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RESEARCH ARTICLE
Bariatric Therapy with Intragastric Balloon Improves Liver
Dysfunction and Insulin Resistance in Obese Patients
Giorgio Ricci &Gianluca Bersani &Angelo Rossi &
Flavia Pigò &Giovanni De Fabritiis &Vittorio Alvisi
Received: 20 February 2008 / Accepted: 29 February 2008
#Springer Science + Business Media, LLC 2008
Abstract
Background Obesity is often associated with fatty liver
(FL). In most cases, bright liver at ultrasound (US) and
increased alanine aminotransferase (ALT) and gamma-
glutamyltranspeptidase (GGT) levels are considered the
hallmarks of nonalcoholic fatty liver disease (NAFLD).
Insulin resistance (IR) is the main link between obesity and
NAFLD. The use of the Bioenterics® intragastric balloon
(BIB) is a safe procedure either for inducing a sustained
weight loss with diet support or for preparing those patients
who are candidates for bariatric surgery. The aim of the
study was to investigate whether the weight loss induced by
intragastric balloon might improve IR and liver enzymes.
The presence or absence of FL at US and the influence of a
body mass index (BMI) decrease ≥10% after BIB (ΔBMI≥
10%) were also considered.
Methods One hundred and three consecutive obese (BMI >
30 kg/m
2
) patients (38 males/65 females; mean age 41.3,
range 20–63 years) underwent BIB insertion under endo-
scopic control. The BIB was removed 6 months later. US,
clinical, and routine laboratory investigations were per-
formed before and after BIB. IR was calculated by the
homeostasis model assessment (HOMA-IR >2.5). Exclu-
sion criteria were hepatitis B virus positive, hepatitis C
virus positive, alcohol consumption >30 g/day, history of
hepato-steatogenic drugs, and type 1 diabetes.
Results Ninety-three patients were eligible for the study.
The BMI significantly decreased in all investigated patients,
and it was ≥10% in 59% of the patients. FL was seen at US
in 70%, impaired fasting blood glucose was present in
13%, ALT exceeded the normal limit in 30.1%, GGT ex-
ceeded the normal limit in 15%, and HOMA-IR was >2.5
in 85%. Median HOMA-IR decreased significantly in FL
(4.71 vs 3.10; p<0.05) and non-FL (3.72 vs 2.81; p<0.01)
groups. Median ALT decreased significantly in the FL
group (31.5 vs 24; p<0.001) and GGT significantly de-
creased in the FL group (31 vs 23.5; p< 0.05). In the FL
group with ΔBMI≥10%, the median values of HOMA-IR
(4.95 vs 2.69; p<0.05), ALT (30 vs 23; p<0.01), and GGT
(28 vs 20; p<0.001) significantly decreased after BIB. In
the non-FL group, HOMA-IR values significantly decreased
(4.07 vs 2.36; p<0.01) in patients with a ΔBMI≥10%; ALT
and GGT did not significantly decrease.
Conclusions Weight loss induced by intragrastric balloon
reduces IR. The ALT and GGT decrease suggests an
improvement in hepatic damage. The benefit depends on
the decrease of BMI higher than 10%.
Keywords Obesity .Fatty liver .
Nonalcoholic fatty liver disease .Insulin resistance .
Alanine aminotransferase .gamma-Glutamyltranspeptidase .
Intragastric balloon .Bariatric therapy
Introduction
The increasing prevalence of obesity, mostly in western
countries, has prompted intensive research on associated
morbidities, as well as on the treatments for achieving
weight reduction. In obesity, visceral fat accumulation,
above all in the liver, namely, nonalcoholic fatty liver
disease (NAFLD), is often associated with a cluster of
metabolic alterations, i.e., type 2 diabetes, hypertension,
and dyslipidemia, namely, the metabolic syndrome [1]. The
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DOI 10.1007/s11695-008-9487-x
G. Ricci (*):G. Bersani :A. Rossi :F. Pigò :
G. De Fabritiis :V. Alvisi
School of Gastroenterology,
University of Ferrara, Ferrara, Italy
e-mail: giorgio.ricci@unife.it
main link among obesity, fatty liver (FL), and the metabolic
syndrome, is represented by insulin resistance (IR) [2].
