Acta Scientific Gastrointestinal Disorders (ISSN: 2582-1091)

Research ArticleVolume 4 Issue 3

Timing of Bariatric Surgery in Liver Transplant Recipients; A Comprehensive Systematic Review

Thamer Kassim, Haitam Buaisha, Jonathan Gapp, Jahnavi Koppala, Ryan Walters, Rajani Rangray* and Sandeep Mukherjee

Creighton University Medical Center, USA

*Corresponding Author: Rajani Rangray, Creighton University Medical Center, USA.

Received: January 06, 2021; Published: February 17, 2021

Citation: Rajani Rangray., et al. “Timing of Bariatric Surgery in Liver Transplant Recipients; A Comprehensive Systematic Review”. Acta Scientific Gastrointestinal Disorders 4.3 (2021): 04-18.

Abstract

Background and Objectives: Rising obesity rates with an associated increased prevalence of nonalcoholic steatohepatitis (NASH) have become a leading cause of end stage liver disease (ESLD). This excess weight poses particular challenges in the care of liver transplant (LT) patients. We conduct a systematic review to investigate the most safe and feasible timing to undergo bariatric surgery in patients with end-stage liver disease undergoing liver transplant.

Methods: We performed a literature search on studies reporting BS associated with LT in adults. There was no enough comparable information to conduct a metanalysis. A systematic review was conducted.

Results: BS prior to LT: Eight retrospective studies with small groups of patients (n: 6 - 78) examined BS prior to LT. Most of these studies suggest that this approach is relatively safe, efficacious and carries a low complication rate. However, one larger study suggested that BS (mainly RGYB) prior to LT may be associated with higher delisting rates or deaths prior to LT. Simultaneous BS and LT: Most of the reported studies are limited in their sample size and follow up duration. They showed improvement in obesity related complications and resulted in effective and durable weight loss. BS after LT: Six studies were reported with overall 43 patient. Improvement in the metabolic comorbidities following BS were noted and no early mortality was reported with respect to BS. Overall complication rates were higher than nontransplant population. Effects on immunosuppression were minimal with no reported graft rejection.

Conclusion: BS performed before, after, or simultaneously to LT seems to be an acceptable option for obese patients with ESLD.

Keywords: Systematic Review; Liver Transplantation; Bariatric Surgery

Abbreviations

BS: Bariatric Surgery; LT: Liver Transplant; LSG: Laparoscopic Sleeve Gastrectomy; SG: Sleeve Gastrectomy; RYGB: Roux-En-Y Gastric Bypass; GB: Gastric Banding

Introduction

  The epidemic of obesity defined as BMI of more than 30 kg/m2 is on the rise worldwide. The projected worldwide prevalence by 2030 for overweight individuals will be 38% and obese individuals will be 20%. In the United States, the prevalence has been increasing over the last decade. It is estimated that by 2030, > 50% of US population will have a BMI of > 30 kg/m2 [1]. Paralleling obesity, prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is also on the rise. The prevalence of NAFLD is has increased from 15% in 2005 to 25% in 2010 and similarly, the prevalence rate of NASH has increased from 33% to 59.1% in same time frame. NASH will be the leading cause of liver transplantation (LT) in the next decade [2]. Liver transplant is challenging in these subgroups of patients due to several issues. The American Association for the Study of Liver Disease (AASLD) and the American Society of Transplantation considers obesity with pre- liver transplant BMI > 40 kg/m2 as a relative contraindication for liver transplantation [3]. There is increased risk of post-liver transplant mortality for patients with a BMI ≥ 40 at 30 days as well as at 1 and 2 years after transplantation in a recent systematic review and meta-analysis [4]. There is also increased prevalence of post- transplant obesity in 30%‐40% of liver transplant recipients within the first 5 years after transplantation [5], associated with immunosuppressive medication, development of metabolic syndrome and recurrence of chronic liver disease. This growing burden of obesity, development of liver disease and the challenges associated before and after liver transplant warrants the urgent need for aggressive weight loss methods. Medical weight loss approach has been effective in decreasing 10% body weight; we review the different bariatric surgeries with respect to liver transplant.

