Exception points for liver transplantation: A Canadian review

Abstract

Background:

Exception points for liver transplant (LT) allocation are used to account for mortality risk not reflected by scoring systems such as the Model for End-Stage Liver Disease with sodium (MELD-Na). Currently, there is no formal policy regarding exception points in Canada, and differences across the country are not well understood. As such, a review of the criteria and exception points granted throughout the country for LT was conducted.

Methods:

Seven LT centres in five provinces were surveyed (Vancouver, Edmonton, London, Toronto, Montréal, Halifax) regarding the indications and criteria for exception points granted, the number of points granted, how points would be accrued, and the maximum points granted.

Results:

Programs in British Columbia and Nova Scotia grant variable exception points based on the median MELD-Na score with modifications; Alberta, Ontario, and Quebec grant exception points using specific values based on the indication. Overall, there was significant heterogeneity regarding exception points granted nationally with agreement only for awarding exception points for hepatopulmonary syndrome and polycystic liver disease. The second most common agreed-upon indications for exception points were portopulmonary hypertension and recurrent cholangitis offered by four provinces. Quebec had the most formal criteria for non-cirrhosis-based conditions.

Conclusions:

There is substantial variance across the country regarding the indications for granting exception points as well as the number of points granted. Future work on developing a national consensus will be important for the development of equity in LT across Canada.

Introduction

Liver transplantation (LT) offers the opportunity to improve quality and quantity of life for patients living with chronic liver disease and its associated complications. In Canada, there were 565 LTs in 2020 (1,2), with the number of LTs performed increasing by 22% over the past 10 years (1). Organ allocation for LT is based on the principle of the ‘sickest’ receiving a compatible organ first. Currently in Canada, the Model for End-Stage Liver Disease with sodium (MELD-Na) score in adults and children ≥12 years of age and the Pediatric Model for End-Stage Liver Disease (PELD) for children <12 years of age (3) are used for organ allocation. Patients are further classified using the CanWAIT system (4) based on their diagnosis and where they are located (ie, home, hospital, intensive care unit [ICU]) (Table 1).

Table 1:

Canadian CanWAIT system (Modified from [4])

CanWAIT score	Definition
4F	Acute liver failure in intensive care unit requiring mechanical ventilation
4	Chronic liver disease in intensive care unit requiring mechanical ventilation
3F	Acute liver failure in intensive care unit not requiring mechanical ventilation
3	Chronic liver disease in intensive care unit for Grade 3 or 4 encephalopathy or renal dysfunction but not requiring mechanical ventilation
2	Chronic liver disease admitted to hospital
1T	Chronic liver disease at home with hepatocellular carcinoma
1	Chronic liver disease at home
0	On hold for liver transplantation

Components of the MELD-Na score are international normalized ratio (INR), bilirubin, creatinine, and sodium with scores ranging from 6–40. The PELD score is based on albumin, bilirubin, INR, growth failure (based on sex, height, and weight), as well as age at listing. Higher scores are associated with an increased 3-month mortality in general (5) although the PELD score may underestimate the risk of mortality (6). Organs are generally offered provincially before being offered nationally; the exception being patients with fulminant liver failure or primary non-function of a graft who are nationally eligible for a LT (Status 3F and 4F) (4,7).

Although the MELD-Na score is good at predicting mortality in most patients (8) and the PELD score is fair in this regard (6), it is recognized that these scores are imperfect and some conditions require assigned exception MELD or exception PELD scores (eMELD/ePELD) to account for this (9), with hepatocellular carcinoma being the classic example. Patients assigned exception points are ranked on the waitlist with the highest of their eMELD/ePELD score or their natural MELD-Na/PELD score. Previous work has shown that there are national differences regarding assigned exception points for hepatocellular carcinoma in Canada (10). When programs were last surveyed in 2014 regarding granting of exception points for non-hepatocellular carcinoma indications, the accepted indications varied among programs although specific details regarding exception points were not reported (4). Having standard uniform policies for transplantation in Canada is important to avoid patients being disadvantaged by policy and the ‘postal-code lottery’ based on where they live (11) as well as potential impacts on program capacity due to patients understandably moving to areas which offer more favourable chances of transplantation. Currently, each program has its own individual policies that are not consistently available publicly. As such, it remains unclear if there is a national consensus on the awarding of exception points for other conditions in LT; given this, the goal of this study was to assess the criteria for how MELD-Na/PELD exception points are granted in Canada.

