Metabolic Parameters Similar Between Lean and Obese NAFLD Patients

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The inter-relationship of HPCs, HSCs, and macrophages was influenced by the stage of fibrosis, but not BMI.

There are many similarities between lean and overweight or obese individuals with non-alcoholic fatty liver disease (NAFLD).

A team, led by Archana Rastogi, Institute of Liver & Biliary Sciences (ILBS), evaluated the prevalence of NAFLD in lean patients and explored clinico-pathological spectrum of lean NAFLD in comparison to over-weight or obese individuals.

The investigators examined patients with histologic-confirmed NAFLD and investigated the role of hepatic stellate cells, macrophage polarization, and their relation to hepatic progenitor cells.


NAFLD, which is 1 of the most common causes of chronic liver diseases, can occur in lean individuals that have normal or low BMI.

“Crucial issue is understanding the clinical, pathobiologic and metabolic characteristics in comparison to obese patients,” the authors wrote. “Very few studies have compared clinicopathological characteristics between lean and obese.”

Existing research has various limitations, including small cohorts of patients, rarely included over-weight individuals as a separate category, and often use non-standardized use of BMI criteria with discordant conclusions.

There is also very little data on liver biopsy-confirmed cohorts nor is there any published studies exploring the role of mediators such as stellate cells, progenitor cells, and macrophages.

In the prospective analysis, the investigators examined 11 years of retrospective cross-sectional data on 1273 consecutive patients diagnosed with NAFLD between 2011-2021.

The team stratified all of the histologically confirmed cases of NAFLD into 3 separate groups based on BMI using the Asian criteria and performed demographic, lab, metabolic, and histological comparisons between lean individuals (21%; n = 267) and overweight (18.2%; n = 232) or obese participants (60.8%; n = 774). At baseline, 13.9% of the lean patient group were underweight weight a BMI less than 18.5 kg/m2.

They also performed histological grading and staging of NAFLD components by NAS-CRN scores and assessed and quantified stellate cells, progenitor cells, and macrophage polarization using immunohistochemical and image analysis.

Comparing Lean and Obese Individuals

The results show leaner patients had a significantly lower BMI and waist circumference, as well as lower fasting glucose levels in comparison with the overweight or obese groups. However, the remainder of metabolic parameters were virtually the same.

On the other hand, lean patients had higher serum ALT levels and histological characteristics, including ballooning of hepatocytes and steatosis than the other groups.

For lean patients with NASH-related cirrhosis, 20.9% had lobular inflammation and advanced fibrosis, which is significantly less common than the other groups of patients.

Further immunophenotypic studies showed the inter-relationship of HPCs, HSCs, and macrophages was influenced by the stage of fibrosis, but was not influenced by BMI.

“Prevalence of NAFLD in lean individuals in a histological-confirmed patient cohort was 21%,” the authors wrote. “Major strengths of this study are large cohort of lean individuals from a single center, inclusion of only histology-confirmed cases, Asia specific BMI criteria usage, comparative clinical, metabolic, immune-morphologic and image analysis-based characterization, inclusion of over-weight in addition to obese patients, and investigating cross-talk of principal patho-physiologic markers.”

The study, “Non-alcoholic fatty liver disease (NAFLD) in lean individuals- Single center large cohort clinicopathologic and immunophenotypic study,” was published online in Pathology – Research and Practice.