MASH: Understanding metabolic disease associated steatohepatitis and its impact on liver health
Recently, the disease has been renamed as Metabolic Disease Associated Steatotic Liver Disease (MASLD). MASLD is the presence of fat in the liver found on any imaging modality (most commonly ultrasonography of the liver) and the presence of any of five cardio-metabolic criteria:
Body Mass Index ≥ 24 kg/m2 or WC> 90 cm (M) 80 cm (F), defined as BMI subgroup;
Fasting serum glucose ≥ 5.6 mmol/L or 2-hour post-load glucose levels ≥7.8 mmol/L or HbA1c ≥5.7 % or diagnosis of DM OR treatment for DM, defined as DM subgroup;
Blood pressure ≥130/85 mmHg or specific antihypertension treatment, defined as HT subgroup;
Plasma triglycerides ≥1.70 mmol/L or lipid-lowering treatment, defined as TG subgroup;
Plasma HDL ≤1.0 (M) and ≤1.3 mmol/L (F) or lipid-lowering treatment, defined as HDL subgroup.
While the correlation for NASH has been retained as Metabolic Disease Associated Steatohepatitis (MASH) to reflect its importance as a pathophysiological state and its impact on the general population, an entity “Metabolic disease associated-alcohol induced liver disease (Met-ALD)” describes MASH patients with significant alcohol intake. These changes highlight issues like the term ‘fatty’ being regarded as a stigmatizing term that prevented patients from seeking appropriate medical help when needed; and, how metabolic disease/dysfunction is directly related to the adverse outcomes associated with the disease, treatment, and management.
Symptoms and Detection
MAFLD, including MASH, is often asymptomatic. If symptoms do occur, they may include fatigue, malaise, and pain or discomfort in the upper right abdomen, where the liver is located. These symptoms are vague and can be easily overlooked, contributing to the disease’s asymptomatic nature.
As MASH progresses, notably when it leads to cirrhosis (severe scarring of the liver), more noticeable symptoms may develop.
These can include:
Itchy skin
Abdominal swelling (ascites)
Shortness of breath
Swelling of the legs
Spider-like blood vessels just beneath the skin’s surface
Enlarged spleen
Red palms
Yellowing of the skin and eyes (jaundice)
MASH often goes undiagnosed until routine blood tests reveal abnormal liver enzymes or imaging studies show a fatty liver. The most definitive method of diagnosing MASH is through a liver biopsy, where a small sample of liver tissue is examined for signs of fat, inflammation, and damage. However, this method is invasive, costly, and unsuitable for regular monitoring.
Recent advances have led to the development of non-invasive imaging biomarkers that can estimate the severity of liver steatosis and fibrosis. These imaging techniques, such as FibroScan, MRI, and ultrasound-based methods, offer promising alternatives to liver biopsy, though they have yet to be universally adopted as the standard diagnostic tools.
Risk Factors for MASH
Risk factors are mainly the cardio-metabolic factors. The principal factor that drives all these metabolic diseases (Diabetes, Hypertension, High Cholesterol) is insulin resistance and mitochondrial dysfunction. A disordered gut microbiome can also have a role to play in the development of MASH. Obesity, around the belly, is also an important risk factor. However, MASH can also be seen in lean individuals (LEAN MASH) that shows the diverse and complex mechanisms that underlie this disorder. High blood pressure, metabolic syndrome, polycystic ovary syndrome (PCOS), and certain genetic tendencies can also contribute to the high prevalence of MAFLD in the general population.
Treatment and Management
To manage MASH, focus on making lifestyle changes to improve the liver’s health. Losing weight through healthy eating, exercising, and changing positive behavior can help. Studies have shown that even a moderate weight loss of 7-10% can significantly improve the condition of the liver by reducing fat, inflammation, and scarring.
2Making changes to your diet is essential for managing MASH. Eating less saturated fats, refined carbohydrates, and added sugars while eating more fruits, vegetables, whole grains, and healthy fats like omega-3 fatty acids can help reduce liver fat and inflammation. Regular physical activity, such as aerobic and resistance exercises, improves the body’s response to insulin and helps with weight loss.
There is ongoing research into medications for MASH, especially for those who don’t respond to lifestyle changes or have advanced liver scarring. These drugs improve how the body uses insulin, processes fats, reduces stress, and decreases inflammation. However, these medications are supportive at best. The most reliable treatment option is to change the metabolic state of the body by building lifestyle and dietary habits that are geared towards reducing metabolic risk.
In severe cases, like when MASH has progressed to cirrhosis, a state where the liver function is compromised, a liver transplant would be the only curative option.
Conclusion
MASH is an important liver condition that is abundantly prevalent, almost to pandemic levels. More importantly, it can lead to significant health issues if not treated. Early detection and intervention are crucial to preventing the progression of cirrhosis and liver failure. While lifestyle changes are essential for treatment, ongoing research into medication therapies offers the potential for more effective management options in the future. However, a keen understanding of the disease and its driving factors can result in taking proactive steps to reduce them. Since the effectiveness of these steps (lifestyle modifications) results only through long-term consistency, it is imperative to adopt these practices as habits and sustain them rather than view them through a narrow prism of short-term ‘treatment’.
(Article Courtesy: Dr Harshavardhan Rao B, Senior Consultant – Department of Medical Gastroenterology, Ramaiah Memorial Hospital)
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