Bariatric surgery provides ‘huge’ reduction in major adverse liver outcomes, CV events
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Adults with nonalcoholic steatohepatitis and obesity have a much lower risk for a major adverse liver outcome or major adverse cardiovascular event if they undergo bariatric surgery vs. nonsurgical treatment, according to study data.
In findings published in JAMA, a group of adults with NASH and obesity who underwent bariatric surgery had an 88% lower risk for major adverse liver outcomes and a 70% reduced risk for a major CV event compared with a matched control group, in addition to significantly greater reductions in body weight and HbA1c.
“There were dual benefits of weight loss,” Steven E. Nissen, MD, chief academic officer in the Heart and Vascular Institute at the Cleveland Clinic, told Healio. “The benefits were a huge reduction in progression of liver disease to cirrhosis, liver cancer or other bad outcomes, and a similarly large reduction in adverse CV outcomes. It’s very striking for a disease that is becoming increasingly common with the obesity epidemic.”
Nissen and colleagues analyzed data from 1,158 adults enrolled in the Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk (SPLENDOR) study (median age, 49.8 years; 63.9% women). All participants were aged 18 to 80 years with obesity, a histologic diagnosis of NASH and the presence of fibrosis on the baseline liver biopsy. Adults who underwent Roux-en-Y gastric bypass or sleeve gastrectomy were placed in the bariatric surgery group (n = 650), and the remaining participants were placed in the nonsurgical care control group (n = 508). Researchers collected incidences of major adverse liver outcomes and major adverse CV events. Adverse liver outcomes included any first occurrence of progression to clinical or histologic cirrhosis, development of hepatocellular carcinoma, liver transplantation or liver-related mortality. CV events included any first occurrence of coronary artery events, cerebrovascular events, heart failure or CV death. Change in body weight and HbA1c between the two groups were also compared.
Lower risk for liver, CV outcomes
In unweighted data, major adverse liver outcomes were observed in five participants in the bariatric surgery group and 40 in the control group. In overlap-weighed analysis, the bariatric surgery group had a cumulative incidence rate of major adverse liver outcomes of 2.3% at 10 years compared with 9.6% for the nonsurgical group. Those who underwent bariatric surgery has a significantly lower risk for major adverse liver outcomes compared with controls (adjusted HR = 0.12; 95% CI, 0.02-0.63; P = .01).
“The people who underwent bariatric surgery have an enormous reduction in their progression of liver disease toward cirrhosis,” Nissen said. “What’s unique about the study is everybody had biopsy-proven NASH; we didn’t use CT scans to look at fat. It was about what happened to the liver histologically.”
Major adverse CV events occurred in 39 people in the bariatric surgery group and 60 in the control group. The cumulative incidence rate for a major adverse CV event was 8.5% in those who underwent bariatric surgery and 15.7% in those who did not undergo surgery. The bariatric surgery group had a 70% lower risk for a major adverse CV event compared with the control group (aHR = 0.3; 95% CI, 0.12-0.72; P = .007).
In secondary analyses, the bariatric surgery group had a greater mean body weight loss compared with the nonsurgical group (22.4% vs. 4.6%; P < .001) and a 1.6% larger reduction in HbA1c (P < .001).
“I do think more people are going to undergo bariatric surgery who have fatty liver disease that’s advancing,” Nissen said. “We don’t want these people to go on to develop liver cancer and cirrhosis and this is a way to reverse it.”
Future implications
Nissen said it’s possible similar reductions in adverse liver or CV events may be observed drugs that provide reductions in body weight similar to bariatric surgery, such as tirzepatide (Eli Lilly). He said similar studies compar incidences of adverse liver and CV events in those taking weightloss drugs control groups are needed.
“It’s going to make it much more interesting to try and get these drugs on the market and to test them to see if a similar benefit can be produced pharmacologically,” Nissen said. “This will have a lot of implications for drug development, it will have a lot of implications for who gets bariatric surgery, and we need to increase people’s attention to fatty liver disease.”
For more information:
Steven E. Nissen, MD, can be reached at nissens@ccf.org.
Perspective
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The data presented by Aminian and colleagues is very impactful for the treatment of NAFLD and NASH in very overweight patients. The study examined major adverse liver outcomes in 1,158 adults with biopsy-proven NASH and examined outcomes following either a bariatric surgery intervention or medical therapy. Bariatric surgery resulted in reduced 10-year incidence of major adverse liver outcomes of 2.3% vs. 9.6 percent without surgery, for an adjusted absolute 10-year risk difference of 12.4%, and major adverse CV events for an adjusted absolute 10-year risk difference of 13.9%.
These data confirm the importance of major weight loss as a modality for the treatment of NAFLD/NASH and for the reduction of CVD- related to metabolic liver disease. Greater emphasis for screening and earlier detection of NAFLD is needed among clinical providers to initiate weight-loss efforts. Patients who do not meet the criteria for bariatric surgery, ie, BMI less than 35 kg/m2, may achieve benefit with diet/exercise, vitamin E and pharmacotherapy with GLP-1 agonists, pioglitazone. The use of statins for CV risk reduction is also indicated in patients with NAFLD.
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