Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun;19(3):596-606.
doi: 10.1007/s12072-024-10768-1. Epub 2024 Dec 20.

Cell-free DNA methylation-based inflammation score as a marker for hepatocellular carcinoma among people living with HIV

Kyeezu Kim #  1   2 , Yinan Zheng #  3 , Brian T Joyce  3 , Drew R Nannini  3 , Jun Wang  3 , Yishu Qu  3 , Claudia A Hawkins  4 , Edith Okeke  5 , Olufunmilayo A Lesi  6 , Lewis R Roberts  7 , Demirkan B Gursel  4 , Fatimah B Abdulkareem  6 , Alani S Akanmu  6 , Mary J Duguru  5 , Pantong Davwar  5 , David Paul Nyam  5 , Rahmat A Adisa  6 , Godwin Imade  5 , Jian-Jun Wei  4 , Masha Kocherginsky  3 , Kwang-Youn Kim  3 , Wasiu L Adeyemo  6 , Emuobor Odeghe  6 , Firas H Wehbe  3 , Chad Achenbach  3 , Atiene Sagay  5 , Folasade Ogunsola  6 , Robert L Murphy  3   4 , Lifang Hou  8   9   10
Affiliations

Cell-free DNA methylation-based inflammation score as a marker for hepatocellular carcinoma among people living with HIV

Kyeezu Kim et al. Hepatol Int. 2025 Jun.

Abstract

Background: People living with the human immunodeficiency virus (HIV) are at a greater risk of developing hepatocellular carcinoma (HCC), potentially due to the stimulation of inflammation by HIV infection. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (cfDNA), may serve as promising minimally invasive biomarkers that can inform diagnosis of HCC.

Methods: Using data from 249 individuals with HIV (114 individuals with normal liver conditions, 69 with fibrosis, 30 with cirrhosis, and 36 with HCC), we constructed a cfDNA methylation-based inflammation score (inflammation-DNAm score) based on 54 CpGs previously associated with circulating C-reactive protein concentrations. Associations of DNAm scores with HCC were assessed using multivariable logistic regression models. Receiver operating characteristic analysis was conducted to assess the performance of discriminating HCC between the inflammation-DNAm score and alpha-fetoprotein (AFP), one of the current screening biomarkers.

Results: A higher inflammation-DNAm score was associated with a 29% increase in the odds of HCC (OR = 1.29, 95% CI = 1.01-1.65). The association remained consistent in the models adjusted for cellular origin proportions. The DNAm score exhibited superior performance in discriminating HCC from controls (AUC = 0.94, 95% CI = 0.90-0.98), compared to AFP (AUC = 0.68, 95% CI = 0.51-0.85).

Conclusions: Our findings suggest that cfDNA methylation-based biomarkers may aid in the detection of HCC in people living with HIV, a population at high-risk of developing HCC.

Keywords: C-reactive protein; Cell-free DNA methylation; Hepatocellular carcinoma; Methylation risk score; Methylation-based inflammation measures.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: All participants provided written, informed consent and the IRB at each institute (JUTH, LUTH, and Northwestern University in Chicago, IL, USA) reviewed and approved the study protocol.

References

    1. Samant H, Amiri HS, Zibari GB. Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management. J Gastrointest Oncol. 2021;12(Suppl 2):S361–S373 - DOI - PubMed - PMC
    1. Joshi D, O’Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet. 2011;377(9772):1198–1209 - DOI - PubMed
    1. Thrift AP, Chiao EY. Are non-HIV malignancies increased in the HIV-infected population? Curr Infect Dis Rep. 2018;20(8):22 - DOI - PubMed - PMC
    1. Davwar PM, Okeke E, Duguru M, Nyam D, Bell K, Odeghe EA, et al. Hepatocellular carcinoma presentation and prognosis among Nigerian adults with and without HIV. PLoS One. 2023;18(3): e0282539 - DOI - PubMed - PMC
    1. Shiels MS, Islam JY, Rosenberg PS, Hall HI, Jacobson E, Engels EA. Projected cancer incidence rates and burden of incident cancer cases in HIV-infected adults in the United States through 2030. Ann Intern Med. 2018;168(12):866–873 - DOI - PubMed - PMC

LinkOut - more resources