NASH (Nonalcoholic Steatohepatitis)

Fatty liver affects millions of people worldwide. This silent but serious condition often goes unnoticed until it progresses to a more severe form known as nonalcoholic steatohepatitis (NASH). NASH liver disease poses a significant health risk, causing inflammation and damage to the liver. Understanding NASH, its causes, and its impact on overall wellness is crucial for early detection and effective management.

What is NASH?

Nonalcoholic steatohepatitis is commonly known as NASH. It is a severe form of nonalcoholic fatty liver disease (NAFLD). This condition occurs when the liver accumulates excessive fat deposits, resulting in inflammation and damage to liver cells.

While a healthy liver contains some fat, NAFLD develops when fat content exceeds 5%. NASH takes this a step further, combining fat accumulation with inflammation. This combination can result in liver damage similar to that caused by alcohol abuse, even in individuals who don't drink.

Causes of NASH

The exact causes of nonalcoholic steatohepatitis (NASH) remain a subject of ongoing research. Scientists are still working to understand why some people develop NASH while others don't. However, several factors are potential contributors to the development of this liver condition, such as:

• Health Conditions and Diseases: Certain health conditions increase the likelihood of developing NASH. These include:
  • Overweight or obesity
  • Insulin resistance or type 2 diabetes
  • High triglycerides
  • Abnormal cholesterol levels (high total cholesterol, high LDL cholesterol, or low HDL cholesterol)
  • Metabolic syndrome 
• Genetics: Research suggests that genetic components play a role in NASH development. Specific genes may make people more susceptible to the condition.
• Diet and Digestive System: While the exact mechanisms are still being investigated, these findings suggest that diet and gut health may influence NASH development. Diets high in fructose may increase the risk of NASH, and changes in gut flora also affect it.
• Other Potential Factors: 
  • Immune system reactions to excessive fatty liver tissue
  • Release of toxic inflammatory chemicals (cytokines) by liver or fat cells
  • Self-destruction (apoptosis) of liver cells
  • Oxidative stress 

Symptoms of NASH Liver Disease

Many people with NASH may not experience noticeable symptoms, particularly in the early stages of this disease.

As NASH progresses and liver damage becomes more severe, individuals may start to experience various NASH symptoms, such as:

• Itchy skin
• Fluid accumulation in the abdomen can cause noticeable swelling (ascites) and discomfort.
• Shortness of breath, especially during physical activity
• Fluid retention can result in swollen legs and ankles.
• Spider-like blood vessels, often on the chest, back, or face
• The spleen may become larger than normal, potentially causing pain or discomfort in the upper left abdomen.
• The palms of the hands may appear redder than usual.
• Yellowing of the skin and eyes is a sign of advanced liver disease.

In cases where NASH has progressed to cirrhosis (severe fibrosis or scarring), additional NASH symptoms may develop:

• Easy bruising and bleeding
• Behavioural changes, such as confusion and slurred speech, may occur due to the toxins buildup in the blood that the damaged liver can't filter out.

NASH Risk Factors

Nonalcoholic steatohepatitis (NASH) has several risk factors that increase an individual's likelihood of developing this liver condition, such as:

• Health Conditions and Diseases: 
  • Overweight or obesity
  • Insulin resistance or type 2 diabetes
  • Abnormal levels of fats in the blood, especially high triglycerides
  • Abnormal cholesterol levels (high total cholesterol, high LDL cholesterol, or low HDL cholesterol)
  • Metabolic syndrome
• Genetic Factors:
  • Research suggests that certain genes may make some individuals more susceptible to NASH. These genetic factors might explain why NASH is more common in some racial and ethnic groups. 
• Diet and Digestive System:
  • The relationship between diet, the digestive system, and NASH is an area of ongoing research:
  • Diets high in fructose may increase the risk of NASH.
  • Studies have found differences between the microbiomes (gut bacteria) of people with NASH and those without.
• Age:
  • While NASH can affect people of all ages, it is more likely to occur in individuals over 50 years old. 

NASH Complications

Nonalcoholic steatohepatitis can lead to serious health issues if left untreated. 

• Liver fibrosis
• Liver Cirrhosis: Approximately 20% of individuals with NASH develop cirrhosis over several years, typically decades.
• Cirrhosis can result in several complications:
  • Ascites: Fluid buildup in the abdominal area
  • Oesophageal varices: Swollen veins in the oesophagus that may rupture and bleed
  • Hepatic encephalopathy: Confusion, sleepiness, and slurred speech
  • Hypersplenism: An overactive spleen leading to low blood platelet counts
  • Liver cancer: Increased risk of developing hepatocellular carcinoma (HCC)
  • End-stage liver failure: Complete loss of liver function

Diagnosis

Doctors apply a combination of methods to diagnose nonalcoholic steatohepatitis (NASH), including:

• Medical History and Physical Exam:
  • The doctor starts by asking about the patient's health history, focusing on conditions that increase the risk of NASH, such as obesity, type 2 diabetes, high levels of triglycerides, or any metabolic syndrome.
• During the physical exam, the doctor:
  • Calculates the patient's body mass index (BMI)
  • Look for signs of an enlarged liver
  • Checks for indicators of insulin resistance, such as darkened skin patches
  • Examines for signs of cirrhosis, like an enlarged spleen or muscle loss
• Blood Tests:
  • The doctors conduct blood tests to check liver enzyme levels, particularly:
  • Alanine aminotransferase (ALT)
  • Aspartate aminotransferase (AST)

Elevated blood levels of these enzymes suggest liver inflammation. 

