Recurrence of Hepatocellular Carcinoma in HCV Liver Transplant Recipients Treated with Direct-Acting Antiviral (DAA) Therapy

Recurrence of Hepatocellular Carcinoma in HCV Liver Transplant Recipients Treated with Direct-Acting Antiviral (DAA) Therapy

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Background

Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain.

Objective

We aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT.

Methods

The study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017.  We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group).

Results

One hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group.  Sofosbuvir-ledipasvir was the most common DAA regimen used pre-LT (10 patients, 29.4%), with genotype 1 being the most common HCV genotype in both the groups (Table 1)

Table 1.  DAA regimen

Twenty-two patients achieved SVR with interferon-based therapy prior to LT. In comparison to the DAA group, a lower proportion of patients in the IFN group underwent deceased donor LT (81.8 vs. 100%, p = 0.02) and a higher proportion of patients had trans-arterial chemoembolization (TACE) (85 vs. 50%, p = 0.02). Time between SVR12 and LT for individual patients achieving SVR with DAAs (Fig 1).

Fig 1. Time between SVR12 and LT for individual patients achieving SVR with DAAs

The Kaplan-Meier estimates of HCC-free survival were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in the DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively (Fig. 2). The difference in HCC-free survival between the 2 groups was not statistically significant with a log-rank p = 0.08) (Fig 2).

Fig 2. HCC-free survival, DAA group versus HCV+ group

In the secondary analysis, the estimates of HCC-free survival were 100, 90.2, and 90.2% at 6, 12, and 24 months in the IFN group. There was no difference in HCC-free survival between the DAA group and the IFN group (log-rank p = 0.45) In a multivariate analysis adjusting for several factors, the impact of DAA use on HCC recurrence after LT did not reach statistical significance, but did show a strong trend (HR 5.17, 95% CI 0.89–29.81, p = 0.07).

Table 2.  Multivariate analysis for post-LT HCC recurrence

Conclusions

A strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. The decision to treat HCV prior to transplant remains a very individualized one that must balance the undoubtable benefits to post-LT graft function with access to hepatitis C-positive organs. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC.

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