Non-alcoholic Steatohepatitis (NASH)

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Non-alcoholic Steatohepatitis (NASH)

Overview

What is non-alcoholic steatohepatitis (NASH)?

Non-alcoholic steatohepatitis (NASH) is liver inflammation caused by a buildup of fat in the liver. NASH is part of a group of liver diseases, known as non-alcoholic fatty liver disease, in which fat builds up in the liver and sometimes causes liver damage that gets worse over time (progressive liver damage).

Although the cause is not known, NASH seems to be related to certain other conditions, including obesity, high cholesterol and triglycerides, and diabetes. Treatment for NASH involves controlling those diseases.

What causes NASH?

The exact cause of NASH is not known. It most commonly affects people who are middle-aged and are overweight or obese, have high cholesterol and triglycerides, or have diabetes. Yet it can occur in people who have none of these risk factors. Excess body fat along with high cholesterol and high blood pressure are also signs of a condition called metabolic syndrome. This condition is closely linked to insulin resistance.

Along with excess fat in the liver, which many people have, several other factors may contribute to the liver damage. These are:

  • Resistance to insulin, which means that the body can't use sugar (glucose) in the way it should. Normally, your body makes insulin after you eat a meal that has sugar in it. Insulin helps the extra sugar in your blood get into your muscles and liver. If your body does not respond to insulin in this way, then the sugar level in your blood will stay high. This is how insulin resistance can increase your chance of developing type 2 diabetes.
  • Changes in how the liver makes fat and what the liver does with fat that is delivered to it by the intestines.

Other factors that have been known to contribute to NASH include:

  • Having had surgeries that shorten the intestines, the stomach, or both, such as jejunal bypass operation or biliopancreatic diversion.
  • Using a feeding tube or other method of receiving nutrition for a long time.
  • Using certain medicines, including amiodarone, glucocorticoids, synthetic estrogens, and tamoxifen.

What are the symptoms?

NASH is a condition that may get worse over time (called a progressive condition). For this reason, you may have no symptoms until the disease progresses to the point that it begins to affect the way the liver works (liver function). As liver damage gets worse, symptoms such as tiredness, weight loss, and weakness may develop.

It may take many years for NASH to become severe enough to cause symptoms. In some cases, the progress of the condition can stop and even reverse on its own without treatment. But in other cases NASH can slowly get worse and cause scarring (fibrosis) of the liver, which leads to cirrhosis. Cirrhosis means that liver cells have been replaced by scar tissue. As more of the liver becomes scar tissue, the liver hardens and can't work normally.

Who is affected by NASH?

Even though many people have fatty liver disease, NASH is less common. Middle-aged people who are obese are most commonly affected by NASH.

How is NASH diagnosed?

To diagnose liver disease, your doctor will ask about your medical history. And you will have a physical exam along with some tests to identify possible causes of liver disease. Imaging tests may include an ultrasound, a CT scan, or an MRI scan. A liver biopsy may be recommended to confirm the diagnosis and to see if your liver has been damaged. In a biopsy, a sample of tissue is collected from the liver and examined under a microscope.

How is it treated?

Although there is no specific treatment for NASH, you can manage the conditions that contribute to the liver damage. This may include reducing your total cholesterol level, losing weight, controlling diabetes, and stopping the use of any medicine that may be causing the symptoms or making them worse. You will also need to avoid drinking excessive amounts of alcohol, because this can make fatty liver disease worse.

Frequently Asked Questions

Learning about non-alcoholic steatohepatitis (NASH):

Being diagnosed:

Getting treatment:

Ongoing concerns:

Living with NASH:

Cause

The exact cause of non-alcoholic steatohepatitis (NASH) is not known. It is most likely caused by a combination of environmental and genetic factors. NASH most often occurs in people who are middle-aged and overweight or obese, many of whom have diabetes or high cholesterol and high triglycerides. But people with none of these risk factors can also get NASH. If you have NASH and diabetes, your insulin levels may be even higher than if you had diabetes alone.

Although there is no clear reason why some people develop NASH and others do not, one possible explanation is that it takes two "hits" for NASH to occur. The first "hit" is the initial buildup of fat in the liver, which many people have. The second "hit" is thought to come from either a family history that makes you more likely to get the disease or from something in your environment. The first hit, the fat buildup, makes you vulnerable to the second hit, when inflammation begins.