Methods

Representatives from each program reported their exception criteria and exception points assigned for each indication. In Canada, there are seven transplant programs located in five provinces each based out of university institutions: University of British Columbia (Vancouver, British Columbia), University of Alberta (Edmonton, Alberta), Western University (London, Ontario), University of Toronto (Toronto, Ontario), McGill University (Montréal, Quebec), Université de Montréal (Montréal, Quebec) and Dalhousie University (Halifax, Nova Scotia). Policies for provinces containing two transplant centres were identical between the two programs. As no patient data was utilized, ethics approval was not required.

Results

Principles of allocation of eMELD/ePELD scores

In British Columbia and Nova Scotia, eMELD scores are assigned based on the median MELD-Na score for all listed patients with modifications to this score based on the indication. Alberta, Ontario, and Quebec assign a fixed eMELD/ePELD score with subsequent adjustments based on time accrued waiting for transplantation.

Complications associated with cirrhosis

Details of the criteria for eMELD points based on indication and eMELD scores granted are summarized in Table 2. All programs assign eMELD scores for hepatopulmonary syndrome and polycystic liver disease, with four of the five different provinces offering exception points for portopulmonary hypertension and recurrent cholangitis. Only Quebec had specific criteria for eMELD points for recurrent hepatic encephalopathy and refractory ascites/hepatic hydrothorax while Ontario was the only province to have specific criteria for refractory pruritus. In Alberta, only hepatopulmonary syndrome had specific criteria for assigning eMELD points with the vast majority of indications for potential eMELD points being decided on a case-by-case basis (eg, recurrent hepatic encephalopathy, cholangitis, portopulmonary hypertension); assignment of eMELD points is typically associated with the frequency of hospital admissions. Notably, there is extensive variability among all the programs with regards to starting eMELD points assigned, increase in eMELD scores and caps on the maximum eMELD that can be assigned for each condition.

Table 2:

Criteria for standard exception points for liver transplant allocation in Canada for complications associated with cirrhosis

Indication	British Columbia	Alberta	Ontario	Quebec	Nova Scotia
Hepatopulmonary syndrome	• PaO2 <60 mmHg or on home oxygen • No other lung disease • MMaT+3	• PaO2 59–56 mmHg: 22 points • PaO2 55–51 mmHg: 24 points • PaO2 <50 mmHg: 26 points • If PaO2 <50 mmHg, increase by 2 points every 3 months	• PaO2 <60 • Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• Significant portal hypertension • Confirmed intrapulmonary shunt • PaO2 <60 mmHg for at least 30 days prior to exception Baseline 24 points, increase by 1 point every month; maximum 28 points	• Portal hypertension • PaO2 <60 mmHg • Confirmed intrapulmonary shunt and exclusion of intracardiac shunts • No alternative pulmonary disease to explain hypoxemia • MMaT-3
Portopulmonary hypertension	• Post treatment MPAP <35 mmHg • PVR <400dynes.s.cm−5 • MMaT+3	• Case-by-case review • Baseline 22 points; increase by case-by-case review	• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points		• MPAP >35 mmHg • PVR >240dynes.s.cm−5 • Initial transpulmonary gradient >12 mmHg • MPAP post treatment <35 mmHg • MMaT-3
Recurrent cholangitis	• ≥2 episodes of bacteremia in last 6 months with ≥1 episode of sepsis requiring vasoactive agents • Presence of abscess • MMaT	• Case-by-case review (ICU admission, no. of hospitalizations, on antibiotics for prophylaxis, complications such as endocarditis or osteomyelitis) • Baseline 22 points; increase by case-by-case review	• Two culture-proven bacteraemia episodes within a 6-month period or who have septic complications of bacterial cholangitis • Infections not related to procedure, should not have biliary tube/stent • Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• Persistent cholestasis • Multiple non-anastomotic biliary strictures • Failed treatment of strictures • ≥2 episodes of complications including cholangitis, hepatic abscess requiring hospitalization within last 6 months • Baseline 24 points, increase by 1 point every month; maximum 28 points
Recurrent hepatic encephalopathy	• ≥2 hospitalizations for unprovoked HE on maximal therapy within last 6 months • MMaT	• Case-by-case review (number of hospitalizations considered) • Baseline 22 points; increase by case-by-case review		• Four hospitalizations for HE in a year lasting for at least a week • No triggers • On maximal therapy • Impacting ability to function at home/work • Baseline 18 points increase by 1 point per month; maximum 26 points
Refractory ascites/hepatic hydrothorax		• Case-by-case review (number of hospitalizations considered) • Baseline 22 points; increase by case-by-case review		• 4 thoracentesis of 1 L in the previous 12 weeks OR 1 episode of infection  • Albumin gradient of ≥11  • No heart failure within 3 months  • Negative cytology  • TIPS contraindicated/ineffective  • Diuretic intolerant/ineffective • Baseline 18 points increase by 1 point per month; maximum 26 points
Refractory pruritus			• Failure of all medical therapies • Receiving plasmapheresis • Elevated serum bile acid levels • Impaired quality of life • Baseline 22 points, increase by 3 points every 90 days

