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

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.

Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors

“…[ 31 , 57 ] A prospective study from MD Anderson Cancer Center indicated that ICIs are safe in HCV-infected patients with solid tumors. [ 14 ] In that study, only 2 of 52 patients (4%) treated with ICIs had HCV reactivation, and those patients were also receiving immunosuppressants such as infliximab and high-dose corticosteroids for ICI-related toxic effects, making it difficult to determine if the reactivation was associated with ICI therapy alone. [ 58 ] None of the other studies we found on ICI therapy in HCV-infected patients with cancer showed any cases of HCV reactivation ( Table 4 ).…”

“…Oncologic professional societies recommend universal HCV screening for all patients with cancer. [ 59 , 60 ] Published data [ 6 , 7 , 14 , 23 , 24 , 31 , 32 , 45 , 57 , 61 , 62 ] support that HCV-infected patients with cancer can be safely enrolled in cancer clinical trials of ICIs; however, these patients should be monitored for hepatitis flare and reactivation (or enhanced HCV replication). The management of HCV in patients with cancer receiving ICIs should be individualized on the basis of the patient’s viral hepatitis status, liver function, cancer treatment plan, and cancer status.…”

“…[ 63 ] Antiviral treatment before, during, or after ICI therapy is safe and can eradicate HCV. [ 14 ] In a recent editorial, it was emphasized that ICI therapy is associated with a favorable prognosis in HCV-infected patients. The authors advocate using ICIs in HCV-infected patients in both clinical practice and cancer clinical trials.…”

“…[ 11–13 ] In addition, immunosuppression used for managing immune-related toxic effects following ICI therapy may cause HCV reactivation, although it remains unclear whether immunosuppression may also cause HBV reactivation. [ 12 , 14 , 15 ] Patients with chronic HBV infection who are receiving ICIs may experience a flare-up of HBV replication, which can cause severe liver damage, liver failure, or even death. [ 16 , 17 ] Despite the unclear safety of ICIs in patients with HBV or HCV infection, recently published data from a European survey of 56 oncology centers showed that only one-third of the respondents would start antiviral prophylaxis for chronic HBV at ICI initiation.…”

Immune-Checkpoint Inhibitors in the Hepatitis C–Infected Patient: To Use or Not to Use?

“…In this issue of The American Journal of Gastroenterology , Yibirin et al (5) demonstrate that those with active HCV infection overall have a good prognosis with concomitant ICI therapy and should not only be considered for this type of cancer therapy but also should not be left out from clinical trials using these therapies.…”