We examined the Chilean Public Health Institute (PHI) registry of candidates listed for a liver transplant from October of 2011 until December of 2014. We included adult candidates (>15 years old) listed for elective cadaveric liver transplant with a MELD score of 15 or higher. Exclusion criteria included: pediatric candidates (≤15 years old), candidates delisted for active substance abuse, surgical contraindication before the start date of the study, and candidates who lost their outpatient controls. This study did not include candidates listed for acute liver failure.

Information used was authorized by the National Transplant Coordinator, the governmental institution responsible for transplant allocation in Chile. All data were de-identified, and additional information was requested in exceptional cases, to the seven centers of liver transplantation in Chile using an anonymous code allocated by the PHI.

The MELD score was calculated based on the previously published model [11]. We used the MELD score for the analysis since the MELD-Na (MELD-Sodium score) was incorporated as a criterion for enlistment in October 2016 (posterior to the follow-up period). We considered an operational MELD score for the analysis: (1) The real MELD score in candidates with liver cirrhosis without exceptions. (2) The adjusted MELD score in candidates with exceptional situations where the real MELD score does not adequately reflect mortality or the quality of life. The exceptions are defined by the Liver Transplant Committee who assign, in a consensual way, an adjusted score to the conditions (expressed in the National Liver Transplant Standards):

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  Malignant liver tumors: including candidates with hepatocellular carcinoma (HCC) per Milan Criteria for LT, without vascular or extrahepatic dissemination [12]. We did not include a downstaging strategy because it was incorporated into our system after the end of the follow-up of the study [13,14]. This condition receives an initial operational MELD score of 20 and posteriorly increases 1 point every two months.

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  Chronic cholestatic diseases: including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and overlap syndrome. We used the Mayo score (≥9.6 in PBC & overlap syndrome and ≥3.6 in PSC) for enlistment, with an initial operational MELD score of 15 [15,16]. We used the Mayo because the MELD score does not adequately predict mortality in this group [17]. Posteriorly, the operational MELD score increases according to a correlation between the Mayo and MELD score previously defined (for example a patient with PBC and a Mayo score of 10.3 obtain an operational MELD score of 20 since mortality is too similar in these cut-off points [28% at 12 months]).

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  Complications from chronic cirrhosis: including refractory ascites (considered in candidates with more than one paracentesis per month for at least 6 months), recurrent spontaneous bacterial peritonitis (SBP) (receiving 1 extra point for each episode of SBP) and recurrent hepatic encephalopathy (requiring multiple hospitalizations, chronic invalidating or persistent after a solved acute liver failure). These conditions can receive an initial operational MELD score of 15 and posteriorly increases 2 points every three months. On the other side, candidates with intense itching refractory to medical treatment and severe impairment of quality of life can be enlisted (requires a photo-documentation showing excoriations of skin); they receive an initial operational MELD score of 15 and posteriorly increases 1 point every three months.

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  Other conditions: hepatopulmonary syndrome, portopulmonary hypertension, type 1 hepatorenal syndrome, polycystic disease (associated with decreased renal clearance <30ml/min, severity impaired quality of life or malnutrition) and metabolic diseases.

The criteria for score assignment in exceptions are the same in all centers for liver transplantation in Chile. Also, every patient enlisted for a liver transplant is presented in a meeting including a representative from every center for liver transplant, where they discuss if every enlistment is appropriate or not.

Continuous data were described using mean and standard deviation (SD), median or interquartile ranges [IQ] (between percentiles 25 and 75%) per data distribution. Nominal data were described using percentages. We compared three groups: 1. Cirrhotic candidates without exceptions, 2. Candidates with HCC and 3. Cirrhotic candidates with exceptions (non-HCC). The main outcome was dropout defined by death, poor physical condition for the transplant or disease progression in HCC (outside Milan criteria). Kaplan–Meier estimates were used to calculate survival curves. Differences in survival curves were compared using a log-rank test. Differences in proportions were tested using the chi-square test (or the Fisher exact test). Additionally, we conducted a multivariate logistic regression to assess the association between MELD score and dropout from the waiting list and mortality post-LT. Odds ratio (OR) and 95% confidence interval (CI) were used to report these results. Statistical analysis was performed with IBM SPSS software version 22.0 (Armonk, NY: IBM Corp.) and STATA software version 13.0 (College Station, TX: StataCorp LP). A p value of <0.05 was considered statistically significant.

