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Clinical and Experimental Hepatology
eISSN: 2449-8238
ISSN: 2392-1099
Clinical and Experimental Hepatology
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Sarajevo Declaration on Integrity and Visibility of Scholarly Publications
2/2025
vol. 11
 
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abstract:
Original paper

Interplay of PNPLA3 and TM6SF2 variants in modulating the risk of hepatocellular carcinoma among Egyptian hepatitis C patients

Inas M. Moaz
1
,
Samar E. Ghanem
1
,
Fatma O. Khalil
1
,
Hossam A. Galbt
1
,
Ahmed S. Elbauomy
1
,
Shimaa K. Elmahdy
1
,
Marwa A. Tahoon
1

  1. National Liver Institute, Menofia University, Egypt
Clin Exp HEPATOL 2025; 11, 2: 169-178
DOI: https://doi.org/10.5114/ceh.2025.151811
Online publish date: 2025/06/26
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Aim of the study:
One of the main causes of cancer-related death worldwide is hepatocellular carcinoma (HCC), which is significantly common in Egypt because of the high prevalence of hepatitis C virus (HCV) infection. The development of HCC has been linked to genetic variations in the TM6SF2 (rs58542926) and PNPLA3 (rs738409) genes. The aim of this study was to assess PNPLA3 and TM6SF2 genetic variants as risk factors for HCC in Egyptian patients with chronic HCV disease.

Material and methods:
The study included 286 participants divided into three groups: 100 healthy controls, 89 chronic HCV patients without HCC, and 97 HCC patients with chronic HCV. Demographic and clinical data were collected. TaqMan assays were used to genotype PNPLA3 and TM6SF2.

Results:
The PNPLA3 CG/GG genotypes were significantly associated with an increased risk of HCC (OR = 6.8, 95% CI: 2.93-15.8 for CG, and OR = 5.49, 95% CI: 1.45-20.85 for GG). The G allele of PNPLA3 was more prevalent in HCC patients (27.4%) compared to controls (7.0%) (p < 0.001). Conversely, the TM6SF2 CT/TT genotypes did not show a significant association with HCC risk (p = 0.93), and the T allele frequency was similar across all groups (p = 0.66).

Conclusions:
The PNPLA3 (rs738409) polymorphism is a significant risk factor for HCC in Egyptian patients with chronic HCV, with the G allele notably increasing the risk. In contrast, TM6SF2 (rs58542926) polymorphisms did not show a significant association with HCC risk in this population. These findings highlight the potential for genetic screening to identify HCV patients at elevated risk for HCC.

keywords:

hepatocellular carcinoma, hepatitis C virus, PNPLA3 TM6SF2 genetic polymorphisms, Egypt
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