Non-Alcoholic Fatty Liver Disease (NAFLD)
Treatment of NAFLD
Despite a growing understanding of the pathology of NAFLD, scientists have been persistently baffled in their attempts to prevent and treat it with drug therapies. Lifestyle interventions such as steady, gentle weight loss and regular exercise have been the only interventions that offered any hope at all.2,9 Insulin-sensitizing drugs, while theoretically of value, have proved disappointing in clinical trials.18,19
The only successful pharmaceutical intervention for dealing with NAFLD has been metformin, which is examined further in this section.
Cholesterol-lowering drugs like statins have no proven benefit to date.4 Further studies are needed to determine if bariatric surgery to induce weight loss benefits patients with NAFLD.9,20
Because of the central role of insulin resistance in the development of NAFLD and NASH, it makes sense to evaluate insulin-sensitizing drugs for their prevention.21,22 No oral antidiabetic drug has as broad a spectrum of action, and as hefty a safety record, as the drug metformin, which is finding a host of new applications outside of diabetes itself.23,24
Studies of metformin for NAFLD and NASH have multiplied in the past few years. Metformin, 500 mg three times daily for six months, produced dramatic improvements in liver blood flow and velocity as detected by Doppler ultrasound exams.25 A similar dose of metformin (20 mg/kg body weight for one year, or approximately 1,450 mg/day for a 160-lb individual) produced reductions in blood markers of liver cell death.26 On the other hand, improved insulin sensitivity has repeatedly been shown in patients with NASH and NAFLD who take metformin, and many studies have now shown sustainable improvements in liver chemistry measurements.21,27 And a recent study showed significant reduction in the prevalence and severity of fatty liver after six months’ treatment with 850 mg metformin twice daily in obese adolescents.28
Metformin is an ideal drug for combination studies because of its safety and compatibility with other therapies. The combination of metformin with the potent antioxidant N-acetyl cysteine (NAC) for 12 months improved liver chemistry results, measurements of insulin resistance, and liver appearance on biopsy.29
Recent evidence shows that metformin blocks the induction of cellular stress proteins in cultured liver cells, protecting them from death induced by fatty acids.30 This novel mechanism adds to metformin’s already impressive array of multitargeted effects on metabolism and fatty liver disease.
What You Have Learned So Far
- One in three Americans now suffers from the stealth condition known as non-alcoholic fatty liver disease or NAFLD.
- NAFLD may go undetected for years, and may progress to liver inflammation and scarring (cirrhosis) or full-blown liver failure.
- While chiefly driven by poor dietary choices linked to metabolic syndrome and “diabesity,” genetic factors can also play a role in NAFLD’s progress.
- Medical science has proved relatively helpless at preventing or treating NAFLD and NASH, leaving millions of Americans vulnerable to their effects.