From the AGA Journals

Bariatric surgery achieved long-term resolution of NASH without worsening fibrosis

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Bariatric surgery also mitigates the cardiovascular risk in NASH

As obesity prevalence increases at an alarming pace, nonalcoholic steatohepatitis (NASH) has become the most common indication for liver transplantation in women and the second most common in men in the United States. Impeding the inflammation and reversing the resultant fibrosis prior to the development of end-stage liver disease and needing liver transplantation are essential goals in NASH management. The lack of Food and Drug Administration–approved pharmacotherapy triggered interest in the effect of weight loss on NASH and short-term benefits were noted.

In this article, Lassailly et al. demonstrated long-term benefits of bariatric surgery in patients with NASH. They prospectively enrolled 180 patients and histologically followed 64 patients at 1 year and 5 years postoperatively. NASH resolved in 84% of patients and fibrosis regressed in >70%. Importantly, advanced fibrosis (F3) regressed in 15/19 patients. Cirrhosis regressed to F3 in two-thirds of patients. No liver-related mortality or decompensation was observed.

These favorable outcomes embolden the practice of referring NASH patients with morbid obesity to bariatric surgery before liver disease severity becomes prohibitive of this approach. NASH pharmacotherapy may become available in the future. However, we must not forget that cardiovascular disease remains a common cause of morbidity and mortality in NASH patients.

With these study findings and previously established benefits of bariatric surgery on mitigating cardiovascular risk and treating relevant metabolic derangements (e.g., diabetes mellitus), pursuing bariatric surgery in NASH patients may be the seed that, if planted early on, can later flourish with resolution of NASH, prevention of cardiovascular disease, metabolic optimization, and potentially longer and healthier life.

Manhal J. Izzy, MD, is assistant professor of medicine, Vanderbilt Digestive Disease Center, Vanderbilt University, Nashville, Tenn.



Bariatric surgery resolved nonalcoholic steatohepatitis (NASH) without worsening fibrosis in 84% of patients with evaluable biopsies, according to the findings of a prospective study.

The study included 180 severely or morbidly obese adults (body mass index >35 kg/m2) with NASH who underwent bariatric surgery at a center in France. Among 94 patients evaluated 5 years later, 68% had follow-up liver biopsies, of whom 84% (95% confidence interval, 73.1%-92.2%) met the primary endpoint of resolution of NASH without worsening of fibrosis. All histologic aspects of NASH had improved, median nonalcoholic fatty liver disease scores (NAS) fell from 5 (interquartile range, 4 to 5) to 1 (IQR, 0-2; P < .001), and 90% of patients achieved at least a 2-point NAS improvement. Hepatocellular ballooning also improved in 87.5% of patients. Baseline severity of NASH did not affect the chances of it resolving at 5 years. “The reduction of fibrosis [was] progressive, beginning during the first year and continuing through 5 years,” Guillaume Lassailly, MD, and associates wrote in Gastroenterology.

NASH is a priority for clinical research because of the substantial risk for subsequent cirrhosis, added Dr. Lassailly of CHU Lille (France). For NASH to resolve, most patients need to lose at least 7%-10% of their body weight, but “only 10% of patients reach this objective with lifestyle therapy at 1 year, and less than half maintain the weight loss 5 years later.” Despite ongoing drug development efforts, no medications have been approved for treating NASH. Although weight loss after bariatric surgery has been reported to resolve NASH in approximately 80% of patients at 1 year, longer-term data have been unavailable, and it has remained unclear whether bariatric surgery can slow or halt fibrosis progression.

All patients in this study had biopsy-confirmed NASH and at least a 5-year history of severe or morbid obesity as well as at least one comorbidity, such as diabetes mellitus or arterial hypertension. Patients were not heavy drinkers, and none had detectable markers of chronic liver disease.

Bariatric surgery produced a median 12-kg/m2 drop in body mass index. At 5-year follow-up, 93% of patients meeting or exceeding this threshold who had biopsies performed showed resolution of NASH without worsening of fibrosis. Furthermore, 56% of patients (95% CI, 42.4%-69.3%) had no histologic evidence of fibrosis, including 45.5% of patients who had bridging fibrosis at baseline.

Participants in this study received intensive preoperative support, including evaluations by numerous specialists, a nutrition plan, and a 6- to 12-month therapeutic education program. Bariatric surgery techniques included Roux-en-Y gastric bypass, gastric banding, and sleeve gastrectomy. A subgroup analysis linked gastric bypass to a significantly higher probability of meeting the primary endpoint, compared with gastric banding. Refusal was the most common reason for not having a follow-up biopsy, the researchers said. “Patients without liver biopsy after bariatric surgery were not significantly different from those with a histological follow-up except for a lower BMI at 1 year. Baseline fibrosis did not influence the probability of undergoing histological reevaluation at 5 years.”

Two study participants died from surgical complications within 1 month after surgery, and one patient died from cardiac dysfunction 4 years later. No fatality was deemed liver related.

The study was funded by the French Ministry of Health, Conseil Régional Nord-Pas de Calais, National de la Recherche, and the European commission (FEDER). The researchers reported having no conflicts of interest.

SOURCE: Lassailly G et al. Gastroenterology. 2020 Jun 15. doi: 10.1053/j.gastro.2020.06.006.

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