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Bariatric surgery in NAFLD and obesity slashes liver and cardiovascular risk

In non-alcoholic fatty liver disease (NAFLD) and obesity, bariatric surgery cut by 90% the risk of advanced liver disease, liver cancer or related death, found a JAMA study. Cardiovascular disease risk was cut by 70%. However, surgical risk was high.

One out of every four American adults has fatty liver disease caused by obesity, not drinking, and there is no medical treatment for it. The only way to keep it in check is to lose weight and eat a healthier diet, reports The New York Times. However, bariatric surgery opens new possibilities.

It writes that the findings of the study in JAMA were striking: of a group of more than 1,100 patients with an aggressive form of fatty liver disease, those who had weight-loss surgery cut their risk of advanced liver disease, liver cancer or related death by almost 90% over the next decade.

Only five of the 650 patients who had bariatric surgery later developed one of those severe liver outcomes, compared with 40 of 508 patients who did not have the procedure. The weight-loss surgery patients were also at significantly lower risk for cardiovascular disease, a finding consistent with earlier research. They were 70% less likely to experience a cardiac event, stroke or heart failure, or to die of heart disease.

Dr Ali Aminian, director of the Cleveland Clinic’s Bariatric and Metabolic Institute and the study’s lead author, said that in all likelihood, weight loss had stopped the disease in its tracks.

“Obesity is the main driver of the fatty liver — it all starts with obesity,” he said. “When we have excess fat that accumulates in the liver, it causes fatty liver; then inflammation comes and gets worse and then scar tissue forms and leads to cirrhosis.

“When a patient loses weight, fat goes away from everywhere, including the liver; inflammation subsides, and some of the scar tissue can reverse and get better. Weight loss is definitely the main factor here.”

Dr Steven Nissen, chief academic officer of the Heart and Vascular Institute at the Cleveland Clinic and the study’s senior author, called the results remarkable. The post-surgical disease result “was the lowest I’ve seen in 30 years of doing studies, an 88% reduction in progression to advanced liver disease,” he said.

The observational study reviewing cases at the Cleveland Clinic over 12 years did not establish a causal link to lower risks of severe liver or heart conditions from weight-loss procedures, but the findings add to mounting evidence that bariatric surgery can provide health benefits beyond weight loss. About 100 million American adults are dangerously obese; around 250,000 undergo bariatric operations each year.

The surgery carries serious risks, however. Sixty-two of the 650 weight-loss surgery patients in the study group developed serious complications after the operation, and four died within a year of having the operation. The most commonly performed procedure is called a sleeve gastrectomy. Only one-fifth of the patients studied in this report had that procedure. Most of them had Roux-en-Y gastric bypass surgery.

The New York Times report adds that more than 40% of American adults struggle with obesity. About 75% have non-alcoholic fatty liver disease, often a silent condition with no obvious symptoms. But one in four or five develop non-alcoholic steatohepatitis, or NASH, which causes fibrosis of the liver, and one in five of those individuals will develop cirrhosis, or scarring of the liver, for which the only cure is a liver transplant.

There are no approved drugs or therapies available for non-alcoholic fatty liver disease. Doctors generally advise patients to lose weight and to switch to a healthier diet in an effort to reduce fat, inflammation and fibrosis in the liver, a vital organ that turns food and drink into nutrients and filters harmful substances from the blood.

After bariatric surgery, obese patients usually lose up to 25% of their body weight, much more than patients who diet to lose weight. After the surgery, they often require less medication to keep conditions like Type 2 diabetes, high blood pressure and high cholesterol under control.

This latest research was a retrospective observational study comparing the long-term outcomes of 650 bariatric surgery patients with 508 closely matched patients who did not have surgery. So it was not a randomiaed controlled trial of the kind considered the gold standard in medicine, which randomly assigns patients with similar characteristics to either an intervention arm or a placebo.

The study reviewed Cleveland Clinic cases of 1,158 obese patients whose liver biopsies from 2004 to 2016 showed they had advanced non-alcoholic fatty liver disease with fibrosis. Women represented more than 60% of the patients; the average age was just under 50; and the median body mass index was 44, considered dangerously overweight. Heart disease was also reduced after weight-loss surgery, as earlier studies have shown: Some 8.5% of those who had bariatric surgery had a cardiac event, compared with 15.7% who did not have surgery.

Study details

Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis

Ali Aminian, Abbas AlKurd, Rickesha Wilson, James Bena, Hana Fayazzadeh, Tavankit Singh, Vance Albaugh, Faiz Shariff, Noe Rodriguez, Jian Jin, Stacy Brethauer, Srinivasan Dasarathy, Naim Alkhouri, Philip Schauer, Arthur McCullough, Steven Nissen,

Published in JAMA on 11 November 2021.

Key Points
Question
Is there an association between bariatric surgery and major adverse liver outcomes or major adverse cardiovascular events in patients with nonalcoholic steatohepatitis and obesity in long-term follow-up?

Findings
In this retrospective cohort study of 1158 patients (including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group) with biopsy-proven fibrotic nonalcoholic steatohepatitis without cirrhosis, bariatric surgery was significantly associated with a lower risk of major adverse liver outcomes (adjusted absolute 10-year risk difference of 12.4%) and major adverse cardiovascular events (adjusted absolute 10-year risk difference of 13.9%).

Meaning
Among patients with nonalcoholic steatohepatitis and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and major adverse cardiovascular events.

Abstract

Importance
No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH).

Objective
To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis.

Design, Setting, and Participants
In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021.

Exposures
Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care.

Main Outcomes and Measures
The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalised method in a multivariable-adjusted Cox regression analysis framework.

Results
A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE.

Among the patients analysed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2).

Conclusions and Relevance
Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

 

New York Times article – Bariatric Surgery May Lower Risk for Severe Liver Disease, New Study Finds (Restricted access)

 

JAMA article – Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis (Open access)

 

See more from MedicalBrief archives:

 

NASH has 50% higher death rate than NAFLD

 

NAFLD a growing health problem in people with HIV

 

Overweight substantially worsens liver-damaging effects of excessive alcohol use

 

Bariatric surgery link to reduced mortality risk in obese patients

 

Bariatric surgery significantly cuts cancer risk in severely obese NAFLD patients

 

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