  The three main bariatric surgical methods, consisting of Roux-en-Y Gastric Bypass (RYGB), Gastric Banding (GB) and Sleeve Gastrectomy (SG), have not been routinely used for liver disease before or after liver transplant or for cirrhotic patients. Multiple studies have shown the safety of these surgeries in non-cirrhotic patients. A recent study has shown resolution of NASH in 85% of patients, confirmed by histological diagnosis at 1 year after bariatric surgery in addition to weight loss, improvement in liver chemistries such as ALT and NAFLD score [6]. The RYGB is the gold standard bariatric surgery but associated with higher rate of complications [7]. This is worrisome especially in the background of liver disease patients who have higher morbidity associated with any type of surgical interventions. There is also concern regarding the absorption of immunosuppressive medications in RYGB patients due to the altered anatomy [8] and close monitoring of the immunosuppressive medications is required. Contrarily, SG has not been associated with any difference in absorption of the immunosuppressive therapy and no dosage changes are needed [9]. The indications of bariatric surgery in general populations are clear: BMI ≥ 40, or more than 100 pounds overweight, BMI ≥ 35 and at least one or more obesity-related co-morbidities such as type II diabetes (T2DM), hypertension, sleep apnea and other respiratory disorders, non-alcoholic fatty liver disease, osteoarthritis, lipid abnormalities, gastrointestinal disorders, or heart disease and inability to achieve healthy weight loss sustained for a period of time with prior weight loss efforts as per the American Society for Metabolic and Bariatric Surgery. The question of extrapolating these indications for liver transplant patients is not clear and very little data are available for advanced liver disease patients. Similarly, the timing of this bariatric surgery in peri liver transplant patient is debatable, whether to perform before simultaneously or after liver transplant. In this systematic review we explore the different types of bariatrics surgeries and the adequate timing of these surgeries with regards to liver transplant.

Materials and Methods

Literature search: A systemic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, Scopus, Google scholar, CINAHL and Cochrane Library databases for studies reporting BS associated with LT in adults submitted in English language only. No limitation regarding the timing of the bariatric surgery in relation to the liver transplant surgery (before, after, or simultaneously). The search was conducted in January 2019 and was not limited to any date range. We used the following keywords in various combinations; “liver transplantation”, “bariatric surgery”, “Gastric Bypass”, “gastric banding”, “Gastroplasty”, and “Gastrectomy.” Bibliography of selected manuscripts and review articles was also manually searched for additional studies which were not identified in the original search.

Study selection: Two authors (TK and JG) independently screened titles and abstracts to identify studies for full text review. 35 potentially relevant article was analyzed for eligibility for systematic review and metanalysis. Studies with 3 or more patients were included for potential metanalysis (refer to the attached table) and information was extracted using a standardized data extraction.

Study

N

Etiology (%)

MELD/Child Pugh at time of bariatric surgery

BMI at surgery (kg/m2), (IQR)

Surgical approach

Complication percentage (%)

Early Mortality (90 days)/ Complication type

Follow up (Months)

EWL at follow up (%)

Improvement in obesity related complications

Sharpton., et al. (2018)

32

-HCV (47)

-NASH (31)

12 (IQR 10-30)

45 (42.1-49.0)

LSG

9.4

Mortality = 0

Complications =3

-Renal insufficiency,

-Hepatic encephalopathy

-Gastric staple leak

24 patients with 12 months follow up.

