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Sleeve Gastrectomy in Non-alcoholic Steatohepatitis …
portosystemic shunts (TIPS) [61]. This score incorporates: total bilirubin, creatinine, and INR, and it is used to prioritize patients for liver transplantation.
A comprehensive review and meta-analysis done by Peng et al. [62] to compare
Child–Pugh versus MELD score for the assessment of prognosis in liver cirrhosis the concluded that both scores have similar prognostic significance in most of
cases of liver disease and more studies are necessary to prioritize their use in specific patient populations.
125
10 Sleeve Gastrectomy in NAFLD and NASH
The hallmark of NAFLD and NASH is insulin resistance, therefore the comorbidities related to metabolic syndrome are usually present in these patients mainly,
diabetes mellitus, hypertension, obstructive sleep apnea and hypercholesterolemia.
Sleeve gastrectomy is therefore beneficial in treating morbid obesity in these
patients and improve the control of their metabolic syndrome. The other advantage
is the treatment of NASFLD and NASH in itself and the treatment of early stages
of liver fibrosis halting the progress to late fibrosis and liver cirrhosis.
Souto et al., performed intraoperative liver biopsies in 521 patients while
undergoing bariatric surgery and found that 95% of patients had NAFLD. NASH
was common among the diabetic patients (59.4%) and prediabetic patients
(49.2%) with higher rates of hepatic fibrosis in diabetic patients (56.4%) compared
to prediabetic patients (29.2%) [63]. We therefore recommend performing routine
liver biopsies in patients with diabetes mellitus, and the performance of preoperative fibroscan along with the addition of liver function tests and coagulation profile
to routine labs in this group of patients.
Many studies reported resolution of NASH in liver biopsies post bariatric surgery [64–66]. A study evaluated 381 patients who underwent bariatric surgery
and had liver biopsy taken at the time of surgery. They followed up the patients
with liver biopsy at 1 and 5 years post bariatric surgery. The percentage of patients
with probable or definite NASH decreased significantly over 5 years, from 27.4 to
14.2% [63].
11 Sleeve Gastrectomy in Liver Cirrhosis
and Transplantation
In discussing liver disease and sleeve gastrectomy, we need to distinguish 7 group
of patients:
1. Liver cirrhosis patients with low MELD score and low Child score with-
out hepatic decompensation in the form of variceal haemorrhage, ascites, and
hepatic encephalopathy who are recently diagnosed and not in the transplant
list.
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M. H. Jamal and R. El-Abd
2. Liver cirrhosis patients with low MELD score and low Child score with-
out hepatic decompensation in the form of variceal haemorrhage, ascites, and
hepatic encephalopathy who are identified only at time of surgery.
3. Liver cirrhosis patients who need liver transplantation, but denied to be listed
due to morbid obesity.
4. Liver cirrhosis patients who are morbidly obese and in the wait list for liver
transplantation.
5. Liver cirrhosis patients who are morbidly obese and in the wait list for liver
transplantation with a diagnosis of NASH as the cause of their cirrhosis.
6. Liver transplant recipients who had their transplant due to NASH and metabolic
syndrome.
7. Liver transplant recipients who are morbidly obese, or with a diagnosis of met-
abolic syndrome.
The studies in the subject may be divided into studies on bariatric surgery in liver
cirrhosis, studies on bariatric surgery in liver cirrhosis before transplant in patients
listed for transplantation and studies on bariatric surgery during or after liver
transplantation. Putting in mind these groups of patients will make us understand
these studies better and allow for a future design of more robust studies to give
evidence-based guidance to future recommendations.
Approximately 1–4% of bariatric patients are diagnosed with liver cirrhosis
[67–69]. The dilemma in this case is which surgery to choose for these patients
and how to work them up preoperatively to capture those patients and avoid a surprise diagnosis at time of surgery, which requires at times deviation from planned
operative course. Another category of patients are those with known liver cirrhosis
who are being worked up for liver transplant listing, who are generally presenting
with more advanced disease. The timing of bariatric surgery in this category of
patients is a matter of debate with scarce studies focusing on this question.
The challenges in performing sleeve gastrectomy in liver cirrhosis patients
include the potential liver failure post operatively, bleeding due to low platelets
and abnormal coagulation profile and increased chances of leak due to lower albumin and relative immunosuppression. Technical challenges also exist mainly due
to the presence of varices in the abdominal wall and around the stomach especially
gastroesophageal varices.