• Imaging Tests: Various imaging tests help doctors visualise the liver and detect fat accumulation and the extent of liver damage:
  • Ultrasound
  • CT scan
  • MRI

Newer imaging techniques like elastography measure liver stiffness to assess fibrosis. Increased liver stiffness may indicate the presence of scarring.

• Liver Biopsy:
  • A liver biopsy is the most definitive measure to diagnose NASH and determine its severity. The biopsy can reveal fat accumulation, inflammation, damage to liver cells, and the extent of fibrosis.

NASH Treatment

The treatment of nonalcoholic steatohepatitis (NASH) includes:

• Lifestyle modifications:
  • Doctors recommend weight loss as a primary approach to managing NASH. A loss of three to five per cent of body weight can reduce liver fat, while a 7% to 10% reduction may be necessary to decrease liver inflammation and fibrosis.
  • Small, frequent meals are advised, and screening for micronutrients and vitamin deficiencies is recommended.
• Medications:
  • Vitamin E: Considered a first-line pharmacological treatment, vitamin E has effectively reduced liver enzyme levels, steatosis, and inflammation.
  • Thiazolidinediones (TZDs)
  • Novel Therapies: Several promising medications targeting different stages of the disease are currently in development, offering hope for more effective NASH treatments in the future.
  • Complications Management: Doctors may use medications, minor medical procedures, and surgery to address cirrhosis-related issues. 
  • Liver Transplant:
    • In cases of liver failure or liver cancer, doctors may recommend a liver transplant to restore health.
    • Research is ongoing to develop new treatments for NASH. As the understanding of NASH pathogenesis and progression evolves, the outlook for NASH therapy is becoming more optimistic.

When to See a Doctor

Nonalcoholic steatohepatitis (NASH) often develops silently with few or no noticeable symptoms. However, certain signs and situations warrant a visit to the doctor, such as:

• Fatigue or a general feeling of being unwell
• Pain or discomfort in the right abdominal area in the upper region
• Abdominal swelling (ascites)
• Shortness of breath
• Swelling in the legs
• Spider-like blood vessels visible just beneath the skin's surface

Preventing NASH

Nonalcoholic steatohepatitis (NASH) can be prevented or its progression slowed through lifestyle changes, including:

• Maintaining a healthy weight prevents NAFLD or lessens its effects.
• A healthy diet can prevent NASH. Eating healthy fats, especially unsaturated fats found in fish, nuts, and fruits (omega-3 fatty acids), instead of less healthy options can improve overall health and help control weight.
• Incorporating more low-glycemic index foods, such as fruits, vegetables, nuts, seeds, and whole grains, into one's diet can affect blood glucose levels. 
• Limit intake of simple sugars and avoid sugary drinks like soda, sports drinks, juices, and sweet tea.
• Regular exercise has an impact on improving liver health.
• Avoid alcohol consumption 

Conclusion

Understanding NASH and its impact on liver health can help in early detection and curating effective treatment plans. This silent but severe condition affects millions worldwide, often progressing unnoticed until significant liver damage occurs. By recognising NASH's risk factors, symptoms, and potential complications, individuals can proactively protect their liver health and overall well-being.

Lifestyle modifications remain the cornerstone of NASH prevention and treatment. As research continues and new therapies emerge, there's hope for improved management of this challenging liver condition. 

FAQs

1. Is NASH reversible?

NASH, or nonalcoholic steatohepatitis, has the potential to be reversible in some cases. The effects of NASH may be reversed with weight loss and healthy lifestyle changes. With early intervention, in some instances, the liver damage may stop or even reverse itself. For others, the disease continues to progress.

2. What does NASH stand for?

NASH stands for nonalcoholic steatohepatitis. NASH is characterised by a fatty, inflamed liver that is not caused by heavy drinking. It is a type of liver disease in which fat builds up in the liver of individuals who drink little or no alcohol. This condition causes inflammation of the liver and damage to the liver cells, which may result in cirrhosis and liver failure.

3. Is NASH liver disease hereditary?

NASH liver disease has a hereditary component, but the inheritance pattern is complex. 

4. Is NASH the same as fatty liver?

NASH is not the same as fatty liver, but it is related. NASH is a severe Non-Alcoholic Fatty Liver Disease (NAFLD). The main characteristic of NAFLD is the accumulation of fat in the liver. In NASH, you have fat in your liver, along with inflammation and liver cell damage. The inflammation and damage can lead to fibrosis or scarring of the liver.

Dr Saket Agrawal

Medical Gastroenterology

CARE Medical Team