Impact of the IL-18 gene polymorphism in response to
                    antiviral therapy in chronic HCV genotype 4 patients

Mandour, Mohamed; Nemr, Nader; Kishk, Rania; Ahmed, Eman

doi:10.1590/0037-8682-0024-2014

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Major Articles • Rev. Soc. Bras. Med. Trop. 47 (2) • Mar-Apr 2014 • https://doi.org/10.1590/0037-8682-0024-2014 copy

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

Authorship SCIMAGO INSTITUTIONS RANKINGS

Introduction

Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited.

Methods

This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples.

Results

In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients.

Conclusions

The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

Discrete variables	Patients (n=123)		Healthy controls (n=123)
Discrete variables	n	%	n	%
Gender
male	83	67.5	71	57.7
female	40	32.5	52	42.3
Residence
urban	70	56.9	68	55.2
rural	53	43.1	55	44.8

Continuous variables	Patients (n=123)	Healthy controls (n=123)
Continuous variables	Mean ± SD	Mean ± SD
Age (years)	42.3 ± 9.1	36.5 ± 8.7
AST (Mean ± SD)	46.0 ± 26.3	20.4 ± 6.6
ALT (Mean ± SD)	48.9 ± 31.8	22.6 ± 6.6

rs1946518 genotype	Patients (n=123)		Controls (n=123)		χ²	p-value
rs1946518 genotype	n	%	n	%	χ²	p-value
AA	20	16.3	26	21.1
CA	63	51.2	58	47.1	0.878	0.645 (NS)
CC	40	32.5	39	31.8

		Non-SVR (n=67)		SVR (n=56)		RR	95% CI
Age <45 years	no	36	53.7	24	42.9	1.24	0.88 – 1.74
Age <45 years	yes	31	46.3	32	57.1
Male gender	no	24	35.8	16	28.6	1.11	0.87 – 1.42
Male gender	yes	43	64.2	40	71.4
Rural residence	no	44	65.7	26	45.6	1.56^* * Statistically significant RR.	1.03 – 2.35
Rural residence	yes	23	34.3	30	53.6
Fibrosis stage	0/6 – 3/6	51	76.1	46	82.1	1.08	0.90 – 1.29
Fibrosis stage	4/6 – 6/6 (ref)	16	23.9	10	17.9
Inflammation grade	0/18 – 8/18	51	76.1	48	85.7	1.13	0.95 – 1.34
Inflammation grade	9/18 – 18/18 (ref)	16	23.9	8	14.3
Antischistosomal antibodies	negative	45	67.2	35	62.5	0.93	0.72 – 1.21
Antischistosomal antibodies	positive (ref)	22	32.8	21	37.5
ALT (>40 IU)	no	40	59.7	19	33.9	1.64^* * Statistically significant RR.	1.16 – 2.32
ALT (>40 IU)	yes	27	40.3	37	66.1
AST (>45IU)	no	43	64.2	27	48.2	1.45	0.96 – 2.17
AST (>45IU)	yes	24	35.8	29	51.8
HCV-RNA ≤ 800,000 IU	no	22	32.8	19	33.9	0.98	0.76 – 1.27
HCV-RNA ≤ 800,000 IU	yes	45	67.2	37	66.1
rs1946518 genotype	CC (ref)	25	37.3	15	26.8	--	--
	CA	29	43.3	34	60.7	1.29	0.95 – 1.76
	AA	13	19.4	7	12.5	0.93	0.44 – 1.98

Predictors	B	SE	p-value	Adjusted OR	95% CI adjusted OR
Predictors	B	SE	p-value	Adjusted OR	lower	upper
Age <45 years	0.266	0.429	0.535	1.304	0.563	3.021
Male gender	0.249	0.437	0.568	1.283	0.545	3.020
Rural residence	0.786	0.408	0.054	2.196	0.987	4.884
Fibrosis stage (0-3)	-0.114	0.544	0.834	0.892	0.307	2.592
Inflammation grade (0-8)	0.691	0.571	0.226	1.996	0.652	6.111
Negative antischistosomal antibodies	-0.271	0.432	0.530	0.763	0.327	1.779
AST (>45 IU)	0.012	0.487	0.980	1.012	0.390	2.629
ALT (>40 IU)	1.113	0.477	0.020*	3.045	1.195	7.759
HCV-RNA ≤ 800,000 IU	0.331	0.445	0.458	1.392	0.581	3.333
rs1946518 (CC)			0.256
rs1946518 (CA)	-0.175	0.455	0.701	0.840	0.344	2.049
rs1946518 (AA)	0.823	0.636	0.196	2.278	0.655	7.923
Constant	-1.962	0.809	0.015	0.141

Treatment outcomes	rs1946518 genotype						p-value^a a Linear-by-linear association chi-square test.
Treatment outcomes	AA (n=20)		CA (n=63)		CC (n=40)		p-value^a a Linear-by-linear association chi-square test.
NVR	0	0.0	8	12.7	3	7.5	0.269
SVR	11	55.0	26	41.3	18	45.0	(NS)
TVR	9	45.0	29	46.0	19	47.5

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[1] CONFLICT OF INTEREST The authors have disclosed all financial and personal relationships with other people or organizations that could inappropriately infl uence or bias the work. No competing interests are declared with this article.