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Steatohepatitis

Steatohepatitis is characterized by maculovesicular steatosis. These patients tend to have lobular and portal inflammation. They may have Mallory’s hyalin, fibrosis or cirrhosis. Really an appearance that resembles alcoholic liver disease. But in the absence of a history of alcohol abuse. This is a common disorder. Depending upon the degree of obesity in a population it may affect up to 1-2% of given populations. Diabetes, obesity and hyperlipidemia are risk factors for this entity. Some of these patients will have iron overload, especially with severe disease.

Occasionally these patients require liver transplantation. Now some series are suggesting that the transplant centers have 1-2% of their patients undergoing transplantation for NASH. There is no effective therapy that’s standard for these patients. Weight loss is frequently advocated but for many of these patients with obesity it’s seldom successful. They’ve been trying to lose weight essentially all their life. I think the other thing that’s been frustrating when weight loss is advocated is oftentimes patients who are told to lose weight and do so, but do so quickly, may actually have what appears to be histologic worsening of their nonalcoholic steatohepatitis. So not only do you have to tell the patient, who is obese with this condition, to lose weight.

Something that seldom seems to happen. Antibiotics have been tested in patients who have nonalcoholic steatohepatitis associated with jejunoileum bypass, but to my knowledge antibiotics have not been tried in the usual type of nonalcoholic steatohepatitis that we see. A small pilot study suggests that clofibrate, a lipid lowering agent, was not useful in patients with hyperlipidemia and NASH. In another study, a recent study, small number of patients, short duration of study suggested gemfibrozil, another lipid lowering agent.

There have been a variety of drugs that have been tested or currently undergoing evaluation. Vitamin E in obese kids has looked quite successful. These kids tend to have vitamin E deficiency for unexplained reasons. When vitamin E has been used in patients, adult patients, with NASH however, the results have not been so promising. Although the studies have oftentimes been obscured by use of vitamin E.

Betaine is a drug that’s approved for use in homocystinuria in animal models of fatty liver. It led to improvement, and in an ongoing clinical trial - that we have a pilot study - has led to improved biochemistry’s and in two patients, in whom liver biopsies have been repeated after a year, histologic improvement as well. This drug is taken as a powder. It’s unpleasant to take and it’s relatively expensive.

In a study from the University of Virginia six obese patients who are not diabetic but had nonalcoholic steatohepatitis received troglitazone for up to four months. Four of these six normalized their ALT, the test that’s usually most abnormal in NASH patients. This was sustained for at least three months, even after the troglitazone was stopped. So the patients received it for up to four months. The drug was stopped, and when they were followed for up to three months later, they still had improvement in biochemistrys.

Ursodeoxycholic acid now seems to be a popular therapy for patients with NASH but the data upon which these decisions have been based are relatively sparse. Twenty-four patients were treated for up to a year with the dose that would be used for treating PBC, 13-15 mg per kilogram. Modest improvement in alkaline phosphatase. This shows, the line here, shows no change. The shaded area here shows the 95% confidence interval.