Clinical utility of telomeres as diagnostic and short-term prognostic markers in loco-regional treatment of hepatocellular carcinoma

doi:10.3748/wjg.v31.i46.112530

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Dec 14, 2025; 31(46): 112530
Published online Dec 14, 2025. doi: 10.3748/wjg.v31.i46.112530

Table 1 Correlation between telomere length (× 10³) according to demographic characteristics and tumor size in the hepatocellular carcinoma and chronic liver disease groups

Telomere length with variables		HCC group	CLD group
Sex	Male	1.2 (1.0-1.8)	1.4 (1.1-2.2)
	Female	1.9 (1.5-2.1)	1.2 (1.0-1.5)
	P value	0.120	0.391
Smoking	Yes	1.2 (0.9-1.8)	1.4 (1.0-1.8)
	No	1.3 (1.0-2.1)	1.2 (1.1-1.9)
	P value	0.378	1.000
Hypertension	Yes	1.3 (0.9-1.8)	1.3 (0.8-1.6)
	No	1.3 (1.0-1.8)	1.4 (1.1-1.9)
	P value	0.851	0.568
Diabetes mellitus	Yes	1.1 (0.9-1.5)	1.2 (0.9-1.5)
	No	1.5 (1.2-2.1)	1.5 (1.1-2.2)
	P value	0.061	0.128
Size	≥ 5 cm	1.1 (1.0-1.5)
	< 5 cm	1.9 (1.3-2.2)
	P value	0.030^a
BCLC staging	0	1.7 (1.1-2.0)
	A	2.1 (1.3-2.3)
	B	1.1 (1.0-1.5)
	P value	0.075

^aP value < 0.05.

HCC: Hepatocellular carcinoma; CLD: Chronic liver disease; BCLC: Barcelona Clinic Liver Cancer.

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Table 2 Comparison of demographic characteristics between the hepatocellular carcinoma and chronic liver disease groups, n (%)

Variables		HCC group (total = 30)	CLD group (total = 30)	P value
Age (years)	mean ± SD	64.0 ± 8.2	61.5 ± 8.6	¹0.267
Age (years)	Range	50.0-78.0	49.0-86.0	¹0.267
Sex	Male	27 (90.0)	23 (76.7)	²0.166
Sex	Female	3 (10.0)	7 (23.3)	²0.166
Smoking		19 (63.3)	16 (53.3)	²0.432
Hypertension		8 (26.7)	6 (20.0)	²0.542
Diabetes mellitus		14 (46.7)	12 (40.0)	²0.602

¹Independent t-test.

²χ² test.

HCC: Hepatocellular carcinoma; CLD: Chronic liver disease.

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Table 3 Hepatocellular carcinoma characteristics including possible cause, tumor size, treatment and response in the hepatocellular carcinoma group

Variables		n	%
Possible cause	HCV	25	83.3
	HBV	2	6.7
	Unknown	3	10.0
HCC treatment	TACE	24	80.0
HCC treatment	RF	6	20.0
Response	Complete	16	53.3
Response	Partial	14	46.7
Size (cm²)	Median (1^st-3^rd IQ)	26.3 (8.4-59.3)
Size (cm²)	Range	1.2-138.0

Total = 30. HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; HBV: Hepatitis B virus; TACE: Transarterial chemoembolization; RF: Radiofrequency; IQ: Interquartile.

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Table 4 Hepatocellular carcinoma characteristics and tumor size before and after treatment in the hepatocellular carcinoma group

Variables		HCC group (total = 30)			P value
Variables		Before	After	Change	P value
Number, n (%)	0	0 (0.0)	16 (53.3)		< 0.001¹^,³
	1	26 (86.7)	14 (46.7)
	2	4 (13.3)	0 (0.0)
Size (cm²; total = 14)	Median (1^st-3^rd IQ)	60.5 (36.7-82.0)	29.1 (14.6-54.6)	-34.3 (-42.5 to -21.4)	< 0.001²^,³
Size (cm²; total = 14)	Range	20.0-138.0	6.6-99.0	-57.6 to 17.6	< 0.001²^,³

¹Marginal homogeneity test.