Previous reports have suggested that IR may be an intrinsic
defect in NAFLD due to the impaired ability of insulin to
suppress lipolysis, leading to increased delivery of free fatty
acids to the liver. Insulin sensitivity is positively related to
adiponectin, an adipose tissue hormone that promotes fatty
acid oxidation in the liver [2–4]. Conversely, IR reduces
adiponenctin with the consequent increase of the visceral
fat, especially in the liver. In subjects with NAFLD,
significantly lower levels of adiponectin were found when
they were compared with body mass index (BMI)-matched
controls [5]. The inflammatory cytokines are also increased
in NAFLD and are positively related to IR [5]. In obese
patients with NAFLD, IR is significantly associated with
increased levels of liver enzymes, confirming the key role
of IR in hepatic injury, throughout liver fat accumulation
[6]. However, the pathogenesis of elevated liver enzymes in
NAFLD has not yet been completely clarified [7]. In
addition, the modest elevations in aminotransferase (ALT)
and gamma-glutamyltranspeptidase (GGT), even near the
upper half of the normal range, have been reported to
predict liver damage in obese patients [8].
Until now, no treatment has been established for
reducing the risk of progressive liver disease associated
with NAFLD, even though weight loss and a low-fat diet
are strongly recommended. Many approaches have been
proposed to induce weight loss. They encompass diet,
lifestyle modifications, medications (metformin, thiazolidi-
nediones), and bariatric treatment [9,10]. Temporary
placement of an intragastric balloon is now widely used
either for those patients who can maintain the weight loss
with diet support or to prepare patients who are candidates
for bariatric surgery or other surgical procedures [11].
The aim of our study was to investigate whether the
weight loss induced by temporary bariatric treatment with
intragastric balloon might lead to modifications of IR and
improvement of liver enzymes. In addition, the presence or
absence of FL at ultrasound (US) and the influence of BMI
decrease ≥10% after Bioenterics® Intragastric Balloon
(BIB) (ΔBMI≥10%) were also considered.
Material and Methods
Patients
From March 2003 through November 2007, 103 consecu-
tive obese (BMI>30 kg/m
2
) patients (38 males/65 females;
mean age 41.3±10.4, range 20–63 years) were admitted to
our digestive endoscopy service for bariatric treatment of
obesity by means of BIB® (Bioenterics, Santa Barbara, CA,
USA) insertion. The BIB was positioned under endoscopic
control and removed 6 months later. Clinical, laboratory
and metabolic determinations were assessed for each
patient before and after BIB insertion. Exclusion criteria
Table 1 HOMA-IR, ALT and GGT in obese patients with (FL) or without (non-FL) FL at US investigation
Basal (t0) 6 months (t6)
FL Non-FL FL Non-FL
HOMA-IR 4.71 (1.80–14.50) 3.72 (1.83–11.80) 3.10 (0.14–16.90)* 2.81 (0.80–6.68)**
ALT U/L 31.5 (10–126) 21 (7–72) 24 (9–73)*** 16.5 (9–61)
GGT U/L 31 (7–106) 18.5 (5–73) 23.5 (6–82)* 14 (6–54)
The basal (t0) values were compared with those obtained after 6 months (t6) of BIB placement
*p<0.05; **p< 0.01; ***p< 0.001
HOMA-IR
*
**
ALT U/L
***
GGT U/L
t0t6t0
t0t6t6
**
Fig. 1 Box representation of Homa-IR, ALT, and GGT in FL and non-FL (dashed box) patients; before (t0) and after (t6) 6 months of BIB
insertion. Significance: Single asterisk,p<0.05; double asterisks,p<0.01; triple asterisks,p< 0.001
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were positivity for hepatitis B virus or hepatitis C virus,
previous or current alcohol consumption >30 g/day, use of
medications with reported hepato-steatogenic effect (amio-
darone, tamoxifene, estrogens), and type 1 diabetes. A
personalized low-calorie diet was provided to each patient
during BIB placement.
Laboratory and Instrumental Investigations
BMI (kg/m
2
) was determined before and after the BIB
placement. Blood samples were obtained from each patient
after an overnight fast. The determinations of blood glucose,
liver enzymes (ALT, GGT), insulin, triglycerides, and HDL
cholesterol were performed by standardized methods at
time 0 (t0) and after 6 months (t6), when BIB was removed.
IR was calculated by the homeostasis model assessment
(HOMA-IR), as fasting serum insulin (μU/ml)×fasting plas-
ma glucose (mmol/l)/22.5; values >2.5 indicate a state of IR
[12]. The presence of FL was demonstrated by abdominal
US, as “bright liver”[13] by two experienced investigators.
Statistical Analysis
Statistical analyses were performed with SPSS 15.0
software (SPSS, Chicago, IL, USA). For comparisons, both
parametric (T Student) and nonparametric (Wilcoxon) tests
were used for values normally or not-normally distributed.
Statistical significance was defined as p<0.05.