Five hundred seventy-three candidates were listed for LT between October 15th 2011 and December 31st 2014. We included 420 elective candidates in the analysis (77.5%); 58.1% were males (n=244). The mean age was 53.6±11.8 years; with a range between 17 and 70 years old (Table 1). In this analysis, we excluded 153 candidates by several criteria previously expressed (pediatric candidates, acute liver failure, active substance abuse, surgical contraindication, candidates who lost their outpatient controls, among others).

Candidates with liver cirrhosis without exceptions represented the most frequent cause of LT (n=177; 42.15%), followed by liver cirrhosis with HCC (n=111; 26.4%), cirrhosis with non-HCC exceptions (n=102; 24.3%) and non-cirrhotic causes (n=30; 7.15%). Table 2 shows the etiology of cirrhosis among cirrhotic candidates (n=390). The predominant etiology was non-alcoholic steatohepatitis (NASH), followed by alcohol-related liver disease, viral hepatitis, autoimmune hepatitis, cholestatic diseases, and others. The non-cirrhotic group (n=30) included hepatorenal polycystic disease, graft failure, hepatic epithelioid hemangioendothelioma, liver adenomatosis, recurrent cholangitis, among others.

In a 38 months’ period, the follow-up rate was 100%. The median follow-up to an event was 5.53 months ([IQ] 1.17–12.6) (Table 1). Transplanted and dropped out candidates stayed on the waiting list a median of 4.25 months ([IQ] 0.7–11.55) and 5.1 months ([IQ] 2.0–9.7), respectively. Candidates still waiting for LT at the end of follow-up stayed a median of 10.4 months ([IQ] 4.2–22.15). Table 3 shows the mean MELD scores at enlistment for the whole population and by groups.

Dropout occurred in 132 candidates (31.4%) (Table 1). Of these candidates, 21.2% occurred because of HCC progression and 78.8% death. Dropout risk at 12-months on the waiting list was 37.6% (Fig. 1). Secondly, at the end of follow-up, only 106 candidates remained on the waiting list (25.2%) (Fig. 1).

Fig. 1.

Waiting list dropout of candidates for liver transplantation (Kaplan–Meier curve). Dropout risk at 12 and 24-months was 37.6% and 54.9%, respectively.

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Out of the 420 candidates who electively enlisted for LT, 182 were transplanted (43.6%), 4 (0.95%) required re-transplantation and 5 (1.19%) needed a double transplant (liver and kidney). Survival at 12 months after LT was 83.2% (Fig. 2). Survival was not significantly different between cirrhotic candidates without exceptions, candidates with HCC and non-HCC plus non-cirrhotic exceptions (p=0.997). The MELD score at LT was 26.74±6.29 (median 26; [IQ] 23.0–30.0). Median follow-up post-LT was 15.75 months ([IQ] 3.68–27.62).

Fig. 2.

Graft survival curve of candidates’ post-Liver Transplantation (post-LT) (Kaplan–Meier curve).

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To identify differences between candidates, we compared the dropout rate between the 3 groups. Dropout for cirrhotic candidates without exceptions was 47.1%, significantly higher than in candidates with HCC and non-HCC plus non-cirrhotic exceptions (37.2% and 26.7%, respectively (p=0.016). Fig. 3 shows the survival rate within the waiting list in the 3 groups of candidates.

Fig. 3.

Liver transplantation waiting list survival, separated by subgroups: cirrhotic candidates without exceptions (LT), candidates with HCC (HCC) and non-HCC plus non-cirrhotic exceptions.

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We additionally assessed the equity within the waiting list comparing the transplantation rate and dropout at 3 and 12 months. At 3 months, the transplantation rate and dropout was higher in cirrhotics without exceptions than in candidates with HCC and non-HCC plus non-cirrhotic exceptions. Also, at 12 months the liver transplantation rate was higher in cirrhotics without exceptions. All differences were statistically significant (p<0.01) (Table 4).

We observed a positive relationship between the MELD score and the probability of transplantation (OR 21.7; p<0.001). There was no relationship between age, sex, the presence of cirrhosis, HCC, other exceptions and probability of transplantation.

The MELD score at the time of LT was not related to mortality post-LT (OR 1.02, IC95% 0.96–1.08; p=0.47); neither was time on the waiting list (OR 1.0, IC95% 0.99–1.0; p=0.52) either. The MELD score at enlistment was also not associated with mortality while on the waiting list (OR 1.0, IC95% 0.96–1.04). Finally, neither age, sex, the presence of cirrhosis, HCC nor other exceptions were related to mortality post-LT.