The Preventable Epidemic of Fatty Liver Disease

There is an epidemic of Fatty Liver Disease in the U.S. that can have grave consequences if not prevented, treated or diagnosed early enough. The good news is that it can be prevented and successfully treated if caught early enough.

Non-Alcoholic Steatohepatitis (NASH)...what is it?

NASH is a common liver disease that is generally without symptoms. It is the most prevalent progressive liver disease in the United States affecting up to 5% of Americans (5 people in every 100).

Although NASH resembles alcoholic liver disease, it occurs in people who drink little or no alcohol (defined as under 7 drinks per week for women and under 14 drinks per week for men*).

The major feature of NASH is a fatty liver (fat deposition in the liver) associated with inflammation. The fatty deposition and inflammation in the liver leads to damage of the liver cells and liver tissue causing liver fibrosis (scarring) in approximately 50% of people with NASH and cirrhosis in up to 25% of people with NASH. Those people who develop cirrhosis will die in 7-10 years if they do not get a liver transplant. Ironically, most people with NASH feel well and are not aware they have a progressive liver disorder. (Hepatology 2006; 43: S99)

NASH Begins with NAFLD

NASH begins with nonalcoholic fatty liver disease (NAFLD) without the associated inflammation, fibrosis and cirrhosis... simply called “fatty liver.” 30 million adults have NAFLD or “fatty liver.” NAFLD is considered to be the primary liver complication of metabolic syndrome i.e., obesity, hypertension, dyslipidemia (high cholesterol and lipids), insulin resistance, and late-onset or type II diabetes.

NAFLD is recognized today as the most prevalent liver disease in the Western population with estimated prevalence rates approaching 34%. That is 1/3 of the population! Some researchers have found prevalence rates to be approaching 50% of the population in patients seen at urban primary care clinics in states such as Texas, known to have the highest rates of obesity.

Nearly 10% of children in the U.S. ages 2-19 have fatty liver. That equals approximately 6.5 million children! Most of those children (81%) with fatty liver are overweight and obese. Nearly 25% of those children already have NASH. (NEJM 2002; 346: 1221) (Pediatrics: Oct 2, 2006)

NASH: Primary Causes and Risk Factors

I am going to focus on the primary causes of NASH, although there are a number of secondary causes and risk factors such as viral hepatitis; autoimmune hepatitis; environmental toxins; and medications and drugs such as steroids, cocaine, synthetic estrogens, and some anticancer drugs.

Both NASH and NAFLD are becoming more common, primarily because of the greater number of Americans with obesity and metabolic syndrome. In the past 10 years, the rate of obesity in the U.S. has doubled in adults and tripled in children. Insulin resistance, type II diabetes and dyslipidemia (aspects of metabolic syndrome) are also becoming more common among Americans.

Over 90% of patients with NAFLD have at least one feature of metabolic syndrome while 30% have the complete syndrome defined as three of the following:

• Central obesity (around the abdomen and flanks),
• Impaired/elevated fasting blood glucose,
• Elevated triglycerides
• Low HDL cholesterol
• High blood pressure
• Elevated uric acid in the blood

NASH: Diagnosis

The first hint of NAFLD and/or NASH is first seen in a blood chemistry test. An elevation of liver enzymes known as transaminases, most specifically the ALT, is suspect for fatty liver particularly in a patient with symptoms and signs of metabolic syndrome as described above when all other risk factors are negative. Next a liver ultrasound is required to visualize fatty infiltration of the liver. Unfortunately, however, an ultrasound can only detect NAFLD when there is more than 30% fatty infiltration. If the ultrasound demonstrates fatty infiltration, a liver biopsy may be required for final diagnosis, particularly if metabolic syndrome is well established.

NASH: The Best Treatment is Prevention

The best treatment for NASH is prevention because, it can be prevented! More than anything, prevention means reducing exposure to environmental toxins and preventing obesity.

Environmental toxins known to cause fatty liver include heavy metals such as lead and mercury, petrochemicals, and organic solvents found in cigarette smoke, paints, automobile exhaust, pesticides, air fresheners, and solvents used for cleaning and dry cleaning.

Preventing obesity in most people means eliminating the over-consumption of nutrient-poor, high-fat (particularly saturated fats), high-sugar (especially high-fructose corn syrup), highly processed fast foods and sodas while encouraging daily aerobic exercise (20 minutes or more) and a healthy diet. High-fructose corn syrup and high-fructose diets are now thought to be a major cause of obesity, type II diabetes, and metabolic syndrome in the U.S. They are also associated with the development of NAFLD. (Gastroenterol 2009; 136[5]: S1: 289) (Endocrine Rev 2009; 30: 96-1126) (Hepatology 2010; 51: 1961-71)

A “healthy diet” to prevent obesity and NASH must be one consisting of colorful, fresh vegetables and fruits; whole grains and legumes; seeds and nuts; fresh, wild-caught fish; and fresh, free-ranged organic fowl, meats and dairy products. Well over 50% of one’s daily intake should come form the vegetable and fruit categories, 30% from seeds, nuts, legumes and whole grains, and 20% from fish, fowl, meat and dairy. Dairy products should be organic and low-fat or non-fat. They should be eaten not drunk…eaten as fermented yogurts, kefirs, and aged cheeses.

