Nonalcoholic Fatty Liver Disease

GENERAL PRINCIPLES

• Nonalcoholic fatty liver disease (NAFLD) is a Clinicopathologic syndrome that encompasses several clinical entities that range from simple steatosis to steatohepatitis, fibrosis, ESLD, and HCC in the absence of significant alcohol consumption.

• NASH is part of the spectrum of NAFLD and is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis.

• NAFLD is associated with an increasing prevalence of type 2 diabetes, obesity, and the metabolic syndrome in the US population.

• NAFLD has become one of the leading causes of liver transplantation in the US.

DIAGNOSIS

Clinical Presentation

The disease may vary from asymptomatic liver fatty infiltration to advanced fibrosis, cirrhosis, and HCC.

Diagnostic Testing

• When hepatic steatosis is detected on imaging and patients have symptoms or signs attributable to liver disease or have abnormal liver biochemistries, they should be evaluated for NAFLD and worked up accordingly.

• In patients with hepatic steatosis detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries, it is reasonable to assess for metabolic risk factors (e.g., obesity, insulin resistance, dyslipidemia) and alternate causes for hepatic steatosis such as significant alcohol consumption or medications.

• Clinical diagnosis can be made based on adequate history, physical examination, laboratory tests, and typical imaging findings after excluding other causes of hepatic steatosis.

• Noninvasive predictive models, serum biomarkers, and imaging studies are increasingly used as surrogate measures of liver fibrosis, inflammation, and steatosis, without replacing liver biopsy.

• VCTE or MRE are useful noninvasive tools to assess liver fibrosis in NAFLD patients. Liver biopsy should be considered in patients at high risk for steatohepatitis or advanced fibrosis or if the diagnosis remains unclear. It remains the gold standard test for the diagnosis of NASH, allowing assessment of the degree of inflammation and fibrosis.

TREATMENT

Nonpharmacologic Therapies

• Therapies to correct or control associated conditions are warranted (weight loss through diet and exercise, ti ght control of diabetes and insulin resistance, appropriate treatment of hyperlipidemia, and discontinuation of possible offending agents).

All patients with NAFLD should be encouraged to lose at least 7%-10% of their body weight. Weight loss has been shown to improve liver enzymes and histology in clinical trials. Weight loss of 3% body weight can lead to improvement of steatosis. At least 7% weight loss can lead to resolution of NASH, while 10% or greater weight loss can lead to fibrosis regression. Weight loss is clearly effective; however, fewer than 20% of patients are able to maintain the lower body weight.

Medications

Medications with long-term efficacy and safety are lacking in NAFLD. Vitamin E and/or pioglitazone may be used but treatment should be given only in biopsy-proven NASH in patients without contraindications with ample discussions of risks and benefits.

Surgical Management

• Bariatric surgery should be considered for otherwise eligible obese patients with NASH. It is not yet considered a specific treatment for NASH, though prospective studies have shown significant improvement/resolution of NASH following bariatric surgery.

• Liver transplantation should be considered in patients with NASH-related ESLD.

Outcome and Prognosis

• Approximately 25% of patients with simple steatosis will progress to NASH.

• Progression to NASH cirrhosis has been reported at a rate of 11% over a 15-year period.

• Cardiovascular disease is the most common cause of death in NAFLD patients.²¹