Resolution of Liver Fat in Non-alcoholic Fatty Liver Disease

Not Applicable

Completed

• Conditions: NAFLD
• Interventions: Other: Low carbohydrate diet

• Registration Number: NCT02558530
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

The major adverse health consequences of obesity occur only when non-alcoholic fatty liver disease (NAFLD) also develops. NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. The first-line approach to NAFLD management is caloric restriction and weight loss, but these remain difficult to achieve. Little attention has been given to dietary carbohydrate restriction, despite recent reports showing that hepatic de novo lipogenesis, a process that converts dietary carbohydrates into fatty acids in the postprandial state, accounts for approximately 25% of liver triglyceride content in hyperinsulinemic subjects with NAFLD. For comparison, only 15% of the liver triglycerides were derived from dietary fatty acids in patients with NAFLD who had consumed a standardized 30% fat diet for four days before being assessed.

Detailed Description

To establish the time-course of hepatic fat loss in NAFLD subjects on a carbohydrate-restricted diet (\<20 g/day), a serial assessments of liver fat during two week diet will be performed. Also, markers of lipid and insulin metabolism, liver function test and changes in gut microbiota during rapid metabolic improvement will be assessed.

The overall aim is to exploit this unique set of human material to determine the specific cellular and molecular pathways that are modified in the early stages of metabolic improvement and fatty liver regression.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-09-21
• Study First Submitted QC: 2015-09-23
• Study First Posted: 2015-09-24
• Primary Completion: 2021-04
• Study Completion: 2021-12
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-11
• Last Update Posted: 2022-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• increased liver fat above 5 % in magnetic resonance spectroscopy
• body mass index 27-39.9 kg/m2

Exclusion Criteria

• liver cirrhosis
• portal hypertension
• chronic liver disease other than NAFLD
• diabetes mellitus or other significant endocrine disease
• any medication acting on nuclear hormone receptors or inducing liver enzymes or self-administration of supplements other than calcium or vitamins/trace elements
• any significant cardiovascular co-morbidity
• history of non-compliance
• genotype (PNPLA3-MM and TM6SF2-TT) promoting liver fat accumulation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Low carbohydrate diet	Low carbohydrate diet	Isocaloric diet, \<20 g carbohydrates per day

Primary Outcome Measures

Name	Time	Method
Liver fat percent by nuclear magnetic resonance imaging	14 days	Liver fat percent measured by nuclear magnetic resonance imaging

Secondary Outcome Measures

Name	Time	Method
De novo lipogenesis measured as Incorporation of new fatty acids (%) to very-low density lipoprotein triglycerides	14 days
Gut microbiota measured as change in microbiome profile from baseline	14 days

Trial Locations

Locations (2)

RPU Diabetes and Obesity, Biomedicum; 🇫🇮 Helsinki, Finland

Wllenberg Laboratory; 🇸🇪 Gothenburg, Sweden