What is Nonalcoholic Steatohepatitis (NASH) (Fatty Liver)?
Nonalcoholic fatty liver disease (NAFLD) refers to the unusual build-up of fat in the liver or ‘hepatic steatosis,’ when there are no other reasons for fat build-up in the liver. While a small amount of fat can be present in the liver of healthy adults, having fat in 5% or more of the liver cells is regarded as abnormal. This disease includes both nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which is identified when there are signs of inflammation and liver cell injury in fatty liver tissue.
Someone who has a history of drinking a lot of alcohol shouldn’t be diagnosed with NAFLD. The safe limit of daily alcohol consumption is viewed as less than 20 grams for men and 10 grams for women. However, these limits can be somewhat vague, particularly for those who used to drink heavily and are prone to developing NASH. NASH can advance to serious liver conditions such as liver fibrosis, cirrhosis, and liver cancer, with around 30% to 40% of patients developing fibrosis.
NASH isn’t a diagnosis made only when all other conditions are ruled out; it may coexist with other liver conditions like chronic hepatitis C. There are two types: primary NASH, which is linked to obesity and diabetes without excessive alcohol intake; and secondary NASH, resulting from exposure to toxins or drugs. This article primarily discusses primary NASH.
What Causes Nonalcoholic Steatohepatitis (NASH) (Fatty Liver)?
Certain conditions are commonly seen in people with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The most notable of these is obesity, which has a strong link to NAFLD.
A group of conditions known as metabolic syndrome is also strongly associated with NAFLD. Metabolic syndrome includes obesity, type 2 diabetes (or a condition known as hyperinsulinemia, where the body produces too much insulin), high blood pressure, and abnormal levels of cholesterol or other fats in the blood. Interestingly, about three out of four people with insulin resistance and type 2 diabetes also have a fatty liver, with a higher number of people showing signs of liver scarring, also known as cirrhosis.
NAFLD has also been associated with other metabolic and genetic conditions such as polycystic ovary disease, conditions that affect the body’s ability to store fat properly (called lipodystrophies), diseases that affect the energy-producing components of our cells (known as mitochondria), Weber-Christian disease (inflammation that damages the body’s fat tissues), and Wilson’s disease (a rare inherited disorder that causes copper to accumulate in the body)
People who are either over-nourished or under-nourished, such as those on a high-nutrient diet given through intravenous feeding tubes, or those with malnutrition-related conditions like Kwashiorkor and celiac disease, have also been associated with NAFLD.
Interestingly, despite having higher rates of obesity and diabetes, African Americans have lower rates of NAFLD compared to Hispanic Americans. Some researchers suggest that this could be because of variation in genes. For instance, a protein named patatin-like phospholipase domain-containing protein 3 (PNPLA3), also known as adiponutrin which helps to break down fat in the body, can increase fat levels in the liver depending on how much is produced. Researchers have found that differences (or polymorphisms) in the gene that makes this protein might explain the different rates of NAFLD among ethnic groups, as Hispanic Americans tend to have higher levels of this protein.
Risk Factors and Frequency for Nonalcoholic Steatohepatitis (NASH) (Fatty Liver)
Nonalcoholic fatty liver disease (NAFLD), which includes Non-alcoholic fatty liver (NAFL) and Non-alcoholic steatohepatitis (NASH), is the most common reason for abnormal liver tests in developed countries. In the United States, about 30% to 40% of adults have NAFLD and around 3% to 12% have NASH. These numbers are growing due to an increase in conditions that make people more likely to get these diseases. Additionally, the prevalence of these disorders varies among different ethnicities, with Hispanics seeing the highest rates, followed by Caucasians and then African-Americans. These conditions can occur at any age, and become more common as people grow older.
- NAFLD, including NAFL and NASH, is the top cause of abnormal liver tests in developed countries.
- In the U.S., 30-40% of adults have NAFLD and 3-12% have NASH.
- These numbers are rising as more people develop conditions that predispose them to these diseases.
- The prevalence of these disorders is highest among Hispanics, followed by Caucasians, and then African-Americans.
- Anyone can develop these conditions, and they become more common with age.
Signs and Symptoms of Nonalcoholic Steatohepatitis (NASH) (Fatty Liver)
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are often asymptomatic, meaning they do not show any visible signs. These diseases are typically found during routine blood tests. However, some people with NASH might experience discomfort or pain in the upper right portion of the abdomen, which could be due to an enlarged liver.
A physical examination might not reveal much. However, it could show an enlarged liver or increased skin pigmentation around the neck and joints due to insulin resistance. If the patient has cirrhosis — another liver condition, some signs such as redness of the palms, tiny blood vessels on the skin, shrinkage of muscles, yellowing of skin and eyes, enlarged spleen, and fluid buildup in the abdomen might be present.
- Discomfort or pain in the upper right part of the abdomen (sometimes)
- An enlarged liver
- Increased skin pigmentation around the neck and joints
- Redness of the palms of the hands (if cirrhosis is present)
- Tiny blood vessels visible on the skin (if cirrhosis is present)
- Muscle shrinkage (if cirrhosis is present)
- Yellowing of skin and eyes (if cirrhosis is present)
- Enlarged spleen (if cirrhosis is present)
- Fluid buildup in the abdomen (if cirrhosis is present)
Testing for Nonalcoholic Steatohepatitis (NASH) (Fatty Liver)
The diagnosis of Non-alcoholic Fatty Liver Disease or Non-alcoholic Steatohepatitis (NAFLD/NASH) typically occurs accidentally. This can happen when standard lab tests show unusual liver results or imaging tests reveal a fatty liver or liver enlargement. The imaging tests may use ultrasound, CT scans, or MRI scans, although ultrasound is often used due to its low cost and availability.