52.4

HTN (75%)

-83% had reduction in antihypertensive medication use in 12 months

Type 2 DM (44%)

-36% resolved

-64% improved

Idriss., et al. (2018)

78

NASH (47.4)

HCV (24.4)

ALD (19.2)

12 (IQR 8-20)

29.7 (25.3-35.6)

RYGB (49)

Not available (29)

Not available

Not available

Not available

Not available

Not available

Moulla., et al. (2018)

9

Not available

Child Pugh A (22.2%)

Child Pugh B (11.1%)

Not categorized (66.7%)

Not available

LRYGB (6)

LSG (3)

0

Mortality = 0

Complications = 0

-No bleeding

-No hepatic decompensation

Not available

Not available

Not available

Safwan., et al. (2017)

11

-NASH (90.9)

-Acute liver failure of unknown origin (9.1)

Not available

Not available

SG (1)

RYGB (9)

Jejunal

Bypass (1)

Not available

Not available

Not available

Not available

Not available

Lin., et al. (2013)

20

Not available

11 (IQR 6–21)

48.3 (38–60.4)

LSG

25

Mortality = 1

Complications =5

-Gastric staple leak

-Renal insufficiency

-Bleeding requiring transfusion

-Hepatic encephalopathy

-Wound infection

24a

66

Not available

Rebibo., et al. (2013)

13

NASH (93)

NASH & ALD (7)

MELD 7 (7-8)

Child Pugh A (100%)

46.3(38.1-56.8)

LSG

7.7

Mortality = 0

Complications =1

-Intrabdominal hematoma resolved with no surgical intervention (1)

-11 patients followed up at 6 months

-5 patients followed up at 12

61.9 (6 months)

73.4 (12 months)

Not available

Shimzu., et al. (2012)

23

Not available

Child Pugh A (95.7%)

Child Pugh B (4.3%)

47.1 (37.8-56.3)

LSG (8)

GB (1)

RYGB (14)

34.8

Mortality = 1

(LSG)

Complications =8

(28.6% LGYB), (37.5% LSG)

-Gastrojejunal anastomotic leak

-Gastrojejunal stricture

-Infected hematoma

-Gastric staple line leak

-Gastric stricture

-GI bleeding

-Pneumonia

-18 patients with 12 months follow up.

-15 patients with mean 37 months follow up

67.5

HTN

-68.7% remission or improved)

Type 2 DM

-86.7%

remission or improved)

DLP

-66.7% remission or improved

Takata., et al. (2007)

6

-NASH (33.3)

-HCV & ALD (33.3)

-HCV & HBV (16.7)

-Autoimmune hepatitis (16.7)

Child Pugh A (66.7%)

Child Pugh B (33.3%)

59 (38–87)

LSG

33.3

Mortality = 0

Complications =2

-Hepatic encephalopathy (1)

-Bleeding requiring exploratory laparotomy (1)

11.5a

33

HTN

DLP

Type 2 DM

-100% either resolved or improved

Table 1: Summary of bariatric surgeries performed in patient with cirrhosis prior to receiving liver transplantation.
Abbreviations: MELD: Model of End-Stage Liver Disease; BMI: Body Mass Index; IQR: Interquartile Range; NASH: Nonalcoholic Steatohepatitis; HCV: Hepatitis C Virus; HBV: Hepatitis B Virus; ALD: Alcoholic liver disease; RYGB: Roux-en-Y Gastric Bypass; LSG: Laparoscopic Sleeve Gastrectomy; SG: Sleeve Gastrectomy.
a: Mean.

Study

N

Etiology (%)

MELD/Child Pugh

BMI at surgery (kg/m2), (IQR)

Surgical approach

Complication percentage (%)

Early Mortality (90 days)/ Complication type

Follow up (Months)

EWL at follow up, %

Improvement in obesity related complications

Zamora-Valdes., et al. (2018)

29

NAFLD alone (52.7)

NAFLD + AAD (20.7)

NAFLD + AIH (6.9)

AAD (3.45)

HHT (3.45)

HCV (3.45)

Allograft failure (3.45)

FHF (3.45)

PBC (3.45)

32a

47a

SG

44.8

Mortality = 2

Complications =10

-Bleeding requiring reoperation (3)

-On HD with persistence of renal failure after LT (3)

-HAT (2)

-Gastric staple line leak (1)

-Mucor mycosis -excised (1)

