Nonalcoholic Fatty Liver Disease

Manal Abdelmalek, MD, MPH, on the Diagnostic Challenges in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease in the United States. Between 30% and 40% of adults have NAFLD, and between 3% to 12% of adults have nonalcoholic steatohepatitis (NASH), according to the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.

Treatment options for NAFLD and NASH are limited. However, new pharmacologic treatment options are on the horizon, making accurate diagnosis and staging of disease a priority.

Gastroenterology Consultant spoke with Manal Abdelmalek, MD, MPH, from the Duke University School of Medicine, at the American College of Gastroenterology (ACG) 2019 Annual Scientific Meeting and Postgraduate Course, where she discussed the challenges associated with diagnosing and staging NAFLD and NASH.

Gastroenterology Consultant: What do you think is the biggest challenge in the diagnosis of NAFLD and NASH?

Manal Abdelmalek: The biggest challenge with diagnosis is not so much the assessment of the presence or absence of the disease, since we can use ultrasonography imaging or liver enzymes alone to risk-stratify severity of disease. While we can readily diagnose the presence of NAFLD via imaging or the ascertainment of metabolic risk factors in the presence of unexplained elevation of liver enzymes, we have not yet been able to use these simple diagnostic modalities to identify the patients who may have negative clinical outcomes from NAFLD and NASH or have underlying advanced hepatic fibrosis. Additionally, the diagnostic testing which would readily be available in the primary care physician or endocrinologist offices may not be readily available in a gastroenterologist’s office.

GASTRO CON: Which biomarkers do you believe are the most useful for diagnosis?

MA: There is an evolving landscape of noninvasive tests for biomarkers—transient elastography, magnetic resonance elastography, and serum‑based biomarkers for algorithms—that can be used to risk-stratify patients with advanced hepatic fibrosis. The algorithms could include the NAFLD Fibrosis Score or the Fibrosis‑4 score (FIB-4). The Enhanced Liver Fibrosis (ELF) test is not yet approved for use in the United States, but it can potentially help stratify those with the highest risk of advanced hepatic fibrosis. Unfortunately, the optimal sensitivity and specificity for all of these tests are not ideal enough yet for population‑based testing. Their performance can vary based on the population for which the tests are being used. So, we still have a long way to go.

GASTRO CON: Why is it important for a gastroenterologist to know how to properly diagnose and stage NAFLD or NASH?

MA: It is important to note that a minority of patients in the entire population of patients with nonalcoholic fatty liver have disease progression that is significant enough to result in increased morbidity and mortality from NAFLD. So, it is impractical to test and treat everybody with benign hepatic steatosis, or even those with potentially mild fatty liver disease, if they are otherwise going to live and die with their disease. The exception to this is if it is imperative from both a health care utilization standpoint and for resource management to simply be able to select them from the population at risk. Patients who are going to have a negative clinical outcome or those who are going to need more tailored clinical care management, whether that be surveillance for hepatocellular carcinoma (HCC), screening for esophageal varices, or to define who is in the highest need of pharmacological therapies when those become available.

GASTRO CON: What are the key takeaways for specialists about the current diagnostic and staging methods for NAFLD and NASH?

MA: The key messages for specialists are, number one, we need to utilize our clinical algorithms to identify the patients who are at highest risk. Simply put, patients at highest risk tend to be patients who have 3 or more risk factors in metabolic syndrome, the presence of diabetes, are older than 50 years, or have a first‑degree family member with unexplained cirrhosis. Secondly, we need to define patients based on either clinical risk factors or surrogate measures that can help us risk-stratify those patients who are potentially more advanced. We need to be able to use FibroScan or elastic transient elastography—maybe even use one of these in combination with serum‑based biomarkers like the FIB-4, the ELF test, or the NAFLD Fibrosis Score—so that we can stratify those patients for proper care and management. The third key message is that we have been in a field for which one could argue that in the absence of therapeutic treatments, more proactive identification of patients was somewhat futile. However, new therapies are on the horizon. We are at a point in time where we may actually be able to lend therapies to change the natural history of the disease.


Manal Abdelmalek, MD, MPH, is a professor of medicine in the Division of Gastroenterology and Hepatology at the Duke University School of Medicine in Durham, North Carolina. She is also director of the NAFLD Clinical Research Program at the Duke University School of Medicine.