Puneet Puri is Medical Director of the Metabolic Liver Disease Clinic, and Michael Fuchs is Chief of Hepatology and Liver Transplantation, both at Hunter Holmes McGuire VAMC in Richmond, Virginia. Puneet Puri is an Associate Professor of Medicine, and Michael Fuchs is a Professor of Medicine, both at Virginia Commonwealth University in Richmond. Correspondence: Michael Fuchs (michael .fuchs2@va.gov)
Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Assessment of disease burden should not be restricted to clinical outcomes as patients can experience a range of symptoms that may have significant impact on their health-related quality of life (QOL) and functional status.20 Using general but not disease-specific instruments, NAFLD patients reported outcomes score low regarding fatigue, activity, and emotions.21 More disease-specific questionnaires may provide better and disease-specific insights as how NASH impacts patients’ QOL.22-24
Economic Impact
There is mounting evidence that the clinical implications of NAFLD directly influence the economic burden of NAFLD.25 The annual burden associated with all incident and prevalent NAFLD cases in the US has been estimated at $103 billion, and projections suggest that the expected 10-year burden of NAFLD may increase to $1.005 trillion.26 It is anticipated that increased NAFLD costs will affect the VHA with billions of dollars in annual expenditures in addition to the $1.5 billion already spent annually for T2DM care (4% of the VA pharmacy budget is spent on T2DM treatment).27-29
Current Patient Care
Obesity, DM, and dyslipidemia are common conditions managed by primary care providers (PCPs). Given the close association of these conditions with NAFLD, the PCP is often the first point of medical contact for patients with or at risk for NAFLD.30 For that reason, PCP awareness of NAFLD is critical for effective management of these patients. PCPs should be actively involved in the management of patients with NAFLD with pathways in place for identifying patients at high risk of liver disease for timely referral to a specialist and adequate education on the follow-up and treatment of low-risk patients. Instead, diagnosis of NAFLD is primarily triggered by either abnormal aminotransferases or detection of steatosis on imaging performed for other indications.
Barriers to optimal management of NAFLD by PCPs have been identified and occur at different levels of patient care. In the absence of clinical practice guidelines by the American Association of Family Practice covering NAFLD and a substantial latency period without signs of symptoms, NAFLD may not be perceived as a potentially serious condition by PCPs and their patients; interestingly this holds true even for some medical specialties.31-39 More than half of PCPs do not test their patients at highest risk for NAFLD (eg, patients with obesity or T2DM) and may be unaware of practice guidelines.40-42
Guidelines from Europe and the US are not completely in accordance. The US guidelines are vague regarding screening and are supported by only 1 medical society, due to the lack of NASH-specific drug therapies. The European guidelines are built on the support of 3 different stakeholders covering liver diseases, obesity, and DM and the experience using noninvasive liver fibrosis assessments for patients with NAFLD. To overcome this apparent conflict, a more practical and risk-stratified approach is warranted.41,42
Making the diagnosis can be challenging in cases with competing etiologies, such as T2DM and alcohol misuse. There also is an overreliance on aminotransferase levels to diagnose NAFLD. Significant liver disease can exist in the presence of normal aminotransferases, and this may be attributed to either spontaneous aminotransferase fluctuations or upper limits of normal that have been chosen too high.43-47 Often additional workup by PCPs depends on the magnitude of aminotransferase abnormalities.
Even if NAFLD has been diagnosed by PCPs, identifying those with NASH is hindered by the absence of an accurate noninvasive diagnostic method and the need to perform a liver biopsy. Liver biopsy is often not considered or delayed to monitor patients with serial aminotransferases, regardless of the patient’s metabolic comorbidity profile or baseline aminotransferases.32 As a result, referral to a specialist often depends on the magnitude of the aminotransferase abnormality,30,48 and often occurs when advanced liver disease is already present.49 Finally, providers may not be aware of beneficial effects of lifestyle interventions and certain medications, including statins on NASH and liver fibrosis.50-53 As NAFLD is associated with excess cardiovascular- and cancer-related morbidity and mortality, it is possible that regression of NAFLD may improve associated risk for these outcomes as well.
