Commentary

The higher prevalence of obese patients evaluated for liver and kidney transplant is growing. It is estimated that the prevalence of obesity is 20 to 30% in liver transplant recipients and approaching 60% of patients undergoing renal transplantation [1, 2]. Often, obesity is a relative barrier or contraindication to transplantation and is inadequately addressed by medical therapy. The reasons for this high prevalence are twofold. First, the promotion of end-stage organ disease by obesity and the associated comorbidities (type 2 diabetes mellitus, hypertension, dyslipidemia, non-alcoholic fatty liver disease). Second, the increase in body weight often seen after transplantation due to maintenance immunosuppressive therapy with steroids and improve general health and appetite following transplantation [3, 4]. Specifically, the morbidly obese patients who undergo organ transplantation tend to gain weight following the procedure [5].

This vicious cycle of obesity, end-stage disease, transplant, and obesity can be broken with bariatric surgery (BS).

BS in the peri-transplant patient is not yet extensively studied and comparative data on long-term outcomes regarding optimal timing and type of bariatric procedure are lacking.

The major cause of mortality in transplant patients is associated with cardiovascular sequela related to obesity [6]. Performing any major surgical procedure on obese patients is more difficult, takes longer, and is subject to a higher rate of operative and peri-operative complications [7, 8]. The surgical outcomes are worse in obese patients when compared with their non-obese counterparts [9, 10]. Large studies show that among kidney transplant recipients, obesity is associated with a higher risk of allograft failure and death [9,10,11,12].

Nevertheless, the only successful remedy for these patients, in the long run, is BS [6].

Currently, there are no universally set guidelines regarding body mass index (BMI) cutoff for potential transplant patients, and yet, most institutions have upper limits for BMIs above which they will not perform the transplant.

Kidney

First, we should distinguish the end-stage renal disease (ESRD) patients from the kidney transplant populations which display different systemic and surgical characteristics. Use of BS has been relatively uncommon among kidney transplant candidates and recipients despite otherwise qualifying indications. On the one hand, delaying BS would not address the technical complications of morbidly obese patients after kidney transplantation. Furthermore, a gastric leak, though an uncommon complication, could be more complicated to manage in a patient on immunosuppressive medication than in chronic renal failure. If sepsis were to develop, it would be conceivable that lowering the immunosuppression would be necessary thereby increasing the risk for graft rejection. Nevertheless, a number of epidemiologic studies with large samples of ESRD patients have indicated paradoxically inverse associations between classic risk factors for cardiovascular disease and mortality [13]. Our experience shows a good experience with 24 ESRD patients undergo laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB), and demonstrates that BS as an effective bridge to kidney transplant with 67% (n = 16) of patients proceeded to kidney transplantation following successful weight reduction in 95% of patients. The mean weight before the transplant was 84 kg and the mean BMI is 29 kg/m2. Mean follow-up post-transplant of 24 months shows that the weight did not increase following transplantation.

In the kidney transplant patients, we demonstrate that the level of immunosuppressive drugs remained stable in both surgical groups (LSG and LRYGB) without the need for any significant changes in drug dosage. In addition, there were no incidences of graft loss or major graft complications, while weight reduction was maintained together with improvement in comorbidities [14].

Liver

When discussing peri-transplant liver patients, there are three options pre-, during, and post-transplant. We are one of the first transplant centers worldwide that offer bariatric procedure for transplanted patients [14,15,16]. There is a lack of experience worldwide performing BS as a bridge to transplantation, with only a few small series [17,18,19].

