Putting non-alcoholic fatty liver disease on the radar for primary care physicians: how well are we doing?

Non-alcoholic fatty liver disease (NAFLD) has emerged as a common cause of chronic liver disease worldwide. The global prevalence estimates are concordant with estimates for obesity, type 2 diabetes, and overall caloric intake. Importantly, the number of individuals experiencing a clinically significant ‘hard’ outcome, such as death, hepatocellular cancer, or the need for liver transplant, from NAFLD is rising [1]. Based on these data, disease models project a doubling or even tripling of the number of individuals who will have end-stage liver disease by 2030 in many regions of the world [2]. These serious public health implications are driving many efforts to gain the attention of health policymakers to tackle the problem on a major ‘war-footing’.

An alternate perspective is that NAFLD is a very common condition where the majority of individuals do not have a liver-related outcome and current efforts to raise awareness may lead to ‘fear mongering’, over investigation, and even over treatment. Both perspectives appear to be reasonable; however, the question remains as to which is closer to the truth lie and how this can inform public health strategies and investment of resources for NAFLD.

In order to dissect the data to unravel the core facts several issues must be considered. First, NAFLD represents a spectrum of disease, from minor accumulation of fat without inflammation or fibrosis to severe steatosis, microscopically visible hepatocellular injury in the form of ballooning, inflammation, and pericellular fibrosis. This latter pattern is further classically seen in zone III and referred to as definite steatohepatitis, whereas intermediate forms are referred to as borderline steatohepatitis [3]. The long-term clinical outcomes are determined by the broad phenotype, i.e., non-alcoholic fatty liver (NAFL) versus non-alcoholic steatohepatitis (NASH), and the fibrosis stage [4]. While markers of disease activity have been considered irrelevant, studies making such claims have significant limitations with their internal and/or external validity. Further, recent rigorously performed studies suggest that changes in disease activity are indeed related to changes in disease progression or regression [5]. Unfortunately, it is not possible to obtain histological data in population-based studies and those defining the burden of disease rely on imaging modalities that measure steatosis, cannot distinguish between NAFL and NASH, and do not assess modest levels of fibrosis. Liver enzymes such as alanine aminotransferase (ALT) are also used as a surrogate for liver injury and, in the absence of alternate causes of liver injury such as viral hepatitis and in the presence of other risk factors for NAFLD such as obesity and type 2 diabetes, it is inferred that NAFLD is the cause of abnormal ALT.

Multiple studies have used either imaging or ALT to ascertain the prevalence of NAFLD. Of the two approaches, those that are imaging based are generally considered more accurate since a substantial proportion of individuals with NAFLD can have normal ALT. Further, of the imaging methods used, MRI is the most accurate, while sonographic evidence of an echogenic liver is only moderately sensitive and not very specific.

The study by Alexander et al. [6] further highlights a lack of awareness of liver disease in general, and NAFLD in particular, underscoring the need for greater physician education. This is likely to be successful only through the development of simple tools that can be implemented in primary care settings to identify those at greatest risk of outcomes, along with effective therapeutics to improve outcomes in these target populations. Ultimately, common sense dictates a need for greater emphasis on healthy living and integrated preventive approaches for NAFLD and complications of the metabolic syndrome.