36

36.3 - 12 months (p=0.049)

34.4 - 24 months (p=0.562)

36.9 - 36 months (p=0.81)

Type 2 DM

HTN

Hepatic Steatosis

Nesher., et al. (2017)

3

NASH (33.3)

NASH + HCV (33.3)

NASH + Wilson (33.3)

24 (23-24)

 

SG

33.3%

Mortality = 0

Complications = 1

-Biliary anastomotic leak & transient AKI

13b (range 3-24)

27.9 - 13 months

HTN

-Resolved in 100%

Type 2 DM

-Resolved in 100%

Heimbach., et al. (2013)

7

NASH (57.1)

NASH+HCV (14.3)

NASH+AAD (14.3)

HHT (14.3)

32 (11-40)

48 (39-52)

SG

42.9

Mortality =0

Complications =3

-Gastric staple line leak (1)

-HAT (1)

-Steroid resistant rejection (1)

17 (range 8-33)

Not available

Type 2 DM

-Improved or resolved in 100%

Hepatis steatosis

-0/7 had findings of steatosis

Table 2: Summary of studies on bariatric surgery performed simultaneously with liver transplantation.
Abbreviations: MELD: Model of End-Stage Liver Disease; BMI: Body Mass Index; IQR: Interquartile Range; NAFLD: Non-Alcoholic Fatty Liver Disease; NASH: Non-Alcoholic Steatohepatitis; FHF- Fulminant Hepatic Failure; PBC: Primary Biliary Cirrhosis; AAD: Alpha 1 Antitrypsin Deficiency; HAT: Hepatic Artery Thrombosis; HHT: Hereditary Hemorrhagic Telangiectasia; HCV - Hepatitis C Virus; AIH: Autoimmune Hepatitis; SG: Sleeve Gastrectomy; AKI: Acute Kidney Injury.
a: Mean.
b: Median.

Study

N

Etiology (%)

MELD/Child Pugh

BMI at surgery (kg/m2), (IQR)

Surgical approach

Complication percentage (%)

Early Mortality (90 days)/ Complication type

Follow up (Months)

EWL at follow up, %

Improvement in obesity related complications

Osseis., et al. (2018)

6

HCV (1)

ALD (2)

NASH (1)

HCV + ALD (1)

ALD + NASH (1)

Not available

43.7 (38-44.9)

LSG (3)

SG (3)

17

Mortality = 1

-Death after 19 months

Complications= 1

-Gastric staple line leak, multi-organ failure, death

37.2b: Range (13-101 months)

76b: Range (25-119)

DM

-100% improved or resolved

-HTN

50% didn’t require medications 1 year after SG

-OSA

66.7% improved

Tsamalaidze., et al. (2018)

12

HCV (5)

NASH (4)

AIH (1)

ALD (1)

Cryptogenic (1)

Not available

45.3a

LSG

33.3

Mortality = 0

Complications = 4

-Sleeve dilation for malnutrition (2)

-Gastrostomy tube placement for malnutrition (1)

-Late drain removal (1)

25.3a

50 (at 12 months)

Type 2 DM

-44% resolution

DLP

43% resolution

HTN

-27% resolution

OSA

-43% resolution

Yemini., et al. (2018)

4

Not available

Not available

41(45-48) *

LSG

LRYGB

25

Mortality = 0

Complications = 1

-Anastomotic leak requiring reoperation

12*

78%*

Not available

Khoraki., et al. (2016)

5

NASH (3)

PBC (1)

HCV (1)

Not available

47.2a

LSG

40

Mortality =0

Complications = 1

-Portal vein thrombosis

33.2 a

43 (at 24 months)

Type 2 DM

-60% achieved resolution

HTN

-40% achieved resolution and didn’t require medications.

