Chronic hepatitis C virus infection represents a significant burden in patients with cancer. Studies show that HCV can negatively impact disease mortality in patients with cancers. Early diagnosis with virologic cure can improve liver and cancer outcomes and survival of patients with HCV-associated non-Hodgkin lymphoma and hematopoietic cell transplant (HCT) recipients [1,2,3].
The current study aimed at assessment of the safety and efficacy of DAAs in the treatment of chronic HCV patients who received chemotherapy for non-hepatic malignancies according to the NCCVH treatment protocol and to compare their results to a group of chronic HCV patients without history of cancer.
In this study, all HCV patients received SOF-based DAAs except only 2 patients who received PAR/OMP/RBV, and this was according to the program of NCCVH at Egypt. SVR was observed in all HCV patients post chemotherapy, none of them discontinued treatment, and only 2 HCV patients without cancer did not achieve SVR (1 relapsed and 1 discontinued). Univariate analysis for factors associated with treatment failure revealed nonsignificant results.
Although patients in our study received DAAS therapy after 2 years of cancer-free status as per NCCVH protocol, other studies as that done by Economides et al. in 2016 suggested safe simultaneous administration of DAAs and chemotherapy in 21 HCV-infected cancer patients (solid or hematological malignancies); no clinically significant drug-drug interactions between DAAs and chemotherapy were observed. Chemotherapy was not discontinued for any patient receiving concomitant DAA therapy with no deaths reported during the study [6].
Another study supported the idea of DAAs in cancer patients where Persico et al. in 2018 found that in HCV-infected patients with diffuse large B-cell lymphoma, disease-free survival was better in patients receiving DAAs than in untreated patients after 52 weeks of follow-up, and antiviral therapy was an independent predictor of better disease-free survival [7].
Treatment of HCV in cancer patients was also recommended by a study done by Tores et al. in 2018 where HCV reactivation and hepatitis flare were observed during chemotherapy in patients with HCV which required discontinuation or dose reduction of chemotherapy. However concomitant use of DAAs with chemotherapy should not be offered if toxic effects from this overlap can occur [8,9,10].
Mortality was observed in 23% of HCV patients post chemotherapy. Merli et al. in 2019 reported 2-year survival rate of 97.4% in patients with diffuse large B-cell lymphoma [11]. Higher mortality rate in our study may be related to having various types of cancer and performing the analysis on longer follow-up period (up to 5 years).
In our cohort, FIB-4 was the only predictor for mortality in HCV patients post chemotherapy. Xu et al. in his study on 2799 HCV-mono-infected patients who had a liver biopsy results concluded that the risks of death and progression to liver failure varied greatly by fibrosis stage, and that policy makers could use these progression risk data in prioritization of treatment for patients with liver disease [12].
In the current study, we observed higher mean age (52 years old) in group of HCV patients post chemotherapy. This may be explained by cancer research in UK where they found that age-specific incidence rates rise steeply from around age 55–59 with a conclusion that adults aged 50–74 accounted for more than half (54%) of all new cancer cases (https://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/age#heading-Zero).
As we evaluated the liver condition for HCV patients encountered in our study, patients with cancer had higher FIB-4 values and more cirrhosis than those without cancer; this was supported by the fact that patients with liver cirrhosis bear a higher risk not only for liver cancer but also for extrahepatic malignancies compared to the general population, and that common habits among the general population like tobacco, alcohol abuse, and the metabolic syndrome represent risk factors for both cancer and cirrhosis [13,14,15,16,17,18].
It was observed that HCV patients post chemotherapy had lower liver stiffness by FibroScan and higher FIB-4 values than those without cancer and without statistical significance; this may be due to the presence of lower platelets count due to chemotherapy.
All initial laboratory data were found to be of no significant difference between both HCV groups encountered in our study except for statistically higher bilirubin and HbA1c in HCV group of patients without cancer, although DM was observed more in patients post chemotherapy than those without cancer (24.1 vs. 14.8%); this was supported by the epidemiologic evidence that diabetes is associated with an increased risk of cancer [19, 20]. The lower levels of HbA1C in post-chemotherapy HCV patients were against the study done by Hershey et al. in 2014 which concluded that chemotherapy and associated symptoms can have a negative impact on the performance of diabetes self-management activities in adults with both diabetes and cancer, increasing the risk for hyperglycemia and development of complications [21].
To our knowledge, this study is among the fewest studies which assessed the efficacy and safety of DAAs for treatment of HCV among cancer patients who received chemotherapy from different non-hepatic malignancies.
Main limitation of the current study is its retrospective nature with lack of data on oncological outcome in patients post chemotherapy.