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INTRODUCTION
As the leading cause of chronic liver disease worldwide, nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and even cirrhosis. 1 Because NAFLD is associated with cardiometabolic risk factors such as obesity, hypertension, hyperlipidemia, and diabetes, treatment of NAFLD entails lifestyle interventions targeting weight loss of 7%–10%, management of comorbidities, and pharmacological treatment for those with biopsy‐proven NASH and fibrosis. 2 Management of NAFLD is detailed in Table 1. Although neither NAFLD nor NASH is a specific indication for bariatric surgery, NAFLD comorbidities may prompt consideration for bariatric surgery in those with a body mass index (BMI) of 35 to 40 kg/m2 and can improve NAFLD/NASH. 2 , 3
TABLE 1.
Treatment of NAFLD and NASH
| Treatment | Indications |
|---|---|
| Lifestyle interventions targeting weight loss through moderate‐intensity exercise and a hypocaloric diet | NAFLD |
| Avoidance of alcohol | NAFLD |
| Management of cardiovascular disease and metabolic comorbidities | NAFLD |
| Pioglitazone | Biopsy‐proven NASH with and without diabetes |
| Vitamin E | Biopsy‐proven NASH without diabetes or cirrhosis |
| Bariatric surgery | Consider in patients with BMI 35–40 kg/m2 (Note: Not a specific treatment of NAFLD or NASH) |
Bariatric surgery is categorized as restrictive or a combination of restrictive and malabsorptive (see Figure 1). Studies on bariatric surgery in NAFLD consist of noncontrolled, nonrandomized, observational cohort studies and several systematic reviews and meta‐analyses. More than 95% of patients who undergo bariatric surgery have biopsy‐proven NAFLD at the time of surgery. 4 Bariatric surgery not only ameliorates or resolves comorbidities in most patients with NAFLD but also improves mortality from malignancy and cardiovascular disease. 2
FIGURE 1.
Types of bariatric surgery
STEATOSIS AND FIBROSIS OUTCOMES
A landmark study from France showed that bariatric surgery led to NASH resolution, without worsening fibrosis (at year 5 biopsy), in 84% of patients (95% confidence interval [CI]: 73.1%‐92.2%), and median NAFLD activity score decreased from 5 (interquartile range [IQR] 4‐5) to 1 (IQR 0‐2; p < 0.001). 5 Similarly, fibrosis decreased from baseline in 70.2% of patients (95% CI: 56.6%‐81.6%) and completely resolved in 56% of all patients (95% CI: 42.4%‐69.3%) and in 45.5% of patients who had bridging fibrosis at baseline. 5 After 5 years, median fibrosis score decreased from 1.5 (IQR 1‐3) at baseline to 0 (IQR 0‐1; p < 0.001). 5 Interestingly, NASH resolution was observed 1 year after bariatric surgery in 84% of patients, with no significant difference between years 1 and 5. 5 In contrast, fibrosis improvement was first seen at year 1 after surgery and continued to improve until year 5 (p < 0.001). 5
A recent meta‐analysis of 2374 patients from 21 studies (1 vertical banded gastroplasty, 2 sleeve gastrectomy, 3 adjustable gastric banding, 12 Roux‐en‐Y gastric bypass (RYGB), 3 multiple procedures) found that 88% of patients (95% CI: 0.80–0.94) had improvement in steatosis, 59% of patients (95% CI: 0.38–0.78) had improvement in steatohepatitis, and 30% of patients (95% CI: 0.21–0.41) had improvement or resolution in fibrosis. 4 Degree of steatosis or fibrosis improvement was not a primary or secondary outcome analyzed in this study. Improvement in steatosis, steatohepatitis, and fibrosis was higher in those who underwent wedge biopsy compared with needle core biopsy and RYGB compared with other procedures (see Table 2). 4 However, wedge biopsies need to be interpreted with caution because they may overestimate the amount of fibrosis in areas near Glisson's capsule. In addition to histological features, bariatric surgery improves biochemical tests in approximately 32% to 96% of patients. 4 Improvement is demonstrated in alanine aminotransferase (ALT) in 62% of patients (95% CI: 0.42–0.82), aspartate aminotransferase (AST) in 32% of patients (95% CI: 0.22–0.42), alkaline phosphatase (ALP) in 45% of patients (95% CI: 0.19–0.71), and gamma‐glutamyl transferase (GGT) in 96% of patients (95% CI: 0.52–1.41). 4 Degree of biochemical improvement varies depending on procedure type (see Table 2), but no procedure has been shown to be superior to another in improving biochemical tests. 4 This may be because of liver function tests acting as poor predictors of NAFLD severity. 6
TABLE 2.
