Are transmembrane 6 superfamily member 2 gene polymorphisms associated with steatohepatitis after pancreaticoduodenectomy?

Author:

Mori Tomotaka12ORCID,Ozawa Eisuke1,Sasaki Ryu1ORCID,Shimakura Akane1,Takahashi Kosuke1,Kido Yoko1,Kanda Yasuko1,Matsuo Satoshi1,Tajima Kazuaki1,Beppu Asami1,Nakao Yasuhiko1,Fukushima Masanori1,Haraguchi Masafumi1,Miuma Satoshi1,Miyaaki Hisamitsu1ORCID,Adachi Tomohiko3,Eguchi Susumu3ORCID,Okano Shinji4,Nakao Kazuhiko1

Affiliation:

1. Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan

2. Department of Gastroenterology and Hepatology Japanese Red Cross Nagasaki Genbaku Hospital Nagasaki Japan

3. Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan

4. Department of Pathology Nagasaki University Hospital Nagasaki Japan

Abstract

AbstractAimAfter pancreaticoduodenectomy, 20–40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin‐like phospholipase domain‐containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear.Methods and ResultsForty‐three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real‐time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver‐to‐spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis‐4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046).ConclusionThe TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.

Publisher

Wiley

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