Prevalence of non-alcoholic fatty liver disease and assessment of a low-carbohydrate high-fat diet as a dietary treatment option

Research output: ThesisPh.D. thesis

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Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern,but the potential burden of NAFLD in Denmark is currently unknown due to the lack ofprevalence data. The current treatment strategy for NAFLD relies primarily on weight-loss,obtained by decreasing calorie intake, however, this strategy have limited success. A lowcarbohydrate high-fat diet (LCHF) has shown promise in improving NAFLD, even whileeating until satiated, but its impact on liver histology remains unclear, and the potentialimpact on cardiovascular disease risk in NAFLD patients is unknown and still debated.


Aims: This thesis aimed to 1) determine the prevalence and severity of NAFLD inDenmark in an unselected and an at-risk population 2) evaluate the effectiveness of acalorie-unrestricted low-carbohydrate high-fat (LCHF) diet compared to a highcarbohydrate low-fat (HCLF) diet on NAFLD-activity score, and 3) assess the impact of aLCHF diet on the plasma lipidome and its potential associations with major adversecardiovascular events (MACE).


Methods: We conducted two studies: Study 1 was a cross-sectional prospectivemulticohort study of unselected participants and at-risk participants from the generalpopulation. We performed controlled attenuation parameter (CAP) and vibration-controlledtransient elastography (VCTE) on all participants to evaluate the prevalence and severityof NAFLD in Denmark. We used the CAP cut-off ≥302 dB/m to diagnose NAFLD andVCTE≥12 kPa to diagnose advanced fibrosis. Study 2 was a six-month randomizedcontrolled diet trial with people who had type 2 diabetes. Participants were randomly unrestricted high-carbohydrate low-fat (HCLF) diet for six months. Liver biopsies wereperformed before and after the intervention, and EDTA plasma samples were collected atbaseline, three months, six months, and nine months (follow-up visit) for massspectrometry lipidomics analysis.


Results: The prevalence of NAFLD in Denmark was 20% in the unselected populationand 43% in the at-risk population. Advanced fibrosis was found in 2% of the unselectedpopulation, in 8% of the at-risk population, and in 18% of people with type 2 diabetes andNAFLD from the at-risk population. We saw no difference between diets in regards toimprovement of ≥2 points in the NAFLD activity score (17% vs 13%; p=0.46). However,the LCHF diet was more effective in improving NAFLD activity score with 1 point comparedto the HCLF diet, with 56% of LCHF participants showing improvements compared to 35%in the HCLF group. Additionally, only 1% of participants on the LCHF diet experienced aworsening of NAFLD, compared to 17% in the HCLF group. Furthermore, the LCHF dietaltered the plasma lipid metabolism, but did not appear to increase the risk of MACE.


Conclusion: NAFLD represents a significant healthcare burden in Denmark, and urgentaction is needed to improve the management of NAFLD. Our study demonstrates that theLCHF diet can improve NAFLD even while eating until satiety, without increasing the riskof MACE. These results suggest that the LCHF diet could be considered as a new dietarytreatment option for individuals with NAFLD. However, healthcare professionals shouldprovide detailed guidance and support to ensure the safe and effective implementation ofthe LCHF dietassigned to either a calorie-unrestricted low-carbohydrate high-fat (LCHF) diet or a calorie
Translated title of the contributionPrævalens af non-alkoholisk fedtleversygdom og undersøgelse af en lav-kulhydrat høj-fedt kost som behandlingsmulighed
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
Supervisors/Advisors
  • Krag, Aleksander, Principal supervisor
  • Hansen, Torben , Co-supervisor, External person
  • Israelsen, Mads Bastrup, Co-supervisor
Date of defence16. Jun 2023
Publisher
DOIs
Publication statusPublished - 23. May 2023

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