Non-alcoholic fatty liver disease is often unknown. It manifests similarly to metabolic syndrome. It can result in non alcoholic fatty liver or non-alcoholic steatohepatitis. These conditions are extremely common in diabetics (69%) and obesity (90%). Thus, the established risks are type II diabetes, metabolic syndrome, hypercholestemia, and obesity. In addition, disease states such as polycystic ovarian syndrome, hypothyroidism, obstructive sleep apnea, and hypopituitarism are concurrent conditions with non-alcoholic fatty liver disease. It commonly presents in Hispanic males.
The etiology and progression is multifactorial. Pathologically, both inflammation and triglyceride accumulation contribute to the disease state. Factors such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and inflammation are involved in the hepatic destruction. If these factors are allowed to precipitate, then complications can result. These complications include fibrosis, cirrhosis, and potential mortality.
Preventing the progression is early diagnosis. Non-alcoholic fatty liver disease must be differentiated from alcoholic liver disease, viral hepatits, and other metabolic liver conditions. This is completed via diagnostic imaging, such as CT ultrasonograpy, and MRI, with the gold standard being MRI. In addition, the common symptoms are ascites, fatigue, gastrointestinal bleeding, and jaundice along with abnormal laboratory values of ALT, AST, iron, prothrombin, and alkaline phosphatase. Liver biopsy is utilized to measure the disease progression, especially fibrosis extent.
However, treatment is available to reduce this progression. First, lifestyle modifications can reduce steatosis. A 3-5% weight loss along with exercise decreases steatosis. In addition, complying to dietary behaviors of 45-60% complex carbohydrate intake, 20-30 grams/day of fiber intake, fructose and simple sugar reduction, 20-25% lean protein intake, < 10% of saturated fats, omega 3 consumption, and > 20% of mono unsaturated fatty acids will decrease fibrosis, inflammation, and lipogenesis. Second, if lifestyle modifications fail to reduce or prevent disease, medications exist to aid in health. There are both old and new drugs of vitamin E, thiazolidinediones, metformin, ursodeoxycholic acid, pentoxifylline, omega-3, obeticholic acid, elafibranor, liragluide, selonseri, aramchol, and cenicriviroc.
There are mixed reviews of some of the older therapies. Vitamin E is recommended for NASH without diabetes or cirrhosis at a dose of 800 units per day and potential for increased prostate cancer, hemorrhagic stroke, and all cause mortality. Pioglitazone is recommended for NASH at a dose of 30 mg per day with potential for weight gain, bone loss, bladder cancer, and congestive heart failure. Metformin is not recommended although studied at doses of 500-3000 mg/day. Ursodeoxycholic acid is not recommended although studied at doses of 28-35 mg/kg/day. Pentoxifylline is recommended for NASH at doses of 1200 mg/ day with potential nausea and vomiting. Omega 3 is recommended as first line therapy at doses of 1-6 grams with potential burping, indigestion, and dysgeusia.
Evidence for new medication use entail improving steatosis and fibrosis. Obeticholic acid improves steatosis and fibrosis with potential itching. Elafibranor aids in fatty liver resolution with potential for nausea, headache, diarrhea, and elevated serum creatinine. Liraglutide improves steatosis and aids in fatty liver resolution with potential weight loss along with injection-site reactions, headache, abdominal pain and vomiting. Selonserti and Aramchol without any definite known improvements but known adversities of abdominal pain, back pain, and fatigue. Cenicriviroc improves fibrosis with potential for fatigue, diarrhea, and headache.
Although the drugs are available, the most optimal treatment is lifestyle modifications. In fact, reducing saturated fat and simple sugar intake has been shown to prevent as well as resolve fatty liver disease. In the presence of non adherence to either lifestyle modifications or drug therapy, fatty liver disease can progress to multiple complications. These complications include irreversible fibrosis, cardiovascular disease, and diabetes, chronic conditions reducing quality of life. As a result, it is significant to comply to healthy lifestyle behavior to maintain liver functionality.
Pharm D, BCPS, BCACP, CDE, MSMTM, BSN, CPTT