Understanding Nonalcoholic Fatty Liver Disease

You may be hearing about nonalcoholic fatty liver disease (NAFLD) on health podcasts, in books on longevity and in visits with your healthcare provider — but do you understand what this “buzzy” disorder has to do with arterial disease root causes and inflammation? Simply put, NAFLD is a condition where the liver collects fat and, over time, this can affect the liver’s function. This month’s newsletter is taking a deep dive into this complex disorder to better understand the nuances of NAFLD, its metabolic health implications, diagnostic strategies and the role of imaging in disease identification and reversal.

Nonalcoholic fatty liver disease has emerged as a significant public health concern, now representing the most common cause of chronic liver disease worldwide. Unlike its previously more common counterpart, alcoholic fatty liver disease (AFLD), NAFLD occurs in individuals who consume very moderate to no alcohol, implicating metabolic factors as the primary drivers of liver fat accumulation. This complex disorder encompasses a spectrum of liver conditions ranging from mild liver fat accumulation to nonalcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and potentially the need for liver transplantation. 

Differentiating Non-alcoholic fatty liver disease (NAFLD) from Alcoholic Fatty Liter Disease (AFLD)

While both NAFLD and AFLD manifest as hepatic (liver) fat accumulation, their causes differ significantly. AFLD results from chronic alcohol consumption, where ethanol metabolism in the liver induces lipid (fat) accumulation, inflammation and hepatocellular injury. In contrast, NAFLD arises in the absence of significant alcohol intake and is primarily driven by metabolic dysfunction and disorders such as insulin resistance, high cholesterol, obesity and visceral adiposity. 

Metabolic Health Implications

The intricate interplay between metabolic risk factors and liver fat accumulation lies at the heart of NAFLD development. Insulin resistance, a hallmark of metabolic syndrome, disrupts the balance between fat cell generation (lipogenesis) and fat cell breakdown (lipolysis), promoting triglyceride storage within the liver cells (hepatocytes). Dyslipidemia, characterized by elevated blood triglycerides and LDL cholesterol, then further exacerbates liver fat storage and inflammation. Obesity, especially fat accumulating around organs (visceral adiposity), amplifies metabolic dysfunction by secreting pro-inflammatory cytokines and adipokines that promote further insulin resistance and liver injury. In short, metabolic dysfunction is both a cause and continued driver of NAFLD, suggesting that metabolic health interventions such as reversing insulin resistance may significantly impact the trajectory of future liver health. 

Diagnosis

Accurate diagnosis of NAFLD necessitates a comprehensive evaluation, including physical exam, laboratory tests and imaging studies. Serum liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), will likely be elevated in NAFLD. As a rule of thumb, if both values are less than 30, the liver is generally felt to be happy and healthy, but when one or the other is persistently elevated, even after adjustments in medications if indicated, further evaluation is warranted.

Non-invasive imaging techniques, such as ultrasound, CT scan and MRI, play pivotal roles in NAFLD diagnosis. Ultrasound, the most widely utilized modality, offers a rapid, cost-effective means of detecting excess liver fat. However, its sensitivity is diminished in obese individuals and for those with only mild liver fat. CT and MRI provide superior sensitivity and specificity for fatty liver disease but are limited by higher costs, radiation exposure and resource availability. 

The Role of Visceral Fat Measurement

In recent years, the assessment of visceral adiposity has gained traction in NAFLD management, reflecting its close association with metabolic dysfunction and liver disease progression. Body composition scans, such as dual-energy X-ray absorptiometry (DEXA), enable precise measurement of visceral fat along with total body fat and lean muscle mass. 

Monitoring changes in visceral fat, alongside biochemical (blood) markers through serial body composition scans, can offer valuable insights into disease progression as well as therapeutic response to lifestyle changes. Reductions in visceral fat have been correlated with improvements in insulin sensitivity, lipid profiles and liver health following lifestyle interventions as well as targeted medical therapy. Additionally, visceral fat measurements complement traditional risk stratification tools by identifying individuals at heightened risk of metabolic complications and liver dysfunction, both of which help in guiding personalized prevention planning.

NAFLD is a multifaceted disorder with far-reaching metabolic implications beyond liver fat accumulation. Its intricate interplay with obesity, insulin resistance and dyslipidemia underscores the importance of a holistic and multidisciplinary approach to diagnosis and management. 

Non-invasive imaging studies (such as DEXA body composition scans) coupled with traditional blood tests can offer valuable insights for risk stratification, disease monitoring and personalized intervention.  If you are interested in your own liver health, start by looking at your AST and ALT on your most recent labs and ask your healthcare provider about the value of body composition testing. 

Using appropriate and careful medical treatments (such as statins, niacin, pioglitazone, diet, exercise and weight loss) for insulin resistance, lipid abnormalities and metabolic syndrome also improves non-alcoholic fatty liver disease.  Monitoring liver health is an essential element to our prevention efforts.  

SOURCES: 

1. Chalasani, Naga, et al. “The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.” Hepatology 67.1 (2018): 328-357.
2. Younossi, Zobair M., et al. “Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.” Hepatology 64.1 (2016): 73-84.
3. Targher, Giovanni, et al. “Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis.” Journal of Hepatology 65.3 (2016): 589-600.
4. Koliaki, Chrysi, et al. “Adaptations of hepatic lipid metabolism in response to obesity and metabolic syndrome.” Cellular and Molecular Life Sciences 73. 5 (2016):  3343-3361.
5. Castera, Laurent, et al. “Noninvasive Assessment of Liver Disease in Patients with Nonalcoholic Fatty Liver Disease.” Gastroenterology 156.5 (2019): 1264-1281.