The exact cause of nonalcoholic 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 some factor in your environment. The first hit, the fat buildup, makes you vulnerable to the second hit, when inflammation begins.²

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.