Nonalcoholic Fatty Liver Disease (NAFLD), Why We Need To Be Responsive.
Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis when no other causes for secondary hepatic fat accumulation (eg, heavy alcohol consumption) are present. NAFLD may progress to cirrhosis and is likely an important cause of cryptogenic cirrhosis., NALFD is now the most common cause of abnormal liver biochemistry in North America and likely in the UK and is also known to be associated with some drugs, genetic defects, obesity, insulin resistance and type 2 diabetes.
- NAFLD covers a spectrum ranging from simple steatosis to steato-hepatitis (NASH) and cirrhosis. Of the UK population about 33% have NAFLD, and 2-5% have NASH.
- It is now the commonest cause of liver disease in the West and accounts for a growing proportion of patients undergoing liver transplantation (15-20%). Most patients commonly present in middle-age.
- There is a need to increase understanding of liver disease and its many causes, to improve patient outcomes and reduce the stigma many patient’s experience. Currently there is a perception that all liver disease is due to alcohol. Yet in medicine today NAFLD is considered as the hepatic manifestation of metabolic syndrome, which is defined notably by increased waist circumference, insulin resistance and dyslipidemia.
Patients with nonalcoholic fatty liver disease (NAFLD) have hepatic steatosis, with or without inflammation and fibrosis. In addition, no secondary causes of hepatic steatosis are present.
NAFLD is subdivided into nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH). In NAFLD, hepatic steatosis is present without evidence of significant inflammation, whereas in NASH, hepatic steatosis is associated with hepatic inflammation that may be histologically indistinguishable from alcoholic steatohepatitis., Other terms that have been used to describe NASH include pseudoalcoholic hepatitis, alcohol-like hepatitis, fatty liver hepatitis, steatonecrosis, and diabetic hepatitis.
Nonalcoholic fatty liver disease (NAFLD) is seen worldwide and is the most common liver disorder in Western industrialised countries, where the major risk factors for NAFLD, central obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome are common. In the United States, studies report a prevalence of NAFLD of 10 to 46 percent, with most biopsy-based studies reporting a prevalence of NASH of 3 to 5 percent., Worldwide, NAFLD has a reported prevalence of 6 to 35 percent (median 20 percent).
- Systemic hypertension
- Insulin resistance or overt diabetes, type 2 and 1
The pathogenesis of nonalcoholic fatty liver disease has not been fully elucidated. The most widely supported theory implicates insulin resistance as the key mechanism leading to hepatic steatosis, and perhaps also to steatohepatitis. Others have proposed that a “second hit,” or additional oxidative injury, is required to manifest the necroinflammatory component of steatohepatitis. Hepatic iron, leptin, antioxidant deficiencies, and intestinal bacteria have all been suggested as potential oxidative stressors.
Most patients with nonalcoholic fatty liver disease (NAFLD) are asymptomatic, although some patients with nonalcoholic steatohepatitis (NASH) may complain of fatigue, malaise, and vague right upper abdominal discomfort. Patients are more likely to come to attention because laboratory testing revealed elevated liver aminotransferases or hepatic steatosis was detected incidentally on abdominal imaging.
Patients with NAFLD may have mild or moderate elevations in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT), although normal aminotransferase levels do not exclude NAFLD. The true prevalence of abnormal transaminases among patients with NAFLD is unclear, since many patients with NAFLD are diagnosed because they are noted to have abnormal aminotransferases. When elevated, the AST and ALT are typically two to five times the upper limit of normal, with an AST to ALT ratio of less than one (unlike alcoholic fatty liver disease, which typically has a ratio greater than two). The degree of aminotransferase elevation does not predict the degree of hepatic inflammation or fibrosis, and a normal alanine aminotransferase does not exclude clinically important histologic injury. Other labatory findings that may be abnormal or high end of normal include gamma γ-Glutamyl transferase (GGT).,
Radiographic findings in patients with NAFLD include increased echogenicity on ultrasound, decreased hepatic attenuation on computed tomography (CT), and an increased fat signal on magnetic resonance imaging (MRI).
