Liver Transplant for Hepatocellular Carcinoma in the United States

Evolving Trends Over the Last Three Decades

Marc Puigvehí; Dana Hashim; Philipp K. Haber; Amreen Dinani; Thomas D. Schiano; Amon Asgharpour; Tatyana Kushner; Gaurav Kakked; Parissa Tabrizian; Myron Schwartz; Ahmet Gurakar; Douglas Dieterich; Paolo Boffetta; Scott L. Friedman; Josep M. Llovet; Behnam Saberi


American Journal of Transplantation. 2020;20(1):220-230. 

In This Article

Materials and Methods

Data Source

The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the SRTR or the US Government. The SRTR data system includes data on all donor, waitlisted candidates, and transplant recipients in the United States, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), US Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors.

Study Population

Our study retrospectively evaluated adult patients who received a deceased donor LT (DDLT) in the SRTR database from 1987 to September 2017 in the United States. LT recipients with HCC were identified using the primary or secondary coding for the diagnosis of HCC at the time of listing or at the time of transplant in the SRTR database. In addition to the aforementioned coding, we included recipients whose providers had sought HCC MELD exception points and were approved, even if the diagnosis of HCC had not been entered. Data regarding incidental HCCs among patients transplanted for their native MELD were not available within the database. Overall, patients below age 18, living donor recipients, or any patient with prior history of organ transplant (except kidney transplant) or other primary or secondary liver malignancies were excluded (Table S1). In line with this analysis and using additional available coding, the underlying etiologies of liver disease at the time of listing were determined. Patients were categorized in the following groups: HCV, ALD, HBV, ALD/HCV, NAFLD, and cryptogenic. Patients who did not have any codes for these diagnoses or had codes under unknown etiology were included in the "unknown" category. Patients who had codes for autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), Budd-Chiari syndrome (BCS), hemochromatosis, alpha-1 antitrypsin deficiency, acute hepatic necrosis (AHN), or other diagnoses were included in the "other" category. Patients with ALD/HCV were considered separately and not included in the calculations for HCV or ALD patients. Patients with combination codes for NAFLD and HCV (n = 89) or NAFLD and ALD (n = 50) were not included in the HCV, NAFLD, and ALD groups.

Statistical Analysis

Categorical variables are reported by percentages, and continuous variables are reported as medians with interquartile ranges (IQR). Differences between qualitative variables were assessed with the Fisher's exact test. Differences between quantitative variables were analyzed with a nonparametric test (Mann-Whitney or Kruskal-Wallis for independent samples).

Survival was calculated for each patient between the date of transplantation relevant to the date of death or retransplant, date of the last follow-up, or the end of the study period in September 2017. Univariate and multivariate Cox regression models were constructed to estimate mortality hazard ratios (HR) and 95% confidence intervals (CI) for baseline clinical and analytical parameters. We constructed two different models for the pre-DAA era (2002–2013) and the DAA era (2014–2017). The model obtained for the pre-DAA era was also applied to the DAA era. All the models were adjusted for known baseline factors related to survival, which were used as covariates (Table S4). Survival curves by HCC etiology following LT were obtained from Kaplan–Meier estimates of mortality probabilities. Differences between survival curves were tested using the log-rank test. Statistical analyses were performed using the SPSS software package (version 24.0; SPSS Inc, Chicago, IL).