New NASH findings may offer potential for treatment
Paul Basilio, MDLinx | May 18, 2017
New research published in the journal Hepatology Communications has uncovered the key inflammatory cells involved in nonalcoholic fatty liver disease. While current management involves a change in diet, no medication has been approved for the disease. These new findings offer a potential target for therapies and possibly a treatment.
Healthy liver (left) and diseased liver (right) with infiltrated CD8 T-cells indicated by arrow. Image courtesy of CHLA.
Healthy liver (left) and diseased liver (right) with infiltrated CD8 T-cells indicated by arrow. Image courtesy of CHLA.
The team of investigators at the Children’s Hospital Los Angeles was led by Rohit Kohli, MBBS, MS.
“The rise in obesity has led to an epidemic of fatty liver disease in both children and adults,” said Dr. Kohli, who is Head of the division of Gastroenterology, Hepatology, and Nutrition at CHLA and an Associate Professor of Pediatrics at the Keck School of Medicine of USC. “However, only a smaller number of these individuals will develop the most severe form of this disease known as nonalcoholic steatohepatitis or NASH.”
Although the exact cause of NASH is still unclear, it occurs in those who are obese, and it may have an association with type 2 diabetes, elevated cholesterol, or other metabolic abnormalities. The disease course is characterized by liver inflammation and damage from deposits of excessive fat in the liver.
In this mouse study, the team conducted a series of experiments to determine how diet contributes to liver inflammation and the progression of NASH. They sought to determine the role that natural killer T cells (NKT) and CD8 T-cells cells play in the development of the disease, and turned their attention to the immune cells involved in adipose tissue inflammation in patients with insulin resistance.
Mice were fed a high fat, high carbohydrate (HFHC) diet to mimic western eating habits. Control animals were fed commercial mouse chow.
After 16 weeks, the mice receiving the HFHC diet had increased inflammation when compared with the control animals. Specifically, infiltration of NKT and CD8 T-cells into the liver was noted.
The experiment was repeated with mice that lack functional NKT cells to examine the contribution of each type of immune cell. After 16 weeks of an HFHC diet, these mice did not become obese or show progression to NASH. This suggests an integral role for NKT cells in the development of these conditions.
In a separate experiment, mice were treated with an antibody that targets CD8 T-cells. These animals became obese on the HFHC diet, but they were protected against NASH. These mice also had less fibrosis and fewer macrophages in the liver.
To show the relevance of the findings in humans, the team analyzed liver biopsy specimens from patients with NASH. Infiltration by CD8 T-cells was present. Infiltration of NKT cells was not observed, but the authors speculate the changes in this cell population could be transient.
“Our findings will help to focus attention on certain inflammatory cell types that appear to be critical to the development of severe liver disease and move us closer to development of a treatment,” said Dr. Kohli.
To read more about the study, click here.