EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Living-donor liver transplant allows for expedited transplant, with outcomes shown to be superior compared with deceased-donor liver transplant due to earlier intervention, with reduced hospital costs. However, they only comprise about 5% of liver transplants nationally. This is due to a limited pool of willing donors and donor exclusions for medical and psycho-social reasons. The leading reason for why potential living liver donors are not eligible is non-alcoholic fatty liver disease. Donor hepatic steatosis limits the number of potential living-donor liver transplants because it is associated with perioperative complications in both donors and recipients. Here, we describe a 37-year-old male potential living donor who presented with hepatic steatosis based on preoperative imaging. Over a 1-year period, he was able to completely reverse his hepatic steatosis by losing about 86 pounds (from 279 to 193 pounds), reducing his body mass index from 40 to 28.55 kg/m². Computed tomography and biopsy results after his weight loss showed that he had no hepatic steatosis, allowing him to become a living donor for his mother. Postoperative periods for both the donor and recipient were uncomplicated. This case suggests that the pool of living liver donors could be expanded through dietary and behavior modifications, thus increasing the number of potential living donors and providing potential recipients with more transplant options. Enlarging this pool of donors will also improve transplant outcomes for donors and recipients and lower overall health care costs compared with deceased-donor liver transplant.

Key words : Allocation, Complications, Contraindications, Donor selection, Liver transplant, Non-alcoholic fatty liver disease

Living-donor liver transplant (LDLT) has been shown to be safe and, in addition, has multiple advantages over deceased-donor liver transplant (DDLT). A study by Humar and associates1 found that the 3-year patient survival rate is increased by 6% (P = .03), hospital stays are reduced by 2 days (P < .01), and there are 26% fewer intraoperative blood transfusions (P < .01) with LDLT. Living-donor liver transplant is also associated with a 5.8% reduction in posttransplant dialysis (P < .01). Furthermore, LDLT is less expensive; one institution calculated a 29.5% reduction in hospital costs for LDLT compared with DDLT.¹ Unfortunately, LDLTs only comprise about 4.8% of liver transplant procedures nationally. The remaining transplants are from deceased donors, a donor population that cannot meet the national demand, and up to 1 in 4 patients on wait lists die before they receive a transplant.¹ Lack of potential donors may be addressed by expanding the LDLT pool. However, patients seeking living liver donations still encounter multiple barriers to transplant because few individuals are willing to undergo a major surgery for organ donation, and many donors are refused for medical or psycho-social reasons.

A 37-year-old white male patient with a medical history of obesity (weight: 279 pounds, body mass index [BMI]: 40 kg/m2) and a history of drinking 4 to 5 beers per week presented for clinical evaluation to become a living donor for his mother. Initially, he was determined to be ineligible for liver donation due to high risk of perioperative morbidity and mortality secondary to morbid obesity (BMI of 40 kg/m²). A triple-phase computed tomography (CT) scan of his liver revealed severe hepatic steatosis (Figure 1). However, he was told that his candidacy would be reevaluated if he could reduce his BMI to about 30 kg/m².

Within 1 year, he presented for reevaluation after losing 86 pounds (weight: 193 pounds, BMI: 28.55 kg/m²) due to a regimented diet and exercise plan. He successfully quit smoking and drinking completely. Triple-phase CT following weight loss showed resolution of hepatic steatosis (Figure 2), as demonstrated by liver volume measurements (Table 1). A liver biopsy taken before transplant showed no steatosis and minor granulomatosis (Figure 3). The left lobe of his liver made up about 39% of total volume, allowing him to donate the right lobe of his liver. After successful transplant of the right lobe of his liver, he continues to maintain his weight loss to below preoperative weight 2 years later (weight: 244 pounds, BMI: 35 kg/m²). Both donor and recipient did not have any postoperative complications related to graft function, and both remain well (Figure 4).