Lin., et al. (2013)

9

Not available

Not available

41 (38-44)

LSG (8)

SG (1)

33.3

Mortality = 0

Complications = 3

-Incisional hernia (1)

-Biliary leak (1)

-Dysphagia requiring conversion to RYGB (1)

3-36

55 (at 6 months)

DM

-Improved

DLP

-Improved

Al-Nowaylati., et al. (2013)

7

HCV (4)

ALD (1)

Jejunoileal Bypass (1)

Hemangioendo-thelioma (1)

Not available

44.3a

RYGB

42.9

Mortality = 2

Complications = 3

-Incisional hernia (2)

-Malnutrition requiring reversal of RYGB (1)

59.1a

BMI 44.3 à 26 kg/m2 (59 months)

Type 2 DM

-Improved

DLP

-Improved

Table3: Summary of studies on bariatric surgery performed after liver transplantation.
Abbreviations: MELD: Model of End-Stage Liver Disease; BMI: Body Mass Index; NASH: Non-Alcoholic Steatohepatitis; ALD: Alcoholic liver disease; RYGB: Roux-en-Y Gastric Bypass; LSG: Laparoscopic Sleeve Gastrectomy; SG - Sleeve Gastrectomy; GB: Gastric Band HCV - Hepatitis C Virus; PBC: Primary Biliary Cirrhosis; AIH: Autoimmune Hepatitis; ALD: Alcoholic liver disease; OSA: Obstructive Sleep Apnea; DLP: Dyslipidemia; EWL: Excess Weight Loss; LT: Liver Transplant; BS: Bariatric Surgery.
a: Mean.
b: Median.
*: Data is represented for all cohort (LT patients were a subgroup of a bigger cohort).

Results and Discussion

BS prior to LT

  Surgical treatment aims to improve accessibility and outcomes of LT. Morbid obesity remains a relative contraindication for LT per AASLD and obese patients suffer from limited access to LT [10,11]. BS in the setting of ESLD have been shown to be effective in weight loss prior to LT [10]. There are eight studies [12-19] to date which examined the role of BS prior to LT. These were retrospective studies with small groups of patients (n of 6-78) [12-19] which examined different aspects of BS prior to LT. There were two case reports, Chmura., et al. [20] and Taneja., et al. [21], reporting RNYGB and LSG, respectively, prior to receiving LT (Supplemental table).

 

Age

Gender

Etiology (%)

MELD/Child Pugh

BMI at surgery (kg/m2), (IQR)

Surgical approach

Surgery associated complication

Follow up (Months)

Weight reduction at follow up (%)

Improvement in obesity related complications

BS prior to LT

                   

Chmura., et al. (2015)

56

Female

 NASH + ALD

Not available

50.9

RYGB

-Intraperitoneal hemorrhage requiring revision surgery

-AKI requiring temporary dialysis

36

50.1

Type 2 DM

-Complete remission

Taneja., et al. (2013)

29

Male

NASH

14/ Child Pugh B

55.3

LSG

None

6

36.3

Not available

Simultaneous BS & LT

                   

Kumar., et al. (2017)

58

Female

NASH

27/Child Pugh C

38.8

SG

Not available

2

25

Not available

Guerrero Pérez., et al. (2017)

54

Male

HCV

30/Child Pugh C

37.7

SG

-ARDS

-CMV infection

-C-Diff infection

24

38

HTN

-Decrease in total medications

DLP

-Stable

OSA

-Resolved

Tariciotti., et al. (2016)

53

Female

HCV

14

38

SG

None

5

Not available

Type 2 DM

-Complete remission

Campsen., et al. (2008)

28

Female

AIH

Not available

42

GB

None

6

45

HTN

-No longer required medications

OSA

-Symptoms improved

Venous stasis

-Improved

BS after LT

                   

Lainas., et al. (2018)

39

Female

FHF

Not available

43.7

SPSG

None

24

EWL - 79.5

HTN

-Improved, requires one medication instead of two

OSA

-Resolved, doesn’t need CPAP

Pajecki., et al. (2014)

33

Female

AIH + HVC

31

37.1 (at time of LT)