Many things can lead to the buildup of fat in the liver. An increase in fat in your diet alone will not cause fatty liver disease.

Several factors may contribute to liver damage from NASH, including:

  • Resistance to insulin, which means that your body is less able to use sugar (glucose).
  • Metabolic syndrome, a cluster of conditions related to the body's metabolism. These conditions include excess body fat (particularly around the waist), high triglycerides, high blood pressure, high blood sugar, and low HDL ("good") cholesterol. These all are linked to insulin resistance.
  • Changes in how the liver makes fat and what the liver does with fat that is delivered to it by the intestines.
  • The release of toxic substances by fat cells.
  • The breakdown of liver cells.
  • Certain drugs, including some antibiotics.
  • Alcohol.

Symptoms

You may have no symptoms in the early stages of non-alcoholic steatohepatitis (NASH). Most people with NASH feel well and don't know that they have the condition. As NASH progresses and liver damage becomes worse, symptoms may develop, including:

  • Fatigue (feeling tired all the time).
  • Unexplained weight loss.
  • General weakness.
  • An aching in the upper right part of your belly.

As NASH advances, cirrhosis develops. Cirrhosis is permanent damage to the liver caused by scarring. If this happens, you may have other symptoms such as:

  • Fluid buildup in your legs and abdomen.
  • Yellowing of your skin (jaundice).
  • Nosebleeds.
  • Blood in your stool.
  • Bruising easily.
  • Weight loss and muscle loss.
  • Abdominal discomfort.
  • Frequent infections.
  • Confusion or trouble thinking.

What Happens

Non-alcoholic steatohepatitis (NASH) is a part of a group of liver diseases known as non-alcoholic fatty liver disease (NAFLD). The buildup of fat in the cells of the liver is called fatty liver, or steatosis, and in itself is not harmful. Many people have fatty liver. In NASH, the fat buildup causes inflammation of the liver, which can lead to symptoms such as fatigue, weight loss, and weakness.

NASH typically appears in people during middle age, in their 40s and 50s, but it can happen earlier or later in life. It occurs equally in men and women.

Early on, the buildup of fat does not affect the function of the liver, and you will have no symptoms. As fat continues to build up and inflammation occurs, liver function begins to decline and symptoms develop. This inflammation may lead to scarring and severe damage of the liver. There is no clear reason why some people with fatty liver develop NASH and others do not.

After the liver has been damaged, there is a much greater chance that the damage will continue and get worse. In some cases, the disease progression can stop and even reverse on its own without treatment. But in other cases NASH can slowly get worse and cause scarring (fibrosis) of the liver, which leads to cirrhosis. Cirrhosis means that the liver has become scarred and hardened and is not able to work normally.

What Increases Your Risk

Non-alcoholic steatohepatitis (NASH) most commonly affects people who are middle-aged and obese.

Factors that increase your risk for developing NASH include:

Certain treatments for other conditions can also increase your risk of NASH. Some examples of how this could happen include:

  • Having had surgery that modifies the intestines, the stomach, or both.
  • Using a feeding tube or other method of nutrition delivery for a long time.
  • Using certain medicines, including amiodarone, glucocorticoids, synthetic estrogens, and tamoxifen.

When to Call a Doctor

Call a health professional immediately if:

You have non-alcoholic steatohepatitis (NASH) and you:

  • Pass out (lose consciousness).
  • Have difficulty breathing.
  • Vomit blood or what looks like coffee grounds.
  • Pass maroon or very bloody stools.
  • Feel dizzy or light-headed, or feel like you may faint.

Make an appointment to see your doctor if you either have been diagnosed with NASH or are at risk for the condition and you experience:

  • Nausea.
  • Vomiting, especially if it includes blood.
  • Diarrhea.
  • Yellowing of the skin or the whites of the eyes (jaundice).
  • Pain in the upper right part of the belly (abdomen).
  • General itching.
  • Swelling of the legs or abdomen.

To determine if you are at risk for NASH, see the What Increases Your Risk section of this topic.

Watchful Waiting

Taking a wait-and-see approach (watchful waiting) is appropriate if you have already been diagnosed with NASH and your symptoms do not change or get worse. You will need regular checkups (about every 6 months) during watchful waiting.

