Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan

Overview

Journal Front Public Health

Specialty Public Health

Date 2021 Oct 4

PMID 34604157

Citations 13

Authors

Wei-Hao Hsu

Shu-Ping Sue

Hsiu-Ling Liang

Chin-Wei Tseng

Hsiu-Chu Lin

Wei-Lun Wen

Mei-Yueh Lee

Affiliations

Soon will be listed here.

Abstract

Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are incretin-based oral antidiabetic drugs. Previous studies have shown an association between increased plasma activity of DPP-4 and chronic hepatitis C virus (HCV) infection. Dipeptidyl peptidase 4 inhibitors may be associated with preventing the development of chronic HCV infection. The aim of this study was to investigate whether the use of DPP-4 inhibitors is associated with a decreased risk of hepatocellular carcinoma (HCC) in patients with diabetes mellitus (DM) and chronic HCV infection. In this retrospective cohort study, we enrolled patients with type 2 diabetes and chronic HCV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The patients were divided into two groups (DPP-4 inhibitor cohort and non-DPP-4 inhibitor cohort) according to whether or not they received DPP-4 inhibitor treatment. Multivariate Cox proportional hazard regression analysis showed a significantly lower risk of HCC in the patients who took DPP-4 inhibitors compared to those who did not. Kaplan-Meier survival analysis demonstrated a significantly higher HCC-free rate in the DPP-4 inhibitor cohort than in the non-DPP-4 inhibitor cohort. The use of DPP-4 inhibitors was associated with a lower risk of HCC in patients with type 2 DM and chronic HCV infection.

Citing Articles

DPP4, a potential tumor biomarker, and tumor therapeutic target: review.

Sun L, Ma Y, Geng C, Gao X, Li X, Ru Q Mol Biol Rep. 2025; 52(1):126.

PMID: 39821530 DOI: 10.1007/s11033-025-10235-6.

Association between dipeptidyl peptidase-4 inhibitor use and risk of Parkinson's disease among patients with diabetes mellitus: a retrospective cohort study.

Huang K, Yang Y, Gau S, Tsai T, Lee C Aging (Albany NY). 2024; 16(16):11994-12007.

PMID: 39177655 PMC: 11386917. DOI: 10.18632/aging.206074.

Comment on Lai et al. Dipeptidyl Peptidase 4 Stimulation Induces Adipogenesis-Related Gene Expression of Adipose Stromal Cells. 2023, , 16101.

Cordero O, Kotrulev M, Gomez-Tourino I Int J Mol Sci. 2024; 25(13).

PMID: 39000199 PMC: 11241282. DOI: 10.3390/ijms25137093.

A review of MASLD-related hepatocellular carcinoma: progress in pathogenesis, early detection, and therapeutic interventions.

Ma Y, Wang J, Xiao W, Fan X Front Med (Lausanne). 2024; 11:1410668.

PMID: 38895182 PMC: 11184143. DOI: 10.3389/fmed.2024.1410668.

The Impact of Statins on the Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib or Lenvatinib.

Han J, Kim J, Cheong J, Kim S, Lim S, Yang M Cancers (Basel). 2024; 16(2).

PMID: 38254739 PMC: 10813381. DOI: 10.3390/cancers16020249.

References

Holst J . Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia. 2006; 49(2):253-60. DOI: 10.1007/s00125-005-0107-1. View

Gallwitz B . Sitagliptin: profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes (update). Drugs Today (Barc). 2008; 43(11):801-14. DOI: 10.1358/dot.2007.43.11.1157620. View

Overbeek J, Bakker M, van der Heijden A, van Herk-Sukel M, Herings R, Nijpels G . Risk of dipeptidyl peptidase-4 (DPP-4) inhibitors on site-specific cancer: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2018; 34(5):e3004. DOI: 10.1002/dmrr.3004. View

Del Campo J, Garcia-Valdecasas M, Gil-Gomez A, Rojas A, Gallego P, Ampuero J . Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy. PLoS One. 2018; 13(1):e0191805. PMC: 5791999. DOI: 10.1371/journal.pone.0191805. View

