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Hepatologist and Liver Transplant | Dr Manas Vaishnav

Fatty Liver Disease (MASLD)


Fatty liver disease refers to a buildup of excess fat in the liver. When this occurs in people who drink little to no alcohol, it was historically called NAFLD (Non-Alcoholic Fatty Liver Disease). Recently, experts have introduced a new name: MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease), to emphasize its link with metabolic factors. In MASLD, fat accumulates in liver cells often due to obesity, insulin resistance, diabetes, and related metabolic issues. It is now the most common cause of chronic liver disease globally, affecting roughly a quarter of the world’s population. Fatty liver by itself often causes no symptoms, but it can progress in some people to liver inflammation (steatohepatitis), fibrosis, cirrhosis, and even liver cancer over time.

(For simplicity, we will use MASLD to refer to this condition, in line with the newer terminology, but many doctors and patients may still know it as NAFLD.)

Symptoms


In the early stages, fatty liver disease (MASLD) usually has no noticeable symptoms. Most people feel entirely normal and are often surprised to learn they have a fatty liver from an ultrasound or blood test done for another reason. Some nonspecific symptoms that a minority of patients report include:

  • Fatigue and low energy.
  • A vague discomfort or dull pain in the upper right abdomen (where the liver is). This is uncommon but may occur if the liver is enlarged and stretching its capsule.

As MASLD progresses to the stage of inflammation (called MASH – Metabolic dysfunction-Associated SteatoHepatitis, formerly NASH), some people may start developing more overt signs:

  • Severe fatigue and weakness (more pronounced).
  • Loss of appetite or feeling full quickly.
  • Occasionally, jaundice (yellowing of eyes/skin) if there’s significant liver inflammation or injury – this is relatively rare in early stages and usually indicates advanced disease.
  • Weight gain (from metabolic syndrome) or unexplained weight loss in advanced stages due to illness.
  • Swelling of the abdomen (from fluid, i.e., ascites) or legs – but these occur only after cirrhosis has developed, a late stage complication.

Often, MASLD is suspected because of elevated liver enzymes on a blood test (ALT, AST) or an ultrasound finding of a “bright” fatty liver. Without screening or incidental findings, many would not know they have it.

Causes


MASLD is fundamentally associated with metabolic dysfunction. Key factors and causes include:

  • Obesity: Especially excess fat around the abdomen. A high Body Mass Index (BMI ≥30) greatly increases risk. Visceral fat (around organs) seems particularly linked to liver fat.
  • Insulin resistance and Type 2 Diabetes: Insulin resistance (often manifested as prediabetes or metabolic syndrome) causes higher levels of blood sugar and insulin, which promote fat storage in the liver. Type 2 diabetes is a strong risk factor – a significant percentage of diabetics have fatty liver.
  • High blood lipids: Elevated triglycerides or dyslipidemia (high cholesterol) contribute to fat deposition in the liver. Many people with MASLD have high triglyceride levels.
  • Metabolic Syndrome: The combination of obesity, high blood pressure, high blood sugar, and abnormal cholesterol is a recipe for fatty liver. MASLD is often considered the liver manifestation of metabolic syndrome.
  • Poor diet and sedentary lifestyle: Diets high in sugary beverages, refined carbs, and saturated fats can foster liver fat accumulation. Fructose (in sugary drinks) in particular has been linked to NAFLD. Lack of exercise contributes to obesity and insulin resistance.
  • Genetic factors: Certain genes (like PNPLA3, TM6SF2, etc.) can make someone more prone to developing fatty liver when faced with metabolic risk factors. Genetics explain why some people develop NASH/cirrhosis while others with similar body type do not.
  • Other causes to exclude: By definition, “non-alcoholic” fatty liver means significant alcohol use isn’t the cause. Heavy drinking → alcoholic liver disease, not MASLD. Light-to-moderate alcohol doesn’t necessarily exclude MASLD. Rare causes include certain medications or metabolic disorders, considered after other tests.

In summary, MASLD is not caused by a virus or a single agent, but rather by a combination of lifestyle and genetic factors that lead to fat build-up in the liver. It often coexists with obesity and diabetes.

Diagnosis


Diagnosis of fatty liver (MASLD) often starts with incidentally noted abnormal tests:

  • Liver imaging: An ultrasound of the abdomen is a common way fatty liver is first detected – the liver appears brighter than normal (due to fat). Ultrasound can suggest moderate to severe fat accumulation but is not sensitive to mild cases. Other imaging like CT or MRI can also detect fat in the liver. A specialized MRI or ultrasound-based test called FibroScan® (transient elastography) can measure liver stiffness (for fibrosis) and has a controlled attenuation parameter (CAP) to quantify liver fat.
  • Blood tests: There’s no single blood test for MASLD, but patients often have mild to moderate elevations in ALT and AST liver enzymes. The ALT is typically higher than AST in fatty liver (opposite of the AST:ALT ratio seen in alcoholic liver disease). However, enzymes can be normal in many patients despite fatty liver. Doctors will also check for features of metabolic syndrome: fasting glucose/A1c (for diabetes), lipid panel (for cholesterol/triglycerides), etc.
  • Exclusion of other causes: Diagnosing MASLD requires ruling out other explanations for liver fat or enzyme elevation. Tests may include hepatitis B and C, autoimmune markers (to exclude autoimmune hepatitis), and iron studies (to exclude hemochromatosis). A medical history is also taken to ensure alcohol intake is below damaging levels. Certain medications or rapid weight loss can also cause fatty liver and need to be considered.
  • Liver biopsy: This is the gold standard to diagnose steatohepatitis (NASH/MASH) and to assess fibrosis. A biopsy can show fat droplets in liver cells, inflammation, and scarring. Not everyone with MASLD needs a biopsy; it’s usually reserved for cases with uncertainty or when severity grading (especially fibrosis stage) would impact treatment. Nowadays, non-invasive tests (FibroScan or blood fibrosis panels) often replace biopsy to gauge fibrosis.

A newer concept is the acronym MAFLD (Metabolic Associated Fatty Liver Disease) which has diagnostic criteria focusing on evidence of fatty liver plus metabolic risk factors. Regardless of terminology, if imaging shows fat in the liver and the person has metabolic risk factors (obesity, diabetes) and no significant alcohol use, the diagnosis of MASLD is made.

An important part of evaluation is determining if the person has just fatty liver (steatosis) or has progressed to steatohepatitis (fat plus liver cell injury and inflammation). Blood tests and scoring systems (like the NAFLD fibrosis score, FIB-4, etc.) or FibroScan can help identify those with advanced fibrosis who need more aggressive intervention or specialist referral.

Treatment


There is currently no single magic-pill medication specifically approved to cure MASLD. However, the condition can often be reversed or improved with lifestyle changes. Key aspects of management include:

  • Weight loss: This is the cornerstone. For overweight or obese patients, a weight reduction of 7–10% of body weight can significantly reduce liver fat and even reverse inflammation and early fibrosis. Weight loss can be achieved through diet and exercise; in some cases of severe obesity, bariatric surgery is considered and has been shown to improve NASH.
  • Dietary changes: A healthy diet is crucial. This typically means a calorie deficit for weight loss. A Mediterranean-style diet (high in vegetables, fruits, whole grains, lean proteins, and healthy fats like olive oil) is often recommended. Reducing simple sugars (especially fructose-laden drinks like sodas or juices) is very important, as high fructose intake is linked to fatty liver. Avoid heavily processed foods and trans fats. Some evidence suggests coffee consumption may be beneficial for the liver.
  • Exercise: Regular physical activity helps improve liver fat content and insulin sensitivity even without major weight loss. Aim for at least 150 minutes of moderate exercise per week (brisk walking, cycling, etc.), plus resistance training if possible. Exercise combined with diet is most effective for reducing liver fat.
  • Control metabolic risk factors: Tight control of blood sugar in diabetics (with diet, oral meds, or insulin as needed) will help. Managing cholesterol and triglycerides with diet or medications (like statins) if indicated – statins can be used in NAFLD if needed for cardiac risk, they are not contraindicated (and may even help the liver). Blood pressure control is also advised. Treating the components of metabolic syndrome will indirectly help the liver.
  • Avoid alcohol and unnecessary medications: Even though MASLD is “non-alcoholic,” any alcohol adds extra load to a fatty liver. It’s generally recommended to minimize or avoid alcohol entirely to prevent compounding liver injury. Also avoid unnecessary drugs/supplements that might hurt the liver.

Medications: While none are officially approved specifically for NAFLD/NASH yet, some are used in certain situations:

  • Vitamin E: At high doses, it has been shown in some trials to help non-diabetic NASH patients reduce liver inflammation. However, there are concerns about long-term high-dose vitamin E (possible increased all-cause mortality or prostate cancer risk in some studies), so it’s used selectively under doctor guidance.
  • Pioglitazone: A diabetes medication that has shown benefits in improving NASH in trials (even in non-diabetics). Side effects include weight gain and fluid retention.
  • Newer medications (in trials): Examples include GLP-1 agonists such as semaglutide, which cause weight loss and have improved NASH in studies, as well as fibrosis-targeted drugs. These may become available in the future as specific therapies.

In patients who progress to cirrhosis from MASLD (sometimes called metabolic-associated steatohepatitis cirrhosis), management includes all the above plus monitoring for complications. Liver transplantation is an option for end-stage liver disease or liver cancer resulting from MASLD – and indeed, NASH cirrhosis is now one of the leading indications for liver transplant in Western countries.

FAQs


 Yes, they refer to the same condition. The term MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) is a new name proposed to replace NAFLD. It was changed to better highlight that metabolic risk factors (like obesity, diabetes, high cholesterol) are at the root of this disease. The older name NAFLD defined it by the absence of significant alcohol use, but the new name defines it by the presence of metabolic dysfunction. Practically, you might hear both terms. MASLD and NAFLD are used interchangeably for now. The disease itself hasn’t changed – just the name and diagnostic criteria are being refined. If you see “MAFLD” (Metabolic Associated Fatty Liver Disease) in some articles, that’s an earlier but similar concept to MASLD. It’s mostly a terminology update; your doctor focusing on your weight, diet, and metabolic health remains the key part of management.