LSG

None

5

EWL - 75

HTN

-Improved, doesn’t need medications

Type 2 DM

-Improved, doesn’t need medications

Elli., et al. (2012)

62

Female

HCV

Not available

53

SG

None

3

BMI 53à 48 kg/m2

Not available

Gentileschi., et al. (2009)

57

Male

HCV

Not available

54

BPD

None

6

21.4

Type 2 DM

HTN

OSA

Butte., et al. (2007)

63

Male

NASH

Not available

41

SG

None

6

BMI 41à 38 kg/m2

Type 2 DM

Tichansky., et al. (2005)

49

Female

HCV

 

54

RYGB

None

4

BMI 54à 43 kg/m2

Type 2 DM

-Complete resolution

HTN

-Complete resolution

Supplementary table: Case reports on timing of bariatric surgery and liver transplantation.
Abbreviations: MELD: Model of End-Stage Liver Disease; BMI: Body Mass Index; NASH: Non-Alcoholic Steatohepatitis; ALD: Alcoholic liver disease; FHF- Fulminant Hepatic Failure; RYGB: Roux-en-Y Gastric Bypass; LSG: Laparoscopic Sleeve Gastrectomy; SG - Sleeve Gastrectomy; SPSG: Single Port Sleeve Gastrectomy; GB: Gastric Band HCV - Hepatitis C Virus; BPD: Biliopancreatic Diversion; AIH: Autoimmune Hepatitis; ALD: Alcoholic liver disease; OSA: Obstructive Sleep Apnea; DLP: Dyslipidemia; EWL: Excess Weight Loss; LT: Liver Transplant; BS: Bariatric Surgery.

Simultaneous BS and LT

  Simultaneous BS and liver transplant surgery was first reported by Campsen in 2008. Campsen., et al. [22] described a 42-year-old female who underwent gastric banding with a repeat LT due to chronic rejection. The patient’s pre transplant BMI was 42 and suffered from diabetes, hypertension, obstructive sleep apnea. The authors report that the patient recovered well from the surgery and was discharged after eight days. At 6 months follow up, the patient had an EWL of 45%. The patient no longer needed treatment for type 2 diabetes or hypertension and had resolution of OSA symptoms. Between 2014 and 2017, three case reports from India, Italy, and Spain [23-25] described simultaneous LT and sleeve gastrectomy to be a relatively safe procedure with no life-threatening complications and showed improved outcomes in obesity related comorbidities.

  In a low evidence - small case series (n = 3) by Nesher., et al. [26] three patients with a median pre-transplant BMI of 46.6 and MELD of 24 underwent simultaneous SG and LT. The etiology of cirrhosis was predominantly related to NASH, with mean estimated weight loss of 27.9% at a median follow up of 13 months. They also describe improved overall obesity related comorbidities and no hepatic steatosis on abdominal ultrasound in two out of three patients. These studies report no significant perioperative complications or surgically related mortality along with improved obesity related outcomes. However, they are limited by their sample size (total n = 7) and short term follow up (5 to 24 months).

  In study at the Mayo clinic in 2013, Heimbach., et al. [27] compared outcomes in patients (n = 7) undergoing simultaneous SG and LT with a cohort who achieved weight loss via a noninvasive method (n = 37). In the SG and LT group, NASH was a primary etiology for cirrhosis in 57%. Two out of the three patients had NASH as a secondary etiology for cirrhosis 66.7%. Age at transplant was similar in the noninvasive and SG groups, 50 (range 31 - 67) vs 48 (range 44 - 60), respectively. MELD scores and BMI at transplantation were both higher in the SG group compared to the noninvasive group [MELD 32 (range 11 - 40) vs 19(range 8 - 35) and BMI 48 (range 39 - 52) vs 33 (range 28 - 40)]. Mean BMI at last follow up in the SG group (17, range 18 - 33 months) vs noninvasive group (35, range 8 - 61 months) was 29 (23 - 35) and 36 (25 - 45) respectively. Obesity related comorbidities including HTN, DM and hepatic steatosis, were significantly improved in the SG group compared to the noninvasive cohort. The SG cohort had no intraoperative complications or surgery related mortality, but three patients had post-operative complications (gastric staple line leak, excess weight loss, and steroid resistant rejection). The authors concluded that SG at the time of LT is a procedure that carries risk but is feasible in carefully selected individuals [27].