Riva A, Laird M, Casrouge A, Ambrozaitis A, Williams R, Naoumov N . Truncated CXCL10 is associated with failure to achieve spontaneous clearance of acute hepatitis C infection. Hepatology. 2014; 60(2):487-96. DOI: 10.1002/hep.27139. View

Baecker A, Liu X, La Vecchia C, Zhang Z . Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors. Eur J Cancer Prev. 2018; 27(3):205-212. PMC: 5876122. DOI: 10.1097/CEJ.0000000000000428. View

Kikuchi M, Fukuyama K, Epstein W . Soluble dipeptidyl peptidase IV from terminal differentiated rat epidermal cells: purification and its activity on synthetic and natural peptides. Arch Biochem Biophys. 1988; 266(2):369-76. DOI: 10.1016/0003-9861(88)90268-8. View

Drucker D, Nauck M . The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548):1696-705. DOI: 10.1016/S0140-6736(06)69705-5. View

Singal A, El-Serag H . Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice. Clin Gastroenterol Hepatol. 2015; 13(12):2140-51. PMC: 4618036. DOI: 10.1016/j.cgh.2015.08.014. View

10.

Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Nagata C . Diabetes mellitus and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2014; 44(10):986-99. DOI: 10.1093/jjco/hyu108. View

11.

McCaughan G, Gorrell M, Bishop G, Abbott C, Shackel N, McGuinness P . Molecular pathogenesis of liver disease: an approach to hepatic inflammation, cirrhosis and liver transplant tolerance. Immunol Rev. 2000; 174:172-91. DOI: 10.1034/j.1600-0528.2002.017420.x. View

12.

Noh R, Lee D, Kwon B, Kim Y, Kim S, Song I . Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection. Gastroenterol Res Pract. 2016; 2016:7476231. PMC: 5021494. DOI: 10.1155/2016/7476231. View

13.

Ragab D, Laird M, Duffy D, Casrouge A, Mamdouh R, Abass A . CXCL10 antagonism and plasma sDPPIV correlate with increasing liver disease in chronic HCV genotype 4 infected patients. Cytokine. 2013; 63(2):105-12. DOI: 10.1016/j.cyto.2013.04.016. View

14.

Kawaguchi T, Kodama T, Hikita H, Makino Y, Saito Y, Tanaka S . Synthetic lethal interaction of combined CD26 and Bcl-xL inhibition is a powerful anticancer therapy against hepatocellular carcinoma. Hepatol Res. 2014; 45(9):1023-1033. DOI: 10.1111/hepr.12434. View

15.

DeCensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B . Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010; 3(11):1451-61. DOI: 10.1158/1940-6207.CAPR-10-0157. View

16.

El-Serag H, Hampel H, Javadi F . The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol. 2006; 4(3):369-80. DOI: 10.1016/j.cgh.2005.12.007. View

17.

Nishina S, Yamauchi A, Kawaguchi T, Kaku K, Goto M, Sasaki K . Dipeptidyl Peptidase 4 Inhibitors Reduce Hepatocellular Carcinoma by Activating Lymphocyte Chemotaxis in Mice. Cell Mol Gastroenterol Hepatol. 2018; 7(1):115-134. PMC: 6260362. DOI: 10.1016/j.jcmgh.2018.08.008. View

18.

Casrouge A, Decalf J, Ahloulay M, Lababidi C, Mansour H, Vallet-Pichard A . Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV. J Clin Invest. 2010; 121(1):308-17. PMC: 3007131. DOI: 10.1172/JCI40594. View

19.

Li Q, Xu H, Sui C, Zhang H . Impact of metformin use on risk and mortality of hepatocellular carcinoma in diabetes mellitus. Clin Res Hepatol Gastroenterol. 2021; 46(2):101781. DOI: 10.1016/j.clinre.2021.101781. View

20.

Zeremski M, Hooker G, Shu M, Winkelstein E, Brown Q, Des Jarlais D . Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection. J Hepatol. 2011; 55(3):545-553. PMC: 3094733. DOI: 10.1016/j.jhep.2010.12.033. View