Clinical trial NCT02558530: Resolution of Liver Fat in Non-alcoholic Fatty Liver Disease
Official title: Rapid Resolution of Human Fatty Liver Disease, the Key to Obesity-related Morbidity and Mortality
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NAFLD
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Sahlgrenska University Hospital
name: Göteborg University
First posted: 2015-09-24
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Liver fat percent by nuclear magnetic resonance imaging
timeFrame: 14 days
Secondary outcomes:
measure: De novo lipogenesis measured as Incorporation of new fatty acids (%) to very-low density lipoprotein triglycerides
timeFrame: 14 days
measure: Gut microbiota measured as change in microbiome profile from baseline
timeFrame: 14 days
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: RPU Diabetes and Obesity, Biomedicum
city: Gothenburg
country: Sweden
facility: Wllenberg Laboratory
Study officials:
affiliation: University of Helsinki
name: Marja-Riitta Taskinen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Rasanen SM, Lee S, Mancina RM, Bergentall M, Pietilainen KH, Soderlund S, Matikainen N, Stahlman M, Bergh PO, Adiels M, Piening BD, Graner M, Lundbom N, Williams KJ, Romeo S, Nielsen J, Snyder M, Uhlen M, Bergstrom G, Perkins R, Marschall HU, Backhed F, Taskinen MR, Boren J. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab. 2018 Mar 6;27(3):559-571.e5. doi: 10.1016/j.cmet.2018.01.005. Epub 2018 Feb 15.