Impact of Hepatitis C Virus Treatment on the Risk of Non-hepatic Cancers Among Hepatitis C Virus-infected Patients in the US

Wei Wang; Vincent Lo Re III; Yi Guo; Hong Xiao; Joshua Brown; Haesuk Park


Aliment Pharmacol Ther. 2020;52(10):1592-1602. 

In This Article

Abstract and Introduction


Background: Hepatitis C virus (HCV) infection is associated with with an increased risk of non-hepatic cancers, but the impact of HCV treatment on non-hepatic cancer is unclear.

Aims: To assess if HCV treatment reduced the incidence of non-hepatic cancers among patients with chronic HCV infection in the US.

Methods: We conducted a retrospective cohort study in MarketScan Databases from January 2005 to December 2016. Multivariable, time-varying Cox proportional-hazards models were used to determine hazard ratios (HRs) of incident non-hepatic cancers in treated and untreated patients with HCV infection. We conduscted subgroup analyses for sex, age, and presence of cirrhosis or diabetes.

Results: Among 62 078 patients with newly diagnosed HCV infection, 17 302 (28%) initiated HCV treatment, among whom 15 322 completed 8–16 weeks treatment (minimally effective treatment). Patients who initiated HCV treatment had an 11% decreased risk of developing an incident non-hepatic cancer compared to untreated patients (HR = 0.89, 95% confidence interval (Cl) = 0.82–0.96). The reduction was slightly higher when patients completed a minimally effective treatment (HR = 0.87; 95% Cl = 0.80 - 0.95). This was observed in most subgroup analyses for those who had a minimally effective treatment including patients with cirrhosis. When we stratified cancer or therapy subtypes, the association remained consistent for pancreatic and lung cancers, and dual HCV therapy.

Conclusions: HCV treatment led to a significantly reduced incidence of non-hepatic cancers among patients with HCV infection. Despite discrepancies between cancer or HCV therapy subtypes, our findings suggest that treating HCV infection can decrease the extrahepatic cancer burden associated with chronic HCV infection.


Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the US, affecting 3.5 million Americans.[1] Around 55%-86% of HCV infections become chronic HCV infections, which is a leading cause of liver complications such as decompensated cirrhosis and hepatocellular carcinoma.[2,3] Beyond liver complications, chronic HCV infection is also associated with extrahepatic manifestations (EHM), which are reported in up to 75% of HCV-infected patients.[4–9]

The impact of HCV treatment on the reduced risk of liver complications among HCV-infected patients has been well studied.[10–12] Furthermore, recent studies suggest that anti-viral therapy for chronic HCV can reduce the risk of developing extrahepatic manifestations, such as chronic kidney disease (CKD) and cardiovascular disease.[9,13,14] HCV treatment may mitigate the risk of both liver disease and extrahepatic manifestations by viral clearance and reductions in hepatic and systemic inflammation.[11,15–19]

Non-hepatic cancer is a relatively uncommon EHM among HCV-infected patients, but it is considered a clinically significant problem due to its severe prognosis and high mortality rate. The direct viral oncogenic impact and indirect influence through the immune system's inflammatory responses are suspected to be important factors in the association between HCV infection and non-hepatic cancers.[20] Recent studies have found that HCV patients are at a 30%-70% higher risk of developing non-hepatic cancers including non-Hodgkin's lymphoma (NHL), pancreatic cancer, head and neck cancer, oesophageal cancer, lung cancer and colorectal cancer.[21] However, little is known about the impact of HCV treatment on the risk of developing non-hepatic cancers. To the best of our knowledge, only two studies have examined the effect of HCV treatment on non-Hodgkin lymphoma among HCV-infected veterans.[19,22]

Therefore, the aim of this study was to determine the impact of HCV treatment on the incidence rates of non-hepatic cancers in chronically HCV-infected patients in the US using real-world data obtained from a nationally representative insurance database. We hypothesised that chronic HCV-infected patients who were dispensed anti-viral treatment would have a reduced risk of developing non-hepatic cancers compared to untreated HCV patients.