A Promising New Development for the Millions of People with Liver Disease

Nearly four in 10 American adults are estimated to have a liver condition that can lead to serious complications and even death. Commonly known as fatty liver disease, the illness often goes undiagnosed until a patient has progressed to permanent scarring and damage to the liver, called cirrhosis.

Until recently, doctors could only hope to intervene by suggesting diet and lifestyle changes, or by helping patients manage related conditions like diabetes or high cholesterol. But those efforts often haven’t been enough. Now a promising new study shows that weight-loss surgery could reduce the chances of severe complications, even in some patients with cirrhosis.

In the study, published in Nature Medicine, researchers looked at data on patients with obesity and cirrhosis related to an advanced form of fatty liver disease called metabolic dysfunction-associated steatohepatitis, or MASH. Obesity is one of the major risk factors for MASH. At the 15-year mark, patients who had bariatric surgery were 72 percent less likely to have developed major complications like liver cancer than similar patients who didn’t have surgery.

The findings, together with emerging research on the benefits of weight-loss drugs, have given doctors new hope for addressing fatty liver disease.

MASH begins with fat buildup on the liver. In some patients, that leads to inflammation and liver fibrosis, or scarring. Research has shown that significant weight loss can reverse fibrosis and improve patients’ long-term outcomes. But research on cirrhosis was much more limited.

“Most people assume that cirrhosis is a death sentence,” said Dr. Rotonya Carr, who is the division head of gastroenterology at the University of Washington. But the emerging data suggest otherwise.

In the new study, researchers at the Cleveland Clinic went back through patient records and identified 168 adults who had obesity — defined as a body mass index of 30 or greater — and cirrhosis caused by MASH. (Cirrhosis can also be caused by long-term alcohol use and hepatitis.) The researchers included only patients who had “compensated” cirrhosis, meaning they had not developed major complications from it.

Among the patients who underwent surgery, 21 percent had at least one “major adverse liver outcome” by 15 years, compared with 46 percent of those who did not have surgery. These outcomes included fluid buildup, confusion caused by toxins in the brain, bleeding in esophageal veins and liver cancer.

Dr. Ali Aminian, director of the Cleveland Clinic’s Bariatric and Metabolic Institute and the lead author of the paper, said the research suggests that significant, sustained weight loss can prevent the downstream consequences of MASH even in some of the sickest patients.

“We have been trying to show, if we take care of obesity and if we help people lose weight, how can we change the trajectory of the disease?” Dr. Aminian said. The study was not funded by drug or device makers, but Dr. Aminian has previously consulted for weight-loss drugmaker Eli Lilly and for companies that make equipment used in bariatric surgery.

Dr. Vandana Khungar, an associate professor of medicine and associate medical director of liver transplant at the Yale University School of Medicine, noted that patients with cirrhosis are at higher risk of complications from surgery. But the results of this study were impressive, she said, in that they showed some patients could have “good safety outcomes and excellent liver outcomes” with surgery. Dr. Khungar was not involved in the study.

She cautioned that individual risk and access to a center with experience treating patients with cirrhosis should still determine whether surgery is a good option.

The study had several limitations. It relied on past patient data rather than patients randomized into treatment groups and followed over time. The sample size was relatively small and included mostly white patients. And although the investigators tried to account for factors that might skew the data, it’s possible that the patients in the two groups were different in some key way.

Still, experts expressed optimism about the study’s implications, particularly if weight loss from new medications proved to have a similar effect on cirrhosis.

In the last several months, a handful of preliminary trials of weight-loss drugs have shown that patients on the medications often see important features of MASH, including liver inflammation, resolve.

Early results from a Phase 3 study of semaglutide (known by the brand names Ozempic and Wegovy) presented at a medical conference in December showed striking effects: 63 percent of patients taking the drug saw their MASH resolve, compared with 34 percent of those taking the placebo. Patients on semaglutide were also more likely to see their fibrosis — which is categorized by Stages 0 to 4 — drop by at least one stage.

None of these trials studied the effects of weight-loss drugs on cirrhosis, which is considered Stage 4 fibrosis. But experts said they’re hopeful that better treatments for it — including, potentially, bariatric surgery — could be on the horizon.