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Hepatitis C virus (HCV) reactivation in patients receiving cancer treatment has been reported in retrospective studies. We sought to determine prospectively the incidence, predictors, and clinical significance of HCV reactivation during cancer treatment. HCV-infected patients receiving cancer treatment at our institution between November 2012 and July 2016 were studied. Reactivation was defined as an increase in HCV-RNA 1 log 10 IU/mL over baseline and hepatitis flare as an increase in alanine aminotransferase to 3 times the upper limit of normal. One hundred patients were studied, 50 with hematologic malignancies and 50 with solid tumors. Reactivation occurred in 23 (23%) patients, including 18 (36%) patients with hematologic malignancies and 5 (10%) patients with solid tumors. In univariate analysis, patients with reactivation were more likely than those without reactivation to have prolonged lymphopenia (median, 95 versus 22 days; P 5 0.01) and to have received rituximab (44% versus 9%; P < 0.0001), bendamustine (22% versus 0%; P < 0.001), high-dose steroids (57% versus 21%; P 5 0.001), or purine analogs (22% versus 5%; P 5 0.02). Rituximab (odds ratio 5 9.52; P 5 0.001), and high-dose steroids (odds ratio 5 5.05; P 5 0.01) retained significance in multivariable analysis. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with reactivation experienced liver failure or liverrelated death within 36 weeks after initiation of cancer treatment. Fourteen patients with hepatitis flare, six of whom had reactivation, required discontinuation or dose reduction of cancer treatment. Conclusion: HCV reactivation occurred in 23% of HCV-infected patients receiving cancer treatment, and most had an unremarkable clinical course. However, reactivation can affect the cancer treatment plan. Our findings suggest that HCV infection should not contraindicate cancer therapy and infected patients should have access to multiple cancer treatments with close monitoring while receiving regimens associated with HCV reactivation. (HEPATOLOGY 2018;67:36-47). SEE EDITORIAL ON PAGE 4H epatitis C virus (HCV) infection is the most common blood-borne infection in the United States, where at least 3.5 million people are currently infected. (1) HCV infection is observed in 1.5% to 32% of cancer patients around the world, depending on the geographic area and type of cancer studied. (2)(3)(4)(5) Among patients with cancer receiving chemotherapy, liver dysfunction caused by hepatitis B virus (HBV) reactivation is a significant problem, (6)(7)(8) occurring in 14% to 72% of patients who did not receive prophylactic antiviral therapy and leading to liver failure in 13% of cases and death in 6% of cases. (6,(8)(9)(10) In contrast, the incidence and consequences of HCV reactivation (HCVr) during cancer treatment remain poorly defined. HCVr appears to be less common and to have less severe consequences than HBV reactivation, (3,7,(11)(12)(13) with only a few fatal cases of fulminant hepatitis attributed to HCV having been rep...

Background: Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. We systematically assessed associations between HCV infection and cancers in the US elderly population. Methods: We conducted a registry-based case-control study using the SEER-Medicare data in US adults aged ≥66 years. Cases (n=1,623,538) were people with first cancers identified in SEER registries (1993–2011). Controls (n=200,000) were randomly selected cancer-free individuals frequency-matched to cases on age, sex, race, and calendar year. We determined associations with HCV using logistic regression. Results: HCV prevalence was higher in cases than controls (0.7% vs. 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR]=31.5; 95%CI=29.0–34.3), intrahepatic bile duct (aOR=3.40; 95%CI=2.52–4.58), extrahepatic bile duct (aOR=1.90; 95%CI=1.41–2.57), pancreas (aOR=1.23; 95%CI=1.09–1.40), anus (aOR=1.97; 95%CI=1.42–2.73), and non-melanoma non-epithelial skin cancer (aOR=1.53; 95%CI=1.15–2.04), myelodysplastic syndrome (aOR=1.56; 95%CI=1.33–1.83), and diffuse large B-cell lymphoma (DLBCL) (aOR=1.57; 95%CI=1.34–1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR=1.92; 95%CI=1.30–2.85) and appendageal skin cancers (aOR, 2.02; 95%CI=1.29–3.16). Inverse associations were observed with uterine cancer (aOR=0.64; 95%CI=0.51–0.80) and prostate cancer (aOR=0.73; 95%CI=0.66–0.82). Associations were maintained in sensitivity analyses conducted among people without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections, and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. Conclusion(s): HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and DLBCL. These results support a possible etiologic role for HCV in an expanded group of cancers.

Background and aim: Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited. Methods: We conducted a retrospective cohort study using data of patients from the U.S. Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test between 10/1999 and 8/2009. Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risk of 8 incident EHMs were evaluated in Cox proportional hazards regression models. Results: Of the 160,875 HCV-infected veterans, 31,143 (19.4%) received AVT, of whom 10,575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared to untreated patients for mixed cryoglobulinemia (adjusted hazard ratio [aHR]=0.61; 95%CI=0.39–0.94), glomerulonephritis (aHR=0.62; 95%CI=0.48–0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95%CI=0.20–0.83), non-Hodgkin lymphoma (NHL) (aHR=0.64; 95%CI=0.43–0.95), diabetes (aHR=0.82; 95%CI=0.76–0.88), and stroke (aHR=0.84; 95%CI=0.74–0.94), but not for lichen planus (aHR=1.11; 95%CI=0.78–1.56) or coronary heart disease (aHR=1.12; 95%CI=0.81–1.56). Risk reductions were also observed when patients with SVR were compared to treated patients without SVR for mixed cryoglobulinemia, glomerulonephritis, PCT, and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL, and stroke. Conclusions: Risks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL, and stroke.

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