The liver adventures of bariatric endoscopy

In the past few decades, endoscopy has overtaken many procedures that were routinely done surgically; the list is impressively long. With the advent of suturing devices, endoscopists are not only capable of closing defects, fixing stents, etc. but are also capable of suturing and remodeling organs such as the stomach. Bariatric endoscopy is a newborn that already runs by its own legs. The massive expansion of bariatric endoscopy is driven by need: today, one-third of the world’s population is overweight or obese and has associated nonalcoholic fatty liver disease (NAFLD) [1]. Bariatric surgery is very effective but invasive; thus, more and more patients and physicians are looking into less invasive treatments such as bariatric endoscopy, specialized diets, lifestyle coaching, and glucose-dependent insulinotropic polypeptide–glucagon-like peptide-1 (GLP-1) receptor agonists [2]. Bariatric endoscopy intended as gastric plication, or better, endoscopic sleeve gastroplasty (ESG), is becoming very attractive to patients; it is scarless, gives less pain, and is associated with fewer short- and long-term complications, and recovery is fast. However, procedures are less effective in patients with higher body mass index (BMI) and more effective in those with lower BMIs. ESG fits vast types of patients, for example, those in whom conservative medical interventions have failed but who are unfit for or decline bariatric surgery, and also pediatric and geriatric populations [3] [4] where surgery is unsuitable.

“As the paper by AlKhatry et al. demonstrates, promising strides have been made in the realm of gastric remodeling techniques such as primary obesity surgery endoluminal 2.0, which present a potential new wave of effective treatment modalities for metabolic dysfunction-associated steatotic liver disease.”

NAFLD is a complex, multifactorial disease caused by a sedentary lifestyle, obesity, poor dietary habits, intestinal flora, genetics, and other factors. The current global prevalence is 25 % and NAFLD is the leading cause of cirrhosis and hepatocellular carcinoma [1]. Typically, NAFLD is associated with numerous extrahepatic metabolic conditions, including type 2 diabetes mellitus, hypertension, overweight and obesity, cardiovascular disease, chronic kidney disease, and many other diseases. Of these, overweight and obesity are predominant in up to 60 % of patients with NAFLD [1]; thus, weight loss is critical. Moreover, in a prospective trial, lean NAFLD patients had lower NAFLD activity scores and controlled attenuation parameter (CAP) compared with obese NAFLD patients, and this was mainly attributed to lesser steatosis and a smaller proportion of ballooning [5].

The first-line treatment for NAFLD is lifestyle intervention, diet, and physical activity, but the main treatment currently is pharmaceutical. There are many different drugs that target different mechanisms of the disease from fat deposition to inflammation and fibrosis. However, weight loss remains the most important factor in obese NAFLD patients. Total body weight loss (%TBWL) of 10 % or more is associated with higher rates of NAFLD activity score reduction and CAP reduction, and even nonalcoholic steatohepatitis (NASH) resolution and fibrosis regression [6]. It is of note that age, sex, nutritional and genetic factors, and type 2 diabetes mellitus have a high impact on the effect of weight loss and NAFLD resolution. The rate of response to obesity treatments depends mostly on these factors. Interestingly, only 10 % of patients achieve enough %TBLW through lifestyle interventions alone, and this is unsatisfactory. Bariatric surgery is effective in improving NAFLD and its consequences but is not suitable for high-risk patients and those with lower BMIs. Gastric balloons have demonstrated improvements in obese patients with NAFLD in the short term, but more is needed. In this context comes ESG, which is not new in the treatment of NAFLD. In small nonrandomized studies, ESG has been shown to be effective in improving serum glucose, insulin resistance, liver histologic activity, transaminases, and imaging-based hepatic steatosis.

In this issue of Endoscopy, AlKhatry et al. report on a prospective, open-label clinical trial in which 42 NAFLD patients underwent either ESG with the primary obesity surgery endoluminal 2.0 (POSE 2.0) procedure and lifestyle modification or lifestyle modification alone [7]. At 12 months, CAP significantly improved in the intervention group, whereas liver stiffness did not. Nearly three-quarters of the patients who underwent the POSE 2.0 procedure achieved ≥ 10 % TBWL, which is the threshold of weight loss for NASH resolution and not only for NALFD. Even if the numbers in this trial are very small, and the follow-up is short, the work of AlKhatry et al. should be considered pioneering in this field, and some considerations are mandatory. First, NAFLD is a vast research topic, a high-burden disease that affects at least one-third of the population on the Earth, and extremely attractive to the drug industry that is investing billions in the discovery of new pharmaceutical treatments. Second, a Medline search for “NAFLD” produces approximately 35 K papers on the topic, with hundreds of patients and randomized trials, mainly with drugs. Third, NAFLD is a complex disease with various degrees of presentation, and the first critical step is selection of patients and treatments. As mentioned, endoscopy historically has overtaken many treatments from surgery but this time it is different. ESG here navigates in the same deep sea where the pharmaceutical industry shares the same interests. The good news is that ESG seems to be noncompetitive with current medical treatments of NAFLD.

Given that the global burden of liver disease is on the rise, a renewed focus on addressing the metabolic dysfunctions associated with fatty liver disorders is mandatory. The reclassification of this illness as metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for the development of efficacious, minimally invasive therapeutic approaches that could halt the progression to end-stage liver disease. As the paper by AlKhatry et al. demonstrates, promising strides have been made in the realm of gastric remodeling techniques such as POSE 2.0, presenting a potential new wave of effective treatment modalities for MASLD. This advancement heralds a burgeoning era in the landscape of therapeutic options, with a combination of endoscopic techniques focused on the stomach and small intestines, and pharmacological interventions based on gut peptides, such as GLP-1 agonists. The key to addressing MASLD might indeed lie in the gut, paving the way for an optimistic future for metabolic endoscopy and the role of comprehensive gastrointestinal strategies in potentially revolutionizing therapeutic approaches for metabolic dysfunction-associated liver conditions. In the meantime, the first steps in the liver adventures of ESG are done!

Publication History

Article published online:
12 September 2023

• References

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