Z Gastroenterol 2019; 57(01): e25
DOI: 10.1055/s-0038-1677104
1. Basic Hepatology (Fibrogenesis, NPC, Transport)
Georg Thieme Verlag KG Stuttgart · New York

Carriage of HSD17B13 rs72613567TA is associated with a reduced risk for developing hepatocellular carcinoma in patients with alcohol-related cirrhosis

F Stickel
1   Department of Gastroenterology and Hepatology, University Hospital of Zürich, Switzerland
,
P Lutz
2   Department of Internal Medicine I, University of Bonn, Germany
,
S Buch
3   Medical Department 1, University Hospital Dresden, TU Dresden, Germany
,
V Rausch
4   Department of Medicine, Salem Medical Centre, Alcohol Research Laboratory, University of Heidelberg, Germany
,
I Silva
4   Department of Medicine, Salem Medical Centre, Alcohol Research Laboratory, University of Heidelberg, Germany
,
J Fischer
9   Department of Hepatology, University Hospital Leipzig, Germany
,
HD Nischalke
2   Department of Internal Medicine I, University of Bonn, Germany
,
J Rosendahl
10   Department of Gastroenterology, University of Halle-Wittenberg, Halle, Germany
,
M Krawczyk
8   Department of Medicine II, Saarland University Medical Center, Homburg, Germany
,
M Casper
8   Department of Medicine II, Saarland University Medical Center, Homburg, Germany
,
S Zopf
12   Medical Department 1, University of Erlangen-Nuremberg, Erlangen, Germany
,
S Marhenke
13   Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
,
F Lammert
8   Department of Medicine II, Saarland University Medical Center, Homburg, Germany
,
A Vogel
11   Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
,
C Datz
20   Department of Internal Medicine, Hospital Oberndorf, Salzburg, Austria.
,
R Sharma
21   Imperial College London, Hammersmith Hospital Campus, London, UK
,
F Eyer
14   Department of Clinical Toxicology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
,
U Spengler
7   Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK
,
J von Felden
15   First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
S Zeissig
3   Medical Department 1, University Hospital Dresden, TU Dresden, Germany
,
A Canbay
16   Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany.
,
J Grove
6   Nottingham Digestive Diseases Centre, Nottingham, UK
,
G Aithal
6   Nottingham Digestive Diseases Centre, Nottingham, UK
,
A McQuillin
7   Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK
,
L Valenti
5   Metabolic Liver Diseases, Università degli Studi Milano Fondazione, Milano, Italy
,
KH Weiss
18   Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
,
S Mueller
19   Department of Medicine, Salem Medical Centre, Alcohol Research Laboratory, University of Heidelberg, Germany
,
MY Morgan
17   UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, UK
,
D Gotthardt
19   Department of Medicine, Salem Medical Centre, Alcohol Research Laboratory, University of Heidelberg, Germany
,
T Berg
9   Department of Hepatology, University Hospital Leipzig, Germany
,
J Hampe
3   Medical Department 1, University Hospital Dresden, TU Dresden, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

Also available at
 

Background and Aims:

Host genetic factors play an important role in the development of alcohol-related cirrhosis. Hepatocellular carcinoma (HCC) complicates the course of this disorder in approximately 20% of affected individuals. The variant rs738409 in the patatin-like phospholipase domain containing-3 (PNPLA3) is an established risk factors for the development of alcohol-related cirrhosis and HCC. Recently, a loss-of-function splice variant rs72613567:TA in the gene coding for hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was reported not only to be associated with a reduced risk for developing alcohol-related cirrhosis but also to attenuate the risk associated with carriage of PNPLA3 rs738409. The aim of this study was to undertake a case control study to determine if carriage of HSD17B13 rs72613567:TA is associated with a lower risk for developing HCC in patients with alcohol-related cirrhosis and whether this variant modulates the risk conferred by PNPLA3 rs738409.

Methods:

The total study population comprised of 2,202 individuals with alcohol-related cirrhosis recruited from Germany, Switzerland, Italy and United Kingdom. Of these 840 had HCC and were designated as cases whilst the remaining 1362 had no evidence of HCC and were designated as controls. Genomic DNA was extracted from whole blood and genotyped for risk variants in PNPLA3 and HSD17B13. The associations between genotypes and the risk of developing HCC were analysed using multivariate logistic regressions. Adjusted allelic and genotypic odds ratios were calculated. Gene-gene interaction was evaluated by inclusion of interaction terms to the regression model.

Results:

The presence of HCC was independently associated with rs72613567 in HSD17B13 (OR 0.72 [CI 0.61 – 0.85], p = 1.00 × 10 – 4) and rs738409 in PNPLA3 (OR 1.83 [CI 1.60 – 2.09], p = 1.62 × 10 – 18) in the additive model controlled for sex, age and country. The reduced risk of developing HCC was evident in both heterozygous (OR 0.75; 95% [CI 0.61 – 0.93], P = 0.008) and homozygous carriers of rs72613567:TA (OR 0.47; 95% [CI 0.30 – 0.74], P = 0.001). The rs72613567-rs738409 SNP-SNP interaction term was not significant P = 0.12.

Conclusion:

In patients with alcohol-related cirrhosis, carriage of the HSD17B13 rs72613567:TA variant is associated with a lower risk for developing HCC, independently of the increased risk conferred by carriage of PNPLA3 rs738409. The HCC risk conferred by the PNPLA3 rs738409was not attenuated by the presence HSD17B13 rs72613567:TA in our cohort.