Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
Hepatol Commun. 2024 May 22;8(6). doi: 10.1097/HC9.0000000000000441. eCollection 2024 Jun 1.
The PNPLA3-rs738409-G, TM6SF2-rs58542926-T, and HSD17B13-rs6834314-A polymorphisms have been associated with cirrhosis, hepatic decompensation, and HCC. However, whether they remain associated with HCC and decompensation in people who already have cirrhosis remains unclear, which limits the clinical utility of genetics in risk stratification as HCC is uncommon in the absence of cirrhosis. We aimed to characterize the effects of PNPLA3, TM6SF2, and HSD17B13 genotype on hepatic decompensation, HCC, and liver-related mortality or liver transplant in patients with baseline compensated cirrhosis.
We conducted a single-center retrospective study of patients in the Michigan Genomics Initiative who underwent genotyping. The primary predictors were PNPLA3, TM6SF2, and HSD17B13 genotypes. Primary outcomes were either hepatic decompensation, HCC, or liver-related mortality/transplant. We conducted competing risk Fine-Gray analyses on our cohort.
We identified 732 patients with baseline compensated cirrhosis. During follow-up, 50% of patients developed decompensation, 13% developed HCC, 24% underwent liver transplant, and 27% died. PNPLA3-rs738409-G genotype was associated with risk of incident HCC: adjusted subhazard hazard ratio 2.42 (1.40-4.17), p=0.0015 for PNPLA3-rs738409-GG vs. PNPLA3-rs738409-CC genotype. The 5-year cumulative incidence of HCC was higher in PNPLA3-rs738409-GG carriers than PNPLA3-rs738409-CC/-CG carriers: 15.6% (9.0%-24.0%) vs. 7.4% (5.2%-10.0%), p<0.001. PNPLA3 genotype was not associated with decompensation or the combined outcome of liver-related mortality or liver transplant. TM6SF2 and HSD17B13 genotypes were not associated with decompensation or HCC.
The PNPLA3-rs738409-G allele is associated with an increased risk of HCC among patients with baseline compensated cirrhosis. People with cirrhosis and PNPLA3-rs738409-GG genotype may warrant more intensive HCC surveillance.
PNPLA3-rs738409-G、TM6SF2-rs58542926-T 和 HSD17B13-rs6834314-A 多态性与肝硬化、肝失代偿和 HCC 相关。然而，在已经患有肝硬化的人群中，这些多态性是否仍然与 HCC 和失代偿相关尚不清楚，这限制了遗传学在风险分层中的临床应用，因为在没有肝硬化的情况下 HCC 并不常见。我们旨在描述 PNPLA3、TM6SF2 和 HSD17B13 基因型对基线代偿性肝硬化患者肝失代偿、HCC 和与肝脏相关的死亡或肝移植的影响。
我们对密歇根基因组倡议中接受基因分型的患者进行了单中心回顾性研究。主要预测因素是 PNPLA3、TM6SF2 和 HSD17B13 基因型。主要结局是肝失代偿、HCC 或与肝脏相关的死亡/移植。我们对我们的队列进行了竞争风险 Fine-Gray 分析。
我们确定了 732 例基线代偿性肝硬化患者。在随访期间，50%的患者发生失代偿，13%的患者发生 HCC，24%的患者进行了肝移植，27%的患者死亡。PNPLA3-rs738409-G 基因型与 HCC 发病风险相关：调整后的亚危险比 2.42（1.40-4.17），p=0.0015，与 PNPLA3-rs738409-GG 相比，PNPLA3-rs738409-CC 基因型。PNPLA3-rs738409-GG 携带者的 5 年 HCC 累积发生率高于 PNPLA3-rs738409-CC/-CG 携带者：15.6%（9.0%-24.0%）vs. 7.4%（5.2%-10.0%），p<0.001。PNPLA3 基因型与失代偿或与肝脏相关的死亡或肝移植的复合结局无关。TM6SF2 和 HSD17B13 基因型与失代偿或 HCC 无关。
在基线代偿性肝硬化患者中，PNPLA3-rs738409-G 等位基因与 HCC 风险增加相关。患有肝硬化和 PNPLA3-rs738409-GG 基因型的患者可能需要更密切的 HCC 监测。
