The greater impact of PNPLA3 polymorphism on liver-related events in Japanese non-alcoholic fatty liver disease patients: A multicentre cohort study

被引：26

作者：

Seko, Yuya ^{[1
]}

Yamaguchi, Kanji ^{[1
]}

Shima, Toshihide ^{[2
]}

Iwaki, Michihiro ^{[3
]}

Takahashi, Hirokazu ^{[4
]}

Kawanaka, Miwa ^{[5
]}

Tanaka, Saiyu ^{[6
]}

Mitsumoto, Yasuhide ^{[2
]}

Yoneda, Masato ^{[3
]}

Nakajima, Atsushi ^{[3
]}

Fjellstrom, Ola ^{[7
]}

Blau, Jenny E. E. ^{[8
]}

Carlsson, Bjorn ^{[7
]}

Okanoue, Takeshi ^{[2
,9
]}

Itoh, Yoshito ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Mol Gastroenterol & Hepatol, Kyoto, Japan

[2] Saiseikai Suita Hosp, Dept Gastroenterol & Hepatol, Suita, Japan

[3] Yokohama City Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Yokohama, Japan

[4] Saga Univ Hosp, Liver Ctr, Saga, Japan

[5] Kawasaki Med Sch, Gen Med Ctr, Gen Internal Med 2, Okayama, Japan

[6] Nara City Hosp, Ctr Digest & Liver Dis, Nara, Japan

[7] AstraZeneca, Res & Early Dev Cardiovasc Renal & Metab, BioPharmaceut R&D, Gothenburg, Sweden

[8] AstraZeneca, Res & Early Dev Cardiovasc Renal & Metab, BioPharmaceut R&D, Gaithersburg, MD USA

[9] Saiseikai Suita Hosp, Dept Gastroenterol, 1-2 Kawazonocho, Suita 5640013, Japan

来源：

LIVER INTERNATIONAL | 2023年 / 43卷 / 10期

关键词：

CVD; HCC; mortality; NAFLD; PNPLA3; GENOME-WIDE ASSOCIATION; AMERICAN ASSOCIATION; HISTOLOGIC FEATURES; DIAGNOSIS; RISK; STEATOHEPATITIS; MANAGEMENT; GUIDELINE; FIBROSIS;

D O I：

10.1111/liv.15678

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & AimsPNPLA3 rs738409 has been associated with an increased risk of liver-related events in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the epidemiology of NAFLD and the impact of PNPLA3 on prognosis in Japan. MethodsA longitudinal multicentre cohort study, the JAGUAR study, includes 1550 patients with biopsy-proven NAFLD in Japan. We performed genetic testing and evaluated outcomes from this cohort. Liver-related events were defined as hepatocellular carcinoma (HCC) and decompensated liver cirrhosis events. ResultsDuring follow-up (median [range], 7.1 [1.0-24.0] years), 80 patients developed HCC, 104 developed liver-related events, and 59 died of any cause. The 5-year rate of liver-related events for each single-nucleotide polymorphism was 0.5% for CC, 3.8% for CG, and 5.8% for GG. Liver-related deaths were the most common (n = 28); only three deaths were due to cardiovascular disease. Multivariate analysis identified carriage of PNPLA3 CG/GG (hazard ratio [HR] 16.04, p = .006) and FIB-4 index >2.67 (HR 10.70, p < .01) as predictors of liver-related event development. No HCC or liver-related death was found among patients with PNPLA3 CC. There was a significantly increased risk of HCC, liver-related events, and mortality for CG/GG versus CC, but no difference between the CG and GG genotypes. ConclusionsIn Japanese individuals, the main cause of death from NAFLD is liver-related death. The greater risk of liver-related events incurred by PNPLA3 G allele was shown in Japan. Risk stratification for NAFLD in Japan is best accomplished by integrating PNPLA3 with the FIB-4 index.

引用

页码：2210 / 2219

页数：10

共 39 条

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