MMaT = Median Model for End-Stage Liver Disease at Transplant; PaO₂ = Partial pressure of oxygen; TIPS = Transjugular intrahepatic portosystemic shunt; MPAP = Mean pulmonary artery pressure; HE = Hepatic encephalopathy; PVR = Pulmonary vascular resistance

Conditions unrelated to complications associated with cirrhosis

Across Canada, there is universal agreement that with primary non-function of a graft or hepatic artery thrombosis within 7 days of liver transplant, patients would be listed status 4F and become eligible for an organ nationally. eMELD points also potentially could be assigned throughout Canada for polycystic liver disease. Full details of criteria and eMELD points assigned are found in Table 3.

Table 3:

Criteria for standard exception points for liver transplant allocation in Canada for conditions not related to complications associated with cirrhosis

Indication	British Columbia	Alberta	Ontario	Quebec	Nova Scotia
Hereditary haemorrhagic telangiectasia	• No extrahepatic disease • Evidence of high output cardiac failure, biliary ischemia, or significant portal hypertension • MMaT+3			• Evidence of cardiac insufficiency within 3 months prior to request • Demonstration of AVM in the liver on imaging or severe bibulbar necrosis • Baseline 18 points, increase by 1 point per month; maximum 26 points
Familial amyloid polyneuropathy	• Evidence of neurological impairment • MMaT	• Baseline 22 points, increase by 2 points every 3 months	• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• If significant heart failure, would accept a heart/liver transplant • EF >40% • Able to walk alone • Evidence of transthyretin mutation • Amyloidosis proven by biopsy • Baseline 18 points, increase by 1 point per month; maximum of 26 points
Cystic fibrosis	• If on lung transplant list as well • MMaT+3	• If poor lung function/deterioration • Baseline 25 points, increase by 2–3 points every 3 months	• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• With decompensated cirrhosis • Baseline 24 points, increase by 1 point every month; maximum 28 points
Cholangiocarcinoma	• MMaT+3	• After laparotomy for node sampling • Baseline 30 points	• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• Received neoadjuvant therapy • Cholangiocarcinoma diagnosed by malignant stricture with at least one of the following: biopsy/cytology consistent with tumour, CA 19–9 >100 without cholangitis, aneulplody • Unresectable lesion; lesion <3 cm in size • No history of biopsy/aspiration transperineally, no extrahepatic metastases • Baseline 24 points, increase by 1 point every month; maximum 28 points
Metabolic disease (eg, Maple syrup urine disease, hyperoxaluria type 1, hereditary amyloid)	• Evidence of neurological impairment • MMaT		• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• Baseline 24 points, increase by 1 point every month; maximum 28 points
Multiple hepatic adenomas				• Unresectable hepatic adenomas with at least one of the criteria: a) Malignant transformation of one lesion <2 cm proven by biopsy, b) glycogen storage disorder, c) Beta-catenin mutation • Baseline 18 points increase by 1 point per month; maximum 26 points
Hepatic epithelioid hemangioendothelioma				• Unresectable liver lesions that are biopsy proven • If any extrahepatic metastatic disease, stable for 3 months prior to exception points • Baseline 24 points, increase by 1 point every month; maximum 28 points
Neuroendocrine tumour	• Primary tumour resected and stable for at least 6 months • ≤50% of liver volume • Age ≤60 • MMaT+3			• Age <65 • Primary lesion and extrahepatic metastatic lesions resected with no growth for 6 months • Unresectable liver lesions, <50% of liver volume • Primary from GI/liver source (drained by portal vein) • Tumour well/moderately differentiated with a mitotic index <20/10 HPF and KI-67 <20% • Baseline 24 points, increase by 1 point every month; maximum 28 points
Polycystic liver disease	• Evidence of portal hypertension or complications due to mass effect (eg, malnutrition), or recurrent cyst infections • MMaT	• Case-by-case review (malnutrition, or infection of cysts) • Baseline 22 points, increase based on case-by-case review	• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• Mayo Class C or D with either hepatic decompensation or significant sarcopenia • Baseline 18 points increase by 1 point per month; maximum 26 points	• If meets one of following criteria:  1. Ascites or variceal bleeding  2. Budd-Chiari-like-syndrome with • Hepato-venous outflow obstruction due to cysts (CT/MRI, Venography)  3. Ascites complicating cyst fenestration procedures  4. Severe malnutrition (as documented by RD assessment) • MMaT-3
Multi-organ transplant requiring same donor		• Case-by-case review	• Liver-lung or liver-heart: 42 points • Liver-bowel: 22 points plus 10% for the risk of 3-month mortality, increase 3 points plus 10% every 90 days; maximum 40 points • Liver-kidney/liver-pancreas: Baseline 22 points, increase by 3 points every 90 days; maximum 40 points
Primary hyperoxaluria	• Evidence of neurological impairment • MMaT		• Baseline 22 points, increase by 3 points every 90 days; maximum 40 points	• Candidate for liver/kidney transplant • Biopsy proven AGT deficiency • GFR <25 ml/min on 2 times separated by 42 days • Baseline 24 points, increase by 1 point every month; maximum 28 points
Repeat liver transplantation		• 25 points, increase based on case-by-case review
Hepatic artery thrombosis post LT (within 7 days)	Status 4F	Status 4F	Status 4F	Status 4F	Status 4F
Primary non function of graft	Status 4F	Status 4F	Status 4F	Status 4F	Status 4F

