Nonpharmacological interventions
Lifestyle modification
Lifestyle modification to achieve weight loss remains a first-line intervention in patients with NAFLD. Weight loss achieved either by hypocaloric diet alone or in conjunction with increased physical activity can be beneficial for all patients with NAFLD. The benefits extend not only to those who are overweight and obese but also to those within normal body weight (lean NAFLD).1,6,7 Weight loss of approximately 3%-5% is necessary to improve hepatic steatosis, but a greater weight loss (7%-10%) is required to improve other histopathological features like necroinflammatory lesions and fibrosis.8-10 Individuals with higher BMI and/or type 2 diabetes (T2D) will require a larger weight reduction to achieve a similar benefit on NAFLD-related features.7,8 Weight loss via lifestyle changes can also decrease hepatic venous pressure gradient (HVPG), with greater declines reported among those with more than 10% weight loss.11
Dr. Naga Chalasani
Weight loss can be achieved through a variety of modalities, but long-term maintenance of lost weight is much more challenging. A combination of a hypocaloric diet with a caloric deficit of 500-1,000 kcal/d, alongside moderate-intensity exercise and intensive on-site behavioral treatment, will likely increase the possibility of a sustained weight loss over time.1,12 A growing body of scientific evidence indicates that a healthy diet that includes a reduction of high-glycemic-index foods and refined carbohydrates; increased consumption of monounsaturated fatty acids, omega-3 fatty acids, and fibers; and high intakes of olive oil, nuts, vegetables, fruits, legumes, whole grains, and fish can have beneficial effects on NAFLD and its severity.13-16 Adherence to these healthy dietary patterns has been associated with a marked reduction in CVD morbidity and mortality and is, thus, a strategic lifestyle recommendation for patients with NAFLD in whom the leading cause of morbidity and death is CVD.1,3
Exercise alone in adults with NAFLD may reduce hepatic steatosis, but its ability to improve inflammation and fibrosis has not been proven in well-designed RCTs.17,18 Physical activity and exercise have been shown to curb both the development and the progression of NAFLD, and beneficial effects could be achieved independent of weight loss.17,19,20 Most importantly, moderate-to-vigorous physical activity is likely associated with lower all-cause and cardiovascular mortality in patients with NAFLD.21
Heavy alcohol intake should be avoided by patients with NAFLD or NASH, and those with cirrhotic NASH should avoid any alcohol consumption given the risk of HCC and hepatic decompensation.1,4,22 Limiting light-to-moderate alcohol intake among patients without cirrhosis is still under debate.1 People with NAFLD may be advised to drink an equivalent of two to three 8-oz cups of regular brewed coffee daily as it has shown certain antifibrotic effects in NAFLD patients.23
Bariatric surgery
Bariatric surgery is an attractive therapeutic option for eligible obese patients with NAFLD. Bariatric surgery has the potential for inducing great weight loss and, therefore, reverses not only the steatosis, inflammation, and fibrosis among NAFLD individuals but also important comorbid conditions like T2D. A recent systematic review and meta-analysis examining data on the effects of bariatric surgery on histologic features of NAFLD from 32 cohort studies (no RCTs included) showed that bariatric surgery was associated with significant improvements in steatosis (66%), lobular inflammation (50%), ballooning degeneration (76%), and fibrosis (40%), and the benefits were significantly higher in those who underwent Roux-en-Y gastric bypass (RYGB). Of note, worsening of liver histology, including fibrosis, could be seen in up to 12% of patients who underwent bariatric surgery.24 The postsurgical weight regained after RYGB could explain partly the lack of fibrosis improvement or even worsening of fibrosis, although further research is needed to clarify these controversial findings.
RYGB and sleeve gastrectomy (SG) are the most commonly performed bariatric surgeries worldwide. Patients who undergo RYGB achieve higher weight loss when compared with those treated with SG.25 Among all bariatric procedures, RYGB could result in a higher proportion of complete resolution of NAFLD than SG, although evidence is inconclusive on fibrosis improvement rates.24,26 Most recently, a single-center RCT has compared the effects of RYGB vs. SG on liver fat content and fibrosis in patients with severe obesity and T2D.27 Data showed that both surgical procedures were highly and equally effective in reducing fatty liver content (quantified by magnetic resonance imaging), with an almost complete resolution of the fatty liver at 1 year of both surgical interventions. The beneficial effects of both GB and SG on fibrosis (assessed by enhanced liver test [ELF]) were less evident with no substantial difference between the two groups. Importantly, 69% of participants had an increase in their ELF scores during the study, despite the majority of participants achieving significant reductions in their body weights and better glycemic control at the end of the study. These findings might be considered with caution as several factors, such as the duration of the study (only 1 year) and lack of a liver biopsy to confirm fibrosis changes over time, could be influencing the study results.
Among all NAFLD phenotypes, those with cirrhosis and, most importantly, hepatic decompensation appear to be at increased risk of perioperative mortality and inpatient hospital stays than those without cirrhosis.28-29 Bariatric surgery is an absolute contraindication in patients with decompensated cirrhosis (Child B and Child C). Among compensated -Child A- cirrhotics, those with portal hypertension are at increased risk of morbidity and perioperative mortality.30 A recent analysis of National Inpatient Sample data suggested that the rates of complications in those with cirrhosis have decreased with time, which could be due to a better selection process and the use of more restrictive bariatric surgery in those with cirrhosis. Low volume centers (defined as less than 50 procedures per year) and nonrestrictive bariatric surgery were associated with a higher mortality rate. These data may suggest that patients with cirrhosis should undergo bariatric surgery only in high-volume centers after a multidisciplinary evaluation.31 Bariatric endoscopy is emerging as a new treatment for obesity, but the long-term durability of its effects remains to be determined.
A recent retrospective cohort study, including 1,158 adult patients with biopsy-proven NASH, has investigated the benefits of bariatric surgery on the occurrence of major adverse liver and cardiovascular outcomes in 650 patients who underwent bariatric surgery, compared with 508 patients who received nonsurgical usual care. This study showed that bariatric surgery was associated with 88% lower risk of progression of fatty liver to cirrhosis, liver cancer, or liver-related death, and 70% lower risk of serious CVD events during a follow-up period of 10 years.32 Within 1 year after surgery, 0.6% of patients died from surgical complications. The potential benefits of bariatric surgery in patients with NAFLD must be balanced against surgical risk, especially in eligible obese individuals with established cirrhosis. Data from a retrospective cohort study have shown that bariatric surgery in obese cirrhotic patients does not seem to associate with excessive mortality, compared with noncirrhotic obese patients.33 More data on immediate complication rates and long-term outcomes in patients with NAFLD by type of bariatric surgery is also required.
NAFLD as a standalone is not an indication for bariatric surgery. However, it could be considered in NAFLD patients who have a BMI of 40 kg/m2 or more without coexisting comorbidities or with a BMI of 35 kg/m2 or more and one or more severe obesity-related comorbidities, including T2D, hypertension, hyperlipidemia, or obstructive sleep apnea. Bariatric surgery must always be offered in centers with an experienced bariatric surgery program.1
