De Novo Lipogenesis in Severity of NAFLD

Completed

• Conditions: Nonalcoholic Steatohepatitis; Obesity, Morbid; Nonalcoholic Fatty Liver Disease; Bariatric Surgery Candidate

• Registration Number: NCT03683589
• Lead Sponsor: University of Missouri-Columbia

Brief Summary

NAFLD is the most prevalent liver disease in the U.S., and there is a serious need to understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH). Previous studies has shown that elevated de novo lipogenesis (DNL) is the unique, early event distinguishing patients with NAFLD from equally-obese subjects with low IHTG. The purpose of this study is to directly by measure DNL in human liver tissue and comparing it to liver histological scores from patient biopsies.

Detailed Description

The development of nonalcoholic fatty liver disease (NAFLD) progresses from a state of elevated intrahepatic triglycerides (IHTG) to liver inflammation, and ultimately, hepatic apoptosis and fibrosis. NAFLD is the most prevalent liver disease in the U.S., and there is a serious need to understand its progression to the advanced state, nonalcoholic steatohepatitis (NASH). Elevated de novo lipogenesis (DNL) is the unique, early event distinguishing patients with NAFLD from equally-obese participants with low IHTG. DNL is the process of liver synthesis of fatty acids (FAs) from carbohydrate. In humans, studies have shown that DNL significantly predicts the magnitude of IHTG, however, it is unknown whether the pathway plays a role in disease progression. Evidence supporting this concept includes the fact that the primary product of DNL is the saturated FA, palmitate, which in cell culture has been shown to significantly contribute to oxidative stress and inflammation. Recent rodent data show that upregulation of DNL through dietary supplementation of sucrose exacerbated the hepatotoxic effects of excess dietary FAs. A preliminary abstract presented by others at the 2017 Liver Meeting suggested that DNL may not be different between patients with low and high liver fibrosis, although these data were collected using an indirect measure of liver disease. Here, in the present study, the hypothesis will be tested directly by measuring DNL in human liver tissue and comparing it to liver histological scores (NAFLD Activity Score, NAS) from patient samples.

Study Timeline

• Study First Submitted: 2018-09-20
• Study First Submitted QC: 2018-09-21
• Study First Posted: 2018-09-25
• Study Start: 2019-02-01
• Primary Completion: 2019-08-21
• Study Completion: 2020-07-31
• Status Verified: 2020-10
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
De novo lipogenesis	Dec 2019	DNL will be measured directly in the liver biopsies

Secondary Outcome Measures

Name	Time	Method
Histological scores (NAFLD activity score)	Dec 2019	Tissue histology will be performed to obtain NAFLD activity score (NAS). A pathologist, trained in determining the NAS of histological samples, grades them for the quantity of fat present, and the levels of inflammation and fibrosis. A score of 0 is considered completely healthy (devoid of any of these three characteristics), while a score of 8 indicates severe pathology, advanced as far as cirrhosis.
Liver enzymes	Dec 2019	AST and ALT will be measured on the day when liver biopsy is collected
FibroScan	Dec 2019	Liver fat and fibrosis will also be measured non-invasively via FibroScan TM

Trial Locations

Locations (1)

University of Missouri; 🇺🇸 Columbia, Missouri, United States