当前位置： SCI文献检索 > JOURNAL OF HEPATOLOGY期刊下所有文献 > Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.

Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.

Abstract：

BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification. METHODS:We examined at-risk individuals (NAFLD cohort, n=2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n=364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5). RESULTS:In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p=0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p<10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p<0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p<10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ∼90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p<10-5) and without cirrhosis (p<0.05). CONCLUSIONS:Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy to detect HCC and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Bianco C,Jamialahmadi O,Pelusi S,Baselli G,Dongiovanni P,Zanoni I,Santoro L,Maier S,Liguori A,Meroni M,Borroni V,D'Ambrosio R,Spagnuolo R,Alisi A,Federico A,Bugianesi E,Petta S,Miele L,Vespasiani-Gentilucci U,Anstee

doi

10.1016/j.jhep.2020.11.024

subject

Has Abstract

pub_date

2020-11-25 00:00:00

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(20)33811-3

pub_type

杂志文章

在线工具

Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.