²Wilcoxon signed-rank test.

³Significant.

HCC: Hepatocellular carcinoma; IQ: Interquartile.

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Table 5 Laboratory findings before and after treatment in the hepatocellular carcinoma group

Variables		Before	After	Change	P value
INR	mean ± SD	1.2 ± 0.2	1.3 ± 0.2	0.1 ± 0.2	0.021¹^,³
INR	Range	1.0-1.7	1.0-1.6	-0.3 to 0.5	0.021¹^,³
Total bilirubin (mg/dL)	mean ± SD	1.0 ± 0.5	1.2 ± 0.5	0.2 ± 0.5	0.084¹
Total bilirubin (mg/dL)	Range	0.2-2.1	0.4-2.2	-1.3 to 1.1	0.084¹
Albumin (g/dL)	mean ± SD	3.8 ± 0.6	3.4 ± 0.4	-0.4 ± 0.4	< 0.001¹^,³
Albumin (g/dL)	Range	2.8-4.8	2.7-4.3	-1.2 to 0.3	< 0.001¹^,³
ALT (U/L)	mean ± SD	28.1 ± 15.4	24.1 ± 15.3	-4.0 ± 16.9	0.201¹
ALT (U/L)	Range	6.0-76.0	9.0-70.0	-62.0 to 43.0	0.201¹
AST (U/L)	mean ± SD	43.8 ± 26.5	38.2 ± 16.8	-5.6 ± 21.9	0.172¹
AST (U/L)	Range	10.0-140.0	21.0-110.0	-86.0 to 21.0	0.172¹
AFP (ng/mL)	Median (1^st-3^rd IQ)	31.5 (6.2-235.0)	11.5 (4.2-101.0)	-14.9 (-192.0 to -1.9)	< 0.001²^,³
AFP (ng/mL)	Range	0.9-800.0	0.8-388.0	-456.0 to 2.9	< 0.001²^,³
Telomere length (× 10³)	Median (1^st-3^rd IQ)	1.3 (1.0-1.8)	1.6 (1.0-1.9)	0.3 (-0.8 to 0.8)	0.504²
Telomere length (× 10³)	Range	0.5-3.5	0.6-5.3	-1.8 to 4.3	0.504²

¹Paired t-test.

²Wilcoxon signed-rank test.

³Significant.

Total = 30. INR: International normalized ratio; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: Alpha fetoprotein; IQ: Interquartile.

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Table 6 Alpha fetoprotein and telomere length before and after treatment between the hepatocellular carcinoma and chronic liver disease groups

Variables		HCC group (total = 30)		CLD group (total = 30)	P value
Variables		Before	After	CLD group (total = 30)	Before	After
AFP (ng/mL)	Median (1^st-3^rd IQ)	31.5 (6.2-235.0)	11.5 (4.2-101.0)	11.5 (4.2-101.0)	0.198	0.999
AFP (ng/mL)	Range	0.9-800.0	0.8-388.0	0.8-388.0	0.198	0.999
Telomere length (× 10³)	Median (1^st-3^rd IQ)	1.3 (1.0-1.8)	1.6 (1.0-1.9)	1.4 (1.1-1.9)	0.626	0.647
Telomere length (× 10³)	Range	0.5-3.5	0.6-5.3	0.4-7.6	0.626	0.647

HCC: Hepatocellular carcinoma; CLD: Chronic liver disease; AFP: Alpha fetoprotein; IQ: Interquartile.

