Treating NAFLD by Defeating Obesity: What Are the Best Options?

Vicki M. Shah, PA-C, DMSc, MMS; Nancy S. Reau, MD


January 21, 2022

Nonalcoholic fatty liver disease (NAFLD) — the hepatic manifestation of metabolic syndrome — is an increasingly common cause of transplantation, hepatocellular carcinoma, and death. Prevalence rates for NAFLD vary, but a recent analysis of middle-aged individuals in the United States placed it at nearly 40%. The same study estimated that the rate of nonalcoholic steatohepatitis (NASH) in this population was 14%. If changes are not implemented, the incidence of NASH is projected to increase up to 56% in the next 10 years.

Obesity is the most common and well-documented risk factor for NAFLD, and as such, the best target for successfully treating it. This requires clinicians to recommend various weight loss interventions, each with varying evidence of success, and implement them before fatty liver disease has taken its toll on the patient's health.

Lifestyle Interventions and Implementation

Several studies have sought to determine whether diet and lifestyle interventions are beneficial in those with type 2 diabetes. Perhaps the most recognizable among these is the Look AHEAD Trial, which reported that significant and long-term improvements in body weight, physical fitness and function, glucose control, quality of life, and healthcare costs were associated with intensive lifestyle intervention. There is a lack of consensus, though, on how aggressively interventions should be escalated, which can result in the delay of weight loss management.


Nutrition is not a one-size-fits-all proposition. The Mediterranean diet is the most extensively studied to date, with reliable research supporting its use for improving quality of life and lowering disease risk. In the Lyon Diet Heart Study, participants who were following a Mediterranean-type diet for 46 months had 50%-70% lower risk for recurrent heart disease.

The Mediterranean diet includes vegetables, beans, nuts, whole grains, seeds, olive oil, and fresh fruits. Cheese and yogurtare the main dairy foods. The diet also includes moderate amounts of fish, poultry, and eggs, with small amounts of red meat and low to moderate amounts of wine. Up to one third of the Mediterranean diet consists of fat, with saturated fats not exceeding 8% of calorie intake.

It is recommended that food preferences, eating behaviors, and meal patterns are tailored to the individual on the basis of cultural background, which can make nutritional counseling difficult to conduct during a routine appointment. Patient success can be limited by time constraints, food availability, nutritional knowledge, and cooking skills.

At their most basic, dietary recommendations call for limiting highly processed foods of minimal nutritional value and energy-dense beverages, choosing complex carbohydrates over simple sugars, and increasing high-fiber foods. The quality of calories becomes more important than reducing the quantity of calories. Unfortunately, data indicate that 2 years after completing a dietary program, individuals with high and low adherence will regain 50% and 99% of weight loss, respectively, regardless of diet macronutrient breakdown.

Physical Activity

The effect of dietary modification is more significant when combined with exercise. Even without diet modification, regular exercise is associated with significant health benefits in those with NAFLD. The American Heart Association recommends at least 150 minutes/week of moderate physical activity or at least 75 minutes/week of vigorous intensity aerobic exercise for health benefits, modest weight loss, and weight gain prevention. For more-robust weight loss and to prevent weight regain after weight loss, it is recommended to complete greater than 300 minutes/week of moderate physical activity or 150 minutes/week of vigorous intensity aerobic exercise.

Recommended exercises include anaerobic strength training using free weights, machines, and resistance bands to increase muscle composition. Leisure time physical activity and transportational or occupational nonexercise activity should be considered as part of physical activity. Conversely, physical activity can be limited by restricted mobility, limited gym access, unsafe outside environments, and failure of previous efforts. The mean adherence rate for prescribed exercise interventions is reported to be between 50% and 66%.

Behavioral Modification

The biological forces that resist weight loss are strong, whereas those that resist weight gain are relatively weak. These forces manifest as hunger before meals, lack of satiety after meals, and eating to facilitate sleep. The urge to eat can be stimulated by various forms of social modeling and prompted by the senses (seeing a juicy cheeseburger, smelling freshly baked cookies, hearing a candy wrapper opening).

Background issues can contribute by ritually eating at the same time without being hungry, being pushed for "clean plate syndrome" as a child, and lacking knowledge about healthy options.

