New Update Focuses on NAFLD in Lean People

Liam Davenport

July 26, 2022

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the US and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, and colleagues. They add that around one quarter of those affected have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma.

Although NAFLD occurs primarily in individuals with obesity or type 2 diabetes, between 7%-20% have a lean body habitus, they write.

There are differences in rates of disease progression, associated conditions, and diagnostic and management approaches between lean and non-lean patients, the authors note, but there is limited guidance on the appropriate clinical evaluation of the former group.

The American Gastroenterological Association therefore commissioned an expert review to provide best practice advice on key clinical issues relating to the diagnosis, risk stratification, and treatment of NAFLD in lean individuals.

The review was published online in Gastroenterology.

Evidence-Based Approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) < 25 in non-Asian persons and < 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD, but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is advised as well.

Fatty Liver Disease in Lean People With Metabolic Conditions

Approached for comment, Liyun Yuan MD, PhD, Assistant Professor of Clinical Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Yuan, who was not involved in the review, told Medscape Medical News that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or are overweight.

Zobair Younossi, MD, MPH, Professor of Medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Virginia, added that there is a lack of awareness that NAFLD occurs in lean individuals, and especially in those who have diabetes.

He told Medscape Medical News that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Younossi declares no relevant relationships.

Gastroenterology. Published online July 13, 2022. Full text

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