HCV Eradication with Direct-Acting Antivirals Does Not Impact HCC Progression on the Waiting List or HCC Recurrence after Liver Transplantation

Abstract

Background The introduction of direct-acting antivirals (DAA) for HCV has led to high rates of HCV eradication. Treatment of patients awaiting liver transplantation (LT) has been controversial. Recent data suggests that DAA treatment may accelerate recurrent HCC. The impact of DAA on delisting for HCC progression or recurrent HCC post-LT has not been well characterized. Methods A retrospective review of both waitlist patients and LT recipients at a single institution was performed. Patient demographics, HCV treatment, HCC features and treatments, biopsy results, and graft and patient survival were evaluated. Patients on the LT waitlist or who were transplanted between January 2014 and December 2015 were included. Data was collected through December 2017 to have a minimum of two years of follow-up. Results In the study period, 128 adult LT were performed. 44 patients were HCV+, and 68.2% (N=30) also had HCC. 38.6% (N=17) of HCV+ patients received DAA pre-LT, and 94.1% (N=16/17) achieved sustained virologic response (SVR) pre-LT. Among untreated HCV+ patients who underwent LT, 81.5% (N=22/27) received DAA post-LT, with 82.6% achieving SVR post-LT (N=18/22). 82.1% (N=23/28) of untreated post-LT patients underwent liver biopsy prior to therapy, and 52.2% had at least F1 METAVIR fibrosis. 87.5% (N=14/16) of active waitlist patients received DAA and achieved SVR. HCV eradication did not result in higher rates of delisting for HCC progression. Due to local HCC listing criteria of total tumor volume and AFP, 60% (N=18/30) of HCV+/HCC patients were beyond Milan criteria at the time of LT. Despite this, there was no difference in HCC recurrence rates post-LT, whether patients achieved SVR pre- or post-LT. Conclusions These data suggest that HCV eradication pre-LT does not significantly impact waitlist time for HCV+ patients with HCC. HCV eradication does not impact rates of delisting for HCC progression or rates of HCC recurrence post-LT.

Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence

“…( 34,35 ) Three single‐center retrospective cohort studies addressed the effect of DAAs and HCC wait‐list progression and recurrence following transplantation. ( 20,21,36 ) Opposing results were previously reported. A nonsignificant higher rate of wait‐list tumor progression and post‐LT recurrence in patients treated with DAAs before transplantation was observed in an Italian study, ( 20 ) whereas a reduced risk of wait‐list tumor progression was observed in a cohort from the University of California, San Francisco.…”

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

“…Early generation DAA regimens, such as SOF + RBV, had lower SVR rates, in line with clinical trial outcomes. Emamaullee et al found only 57% SVR with a 24‐week course of SOF + RBV. In our analysis, suboptimal regimens resulted in an SVR of 76.3%.…”

“…There are several issues relevant to DAA therapy among patients with HCC. First, initial data suggested a potential increased risk of HCC recurrence, although subsequent studies did not support these findings . Second, in response to the controversy around HCC recurrence risk, the timing of DAA therapy in relation to HCC management became a point of debate .…”

“…First, initial data suggested a potential increased risk of HCC recurrence, [8][9][10][11][12][13][14] although subsequent studies did not support these findings. [15][16][17][18][19][20][21][22] Second, in response to the controversy around HCC recurrence risk, the timing of DAA therapy in relation to HCC management became a point of debate. [23][24][25] For example, some recommended DAA treatment deferral (ie at least 4-6 months) following potentially curative HCC management.…”

Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection

“…Changes in the immune function may not affect the HCC recurrence rate according to the report that HCV eradication by DAA does not impact rates of delisting for HCC progression or rates of HCC recurrence post-liver transplantation. 46 We previously reported that the altered immune response after DAA therapy might affect the severity of HCC recurrence, not the recurrence rate, 47 but the conclusion was withheld because there was a problem with the statistical analysis. Considering that many clinicians have thought that an unexpected recurrence has occurred, [14][15][16][17] the promotion of recurrence by DAA might be a phenomenon that is extremely rare but possible in practice so that one cannot show a statistically significant difference.…”