Treatment of Fatty Liver Disease—Time to Implement Common Sense Measures

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases in which excess fat deposits in the liver (steatosis, NAFL) are separate from but can progress to inflammation and fibrosis (nonalcoholic steatohepatitis, NASH), fibrosis, and cirrhosis. Nonalcoholic fatty liver disease has become a major public health issue, affecting about 25% of adults worldwide and two-thirds of adults with obesity. 1 Hepatocellular carcinoma associated with NAFLD increased 10-fold between 2000 and 2010, and trends suggest that NAFLD will emerge as the leading cause of end-stage liver disease in the coming decades. 2 Beyond liver disease, patients with NAFLD are at significant risk of cardiovascular morbidity and mortality. 3 Approximately 20% of patients with NAFLD progress to NASH, which is associated with more rapid rates of fibrosis and liver-related mortality. Liver biopsy is the gold standard for classification of NAFLD. However, owing to cost and risk for morbidity, biopsy is often reserved for cases of clinical suspicion for NASH or advanced fibrosis. Noninvasive assessment of fibrosis stage such as clinical prediction rules (eg, NAFLD Fibrosis score, FIB-4) and/or imaging (ultrasonography or magnetic resonance-based elastography) are also helpful for diagnosing and staging of NAFLD. Obesity is the most common and well-documented risk factor for NAFLD.The link between obesity and NAFLD has prompted investigation of weight loss interventions as a potential treatment for NAFLD. However, there has been considerable variability in intervention types and outcome measures. The metaanalysis by Koutoukidis et al 4 in this issue of JAMA Internal Medicine better characterizes the impact of weight loss interventions and builds a compelling case for implementing formal weight loss programs as a mainstay in the treatment of NAFLD. In their systematic review of 22 randomized clinical trials that included 2588 participants with NAFLD, Koutoukidis et al 4 found that weight loss interventions were associated with improvements in blood biomarkers of liver disease, as well as radiologic and histologic markers. 4 This study confirms the importance of weight loss interventions in the treatment of NAFLD. Koutoukidis et al 4 specifically observed the association between weight loss by various intervention types and improvement in liver blood biomarkers, such as alanine transaminase (ALT) and aspartate transaminase (AST), and improvement in steatosis based on a collection of outcome measures from various studiesincluding histologic analysis, magnetic resonance imaging, ultrasonography, and NAFLD activity score. Whereas AST and ALT are surrogate markers for steatosis and NASH, they are

Advanced liver fibrosis and the metabolic syndrome in a primary care setting

“…Fibrosis is the result of advanced NAFLD liver injury and accurate identification is critical, because fibrosis itself predicts adverse outcomes 16,23,24 . The prevalence of NAFLD‐associated fibrosis has surged, with a more than twofold increase over the past two decades, and is associated with increased mortality, liver cancer and liver transplantation 25,26 .…”