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Should We Screen for NASH?

Manal F. Abdelmalek, MD, MPH

Professor of Medicine
Division of Gastroenterology and Hepatology
Duke University
Durham, North Carolina

Manal F. Abdelmalek, MD, MPH, has disclosed that she has received consulting fees from 89 Bio, Bristol-Myers Squibb, Madrigal, Hanmi Pharma, Intercept, NGM Biopharmaceuticals, Novo Nordisk, and TaiwanJ; and funds for research support from Allergan, BI, Bristol-Myers Squibb, Celgene, Galactin, Galmed, Genfit, Gilead Sciences, Enyo, Hanmi Pharma, Intercept, Madrigal, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Progenity, Poxel, TaiwanJ, and Viking.

View ClinicalThoughts from this Author

Released: March 16, 2021

Nonalcoholic fatty liver disease (NAFLD) can progress in a minority of patients to advanced liver disease and has quickly become the most common chronic liver disease in the United States and in many developed countries worldwide. The most recent worldwide prevalence estimates for NAFLD among adults is approximately 25%. The worldwide prevalence estimates of nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is 3% to 5%. These prevalence estimates nearly double in patients with diabetes, as NAFLD is closely linked with metabolic syndrome, obesity, and diabetes. With an estimated prevalence of 1% to 2% of adults with advanced hepatic fibrosis due to NASH, the potential burden on public health is enormous.

Early Identification
Despite the high prevalence of NAFLD, awareness for this otherwise asymptomatic condition is low. Whereas gastroenterologists and hepatologists diagnose and stage NAFLD with intention, other healthcare professionals typically discover NAFLD incidentally. The asymptomatic nature of the disease, low awareness, and lack of intentional diagnosis/staging results in patients being diagnosed and referred when symptoms related to advanced liver disease become clinically evident—a time at which there is increased risk for adverse outcomes and when treatment options have little benefit. Identifying NAFLD in the primary care setting can help with early intervention and prevention strategies that can decrease risk of disease progression.

Advanced Hepatic Fibrosis
Hepatic fibrosis
is the strongest predictor for adverse clinical outcomes. Although the transition from mild-stage to intermediate-stage fibrosis may span many years and although disease activity may even wax and wane, the transition from bridging fibrosis (stage 3) to cirrhosis (stage 4) can occur in approximately 20% of patients in as quickly as 2-3 years. Likewise, approximately 20% of those with cirrhosis may have an adverse liver-related clinical event within 2-3 years.

Need for Routine Screening?
NAFLD is the outcome of a physiologic problem of altered metabolism. The metabolic syndrome is strongly associated with NAFLD as well as cancer, cardiovascular disease, diabetes, obesity, and chronic kidney disease. Although guidance for screening for other complications of metabolic syndrome exist, routine screening patients for NAFLD—even those at high risk—is not currently recommended by the AASLD owing to uncertainties around diagnostic tests and treatments options, along with knowledge gaps related to long-term benefits and cost-effectiveness of screening. However, guidance from the AASLD, the EASL-EASO-EASD, and ADA do recommend healthcare professionals have a “high index of suspicion for NAFLD/NASH, particularly in patients with type 2 diabetes,” the cohort of patients at highest risk for significant (stage ≥ 2) hepatic fibrosis. They all call out patients with type 2 diabetes as warranting workup.

Risk Stratification
Risk-stratifying patients with NASH boils down to recognizing risk factors for advanced hepatic fibrosis. The strongest risk factors for NAFLD/NASH are the presence of type 2 diabetes, aged older than 50 years, and a first-degree family member with NASH or NASH-related cirrhosis. Other clinical predictors of NASH with hepatic fibrosis include the presence of ≥ 3 features of metabolic syndrome, elevated liver aminotransferases, dyslipidemia, polycystic ovary syndrome, or obstructive sleep apnea.

FIB-4 Index
One simple and cost-effective tool to assist with risk-stratification of NAFLD/NASH is the Fibrosis-4 (FIB-4) Index for Liver Fibrosis. The FIB-4 score is calculated using liver biochemistries, age, and platelet count, which are readily available from routine bloodwork.

FIB-4 has an excellent negative predictive value, allowing for confident exclusion of patients with a low likelihood of advanced hepatic fibrosis. Patients with a low FIB-4 score (< 1.3) can be followed in a primary care setting with repeat annual FIB-4 measures to assess change over time.

Coupling the FIB-4 score with transient elastography or magnetic resonance elastography, or performing these tests sequentially, can optimize performance of a noninvasive approach to risk stratification. A liver biopsy may be required if there is concern for competing diagnoses or discordant or indeterminate results from noninvasive biomarkers, but biopsy should be performed selectively owing to its increased cost and risk.

The broader utilization of noninvasive biomarkers, when coupled with ascertainment of clinical risk factors, will facilitate identifying those patients who require referral to a specialist for consideration of liver biopsy and tailored therapeutic approaches.

Your Thoughts?
Do you screen for NAFLD or NASH in your patients? Answer the polling question and join the conversation by posting in the discussion section.

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