Episode 172: NAFLD and Obesity

Episode 172: NAFLD and Obesity

Future Dr. Nguyen explains the pathophysiology of non-alcoholic fatty liver disease and how it relates to obesity. Dr. Arreaza gives information about screening and diagnosis of NAFLD. 

Written by Ryan Nguyen, MS4, Ross University School of Medicine. Comments by Hector Arreaza, MD.

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Introduction/Pathophysiology
Nonalcoholic fatty liver disease (NAFLD) refers to the buildup of excess fat in liver cells, occurring without the influence of alcohol or drugs. Nonalcoholic steatohepatitis (NASH) represents a more severe form of NAFLD, characterized by inflammation and liver cell injury due to fat accumulation. If left untreated, NASH can progress to liver fibrosis or cirrhosis. Typically, NAFLD/NASH is diagnosed after other liver conditions are ruled out, making it a diagnosis of exclusion.

NAFLD -> NASH -> Cirrhosis -> Liver failure. Another term for NAFLD is metabolic dysfunction-associated steatotic liver disease. 

Fatty liver disease is identified when more than 5% of liver weight consists of fat, whereas, NASH is diagnosed when this fat accumulation is accompanied by inflammation and liver cell injury, sometimes leading to fibrosis. Understanding these distinctions is crucial in recognizing and managing the spectrum of liver conditions associated with obesity and metabolic syndrome.

BMI serves as a tool to gauge body fat levels: individuals are categorized as normal weight if their BMI falls between 18.5 and 24.9, overweight if it ranges from 25 to 29.9. Class I obesity is diagnosed with a BMI of 30 to 34.9, class II obesity between 35 and 39.9, and class III obesity when BMI exceeds 40.

Obesity puts you at risk of NAFLD, but you can also see NAFLD in non-obese patients, but the prevalence is very low, about 5%. What did you learn about the demographics of NAFLD?

NAFLD is most widespread in regions like South Asia, the Middle East, Mexico, Central and South America, with prevalence rates exceeding 30%. In the United States, prevalence varies with approximately 23-27%, notably higher among Asians at 30%, followed by Hispanic individuals at 21%, White individuals at 12.5%, and Black individuals at 11.6%. 

Across all racial groups, obesity plays a significant role, affecting more than two-thirds of individuals diagnosed with NAFLD. Understanding these demographics underscores the global impact of obesity on NAFLD prevalence.

Diagnosis: Screening/Labs/Imaging/Tools

The American Association for the Study of Liver Diseases does not recommend screening for NAFLD, but if it is discovered an appropriate workup is warranted. 

AST/ALT Ratio

Liver health can be assessed by a series of tests aimed at assessing fat accumulation, inflammation, and fibrosis. Initial screening often includes laboratory tests such as measuring the ratio between aspartate transaminase (AST) and alanine transaminase (ALT), where a ratio less than 1 may suggest possible NAFLD, although it is not diagnostic on its own. Normally, AST is slightly more elevated than ALT. So, if the AST/ALT ratio is lower, then means that ALT is higher than AST. 

FibroSure®.

Additionally, you can measure indirect markers of fibrosis with tests such as FibroSure or FibroTest blood tests that combine several biomarkers including age, sex, gamma-glutamyl-transferase (GGT), total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, and ALT to provide insights into liver health.

Some people may be more familiar with FibroSure before Hepatitis C treatment. You can get a fibrosis score (F0-F4), and it is considered significant fibrosis if the score is > or equal to F2. Imaging plays a crucial role in diagnosing NAFLD without the need for invasive procedures like liver biopsy. Vibration-controlled transient elastography (Fibroscan) uses ultrasound to measure liver stiffness, indicating potential fibrosis and inflammation. While noninvasive and portable, it focuses solely on liver ultrasound and may not be universally accessible. MRI with proton density fat fraction (MRI-PDFF) offers a comprehensive assessment of liver fat content, commonly used in clinical and research settings for NAFLD and NASH evaluation.

For evaluating hepatic fibrosis in patients with suspected NAFLD, tools like the Fibrosis-4 Index (FIB-4) incorporate age, AST, ALT, and platelet count to estimate the likelihood of liver disease progression. These screening methods collectively aid in diagnosing and monitoring NAFLD, particularly in individuals at risk due to factors like prediabetes, type 2 diabetes, obesity, and abnormal liver enzyme ratios. 

With the FIB-4 you can get a faster answer than FibroSure because you only need 4 elements: Age, platelet count, AST and ALT. Cirrhosis is less likely if FIB-4 is <1.45, it is considered intermediate if it is between 1.45 and ≤3.25, and cirrhosis is more likely with a score >3.25. Understanding these diagnostic approaches is essential for early detection and management of NAFLD in clinical practice.

Some researchers are invested in diagnosis and treating NAFLD while others recommend against labeling patients with NAFLD. A 2018 Lancet article concluded that the risks of over-diagnosing and overtreating NAFLD exceed the benefits of screening or periodic imaging because of “the low hepatic mortality, high false-positive rate of ultrasonography, selection bias of current studies, and lack of viable treatment.” However, patients who suffer from metabolic syndrome should be counseled about dietary modification and physical activity regardless of their liver condition. 

NAFLD and obesity

Fatty liver disease is often caused by multiple insults towards either genetically or environmentally predisposed individuals. Family history of NAFLD and having specific genetic variants are important risk factors for NAFLD. Those with prior health conditions can have increased susceptibility to NAFLD including T2DM leading to insulin resistance, metabolic syndrome, sleep apnea, hepatitis C, and cardiovascular or chronic kidney disease. 

