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Observational Study
. 2023 Sep 1;118(9):1609-1617.
doi: 10.14309/ajg.0000000000002361. Epub 2023 Jun 13.

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication in Infected Patients With Solid Tumors

Marcel Yibirin  1 , Khalis Mustafayev  1 , Jeff Hosry  1 , Pooja Pundhir  1 , Joseph Klingen  1 , Eduardo Yepez Guevara  1 , Bruno P Granwehr  1 , Ahmed Kaseb  2 , Aung Naing  3 , Sapna Patel  4 , Amishi Y Shah  5 , Ferdinandos Skoulidis  6 , Hussein A Tawbi  4 , Lan Wang  7 , Ethan Miller  7 , Hao Chi Zhang  7 , Amado Zurita-Saavedra  5 , Harrys A Torres  1   7
Affiliations
Observational Study

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication in Infected Patients With Solid Tumors

Marcel Yibirin et al. Am J Gastroenterol. .

Abstract

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men (41; 79%), White (31; 59%), without cirrhosis (34; 65%), and with HCV genotype 1 (40; 77%). Four patients (7.7%) experienced HCV inhibition while receiving ICI including 1 patient who developed undetectable viremia for 6 months in the absence of direct-acting antivirals (DAA). Two patients (4%) developed HCV reactivation, both while receiving immunosuppressive therapy for ICI-related toxic effects. Adverse events occurred in 36 patients (69%), and 39 of the 47 adverse events (83%) were grade 1-2. Grade 3-4 adverse events occurred in 8 patients (15%), and in all cases, they were related to ICI, not to HCV. No HCV-associated liver failure or death occurred.

Discussion: Inhibition of HCV replication with virologic cure can develop in patients receiving ICI without DAA. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICI are safe in HCV-infected patients with solid tumors. Chronic HCV infection should not be considered a contraindication for ICI therapy.

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Conflict of interest statement

Dr. Torres is or has been the principal investigator for research grants from the National Cancer Institute, Gilead Sciences and Merck & Co., Inc., with all funds paid to MD Anderson Cancer Center. Dr. Torres is or has been a paid scientific advisor for Dynavax Technologies, AbbVie, Inc., Gilead Sciences, Janssen Pharmaceuticals, Inc., and Merck & Co., Inc.; MD Anderson Cancer Center is managing the terms of these arrangements in accordance with its conflict-of-interest policies. The other authors report no conflicts of interest.

Figures

Figure 1.
Figure 1.
A. Changes in serum HCV RNA in the 48 patients with solid tumors on ICIs without antiviral therapy. B. Changes in Serum HCV RNA and ALT in the patient with virologic cure of HCV on ICIs without antiviral therapy. The patient developed virologic HCV cure on induction of nivolumab and ipilimumab, followed by maintenance treatment with nivolumab without DAAs. HCV viremia was not detected 19 months after starting ICI therapy. Abbreviations: ALT, alanine aminotransferase; DAA, direct acting antivirals; HCV, hepatitis C virus; ICI, immune checkpoint inhibitor; RNA, ribonucleic acid.
Figure 2.
Figure 2.
Role of ICIs in immunoregulation in patients with chronic HCV infection. CTLA-4 and PD-1 expression are essential for the survival and functioning of T cells during chronic infection. Blockade of PD-1, PD-L1, or CTLA-4 may induce either the anti-tumor (A) or anti-viral (B) immune response by activating tumor-specific (A) or HCV-specific (B) cytotoxic T cells. Created with BioRender.com.
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