How is NASH diagnosed?

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Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by inflammation and damage to liver cells as well as fat accumulation in the liver. NASH would progress to cirrhosis or liver failure if left untreated. Diagnostic evaluation consists of a blend of clinical assessment, laboratory studies and imaging procedures, and at times, liver biopsy. The following explains how NASH is diagnosed:

1. Physical Examination and Medical History
Assessment of Risk Factors: The doctor will assess whether the patient is at risk of having NASH, including:

Obesity

Type 2 diabetes

Metabolic syndrome

Hypercholesterolemia or hypertriglyceridemia

Hypertension

Alcohol Use: The doctor will ask about alcohol consumption to rule out alcohol-induced liver disease, which may have a similar presentation to NASH.

Physical Examination: The doctor can look for signs of fatty liver, hepatomegaly, and other systemic signs of liver disease.

2. Laboratory Tests
Blood Tests: Blood tests are helpful in providing hints but not diagnostic by themselves in the diagnosis of NASH.

Liver Function Tests (LFTs): Raised levels of liver enzymes (such as AST and ALT) can be suggestive of inflammation of the liver, though they may not always be elevated in NASH.

Lipid Profile: Raised triglycerides or cholesterol levels can point towards metabolic derangement, which is common in patients with NASH.

Blood Glucose and Insulin Sensitivity Tests: Patients with NASH often have elevated blood glucose or insulin resistance.

Markers of Inflammation: Certain markers, including C-reactive protein (CRP), may be elevated in inflammation of the liver.

Non-invasive markers of liver stiffness: Certain blood tests like Fibrosis-4 (FIB-4) index or NAFLD fibrosis score (NFS) may estimate liver fibrosis, a sign of significant liver damage, without a biopsy.

3. Imaging Studies
Imaging techniques are used to assess liver fat, fibrosis, and other structural changes.

Ultrasound: It is the most common technique used to detect fatty liver. Though it can suggest evidence of deposition of liver fat (steatosis), it cannot differentiate between simple fatty liver (NAFLD) and advanced stages like NASH.

Elastography (FibroScan): This is a dedicated ultrasound technology that measures liver stiffness as a surrogate of fibrosis. Stiffness can be indicative of advanced liver disease, such as NASH-induced fibrosis.

Magnetic Resonance Imaging (MRI): MRI-based techniques, like MRI-PDFF (proton density fat fraction), can provide a more accurate quantitation of liver fat and even detect fibrosis. It can be employed to assess the degree of liver injury.

CT Scan: Less frequently used, though it can diagnose fatty liver and liver injury. However, it is less sensitive in showing the degree of fat or fibrosis compared to other imaging options.

4. Liver Biopsy
Gold Standard for Diagnosis: Liver biopsy is the gold standard to diagnose NASH and its severity. During the procedure, a small amount of liver tissue is removed and examined under a microscope to search for:

Fat deposition in liver cells (steatosis)

Liver tissue inflammation

Cell damage, such as ballooning of liver cells

Fibrosis or scarring

Grading and Staging: NASH is graded by

NAFLD Activity Score (NAS): A grading score to determine the degree of inflammation and liver cell injury.

Fibrosis Staging: The degree of scarring in the liver is quantified, typically by means of systems such as the Ishak or Metavir staging systems.

Limitations: Even though liver biopsy is the most accurate, it’s invasive, carries risks like bleeding and infection, and is typically only done if other tests reasonably well indicate advanced disease or where the diagnosis is uncertain.

5. Non-invasive Tests and Biomarkers
Over the years, non-invasive tests have been developed to diagnose and assess NASH without going for liver biopsy. They consist of:

NAFLD Fibrosis Score (NFS): A score based on the parameters of age, diabetes, liver enzymes, and platelet count, used to estimate risk for advanced fibrosis of the liver.

Fibrosis-4 (FIB-4) Index: A widely used blood test score to aid assessment of the risk of advanced fibrosis of the liver.

Steatotic Index (SI) and FIB-4 both: These tests can also be used to assess liver fat and fibrosis but require further affirmation in some instances.

Genetic Testing: There are tests in development to identify genetic factors making individuals prone to NASH, but this is not yet standard procedure for diagnosing the condition routinely.

6. Follow-Up and Monitoring
If NASH has been diagnosed, follow-up assessments are typically performed to monitor progression of the disease, including liver stiffness (fibrosis) and changes of liver enzymes. Non-invasive markers, e.g., FibroScan, or blood markers can help determine progression of the disease without having to repeat biopsies.
Diagnosis of NASH typically involves a combination of history, blood testing, and imaging. Liver biopsy remains the gold standard test and stage but perhaps reserved for a situation where there is diagnostic uncertainty or in cases of suspected severe liver injury. With greater use of non-invasive imaging, one can now better assess the degree of liver injury and fibrosis, reducing the need for multiple biopsies.