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Table 7 Correlations between alpha fetoprotein (ng/mL) and age, telomere length, Model for End-Stage Liver Disease, Child-Pugh score and tumor size before and after treatment in the hepatocellular carcinoma and chronic liver disease groups (Spearman correlation test)

AFP with variables		HCC group (total = 30)			CLD group (total = 30)
AFP with variables		Before	After	Change	CLD group (total = 30)
Age (years)	r value	-0.110			0.000
Age (years)	P value	0.561			0.999
Telomere length (× 10³)	r value	-0.182	0.147	-0.196	0.084
Telomere length (× 10³)	P value	0.335	0.437	0.298	0.659
MELD score	r value	0.304	0.349	0.005	0.150
MELD score	P value	0.102	0.059	0.978	0.430
Child-Pugh score	r value	0.214	0.350	-0.163	0.046
Child-Pugh score	P value	0.257	0.058	0.390	0.809
Tumor size (cm²)	r value	0.422	0.112	0.209
Tumor size (cm²)	P value	0.02¹	0.703	0.474

AFP: Alpha fetoprotein; HCC: Hepatocellular carcinoma; CLD: Chronic liver disease; MELD: Model for End-Stage Liver Disease.

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Table 8 Correlations between telomere length (× 10³) and age, tumor size, Model for End-Stage Liver Disease and Child-Pugh scores before and after treatment in the hepatocellular carcinoma and chronic liver disease groups (Spearman correlation test)

Telomere length with variables		HCC group (total = 30)			CLD group (total = 30)
Telomere length with variables		Before	After	Change	CLD group (total = 30)
Age (years)	r value	-0.100			-0.047
Age (years)	P value	0.599			0.805
MELD score	r value	-0.027	-0.130	0.074	-0.174
MELD score	P value	0.887	0.493	0.696	0.357
Child-Pugh score	r value	-0.027	0.028	-0.129	0.182
Child-Pugh score	P value	0.888	0.882	0.496	0.335
Tumor size (cm²)	r value	-0.157	0.130	0.292
Tumor size (cm²)	P value	0.408	0.659	0.311

HCC: Hepatocellular carcinoma; CLD: Chronic liver disease; MELD: Model for End-Stage Liver Disease.

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Table 9 Comparison of alpha fetoprotein and telomere length before and after treatment according to response in the hepatocellular carcinoma group (Mann-Whitney test)

Variables		Response		P value
Variables		Complete (total = 16)	Partial (total = 14)	P value
AFP (ng/mL)	Before	57.6 (4.5-72.4)	291.2 (9.1-500.0)	0.028^a
	After	11.5 (3.3-16.0)	147.4 (8.4-283.0)	0.011^a
	Change	-46.1 (-48.4 to -0.5)	-143.8 (-206.3 to 2.1)	0.119
Telomere length (× 10³)	Before	1.5 (0.9-2.1)	1.4 (1.0-1.5)	0.480
	After	1.8 (0.8-2.0)	1.6 (1.1-1.9)	0.318
	Change	0.3 (-1.1 to 0.8)	0.3 (-0.2 to 0.8)	0.454

^aP value < 0.05.

Data are presented as median (1^st-3^rd interquartile). AFP: Alpha fetoprotein.

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Table 10 Linear regression analysis of independent factors affecting telomere length in the hepatocellular carcinoma group

Factors	Regression coefficient (β)	SE	P value	95%CI	R²
DM	0.477	0.174	0.011	0.120-0.833	0.845
Male sex	0.641	0.246	0.015	0.137-1.145	0.845

DM: Diabetes mellitus; β: Regression coefficient; 95%CI: 95% confidence interval; R²: Coefficient of determination.

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Citation: El-Nakeep S, AbdelAziz H, Michael TG, ElGhandour AM, Abdelsattar HA, Awad FMR, Kasi A. Clinical utility of telomeres as diagnostic and short-term prognostic markers in loco-regional treatment of hepatocellular carcinoma. World J Gastroenterol 2025; 31(46): 112530
URL: https://www.wjgnet.com/1007-9327/full/v31/i46/112530.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i46.112530