Who to See

Your family doctor, general practitioner, or pediatrician can diagnose non-alcoholic steatohepatitis (NASH). You may be referred to a specialist, such as a gastroenterologist or a hepatologist.

Exams and Tests

No single test can accurately diagnose non-alcoholic steatohepatitis (NASH). Your doctor will ask about your medical history and do a physical examination along with a number of other tests. These tests can rule out other conditions that may be causing your symptoms. A diagnosis of NASH requires that you have:

  • No history of significant alcohol intake (more than 1 to 2 drinks a day).
  • No other liver diseases.
  • Fat buildup in the cells of your liver.

Imaging tests can detect whether fat is building up in the cells of your liver. But imaging tests cannot show whether this has led to liver inflammation or scar tissue. They are used to rule out other causes of liver disease and to rule out liver tumours if cirrhosis is present. Imaging tests that may be done include:

A liver biopsy may be done to confirm a diagnosis of NASH. In a liver biopsy, a sample of tissue is taken from the liver and examined under a microscope to look for abnormal tissue.

Treatment Overview

There is no proven effective treatment for non-alcoholic steatohepatitis (NASH). But making lifestyle changes that decrease your risk of liver damage may help to keep the disease from getting worse.

In general, treatment is aimed at managing conditions that contribute to NASH or make it worse. These include obesity, high cholesterol, and diabetes. If you have NASH, you should also minimize your alcohol use and stop taking any medicines that may be harmful to your liver.

Controlling your weight and cholesterol

Losing weight and lowering your cholesterol can help stop or limit the damage done to your liver. The most effective way to do this is to modify your diet and get regular exercise.

Experts recommend that you gradually lose 10% of your total body weight, at a rate of no more than 0.5 kg (1 lb) to 1 kg (2 lb) a week.1 Losing just 10% of your weight can help your body use insulin more effectively. This would mean, for example, losing 9.1 kg (20.0 lb) if you weigh 91 kg (200 lb). This can decrease the amount of fat that builds up in your liver and limit the damage it does to the cells of your liver.

But it is very important that you lose weight gradually, not rapidly. Rapid weight loss can cause greater harm to your liver by increasing inflammation and scar tissue. You should lose 0.5 kg (1 lb) to 1 kg (2 lb) a week until you have met your goal of 10% of your total body weight.

Avoid crash or fad diets. Weight-loss drugs have not been proved effective for the treatment of NASH. And surgeries such as intestinal bypass can make NASH worse.

Weight loss is best achieved through modifying your diet and getting more exercise. For more information on obesity and how you can safely and effectively lose weight, see the topics Obesity and Weight Management.

Lowering your cholesterol can also help your liver. Although there is no evidence that cholesterol-lowering drugs can help stop damage to your liver from NASH, following a heart-healthy diet and lowering your cholesterol as part of a weight-loss plan may help. For more information on high cholesterol and how you can reduce it, see the topic High Cholesterol.

One safe and effective way of controlling your cholesterol without taking medicine is by following a program called Therapeutic Lifestyle Changes. This program involves losing excess weight, increasing your activity, and eating meals that are low in saturated fat. Done together, these changes may help you lower your cholesterol by 10% to 20%.

Controlling diabetes

Diabetes is common in people who have NASH—up to 75% of people with NASH have diabetes. Resistance to insulin contributes to the development of NASH. If you have diabetes, keep your blood sugar in a safe range to help prevent fat buildup in and damage to your liver.

For more information on controlling diabetes, see the topic Type 2 Diabetes: Living With the Disease.

Prevention

The only way to prevent non-alcoholic steatohepatitis (NASH) is to prevent fat from building up in your liver. A healthy lifestyle that includes routine exercise and a healthful diet is the best way to prevent fat buildup. A healthy diet also can decrease your body's resistance to insulin, which is the best way to prevent fat buildup.

One safe and effective way to control your cholesterol without taking medicine is a program called Therapeutic Lifestyle Changes. This program involves losing excess weight, increasing your activity, and eating meals that are low in saturated fat. Done together, these changes may help you lower your cholesterol by 10% to 20%.