  Zamora-Valdes., et al. [28] updated their study at Mayo clinic in 2018 with an increase in sample size. Forty-five patients underwent LT alone vs 29 undergoing SG and LT. NAFLD was present in 48.9% of the overall cohort with higher prevalence in the LT+ SG cohort compared to LT alone 76.9% vs 44.4% respectively. Overall survival was better in the SG cohort as there was one mortality (3.4%) compared to four in the noninvasive cohort (8.2%). In order to assess long term outcomes, the authors examined patients who were able to follow up in 3 years (LT alone n = 36 vs LT+SG n = 13). There was a significant maintenance in weight loss between BMI at listing and at 3 year follow up in the SG group (49.0 +/- 4.6 vs. 30.9 +/- 13.2) respectively. In the noninvasive group, BMI at listing and last follow up showed no significant changes (40.06 +/- 2.99 vs. 38.53 +/- 6.53) respectively. Complications related to SG included gastric staple line leak and bleeding which required re-operation. Overall obesity related complications in the SG and LT group showed lower prevalence at 3 years when compared to the noninvasive group. This was demonstrated as improved overall cardiovascular risk factors and less patients requiring medications for DM, HTN and dyslipidemia [28].

  In summary, studies on simultaneous BS and LT show improvement in obesity related complications and results in more effective and durable weight loss. A further advantage of combined BS and LT surgery is the elimination of two separate procedures when compared to BS prior or after LT. On the other hand, BS and LT carry post-operative risk and careful selection of patients is important for the procedure’s safety and feasibility. Moreover, these studies are limited in their sample size and duration of follow up. Further studies are also needed to assess the effects on immunosuppressive medications and graft survival.

BS after LT

  Initiation of immunosuppressive therapy following LT coupled with decreased activity levels following this major surgery can lead to onset or worsening of the metabolic syndrome [29,30]. This worsening has negative effects on both quality of life and decreases transplant recipient survival and possibly graft function in morbidly obese [31]. For transplant patients with history of cirrhosis secondary to NASH, recurrence following LT is related to post-transplant BMI [32] and can be particularly severe [45]. Also, with increased lifespan for transplant patients, the sequalae of metabolic disease become a life-limiting factor for this population [31,33,34]. Bariatric surgery (BS) has been used to good effect for weight-loss with associated improvement in related comorbidities in the non-transplant population [35]. Post-transplant patients carry increased surgical risk due to immunosuppression with increased infection rates, decreased healing [36,37] and more complicated peritoneal access due to presence of adhesions from transplantation. We review six studies where BS was performed on patients with previous LT. Overall 43 patients were assessed for mortality, complications, percent excess weight loss (%EWL), resolution of metabolic disease and immunosuppressive regimen.

  No early mortality was reported with respect to BS (within 90 day of procedure), however 3 cases (7%) of delayed mortality are reported. Al- Nowaylati., et al. [38] reports mortality in two patients at 6 months and 9 months from Fournier’s Gangrene with history of penile prosthesis in situ and esophageal cancer, respectively. Osseis., et al. [39] reports a death at 19 months after laparoscopic sleeve gastrectomy (LSG) due to complications from a gastric staple line leak, ultimately leading to multi-organ failure.

