If You Are Thin with MASLD, You Are More At Risk!

MASLD is the latest term used for fatty liver. MASLD stands for Metabolic Dysfunction Associated Steatotic Liver Disease.

Fatty liver or NAFLD (non-alcoholic fatty liver disease) is fat deposition in the liver. It is common in individuals with obesity, Diabetes, and other metabolic conditions.

When individuals with fatty liver have elevated levels of liver enzymes or a liver biopsy is performed which shows inflammation, it is then called steatohepatitis.

In alcoholic individuals, it is called ASH (alcoholic steatohepatitis). In non-alcoholics, it is termed NASH (non-alcoholic steatohepatitis.

In 2020, new terms, MAFLD and MASH, were proposed. MAFLD stands for Metabolic Dysfunction Associated Fatty Liver Disease. MASH stands for Metabolic Dysfunction Associated Steatohepatitis.

In June 2023, the new term, MASLD (Metabolic Dysfunction Associated Steatotic Liver Disease) was chosen with consensus [Ref].

Both MAFLD and MASLD are diagnosed by imaging, biopsy, or liver biomarkers, however, there are slight differences:

• The waist circumference has been set at a cut-off of 94 cm in men and 80 cm in women in individuals with MASLD. In MAFLD, the waist circumference has been set as 102 for Caucasians and 88 for Asians.
• In addition, two extra parameters indicative of insulin resistance and inflammation have been added to the criteria of MAFLD: hs-CRP >2 mg/L and HOMA-IR of 2.5 or more

Other parameters including obesity/ overweight, hypertension/ prehypertension, and Dyslipidemia are the same for both [Ref].

Obesity and being overweight is one of the hallmarks of fatty liver diseases, however, recent studies show that lean individuals are more likely to develop advanced fibrosis and may have poor outcomes compared to obese individuals.

Here is a study published recently.

Key points of the Study:

• A new study has discovered that NAFLD is more common in lean individuals, with a prevalence of 5.3%.
• Despite having a better metabolic profile, lean individuals with NAFLD exhibited a higher prevalence of advanced fibrosis (3.7%) compared to their non-lean counterparts (1.7%).
• Lean status in people with nonalcoholic fatty liver disease (NAFLD) was linked to a higher risk of advanced fibrosis, liver-related events, chronic kidney disease, and overall mortality, even after controlling lifestyle habits, metabolic risk factors, and demographics.
• Researchers revealed that the severity of fibrosis was correlated with adverse outcomes, including liver-related events and overall mortality, irrespective of lean or non-lean status and regardless of other traditional risk factors.
• This large community-based cohort study reinforces the understanding that NAFLD in slim people is more severe.

The link between Obesity and MASLD:

Being overweight is closely connected to problems with how your body processes food. When a person is obese, especially with significant belly fat, it makes it harder for their body to use insulin and manage things like cholesterol and blood pressure.

Hence, metabolic disorders are more prevalent in diabetics as well as obese people. [ref]

Fat cells also release substances that can cause inflammation throughout the body, making these issues worse.

So, it is really important to tackle obesity by making lifestyle changes and controlling weight to keep these health issues in check.

However, this guideline to maintain a healthy lifestyle was directed at overweight or obese patients still now.

The latest research has concluded that non-alcoholic fatty liver disease (NAFLD) or MASLD in lean individuals is associated with advanced fibrosis and has a more protracted course.

The name of NAFLD has been changed to metabolic dysfunction-associated steatotic liver disease (MASLD) [ref].

In an extensive community-based study, it was conclusively established that Non-Alcoholic Fatty Liver Disease (NAFLD) in lean individuals is associated with more severe outcomes, including advanced fibrosis, liver disease progression, chronic kidney disease, and overall mortality [Ref]

This emphasizes the significance of recognizing and addressing the severity of NAFLD in lean populations to implement effective clinical management and preventive strategies.

MASLD in Lean Individuals: Study methodology:

NASH-CO was a community-based research project that looked at the degree of liver damage and clinical outcomes in a lean population with non-alcoholic fatty liver disease (NAFLD).

The researchers analyzed data from 169,303 participants in the Constances cohort after excluding those with extreme alcohol consumption, viral hepatitis, and other liver diseases, resulting in a final sample size of 137,206 subjects.

NAFLD and fibrosis were diagnosed using the Fatty Liver Index and the Forns Index. Participants were followed for a median duration of 3.58 years.

The prevalence of NAFLD was determined, and comparisons were made between lean and nonlean NAFLD subjects.

Furthermore, adjustments were made for demographics, metabolic risk factors, and lifestyle, and statistical analyses, including odds ratios and hazard ratios, were employed to assess associations between lean status and advanced fibrosis, liver-related events, chronic kidney disease, and overall mortality.

Summary of the findings:

In addition, liver-related events, kidney disease, and overall death rates were high in lean individuals with NAFLD/ MASLD.

Previous studies mentioning MASLD in Thin Individuals:

Even though there is less awareness regarding the association between slim humans and NAFLD, this is not the first time research has investigated it.

A Chinese study from 2013 investigated nonalcoholic fatty liver disease (NAFLD) prevalence and risk factors in non-obese adults. In this cross-sectional study, 7.27% of 6,905 nonobese subjects had NAFLD.

In a 5-year follow-up of 5,562 subjects initially NAFLD-free, developed NAFLD.

Age, gender, BMI, waist circumference, triglycerides, HDL cholesterol, serum uric acid, hemoglobin, and platelet count were independently associated with NAFLD. [ref]

Then in 2015, a Japanese research found that NAFLD was prevalent in 15.2% of their non-obese subjects because of their lifestyle and metabolic factors. [ref]

Research from 2017 also recognized that a significant portion of NAFLD patients are lean, and this disease can become a leading cause of end-stage liver disease. [ref]

A 2019 study discovered that non-alcoholic fatty liver disease (NAFLD) can strike even thin people.

But this phenomenon is associated with things like increasing body fat, insulin resistance indicators, acute phase reaction, and a higher chance of type 2 diabetes.

These cases frequently have higher visceral adipose tissue but lower overall body mass index (BMI) threshold [ref].

Another research from 2021 stated that almost 10-20% of NAFLD patients are lean. It is estimated that 8 to 10 million people in the United States alone are impacted by this condition known as “lean NAFLD.” [ref].

Treating MASLD/ NAFLD:

There is no consensus on one specific treatment for MASLD or NAFLD. Diet and exercise are the key lifestyle interventions that can have a better impact on the disease progression.

GLP-1 analogs such as Ozempic (Semaglutide) and Mounjaro (Tirzepatide) may be best for obese and overweight individuals with NAFLD/ MASLD and comorbid diabetes.

For Non-Diabetics, Wegovy and Zepbound may be indicated for treating MASLD.

However, for lean individuals, Pioglitazone may be the best option as it is one of the two drugs to have a better effect on the outcomes of patients with NAFLD/ MASLD.