Steatohepatitis

by Stephanie Reid, MD FRCPC
May 19, 2022

What is steatohepatitis?

Steatohepatitis is a type of fatty liver disease. It is associated with inflammation and the build up of fat inside specialized liver cells called hepatocytes.

What are the types of steatohepatitis?

There are two major types of steatohepatitis: non-alcoholic and alcoholic. Alcoholic steatohepatitis occurs due to alcohol use. Non-alcoholic steatohepatitis can be caused by a variety of conditions including central obesity, diabetes, and dietary factors. When looking at a liver tissue sample under the microscope, it is not possible to tell the difference between alcoholic and non-alcoholic steatohepatitis reliably, and often the distinction needs to be made by other doctors in your healthcare team after considering both your history, symptoms, and pathological results.

What are the symptoms of steatohepatitis?

Steatohepatitis can present in a variety of ways. Some patients have no symptoms and the disease is discovered incidentally when a radiological image (a CT scan or ultrasound) of the abdomen is performed. It may also be discovered when a blood test shows elevated liver enzymes. Patients with steatohepatitis may also experience abdominal pain or a serious medical condition called ‘liver failure’. In all of these situations, your doctor may order a liver biopsy to determine if steatohepatitis is present.

How do pathologists make the diagnosis of steatohepatitis?

A diagnosis of steatohepatitis requires a liver biopsy.  Your pathologist will look for four major microscopic features to determine the presence of and severity of steatohepatitis: steatosis, ballooning hepatocytes, lobular portal inflammation, and fibrosis. These features are described in greater detail in the sections below.

Microscopic features of steatohepatitis

Steatosis

Steatosis is the term used to describe the presence of fat droplets within the hepatocytes. Steatosis can be a diagnosis on its own, or it can be a part of steatohepatitis. In steatosis, the hepatocytes contain clear areas of fat droplets when viewed under a microscope.

Pathologists use a scale to describe the amount of fat in a liver with steatosis. The scale is based on the percentage of liver cells that contain fat droplets:

The scale used by most pathologists includes:

• Mild – Fat droplets are seen within less than  33% of the hepatocytes in the biopsy.
• Moderate – Fat droplets are seen within 33 – 66 % of hepatocytes in the biopsy.
• Severe – Fat droplets are seen within greater than 66 % of hepatocytes in the biopsy.

Ballooning hepatocytes

Ballooning is a word pathologists use to describe damaged or dying hepatocytes. They are called ‘ballooning’ because the hepatocyte swells to several times its normal size and the body of the cell becomes clear. Ballooning hepatocytes must be present in order to make a diagnosis of steatohepatitis. The number of ballooning hepatocytes present will be described as mild, moderate, or severe.

Lobular or portal inflammation

The liver is made up of three main compartments:

1. Lobule – The lobule is the part of the liver made up of specialized liver cells called hepatocytes.
2. Portal tract – The portal tract contains three parts: a vein, an artery, and a bile duct.
3. Central vein – The central vein is a blood vessel that brings blood into the liver.

Inflammatory cells can enter any of these areas and prolonged inflammation can damage the liver. If inflammatory cells are seen in your tissue, your pathologist will describe their location and the types of inflammatory cells present. The amount of inflammation will also be described on a scale of mild, moderate, or severe. Lobular inflammation is commonly seen in steatohepatitis.

Fibrosis

Fibrosis is a type of scar tissue that forms in the liver after damage. Because steatohepatitis damages the liver, there is a risk of developing fibrosis. Most pathology reports comment on the amount of fibrosis and will assign it a ‘stage’. The stage is dependent on multiple factors including the extent of initial injury, the length of time injury was occurring, and which parts of the liver were damaged. Too much fibrosis disrupts the architecture of the liver and prevents it from functioning properly.

There are several different classification systems used to stage fibrosis but all of them include the type and amount of fibrosis seen. Cirrhosis is the last stage of fibrosis and it is characterized by large fibrous bands that form nodules in the liver. These nodules prevent the liver from carrying out its normal functions and may lead to a medical condition called ‘liver failure’.

Other features that may be described in your report for steatohepatitis

Adequacy

The liver is divided into ‘zones’ and at the center of each zone is a structure called a ‘portal tract’. Portal tracts are important because they contain blood vessels and channels that move other substances such as bile in and out of the liver.

When examining a liver biopsy, your pathologist must first determine if the sample contains the minimum amount of portal tracts required to make an accurate diagnosis. The adequacy of the biopsy may be reported simply as “yes” or “no”, or the number of portal tracts seen may be stated.

Fragmentation

The condition of the liver biopsy when viewed under the microscope is usually described. If the liver biopsy is brittle and has broken apart this will be described, as it may be a clue to specific liver conditions.

Mallory bodies

Mallory bodies form as a result of damage to hepatocytes. When viewed under the microscope, they look like dense pink material inside the cells. Mallory bodies are often found in steatohepatitis and will be described in your report if seen.

Bile ducts

The liver produces a substance called bile which is used to remove toxins from the body and digest food. The bile produced in the liver drains through channels called bile ducts into the small bowel. Each portal tract contains one bile duct. Some liver diseases affect the bile ducts. For this reason, your pathologist will examine the bile ducts in your tissue sample to see if the normal amount of bile ducts are present and if any of the bile ducts are damaged.

Cholestasis

Cholestasis is a word pathologists use to describe bile trapped in the liver. Trapped bile is important because it can cause liver injury. If cholestasis is seen, your pathologist will describe its location within the liver and the amount of trapped bile will be described as mild, moderate, or severe.

Iron

Iron can build up within the liver as a result of the abnormal breakdown of iron, increased iron in the body (such as after multiple blood transfusions), or when the liver is not functioning properly (as in liver cirrhosis). This excess iron can be seen within the hepatocytes or within immune cells called macrophages. If iron is present in your tissue, your pathologist will report its location and severity.