Management of patients with non-alcoholic fatty liver disease (NAFLD) requires combined efforts of general practitioners, hepatologists, and other experts, Herbert Tilg explains in a Mentoring, Education, and Training Corner article in the August issue of Gastroenterology.
NAFLD has become the most common liver disease worldwide. It ranges from simple steatosis in the absence of inflammation to nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. The prevalence is as high as 30% in the United States and parts of Asia, and rates are along with those of obesity and type 2 diabetes. More than 10% of patients with NAFLD are believed to have nonalcoholic steatohepatitis (NASH).
What is the best way to identify and manage these patients?
Tilg explains when to suspect that a patient has NAFLD, and provides an algorithm for diagnosis. He states that assessment of fibrosis is the most important task in the management of patients with NAFLD.
The NAFLD fibrosis score, fibrosis 4 calculator, enhanced liver fibrosis test, and FibroTest can be used to identify patients with advanced fibrosis, and results associate with cardiovascular and liver-related mortality. Tilg writes that although transient elastography is the most common technique used to define fibrosis stage of patients with NAFLD, it has limitations in evaluation of the very obese population and inter-investigator reliability. Tilg states that magnetic resonance elastography is now the most accurate method to assess stage of fibrosis.
Tilg explains that a definite diagnosis of NASH is important because inflammation and/or fibrosis dictate the long-term prognosis of this disease, which might ultimately require liver transplantation. Whereas liver-related long-term complications develop in patients with definite NASH, NAFLD has in general a high rate of extra-hepatic complications, including cardiovascular complications, chronic kidney disease, diabetes, and cancer.
Although there is no established treatment for NASH, therapeutic strategies are in development.
Lifestyle changes, such as weight reduction, reduce features of NAFLD. NASH disappeared in 85% of patients who underwent bariatric surgery, and fibrosis was reduced in more than 30% of patients. Diets high in protein (either animal or plant) significantly reduced liver fat in patients with diabetes and NAFLD, independently of body weight, and reduced markers of insulin resistance and hepatic necroinflammation. The diets appear to mediate these changes via lipolytic and lipogenic pathways in adipose tissue. Tilg also reviews the evidence that exercise reduces liver fat.
Tilg explains developments in pharmacotherapy for NAFLD, stating that although no drugs have been approved for treatment of NAFLD, agents such as thiazolidinediones (PPAR-gamma agonists), which reduce liver fat content, have shown effects in patients with NASH. Tilg remarks on results of trials with vitamin E, glucagon-like peptide-1 agonists, liraglutide, and an agonist of PPARs-alpha and -delta. He also discusses trials underway to target metabolic pathways, oxidative stress and inflammation, gut microbiota, and fibrosis (see figure).
Tilg explains the importance of following patients for liver complications such as hepatocellular carcinoma (HCC) as well as extrahepatic and systemic complications. Patients with a diagnosis of NAFLD require life-long monitoring for cardiovascular disorders, chronic kidney disease, diabetes, and non-liver malignancies such as colon neoplasias.
Tilg concludes that NAFLD is a syndrome with many features, so it is essential for physicians to consider patients in a holistic manner. It is important to search for signs of arterial hypertension, diabetes, and sleep apnea. Only a broad awareness in the medical community can lead to proper diagnosis and effective management and treatment.