One of the leading reasons why potential donors are not eligible for LDLT is hepatic steatosis. Given the current obesity epidemic in the United States, affecting 37% of the population, elevated BMI is a significant barrier to transplant because hepatic steatosis has a profoundly negative impact on outcomes for recipients of LDLTs.² A global survey of selection policies for living liver donors at 24 centers with a combined experience of over 19 000 LDLTs found that, to meet transplant criteria, the median upper BMI limit of donors should be 33 kg/m². At 63% of these centers, age influenced the upper limit of BMI inversely, meaning older donor candidates typically had a lower BMI. All centers factored in macrovesicular steatosis, and half of all centers took microvesicular steatosis into consideration when evaluating donor candidacy.³

Significant steatosis is considered a contraindication to living donation because it is associated with primary nonfunction (PNF) and poor graft function.^4-7 Typically, transplant is reserved for livers from deceased donors with mild macrosteatosis (< 30%) because these grafts have similar success rates to those of nonsteatotic livers. In living donors, up to 20% steatosis has been found to be a safe upper limit.⁸ Others go further to say that livers with greater than 20% macrovesicular steatosis require rigorous liver donor treatment (ie, diet, exercise, and weight loss-promoting medications) to ensure a successful LDLT outcome.⁹ Some have noted that there may be a 1-to-1 direct relationship between percentage of steatosis and percent PNF (i.e. a 1% increase in steatosis leads to a 1% rise in PNF).¹⁰ Steatosis impacts donor outcomes due to impaired hepatic regeneration.⁹ Donor steatosis is also associated with increased morbidity, mortality, transfusion requirements, and surgical time.¹¹ One study of 67 LDLT recipients found that higher preoperative macrovesicular steatosis (5% to 30%) was significantly associated with increased rates of intrahepatic cholestasis and transient hyperbilirubinemia during the regeneration period after transplant (P < .001). This study also found an association between higher rates of PNF and higher preoperative macrovesicular steatosis.¹²

Perkins and colleagues¹³ showed that steatosis could be reversed through a protein-rich diet, exercise, and fibrate use for a period of 2 weeks to 2 months. This treatment regimen was found to reduce macrovesicular steatosis (P = .0028) as well as body weight (P = .0033) and BMI (P = .0033). Peak total bilirubin, postoperative prothrombin time, and peak alanine aminotransferase levels were analyzed before and after the study intervention as a proxy for liver function. These values had normalized after the study period, which led to a decreased rate of complications after LDLT.¹³ In contrast, our study patient neither used this specific regimen nor pharmacologic medications for weight loss (i.e. bezafibrate). This suggests that weight loss by any means may be equally as effective as pharmacologic treatment, which can cause side effects, including hepatotoxicity.¹⁴

When steatotic grafts are the only option, especially in Asia where deceased donors are scarcely available, transplant surgeons have attempted to solve this issue through a dual-graft LDLT, in which a severely steatotic graft (> 60% steatosis) and a small nonsteatotic liver graft are both grafted. This strategy has shown favorable results, as the previously steatotic graft (70% and 80% steatosis in 2 different cases) spontaneously cleared the steatosis at 24 and 14 days posttransplant, respectively (no steatosis and < 3% steatosis, respectively). The mechanism of postoperative steatosis reversal is not yet understood; however, it may be due to steatotic graft fat mobilization in the postoperative period, when the recovering patient is typically hypermetabolic in response to the physiologic stress of surgery.

Our report shows that the pool of potential living donors can be increased simply by reversing steatosis through preoperative weight reduction. This idea avoids use of dual grafts and use of pharmacologic agents for weight loss. Furthermore, it shows that the pool of living liver donors may be expanded through preoperative weight loss, leading to potentially better outcomes and lower hospital costs compared with DDLT.

We report a case of a living donor who was able to adequately reverse his hepatic steatosis through diet and exercise, reducing his liver volume by 46%. This case shows that even obese donors can be considered for liver donation if they are otherwise medically suitable and able to adequately lower and maintain their BMI below 30 kg/m². This potentially increases the number of living donors present in the United States by countering steatosis, the leading cause of donor ineligibility. Doing so not only improves patient and recipient outcomes and lowers hospital costs, as previously discussed, but also reduces the number of patients who deteriorate and die while on wait lists for a deceased liver donor.

Volume: 20 Issue: 9 September 2022

FULL TEXT