A sedentary lifestyle and unhealthy nutrition (especially high intake of processed carbohydrates) cause an increase in free fatty acids leading to hepatic fat deposition → ballooning of hepatocytes → leading to hepatocyte injury/death → inflammation with fibroblast recruitment → end result of fibrosis/cirrhosis. Just a quick reminder, NAFLD is defined as fatty liver with >5% hepatic fat and NASH is defined as fatty liver with >5% hepatic fat with inflammation, hepatocyte injury, with or without fibrosis that we can determine through imaging. 

A leading concern for the development of NAFLD is the consumption of high fructose corn syrup.  High fructose corn syrup (HFCS), commonly found in candy, processed sweets, soda, fruit juices, and other processed foods, is linked to non-alcoholic fatty liver disease (NAFLD). Unlike natural whole fruits, which contain fiber and are generally healthier due to their slower absorption, HFCS lacks fiber and is quickly absorbed, leading to rapid transport to the liver. This process contributes to NAFLD by increasing the hepatic synthesis of lipids and interfering with insulin signaling. To avoid HFCS, individuals are encouraged to consume whole fruits rather than fruit juices and adopt diets rich in whole grains, lean meats, plant-based proteins, fruits, and vegetables, such as the Mediterranean or DASH diets, which are less likely to promote NAFLD, especially in those with healthy body weight.

NAFLD treatment.

Avoiding alcohol seems very obvious, but we need to mention it. Avoiding heavy alcohol consumption is recommended and complete abstinence is suggested.

Weight loss is crucial; even a modest reduction of 3–5% in body weight can alleviate hepatic steatosis, with greater improvements typically seen with 7–10% weight loss, particularly beneficial for addressing histopathological features of NASH, such as fibrosis. We must focus on tailored medical nutrition therapy and regular physical activity. 

A strategic meal plan is essential, emphasizing achieving a healthy body weight while limiting trans fats and ultra-processed carbohydrates. Options like the Mediterranean diet, which balances lean proteins and restricts processed carbohydrates have shown promise. 

Dynamic aerobic and resistance exercises play a significant role in managing NAFLD. They help maintain a healthy weight and enhance peripheral insulin sensitivity, reduce circulating free fatty acids and glucose levels, and boost intrahepatic fatty acid oxidation while curbing fatty acid synthesis. These benefits contribute to mitigating liver damage associated with NAFLD, offering therapeutic advantages beyond mere weight reduction.

Exercise may not be a great tool for weight loss, but it is a great tool for weight maintenance, liver health, and overall health as well. “Most patients with NAFLD die from vascular causes, but NAFLD puts patients at increased risk of cardiovascular death”. 

Medications for NAFLD.

Regarding pharmacotherapy, while no medications are currently FDA-approved specifically for NAFLD treatment, some options show promise in clinical settings. Vitamin E supplementation at 800 IU (international units) daily has demonstrated biochemical and histological improvements in NASH cases without diabetes or cirrhosis, though long-term use may elevate prostate cancer risks. It is important to make a shared decision with the patient before starting Vitamin E supplementation. 

Medications like pioglitazone can reduce liver fat and improve NASH, even as they may increase body weight. But our favorite, GLP-1 receptor agonists, such as liraglutide and semaglutide, also show potential in reducing liver fat and improving NASH symptoms, and this is an emerging therapeutic option for managing this condition.

If you decide to treat, then you should monitor as part of the treatment. An aminotransferase check is recommended 6 months after starting a weight loss program. If levels do not improve or do not return to normal after 5-7% of weight loss, another cause of elevated transaminases needs to be investigated.

You also need to monitor fibrosis in patients with >F2. If fibrosis has been proven by liver biopsy, you can order FibroSure every 3-4 years. 

Having a fatty liver may be a red flag that your patient has a metabolic problem. If you discover it, start interventions that would benefit not only the liver but the whole metabolic profile of your patient. The Obesity Medicine Association (OMA) issued a Clinical Practice Statement (CPS) regarding NAFLD and obesity stating that patients with obesity are at increased risk for NAFLD and NASH. It recommends that clinicians strive to understand the etiology, diagnosis, and optimal treatment of NAFLD with a goal to prevent NASH in their patients.

Regular exercise, even walking 30 minutes a day can show many benefits in curbing fatty accumulation in the liver. Having a proper diet with avoidance of high fructose corn syrup can overall help in reducing NAFLD/NASH. 

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Conclusion: Now we conclude episode number 172, “NAFLD and Obesity.” Future Dr. Nguyen explained that NAFLD and obesity are closely related and NAFLD can lead to NASH and cirrhosis in some patients. Dr. Arreaza explained that screening may not be recommended by some medical societies, but others are in favor of screening and treating this disease. However, most people agree that NAFLD is a sign of metabolic disease and a good reason to talk about healthy eating and physical activity with our patients. There are no FDA-approved medications to treat NAFLD, but some evidence suggests that Vitamin E can improve it and GLP-1 receptor agonists are a promising option. 

This week we thank Hector Arreaza and Ryan Nguyen. Audio editing by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

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References:

Karjoo S, Auriemma A, Fraker T, Edward H. Nonalcoholic fatty liver disease and obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. https://doi.org/10.1016/j.obpill.2022.100027.Curry M, Afdhal N. Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations.  https://www.uptodate.com/contents/noninvasive-assessment-of-hepatic-fibrosis-overview-of-serologic-tests-and-imaging-examinationsRoyalty-free music used for this episode: Cool Groove (Alt-Mix) by Videvo, downloaded on Nov 06, 2023, from https://www.videvo.net