Mental stress, emotional eating, and pleasure eating can also cause overeating.

All of these behaviors can be changed with motivational interviewing or formal psychological care; however, access might be limited for these services.

Weight Loss Medications

Providers should consider pharmacotherapy when diet, exercise, and behavior modification do not produce sufficient weight loss. Medication can facilitate management of eating behavior and slow progression of weight gain or regain.

The choice of medication should be tailored to the patient with consideration of comorbid conditions and drug-drug interactions. Unfortunately, the development and insurance coverage of weight loss medications have been slower than the obesity crisis.

It is also important to counsel patients on how weight medications are most effective when combined with other interventions.

Bariatric Surgery

Surgical weight intervention is generally the last stop after all other alternatives have failed. Over the last two decades, bariatric surgery has evolved with laparoscopic and endoscopic techniques, improved perioperative outcomes, better patient selection, and sustained long-term weight loss success.

As of 2016, the most-common bariatric surgeries in the United States are laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy. Newer endoscopic options include gastroplasty, intragastric balloon, malabsorptive bariatric procedure, and gastric electrical stimulation for the modulation of gastric emptying. When compared with laparoscopic surgeries, the endoluminal interventions have been shown to be safer and more cost-effective but result in less weight loss.

Prior to consultation, patients must meet multiple criteria for bariatric surgery, including a low mortality risk for surgical intervention, pathogenic body fat, previous attempts to reduce body weight, and a commitment to improved health with consistent follow-up.

Bariatric surgery has been shown to achieve long-term weight loss and improvement of metabolic syndrome comorbidities. In patients with NAFLD, it can improve aminotransferase levels and histologic fibrosis. Patients with NASH who had bariatric surgery and have achieved weight loss of 10% or more had a higher rate of fibrosis regression on liver biopsies.

NASH Cirrhosis: The Highest-Risk Group

The obesity rate for patients with cirrhosis is equivalent to the general population, at approximately 30%. Surgical interventions are often deferred until after the disease has progressed to end-stage. The concerns of higher risk for mortality and decompensation arise when weighing the option of bariatric surgery for patient with cirrhosis.

The American Gastroenterology Association recommends bariatric surgery for patients with compensated cirrhosis who are obese when lifestyle interventions have failed for weight loss. This population, however, does require additional considerations, including having an experienced bariatric surgeon and medical team, completing preoperative portal hypertension assessment, and reviewing liver transplant candidacy.

Bariatric surgery in compensated cirrhosis has a mortality risk of 0.9%, which is slightly higher than the 0.3% risk for patients without cirrhosis; for decompensated cirrhosis, the mortality risk is significantly higher at 16.3%. Therefore, the only option for bariatric surgery in this population is with or after liver transplant.

The Single Most Important Lifelong Intervention

The recognition of obesity as a disease — and not an individual's failure — allows healthcare professionals to provide evidence-based treatments of nutritional interventions, behavioral modifications, pharmacologic therapy, and possible surgery.

Most patients do not have the adequate tools to be successful at weight loss. Frequently, they are simply told by medical providers to lose weight without the knowledge or support to implement lifestyle changes. Achieving even 10% weight loss helps with hypertension, insulin resistance, hyperlipidemia, obstructive sleep apnea, fatty liver disease, and mood, signaling it as the single most important lifelong intervention for improving health in the United States.

Given that bariatric surgery provides the most durable weight loss option, this might be a more appropriate treatment option at a time point before end-stage complications arise secondary to obesity.

Vicki Shah PA-C, DMSc, MMS, is the solid organ transplant lead advanced practice provider at Rush University Medical Center in Chicago. She has an obesity medicine certificate from the Obesity Medicine Association, as well as a successful weight intervention clinic in liver disease. She is a national speaker for continuing medical educational conferences with the Chronic Liver Disease Foundation. She serves on the editorial board for Clinical Liver Disease, a multimedia review journal, as well as educational chair for the AASLD Associates special interest group and member for AASLD NASH special interest group. She continues to have an active role in the American Liver Foundation as a Great Lakes board member and Medical Advisory Committee member.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently, as a member of, a web-based resource from the AASLD and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.

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