Improvement in liver histology and biochemical testing based on biopsy or procedure type
| Liver histology | ||||
|---|---|---|---|---|
| Steatosis | Steatohepatitis | Fibrosis | ||
| Biopsy type | ||||
| Wedge biopsy | 92% | 83% | 47% | |
| Needle core biopsy | 86% | 47% | 26% | |
| Procedure type, % (95% CI) | ||||
| RYGB | 91% (0.82–0.97) | 60% (0.34–0.84) | 31% (0.17–0.46) | |
| LAGB | 75% (0.65–0.83) | 76% (0.66–0.84) | 47% (0.33–0.62) | |
| Pooled average of other procedure types | 88% (0.80–0.94) | 59% (0.38–0.78) | 30% (0.21–0.41) | |
| Biochemical Test | ||||
| ALT | AST | ALP | GGT | |
| Procedure type, % (95% CI) | ||||
| Roux‐en‐Y gastric bypass | 58% (0.22–0.94) | 34% (0.14–0.54) | 25% (0.12–0.38) | 89% (0.24–1.55) |
| LABG | 68% (0.55–0.81) | 32% (0.20–0.45) | 72% (0.09–1.35) | 34% (0.08–0.60) |
| Sleeve gastrectomy | 79% (0.60–0.97) | 32% (0.02–0.67) | N/A | Not enough information |
| Pooled average of other procedure types | 62% (0.42–0.82) | N/A | 45% (0.19–0.71) | N/A |
Note: The top of the table shows improvement in liver histology based on biopsy or procedure type. The bottom of the table shows improvement in biochemical tests based on procedure type. Findings are based on a 2019 systematic review and meta‐analysis of 2374 patients from 21 studies (1 vertical banded gastroplasty, 2 sleeve gastrectomy, 3 adjustable gastric banding, 12 RYGB, 3 multiple procedures). 4
SURVIVAL OUTCOMES
Bariatric surgery was also found to have fewer major adverse liver outcomes at 10 years (2.3%) compared with a nonsurgical group (9.6%) (p = 0.01). 7 Indeed, major adverse cardiac events (leading cause of death in NAFLD) were also less in the bariatric group at 10 years (8.5%) compared with the nonsurgical group (15.7%) (p = 0.007). 7
MECHANISMS OF NAFLD IMPROVEMENT THROUGH BARIATRIC SURGERY
Aside from sustained weight loss over the long term, bariatric surgery improves NAFLD through metabolic changes that occur early in the postprocedure period (see Figure 2). Proposed mechanisms of these metabolic changes include alterations in bile homeostasis, changes in gastrointestinal hormones, changes in eating habits, improvement of type 2 diabetes, and shifts in the gut microbiota. 8
FIGURE 2.
Proposed metabolic mechanisms for NAFLD improvement after bariatric surgery
Bariatric surgery may lead to increased delivery to bile acids to the terminal ileum, stimulating endocrine L cells to release incretins such as glucagon‐like peptide 1 (GLP‐1) and satiety gut hormones such as peptide YY (PYY). 9 Release of PYY and GLP‐1 then activates anorexigenic pathways and increases insulin production, release, and sensitivity, thereby ameliorating type 2 diabetes. 9
Alterations in anorexigenic gut hormones, bile acids, and postingestive dumping symptoms lead to lower brain‐hedonic responses to food stimuli on functional magnetic resonance imaging in obese patients who undergo RYGB. 10 Decreased activation of the brain reward systems is associated with reduced palatability of high‐fat and sweet food, lower consumption of dietary fat, and healthier eating habits. 10
Vertical sleeve gastrectomy and RYGB in animal models are associated with increased levels of serum bile acids, likely because of increased absorption and gut microbiome changes. 8 Bile acids, which bind to G protein–coupled BA receptor 1 (TGR5) and farnesoid‐X receptor receptors, have long been known to assist in energy homeostasis, cholesterol metabolism, and lipid digestion.
By modifying the digestive tract's anatomy, changing food transit times, and changing bile acid secretion and intraluminal pH, bariatric surgery impacts gut microbiome biodiversity, functionality, and derived metabolites. 11 For instance, compared with sleeve gastrectomy, RYGB has shown more pronounced increases in the phyla Proteobacteria and Bacteroidetes, the family Streptococcaceae, and the species Akkermansia muciniphila and Streptococcus salivarius and decreases in the phylum Firmicutes and the family Bifidobacteriaceae, which may influence metabolism and weight loss. 11
CONCLUSION
Although bariatric surgery is not recommended as a specific treatment for NAFLD in and of itself, bariatric surgery is associated with improvement in steatosis, steatohepatitis, fibrosis, and biochemical testing in a significant proportion of patients. Beyond sustained long‐term weight loss, bariatric surgery ameliorates NAFLD through stimulated secretion of incretins and satiety hormones, alterations in bile acid homeostasis, amelioration of type 2 diabetes, impact on the gut microbiome, and changes in eating habits. Further controlled, longitudinal studies are needed to draw firmer conclusions regarding bariatric surgery as a therapy for those with NASH and advanced fibrosis or cirrhosis.
CONFLICT OF INTEREST
M.N. has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novartis, Novo Nordisk, Allergan, Blade, EchoSens, Fractyl, Terns, OWL, Siemens, Roche Diagnostic, and Abbott; has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Shire, Viking, and Zydus; is a minor shareholder or has stocks in Anaetos and Viking. N.A. has been on the advisory board for Gilead and Allergan, and is on the speaker's bureau for Intercept and Gilead.
Truong E, Noureddin M. Improvement in nonalcoholic fatty liver disease through bariatric surgery. Clinical Liver Disease. 2022;20:13–17. 10.1002/cld.1229
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