Results
Ten patients met exclusion criteria. Ninety-three patients
were eligible for the retrospective study. BMI decreased
significantly after BIB in all patients (42.1 ±5.8 vs 37.8±
5.5; p<0.001). The BMI decrease was higher than 10%
HOMA-IR
ALT U/L
GGT U/L
HOMA-IR
ALT U/L
GGT U/L
**
***
**
*
t0t6
t6t0
FL non-FL
Fig. 2 Box representation of
Homa-IR, ALT, and GGT in FL
and non-FL patients; before (t0)
and after (t6) 6 months of BIB
insertion, with decrease of BMI
≥10% (dashed box) or <10%.
Significance: Single asterisk,
p<0.05; double asterisks,p<0.01;
triple asterisks,p<0.001
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pre-BIB value (ΔBMI≥10%) in 59% of the patients.
Before BIB placement, “bright liver”echo pattern at US
investigation, consistent with FL (FL group), was observed
in 70%; impaired fasting blood glucose (≥125 mg/dL;
≥6.9 mmol/L) was observed in 13%; ALT exceeded normal
limits (40 U/L) in 30.1%; GGT exceeded normal limits
(50 U/L) in 15%; and HOMA-IR was >2.5 in 85% of
patients. The values of hypertrigliceridemia (≥150 mg/dL)
present in 33.3%, HDL cholesterol levels ≤40 mg/dL in
32%, and arterial hypertension in 22.2% did not signifi-
cantly change after 6 months of BIB placement. HOMA-IR,
ALT, and GGT values (not normally distributed) in obese
patients with FL or without FL (non-FL) at US investiga-
tion are expressed in Table 1and by box plot representation
as medians and interquartile ranges (Fig. 1).
Tab le 1shows medians and ranges of investigated
values. Median HOMA-IR decreased significantly in the
FL (4.71 vs 3.10; p<0.05) and non-FL (3.72 vs 2.81;
p<0.01) groups of obese patients after 6 months of BIB
placement. Median ALT decreased significantly in the FL
group (31.5 vs 24; p<0.001) and GGT significantly
decreased in the FL group (31 vs 23.5; p<0.05). By means
of box plot representation, Fig. 2shows the changes
between the groups with distinction of FL or non-FL and
ΔBMI≥10% or <10%. In the FL group with ΔBMI≥
10%, median values of HOMA-IR (4.95 vs 2.69; p<0.05),
ALT (30 vs 23; p<0.01), and GGT (28 vs 20; p<0.001)
significantly decreased after BIB. In the non-FL group with
ΔBMI≥10%, HOMA-IR values significantly decreased
(4.07 vs 2.36; p<0.01); ALT and GGT did not significantly
decrease.
Discussion
In obese and severely obese subjects, liver fat accumulation
commonly occurs, increasing the risk of hepatic disease
progression from NAFLD to cirrhosis [1–5]. In such
patients, especially when other comorbidities are also
present, weight loss is strongly recommended. However,
diet restrictions often fail to induce a sustained body weight
reduction. In subjects with BMI higher than 35, or 30 with
comorbidities, bariatric therapy is widely applied to obtain
weight loss [10,11].
Temporary intragastric balloon placement is considered a
safe procedure for those obese patients who do not meet the
requirements for a prompt surgical approach [14,15]. In
our study, we confirmed that BIB could induce a significant
BMI reduction in all patients. More than half of the patients
showed an appreciable BMI decrease ≥10%. Nevertheless,
US investigation showed “bright liver,”consistent with FL,
in the majority of our patients (70%). In addition, IR was
demonstrated by HOMA index >2.5 in 85% of all cases.
After BIB, HOMA-IR was significantly reduced in all
patients, and the decrease was independent of the presence
or absence of FL at US. Basal (t0) ALT and GGT values
were higher than normal in less than one third of all
patients. The patients with a decrease of BMI ≥10%
showed an improvement of insulin impairment by a
significant decrease of HOMA-IR in both the FL and
non-FL groups. Only in FL patients, the improvement of
liver dysfunction was shown by a significant decrease of
both enzymes only with a reduction of BMI ≥10% (Fig. 2).
