Non-alcoholic fatty liver disease (NAFLD) is a common condition that, without signs of fibrosis, may be benign. But with fibrosis, NAFLD can progress to non-alcoholic steatohepatitis (NASH), cirrhosis of the liver and death, according to speakers at Saturday’s DDW Combined Clinical Symposium on Therapeutic Approaches in NAFLD.
The risk factors for progression of NAFLD include older age (50 years and older), race (especially Mexican Americans), weight gain, insulin resistance and diabetes, said Kris V. Kowdley, MD, FASGE, AGAF, director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center and clinical professor of medicine at the University of Washington, Seattle.
“Cardiovascular disease is much more common than liver disease as a cause of death in NAFLD patients,” Dr. Kowdley said. Studies have shown that cardiovascular disease accounts for about 25 percent of deaths in these patients versus 13 percent from liver disease. In addition, the risk of mortality increases as fibrosis advances from minimal to severe.
NAFLD can also progress to hepatocellular cancer. One study indicated that about 13 percent of patients with hepatocellular cancer have NAFLD, with the greatest risk of cancer among obese men over 50 years of age, Dr. Kowdley said.
Lifestyle modifications such as weight loss, increased exercise, getting a good night’s sleep, and eating healthy foods have been used to improve the histopathology of NAFLD and help patients manage comorbidities, said Stephen A. Harrison, MD, associate dean of the Uniformed Services Health Education Consortium and professor of medicine at the Uniformed Services University of the Health Sciences, San Antonio, TX.
Dr. Harrison recommended a loss of nine to 10 percent of body weight to improve the histological findings of NASH and moderate exercise three to five times a week to help reduce the risk of cardiovascular disease and diabetes. “Exercise coupled with a moderate caloric-restricted diet utilizing low-glycemic index foods is optimal,” he said.
If lifestyle changes don’t work, pharmaco-therapy holds promise, said Paul Angulo, MD, professor of medicine and chief of hepatology at the University of Kentucky College of Medicine, Lexington. “Achieving and maintaining appropriate body weight is a difficult task to accomplish by most obese people,” Dr. Angulo noted.
Several drugs have been tested in NASH patients, including the insulin sensitizers metformin and pioglitazone, the weight-loss medications orlistat and rimonabant, the ACE inhibitors losartan and telmisartan, and the lipid-lowering statins and fibrates. However, metformin, orlistat, rimonabant and losartan have been found to be either minimally effective or unsafe in this patient population.
To date, vitamin E therapy has shown the strongest evidence of efficacy for NASH patients. In one study, vitamin E therapy was associated with a significant improvement in NASH patients compared to placebo. But the same study showed that the rate of improvement associated with pioglitazone therapy was not significant, Dr. Angulo said. However, vitamin E therapy has not been evaluated in NASH patients with diabetes.
Bariatric surgery is another potential treatment option for the management of NAFLD and NASH, said Raj Vuppalanchi, MD, associate professor of medicine in the division of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis. A variety of procedures are used, including gastric banding, sleeve gastrectomy and Roux-en-Y surgery.
A Cochran analysis of 21 prospective or retrospective cohort studies has shown that bariatric surgery reduces steatosis or inflammation in NASH, and four of those studies described some deterioration in the degree of fibrosis, Dr. Vuppalanchi said. However, no randomized clinical trials or quasi-randomized clinical studies have been conducted to assess the safety and effectiveness of bariatric surgery for NASH, he added.
And, although bariatric surgery may be safe to pursue in NAFLD patients who satisfy the criteria for this therapy, cirrhosis with portal hypertension appears to be a contra-indication, Dr. Vuppalanchi said.
Finally, extrahepatic complications and comorbidities of NAFLD such as obesity, type 2 diabetes, dyslipidemia and the metabolic syndrome, should be assessed and addressed in all patients with NAFLD, said Naga P. Chalasani, MD, professor of medicine and chief of gastroenterology and hepatology at Indiana University School of Medicine.
Since these patients are at significant risk for cardiovascular morbidity and mortality, clinicians should consider providing aggressive lipid-lowering therapy and advising patients to avoid consuming heavy amounts of alcohol, though evolving evidence suggests that non-heavy drinking may have hepatic and metabolic benefits, Dr. Chalasani said.
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