• May 2020

    Management of non-alcoholic steatohepatitis must focus on obesity treatment

The obesity epidemic in the United States continues to grow. Estimates are that currently 70 percent of the U.S. population is either overweight or obese. In 2013, the American Medical Association recognized obesity as a disease defined as chronic, relapsing, multifactorial and neurobehavioral where an increase in body fat promotes tissue dysfunction and abnormal physical stress to the body because of fat mass.

A major consequence of the obesity epidemic is an alarming increase in the incidence of non-alcoholic fatty liver disease (NAFLD), a constellation of liver abnormalities, including hepatomegaly and elevated liver function tests. In the general population, the incidence of NAFLD ranges from 15 to 30 percent. However, the prevalence ranges from 57 to 74 percent in those patients with a BMI greater than 30 and up to 90 percent in those whose BMI is over 40.

“Not all patients with fatty liver have liver-related problems,” says Hussien Elsiesy, MD, a transplant hepatologist on the medical staff of Baylor Scott & White All Saints Medical Center – Fort Worth. “A subgroup of those with NAFLD will develop liver inflammation or non-alcoholic steatohepatitis (NASH), which increases the risk for cirrhosis. NASH is becoming one of the most frequent causes of cirrhosis and the most common indication for liver transplant in the United States.”

Because there are not yet any FDA-approved medications for NASH, the management of NASH must address removing fat from the liver. Studies have shown that gradual weight reduction, with or without exercise, leads to improvement of liver enzymes, improvement of liver fat, improvement of hepatic inflammation and a slow improvement of liver fibrosis in patients with NASH.1

A 2010 study sponsored by the National Institutes of Health also supports the benefits of weight loss in the management of NASH.2 In the randomized controlled trial, 31 patients were randomized 2:1 to either an intensive life intervention of diet, exercise and behavioral modification or a control group that received general diet and exercise education. Patients underwent paired liver biopsy at the beginning of the study and at 48 weeks. At the end of the study, patients in the intervention group had an average weight loss of 9.3 percent versus 2 percent in the control group.

“The intervention group had a significant weight loss, as well as a significant reduction in their BMIs,” Dr. Elsiesy says. “But what is more important, two-thirds of the patients had a drop in their NASH scores of three points. So the majority of the patients had no evidence of NASH at the end of the study. There was no significant change in fibrosis scores, but 48 weeks may be too early to see significant histologic improvement.”

So among the many diet plans – low calorie, low fat, low carbohydrate, Mediterranean – which is the most effective for patients with NASH? While benefit can be obtained with net weight loss regardless of the plan chosen, recent research has shown that the Mediterranean diet, in the long run, is the most effective for inducing weight loss, together with the beneficial effect on all risk factors associated with NAFLD and metabolic syndrome, which shares many risk factors with NAFLD such as obesity, hypertension, insulin resistance and dyslipidemia.3

The Mediterranean diet consists primarily of eating whole grains, vegetables, fruit, olive oil, garlic and nuts. Fish, white meat, legumes and red wine are allowed in moderation. The diet limits red meat, processed meats and sweets. The Mediterranean diet is characterized by a beneficial fat profile consisting of a low consumption of saturated fat and cholesterol and a high consumption of monounsaturated fatty acid (MUFA) with a balanced PUFA omega-6 to omega-3 ratio, along with a high content of complex carbohydrates and fibers.  “It is important to take a detailed history about a patient’s weight and explain the need for weight loss before they go into full-blown cirrhosis,” Dr. Elsiesy says. “I usually start patients on a low-carb diet for three to six months to start a more rapid weight loss, and then switch them to the Mediterranean diet which is a more natural way of eating. When combined with increased physical activity, we see an almost universal improvement in a patient’s liver enzymes.”

1Koopman KE, Hepatology 2014, EASL-EASD-EASO clinical practice guideline of NAFLD, J Hepatology 2016

2Kittichai Promrat, Hepatology 2010

3Francesco Sofi and Alessandro Casini, World J Gastroenterol. 2014 June 21; 20(23): 7339-7346