Complex Questions Surround Potential of Weight Loss Procedures to Reverse NAFLD

Evidence shows that weight loss achieved through bariatric and endoscopic surgery can help treat and reverse nonalcoholic fatty liver disease (NAFLD), but optimal procedure selection and timing vary by patient factors, according to speakers at Digestive Disease Week 2022.

John Morton, MD, MPH, of Yale University School of Medicine, began the session by characterizing NAFLD as a disease that needs more prominence and more treatment tools at clinicians’ disposal. Mortality from NAFLD is increasing, and specialty societies recognize the potential for weight loss surgery to alleviate NAFLD and prevent progression to nonalcoholic steatohepatitis (NASH) and liver fibrosis. Indeed, a meta-analysis found that bariatric surgery resolves steatosis 91.6% of the time, but resolution rates post surgery are only 81.3% for steatohepatitis and 65.5% for fibrosis.

Clearly, improvement is “very much related to the stage of disease, so what does it call for? Earlier intervention,” said Morton.

However, he noted that certain types of bariatric surgery can change alcohol metabolism in that patients become legally intoxicated from the same amount of alcohol that had less of an effect prior to surgery, so clinicians must advise patients to be cautious with their alcohol intake after gastric bypass. For a patient who has both NASH and issues with alcohol use, a gastric sleeve may be a better option. Surgeons can avail themselves of online risk-benefit calculators that allow them to input patient characteristics and compare the various procedures.

Overall, however, bariatric surgeries are a safe and effective option, and data demonstrate their positive impact on the liver function levels that are a marker of NAFLD, Morton said.

Violeta Popov, MD, PhD, of NYU Langone Health, noted that that weight loss is the only therapy recommended by guidelines to treat NAFLD, as there are currently no approved medications for it. Her presentation focused on research surrounding the effectiveness of endoscopic therapies to induce weight loss and improve liver outcomes, as well as the advantages and drawbacks of each procedure. For instance, intragastric balloons filled with fluid or gas result in improvements in metabolic outcomes and liver enzymes, but this procedure is often not covered by insurance. She also highlighted some exciting potential endoscopic bariatric therapies currently under investigation, such as duodenal-jejunal bypass sleeves, and advised the audience to keep their eyes out for the potential approval of new and more effective medications for weight loss.

Beyond selecting the right procedure, a key to successful endoscopic surgery is to select the right patients, not just in terms of their clinical criteria but also their social support and preparation, Popov said. In her clinic, the most important predictor of long-term success is patient adherence to follow-up visits with a multidisciplinary team including the patient’s bariatric surgeon, endoscopist, dietician, hepatologist, psychologist, and primary care provider. The multispecialty team’s ability to provide a continuum of care is essential because “obesity and NAFLD are chronic diseases, and it’s unlikely that one intervention will have long-lasting impact.”

Next, Julie Heimbach, MD, of the Mayo Clinic, discussed selecting the right timing of weight loss surgery—specifically, whether it should be performed before or after liver transplant in patients with NASH. There are limited data available to help answer this question, she said, but in some situations, a simultaneous approach is warranted.

Her research shows that combined liver transplant and gastric sleeve resection for patients with end-stage liver disease is an effective option that results in weight loss maintained over the long term. A follow-up study in these patients found that all 29 patients who received a combined liver transplant and gastric sleeve maintained at least 10% body weight loss 3 years later, compared with just 29.4% of a 36-patient cohort who received only the liver transplant.¹

Determining when to perform surgery depends on the patient, but the why to do so is also important, Heimbach explained. She presented a case study of her patient who was referred to hospice due to his decompensated cirrhosis but is now clinically stable and has maintained a significant decrease in body mass index after undergoing the combined surgery. She relayed his statement, “One day I am dying, the next week I am not. That just doesn’t happen,” drawing impressed murmurs from the crowd.

Finally, Pichamol Jirapinyo, MD, MPH, of Brigham and Women’s hospital, presented results from her abstract on the outcomes of an endoscopic gastric plication procedure—called primary obesity surgery endoluminal, or POSE—in patients with NAFLD and fibrosis.² At 6 to 12 months after the procedure, 68% of patients experienced regression of fibrosis by at least 1 stage, and 96% experienced no worsening in fibrosis stage. Secondary outcomes such as insulin resistance, glycated hemoglobin, and alanine aminotransferase levels also improved significantly.

In response to a question from Popov about outcomes among patients with advanced fibrosis, Jirapinyo noted that her research team empathizes with such patients because they have few treatment options available to them. There is a higher adverse event rate among this group, but she advocated for further study to help weigh the risks and benefits of the procedure.

“Otherwise, they have no option; otherwise, you’re waiting for them to [develop] decompensated cirrhosis,” Jirapinyo explained. “But by offering these procedures, they can lose 15% of their weight, and we’re showing that fibrosis regressed.”

References

1. Zamora-Valdes D, Watt KD, Kellogg TA, et al. Long-term outcomes of patients undergoing simultaneous liver transplantation and sleeve gastrectomy. Hepatology. 2018;68(2):485-495. doi:10.1002/hep.29848

2. Jirapinyo P, Zucker SD, Thompson CC. The effect of endoscopic gastric plication on liver fibrosis in patients with nonalcoholic steatohepatitis. Presented at: Digestive Disease Week 2022; May 21-24, 2022; San Diego, CA. Presentation 431.