Steatosis

Steatosis is the build-up of fat within the liver. This sometimes triggers inflammation of the liver. It is also known as ‘fatty liver’. The significance and relationship of steatosis to the hepatitis C virus (HCV) has only recently been begun to be understood.

There are two different forms of steatosis found in people with HCV: metabolic steatosis and HCV-induced steatosis.

  • Metabolic steatosis can result from obesity, raised blood fat levels (hyperlipidemia), insulin resistance and type 2 diabetes. It is not caused by HCV, but the presence of this form of steatosis and the presence of HCV can lead to a quicker progression of scarring or fibrosis.
  • HCV-induced steatosis is fatty infiltration that is directly caused by the presence of the virus. It is possible for people with HCV to have both forms of steatosis at the same time.

Although it appears that all genotypes can trigger steatosis, the risk of developing steatosis is significantly higher for people with genotype 3. There is a complex reaction between the genotype 3 virus and liver cells which is not seen in other genotypes.

This places the group at a much higher risk of developing the condition. Around 40% of people with hepatitis C have steatosis, compared to about 14% to 31% of the general population. However, 60-80% of people with genotype 3 have moderate or severe steatosis.

Both forms of steatosis increase the risk of disease progression in HCV infection. They also reduce the likelihood of responding to HCV treatment, and may possibly contribute to the development of liver cancer in people who have cirrhosis.

It is helpful to know which type of steatosis you might have in order to manage it or be better placed to decide whether to undergo treatment or not.

Although there is no direct treatment for steatosis, regular exercise and good diet can significantly reduce the amount of fat in the liver. For people with genotype 3, antiviral treatment can often significantly reduce or even eliminate steatosis. However, this does not seem to apply to other genotypes.

Metabolic Steatosis

The causes of metabolic steatosis are not completely understood. So far it is known to be linked to high body mass index (a measure of obesity), altered blood fat levels (e.g. triglycerides, cholesterol), elevated blood glucose, insulin resistance and type 2 diabetes.

The condition causes a build-up of globules of fat in the liver, sometimes along with inflammation. It is unclear exactly how the build-up of fat damages the liver. A number of different theories of possible mechanisms have been suggested:

  • Oxidative damage. This is when highly reactive oxygen molecules such as free radicals, produced as a result of the cells’ normal chemical reactions, interact with other molecules damaging the cells and tissue of the liver.
  • Increased vulnerability to apoptosis. This is when the immune system causes the death of certain cells to try and protect the rest of the liver.
  • Altered liver cell regeneration. This is when liver cells regenerate into deformed cells.

HCV-induced steatosis

On average, steatosis is about two and a half times more common in people with HCV than in the general population.

Biopsy samples in people with HCV who have steatosis tend to show that fat accumulates around the portal areas, rather than in the middle of the lobules of the liver which is usually the case with Non Alcoholic Fatty Liver Disease (NAFLD). This suggests that it is the virus rather than any other factor which acts as the trigger.

For people with genotype 3, the link between steatosis and the virus has now been established. Up to 80% of people with genotype 3 have moderate to severe steatosis. It seems that a complex interaction occurs between the core protein of genotype 3 and the liver cells leading to steatosis. This is not seen in other genotypes.

It also seems that the severity of steatosis in these patients is directly related to their viral load. The higher the viral load, the greater the amount of steatosis. This link has not been observed in other genotypes.

Sometimes people with genotype 3 who achieved sustained virologic response (SVR) through treatment have a marked decrease (or even complete elimination) of steatosis. If they relapse though, steatosis reappears. People with other genotypes show no improvement in the level of steatosis after successful treatment.

Symptoms

Many people with steatosis experience no symptoms. Symptoms that people do experience are nonspecific and liver enzymes levels are not necessarily raised. As with fibrosis, the definitive way to diagnose steatosis is a liver biopsy.

Steatosis and progression of HCV

It is not yet clear whether metabolic steatosis or HCV-induced steatosis both carry the same level of risk of increasing the disease’s rate of progression. There is a definite link between the severity of steatosis and the extent of scarring on the liver. Recent studies have shown that higher grades of steatosis relate to higher grades of scarring with more rapid development of fibrosis and cirrhosis.

Steatosis is also known to reduce the likelihood of responding to HCV treatment. It may also contribute to the development of liver cancer (HCC) in those with cirrhosis. Few studies have yet separated the two types of steatosis when examining its effects on fibrosis progression in people with HCV. It has been suggested, but not confirmed, that when people with genotype 3 have both forms of steatosis, the combination may trigger severe advancement of fibrosis.

Steatosis and HCV treatment

There is increasing evidence that steatosis can reduce the effects of treatment. Some studies have shown that people with steatosis were less likely to achieve a sustained virologic response (SVR) even when taking into account other facts that might induce steatosis.

One study found that sustained virologic response rates were 18-32% lower in people steatosis compared to people without steatosis, adjusted for other co-factors that affect treatment such as genotype, fibrosis score and viral load level.

Treatments for Steatosis

There is currently no treatment for steatosis. However, there are strategies that help to reduce the amount of fat in the liver. Diet, exercise and maintaining a healthy weight are important strategies to help reduce and possibly eliminate steatosis.

A recent study found that HCV patients who participated in a diet and exercise programme for three months lowered their grade of steatosis and their fibrosis score.