Hepatocellular Carcinoma Is the Most Common Indication for Liver Transplantation and Placement on the Waitlist in the United States

Abstract

Background & aims: Management strategies for patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) have changed, along with liver allocation policies based on model for end-stage liver disease score. We investigated etiologic-specific trends in liver transplantation in the United States during different time periods.

Methods: We performed a retrospective study, using the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry data, to identify all adult patients registered for liver transplantation in the United States from January 1, 2004, through December 31, 2015. For subjects listed with multiple diagnoses, HCC was considered the primary listing diagnosis. To determine whether availability of direct-acting antiviral agents, which began in 2011, affected pretransplant (death or drop-out) and post-transplant outcomes for patients with HCV infection, we compared data from the time periods of 2004 to 2010 and 2011 to 2014. We used competing-risk analysis to compare differences in end points between these periods. Differences between periods in pretransplantation and post-transplantation outcomes were estimated using Kaplan-Maier analysis and compared using the log-rank test. Associations between year of listing and pre-liver transplant outcome, and year of liver transplant and survival after transplant, were examined using the log-rank test. Proportional hazard regression was used to evaluate the reliability of the time period effect with potential confounders.

Results: Among 109,018 registrants, 18.5% were registered for liver transplantation because of HCC. In 2015, HCC was the leading diagnosis among registrants (23.9% of registrations) and recipients (27.2% of recipients). Between 2004 and 2015, the ratio of registrants with vs without HCC increased 5.6-fold for patients with HCV infection, 1.9-fold for patients with hepatitis B virus (HBV) infection, 2.7-fold for patients with alcohol abuse, and 10.2-fold for patients with nonalcoholic steatohepatitis. After adjusting for covariates, we associated the period of 2011 to 2014 with a decreased probability that HCC registrants would undergo liver transplantation (hazard ratio [HR], 0.62; P < .0001). The period of 2011 to 2014 also was associated with a decreased probability of drop-out owing to deterioration or death from HCV-induced (HR, 0.90; P = .0003), HBV-induced (HR, 0.71; P = .002), or alcohol-induced (HR, 0.90; P = .01) liver disease, and an increased probability of delisting as a result of clinical improvement in patients with HCV infection (HR, 3.4; P < .0001), HBV infection (HR, 2.3; P = .004), or alcohol abuse (HR, 2.2; P < .0001). The period of 2011 to 2014 was associated with a decreased risk of graft loss or death, with the largest effect seen in HCV-infected recipients (HR, 0.76; P < .0001).

Conclusions: HCC was the leading indication for liver transplantation in the United States in 2015. Despite this, the probability of liver transplantation decreased the most in registrants with HCC. Pretransplantation and post-transplantation outcomes have improved, particularly in patients with HCV infection.

Keywords: Database; LT; Liver Cancer; UNOS/OPTN.

Figure 1

Number of new liver transplant waitlist registrants and recipients in the United States, 2004–2015 A: Number of new registrants with HCC as a separate indication B: Number of new recipients with HCC as a separate indication C: Number of new registrants with classified by underlying liver disease diagnosis D: Number of new recipients with classified by underlying liver disease diagnosis In panel B and D, the number of LT recipients does not reflect all LT recipients in each index year as only recipients who were listed after 2004 were included (LT recipients who were registered before 2004 were not included in the current figure)

Figure 2

Number of HCC registrants (Panel A) and the ratio of HCC versus non HCC (panel B) among new liver transplant waitlist registrants with different underlying etiologies of liver disease The Y-axis of panel A is split. The interval between tick marks is 50 in the lower Y-axis and 200 in the upper Y-axis Panel A: Number of HCC registrants with underlying etiology of HCV, HBV, Alcohol or NASH Panel B: The ratio of registrants with HCC versus non-HCC classified by underlying etiology of liver disease

Figure 3

Trends in the probability of liver transplant, drop out due to death or deterioration, and delisting due to clinical improvement among new liver transplant waitlist registrants in the United States, 2004–2014 *indicates p<0.05 LT indicates liver transplant; Drop indicates drop out of list due to death or clinical deterioration; Improve indicates delisting due to clinical improvement The X-axis indicates months after listing The Y-axis indicates probability of LT, drop out due to drop out due to death or deterioration, and delisting due to clinical improvement

Figure 4

Trends in post-transplant graft failure among liver transplant recipients, 2004–2014 The X-axis indicates months after Liver transplant The Y-axis indicates probability of graft failure.