Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612703
Poster Visit Session II Clinical Hepatology – Friday, January 26, 2018, 2:35pm – 3:20pm, Room 120
Georg Thieme Verlag KG Stuttgart · New York

Could inherited predisposition drive fatty liver disease in non-obese Germans? Results from eight tertiary referral centers

M Krawczyk
1   Department of Medicine II, Saarland University Medical Center, Homburg
2   Medical University of Warsaw, Laboratory of Metabolic Liver Diseases, Centre for Preclinical Research, Department of General, Transplant and Liver Surgery, Warsaw
,
H Bantel
3   Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover
,
M Rau
4   University Hospital Würzburg, Division of Hepatology, Department of Medicine II, Würzburg
,
J Schattenberg
5   Johannes Gutenberg University, Department of Medicine I, University Medical Center Mainz, Mainz
,
F Grünhage
1   Department of Medicine II, Saarland University Medical Center, Homburg
,
A Pathil
6   University of Heidelberg, Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg
,
S Weber
1   Department of Medicine II, Saarland University Medical Center, Homburg
,
M Demir
7   University Hospital of Cologne, Clinic for Gastroenterology and Hepatology, Cologne
,
J Kluwe
8   Hamburg University Medical Center, I. Department of Medicine, Hamburg
,
T Boettler
9   University of Freiburg, Department of Medicine II, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg
,
A Geier
4   University Hospital Würzburg, Division of Hepatology, Department of Medicine II, Würzburg
,
F Lammert
1   Department of Medicine II, Saarland University Medical Center, Homburg
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

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Background:

Although non-alcoholic fatty liver disease (NAFLD) is most common among obese individuals with metabolic syndrome, increasing evidence demonstrates that NAFLD might also develop in the absence of these characteristics. As shown by others and us, three critical gene variants, i.e. PNPLA3 p.I148 M, TM6SF2 p.E167K and MBOAT7 rs641738, are associated with higher liver fat contents. Here we aim to investigate to which extent these variants modulate NAFLD risk and disease progression in non-obese patients without diabetes.

Patients and methods:

Patients with biopsy-proven NAFLD were recruited at eight academic medical centers within the German NAFLD-CSG network. All patients fulfilled the following criteria: (i) BMI < 30 kg/m2, (ii) absence of type 2 diabetes, and (iii) hepatic steatosis grade ≥ S1 at liver biopsy. The prosteatotic PNPLA3, TM6SF2 and MBOAT7 polymorphisms were genotyped using TaqMan assays and compared with the NAFLD-CSG cohort (n = 515, Krawczyk et al. J Lipid Res 2017) as well as a control population (n = 174, Arslanow et al. Liver Int 2016). Serum CK18-M30 concentrations were measured by ELISA.

Results:

In total, 63 patients with NAFLD (39 men, age 20 – 72 years) fulfilled the inclusion criteria. In these patients the frequency of the PNPLA3 p.I148 M allele (74.6%), but not of the TM6SF2 or MBOAT7 polymorphisms, was significantly (P < 0.05) higher as compared to the other patients in the NAFLD CSG cohort (54.9%) or controls (40.2%). The presence of the minor PNPLA3 p.I148 M risk allele increased the odds of developing NAFLD (OR = 3.29, P < 0.001) and was associated with higher steatosis, more advanced fibrosis, and serum CK18-M30 levels (all P < 0.01). According to the population attributable fraction (PAF), 49.8% of NAFLD cases could be eliminated if the PNPLA3 mutation was absent. On the other hand we did not detect any association of TM6SF2 and MBOAT7 polymorphisms and NAFLD phenotypes.

Conclusions:

Variant PNPLA3 might be one of the major drivers of NAFLD risk in non-obese patients without diabetes, and it also substantially enhances chronic liver injury in this setting. Since non-obese patients lack most of the phenotypic characteristics commonly associated with NAFLD, we reckon that genetic analysis could help to identify patients requiring specific drug therapies.