  Complications following BS included three wound infections [38,39], 1 anastomotic leak in Roux-en-Y gastric bypass (RYGB) requiring reoperation [40], 1 intraoperative bleed requiring splenectomy and portal vein thrombosis in the same patient [41], 3 with incisional hernias following open RYGB [38,42], 1 reversal of open RYGB due to malnutrition and a recalcitrant duodenal ulcer [38], 1 bile leak [42], dysphagia requiring conversion to RYGB [42], 3 with poor PO intake requiring pneumatic dilation and one with gastrostomy tube (required for oral immunosuppressive mediations) [43] and 1 late drain removal [43]. Altogether, fifteen patients of 43 (35%) experienced complications related to BS. This aggregate complication rate remains well above rates reported in the non-transplant population [44]. Contributing factors are likely poor healing secondary to immunosuppressive regimens, increased risk of incisional hernia, presence of adhesions from previous transplant surgery, increased chance for infection due to immunosuppression and presence of foreign objects from previous transplant surgeries and repairs such as mesh for prior incisional hernia repair.

  Effects on immunosuppression have been a concern unique to the post-transplant population with some apprehension regarding acute graft failure with decreased absorption of immunosuppressive medication. Among the studies reviewed, five reported the immunosuppressive regimens prior to and following BS. One reported no changes [43], one improved the amount of time of tacrolimus within therapeutic range from 39% to 47% without change in dosing [40], one required reduction in dosing [41], two studies reported increased dosing of immunosuppression [38,42]. No cases of acute graft rejection were reported.

  Surgical approaches in patients undergoing BS are varied. Overall, 32 patients (74%) underwent sleeve gastrectomy with a majority being via laparoscopic approach. Al-Nowaylati., et al. [38] performed open RYGB on all 7 of their patients, citing a concern for adhesions likely to be present in post-transplant patients. Yemini., et al. [40] used both LSG and LRYGB, though they do not account for how many of the LT patients underwent each procedure. They conclude that since stability of immunosuppressive regimens is present in both LSG and LRYGB, LSG may actually be less desirable than LRYGB in the long term, due to chronic leaks along the major gastric curvature in SG. On the other hand, many authors have cited the need to maintain endoscopic access to the biliary system as a reason to favor SG over RYGB. Further longitudinal studies would be needed to determine the rate of biliary access required in post RYGB patients and to further assess morbidity and mortality benefits in maintaining biliary access.

  Regarding weight-loss and improvement in metabolic comorbidities, five of the studies reported a mean %EWL which ranged from 46.5 to 76 at 12 months. Yemini., et al. reported a %EWL of 69% for LSG and 75% for LRYGB at 1 year from BS. Another group compared weight loss between transplant vs nontransplant patients undergoing LSG and showed 55% EWL in transplant patients and 50% EWL in non-transplant patients. Osseis., et al. [39] reported the highest %EWL of 76 at 12 months post SG while Khoraki., et al. [41] reported %EWL of 46.5, also all with patients undergoing SG. All 6 groups reported improvement in the metabolic comorbidities following BS with some patients able to achieve complete remission for diabetes, OSA, HTN, hyperlipidemia and NASH. Tsamalaidze., et al. [43] compared resolution of metabolic comorbidities between transplant and non-transplant patients undergoing BS. They found that resolution of diabetes, cardiac disease, hypertension, obstructive sleep apnea and hyperlipidemia occurred at similar rates between the two groups. Resolution of nonalcoholic steatohepatitis in their study could not be assessed as none of the LT patients had NASH at onset.

  The long-term effect of BS on graft function is yet to be determine and longitudinal trials are needed to further inform whether the increased surgical risks in the LT population are acceptable in relation to benefit derived from BS for treatment of metabolically related comorbidities. While complication rates are high in the post LT population, improvement in patient selection may be able to mitigate this risk. It will also be important, in the future, to study not only durability of graft function and safety of bariatric procedures but also quality of life outcomes in post LT bariatric patients to help guide appropriateness of BS.

Conclusion

  Bariatric surgery seems to be a safe option for patients with ESLD undergoing liver transplant regardless of the timing of the procedure in relation to the LT surgery. However, more studies are needed to evaluate the effect of nutritional status following RYGB on the outcome of LT surgery. Further studies are needed to assess the long-term effect of BS on graft function and immunosuppression medications.

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Copyright: © 2021 Rajani Rangray., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



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