Organic is stressed here because pesticides and herbicides are a principle source of environmental toxins and are most concentrated in animal fats and oily foods.

There are specific foods and spices scientifically demonstrated to have liver-protective effects and should be routinely included in one’s diet. Some of these include: Artichoke leaves and hearts; beets; radishes; garlic; omega-3 fatty acids from fish oils; cabbage family vegetables especially broccoli, cauliflower and Brussels sprouts; turmeric; ginger; and green tea.

NASH: Treatment

NASH can be prevented and successfully treated if caught early enough. The following nutritional supplements are well studied compounds that are used in the treatment of NASH.

Fish Oils: Omega-3 fatty acids have been shown to improve insulin sensitivity and lower markers of liver inflammation in animal models and clinical trials.

N-Acetylcysteine (NAC): Animal and human studies of NAC have shown it to have powerful antioxidant activity. It is effective in promoting normal liver detoxification. As a sulfur source, NAC stimulates glutathione (an important antioxidant produced in the body) synthesis and activity thereby promoting liver detoxification and the scavenging of free radicals.

Alpha Lipoic Acid (ALA): ALA increases cell sensitivity to insulin and is liver-protective and regenerative. It is essential to the proper metabolism of carbohydrates.

Vitamin E: Vitamin E decreases liver fibrosis by reducing the release of TGF-1, a peptide in the liver shown to cause liver fibrosis. Supplementation of 300 IUs daily over 12 months has been shown to significantly reduce inflammation, fibrosis and fatty infiltration.

Vitamin D: Low vitamin D levels are associated with the severity of fatty infiltration, inflammation and fibrosis in the liver. The lower the vitamin D levels the greater the severity.

L-Carnitine: L-carnitine supplementation over 12 months has been shown to induce regression of NASH in clinical trials even if both plasma and hepatic carnitine levels have been shown to be normal.

Liver-protective botanicals: There are a number of scientifically proven, liver-protective botanical compounds that can be used to decrease fatty infiltration and inflammation in the liver.

Silymarin: Silymarin is a well studied flavonoid from milk thistle. It has liver-protective effects that are accomplished via several mechanisms including antioxidation, inhibition of lipid peroxidation, enhanced liver detoxification via inhibition of Phase I detoxification and enhanced glucuronidation, and protection of glutathione depletion. Silymarin can stimulate liver cell regeneration as well.

Picrorhiza: Picrorhiza increases bile production in the liver and has also been shown to protect the liver from damage by several potent liver toxins, offering protection as good as or better than silymarin. The liver-protective effects of Picrorhiza may be due to its antioxidant activity and free radical scavenging. Like silymarin, Picrorhiza can stimulate liver regeneration, possibly via stimulation of nucleic acid and protein synthesis. Picrorhiza also benefits individuals with acute hepatitis. In a double-blind study, it reduced bilirubin and the liver enzymes ALT and AST significantly compared to placebo.

Catechin compounds: Catechins are antioxidant flavonoid compounds found primarily in green tea. They have been shown to stimulate liver lipid metabolism and fat breakdown in the liver. They reduce fatty infiltration in the liver and are liver-protective.

Curcumin: Curcumin is the yellow pigmented flavonoid in turmeric. It is one of the most researched natural compound today, studied for its anti-oxidant, anti-inflammatory, anticancer, and liver-protective effects.

Weight Loss is also a prescribed treatment for NASH.

Weight Loss: Weight loss can improve liver biopsy results in patients with NASH. This should not be a radical weight loss but average approximately 1-2 pounds per week.

NASH: Summary

There is an epidemic of NASH in the U.S. that parallels the epidemic of obesity and metabolic syndrome. It can have grave consequences if not prevented, treated or diagnosed early enough. The good news is it can be prevented and successfully treated if caught early enough.

Interesting Question for Those Over 40: 

Did Crosby have Nash when he had his liver transplant or was he Still too Young?

References

Ailment Pharmacol Ther 2010; 31: 679

Ailment Pharmacol Ther 2001; 15: 1667

Biochem Pharmacol 1972; 21(4): 594-600

Dig Dis Sci 2007; 52: 2387

Endocrine Rev 2009; 30: 96-1126

Fitoterapia 1999;70:54–7

Gut 2002; 51: 89-94

Gastroenterol 2009; 136(5): S1: 289

Hepatology 2010; 51: 1961-71

Hepatology 2006; 43: S99

J Am Coll Nutr 2007; 26:373S-388S

J Hepatol 1992; 14: 259

NEJM 2002; 346: 1221

Nutr Metab Cardiovasc Dis 2007; 17: 517

Pediatrics: Oct 2, 2006

Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. 3rd ed, Berlin: Springer, 1998

Toxicology 2008; 243(3): 261-270

* A standard drink equals 12 ounces beer, 5 ounces wine, 1.5 ounces 80-proof spirits.