Work

Inhibition of Hepatitis C Virus Replication Induced by Chemotherapy: A Prospective Observational Study

Year: 2018

Type: article

Abstract: To the Editor—In patients with untreated chronic hepatitis C virus (HCV) infection, serum HCV-RNA levels are stable, varying within 0.5 log10 IU/mL [1]. We previously showed that 23% of HCV-infected patients receiving cancer treatment experienced HCV reactivation (increase in HCV-RNA level >1 log10 IU/mL), and of patients with HCV reactivation, 43% had hepatitis flare (alanine aminotransferase [ALT] increase to ≥3 times the upper limit of normal) and 26% required cancer treatment modification [2]. Herein, we report chemotherapy-induced inhibition of HCV replication (“HCV inhibition”) and clinical implications of this phenomenon. HCV-infected patients with cancer (any type) followed at our institution during 2012–2017 and receiving chemotherapy but not anti-HCV therapy were enrolled in a prospective observational study. HCV inhibition (decrease in HCV-RNA level ≤1 log10 IU/mL from baseline) following chemotherapy initiation was sought. Elevated baseline ALT level was defined as ALT >56 IU/L. Our study included 139 patients. HCV inhibition was detected in 17 patients (12%): 12 of 77 (16%) with solid tumors and 5 of 62 (8%) with hematologic malignancies (Table 1). In multivariable analysis, sorafenib (odds ratio [OR], 16.7; P = .003), lenalidomide (OR, 37.5; P = .0008), and platinum-based regimens (OR, 8.6; P = .009) were associated with HCV inhibition (Supplementary Table 1). One patient had undetectable HCV-RNA at week 12 of sorafenib but detectable viral load at week 24. Twelve patients with HCV inhibition had elevated baseline ALT level, of whom 8 had ALT normalization concomitant with HCV inhibition (Figure 1). Characteristics of the 17 Patients With Hepatitis C Virus Inhibition Following Chemotherapy Abbreviations: 5-FU, fluorouracil; CMML, chronic myelomonocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDS, high-dose steroids; MDS, myelodysplastic syndrome; OPC, oropharyngeal cancer; SCC, squamous cell carcinoma. aAgents in bold are common chemotherapy agents that our findings suggest are associated with HCV inhibition. Characteristics of the 17 Patients With Hepatitis C Virus Inhibition Following Chemotherapy Abbreviations: 5-FU, fluorouracil; CMML, chronic myelomonocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDS, high-dose steroids; MDS, myelodysplastic syndrome; OPC, oropharyngeal cancer; SCC, squamous cell carcinoma. aAgents in bold are common chemotherapy agents that our findings suggest are associated with HCV inhibition. Representative changes in alanine aminotransferase (ALT) level over time in 2 patients with hepatitis C virus (HCV) inhibition. To our knowledge, this is the first prospective study of chemotherapy-induced HCV inhibition and ALT normalization. A low HCV viral load, regardless of HCV eradication, has been associated with a higher 5-year overall survival rate in patients with hepatocellular carcinoma [3]. Sorafenib inhibits HCV replication in vitro [4]. However, a clinical study did not show anti-HCV activity of sorafenib [5]. In our study, sorafenib led to undetectable HCV-RNA in 1 patient, but the antiviral effect disappeared, possibly because sorafenib area under the curve decreases over time [6]. Immunomodulatory drugs affecting T cells (eg , lenalidomide and thalidomide) are used to treat hematologic cancers. To our knowledge, we are the first to report HCV inhibition after lenalidomide; we previously reported HCV reactivation after thalidomide [7]. Platinum drugs, which are used widely to treat solid tumors, enhance cancer cell killing through dendritic cell–induced T-cell activation [8, 9]. Our findings suggest that using lenalidomide over thalidomide in patients with hematologic cancers and using platinum-based chemotherapy in patients with solid tumors might reduce the risk of HCV reactivation and hepatitis flare and, thus, the need for chemotherapy modification in HCV-infected patients. Limitations of our study include the fact that most patients received combination cancer therapy, which limits understanding of the impact of each agent, and the nonuniform timing of measurement of HCV-RNA levels in relation to chemotherapy administration, which precluded study of the relationships between serum HCV-RNA and ALT levels. In conclusion, our findings suggest that selected chemotherapeutic agents may induce HCV inhibition, thereby preventing hepatitis flares, which are clinically relevant when definitive HCV treatment with direct-acting antivirals is delayed, difficult (eg, after multiple treatment failures), or contraindicated. Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Acknowledgments. We thank Stephanie P. Deming from the Department of Scientific Publications at MD Anderson Cancer Center for editorial assistance. Financial support. This study was supported by the National Cancer Institute, National Institutes of Health (award number P30CA016672). Potential conflicts of interest. H. A. T. is or has been the principal investigator for research grants from Gilead Sciences and Merck & Co, Inc, with all funds paid to MD Anderson Cancer Center, and is or has been a paid scientiﬁc advisor for Gilead Sciences, Merck & Co, Inc, and Dynavax Technologies (the terms of these arrangements are being managed by MD Anderson Cancer Center in accordance with its conflict of interest policies). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Source: Clinical Infectious Diseases

DOI: 10.1093/cid/ciy387

Authors: Jeff Hosry, Georgios Angelidakis, Ahmed Kaseb, Ying Jiang, Harrys A Torres

Institution: The University of Texas MD Anderson Cancer Center

Language: English

Topic: Hepatitis C virus research

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute