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Weight loss: Pharmacological
and non-pharmacological
interventions
Dr Guillaume Lassailly
CHRU de Lille, INSERM U995
Lille, France.
Lunch Breakout Session4
Weight loss : Non
pharmacological
interventions
1. Bariatric Surgery
A. Background of Bariatric Surgery
B. Results in NASH
C. Indications & Contra-indication
D. Risk & population
2. Endoscopic alternative :
Ex: Endobarrier®
Summary
Weight loss : Non
pharmacological
interventions
1. Bariatric Surgery
A. Background of Bariatric Surgery
B. Results in NASH
C. Indications & Contra-indication
D. Risk & population
2. Endoscopic alternative :
Ex: Endobarrier®
Summary
Villar-Gomez E, Gastroenterology 2015
Weight loss and NASH
Medical strategy is benefic in 10% of patients
Could bariatric surgery be a therapeutic option for WL or NASH ?
Ref: Obépi 2012
Obesity,
The French data
Prevalence of obesity according to the generationPrevalence of obesity in the French population
Prevalence of obesity and severe obesity (BMI > 35 kg/m2) is increasing.
This evolution concerns all generations.
Surgery is increasing, but…
Only 1% of candidate for bariatric surgery are referred to the surgeon
Wolfe BM, Gastroenterology 2007
Evolution in FranceEvolution in USA
• As a consequence of the high prevalence of obesity, bariatric surgery became frequent and common a surgical procedure.
Sjöström L et al, nejm 2007
What about long term data …
Efficacy of bariatric surgery on weight loss
Band : 10-20% WL
Sleeve : 15-20% WL
Bypass : 20-35% WL
For morbid obese patients bariatric
surgery is more effective than
medical strategy
Sjöström L et al nejm 2007
Results of bariatric surgery
Reduces overall mortality Reduces CV events
Sjostrom L et al, JAMA 2012
Schauer PR et al nejm 2012,
Schauer PR et al nejm 2017
Bariatric surgery and diabetes
Bariatric surgery improves & can induce diabetes remission at 5
year (25-45%)
Bariatric surgery as a preventive
treatment for metabolic complications
Comparison of 1700 patients undergoing bariatric surgery matched with control group
this approach could interesting to prevent liver complications in morbid obese patients …
but no data are available.
Carlsson et al, nejm 2012
Weight loss : Non
pharmacological
interventions
1. Bariatric Surgery
A. Background of Bariatric Surgery
B. Results in NASH
C. Indications & Contra-indication
D. Risk & population
2. Endoscopic alternative :
Ex: Endobarrier®
Summary
Evolution of histological features of
NAFLD after bariatric surgery
Lassailly et al , Gastroenterology 2015
Evolution after 1 year
Before surgery After surgery
Efficacy of bariatric surgery on NASH
Lassailly et al , Gastroenterology 2015
Evolution 1 year after surgery
Dixon et al, Hepatology 2004
85 % of NASH disappearance
Klein S, Gastroenterology 2006
Evolution of fibrosis
Improvement of fibrosis biomarkers Improvement of fibrosis after surgery
Lassailly G, Gastroenterology 2015
One year characteristics: Comparison of patients with refractory/persistent NASH at 1 year
(non responders: NR) vs patients with NASH disappearence (Responders: N):
R NR
* *
1/Q
UIC
KI
ΔB
MI
-5
5
15
25
35
2,0
2,5
3,0
3,5
4,0
4,5
5,0
5,5
R NR
Weight loss Insulin Resistance Index
Lassailly et al, Gastroenterology 2015
What about the patients with persistent
NASH at 1 year ?
Mathurin P et al, Gastroenterology 2006
Klein S, Gastroenterology 2006
Steatosis & insulin resistance.
Association before and after surgery
IR is improved after surgery
Histology is associated
to IR profile before and
after surgery
Gut hormones After Bariatric surgery
GLP-1 ↑
Ghrelin ↓ (sleeve)
PYY ↑
PP ↑
Oxyntomodulin ↑
Acosta A et al, Gut 2014; Lassailly G et al, J Hepatol 2013
Optimizing gut hormones
Improves : IRChanges in appetite and tasteGut microbiota
Daily calories Weight
1. Appetite
2. Satiety
behavior
Gut hormones
Gut-brain Axis
Appetite and satiety are controlled by l’hypothalamus in relation with the limbic system (emotion & reward area).
PYYOxytomodulinGLP-1LeptinInsulin/glucagon
Acosta A et al, Gut 2014
Orexigene hormone Anorexigene Hormones
Ghreline PYY
GLP-1
Cholécystokinine
Vagual nerve*
Changing eating behavior
Taste
AppetitePleasure
Van Vuuren MAJ et al , Obes Surg 2017
Time 1 : 6 week after surgeryTime 2 : 8 month
Changing eating behavior
Weight loss : Non
pharmacological
interventions
1. Bariatric Surgery
A. Background of Bariatric Surgery
B. Results in NASH
C. Indications & Contra-indication
D. Risk & population
2. Endoscopic alternative :
Ex: Endobarrier®
Summary
Current validated indications
Indication
- BMI > 40 kg/m²
- BMI > 35 kg/m² with a least one complication secondary to severe obesity
o Cardiovascular disease
o Sleep Apnea
o Type 2 diabetes
o NASH (in France, HAS recommandation 2009)
HAS 2009 : No recommandation for the BMI between 30 and 35 kg/m².
FDA : gastric Banding if
- BMI > 40 kg/m²
- Or BMI > 30 kg/m² with :
o Aretrial Hypertension
o Obstructive Sleep apnea
o Diabetes
Current validated contra-indications
Contra-indication
Alcohol > 20g/j for women and 30g/j for men
Presence of Helicobacter pylori resistant to medical therapy
Gastric or duodenal Ulcer in the past 2 month
Gastric Dysplasia or history of gastric cancer
Gastroesophagal reflux resistant to treatement ( for sleeve gastrectomy)
Chronic Diarrhea
Eating disorders (according to DSM V)
Prader-Willi syndrome
Severe Mental diseases
Cirrhosis
Disease related to short term life threating or aenesthesiological contra-
indications
Weight loss : Non
pharmacological
interventions
1. Bariatric Surgery
A. Background of Bariatric Surgery
B. Results in NASH
C. Indications & Contra-indication
D. Risk & population
2. Endoscopic alternative :
Ex: Endobarrier®
Summary
Risk and morbidity of bariatric surgery
LABS Consortium, nejm 2009
Related to 30 days morbidityand mortality-Extreme BMI-History of deep-veinthrombosis-Obstructive Sleep Apnea-Inability to walk > 200 ft
Other complications bariatric surgery
Complications after bariatric surgery
Gobal mortality 0.1-0.5%
Rate of rehospitalization at 1 year
-20% for bypass
-15% gastric banding
(related to complications : 6-9%)
General complications Specific complications
PE & deep-vein thrombosis (3.3%)* Gastro-esophagal reflux (sleeve = 20%)
Parietal Infection (open: 10-15% vs. Lap : 3-4%) Gastric fistula (2-5%) (sleeve +++)
Vomiting (8-20%) Gastric stenosis
Hemorraghe (ulcer anastomosis) (0.6-4%) Band migration (2-5%)
Dumping syndrom Anastomotic stenosis (6-20%)
Post-operative hypoglycemia Band dysfunction (0.4-1.7%)
Malnutrition
Diarrhea (40-55%)
Gallstone (40% long term after surgery)
Buchwald et al, JAMA 2004 ; Flum D.R. et al, JAMA 2005 ;
Zingmond DS et al, JAMA 2005; O. Emungania FMC Gastro2010
* Implicated in 30% of death
NIS (National Inpatients Sample): 1998-2007
• Mortality of compensated cirrhosis (N=3888):
– 0,9% vs 0,3%
– increased risk x 2-3
• Mortality of decompensated cirrhosis (N=62):
– 16,3% vs 0,3%
– Increased risk x 21 Mosko JD et al Clin Gastroenterol Hepatol, 2011
Retrospective monocentric study:
2119 patients opérés: Gastric Bypass
N= 30 cirrhosis
BMI: 50 vs 48 kg/m2
Gender ratio 1.3
Diabetes: 70 vs 21%
Diagnosis of cirrhosis was performed durinf the procedure in 90% des cas 30% of
morbidity, but no decompensation, no death at 1 year.
Dallal RM et al, Obes Surg 2004
Data in cirrhotic patients
Efficiency and cost-efficiciency of
bariatric surgery in NASH
Klebanoff MJ, Hepatology 2016
Benefit appears in severe patients
And are also those with the highest risk of complications
Which procedure should be
proposed ?For weight loss / or metabolic effect ?
We may have to adjust the gastric band a little
Gastric Banding vs Bypass
Aterburn D et al, JAMA surg 2014
Patients present more complications after bypass than banding.But bypass is more effective than gastric banding.
Gastric Banding vs Bypass
Nguyen et al, Annals of Surgery 2017
10 years results : gastric banding vs bypass
Laparascopic sleeve gastrectomy vs
laparoscopic Roux en y gastric bypass
Salminen et al, JAMA 2018Peterli et al, JAMA 2018
Study evaluating the superiority of bypassNo equivalence between bypass and sleeve, no differenceNo difference in terms of morbidity and mortality
Weight loss : Non
pharmacological
interventions
1. Bariatric Surgery
A. Background of Bariatric Surgery
B. Results in NASH
C. Indications & Contra-indication
D. Risk & population
2. Endoscopic treatment
Summary
Intragastric Balloon
Fuller et al, Obesity 2013
Mild effect of intra-gastric balloon
Significant relapse at long term.
Mortality 0.1%
Eating Behavior therapy is recommanded
Provisional device (around 6 month to 1 year)
Indication : BMI 27-40 kg/m2
Or patients refusing bariatric surgery
In 2009, French Health authorities did ot
recognize the clinical benefit compared
to medical and lifestyle therapy.
Données HAS 2009
Intragastric Balloon
Withdrawal 2018 : ORBERA & ReShape
MORTALITY between Balloon vs. LAGB = 0.1% vs 0.1-0.2%
Alternatives ?
Endobarrier, Gasto-Liner
1. Interesting, but recurrence after explantation of the device
2. Efficacy on NASH : data are lacking
Betzel et al, Surg Endosc 2016
Indication BMI > 30 kg/m2 with type 2 diabetes
Provisional device
Conclusion
• In weight loss strategies bariatric surgery seems to be effective and secure. Benefit > Risk
• Patients referred to bariatric surgery must be properly evaluated.
• Question : Is surgery suitable for NASH with BMI < 35 kg/m² ? Only for F3 NASH patients ? Is medical therapy better
BMI < 30 BMI : 30 - 35
Medical therapy Bariatric surgery therapy
Weight loss: Pharmacological
and non-pharmacological
interventions
Prof. Manuel Romero-GómezDigestive Diseases and ciberehd. HUVRocío. SeLiver Group.
Institute of Biomedicine of Seville. University of Seville. Sevilla, Spain.
Lunch Breakout Session4
Agenda
• The main aim weight loss and avoiding regain
• Impact of weight loss on NAFLD/NASH
• How could we reach weight loss:– Diet
– Physical activity
– Drugs
– Endoscopy/surgery
• Avoiding weight regain
Blackburn G. Obes Res. 1995;3(suppl 2):211-216; Foster GD. Arch Intern Med. 2009;169:1619-1626; Greg EW. JAMA. 2012;308:2489-2496; Sjostrom L. J Intern Med. 2013;273:219-234; Christou NV. Surg Obes Relat Dis. 2008;4:691-695.
How much weight loss is required to ameliorate/reversecomorbidities?
Previous improvements +
Reductions in CVD events
Reductions in all-cause mortality
Reductions in cancer risks
(only with bariatric surgery
≥ 15%
≥ 5%
T2D prevention and control
Weight-related QoL
Improvements in CVD risk
HDL-C, cholesterol,
triglycerides, BP
Previous improvements +
T2D remission
Improvements in sleep apnea
Reductions in intima-media thickness
≥ 10%
Weight loss is an excellent surrogate markerGreater WL – Bigger benefits
NASH
therapy
Diet
Calories
MacronutrientsBEYOND CALORIES
Geometry of Nutrition
Alcohol Coffee
Physical activity
Sedentary behavior
Physical activityMultidisciplinary
approach
Exercise
Drugs
T2DM drugs
Obesity drugs
Liver-targeted drugs
Gut-Liver Axis
Fat-Liver Axis
Brain-Liver axis
Weight Loss
What is the best program to weight loss? Diet
Weight loss (Kg)
Type of diet 6 months, 12 months
Low carbohydrate 8.73 (7.27-10.20) 7.25 (5.33-9.25)
Low fat 7.99 (6.01-9.92) 7.27 (5.26-9.34)
Meta-analysis of 48 RCT
7286 overweight/obese subjects
Effectiveness of two type of diets (low-carbohydrate vs. Low-fat)
Outcome: weight loss rates at 6 and 12 months
Johnston BC, et al JAMA. 2014;312:923-933
Dietary composition may have a similar effect on weight loss rates
Sacks FM et al. N Engl J Med. 2009;360:859–873.
RCT – 811 overweight / obese pts
515 females and 296 males
Randomly assigned to one of four diet groups
No significant difference were observed on WL rates during the run-in and maintenance phases
0
–1
–2
–3
–4
–5
–6
–7
Wei
ght
Loss
(kg
)
0 6 12 18 24
Months
Diet Composition (%)Carbohydrate / Protein / Fat
65/15/20 (low-fat, average protein)
55/25/20 (low-fat, high-protein)
45/15/40 (High-fat, average-protein)
35/25/40 (High-fat, high-protein)
WL phase Maintenance phase
Diets represented a deficit of 750 kcal/day
8% or less of saturated fat
CH low-glycemic index (all diets)
Behavioral therapies (individual and group sessions)
90 minutes of moderate exercise per week
R/ 30-35% - WL>5% and 14-15% - WL>10%
Diet adherence associated to long-term success
IMPACT OF DIET AND PHYSICAL ACTIVITY ON NAFLD
Promrat K, et al. Hepatology 2010 ; 51: 121–129.
WL: -9.3% vs -0.2%
Physical exercise in NAFLD
Hickman et al., J Diabetes Metab 2013, 4:8
N=21 NAFLD
26 w
↓ 500 kcal/d vs exercise 60 min 3 times per week
DIET: ↓WL: 9.7 ± 4.6% Exercise: no change
Physical exercise in NAFLD
Hickman et al., J Diabetes Metab 2013, 4:8
N=21 NAFLD
26 w
↓ 500 kcal/d vs exercise 60 min 3 times per week
DIET: ↓WL: 9.7 ± 4.6% Exercise: no change
What is the best program to weight loss? Physical activity
High activity required for weight loss maintenance
Jakicic JM et al. Arch Intern Med. 2008;168:1550–1560
Marginal benefit adding structured exercise to diet during run-in phase
Heilbronn LK, et al. JAMA. 2006;295:1539-1548
48 overweight subjects were randomized into 4 groups.
1. Control group (no caloric restriction).
2. Calorie restriction (25%).
3. Calorie restriction (12.5%) plus 12.5% increase in energy expenditure by structured exercise).
4. Very low calorie diet (890 kcal/d] until 15% reduction in body weight, followed by a weight maintenance diet).
RCT / 201 overweight and obese women
All were told to reduce 1200-1500 kcal/d
Randomly assigned to 4 groups of exercise
on PA energy expenditure and intensity
1.Moderate intensity/energy expenditure
2.Moderate intensity/ high energy exp.
3.Vigorous intensity/moderate energy exp.
4.Vigorous intensity/high energy exp.
How to assess activity?
• Sedentary behaviour:– Total amount of time sitting
– Number of breaks
• Physical activity:– Inactive
– Minimally active
– Health-enhancing physically active
• Exercise:– Aerobic exercise
– Resistance exercise
– High intensity intermittent exercise
– Vigorous aerobic exercise
How to prescribe exercise?
Sedentary behaviour & physical activity in NAFLD
22,8%
28,2%31,8%
0
10
20
30
40
<5h/d 5-9 h/d >10 h/d
Sedentary behaviour
Prevalence of NAFLD
25,5%29,7% 28,1%
0
10
20
30
40
HEPA MinA Inactive
Physical activity
Prevalence of NAFLD
Ryu S et al. J Hepatol 2015
Triple hit behavioural phenotype
NAFLD
Sedentary behaviour
Low physical activity Poor diet
(High Fat & low
PUFA/MUFA)
NAFLD is associated with low levels of physical activity, longer period sitting and no breaks (sedentary behaviour) and western diet.
Romero-Gómez M, Zelber-Sagi S, Trenell M. J Hepatol 2017
PNPLA3 Influences Response to Lifestyle Modification in NAFLD
Shen et al, J Gastro Hep 2015
IHTG change: CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6% and GG: 11.3 ± 8.8% (p=0.002)
Lifestyle Intervention Control
-1,09
-0,42 -0,3-0,35
-3,9
-1,5-1,2 -1,3
NAS Steatosis Ballooning Lob. Inflamm
WL< 7% WL >7%
-1,7
-0,54 -0,45-0,63
-3,9
-1,8
-0,9-1,22
NAS Steatosis Ballooning Lob. Inflamm
WL< 10% WL >10%
Weight loss and histological outcomes of NAFL patients
How much impact the duration of ILI?
Vilar-Gomez E, et al Gastroenterology 2015; 149:367-378
Vilar-Gomez E, et al. APT 2009; 30:999-1009.
ILI – 24 weeks
-1,18
-0,41-0,53 -0,24
-3,45
-1,36 -1,27
-0,82
NAS Steatosis Ballooning Lob. Inflamm
WL< 7% WL >7%
ILI – 48 weeks
-1,08
-0,39 -0,44-0,46
-3,4
-1,45
-1 -0,96
NAS Steatosis Ballooning Lob. Inflamm
WL< 9% WL >9%
Orlistat – 36 weeks
ILI – 52 weeks
Pomrat K, et al. Hepatology 2010; 51:121-129.
Harrison S, et al. Hepatology 2009;49:80-86.10
Adapted from Johnson et al. Exercise and Liver: Implications for therapy in fatty liver disorders, Semin Liv Dis 2012
Weight
loss
Exercise
Physical
activity
Diet
Weight loss a major driver in NASH resolution
Weight Loss via Lifestyle Modification Significantly Reduces
Features of Nonalcoholic Steatohepatitis
N=293 NASH proven patients
Low-fat hypocaloric diet + walking 200 min/week + questionnaire +
Group sessions
Vilar-Gomez, Romero-Gomez, Gastroenterology 2015; 149:367-378
❑ Lifestyle changes focusing on weight loss remain the cornerstone of NASH treatment.
❑WL between 7-10% may improve NAS score and their components.
Inclusion criteria:
-Patients aged ≥ 18 years
and both sexes
-Histologic diagnosis of
definite NASH.
Exclusion criteria:
- Borderline NASH or cirrhosis.
-Alcohol consumption >20 g/d men
> 10 g/d women
-Uncontrolled T2DM (Hb A1c > 9)
-Medications for NASH.
5% 7% 10%
26%
38%
64%
50%
90%
81%
NASH-resolution
FIBROSIS-regression
% Patients achieving WL 12% 9% 10%
% Weight loss (WL)
STEATOSIS improvement 76% 100%65%
10%
35%
45%
70%
52 weeks of lifestyle intervention
Romero-Gómez M, Zelber-Sagi S, Trenell M. J Hepatol 2017
• GLP1 RA: Liraglutide
• Naltrexone HCL/Bupropion HCL-ER
• Orlistat
Drugs options fro weight loss in NASH
Dual anti-obesity and anti-NASH effects of GLP-1 agonists
Van Gaal L. European Congress on Obesity (ECO) 2015. Abstract 0S2.1.
N= 52 (17 T2DM & 27 F3/F4)45 paired liver biopsies
39%
9%
0 10 20 30 40 50
Liraglutide
Placebo
NASHRES
P<0.04; O.R. 6.43 (1.2-34.4)
Armstrong MJ et al. Lancet 2016
SEMAGLUTIDE
88
90
92
94
96
Bo
dy
we
igh
t(k
g)
Time (weeks)
Impact of GLP1 ra on weight loss
Semaglutide 0.5 mg
Dulaglutide 0.75 mg
Semaglutide 1.0 mg
Dulaglutide 1.5 mg
Body weith Overall mean at baseline: 95.2 kg
• “Investigation of Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholicSteatohepatitis”. https://clinicaltrials.gov/ct2/show/NCT02970942
• Weight Loss and Maintenance in T2D (1.0-2.4 mg) https://clinicaltrials.gov/ct2/show/NN9536-4374
Promoting weight loss and avoiding weight regain
NUTRITION & PHYSICAL ACTIVITY ASSESSMENT
PSYCHOLOGICALASSESSMENT
HEPATOLOGISTASSESSMENT
MULTIDISCIPLINARYTEAM
NUTRITIONALCOUNSELING
EXERCISEPROGRAM
PSYCHIATRICPROGRAM
SURGERYDRUGTHERAPY
Modified from Karmali et al. Obes Surg 2013
FOLLOW-UP VISITS
Hypocaloric Mediterranean diet for weight loss and NASH resolution
Early breakfast:
1 HYPOCALORIC piece of FRUIT (avoid bananas, grapes, custard apple, fig and
do not mix fruit types)
1 SKIM YOGURT or 1 glass of skim milk
1 COFFEE or tea with skimmed milk without sugar
Sometimes (2-3 times per week) you could add a couple of biscuits of whole
bread or ½ toast of wholemeal bread with olive oil (1 supper spoon) or
margarine (10 grs) or wholegrain cereals without sugar (30 grs)
Midmorning:
1 infusion (tea, coffee, chamomile, mint pennyroyal) with saccharin
[You can repeat infusions several times per day]
1 HYPOCALORIC piece of FRUIT (avoid bananas, grapes, custard apple, fig and
do not mix fruit types) or 1 SKIM YOGURT.
Occasionally (1-2 times per week) you could add ½ vegetable sandwich or ham
sandwich without cheese.
Hypocaloric Mediterranean diet for weight loss and NASH resolution
Lunch:
SALAD (lettuce, endives, tomato, pepper, onion, asparagus, mushrooms,
cucumber, spinach, heart of palm, little corncob) or COOKED VEGETABLES,
GRILLED VEGETABLES (cucumber, pepper, cauliflower, broccoli, cabbage,
asparagus, mushrooms, spinach, chard, zucchini, eggplants, leek, green been,
beet, carrots, pumpkin, artichokes)(potatoes, sprouts, pea, broad beans with
moderation) or VEGETABLE SOUP
Cooked or Grilled Fish or grilled chicken or turkey (without skin) or beef
every other day.
Sometimes (3 days per week) you could change fish or meat to a dish of rice,
pasta, potatoes, vegetables in stew without fat or sauce.
Hypocaloric Mediterranean diet for weight loss and NASH resolution
Snack:
Orange juice (two pieces) or fruit (Kiwi or strawberry) or any other fruit.
Infusion/coffee
1 SKIMMED YOGURT
Dinner:
vegetable soup or salad or cocked or grilled vegetables (different from the
lunch)
Eggs (omelette or cooked) (2 whites and ½ yolk) or fish or meat cooked or
grilled or York ham or turkey ham or seafood with shell or natural tune
Sometimes you could add fresh cheese or Iberico ham without fat.
Optional fruit
How sustainable is weight loss after ILI?
8-Year weight loss in the Look AHEAD Trial
-8,5
-4,16 -4,7
-0,63-1,01
-2,1
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
0 1 2 3 4 5 6 7 8
Years
ILI
DSE
Repeated measures adjusted for clinic and baseline level. P value for average effect across all visits: P < 0.0001.DSE, diabetes support and education; ILI , intensive lifestyle intervention.Look AHEAD Research Group, Obesity 2014; 22:5-13.
Look AHEAD – RCT including 5,145 overweight/obese with T2D
Effects of intentional weight loss on CV morbidity and mortality
Pts were randomly assigned to ILI or diabetes support and education.
68%
50%
38%
27%
16%11%
0%
10%
20%
30%
40%
50%
60%
70%
80%
1 year 8 Year
>= 5% >=10% >=15%
Mea
n c
han
ges
in b
od
y w
eigh
t (%
) fr
om
bas
elin
e
Pro
po
rtio
n o
f p
atie
nts
54%
Regain
Borek AJ et al. Applied Psychol, 2018. doi:10.1111/aphw.12121
BETTER INTREVENTION I BETTER CONTROL
weight loss between intervention and control groups was 3.49 [95% CI 4.15, 2.84], 3.44 [4.23, 2.85], and 2.56 kg [3.79, 1.33] at follow-up closest to 6, 12, and 24 months, respectively.
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idin
g W
eigh
t lo
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egai
n