Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals

Background & Aims

The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC.

Methods

A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015.

Results

A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p = 0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p <0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio = 8.5, 95% confidence interval = 3.90–18.49).

Conclusions

The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR.

Lay summary

The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer.

Introduction

Hepatitis C virus (HCV) has been the leading cause of cirrhosis in the United States for several decades [1]. Until recently, the standard of care for HCV treatment was interferon based therapy (IFN), which was wrought with intolerable side effects, long treatment duration, and suboptimal sustained virologic response (SVR) rates of approximately 40% for patients with genotype 1 [2], [3]. SVR rates were lower in patients with advanced fibrosis [4]. The approval of direct-acting antiviral agents (DAA) has subsequently revolutionized therapy for HCV. SVR rates are consistently over 90% for genotype 1 despite the presence of cirrhosis [5]. Furthermore, the all-oral DAA regimens are well tolerated and require a shorter length of therapy than the IFN-based therapies.

Cirrhosis in the setting of HCV is a leading risk factor for the development of hepatocellular carcinoma (HCC) with an annual incidence rate of 1–4% per year [6]. The availability of DAAs has led to a significant increase in the number of patients receiving HCV therapy, including those with cirrhosis and HCC. The impetus to treat HCV in patients with known HCC is similar to those without HCC: to ameliorate ongoing inflammation and the development of further fibrosis that ultimately can lead to the clinical consequences of portal hypertension. The registration trials that led to the approval of the DAAs excluded patients with HCC [7], [8], [9], [10] or included only a few patients with HCC [11]. The only trial that was dedicated to patients with HCC was a phase II trial that examined the use of sofosbuvir and ribavirin pre-transplant in patients with HCC listed for liver transplantation, 70% of whom achieved post liver transplantation SVR [12]. Initially patients received treatment for 24 weeks or until they underwent liver transplantation. However, after observing 3 pre-transplant virologic relapses in HCC patients who had received the standard 24 weeks of therapy, the trial was revised to continue treatment in all individuals for 48 weeks or until they underwent liver transplantation [12]. It should be noted that sofosbuvir and ribavirin has lower SVR rates in patients with genotype 1 than current regimens and is no longer recommended [13], [14].

The efficacy of HCV therapy with contemporary highly effective, all-oral DAA regimens in patients with HCC is currently unknown. Patients with HCC may have lower rates of SVR as the tumor may serve as a viral reservoir, providing an immune tolerant environment for the HCV. The aim of our study was to determine if the presence or history of HCC impacted the likelihood of achieving SVR with highly effective, all-oral DAAs regimens.