MMaT = Median Model for End-Stage Liver Disease at Transplant; AVM = Arteriovenous malformation; EF = Ejection fraction; RD = Registered dietitian; GI = Gastrointestinal; HPF = High powered field; AGT = Alanine glyoxylate aminotransferase; GFR = Glomerular filtration rate; LT = Liver transplant; CA 19-9 = Carbohydrate antigen 19-9

Nova Scotia does not assign exception points for any other conditions that are not related to complications associated with cirrhosis. The other four provinces would assign eMELD points for familial amyloid polyneuropathy, cystic fibrosis, familial amyloid polyneuropathy, cholangiocarcinoma, and primary hyperoxaluria. No province specifically assigns eMELD for primary sclerosing cholangitis but any eMELD points assigned are based on the presence of refractory cholangitis or cholangiocarcinoma.

Quebec is unique in that it has specific criteria and eMELD scores for several diagnoses that are not formally encoded by the other programs including hereditary haemorrhagic telangiectasia, multiple hepatic adenomas, hepatic epithelial hemangioendothelioma, and neuroendocrine tumours. Notably, Ontario is the only province with formal criteria and eMELD points for multiorgan transplantation while Alberta is the only province who assigns an eMELD of 25 for patients requiring a repeat LT; all other provinces use the MELD-Na score for allocation of LT in a patient requiring re-transplantation. Of note, the Alberta program considers the number of hospitalizations, infection episodes, malnutrition, and other complications (including poor quality of life) when assigning additional exception points in the setting of repeat LT.

Pediatric transplantation

Only Alberta and Ontario have formal criteria for allocation of ePELD or eMELD focusing on metabolic disorders (eg, urea cycle defects), and hepatoblastoma with similar eMELD/ePELD points assigned (Table 4). Alberta has specific criteria for eMELD/ePELD points for children with chronic liver disease prioritizing children with complicated disease; this does not exist in any other province.

