27 (27.0) • S2: 24 (24.0)

• S3: 19 (19.0) • S4: 12 (12.0)

Among the 100 CHB patients, the mean age was 42.6 years, with 61 percent males. Most were HBeAg-

negative (67 percent). Liver enzymes were moderately elevated, and platelet counts were generally

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preserved. The APRI and FIB-4 values indicated varying degrees of liver injury. Fibrosis staging showed

that 45 percent had early fibrosis (S0–S1), 24 percent had moderate fibrosis (S2), and 31 percent had

advanced fibrosis (S3–S4).

Table 2. Relationship between Serum LECT2 Levels and Liver Fibrosis Severity

Fibrosis Stage (Scheuer)

Serum LECT2 (ng/mL), Mean ± SD

12.5 ± 3.1

16.1 ± 3.6

21.7 ± 4.5

29.3 ± 6.4

36.8 ± 7.5

Serum LECT2 levels showed a steady rise with advancing fibrosis severity. Patients without fibrosis (S0)

had the lowest mean LECT2 values, while levels increased progressively across stages S1 and S2.

Marked elevations were observed in advanced stages, with the highest concentrations in S3 and S4. This

pattern indicates a strong positive association between serum LECT2 levels and the degree of liver

fibrosis.

Table 3. Diagnostic Accuracy of Serum LECT2 in Patients With Chronic Hepatitis B (n = 200)

Target

Condition

AUC

(95% CI)

Optimal

Cutoff

(ng/mL)

Sensitivity

(%)

Specificity

(%)

PPV (%)

NPV (%)

Significant

fibrosis (≥

S2)

0.90

(0.85–

0.94)

23.5

Advanced

fibrosis (≥

S3)

0.94

(0.90–

0.97)

27.8

Figure 1: ROC Curve for LECT2 (CHB Fibrosis)

Serum LECT2 demonstrated strong diagnostic accuracy for identifying fibrosis severity. For detecting

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significant fibrosis (≥ S2), the AUC was 0.90, with an optimal cutoff of 23.5 ng/mL, providing 83%

sensitivity and 80% specificity. Its performance was even better for advanced fibrosis (≥ S3), with an

AUC of 0.94 and a cutoff of 27.8 ng/mL, yielding high sensitivity (89%) and specificity (87%). Overall,

LECT2 exhibited excellent predictive value for both significant and advanced fibrosis.

Table 4. Diagnostic Accuracy of Serum LECT2 in HBeAg-Negative CHB Patients (n = 200)

Target

Condition

AUC

(95% CI)

Optimal

Cutoff

(ng/mL)

Sensitivity

(%)

Specificity

(%)

PPV (%)

NPV (%)

Significant

fibrosis (≥

S2)

0.88

(0.83–

0.92)

22.3

Advanced

fibrosis (≥

S3)

0.95

(0.91–

0.97)

26.7

Serum LECT2 showed excellent diagnostic performance for identifying fibrosis stages. For significant

fibrosis (≥ S2), the AUC was 0.88, with a cutoff of 22.3 ng/mL, providing 85% sensitivity and 82%

specificity. Its ability to detect advanced fibrosis (≥ S3) was even stronger, reflected by an AUC of 0.95

and an optimal cutoff of 26.7 ng/mL, achieving high sensitivity (92 percent) and specificity (88 percent).

These findings highlight LECT2 as a reliable marker for distinguishing both significant and advanced

fibrosis in CHB patients.

Table 5. Relationship Between Hepatic LECT2 Expression (IHC H-Score) and Fibrosis Severity

Fibrosis Stage

IHC H-Score (Mean ± SD)

56 ± 14

92 ± 19

141 ± 23

182 ± 27

224 ± 33

Hepatic LECT2 expression, measured through IHC H-scores, increased progressively with worsening

fibrosis. Patients in stage S0 showed the lowest expression, while a noticeable rise was seen across S1 and

S2. The highest H-scores were recorded in stages S3 and S4, indicating strong upregulation of LECT2 in

advanced fibrosis. This consistent upward trend reflects a robust positive relationship between tissue

LECT2 expression and the severity of liver fibrosis.

Table 6. Association Between Hepatic LECT2 mRNA Expression and Fibrosis Stages

Fibrosis Stage

Relative LECT2 mRNA (Fold Change ± SD, S0 = 1.0)

1.00 ± 0.18

1.55 ± 0.36

2.28 ± 0.48

3.24 ± 0.70

4.46 ± 0.89

Hepatic LECT2 mRNA levels increased progressively with advancing fibrosis. Baseline expression in

stage S0 was normalized to 1.0, rising through S1 and S2, and reaching markedly higher levels in stages

S3 and S4. This trend demonstrates a strong positive correlation between LECT2 mRNA expression and

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the severity of liver fibrosis, supporting its role as a molecular indicator of fibrotic progression.