If you have diabetes, keeping your blood sugar in a safe range and staying at a healthy weight can help prevent NASH. For more information on how to control blood sugar, see the topic Type 2 Diabetes: Living With the Disease.

If you already have NASH or if tests show that fat has already built up in your liver, modifying your diet and getting routine exercise can help reduce the risk of further liver damage. You should also minimize your use of alcohol, which can increase damage to your liver, and avoid any medicines that may harm the liver.

Home Treatment

There is no specific treatment for non-alcoholic steatohepatitis (NASH), so doctors recommend that you treat the conditions that are associated with it. These include obesity, high cholesterol and high triglycerides, and diabetes. By taking steps to lose weight, lower your cholesterol, and control your diabetes, you can stop or limit the damage to your liver from NASH.

If you are obese, losing weight can help stop or limit the liver damage from NASH. Experts recommend that you gradually lose 10% of your total body weight. It is important that you lose this weight gradually, at a rate of about 0.5 kg (1 lb) to 1 kg (2 lb) a week.1 Losing weight too rapidly through a crash diet or a surgical procedure can cause even more damage to your liver. For more information on obesity and how you can safely and effectively lose weight, see the topics Obesity and Weight Management.

High cholesterol and high triglycerides mean that you have large amounts of fat in your blood. High cholesterol increases your risk of fat building up in your liver, which can lead to NASH. Drugs that lower cholesterol levels have not been proved effective for treating NASH. But a heart-healthy diet can lower your cholesterol and may improve NASH. For more information on high cholesterol and how you can reduce yours, see the topic High Cholesterol.

One safe and effective way of controlling your cholesterol without taking medicine is a program called Therapeutic Lifestyle Changes. This program involves losing excess weight, increasing your activity, and eating meals that are low in saturated fat. Done together, these changes may help you lower your cholesterol by 10% to 20%.

If you have diabetes, keeping your blood sugar in a safe range can help improve NASH. For more information on how to control blood sugar, see the topic Type 2 Diabetes: Living With the Disease.

Alcohol can make liver damage worse, so you should minimize your alcohol use if you have NASH.

You should also stop taking any medicines that may be harming your liver. Ask your doctor or pharmacist about all medicines you are taking.

Other Treatment

Insulin resistance is a major risk factor for non-alcoholic steatohepatitis (NASH). But medicines that treat insulin resistance, such as thiazolidinediones and metformin, are not proved to be effective specifically for treating NASH. These medicines are currently being studied for how well they work in treating NASH.

Damage to liver cells from free radicals is also thought to contribute to NASH. Medicines that prevent this damage, including certain antioxidants and vitamins E and C, have shown in early tests that they may be useful in treating NASH. But the long-term safety and effectiveness of these drugs in treating NASH is still being studied.

Other Places To Get Help

Organization

Canadian Liver Foundation
2235 Sheppard Avenue East
Suite 1500
Toronto, ON  M2J 5B5
Phone: (416) 491-3353
1-800-563-5483
Fax: (416) 491-4952
Email: clf@liver.ca
Web Address: www.liver.ca
 

The Canadian Liver Foundation funds medical research and offers education and support programs for liver disease patients, their families and friends, health professionals, and the general public.


References

Citations

  1. National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases (1998). Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Available online: http://www.nhlbi.nih.gov/guidelines/obesity/ob_gdlns.pdf.

Other Works Consulted

  • Ahmed A, et al. (2006). Nonalcoholic fatty liver disease section of Alcoholic and nonalcoholic fatty liver disease. In MM Wolfe et al., eds., Therapy of Digestive Disorders, 2nd ed., pp. 551–564. Philadelphia: Saunders Elsevier.
  • American Gastroenterological Association (2002, reapproved 2008). AGA technical review on nonalcoholic fatty liver disease. Gastroenterology, 123(5): 1705–1725.
  • Collantes R, et al. (2004). Nonalcoholic fatty liver disease and the epidemic of obesity. Cleveland Clinic Journal of Medicine, 71(8): 657–664.

Credits

By Healthwise Staff
Primary Medical Reviewer Kathleen Romito, MD - Family Medicine
Specialist Medical Reviewer W. Thomas London, MD - Hepatology
Specialist Medical Reviewer Andrew Swan, MD, CCFP, FCFP - Family Medicine
Last Revised October 12, 2009

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information.