Table 4:

Criteria for standard exception points for pediatrics

Indication	British Columbia	Alberta	Ontario	Quebec	Nova Scotia
Chronic liver disease		24 points-increase by 4 points every 90 days; maximum 30 points If complications, (mechanical ventilation, severe GI bleed (30 cc/kg of replacement/24 h), GCS <10, or renal failure and need for HD), 40 points	24 points-increase by 3 points every 90 days; maximum 39 points If complications, (mechanical ventilation, severe GI bleed (30 cc/kg of replacement/24 h), GCS <10, or renal failure and need for HD) 43 points
Liver malignancy		30 points and if not transplanted in 1 month, assigned 39 points
Hepatopulmonary syndrome		30 points and if not transplanted in 1 month, assigned 39 points
Portopulmonary hypertension		30 points and if not transplanted in 1 month, assigned 39 points
Hepatoblastoma		30 points and if not transplanted within one month increase to Status 4	30 points and if not transplanted in 30 days, assigned 38 points
Metabolic conditions		Baseline 29 points, 2-point increase every 60 days; maximum 39 points Urea cycle defect with rapidly progressive disease, 40 points	Baseline 29 points, 3-point increase every 90 days; maximum 38 points
Multivisceral transplant (same donor)		List status 3F	Liver-lung or liver-heart: 42 points Liver-bowel: Baseline 30 points, if not transplanted in 30 days assigned 38 points Liver-kidney/liver-pancreas: Baseline 22 points, increase by 3 points every 90 days; maximum 40 points
Primary hyperoxaluria		For children <1 year old, baseline 40 points	Baseline 22 points, increase by 3 points every 90 days; maximum 40 points

GI = Gastrointestinal; GCS = Glasgow Coma Score; HD = Hemodialysis

Discussion

In our study, we found eMELD points are more commonly assigned for complications associated with cirrhosis across Canada but are much less established for other indications. There was national consensus regarding assigning eMELD points for primary non-function of the graft as well as acute hepatic artery thrombosis. There was significant heterogeneity throughout the programs with only Alberta and Ontario having specific criteria for eMELD/ePELD points for pediatric patients.

The rationale for assigning eMELD/ePELD points for patients living with liver disease is to account for mortality risk not reflected by their natural MELD-Na/PELD scores. This needs to be balanced out to avoid negative outcomes in patients listed by their natural MELD-Na/PELD score; akin to adjustment required for patients receiving exception points for hepatocellular carcinoma. Patients with MELD exception points in the past have been demonstrated to have lower risks of delisting or waitlist mortality (12,13) and an increased likelihood of obtaining a transplant (14). In the United States, rates of removal from the waitlist between patients assigned exception points and those with natural MELD-Na are becoming more similar with changes in policies on how exception points are granted (15).

In contrast to Canada, in the United States, there are clearly defined criteria and policy for assigning automatic eMELD scores for the seven following conditions by the Organ Procurement and Transplantation Network (OPTN) Liver and Intestinal Organ Transplantation Committee: cholangiocarcinoma, hepatopulmonary syndrome, portopulmonary hypertension, familial amyloid polyneuropathy, cystic fibrosis, metabolic diseases, and primary hyperoxaluria. Full details about criteria and eMELD points assigned by the OPTN are listed in Table 5. In Canada, only the Ontario and British Columbia programs formally offer exception points for all these diagnoses. Quebec does not offer exception points for portopulmonary hypertension and Alberta offers exception points on a case-by-case basis. Neither Alberta nor Nova Scotia offers exception points for metabolic disease. Nova Scotia only offers exception points for two of these seven conditions, hepatopulmonary syndrome and portopulmonary hypertension.

Table 5:

Standardized exception points in the United States (Modified from [19])

