Research finds | Nearly 26% of thin people also have fatty liver and need to lose weight to improve metabolic disorders!

Metabolic-associated fatty liver disease (MAFLD), commonly known as fatty liver, is one of the most common chronic liver diseases in the world. MAFLD is mainly caused by metabolic disorders (such as overweight, obesity, etc.), and the pathological process is manifested as liver inflammation and liver fibrosis. Some MAFLD may lead to end-stage liver disease, liver cancer and liver transplantation.

MAFLD kills about 20 million people worldwide each year, and according to the Global Burden of Disease (GBD) study, MAFLD is the main cause of the rapid increase in the incidence of cirrhosis, liver failure, and liver cancer. The incidence of MAFLD has been increasing over the past few decades, which is related to the changes in the overall population's lifestyle of high-calorie diet and lack of exercise.

However, it should be emphasized that not all MAFLD patients are overweight or obese. MAFLD patients with normal weight (BMI = 18.5-24.9 kg/m2) are called "thin MAFLD" patients, and the management of this group of fatty liver patients has become a focus of clinical attention.

Recently, Nature Reviews Gastroenterology & Hepatology, a subsidiary of Nature, published a major review, which elaborated in detail on the characteristics, epidemiological manifestations, pathogenesis, and management recommendations of lean MAFLD.

Screenshot source: Nature Reviews Gastroenterology & Hepatology

Definition of MAFLD

According to the latest standards, patients with hepatic steatosis can be diagnosed with MAFLD if they meet at least one of the following three criteria:

Being overweight or obese;

Have type 2 diabetes;

Evidence of metabolic disorder (if the patient is of normal weight);

For people of European descent, the criteria for normal weight, overweight and obesity in adults are: BMI = 18.5-24.9 kg/m2, BMI = 25-29.9 kg/m2, BMI ≥ 30 kg/m2. For Asians, the criteria for normal weight, overweight and obesity in adults are: BMI = 18.5-22.9 kg/m2, BMI = 23.0-24.9 kg/m2, BMI ≥ 25.0 kg/m2.

In addition, according to the definition in the international expert consensus on MAFLD, overweight or obese patients with hepatic steatosis are considered to have MAFLD; for people with normal weight, the diagnostic criteria for "lean MAFLD" are that patients must have evidence of hepatic steatosis and metabolic disorders (at least two relevant risk factors, including increased waist circumference, hypertension, low HDL-C levels, hypertriglyceridemia, impaired fasting glucose, insulin resistance and chronic subclinical inflammation).

Timely diagnosis of MAFLD helps to better predict the progression and prognosis of liver disease and comorbidities (such as cardiovascular disease, chronic kidney disease, lung function impairment, and cognitive impairment).

Characteristics of lean MAFLD

The incidence of lean MAFLD reported in different countries and regions around the world varies greatly, ranging from 5% to 26%. Lean MAFLD cases account for 15% to 50% of all MAFLD cases.

In China, according to a study of 810 subjects with normal weight, the incidence of lean MAFLD is about 17.5%; another study of 911 general population (without type 2 diabetes) in Hong Kong, China, showed that the incidence of lean MAFLD is about 19.3%.

Clinically, it is difficult to distinguish lean MAFLD from other types of MAFLD from a morphological perspective. The results of some cross-sectional studies have shown that the histological and metabolic characteristics of lean MAFLD patients are better than those of obese MAFLD patients. This is manifested as:

Lower histological severity: such as low proportion of steatohepatitis and advanced fibrosis;

The degree of metabolic abnormality is low: for example, the prevalence of diabetes, hypertension, dyslipidemia, liver cirrhosis, and cardiovascular disease is low.

The paper points out that there is currently little data on the long-term prognosis of thin MAFLD patients, and the conclusions are contradictory. Overall, the long-term outcomes of thin MAFLD patients are worse than those of healthy individuals, and may be similar to the prognosis of MAFLD patients with overweight/obesity.

Pathogenesis of lean MAFLD

Although the pathophysiological mechanism of lean MAFLD is still unclear, it is generally believed that metabolic disorders (such as cardiovascular metabolic diseases) may be the key determinants of the onset of lean MAFLD.

The paper emphasizes that under the combined effects of multiple factors such as genetics, lifestyle factors (such as alcohol intake, diet quantity/quality, physical exercise), enterohepatic circulation, and intestinal flora, the metabolic state of an individual is constantly changing, and adverse metabolic states will increase the risk of MAFLD.

▲Pathogenic factors of lean MAFLD (Image source: Reference [1])

In addition, the results of epigenome studies suggest that the pathogenesis of lean MAFLD may be related to genetic-environmental interactions. Specifically, an adverse intrauterine environment may induce changes in fetal metabolic processes, increasing the risk of MAFLD in adulthood.

A study of 90 children with MAFLD demonstrated that intrauterine growth retardation was associated with more severe histological insulin resistance and disease progression, an association that was independent of BMI.

Management of lean MAFLD

Due to the lack of research evidence, there are currently no specific guidelines for the management of thin MAFLD patients. Data from some observational studies suggest that weight loss in thin MAFLD patients may have the same effect as weight loss in obese MAFLD patients (although the target weight loss value for thin MAFLD patients may be lower).

A longitudinal study of 16,738 adults with MAFLD (including 2,383 with lean MAFLD) showed that weight loss was dose-dependently associated with the remission of fatty liver in both normal-weight MAFLD subjects and overweight/obese MAFLD subjects.

The Asia-Pacific Association for the Study of the Liver (APASL) guidelines state that for lean MAFLD patients, a 3% to 5% weight loss may be sufficient.

In addition, diet quality is one of the main modifiable risk factors for metabolic health, and its impact is independent of BMI and waist-to-hip ratio. Therefore, regardless of the patient's BMI status, they should receive professional dietary advice. Similarly, regardless of whether they have lean MAFLD or not, MAFLD patients should also increase daily physical exercise and reduce sedentary behavior to improve metabolic and cardiovascular health.

References

[1] Eslam, M., El-Serag, HB, Francque, S. et al. Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight. Nat Rev Gastroenterol Hepatol (2022). https://doi.org/10.1038/s41575-022-00635-5