Multiple therapies have been investigated for the treatment of nonalcoholic fatty liver disease (NAFLD). Weight loss is the only therapy with reasonable evidence suggesting it is beneficial and safe. Conventionally, the following strategies are typically employed.
- Weight loss for patients who are overweight or obese.
- Hepatitis A and B vaccinations should be given to patients without serologic evidence of immunity.
- Treatment of risk factors for cardiovascular disease.
- Pharmacological agents, such as pioglitazone, are not recommended. Numerous other drugs have been examined for the treatment of NASH. While some have shown initial promise, none has been studied sufficiently to recommend its use as a primary treatment for NASH.
- Alcohol avoidance is recommended.
In my opinion and experience, I have routinely screened my patients with high normal GGT levels, in isolation or in conjunction with high normal or elevated AST and/or ALT levels with a liver ultrasound and have frequently seen evidence of NASH and NAFL on the radiology report. Typically, their medical doctor, unfortunately, has brushed this off as if there was nothing to be done about it besides weight loss, if indicated.
This is where nutritional and nutraceutical therapies have an enormous role to play. A diet rich in organic fruits and vegetables (the more varied the colours, the better), avoidance of refined, processed, and charred foods are beneficial. I also recommend my patients to avoid trans and saturated fats, along with nitrates/nitrates and high fructose corn syrup. Lastly, I recommend them to include a diet rich in green tea, fresh fish and liver supportive foods.
The following nutrients have shown the greatest clinical efficacy in addressing and even reversing the spectrum of NAFLD.
- N-acetyl-cysteine (NAC): 600 mg twice daily, best taken away from food.
- Vitamin C: 500-1000 mg daily. Reference is same as above.
- Omega 3 essential fatty acids: 2 grams-4 grams daily.
- Vitamin E: 400 IU twice daily with food.
- L-carnitine: 1 gram twice daily.
- Betaine: 20 grams daily (1-6 grams/day may beneficial if used in conjunction with other therapies).
- Choline: 250-1,000 mg daily.
- Inositol: 500-1,500 mg daily.
Other nutrients with potential benefits in the treatment of NAFLD include pantethine or pantothenic acid, taurine, magnesium, zinc with copper, vitamin B6, biotin, manganese and lysine.
 Younossi ZM, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011 Jun;9(6):524-530.e1; quiz e60. Epub 2011 Mar 25. View Abstract
 Williams CD, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124. View Abstract
 Vernon G, et al. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. Epub 2011 May 30. View Abstract
 Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120:1640. View Abstract
 Charatcharoenwitthaya P, et al. The spontaneous course of liver enzymes and its correlation in nonalcoholic fatty liver disease. Dig Dis Sci. 2012 Jul;57(7):1925-31. Epub 2012 Feb 29. View Abstract
 Banderas DZ, et al. γ-Glutamyl transferase: a marker of nonalcoholic fatty liver disease in patients with the metabolic syndrome. Eur J Gastroenterol Hepatol. 2012 Jul;24(7):805-10. View Abstract
 Tetri LH, et al. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G987-95. View Abstract
 Qureshi AA, Sami SA, Salser WA, Khan FA. Synergistic effect of tocotrienol-rich fraction (TRF(25)) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans. J Nutr Biochem. 2001 June 12(6):318-329 View Abstract
 Malaguarnera M, et al. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis–a randomized and controlled clinical trial. Am J Gastroenterol. 2010 Jun;105(6):1338-45. View Abstract
 Buchman AL, et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology. 1995 Nov;22(5):1399-403. View Abstract
 Gaby AR. Nonalcoholic fatty liver disease in Nutritional Medicine, pg 493. 2011.
 Gaby AR. Nonalcoholic fatty liver disease in Nutritional Medicine, pg 494. 2011.
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