january 24th, 2022
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Non Alcoholic Fatty Liver Disease, NAFLD
Non Alcoholic Steatohepatitis, NASH
When I was in medical school in the early 90's, the primary cause of fatty liver disease in adults was alcohol abuse. Over the last 20 years, the obesity epidemic and associated fatty liver disease, NAFLD, has taken over first place. Unfortunately, this is no longer an adult only phenomena. Akin to type II diabetes mellitus, children are now suffering increasing rates of NASH and then NAFLD.
It is now the most common liver disorder in children. Incidence is now greater than 33% for obese boys and 25% for obese girls. (Yu et. al. 2019) According to the CDC, there are 13.7 million obese children in the United states. That equates to roughly 4,000,000 children and adolescents with NAFLD and/or NASH. This a completely preventable national tragedy.
Studies have noted a 4-fold increased risk of NAFLD in Hispanic, compared to non-Hispanic adolescents. White and Asian children also have relatively high prevalence compared to African-American children. Other studies note gender differences with higher percentages in male compared to female children.(Vox et. al. 2020)
What is NASH and NAFLD? NAFLD is defined as greater than 5% of the liver cells having fatty deposition by biopsy or radiographic evidence without any inflammation. In about a fifth of these NAFLD patients, inflammation will set in leading to liver cell damage and subsequently fibrosis and scarring. Unchecked, this fat deposition will continue in more liver cells causing increased cellular damage and ultimately leading to cirrhosis or liver cancer and ultimately liver death and human demise.
The etiology is believed to be a combination of many different metabolic triggers including the Standard American Diet, its effects on the intestinal microbiome, a sedentary lifestyle all combined and in the face of dysfunctional genetic risks. Overconsumption of fructose sugar in the form of sweetened beverages and processed foods is the leading contributor to disease. "Fructose consumption has been associated with NAFLD severity in both cross-sectional and interventional studies. There is evidence that fructose consumption was independently associated with NASH in obese children with NAFLD; it also showed that fructose intake was independently linked to hyperuricemia. An intervention with a low-fructose diet in pediatric NAFLD demonstrated that fructose intake correlated strongly with plasma ALT, aspartate aminotransferase (AST), and insulin resistance, independently of weight loss. Furthermore, a recent study showed that a 9-day-long fructose restriction led to significantly decreased liver fat, visceral fat, and hepatic de novo lipogenesis in obese children." (Hartmann et. al 2018)
As fructose drives up the metabolite uric acid in the liver, the inflammation that follows is mediated by the NLRP3 inflammasome which induces local damage and destroys the powerhouse of the liver cells known as the mitochondria. The associated intestinal microbial dysbiosis releases immune activating lipopolysaccharides into the systemic blood stream and induces a depletion of liver cell protective choline. Excess systemic glucose and free fatty acids independently drive more immune dysregulation further increasing mitochondrial reactive oxygen species inducing apoptosis and cell death.
Clinically, NAFLD and NASH are relatively asymptomatic form decades. Over prolonged periods of disease, the patient may start to feel chronically fatigued and have nonspecific abdominal pain. Diagnostic clues begin with a liver enzyme test called an ALT or alanine aminotransferase and lipid tests like triglycerides and lipoproteins. If significantly elevated, an ultrasound can give more concrete evidence of disease. The only definitive proof is through a liver biopsy.
This is a devastating silent killer if left unchecked. Obviously, we want to catch this disease well before these symptoms develop. If you or your child suffers from obesity, diabetes, high blood pressure or metabolic syndrome, we highly encourage you to have your liver tested via a screening blood test.
Treatment: The simple answer is always the one least well received.
1) Avoid simple refined sugar and flour in all of its forms. Absolutely no fructose or high fructose corn syrup based foods or beverages.
2) Reduce the consumption of fruits especially as juice or smoothies until the liver and your weight are stabilized. Then adding back whole fruit and smoothies is a good idea.
3) Increase daily exercise to 60 minutes. Start slow and work your way up to 60 minutes. Walking as a family is a great start.
4) Minimize screen time as it encourages overeating and sedentary behaviors.
5) Talk to your doctor about taking vitamin E oil, omega 3 fatty acids and choline to help protect the liver cells from damage.
Dr. M
Nobili Nature Reviews Gastro and Hepatology
Goldner Gastroenterology
Yu J of Pediatrics
Hartmann Clinical Liver Disease
Vos J of Pediatric Gastro and Nutrition
Torquato Nature Scientific Reports
Mann J of Expert Review of Gastro and Hepatology
Ibrahim J of Pediatric Gastro and Nutrition
Felix BMC Pediatrics
Cifarelli J Cellular Molec Gastro Hepatology
