Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B” Shang-Chin Huang, Jia-Horng Kao Clinical and Molecular Hepatology.2026; 32(1): e117. CrossRef
Correspondence to editorial 1 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues” Rui Huang, Mindie H. Nguyen Clinical and Molecular Hepatology.2026; 32(1): e83. CrossRef
Backgrounds/Aims Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
Methods The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC).
Result s: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice.
Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.
Citations
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Hepatic fat, not visceral fat, is associated with gallbladder polyps: A study of 2643 healthy subjects Seon Hee Lim, Donghee Kim, Jin Hwa Kang, Ji Hyun Song, Sun Young Yang, Jeong Yun Yim, Su Jin Chung, Joo Sung Kim, Sang‐Heon Cho Journal of Gastroenterology and Hepatology.2015; 30(4): 767. CrossRef
Visceral Adipose Tissue Area as an Independent Risk Factor for Elevated Liver Enzyme in Nonalcoholic Fatty Liver Disease Goh Eun Chung, Donghee Kim, Min Sun Kwark, Won Kim, Jeong Yoon Yim, Yoon Jun Kim, Jung-Hwan Yoon Medicine.2015; 94(9): e573. CrossRef
Nonalcoholic Fatty Liver Disease as a Risk Factor of Arterial Stiffness Measured by the Cardioankle Vascular Index Goh Eun Chung, Su-Yeon Choi, Donghee Kim, Min-Sun Kwak, Hyo Eun Park, Min-Kyung Kim, Jeong Yoon Yim Medicine.2015; 94(12): e654. CrossRef
Visceral Obesity Predicts Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Su Jong Yu, Won Kim, Donghee Kim, Jung-Hwan Yoon, Kyoungbun Lee, Jung Ho Kim, Eun Ju Cho, Jeong-Hoon Lee, Hwi Young Kim, Yoon Jun Kim, Chung Yong Kim Medicine.2015; 94(48): e2159. CrossRef
Role of physical activity in nonalcoholic fatty liver disease in terms of visceral obesity and insulin resistance Min‐Sun Kwak, Donghee Kim, Goh Eun Chung, Won Kim, Yoon Jun Kim, Jung‐Hwan Yoon Liver International.2015; 35(3): 944. CrossRef
Cholecystectomy is independently associated with nonalcoholic fatty liver disease in an Asian population Min-Sun Kwak World Journal of Gastroenterology.2015; 21(20): 6287. CrossRef
Management of Non-alcoholic Fatty Liver Disease Jaechan Leem, Eun Hee Koh The Journal of Korean Diabetes.2014; 15(2): 93. CrossRef
Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition Joo Lee, Simonetta Friso, Sang-Woon Choi Nutrients.2014; 6(8): 3303. CrossRef
The Diagnosis of Nonalcoholic Fatty Liver Disease Moon Young Kim Korean Journal of Medicine.2014; 86(4): 405. CrossRef
Clinical Correlation between Serum Cytokeratin-18 and Metabolic Parameters in Patients with Sonographic Non-alcoholic Fatty Liver Disease Dong Shin Kwak, Dae Won Jun, Yong Kyun Cho, Seung Min Lee, Se Hwan Lee, In Sub Jung, Sung Won Lee, Jae Keun Park, JungHoon Lee, Eun Young Lee, Min Rho, Kang Lok Lee, Jun Kwon Ko, Soon-Eung Park The Korean Journal of Gastroenterology.2014; 64(4): 206. CrossRef
Pharmacologic Therapy for Nonalcoholic Fatty Liver Disease Sang Hoon Park Korean Journal of Medicine.2014; 86(4): 425. CrossRef
Association of nonalcoholic fatty liver disease with cardiovascular risk factors in obese adolescents: The role of interdisciplinary therapy Priscila L. Sanches, Aline de Piano, Raquel M.S. Campos, June Carnier, Marco T. de Mello, Natália Elias, Francisco A.H. Fonseca, Deborah C.L. Masquio, Patrícia L. da Silva, Flavia C. Corgosinho, Lian Tock, Lila M. Oyama, Sergio Tufik, Ana R. Dâmaso Journal of Clinical Lipidology.2014; 8(3): 265. CrossRef
Comparison on the Efficacy and Safety of Biphenyl Dimethyl Dicarboxylate and Ursodeoxycholic Acid in Patients with Abnormal Alanine Aminotransferase: Multicenter, Double-blinded, Randomized, Active-controlled Clinical Trial Sae Hwan Lee, Gab Jin Cheon, Hong Soo Kim, Young Don Kim, Sang Gyune Kim, Young Seok Kim, Soung Won Jeong, Jae Young Jang, Boo Sung Kim The Korean Journal of Gastroenterology.2014; 64(1): 31. CrossRef
Nonalcoholic Fatty Liver Disease: Lifestyle Modification Ki Deok Yoo, Dae Won Jun Korean Journal of Medicine.2014; 86(4): 416. CrossRef
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