As previously reported, enzyme levels, even within the
upper half of the normal range, may predict the early stages
of FL disease in obesity [6–8]. After 6 months of BIB
placement, we observed a significant decrease of both
enzymes. In accordance with other studies [16,17], we
confirm that weight loss may reduce the risk of liver injury
progression by normalizing the liver enzymes with lowered
spread of values from medians (Fig. 1). ALT values better
than GGT showed this behavior after BIB. It has been
reported that ALT is the biomarker of liver dysfunction,
more sensitive than other liver enzymes [4–6]. On the basis
of our data, it could be suggested that a high BMI generally
induced IR, as demonstrated by high HOMA values in the
majority of obese patients. Visceral adiposity, namely, FL,
throughout insulin sensitivity impairment, worsens hepatic
function in which ALT should be considered a reliable
biomarker. ALT elevations, even in the upper half of the
normal range, must be monitored in obesity because they
predict the liver disease progression [6–8]. Weight loss is
strongly recommended to reduce liver injury due to visceral
adiposity, as well as to reduce the impairment of insulin
sensitivity [17,18]. Such an end-point would be better
achieved in those patients with BMI decrease ≥10%. In this
way, even temporary bariatric treatment by means of BIB,
associated with diet restriction, may provide a sustained
benefit on liver function and on insulin sensitivity.
References
1. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty
liver, steatohepatitis, and metabolic syndrome. Hepatology.
2003;37:917–23.
2. Bugianesi E, McCullogh AJ, Marchesini G. Insulin resistance: a
metabolic pathway to chronic liver disease. Hepatology.
2005;42:987–1000.
3. Utzschneider KM, Kahn SE. The role of insulin resistance in
nonalcoholic fatty liver disease. J Clin Endocrinol Metab.
2006;91:4753–61.
4. Wallace TM, Utzschneider KM, Tong J, et al. Relationship of liver
enzymes to insulin sensitivity and intra-abdominal fat. Diabetes
Care. 2007;30:2673–8.
5. Hui JM, Hodge, A, Farrell GC, et al. Beyond insulin resistance in
NASH: TNF-αor adiponectin? Hepatology. 2004;40:46–54.
6. Marchesini G, Avagnina S, Barantani EG, et al. Aminotrasferase and
gamma-glutamyltranspeptidase levels in obesity are associated
OBES SURG
with insulin resistance and the metabolic syndrome. J Endocrinol
Invest. 2005;28:333–9.
7. Burgert TS, Taksaly SE, Dziura J, et al. Alanine aminotransferase
levels and fatty liver in childhood obesity: associations with
insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol
Metab. 2006;91:4287–94.
8. Chang Y, Ryu S, Sung E, et al. Higher concentrations of alanine
aminotrasferase within the reference interval predict nonalcoholic
fatty liver disease. Clin Chem. 2007;53:686–92.
9. Bellentani S, Delle Grave R, Suppini A, Marchesini G, and the
Fatty Liver Italian Network (FLIN). Behavior therapy for
nonalcoholic fatty liver disease: the need for a multidisciplinary
approach. Hepatology. 2008;47:746–54.
10. Wolf AM, Beisiegel U. The effect of loss of excess weight on the
metabolic risk factors after bariatric surgery in morbidly and
super-obese patients. Obes Surg. 2007;17:910–9.
11. Mathus-Vligen EM, Tytgat GN. Intragastric balloon for treatment-
resistant obesity: safety, tolerance and efficacy of 1-year balloon
treatment followed by 1-year balloon-free follow-up. Gastrointest
Endosc. 2005;61:19–27.
12. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model
assessment: insulin resistance and beta-cell function from plasma
fasting glucose and insulin concentrations in man. Diabetologia.
1985;28:412–9.
13. Palmentieri B, de Sio I, La Mura V, et al. The role of bright liver
echo pattern on ultrasound B-mode examination in the diagnosis
of liver steatosis. Dig Liver Dis. 2006;38:485–9.
14. Genco A, Cipriano M, Bacci V, et al. Bioenterics® Intragastric
Ballon (BIB®): a short-term double-bind, randomised, controlled,
crossover study on weight reduction in morbidly obese patients.
Int J Obes. 2006;30:129–33.
15. Rossi A, Bersani G, Ricci G, Petrini C, De Fabritiis G, Alvisi V.
Intrgastric balloon insertion increases the frequency of erosive
esophagitis in obese patients. Obes Surg. 2007;17:1346–9.
16. Hickam IJ, Johnsson JR, Prins JB, et al. Modest weight loss and
physical activity in overweight patients with chronic liver disease
results in sustained improvements in alanine aminostransferase,
fasting insulin, and quality of life. Gut. 2004;53:413–9.
17. Al-Momen A, El-Mogy I. Intragastric balloon for obesity: a retro-
spective evaluation of tolerance and efficacy. Obes Surg. 2005;15:101–5
18. Dixon JB, Bhathal PS, O’Brien PE. Weight loss and non-alcoholic
fatty liver disease: falls in gamma-glutamyl trasferase concen-
trations are associated with histologic improvement. Obes Surg.
2006;16:1278–86.
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