Indication	Criteria	eMELD points assigned
Hepatopulmonary syndrome	1. Presence of portal hypertension (ascites, varices, splenomegaly, or thrombocytopenia) 2. Presence of pulmonary shunt 3. PaO2 <60 mmHg on room air within 30 days of initial request 4. No clinically significant underlying primary pulmonary disease	3 points below MMaT (>18 yrs) MMAt (12–18 yrs) MPaT (<12 y)
Portopulmonary hypertension	1. Initial MPAP level ≥35 mmHg and initial PVR level ≥240 dynes.s.cm−5 2. No other causes of pulmonary hypertension 3. Initial transpulmonary gradient to correct for volume overload 4. Documentation of treatment 5. Post treatment MPAP <35 mmHg and post treatment PVR <400 dynes.s.cm−5 within 30 days of exception request 6. Presence of portal hypertension	3 points below MMaT (>18 y) MMAt (12–18 y) MPaT (<12 y)
Familial amyloid polyneuropathy	1. Listed for heart transplant or echocardiogram within 30 days of initial exception showing ejection fraction <40% 2. Patient can walk without assistance 3. Confirmation of TTR gene mutation 4. Biopsy proven amyloid	3 points below MMaT (>18 y) MMAt (12–18 y) MPaT (<12 y)
Cystic fibrosis	1. Diagnosis confirmed by genetic analysis 2. FEV1 <40% predicted within 30 days of initial exception request	3 points below MMaT (>18 y) MMAt (12–18 y) MPaT (<12 y)
Cholangiocarcinoma	Unresectable hilar cholangiocarcinoma without extrahepatic spread; protocol includes neoadjuvant therapy and laparoscopy One of the following: • Biopsy/cytology results showing malignancy • CA 19–9 >100 U/mL in absence of cholangitis • Aneuploidy • Hilar mass <3 cm in radial diameter	3 points below MMaT (>18 y) MMAt (12–18 y) MPaT (<12 y)
Metabolic disease	Urea cycle disorder or organic acidemia	MMAt (12–18 y) MPaT (<12 y) Status 1B if not transplanted in 30 days
Primary hyperoxaluria	1. Listed for kidney transplant 2. AGT deficiency proven 3. eGFR <25 ml/min on two occasions at least 42 days apart	MMaT (>18 y) 3 points above MMAt (12–18 y) 3 points above MPaT (<12 y)

MMaT = Median Model for End-Stage Liver Disease at Transplant; PaO₂ = Partial pressure of oxygen; MPAP = Mean pulmonary arterial pressure; PVR = Pulmonary vascular resistance; TTR = Transthyretin; FEV₁ = Forced expiratory volume at 1 second; CA 19-9 = Carbohydrate antigen 19-9; AGT = Alanine glyoxylate aminotransferase; eGFR = estimated glomerular filtration rate

In addition to the defined policy for exception points by the OPTN in the United States, there is published guidance for discretional granting of exception points for other conditions in adults by the National Liver Review Board (16). These are based on recommendations made by the MELD Exception Study Group and Conference in 2016 (17,18). In the guidance, exception points are not recommended for ascites, hepatic encephalopathy, hepatic hydrothorax, GI bleeding, chronic rejection, pruritus, small for size syndrome post liver transplantation or hepatic artery thrombosis beyond 14 days post-liver transplantation. Suggested indications and criteria for granting exception points exist for patients with hepatic epithelioid hemangioendothelioma, hereditary hemorrhagic telangiectasia, multiple hepatic adenomas, neuroendocrine tumours, and polycystic liver disease; many of Quebec’s policies for these indications are based on this guidance from the OPTN.

For pediatric patients in the United States, transplant is prioritized by policy for patients with biopsy proven hepatoblastoma, certain metabolic disease, as well as chronic liver disease with a MELD/PELD >25 with organ failure including being on a ventilator, GI bleeding requiring 30 mL/kg red blood cell replacement in the previous 24 hours, renal insufficiency requiring dialysis, or having a Glasgow coma scale <10 (19). These criteria for allocation of exception points are like what is used in Alberta. Non-binding guidance from the OPTN also suggest that pediatric patients with hepatic epithelioid hemangioendothelioma, neuroendocrine tumours, recurrent cholangitis, portal hypertension complications, pruritus, metabolic bone disease, or growth failure/nutritional deficiency may potentially be considered for exception points (20); no Canadian program offers exception points formally for these indications in children.

A potential factor that may affect development of national policies is how health care is delivered. In Canada, health care is funded by a combination of provincial and federal funding and administered provincially (21), which may play some role in the heterogeneity of policy, similar to that of substance use in transplant recipients (22). Standardization of criteria for granting eMELD/ePELD points is important to ensure that patients throughout Canada receive equitable treatment for access to transplant based on their diagnosis. There are a number of challenges with developing standardized policies; some exception points granted may not be evidence based given that the goal is to ensure that patients granted exception points have a similar mortality to those with the same natural MELD-Na/PELD score (9). In addition, there are geographical differences with regards to MELD-Na/PELD scores (15), meaning that fixed eMELD/ePELD scores may have different value depending on where one is living. As such, an eMELD of 28 may be more competitive for transplant in one province but not in another. To try and mitigate this, the use of the median MELD/PELD score as a baseline has been introduced in the United States and is currently being used by British Columbia and Nova Scotia for their allocation. A national shift to the use of median MELD scores for all indications including hepatocellular carcinoma may help with this potential inequity.