The good news is that fatty liver (and even NASH with early fibrosis) can be reversed in many cases. The liver is a resilient organ. If you can reduce the fat drivers – for instance, lose weight, improve diet, control diabetes – the fat content in the liver drops and inflammation can subside. Studies show that losing around 7-10% of body weight can not only reduce liver fat but also reverse inflammation and some fibrosis in a significant proportion of patients. Even in cases with fibrosis (scar tissue), if the cause is addressed, fibrosis can improve over time. However, if it has progressed all the way to cirrhosis, that severe scarring is usually not fully reversible (short of transplant), though its progression can be halted or slowed. The earlier in the disease you intervene, the more likely you can completely normalize the liver. Many patients who commit to lifestyle changes have seen their liver enzymes normalize and imaging improve, essentially “defatting” their liver. So yes, fatty liver is often reversible if you tackle the root causes.

There isn’t a single “fad” diet specifically for fatty liver, but research and expert opinion suggest the Mediterranean diet is very beneficial. This diet emphasizes fruits, vegetables, whole grains, lean proteins (like fish and poultry), legumes, and healthy fats (like olive oil and nuts), while limiting red meat, refined carbs, and sugars. It has been shown to improve fatty liver parameters and also helps with weight loss and cardiovascular health. Generally, a diet for MASLD should focus on:
– Calorie reduction if weight loss is needed.
– Low in simple sugars, especially fructose (cut out sugary drinks, limit sweets). Sugary beverages are strongly linked to fatty liver.
– Higher in fiber and complex carbs instead of refined carbs (choose whole grain bread/pasta, brown rice instead of white, etc.).
– Rich in healthy fats (olive oil, avocados, omega-3 rich fish like salmon) as opposed to saturated/trans fats.
– Adequate protein (including plant-based proteins) to help maintain muscle during weight loss.
– Limited processed foods and fried foods.
Also, if overweight, any diet that you can stick to that leads to weight loss will help the liver – be it Mediterranean, DASH, or other balanced diets. Avoid crash or extreme diets; slow, steady weight loss is safer for the liver (rapid weight loss can, paradoxically, worsen liver inflammation transiently or lead to gallstones). It may be helpful to consult a dietitian who can tailor a plan to your tastes and medical needs.

Pregnant women are at the highest risk – especially in the third trimester, hepatitis E can be devastating, with a maternal mortality rate of 20% or higher. So they are the single most vulnerable group. Apart from pregnancy, people with pre-existing chronic liver disease are at risk for more severe acute hepatitis (any acute hepatitis on top of chronic liver issues can precipitate liver failure). Also, individuals with weakened immune systems (like organ transplant patients or those on chemotherapy) might have difficulty clearing the virus, potentially leading to chronic infection, although that’s rare. In general, young healthy adults usually recover fully, but vigilance is needed in those high-risk categories.

There is no magic pill yet. Vitamin E at a dose of 800 IU daily has shown some benefit in non-diabetic patients with NASH (steatohepatitis). Some liver specialists might prescribe it if you fit that category. However, it’s not for everyone (e.g., not typically recommended if you have diabetes or cirrhosis due to mixed data on outcomes). Pioglitazone, a diabetes medicine, is sometimes used in NASH patients (including some non-diabetics) as it can improve liver histology – but it can cause weight gain, which is counterproductive, so its use is careful. Newer diabetes drugs like GLP-1 agonists (e.g., liraglutide, semaglutide) cause weight loss and have shown promise in treating NASH in trials; if you have type 2 diabetes, your doctor might choose one that could benefit your liver as well. Statins can be safely taken if you have high cholesterol – they primarily protect your heart, but there’s evidence they’re safe in fatty liver and might even reduce liver inflammation a bit. Avoid unproven “liver cleanse” supplements – many have no benefit and some could harm the liver (remember, “natural” doesn’t equal “safe”). Always talk to your doctor before taking any supplement. The mainstay remains diet and exercise; medications are considered on an individual basis, often to treat accompanying conditions (like diabetes or high lipids) with the side benefit of helping the liver.

Yes. It’s a common misconception that normal liver blood tests mean the liver is fine. Many individuals with fatty liver disease have normal ALT and AST levels or only very mildly elevated levels. Enzymes can even fluctuate – sometimes normal, sometimes a bit high. You could have significant liver fat or even fibrosis and still have near-normal blood tests. Ultrasound or FibroScan findings, or risk factors, might prompt a diagnosis despite normal enzymes. So a normal ALT/AST doesn’t completely rule out MASLD. Doctors look at the whole picture: risk factors (obesity, etc.), imaging, and so forth. If you have known risk factors and normal enzymes, it’s still worth pursuing weight loss and healthy habits, as silent fatty liver could still be present. Periodic rechecking is also advised. In short, normal liver enzymes = great, but with context. It’s possible to have “biochemical silence” while the disease is present, especially in early stages.