NASH: The Next Frontier

| November 1, 2021

Christopher D. Still, DO, FACP, FTOS, is the Co-clinical Editor of Bariatric Times; Medical Director for the Center for Nutrition and Weight Management, and Director for Geisinger Obesity Research Institute at Geisinger Medical Center in Danville, Pennsylvania.

Dear Colleagues,

Since October was National Liver Awareness Month, I thought I would again take this opportunity to discuss one of the most underdiagnosed comorbid conditions of obesity—nonalcoholic fatty liver disease (NAFLD). NAFLD is a growing epidemic that deserves our attention, especially as weight management experts. With effective therapies now available for the treatment of hepatitis C virus (HCV) infection, the most common cause of chronic liver disease has become fatty liver disease. Moreover, nonalcoholic steatohepatitis (NASH)—a disease under the NAFLD umbrella—is now one of the leading causes of liver transplants in adults in the United States.1 

NAFLD encompasses a wide spectrum of fatty liver disorders all caused by the buildup of extra fat in liver cells. While it is normal for the liver to contain some fat, if fat content rises to more than 5 to 10 percent of the liver’s weight, then it is considered a fatty liver, or steatosis. Steatosis can progress to fibrosis and NASH, which causes inflammation and accumulation of fat and scar tissue in the liver. NASH can then progress even further to cirrhosis. These conditions can cause enough liver damage to require liver transplantation.

As many as 80 percent of patients with obesity have NAFLD.2 The problem is that, although prevalent, the condition often goes undiagnosed because 1) patients do not present with definitive physical symptoms and 2) in-depth examination of NAFLD severity requires further testing. Ultrasounds do not show histological changes that occur along the NAFLD spectrum, and liver function studies show only a minimal picture. The gold standard for detection is liver biopsy, but very few people who meet the criteria want to go through with one, as it is invasive. A less invasive transient elastography, which measures liver stiffness, can be performed to better stratify patients requiring liver biopsy.

From a clinical standpoint, you cannot really blame people for choosing to forgo biopsy because, although other therapies are being developed, as of now the only treatment is weight loss. Agents such as vitamin E and pioglitazone can be considered in patients with NASH, but concerns about their efficacy and side effects remain. Modest weight loss of 5 to 10 percent has been shown to improve NAFLD.3 Bariatric surgery resolves NASH in such patients where lifestyle modifications have failed and is recommended for patients with a body mass index (BMI) of 35kg/m2 or greater.4,5 Another clinical conundrum of NAFLD is that its progression varies among individuals. Some stay in the earlier stage of steatosis, and others move on to develop fibrosis, NASH, and cirrhosis. Research is being focused on predicting those who are at risk of disease progression so more targeted interventions can be developed for this patient population. We are interested in learning more about the impact of proteomics, genetics, and other markers to increase the sensitivity and specificity of noninvasive testing.

Both clinicians and patients need to be aware of NAFLD, the importance and accuracy of testing methods, and the role of weight loss in disease improvement. We can start by clarifying a common misconception that one can only get liver damage through alcohol consumption. When I tell patients that we’d like to perform a liver biopsy at the time of their bariatric surgery, I’m often met with the following response: “I don’t have to worry about liver damage because I don’t drink.” A lot of people have no idea that they can get the same type of cirrhosis without consuming alcohol. In addition, patients who do consume alcohol are doubly at risk for liver damage, with alcohol and fat taxing the liver simultaneously.

As mentioned above, pharmacotherapies are of high value for patients with NASH. There are at least four companies that currently have Phase III development for NASH, and one might be approved early in 2022. This is great news, but in the meantime, we should continue to educate patients and healthcare providers about the importance of aggressive weight management through diet, exercise, behavior modification, weight loss medications, and, most importantly, bariatric surgery in patients with a BMI or
35kg/m2 or greater and NASH.

Happy Fall everyone!

Be well,

Christopher D. Still, DO, FACP, FTOS


  1. Mahmud N. Selection for liver transplantation: indications and evaluation. [published online ahead of print, 2020 Jun 19]. Curr Hepatology Rep. 2020;1–10.
  2. Milić S, Lulić D, Štimac D. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World J Gastroenterol. 2014;20(29):9330–9337.
  3. Lazo M, Solga SF, Horska A, et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with Type 2 diabetes. Diabetes Care. 2010;33(10):2156–2163.
  4. Laursen TL, Hagemann CA, Wei C, et al. Bariatric surgery in patients with non-alcoholic fatty liver disease–from pathophysiology to clinical effects. World J Hepatol. 2019;11(2):138–149. 
  5. Lassailly G, Caiazzo R, Ntandja-Wandji L-C, et al. Gastroenterology. 2020;159(4):1193–1194. 

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