To date, most of the work with transplant allocation in Canada has focused on the general listing allocation through the MELD-Na score and allocation for pediatric patients (3). There has been limited discussion regarding standardized exception points with the most work thus far being done in hepatocellular carcinoma although there still remains significant heterogeneity (10). This article is the first to explicitly review provincial polices for granting eMELD/ePELD points and highlights the need for discussion to try and improve equity for patients listed for LT in Canada and standardize policies. Standard national policies are critical for the goal of offering as equitable access to liver transplantation in Canada as possible acknowledging the geography of the country and individual program characteristics. Although having one national list would potentially improve equity for patients, such as in the United States, this logistically would be extremely difficult in Canada due to the significant geographical distances between programs. With current policy heterogeneity in the country, a patient with refractory ascites and a low MELD-Na score would potentially be competitive for transplant in Quebec but not in British Columbia. Further, patients will understandably consider moving to programs which will offer the highest chances of transplantation with a key example being alcohol associated liver disease and differing criteria for listing (22). Notably, many patients do not have the resources to be able to move provinces which may led to further inequity based on socio-economic status.

Going forward, given the significant differences across the country for transplant policies (10,22) and restrictions, developing national consensus through organized meetings and conferences would be of critical importance. Organization of these meetings should involve key national and regional organizations such as the Canadian Association for the Study of the Liver, the Canadian Society of Transplantation, Canadian Blood Services, Trillium, and Transplantation Quebec. Attendance at these conferences should involve transplant hepatologists, transplant surgeons, allied health as well as patient representation with a priori development of specific questions and use of Delphi methodology; key questions to answer for exception point assignment would be which diagnoses should be granted exception points, how will these diagnoses be defined, specific points assigned, and accrual of points, if applicable. Similarly, for hepatocellular carcinoma, eligibility for exception points, points granted, and downstaging criteria needs to be clarified. Specifically, when developing policy-based standard national exceptions, we need to ensure the evidence supports the inclusion of the indication and that scores assigned are reflective of the mortality risk as best possible, acknowledging that the use of exception points is imperfect given variability in disease biology between individuals. With any change to the exception point allocation system, ongoing monitoring of waitlist dropout/mortality, transplantation rates and mortality rates for each indication on at least an annual basis will be crucial to inform the impact of these policies and ensure there are no unintended consequences which can be nationally tracked through the CIHI organ registry.

Potentially converting to a median MELD score-based system for each regional list may help account for geographical differences with regards to access to LT transplantation and help balance things nationally; the impact of this change on waitlists could be modelled for the five programs that do not currently use this system prior to a conversion. Evolution of transplant policy is probably best done in a staged approach as multiple changes may be difficult to implement all at once and so considering a national switch to median MELD might be a subsequent step towards improving transplant equity in Canada after working on standardizing listing policies and exception point allocation.

Conclusions

Exception points for patients listed for liver transplant are granted across the country for a variety of conditions including those associated with cirrhosis and those that are not. There is significant heterogeneity among all the programs in Canada although consensus exists on a few areas. This study highlights the need for a national consensus conference which may be the first step in resolving national differences. Creation of national, transparent exception criteria can help reach equity in LT in Canada.

Contributions:

Conceptualization, M Brahmania, SE Congly; Methodology, SE Congly, M Brahmania; Data Acquisition, V Marquez, RA Bhanji, M Bhat, P Wong, G Huard, JH Zhu, M Brahmania; Writing – Original Draft, SE Congly; Writing – Review & Editing, V Marquez, RA Bhanji, M Bhat, P Wong, G Huard, JH Zhu, M Brahmania, SE Congly.

Ethics Approval:

N/A

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Data Accessibility:

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

Funding:

No funding was received for this work.

Disclosures:

The authors have nothing to disclose.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A