Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. NAFLD affects 30%-40% of people in Western countries, and non-alcoholic steatohepatitis (NASH), one of the most severe types of NAFLD, is thought to affect 20%-30% of those with NAFLD.
The symptoms of non-alcoholic fatty liver disease can include:
1. Fatigue
2. Weight loss resistance
3. Digestive problems such as constipation or diarrhea
4. Lack of appetite at times
5. Nausea and vomiting (only if the liver is inflamed) or stomach enlargement (if steatosis is present).
Few therapies are available for NASH patients that achieve sustained weight loss and improvement in non-invasive biomarkers associated with hepatic fibrosis. The present study evaluated the ability of salsalate to improve non-invasive biomarkers associated with hepatic fibrosis and obesity parameters in obese adults with non-alcoholic fatty liver disease.
Salsalate is a non-steroidal anti-inflammatory drug, which is efficacious in reducing liver fat levels.
Participants with non-alcoholic fatty liver disease were randomized into one of three groups consecutively over 12 months: placebo for 2 months, low dose salsalate for 4 months, and high dose salsalate for 8 months. The primary outcome was the change in noninvasive hepatic fibrosis markers using transient elastography between baseline and endpoint. An interim analysis showed decreased noninvasive markers of hepatic fibrosis at 4 months on both doses of salsalate compared to baseline (placebo) noninvasive marker.
A total of 48 participants completed the study. The non-invasive marker declined by 13.6% in the placebo group, 24.4% in the low dose salsalate group, and 30.5% in the high dose salsalate group.
Weight decreased 5%, 14%, and 17%, respectively, for placebo, low dose, and high dose salsalate groups at 12 months (p=0.04). Body mass index in all groups was highly correlated with non-invasive markers of hepatic fibrosis (r=-0.49 to -0.60 p<0.001).
Sensitivity analyses showed that weight loss achieved during 4 months continued during 8 months on medication. This is an important finding showing that non-invasive markers associated with hepatic fibrosis improved when weight loss was sustained.
Salsalate is non-toxic and well-tolerated and can improve noninvasive markers associated with hepatic fibrosis in NAFLD patients and improve weight and body mass index. This study shows that noninvasive markers associated with hepatic fibrosis improved along with obesity parameters during a one-year period on salsalate, which is an important finding showing that non-invasive markers associated with hepatic fibrosis improved during that time loss were sustained.
This means that non-alcoholic fatty liver disease patients who lose weight have a greater chance of reversing the effects of non-alcoholic fatty liver disease than those who do not lose weight.