Liver Transplantation for Polycystic Liver Disease: Definitely Not a Cosmetic Surgery

In the absence of life-threatening complications, many centers are reluctant to consider liver transplantation in patients with polycystic liver disease (PLD), even if this condition is responsible for major disabling and significant deterioration in quality of life. The main objection is organ shortage because these patients can live with a markedly enlarged liver. European guidelines have proposed that liver transplantation can be an option for selected patients in the following situations: (1) massive hepatomegaly with diffuse cysts and severely impaired quality of life, (2) specific complications (severe malnutrition, ascites, portal hypertension, outflow obstruction, and recurrent hepatic cyst infections), and (3) failure of nontransplant options.1 In patients with associated end-stage polycystic kidney disease, simultaneous liver and kidney transplantation (SLKT) should be proposed. Because the model for end-stage liver disease (MELD) score is not relevant to assess the severity of PLD, transplantation is considered a MELD exception. In the United States, according to the most recent MELD exceptions update (2019), extra points are now assigned on the basis of the median MELD score at transplantation (MMaT) in the area where candidates are listed.2 In this issue of Transplantation, Miyake et al3 showed that the implementation of the new MMaT allocation policy resulted in a significantly higher 1-y transplant probability for patients with PLD compared with previous policies, 55.7% versus 37.9% (P = 0.001) at the national level. Interestingly, this difference was only significant in high MMaT centers (52.4% versus 27.5%; P = 0.001), whereas the probability remained around 60% in low MMaT centers. In this series, 1-y waiting list mortality for patients with PLD was around 7%, which is surprisingly high. The authors confirm the excellent posttransplant outcomes, with 1-y survival rate exceeding 90%. Although no debate exists on the need for kidney transplantation in patients with end-stage polycystic kidney disease, there is no consensus on the place for liver transplantation in patients with PLD. According to the United Network for Organ Sharing and Eurotransplant allocation policies, "severe symptoms associated with massive hepatomegaly and severe malnutrition" are required to qualify for MELD exception points. However, the term "severe symptoms" is based on patient-reported generic outcomes in gastrointestinal diseases, and it does not capture some specific aspects of PLD, particularly abdominal distension, dyspnea, and reduced mobility. In addition, these criteria are neither standardized nor objective. Although the main objective of allocation is to achieve a compromise between low waiting list mortality and excellent survival rates after transplantation, the primary objective in PLD is to improve quality of life. Thus, the objective of the MELD exception would give the highest priority to the patients with the highest benefit from transplantation in terms of quality of life in the broadest sense. Consequently, the metrics needed to determine which patients with PLD should be transplanted are very different in nature from those used for patients with cirrhosis. Malnutrition and sarcopenia are markers of severity that should be considered in decision-making for liver transplantation. Although increasing evidence suggests that sarcopenia based on imaging is associated with increased waiting list mortality in cirrhosis, no such data exist in PLD. Intuitively, those with poor nutritional status and advanced sarcopenia are likely to derive a major quality-of-life benefit from transplantation. No correlation between sarcopenia and the severity of disability has been established. The volume of the liver also plays an important role, but experience shows no good correlation between liver volume in an individual and perceived handicap. Reduced autonomy may be related to a synergistic interaction between sarcopenia and increased volume of the abdomen. Specific scores to assess caloric protein malnutrition are used to assess nutritional status, but none of them identified an optimal window for liver transplantation. Finally, psychological aspects are particularly important in the transplant decision-making process; however, they are frequently overlooked. PLD predominates in women and many of them have a poor self-image. In particular, the way other people look at a distended abdomen while they are obviously no longer of childbearing age can be devastating. A disease-specific questionnaire covering physical and psychological aspects and quality of life has been proposed and validated in a Dutch and US patient cohort in 2016 and could be helpful.4 Beyond the indication, the timing for SLKT in patients remains a complex issue. In general, the results of preemptive kidney transplantation are better than those of transplantation in patients on dialysis. Indeed, a recent study suggests that preemptive transplantation is associated with a decreased risk of kidney graft failure (hazard ratio 0.57; 95% confidence interval, 0.51-0.63) compared with transplantation after dialysis, regardless of its duration and after adjustment for both recipient characteristics and donor type.5 Therefore, a strategy consisting of proposing SLKT rather than liver transplantation alone in symptomatic PLD patients with a glomerular filtration rates of <30 mL/min seems a reasonable option. The argument supporting SLKT rather than sequential liver and kidney transplantation is that the liver is immunoprotective for the kidney when the donor is the same. Studies have shown that in HLA-mismatched and sensitized patients, rejection-free survival is higher and the incidence of kidney graft loss because of chronic rejection is lower after SLKT.6 Interestingly, a positive crossmatch may become negative after liver graft reperfusion.7,8 The results presented by Miyake et al3 in this issue of Transplantation are encouraging. However, only 55.7% polycystic liver and kidney disease eventually received SLKT within 1 y after registration which can be considered a too small proportion. More details should be given on the reasons for a 7% waiting list mortality and why only about 50% of patients did have MELD exception. Overall, only 317 patients with polycystic liver and kidney disease listed were identified in the US between 2016 and 2021, representing a very small proportion of all candidates. Therefore, reluctance for transplantation in symptomatic patients with PLD is no longer justified because the transplant benefit is huge, long-term kidney graft survival seems high, and the impact on transplantation for other indications is very limited. Liver transplantation for PLD remains a complex procedure and patients should be oriented to experienced centers.9,10