Do you want to learn more about the treatment of NASH or how to deal with it? Ask me anytime!
Non-alcoholic steatohepatitis (NASH) is a liver condition that can advance from non-alcoholic fatty liver disease (NAFLD) to inflammation and damage to the liver, which may eventually lead to cirrhosis or liver failure. NASH treatment typically involves managing its causative factors, managing associated conditions, and in other cases, using medications. The following are the treatment methods for NASH:

1. Lifestyle Changes
The first line of treatment for NASH includes lifestyle modifications, specifically dietary, exercise, and weight changes:

Weight Loss: Mild to moderate weight loss of about 5-10% of body weight has been shown to lead to a significant reduction in liver fat and inflammation in patients with NASH. A moderate weight loss will improve liver function and can even reverse some of the liver damage due to NASH.

Exercise: Regular physical exercise, including aerobic and strength training exercises, can reduce liver fat, improve insulin sensitivity, and reduce inflammation.

Diet:

An anti-inflammatory, balanced diet can help promote liver health. This typically includes:

Low-glycemic index foods: Helps regulate blood sugar and insulin levels.

Healthy fats: Such as omega-3 fatty acids from fatty fish (salmon, mackerel) or flaxseeds and walnuts.

High-fiber foods: Such as fruits, vegetables, and whole grains.

Reducing saturated fats: Limiting animal foods with high fat content and processed foods.

Reducing sugar and refined carbohydrates to prevent excessive fat buildup in the liver.

2. Treatment of Underlying Conditions
The majority of patients with NASH have underlying conditions such as obesity, type 2 diabetes, hypertension, and hyperlipidemia (high cholesterol) that cause liver damage. These conditions can be controlled by treating them:

Diabetes Control: Glucose blood regulation is key to the management of NASH. Drugs such as metformin, GLP-1 receptor agonists, or SGLT2 inhibitors may be prescribed to improve insulin sensitivity and decrease liver fat.

Cholesterol Control: Statins or other lipid-lowering medications may be given to regulate raised cholesterol levels, as increased levels of lipids can accelerate the deposition of liver fat.

Blood Pressure Control: Lifestyles change or antihypertensive treatment with drugs (e.g., ACE inhibitors, ARBs) can reduce the risk of liver damage.

3. Medications (In Research and New Treatments)
Several medications are under investigation for their potential to treat NASH, and some of them could become available soon:

Vitamin E: According to some studies, vitamin E, an anti-oxidant, can reduce liver inflammation and damage in NASH patients, particularly non-diabetic. It is generally recommended in patients with NASH established through biopsy.

Pioglitazone: A medication which increases the sensitivity to insulin, pioglitazone (a medication used for diabetes) may prove useful to cure NASH, particularly in type 2 diabetic individuals or those resistant to insulin. But side effects like weight gain and edema can limit its use.

Obeticholic Acid: An FXR agonist which looks very promising clinically to treat NASH by suppressing liver inflammation and fibrosis. In pipeline for approval.

Cenicriviroc: A CCR2/CCR5 antagonist with some cited potential in reducing liver fibrosis and inflammation in NASH patients.

Aramchol: A developmental drug that modulates liver fat metabolism and has been reported to have very promising outcomes in clinical trials for the treatment of NASH.

Seladelpar: An experimental drug that acts on PPARδ receptors to reduce liver fat and inflammation, and has been promising in clinical trials for NASH.

4. Bariatric Surgery
For patients with severe obesity and advanced NASH, bariatric surgery such as gastric bypass or sleeve gastrectomy can be considered. This is usually a consideration after lifestyle changes and medications have been unsuccessful, and cirrhosis or liver failure is a risk. Bariatric surgery has been found to lead to significant weight loss and improvement of the liver, potentially even reversal of NASH.

5. Liver Transplantation (In Advanced Cases)
In advanced liver cirrhosis or liver damage due to NASH, liver transplant can be needed if liver failure is attained. Transplantation is generally a final measure when other therapies fail, and the liver’s functioning is affected.

6. Alternative and Complementary Therapies
Although there is no much evidence regarding alternative therapies, some will gain benefit from certain complementary therapies:

Milk Thistle (Silymarin): Its protective effects on the liver make milk thistle sometimes used in patients with liver disease. Evidence of its efficacy with NASH is mixed, and caution should be used when employing it.

Turmeric (Curcumin): Turmeric’s anti-inflammatory and antioxidant properties may make it helpful in reducing inflammation in the liver in some NASH patients, but more research is needed.

Probiotics: Some research indicates that probiotics may potentially improve gut health and lower inflammation in the liver, possibly favoring those suffering from NASH, but the method needs to be further studied.

7. Regular Monitoring and Liver Biopsies
NASH patients should be regularly checked for liver function through tests of blood (e.g., liver enzyme levels, bilirubin, and albumin) and imaging tests (e.g., ultrasound, CT scan, or MRI). In some cases, the liver can be biopsied to assess the extent of the damage to the liver (e.g., the intensity of the inflammation or fibrosis).
Management of NASH is primarily by means of lifestyle modifications, such as weight loss, exercise, and a healthy diet, along with the management of underlying conditions like diabetes, high cholesterol, and obesity. Drug therapy in the form of vitamin E and pioglitazone may be attempted in some cases, and newer drugs like obeticholic acid and cenicriviroc are being investigated. Bariatric surgery and transplantation of the liver can be provided in extreme situations, and constant monitoring is necessary to assess the progress of the disease.