Impact of Hepatitis C Treatment on Long-term Outcomes for Patients with Hepatocellular Carcinoma Public

Abstract

The purpose of this study was to 1) assess the impact of hepatitis C virus(HCV) treatment on survival in patients with hepatocellular carcinoma(HCC) at safety net hospitals(SNH) and tertiary referral centers(TRC) 2) determine the barriers to receiving HCV treatment and 3) assess the impact of timing of DAA therapy on rates of SVR and RFS in patients undergoing liver transplantation(LT).

For aims 1 and 2, patients from the US Safety Net Collaborative Database(2012-2014) with HCV and HCC were included. For all patients, HCV treatment was associated with improved median OS compared to no HCV treatment(70vs21 months, p<0.01). On MVA, HCV treatment was associated with improved OS. Considering patients who underwent complete tumor extirpation, those who received HCV treatment had improved median RFS compared to those who did not(91vs80 months, p=0.03). On MVA, factors associated with not receiving HCV treatment included Black race, uninsured status, and treatment at a SNH(all p<0.03). When this patient demographic received HCV treatment, however, the degree of improvement in survival was similar regardless if treated at a TRC or SNH.

For aim 3, patients from the US Hepatocellular Carcinoma Liver Transplantation Consortium(2015-2019) with primary HCV-associated HCC who underwent LT and completed DAA therapy were included. 427 HCV interferon treatment-naive patients who achieved SVR with DAAs had improved 5-year RFS(93%vs76%, p<0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78%(p<0.01) and 5-year RFS of 93%, 100%, and 83%(p=0.01).

HCV treatment for patients with HCC portends improved survival and oncologic outcomes, irrespective of clinical stage, HCC treatment modality, or type of treatment facility. Despite this, given associated barriers, a minority of patients treated at SNH receive HCV treatment. Efforts must be directed towards removing obstacles that prevent this vulnerable patient population from receiving the standard-of-care treatment for HCV with HCC.

The optimal timing of DAA therapy appears to be 0-3 months after liver transplantation for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A randomized prospective trial is warranted to validate these results.

Table of Contents

INTRODUCTION: 1

AIMS 1 & 2: 3

METHODS: 4

RESULTS: 6

DISCUSSION: 9

CONCLUSIONS: 13

AIM 3: 14

METHODS: 15

RESULTS: 17

DISCUSSION: 19

CONCLUSIONS: 24

STRENGTHS AND LIMITATIONS: AIMS 1 & 2: 25

STRENGTHS AND LIMITATIONS: AIM 3: 26

CONCLUSIONS: 27

TABLES: 34

TABLE 1.1: 34

TABLE 1.2: 36

TABLE 1.3: 37

TABLE 1.4: 38

TABLE 2.1: 40

TABLE 2.2: 42

TABLE 2.3: 43

FIGURES: 45

FIGURE 1: 45

FIGURE 2.1: 46

FIGURE 2.2: 47

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Oncology
Mot-clé	Hepatocellular Carcinoma Hepatitis C Virus
Committee Chair / Thesis Advisor	Amita Manatunga, Emory University
Committee Members	Shishir Maithel, Emory University

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