Impact of Sofosbuvir‐Based Therapy on Liver Transplant Candidates with Hepatitis C Virus Infection

Abstract

BACKGROUND Sofosbuvir use in patients with decompensated cirrhosis may be associated with reduced liver transplant waitlist mortality and reduced need for transplant. METHODS Data from the Scientific Registry of Transplant Recipients were linked with a national database of pharmacy claims. All adult patients on the liver transplant waitlist on January 1, 2014, or added to the list during 2014, with hepatitis C virus as reason for listing were identified (2009 patients). A subgroup of 1093 unique patients had consistent pharmacy claim capture and observations. We compared patients who were and were not treated with all sofosbuvir-based regimens. RESULTS During the study period, 154 patients received sofosbuvir-based regimens. These patients had lower model for end-stage liver disease scores and significantly longer waiting times. We found a trend toward significance for more sofosbuvir-treated than untreated patients being removed from the waitlist due to improved condition (4.54% vs 3.19%, p=0.03). In a propensity score-adjusted analysis, sofosbuvir-treated patients were less likely to undergo transplant (hazard ratio 0.57, 95% confidence interval 0.37-0.89, p=0.01). CONCLUSION During the study period reflecting early sofosbuvir use, few liver transplant candidates received sofosbuvir. Use was associated with lower incidence of transplant and a trend toward more waitlist removals due to improved condition.Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and a common indication for liver transplant worldwide. 1 Despite recent advances in direct-acting antivirals (DAAs), the number of patients on the transplant waitlist is projected to remain substantial. Liver transplant is the only lifesaving option for patients who develop decompensated cirrhosis. 2 Before 2011, the standard regimen of anti-HCV therapy was dual therapy with pegylated interferon alpha plus ribavirin for 24-48 weeks, which produced cure rates of 70-80% for HCV genotypes 2 and 3, and 45-60% for genotypes 1

Outcomes of Interferon-free Direct Acting Antivirals in Patients with HCV-related Decompensated Cirrhosis: A Systematic Review and Meta-analysis

“…Of 5691 articles initially identi ed, 51 full articles were reviewed for eligibility, but only 8 10,12,[21][22][23][24][25][26] met the criteria and were included in systematic review (Fig. 1).…”

“…1). Among them, ve 10,12,23,24,26 , four 10,12,25,26 and three 12,21,22 studies reported overall survival, HCC occurrence, and MELD score, respectively. Characteristics of included studies are described in Table 1.…”

“…We performed a systematic review and meta-analysis to estimate relative treatment effect of DAA relative to standard treatment based on data from eight cohorts 10,12,[21][22][23][24][25][26] . We found that the DAA treatments could prolong overall survival and HCC-free survival probability.…”

“…Five studies 10,12,23,24,26 reported KM curves of overall survival data which was allowed to generate IPD by treatment groups. The one-stage meta-analysis by mixed-effect Weibull regression 19 was used to t overall survival on treatment groups.…”

Outcomes of direct-acting antivirals in patients with HCV decompensated cirrhosis: a systematic review and meta-analysis

“…However, only 8 studies met the inclusion criteria ( 10 , 13 , 22 – 27 ) and were included in the systematic review ( Figure 1 ). Among them, five studies reported OS ( 10 , 13 , 24 , 25 , 27 ) four studies reported HCC occurrence ( 10 , 13 , 26 , 27 ) and three reported MELD scores ( 13 , 22 , 23 ). The characteristics of the included studies are summarized in Table 2 .…”