BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.
Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.
“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.
The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.
Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).
While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.
Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.
During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.
“This is wonderful data that shows surgery is very effective,” one attendee said.
“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”
The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.
*This story was updated on November 15, 2019.
SOURCE: Pais R et al. The Liver Meeting 2019,