The diagnosis of NAFLD should only be confirmed when a person is found not to be consuming excessive alcohol (more than 20 g/day for men and more than 10 g/day for women) and is not suffering from any other identified liver diseases like viral hepatitis, autoimmune hepatitis, or drug-induced liver disease.
Certain liver enzymes known as Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are typically a little elevated. It’s common to see the level of ALT being double than AST for patients having NAFLD. This pattern helps to distinguish NAFLD from alcoholic hepatitis, where AST is usually double than ALT ratio. However, for advanced stages of NASH or cirrhosis, this pattern could change, and the level of AST may become higher than ALT. Other substances like bilirubin, albumin, and INR are generally normal but can be elevated in patients who develop cirrhosis.
A liver biopsy is often needed to confirm the diagnosis of NASH and understand the extent of liver fibrosis when someone persistently has unexplained elevated liver enzymes. However, a biopsy may not be necessary if these enzymes are normal, and the only identified issue is a fatty liver found on an imaging scan. A biopsy is considered the best method for diagnosis, but it may be inaccurate due to some biases such as observer interpertation and the fact that liver biopsies only sample a tiny fraction of the liver, which may not be affected by NAFLD uniformly.
Several signs visible under a microscope can help identify the different stages of NAFLD. These range from the presence of fat within the liver cells (referred to as steatosis), inflammation, and liver cell damage (called hepatocyte ballooning).
Many non-invasive tests are also used to estimate the severity of fibrosis in NAFLD patients, such as blood tests and imaging techniques. Among those, FibroScan (a type of ultrasound) is commonly used. It measures the stiffness of the liver, which can indicate fibrosis. A higher score on these tests can suggest advanced fibrosis (advanced stage of liver scarring), and a lower score suggests a low risk of fibrosis.
So, putting it all together, a NAFLD diagnosis should be considered for patients with certain metabolic syndrome symptoms, abnormal liver test results, or radiological evidence of fat in the liver. And it’s usually in case there are no risk factors for alcoholic liver disease or other chronic liver conditions. Doctors can use various blood tests or imaging test scores to estimate the risk of advanced fibrosis. And this way, they can reserve a more invasive procedure, like a liver biopsy, for only those patients who are at high risk for advanced fibrosis.
Treatment Options for Nonalcoholic Steatohepatitis (NASH) (Fatty Liver)
The primary aim of treatment is to change your lifestyle to lose between 5% and 10% of your weight. Both chemical and physical health improvements have been observed in patients who have lost weight through reduced calorie intake and exercise. Drinking a couple of cups of caffeinated drip coffee could be a part of these lifestyle changes, as it’s been linked to decreased liver fibrosis and a lower chance of liver cancer. Studies suggest that removing high fructose corn syrup from your diet and increasing your intake of omega-three fats could be beneficial.
Thiazolidinediones, a type of medication, seem to be helpful in improving the body’s response to insulin and in preventing inappropriate breakdown of fats in fat cells. However, their side effects, which may include weight gain, worsening of heart failure, and osteoporosis, limit their use. Antioxidants like vitamin E might bring modest benefits and are probably safe for non-diabetic patients. A dose of 800 units a day might be offered after explaining the risk of increasing overall death rates with high dose vitamin E therapy. For diabetic patients, a dose higher than 400 units per day is not recommended.
Bariatric surgery, which is surgery to help lose weight, is an effective treatment and can be considered for extremely overweight patients who meet other criteria for this surgery. Even if a patient already has abnormal liver test results, they should not stop taking statins, which are drugs to lower cholesterol levels. The last option is liver transplantation for patients with advanced cirrhosis – a disease that causes scarring of the liver – with the reminder that this liver disease can come back after a transplant.
What else can Nonalcoholic Steatohepatitis (NASH) (Fatty Liver) be?
- Alcohol-related liver disease
- Alcohol addiction
- Alpha-1 antitrypsin deficiency (a genetic disorder that may result in lung and liver disease)
- Autoimmune hepatitis (a disease where the body’s immune system attacks the liver)
- Celiac disease (an autoimmune disorder affecting digestion)
- Cirrhosis (scarring of the liver)
- Drug-induced liver damage
- Hemochromatosis (an iron overload disorder)
- Hepatitis A (a viral liver infection)
- Hepatitis B (a viral infection that attacks the liver)
- Hepatitis C (a liver infection caused by a virus)
- Hepatitis D (a serious liver disease caused by the hepatitis D virus)
- Hepatitis E (a liver disease caused by the hepatitis E virus)
- Hyperthyroidism (overactivity of the thyroid gland)
- Hypothyroidism (underactivity of the thyroid gland)
- Isoniazid-induced liver damage (a side effect of a medication commonly used to treat tuberculosis)
- Malabsorption (a condition that prevents absorption of nutrients through the intestines)
