AUTHOR=Abdel-Razik Ahmed , Shabana Walaa , El Nakib Ahmed Mohamed , Abdelsalam Mostafa , Abdelwahab Ahmed , Hasan Ahmad S. , Elzehery Rasha , Elhelaly Rania , Fathy Aya Ahmed , Mostafa Sally Abdallah , El-Wakeel Niveen , Moemen Dalia , Eldars Waleed , Yassen Ahmed H. TITLE=De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver? JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.662431 DOI=10.3389/fcimb.2021.662431 ISSN=2235-2988 ABSTRACT=Background and Purpose

The advanced glycation end products (AGEs) have been implicated in different diseases’ pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis.

Methods

Only 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period.

Results

HCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P <0.001), and AGEs levels (P <0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P<0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P<0.001), using the receiver operating characteristic curve, for prediction of HCC development.

Conclusion

This work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.