title: Hepatitis C virus reactivation in cancer patients in the era of targeted therapies.
abstract: The purpose of this review is to summarize the evidence of hepatitis C reactivation in cancer patients in the era of targeted therapies. Targeted therapies are novel therapeutics frequently used in cancer patients. During treatment with targeted therapies, viral replication is one of the major problems that can occur. The PubMed database, ASCO, and ASCO Gastrointestinal Cancer Symposium abstracts were searched up until September 15, 2013 using the following search keywords: "targeted therapies, rituximab, alemtuzumab, brentuximab, hepatitis, hepatitis C reactivation, tyrosine kinase inhibitors, imatinib, mammalian target of rapamycin (mTOR) inhibitors, everolimus, anti-HER therapies, trastuzumab, pertuzumab, lapatinib, anti-epidermal growth factor receptor therapies, cetuximab, panitumumab, and ipilimumab". Papers considered relevant for the aim of this review were selected by the authors. The data about rituximab-induced hepatic flare in hepatitis C virus (HCV) positive patients is controversial. However, there is the possibility of life-threatening hepatic flare that can develop after HCV ribonucleic acid (HCV-RNA) viral load increases. Routine follow-up of liver function tests should be advised. Especially in high-risk patients, such as those with baseline chronic active hepatitis and cirrhosis, and where there are plans to administer rituximab concomitantly with corticosteroids, it is advised to have close follow-up of HCV viral load. The data is insufficient to make accurate statements about the association of alemtuzumab therapy and HCV reactivation. However, alemtuzumab may cause deep immunosuppression. Due to this, it is better to follow up with liver function tests and HCV RNA levels during alemtuzumab therapy. Brentuximab has effects on antibody dependent cellular toxicity and may decrease humoral immunity. Thus, we believe that during brentuximab treatment of HCV infected patients, clinicians may encounter hepatitis C reactivation. There have been no reported cases of hepatitis C reactivation with imatinib therapy. However, there are many reports of hepatitis B reactivation with imatinib treatment. Based on the evidence of hepatitis B reactivation with imatinib and the effects of imatinib on immune system functions, we suggest that imatinib therapy might be a risk factor for HCV reactivation. Anti-human epidermal growth factor receptor 2 therapies are not associated with hepatic flare in HCV infected patients. Post-transplant studies reported that mTOR was safely administered to patients with active hepatitis C without causing hepatic flare. Cetuximab and panitumumab have not been associated with HCV reactivation. Two cases of HCV infected melanoma were safely treated with ipilimumab without any HCV reactivation or hepatic flare. Targeted therapies are a new and emerging area of oncology treatment modalities. While treating HCV infected cancer patients, clinicians should be mindful of the immunosuppressive properties of targeted therapies. Further randomized trials are needed to establish algorithms for this issue.
authors.affiliation: Ozan Yazici, Mehmet Ali Nahit Şendur, Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara 06100, Turkey.
authors.forename: Ozan
authors.initials: O
authors.lastname: Yazici
authors.affiliation: Ozan Yazici, Mehmet Ali Nahit Şendur, Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara 06100, Turkey.
authors.forename: Mehmet Ali Nahit
authors.initials: MA
authors.lastname: Sendur
authors.affiliation: Ozan Yazici, Mehmet Ali Nahit Şendur, Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara 06100, Turkey.
authors.forename: Sercan
authors.initials: S
authors.lastname: Aksoy
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D015398:Signal Transduction; D016896:Treatment Outcome; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: Cancer, Rituximab; Hepatitis C; Hepatitis C reactivation; Monoclonal antibodies