Common Misconceptions in Hepatology: Nonalcoholic Fatty Liver Disease

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Abbreviations

NAFLD

nonalcoholic fatty liver disease

NASH

nonalcoholic steatohepatitis

“You want to see my patients with fatty liver? Is it really a big deal? There’s no way to treat it, right? Aren’t you just going to tell them to exercise and lose weight?”

This is a conversation I have with many health care providers that often ends in them gaining newfound appreciation for the management of nonalcoholic fatty liver disease (NAFLD). The purpose of this article is to dispel some misconceptions about NAFLD.

“What’s the big deal about fatty liver?”

NAFLD is the liver manifestation of the metabolic syndrome: characterized by histological or radiographic evidence of fat accumulation in the liver (hepatic steatosis), with or without associated inflammation or fibrosis (steatohepatitis) in the absence of alcohol or other causes of liver fat.1 It has a high prevalence rate, affecting 25% of individuals in North America.2 Importantly, whereas hepatic steatosis increases the risk for cardiovascular morbidity for all patients, the 30% of patients with NAFLD who have nonalcholic steatohepatitis (NASH) have a 40% risk for development of progressive liver injury, with roughly 20% experiencing the development of cirrhosis. Given the high overall prevalence, this represents a large cohort of patients at risk for advanced liver disease. In fact, the prevalence of NAFLD as an indication for liver transplant has increased 170% over a 10‐year period. NAFLD is currently the second most common liver disease for patients listed for liver transplant and is expected to become the number one indication for liver transplant in the next several years.3 In addition, although the risk for hepatocellular carcinoma in patients with cirrhosis is generally well known, more than 30% of NASH‐related hepatocellular carcinoma occurs in patients without cirrhosis, highlighting the need to closely monitor the most at‐risk patients (NASH with advanced fibrosis and metabolic syndrome).4

“Why do they need to see a specialist?”

A fundamental aspect of NAFLD management is the confirmation and staging of the disease to distinguish patients with simple steatosis who have an overall benign liver‐related prognosis, from those who have NASH and are at risk for progressive liver injury, from those who have an alternative diagnosis altogether. Due to the high prevalence, a portion of patients diagnosed with “NAFLD” may have an alternative or coexisting liver disease such as viral, autoimmune, or alcoholic liver disease. Ruling out and/or managing these other chronic liver conditions (that can often cause synergistic liver injury) is critical to NAFLD management. Staging of NAFLD is equally important to provide patients with valuable prognostic information and to tailor therapeutic interventions to an individual’s risk level, including those incidentally found to have cirrhosis. Importantly, simple liver function tests are not predictive of disease activity and can often be normal in patients with advanced liver fibrosis.

NAFLD diagnosis and staging can be achieved noninvasively, by imaging and elastography‐based methods, respectively. However, these modalities encompass inherent limitations and confounders. Ultrasound findings of “increased echogenicity indicative of hepatic steatosis” are nonspecific and cannot definitively distinguish hepatic fat from inflammation or fibrosis, and thus cannot rule out concurrent or alternative liver diseases. Similarly, transient elastography is subject to multiple common confounding factors including obesity. Given these issues, liver biopsy remains the gold standard for NAFLD diagnosis and staging. Determining which patients require histological confirmation with liver biopsy is another important aspect of subspecialist evaluation of NAFLD.

“But I thought that there’s nothing that you can do about NAFLD?”

The absence of a US Food and Drug Administration–approved medication for NAFLD is not synonymous with the absence of therapy for NAFLD. Specific lifestyle modifications and a variety of medical and surgical treatments have demonstrated efficacy in altering the disease course of NAFLD. It is important to understand these various therapeutic options and tailor treatment strategies based on an individual’s risk for progressive disease.

All patients with NAFLD should be encouraged to lose weight. A 7% weight loss has been shown to reduce liver fat and inflammation.5 Specific lifestyle modifications seem to be particularly effective at treating NAFLD. For example, a Mediterranean diet was shown to be more effective at reducing liver fat and inflammation than a low‐fat, high‐carbohydrate diet despite inducing similar amounts of weight loss.6 Management of comorbid metabolic conditions such as dyslipidemia and diabetes is also critical to NAFLD management and often requires referral to specialty care. Fortunately, many NAFLD‐directed lifestyle management strategies offer benefit across the spectrum of metabolic disorders.

“But does telling them to lose weight really work? Sometimes I feel like I am just wasting my time.”

Patients with NAFLD often struggle with weight loss. Physician acknowledgment and discussion of obesity can have a positive impact on patient success with weight loss.7 Nonetheless, because of a variety of factors, including time resources and provider frustration or discomfort discussing weight issues, obesity is greatly underaddressed in health care settings. Many providers report feeling underequipped with evidence‐based recommendations for obesity management.8 To address these inadequacies, many providers are pursuing specialized training in obesity medicine. Obesity medicine specialists are trained in the genetic, biological, environmental, social, and behavioral factors contributing to obesity and use a multifaceted approach to obesity treatment.9 Importantly, these specialists have developed practice infrastructure that allows them to provide an intensive multidisciplinary approach to obesity management with frequent visits and adjunctive care provided by dieticians, exercise physiologists, pharmacists, psychologists, and surgeons.

“Fair enough, but some patients will still struggle with weight loss. Is there no other treatment?”

Previous studies of agents designed to alter NASH disease course, including thiazolidinediones, vitamin E, and pentoxifylline, have demonstrated limited effectiveness in select populations. However, there are several large, late‐stage clinical trials of agents that in preliminary testing have shown significant benefit in altering NASH disease course.10 Approval of these therapies is eagerly anticipated, but for patients with advanced NASH who may not be able to wait, one should consider referral to a center with access to these clinical trials. Several studies have also shown the benefit of bariatric surgery in altering the course of NASH and the metabolic syndrome.11 In patients with advanced NASH, this therapeutic option may be a reasonable approach before patients develop cirrhosis with portal hypertension, which may preclude surgical therapy.

In conclusion, NAFLD is a highly prevalent disorder that can result in progressive liver injury and failure. Clear diagnosis and staging is a critical aspect of NAFLD management to tailor therapies based on patient prognosis. NAFLD therapy exists and can change disease course, but requires specialized intensive care plans for weight loss or referral for adjunctive therapies. The future burden of NAFLD on our patient population and health care system demands that the disease be recognized and appropriately managed now, when preventative or disease‐altering interventions can be instituted.