Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct‐acting antiviral therapies in the United States

Abstract

Summary Direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection achieve high cure rates, reducing HCV‐related disease progression to cirrhosis and hepatocellular carcinoma. We aim to evaluate the impact of DAAs on US liver transplant (LT) waitlist outcomes. We retrospectively evaluated US adults (age ≥18) with and without chronic HCV listed for LT before and after the widespread use of sofosbuvir, allowing a 6‐month period after approval (Era 1: 1/1/2002‐5/31/2014 vs Era 2: 6/1/2014‐12/31/2016) using the United Network for Organ Sharing registry. Overall, LT waitlist survival and likelihood of receiving LT were evaluated with multivariate Cox regression models. From 2002 to 2016, 158 045 patients were listed for LT. While the number of patients listed for HCV has been decreasing since 2012, the proportion of HCV patients with concurrent HCC is increasing by 3.33% per year (R2: 0.99, P < 0.001 by simple linear regression). While there was no difference in likelihood of LT between HCV and non‐HCV patients, those listed in Era 2 had lower likelihood of LT (HR: 0.91, P < 0.001), more pronounced in the HCV cohort (HR: 0.83, P < 0.001) compared to the non‐HCV cohort (HR: 0.93, P < 0.001). Compared to non‐HCV patients, higher waitlist mortality was seen in HCV patients in Era 1 (HR: 1.08, P < 0.001) but not in Era 2 (HR: 1.02, P = 0.75). Since the introduction of DAAs for HCV treatment, number of patients with HCV listed for LT has declined. In the post‐DAA era, HCV patients on the LT waitlist had improved waitlist mortality.

Monitoring liver transplant rates in persons diagnosed with hepatitis C: a data linkage study, England 2008 to 2017

“…Through linked data, we identified a decline in HCV-associated liver transplant rates after 2014, consistent with unlinked published data for England [2,8] and internationally [9-11]. A separate study within the UK [8], using unlinked data, reported registered transplants for patients with HCV-related cirrhosis fell from 10.5% in 2013 to 4.7% in 2016.…”

“…Vaziri et al reported that the proportion of liver transplants attributed to HCV-associated cirrhosis fell from 10.5% to 4.7% between 2013 and 2016 and the proportion of liver transplants for cancer-associated HCV fell from 46.4% to 33.7% over the same period [8]. Similar results have been found in Italy, the United States (US) and Argentina [9-11]. A declining contribution of HCV-associated cirrhosis and cancer to transplants is helpful but is not a substitute for monitoring rates of HCV-associated transplants and may be limited by under-reporting of HCV coding in the liver transplant dataset, as has been observed in death registry data [12].…”

“…A downward trend was identified in liver transplants among patients with decompensated cirrhosis in Argentina [11]. A decline has also been reported in the US [9] among patients waiting for a transplant, with a lower likelihood of being on the waiting list in the DAA era compared with the pre-DAA era (Hazard Ratio 0.83). The decrease in liver transplant incidence in England among individuals with HCV within this study contrasts with the trend observed for all liver transplants, where rates have increased in recent years, albeit on a much smaller scale.…”

Barriers to initiation of hepatitis C virus therapy in Germany: A retrospective, case-controlled study

“…Education regarding the potential consequences of disease progression in the absence of treatment is also important, especially as a fear of treatment or side effects was associated with a longer disease duration in this study. The latter increases the risk of serious complications of CHC infection, such as hepatic decompensation or hepatocellular carcinoma [17,45,46]. In this real-world study, 28% of the documented patients with chronic HCV infection did not receive indicated CHC treatment, despite the availability of effective pangenotypic interferon-free DAAs.…”

Lymphovascular invasion on explant is associated with presenting tumor characteristics and not direct acting antiviral utilization in hepatitis C candidates undergoing liver transplantation

“…Introduction of highly effective and tolerable direct-acting antivirals (DAA) has improved waitlist mortality and lowered risk of disease progression among chronic hepatitis C virus (HCV) patients awaiting liver transplantation (LT) [1]. Optimal timing of DAA therapy in waitlist active candidates remains a subject of debate.…”