Severe Non-Alcoholic fatty liver disease treated by Omega-3 – RCT April 2018

Non-Alcoholic fatty liver disease severity and metabolic complications in obese children: Impact of Omega-3 Fatty Acids

The Journal of Nutritional Biochemistry. online 10 April 2018, https://doi.org/10.1016/j.jnutbio.2018.03.025
S. Spahisa, b, c, F. Alvareza, d, N. Ahmede, J. Duboisa, f, R. Jalbouta, M. Paganellia, K. Grzywacza, E. Delvina, N. Perettig, Emile Levya, b, c, ,

47 page PDF with excellent tables was on Sci-Hub April 2018

Although n-3 polyunsaturated fatty acids (PUFA) revealed promising therapeutic results in non-alcoholic fatty liver disease (NAFLD), which is considered as the most prevalent cause of chronic hepatic disease, inconsistencies are calling for further confirmatory trials to demonstrate therapeutic efficacy and safety.

The study, registered as NCT02201160 on www.clinicaltrials.gov, was designed to compare two groups of NAFLD with a different severity, and to evaluate the efficacy of n-3 PUFA supplementation.

Twenty young male participants of French Canadian origin with NAFLD were enrolled and classified into moderate (mNAFLD) and severe (sNAFLD) fatty liver groups, according to transaminase levels, ultrasonography, NAFLD Activity Score and fatty liver index (FLI). The sNAFLD patients were assigned to consume 2 g of n-3 PUFA for 6 months. sNAFLD patients displayed higher insulinemia, insulin resistance (IR), oxidative stress (OxS), systolic blood pressure and the risk lipid indicators of cardiovascular diseases.

Supplementation of n-3 PUFA for 6 months resulted in a significant increase in concentrations of eicosapentaenoic and docosahexaenoic acids in RBC along with an attenuation of hepatic steatosis as reflected by the reduction of the FLI, ALT and ALT/AST ratio.

Moreover, the n-3 PUFA improved the lipid profile and carotid intima-media thickness, while reducing metabolic and OxS markers and raising adiponectin.

In conclusion, NAFLD severity was essentially related to IR. Treatment with n-3 PUFA has an evidently beneficial effect on liver steatosis and related metabolic abnormalities. Furthermore, the cross association of omega-3 index with cardiometabolic markers may serve as a predictor for cardiovascular risk disorders in NAFLD.

Abbreviations
APO, Apolipoprotein; BMI, body mas index; CTR, control; CVD, cardiovascular disease; DHA, Docosahexaenoic acid; DBP, diastolic blood pressure; EPA, Eicosapentaenoic acid; FA, Fatty acids; IL, Interleukin; IMT, Intima-media thickness; IR, Insulin resistance; FLI, Fatty liver index; GC, gas chromatography; GGT, γ-glutamyl transferase; LDL-C, Low-density lipoprotein cholesterol; MDA, Malondialdehyde; MetS, metabolic syndrome; NAFLD, Non-alcoholic fatty liver disease; OxS, oxidative stress; OxLDL, Oxidized LDL; PUFA, Polyunsaturated fatty acid; RBC, red blood cell; SBP, systolic blood pressure; TG, Triglycerides; VLCFA, Very long chain FA

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Another NAFLD gene study April 2019

Vitamin D status and associated genetic polymorphisms in a cohort of UK children with non-alcoholic fatty liver disease
Gibson, Philippa S., Quaglia, Alberto, Dhawan, Anil, Wu, Huihai, Lanham-New, Sue, Hart, Kath, Fitzpatrick, Emer and Moore, J. Bernadette (2018) Vitamin D status and associated genetic polymorphisms in a cohort of UK children with non-alcoholic fatty liver disease Pediatric Obesity.
 Download the PDF from VitaminDWiki

Background: Vitamin D deficiency has been associated with non-alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown.

Objectives: To determine in UK children with biopsy-proven NAFLD: (i) vitamin D status throughout a 12-month period; (ii) interactions between key vitamin D-related genetic variants (NADSYN1/DHCR7, VDR, GC, CYP2R1) and disease severity.

Methods: In 103 pediatric patients with NAFLD, serum 25-hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy and examined in relation to NAFLD activity score and fibrosis stage.

Results: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (<25nmol/l, 25.5%) or insufficient (<50nmol/l, 55.3%). Patients had significantly lower 25OHD levels in winter months (95%CI: 22.7-31.2nmol/l) when compared to spring (30.5-42.1nmol/l; P=0.0089), summer (36.3-47.2nmol/l; P<0.0001) and autumn (34.2-47.5nmol/l; P=0.0003). Polymorphisms in the NADSYN1/DHCR7 (rs3829251, rs12785878), and VDR (rs2228570) genes were independently associated with increased steatosis; while a GC variant (rs4588) was associated with increased inflammation in liver biopsies.

Conclusions: Children with NAFLD in the UK have particularly low winter vitamin D status; with vitamin D insufficiency prevalent throughout the year. Polymorphisms in the vitamin D metabolic pathway are associated with histological severity of pediatric NAFLD.