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 fo...

How I treat acute myeloid leukemia presenting with preexisting comorbidities

“…62 Nevertheless, this is clearly an area of flux in the era of novel therapies for HCV. There has been a suggestion that patients receiving potent immunosuppressive targeted therapies should be closely monitored for potential development of hepatic flare, 63 but this is controversial in a new era of clinical investigations, and there are no special guidelines for patients with AML.…”

Sustained Viral Response to Ipilimumab Treatment in a Patient with HCV Chronic Infection and Metastatic Melanoma: A Case Report

“…Also, for those 40% to 60% of patients with a target activating mutation, such as BRAF V600E or K, it is unknown what the best Ipilimumab; none had to stop treatment because of liver toxicity [9]. Yazici [10] in their review article also described two melanoma patients safely treated with ipilimumab who did not experience any HCV flare.…”

Вирусные Гепатиты В И С У Детей С Онкогематологической Патологией

“…Большинство наблюдений посвящено активации ВГВ-инфекции, однако на фоне широкого исполь-зования моноклональных антител в онкогематоло-гической практике также появились сообщения о реактивации ВГС-инфекции [15,32]. В исследова-ниях, включавших взрослых пациентов с онкогема-тологическими заболеваниями (ОГЗ), реактивация ВГВ-инфекции на фоне иммуносупрессивной тера-пии отмечена почти у 50 % больных [31].…”

“…При коротких курсах возможно использование ламивудина, а при более длительной терапии -препараты с более высоким генетиче-ским барьером резистентности (энтекавир, тенофо-вир). Относительно гепатита С у больных с ОГЗ на сегодняшний день нет специальных рекомендаций по ведению [20,25]. Единственная схема лечения, рекомендуемая сейчас в педиатрической практике, базируется на комбинации интерферона-альфа с рибавирином.…”