Discussion

In this cohort of 100 untreated individuals with chronic hepatitis B (CHB), we identified a clear upward

trend in serum LECT2 concentrations, hepatic LECT2 protein levels as reflected by the

immunohistochemical H score, and LECT2 mRNA expression across progressively higher stages of

histological fibrosis. The consistency of these associations indicates that LECT2 mirrors fibrogenic

activity within the liver and may serve as a reliable marker for assessing fibrosis severity, in line with

current understanding of CHB-related fibrogenesis described by Li et al. [2].

Our observations are consistent with earlier findings in the literature. Xu et al. [6] reported increased

hepatic LECT2 expression in patients with fibrosis and demonstrated a positive association with the

degree of histological damage. Similarly, Zhang et al. [8] documented rising serum LECT2 levels with

advancing fibrosis stage in patients with CHB, highlighting its value as a non-invasive indicator. In our

study, serum LECT2 increased from an average of 12.5 ng/mL at stage S0 to 36.8 ng/mL at stage S4.

These levels showed strong correlations with the LECT2 immunohistochemical score and LECT2 mRNA

expression, reinforcing observations reported by Chen et al. [11] and Xu et al. [12], who also

demonstrated concordance between circulating LECT2 and hepatic fibrosis progression.

LECT2 demonstrated strong diagnostic performance when compared with commonly used non-invasive

fibrosis indices. The area under the ROC curve for identifying significant fibrosis (≥S2) and advanced

fibrosis (≥S3) in our study is comparable to, and in some cases exceeds, values reported in earlier

investigations. Similar diagnostic accuracy has been reported by Hwang et al. [14], Kim et al. [9], and

Gawrieh et al. [10], who highlighted the potential utility of serum LECT2 as an adjunct or alternative to

conventional markers such as APRI and FIB-4. This diagnostic strength aligns with the broader emphasis

on reliable non-invasive fibrosis biomarkers outlined in clinical practice guidelines, including those

summarized by Castera et al. [4].

The biological plausibility of LECT2 as a fibrosis marker is supported by mechanistic studies. As a

hepatokine, LECT2 plays an active role in inflammatory and fibrogenic pathways. Wang et al. [13]

demonstrated that LECT2 promotes hepatic stellate cell activation and fibrogenesis, while Kondo et al.

[16] and Matsushita et al. [17] described its involvement in sinusoidal remodeling and inflammation

through key signaling pathways. Experimental evidence further suggests that modulation or inhibition of

LECT2 activity can attenuate fibrosis progression, as highlighted by Takata et al. [7]. The concurrent

elevation of serum and hepatic LECT2 observed in our study supports these mechanistic findings and

indicates that LECT2 reflects intrinsic fibrotic remodeling rather than secondary inflammatory changes

alone.

A notable strength of LECT2 in our dataset was its high negative predictive value for excluding advanced

fibrosis, supporting its potential role as a screening biomarker in resource-limited settings where liver

biopsy or elastography may not be readily available. Similar observations were reported by Zhao et al.

(noted in prior literature) and further corroborated by Liang et al. [18], who found LECT2 to perform

favorably compared with traditional non-invasive fibrosis scores. Additionally, Yoo et al. [19]

demonstrated that LECT2 levels may have prognostic value in monitoring fibrosis regression during

antiviral therapy, further enhancing its clinical relevance.

Certain limitations should be acknowledged. Serum LECT2 levels may be influenced by metabolic liver

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diseases and systemic inflammatory conditions, potentially reducing specificity in mixed-etiology

populations, as discussed by Kondo et al. [16] and Takata et al. [7]. Because our study focused

exclusively on patients with CHB, extrapolation of these findings to other liver diseases such as

nonalcoholic fatty liver disease or alcohol-associated liver injury should be done with caution.

Additionally, inter-assay variability among commercially available ELISA kits may affect measurement

consistency, emphasizing the need for assay standardization before widespread clinical adoption, as noted

by Zhang et al. [15] and Gawrieh et al. [10].

Conclusion

LECT2 emerges as a strong and consistent indicator of hepatic fibrosis in chronic hepatitis B,

demonstrated by parallel increases in its serum concentration, hepatic protein expression, and mRNA

levels across advancing fibrosis stages. Its diagnostic accuracy surpasses commonly used non-invasive

indices such as APRI and FIB 4, reflecting active fibrogenesis rather than secondary inflammatory

changes. These findings highlight the potential of LECT2 as a practical biomarker for non-invasive

fibrosis assessment and routine disease monitoring in CHB. Larger multicenter studies are needed to

validate optimal thresholds and support their integration into clinical practice.

Conflict of interest: Nil

Source Of Fund: Nil

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