Non-alcoholic steatohepatitis (NASH) is considered the most common chronic liver disease in the Western world [20, 21]. NASH describes a spectrum of liver injury caused by triglyceride accumulation in hepatocytes and ranges in severity from benign steatosis to steatohepatitis and ultimately fibrosis and cirrhosis [22]. In 1980, Ludwig et al. [23] named the condition of NASH to describe the liver disease seen in 20 patients without a history of alcohol abuse who demonstrated histologic evidence of marked hepatic steatosis associated with lobular hepatitis, focal necrosis with inflammatory infiltrates, and Mallory bodies. Most of these patients were female, were obese, and had obesity-related diabetes [23]. Over the past three decades, non-alcoholic fatty liver disease has emerged as the most common liver disease in the Western world affecting an estimated 25% of the adult population [24]. As a result, in 2017, NASH-related hepatocellular carcinoma (HCC) represented 18% of all HCC listings to liver transplant which was an 8.5-fold increase from 2002, and the trend is still steadily growing at approximately 1.9 percentage points per year over the last 4 years [25]. Recently, NASH has become the second leading indication for liver transplantation [26].

Specifically, to this population, it has the potential to influence the incidence of NASH in the post-transplant setting. BS is associated with an improvement of all NASH histologic features. Takata and Lin [27] reported promising results concerning metabolic comorbidities but significantly higher post-operative complication rates compared to the general population. There remains of no consensus on which bariatric modality is best suited for the patient with cirrhosis [28]. Current available data suggest that the less invasive laparoscopic approach would be safer to perform in cirrhotic patients. In general, LRYGB provides the most potential for weight loss but may have a greater risk of vitamin deficiencies compared to LSG that may further lead to progressive hepatic dysfunction.

Both compensated and uncompensated cirrhosis are associated with significantly increased rates of mortality in patients having elective surgery compared with patients without liver disease [29]. BS in cirrhotic patients should be done only in very selected patients, particularly with low model for end-stage liver disease (MELD) scores without significant portal hypertension [29].

Combined BS and liver transplantation may prolong operative time and complexity of the procedure. In addition, inadequate immunosuppressive medication absorption and poor nutritional status of the patients immediately after transplant may complicate and limit the use of this approach. Campsen et al. [30] described the first case report of combined BS at the time of liver transplant. In addition to weight reduction at 6-month follow-up, the patient had a resolution of her type 2 diabetes mellitus and hypertension and no post-operative complications. Recently published by our group, a series of 3 patients who underwent simultaneous liver transplant and sleeve gastrectomy [16]. The 3 patients with a median BMI of 46.6 kg/m2 and a median MELD of 24 underwent a simultaneous liver transplant and sleeve gastrectomy. None of the patients experienced any problems with immunosuppressive medications intake or graft rejection or dysfunction. Two of the patients had a complete remission of hypertension and diabetes. All three are currently alive with normal allograft function.

According to the post-liver transplant group, recent reports support the contention that this unique subgroup of obese post-transplanted patients is suitable for BS. A systemic review by Lazzati et al. [31] determined that BS is feasible and effective in patients after liver transplant. The morbidity rates were higher than the general population undergoing BS, but they remained acceptable (9% versus 5%, respectively) [31, 32]. Lin et al. [19] recently reported nine LSG procedures in patients after liver transplantation and did not observe any significant changes in dosing of tacrolimus or medication trough levels. Technical feasibility should be considered when choosing the type of bariatric procedure. In many studies, the most common procedure has been sleeve gastrectomy, with up to 100% in some series [31, 33, 34].

BS is the most effective solution for morbid obesity, and the number of patients undergoing it is consistently growing [35, 36].

With the most up to date data [37,38,39], strong recommendations cannot be made since most of the studies are case reports, small-sized, with a retrospective design and short mean follow-up, generally less than 5 years. In the light of the limited available data, pre-transplantation BS might be a reasonable approach for obese patients, whereas concomitant/post-transplantation BS might be considered for highly selected patients. The optimal type of BS remains unclear, but sleeve gastrectomy seems to be the preferred approach by most surgeons [28, 33, 34, 40]. As for immunosuppressive therapy after BS in our pharmacokinetic study of transplant recipients, tacrolimus blood levels were maintained at therapeutic range after bariatric surgery [14]. This is most probably explained by tacrolimus extensive enteric absorption, estimated to occurred mainly in the proximal duodenum, however, it was shown in a model of short-bowel piglets that the drug can be absorbed from the colon as well [41, 42]. Comparative data on long-term outcomes regarding optimal timing and type of bariatric procedure are lacking.