One of the earlier studies on the subject was by Mosko et al. [70], which evaluated patients who underwent bariatric surgery in the US, using the Nationwide
Inpatient Sample (NIS) database. The outcomes of patients undergoing bariatric
surgery were divided into three groups according to their liver disease: Patients
with no cirrhosis, compensated cirrhosis and decompensated cirrhosis (mainly
those with varices and ascites). They found that 3888 bariatric surgeries were performed in the US between 1998 and 2007 on compensated cirrhotic patients and
62 on decompensated cirrhotic patients. They reported that patients without cirrhosis had lower mortality rates than those with compensated and decompensated
cirrhosis (0.3% vs. 0.9% and 16.3%, respectively). Patients with compensated
Sleeve Gastrectomy in Non-alcoholic Steatohepatitis …
127
cirrhosis had a more than twofold higher mortality rate (odds ratio, 2.17; 95%
confidence interval, 1.03–4.55) than those without cirrhosis, while patients with
decompensated cirrhosis had a greater than 20-fold higher mortality rate (odds
ratio, 21.2; 95% confidence interval, 5.39–82.9), with a combined mortality rate
of all cirrhotic patients at 1.2%. An important finding of this study is the relation
between hospital bariatric volume and mortality in cirrhotic patients. In patients
with decompensated cirrhosis, the mortality rate was 41% at low-volume centers (Performing less than 50 procedures per year), whereas there were no deaths
among decompensated inpatients after bariatric surgery at high volume centers
(Performing more than 100 procedures per year). In terms of the type of procedures performed, 85% of compensated cirrhotics underwent malabsorptive procedures and 57% of decompensated cirrhotics underwent the same [70].
A study on 23 patients with cirrhosis undergoing bariatric surgery revealed a
complication rate of 35%. Most of the patients underwent laparoscopic Roux En Y
Gastric Bypass (RYGB) and eight patients had sleeve gastrectomy with only one
patient undergoing Laparoscopic adjustable gastric banding (LAGB). Only 12 of
those patients were known cirrhotics and 11 patients were found to have cirrhosis
at time of surgery, which changed the decision from the performance of RYGB
to Sleeve gastrectomy in two of those eight patients. All the cohort were Child A
except one Child B, and in two patients TIPS were performed before surgery in
the form of sleeve gastrectomy. None of the patients developed hepatic decompensation and only one sudden death was reported 9 months after surgery due to
unknown causes. Excess weight loss was adequate 67% ± 24.8% at 37 months
follow-up [67].
Wolter et al. [71] identified 302 patients who underwent bariatric surgery and
got a liver biopsy at time of surgery due to surgeon judging that the liver looked
abnormal. Of the cohort 12 patients (4%), were found to have liver cirrhosis and
82.3% had an abnormal liver biopsy. Sleeve gastrectomy was performed in 49.7%,
Roux-Y gastric bypass in 48.3%, and the rest were biliopancreatic diversions/duodenal switch as well as LAGB. All procedures were performed laparoscopically.
Revisional bariatric surgery was performed in 11.6%. They reported a mortality
rate of 0.3%, leak rate at 1%, and postoperative bleeding occurred in 3.3%. One
patient developed portal vein thrombosis and one patient acute pancreatitis. They
reported no postoperative hepatic decompensation and no association between histological findings and perioperative outcomes.
A Spanish multi-center study [72] included 41 patients with liver cirrhosis undergoing bariatric surgery, in which all but one were Child A patients. The
majority of this cohort (68.3%) underwent sleeve gastrectomy. At one and five
years of follow-up after surgery percentage of total weight loss (%TWL) was
26.33 ± 8.3% and 21.16 ± 15.32% respectively. They reported an early complication rate of 17% with one leak and no mortality. Hepatic decompensation was
seen in the form of ascites in two patients only, less than 30 days post operatively.
Type II DM went into remission in 53.6% of patients after one year of follow-up.
What’s interesting in this study is that only one patient is undergoing assessment
for liver transplantation after 5 years of follow-up, with 20% of patients with
128
M. H. Jamal and R. El-Abd
child A progressing in their score and the one child B patient remaining without progressing. Six patients 14% found to have hepatocellular carcinoma in the
follow-up period. We cannot deduct from this study that weight loss delays progression of liver disease, but it can be inferred and more studies are needed to confirm this hypothesis.
A study on 13 patients with Child A cirrhosis who underwent sleeve gastrectomy between March 2004 and January 2013 reported no mortality and a complication rate of 7.7%. Cirrhotic patients who underwent sleeve gastrectomy were
matched to those without cirrhosis undergoing sleeve gastrectomy and found that
complication rate and weight loss did not differ [73]. Therefore, we can see that
benefits can outweigh risks in the absence of varices and especially in Child A
patients. First of all, there is a possibility that sleeve gastrectomy causing weight
loss and amelioration of metabolic syndrome can improve cirrhosis and reverse
it in its early stages, thus saving the patient from undergoing a liver transplant.
Secondly, there can be a delay in the progression of liver disease and a delay of the
timing for transplantation, thirdly even if the patient progresses to requiring liver
transplantation, weight loss post sleeve will improve the outcome of liver transplantation in terms of short and long term morbidity and mortality and fourthly
many canters consider BMI >40 as a contraindication for liver transplantation
and reducing the BMI by undergoing sleeve gastrectomy will qualify patients
to be listed for liver transplantation. All these hypotheses require more extensive research to prove them, but there are reports utilizing Scientific Registry of
Transplant Recipients (SRTR) data showing reduced post-transplant survival in
obese liver transplant recipients [74]. A study by Conzen et al. [75] examined the
effect of obesity in 785 patients undergoing orthotropic liver transplantation at a
single institution. They found that a BMI of >35 kg/m2 was associated with NASH
cirrhosis, higher MELD score, and longer wait times for transplant. They found no
difference in the operative time, intensive care unit or hospital length of stay, or
perioperative complications. However, compared with non-obese recipients, recip-
2
ients with a BMI of >40 kg/m
showed significantly reduced 5-year graft (49.0%
versus 75.8%; P < 0.02) and patient (51.3% versus 78.8%; P < 0.01) survival.
Not all studies show that obesity carries a negative effect on liver transplantation, a study utilizing the Organ Procurement and Transplantation Network
(OPTN) database included 48,226 patients who underwent liver transplantation
between 2002 and 2013. They divided the cohort according to MELD score into 4
categories with MELD4 having those with a MELD of 25 and above. They found
different outcomes according to the interaction between MELD and the BMI,
where in MELD4 group the BMI did not affect the outcome and in MELD3 which
contained patients with a MELD score between 19 and 24 the survival outcome
actually increased with the increase in BMI [76]. Without stratifying patients for
MELD score, the study found that the best survival was in those with a BMI of
around 34. The study reported a relatively higher than expected mortality in the
cohort at 25% with a mean of 1371 days follow-up. The issue is that at time of
Sleeve Gastrectomy in Non-alcoholic Steatohepatitis …
129
transplanting listing the MELD score differs than the time when a patient receives
the transplant, therefore stratifying patients according to MELD may not influence
the clinical decision of listing that is a controversy for morbidly obese patients.
The same database (OPTN) were utilized in earlier studies showing worse outcome in obese patients [77, 78].
The cause of liver disease should be factored when examining studies looking at the relation of morbid obesity to liver transplant outcome. A metanalysis
included studies from 1990 to 2013 looking at the impact of morbid obesity on
liver transplant recipient survival. The authors examined thirteen studies that
included 2275 obese and 72 212 non-obese patients, and found no difference in
mortality between the two groups and no difference in mortality even when they
performed a subgroup analysis looking at different BMI groups. However they
found that obese patients had worse survival than non-obese when analysing the
studies that had similar causes of liver disease [79].
In a single center study from Spain 11 obese liver transplant recipients (BMI
>35) were identified out of 180 liver transplants performed between 2007 and
2013. The study found that the mortality of the obese group was clearly higher
when compared to those with a BMI between 20–25 (72.7% vs. 38.9%; P =
0.032). They found no difference in postoperative morbidity or ICU and hospital
stay between the groups, but obese patients were more likely to have portal vein
thrombosis prior to transplants [80].
An important concept that should be taken into consideration, is that patients
who are obese maybe less likely to be listed for liver transplant, therefore when
examining studies looking at liver transplants in obese patients we should take into
consideration that these are actually the patients who were discussed and approved
for transplant listing, and they should be in theory the best group in terms of overall health conditions in comparison to the whole cohort of obese patients requiring
liver transplant. A study using the 2003–2013 United Network for Organ Sharing
(UNOS) data examined the association between obesity and DM and liver transplant wait list survival in hepatitis C patients. The study identified 43,478 chronic
hepatitis C patients on the wait list for liver transplantation. Obesity was found to
be associated with lower probability of receiving liver transplant (OR, 0.91; 95%
CI, 0.85–0.97; P < 0.01), but lower probability of waitlist mortality (OR, 0.80;
95% CI, 0.72–0.89; P < 0.001) when compared to no obese patients. DM among
HCV patients did not impact probability of waitlist survival or receiving liver
transplant. When evaluating post liver transplant survival, compared to non-obese,
non-DM patients, obese HCV patients had significantly lower post liver transplant
mortality (HR 0.86; 95%CI, 0.81–0.92; P < 0.001); whereas, HCV patients with
DM had significantly higher post-LT mortality (HR, 1.22; 95% CI, 1.12–1.33; P
< 0.001). This highlight the complex interaction between metabolic syndrome and
not obesity only on the outcome of liver transplantation and the need to evaluate
the overall survival of obese patients with liver disease and not only those who
will make it for transplantation [81].
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M. H. Jamal and R. El-Abd
12 Timing of Sleeve Gastrectomy in Liver Transplant
Patients
The ideal timing for the performance of bariatric surgery in transplant candidates
and recipients remain controversial. We need to distinguish between patients with
early cirrhosis and patients who are declined to be listed for liver transplant and
patients with cirrhosis who are already approved to be listed for transplantation.
In this section we answer the question about the timing of liver transplantation in
patients who are approved and listed for it.
13 Sleeve Gastrectomy Pre-transplant
The advantage of performing sleeve gastrectomy pre-transplant in patients who
are listed for liver transplantation is that it may delay the need for transplantation
and optimize patients’ comorbidities such as DM II, hypertension, sleep apnoea
and other obesity related comorbidities, thus improving liver transplant immediate postoperative outcomes and graft survival. The major disadvantage is increasing morbidity and mortality of sleeve gastrectomy due to hepatic decompensation,
bleeding and leak. Optimizing the patient preoperatively is essential and identifying those with more advanced disease will allow better selection for those who will
do well with sleeve gastrectomy pre liver transplantation. In general, patients with
Child A cirrhosis without portal hypertension will be ideal to have their sleeve gastrectomy pre-liver transplant, but not all these patients will be listed for transplants.
In the previous section we reviewed studies on this group of cirrhotic patients.
A study on patients listed for liver transplant and underwent sleeve gastrectomy
included 32 patients with a median MELD score of 12 and a median BMI of 45. All
of these patients had history of hepatic decompensation where 22% had a history
of variceal haemorrhage, 44% had a history of ascites, and 38% had a history of
hepatic encephalopathy. Hepatitis C virus was the most common primary etiology
of liver disease (47%), followed by non-alcoholic fatty liver disease (31%), alcohol (9%), and hepatitis B virus (6%). Half of the patients were classified as Child–
Pugh classification B and 5 of them underwent TIPS. They reported no liver related
morbidity and no mortality but only one sleeve leak managed conservatively. Most
patients 27/32 84% had either a stable or improved MELD score at 6 months postoperatively. In terms of liver transplant listing, 28 (88%) patients were considered
eligible, with 7 patients considered too good to be listed due to their low MELD
score post sleeve gastrectomy and 2 of those 7 patients were child B patients [82].
14 Simultaneous Liver Transplant and Sleeve
Gastrectomy
Proponents of performing bariatric surgery at the time of liver transplantation, cite
the avoidance of a second procedure, theoretical reduction of incidence of incisional hernia and the technical ease as most incisions for liver transplantation
Sleeve Gastrectomy in Non-alcoholic Steatohepatitis …
131
give good access to the left upper quadrant. More importantly performing sleeve
gastrectomy at the time of liver transplantation with a new functioning liver will
lead to the reduction of post-operative complications especially those related to
liver decompensation that might occur when performing bariatric surgery pre liver
transplantation. There are few reports published from groups performing the two
operations simultaneously, but the largest experience comes from the Mayo Clinic
in the USA, that published two studies on their outcomes [81, 83].
Heimbach et al. included 44 patients who are listed for LT with a BMI >35. All
patients were enrolled in a pretransplant weight loss program, and 37 were able to
reduce their weight with conservative measures and with ascites weight deducted.
Seven patients underwent sleeve gastrectomy at time of LT in this cohort of
patients. There were three deaths in patients who received LT without sleeve gastrectomy, and three patients lost their graft and needed retransplant. Weight regain
to a BMI >35 was seen in 21/34 (60%) patients, DM post LT was seen in 12/34
(35%) patients and steatosis on ultrasound in 7/34 (20%) patients. No deaths or
graft losses were seen in the combined sleeve and LT group but one patient had
gastric leak and one patient had excessive weight loss. No patients in this group
developed steatosis or post LT DM, and all patients had good weight loss with a
mean BMI of 29, from a mean BMI of 48. All patients in the combined sleeve LT
group had NASH, except one patient while 12/37 (32%) patients in the LT only
group had NASH [83]. The same group published another report on their experience with longer follow-up [81]. In their updated report they included 49 patients
with at least 3 years of post-transplant follow up, in which 13 patients underwent
simultaneous LT and sleeve, while 36 patients managed to lower their BMI to
below 35 and underwent LT alone. In the LT alone group, all regained their weight
with a BMI more than 35 after 3 years of follow-up except 8/36 (22%) patients. In
the simultaneous LT and sleeve group the %TBWL was (34.8 ± 17.3) compared
to (3.9 ± 13.3) in the LT only group at three years follow-up. One patient from the
LT and sleeve group died and four in the LT alone group at 3 years follow-up, however there were no statistically Signiant difference in survival between the groups.
15 Sleeve Gastrectomy After Liver Transplantation
The advantage of performing sleeve gastrectomy post transplantation is in mainly
avoiding the complications resulting from hepatic decompensation, however surgical adhesions, including adhesions of the left lobe to the stomach as well as adhesions from incisional hernias can complicate these surgeries. Patients will be on
immunosuppression, which can increase post-operative complications and will
require special attention to monitor immunosuppression and avoid sub therapeutic
levels due to inability to take medications or drug toxicity due to dehydration.
A single institution study reported 15 sleeve gastrectomies in patients post liver
transplantation with median time from LT to sleeve at 2.2 years. They report no
major complications, in particular no leak, no bleeding requiring reoperations or
transfusion, no liver allograft rejection and no mortality. In the diabetic patients in
their cohort, 60% stopped using insulin [84]. Another study evaluated 12 patients
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M. H. Jamal and R. El-Abd
who underwent sleeve gastrectomy post LT and matched them to 36 patients who
had sleeve gastrectomy without LT, reported three (25%) major complications in
sleeve post LT group, where two patients required balloon dilatation due to poor
oral intake and one patient requiring laparoscopic gastrostomy tube insertion due
to poor oral intake. They report no mortality and no change in immunosuppression
post sleeve and no liver related morbidity [85]. A study included six patients only
who underwent sleeve gastrectomy post liver transplant. Three of these patients
had their sleeve gastrectomy using an open approach due to incisional hernias.
One patient had gastric fistula, requiring multiple interventions followed by death
19 months postoperatively and one patient developed chronic mesh infection
requiring surgical removal [86].
Summary of Recommendations:
• Perform sleeve gastrectomy in Child A patients due to any cause of liver dis-
ease in morbidly obese patients with a BMI >35
• Perform sleeve gastrectomy in Child A patients due to NASH in patients with a
BMI >32
• Perform sleeve gastrectomy in Child A patients due to NASH and Type II DM
in patients with a BMI >30
• In patients with Child B, without varices or after TIPs and in case the patient is
not approved for listing for liver transplantation due to morbid obesity a sleeve
gastrectomy can be considered.
• In all other morbidly obese patients i.e. patients with Child B and C. We rec-
ommend performing sleeve gastrectomy at time of transplantation or post
transplantation.
• In investigating diabetic patients preoperatively for sleeve, an abdominal ultra-
sound is highly recommended and a fibro scan is recommended.
• In investigating patients with Liver cirrhosis, referral to a cardiologist is highly
recommended.
Better data is needed in the subject as most studies are case series. In particular a
randomized controlled trial is required.
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M. H. Jamal and R. El-Abd