PDF(Pubmed)
Abstract：
UNASSIGNED: Autoimmune hepatitis (AIH) is a relatively rare autoimmune disease with a strong genetic background. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148 M (rs738409 C/G) variant has been associated with hepatic inflammation and fibrosis in chronic hepatic diseases beyond metabolic dysfunction-associated steatotic liver disease (MASLD).
UNASSIGNED: Our aim was to investigate the significance of PNPLA3 I148 M variant in AIH.
UNASSIGNED: Two hundred AIH patients, followed in our centre, were evaluated while 100 healthy subjects served as controls. Genotyping was performed with allelic discrimination end-point polymerase chain reaction (PCR).
UNASSIGNED: The I148 M variant was present in 95/200 (47.5 %) AIH patients compared to 47/100 (47 %) healthy controls (p = 1.000). Patients with GG/CG genotypes were more likely to present with decompensated cirrhosis at diagnosis (GG/CG 6.3 % vs. CC 1 %, p = 0.039). Comorbidity with cardiometabolic risk factors and concurrence of MASLD was similar across genotypes. Simple steatosis was present in 37/186 (19.9 %) and steatohepatitis in 14/186 (7.5 %) patients with available liver biopsy without correlation with PNPLA3 genotype. Fibrosis stage and grade of inflammation were not correlated with any genotype. Response to treatment was also independent of the presence of the I148 M variant, even though a longer time was needed to achieve complete biochemical response in those carrying the GG/CG genotypes (p = 0.07). On Kaplan Meier analysis homozygosity for the G allele corelated with reduced survival free of decompensation (p = 0.006), cirrhotic events (decompensation, liver transplantation, hepatocellular carcinoma; p = 0.001) and liver-related death or liver transplantation (p = 0.011) in treated patients.
UNASSIGNED: The PNPLA3 I148 M variant in AIH patients is associated with increased risk of advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related death or liver transplantation, regardless of the presence of MASLD. This signifies a potential role for the PNPLA3 I148 M variant as a new AIH biomarker allowing to identify patients at increased risk of disease progression.
UNASSIGNED: Our aim was to investigate the significance of PNPLA3 I148 M variant in AIH.
UNASSIGNED: Two hundred AIH patients, followed in our centre, were evaluated while 100 healthy subjects served as controls. Genotyping was performed with allelic discrimination end-point polymerase chain reaction (PCR).
UNASSIGNED: The I148 M variant was present in 95/200 (47.5 %) AIH patients compared to 47/100 (47 %) healthy controls (p = 1.000). Patients with GG/CG genotypes were more likely to present with decompensated cirrhosis at diagnosis (GG/CG 6.3 % vs. CC 1 %, p = 0.039). Comorbidity with cardiometabolic risk factors and concurrence of MASLD was similar across genotypes. Simple steatosis was present in 37/186 (19.9 %) and steatohepatitis in 14/186 (7.5 %) patients with available liver biopsy without correlation with PNPLA3 genotype. Fibrosis stage and grade of inflammation were not correlated with any genotype. Response to treatment was also independent of the presence of the I148 M variant, even though a longer time was needed to achieve complete biochemical response in those carrying the GG/CG genotypes (p = 0.07). On Kaplan Meier analysis homozygosity for the G allele corelated with reduced survival free of decompensation (p = 0.006), cirrhotic events (decompensation, liver transplantation, hepatocellular carcinoma; p = 0.001) and liver-related death or liver transplantation (p = 0.011) in treated patients.
UNASSIGNED: The PNPLA3 I148 M variant in AIH patients is associated with increased risk of advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related death or liver transplantation, regardless of the presence of MASLD. This signifies a potential role for the PNPLA3 I148 M variant as a new AIH biomarker allowing to identify patients at increased risk of disease progression.
摘要：
■自身免疫性肝炎（AIH）是一种相对罕见的自身免疫性疾病，具有很强的遗传背景。含patatatin样磷脂酶结构域的蛋白3（PNPLA3）I148M（rs738409C/G）变体与代谢功能障碍相关的脂肪变性肝病（MASLD）以外的慢性肝病中的肝脏炎症和纤维化有关。
■我们的目的是研究PNPLA3I148M变体在AIH中的意义。
■两百名AIH患者，在我们的中心，进行评估，同时100名健康受试者作为对照。用等位基因区分终点聚合酶链反应(PCR)进行基因分型。
■与47/100（47％）健康对照相比，I148M变体存在于95/200（47.5％）AIH患者中（p=1.000）。GG/CG基因型患者在诊断时更有可能出现失代偿性肝硬化（GG/CG6.3％vs.CC1%,p=0.039)。与心脏代谢危险因素的合并症和MASLD的合并症在基因型之间相似。单纯性脂肪变性存在于37/186（19.9％）和14/186（7.5％）的脂肪性肝炎患者，可进行肝活检，与PNPLA3基因型无关。纤维化阶段和炎症等级与任何基因型无关。对治疗的反应也独立于I148M变体的存在，即使携带GG/CG基因型的患者需要更长的时间才能达到完全的生化反应（p=0.07）。在KaplanMeier分析中，G等位基因的纯合性与无失代偿的存活率降低相关（p=0.006），肝硬化事件(代偿失调，肝移植,肝细胞癌；p=0.001）和治疗患者的肝脏相关死亡或肝移植（p=0.011）。
■AIH患者的PNPLA3I148M变异与诊断时晚期疾病的风险增加以及无肝硬化事件和肝脏相关死亡或肝移植的生存率降低相关。不管MASLD的存在。这表明PNPLA3I148M变体作为一种新的AIH生物标志物具有潜在的作用，可以识别疾病进展风险增加的患者。
■我们的目的是研究PNPLA3I148M变体在AIH中的意义。
■两百名AIH患者，在我们的中心，进行评估，同时100名健康受试者作为对照。用等位基因区分终点聚合酶链反应(PCR)进行基因分型。
■与47/100（47％）健康对照相比，I148M变体存在于95/200（47.5％）AIH患者中（p=1.000）。GG/CG基因型患者在诊断时更有可能出现失代偿性肝硬化（GG/CG6.3％vs.CC1%,p=0.039)。与心脏代谢危险因素的合并症和MASLD的合并症在基因型之间相似。单纯性脂肪变性存在于37/186（19.9％）和14/186（7.5％）的脂肪性肝炎患者，可进行肝活检，与PNPLA3基因型无关。纤维化阶段和炎症等级与任何基因型无关。对治疗的反应也独立于I148M变体的存在，即使携带GG/CG基因型的患者需要更长的时间才能达到完全的生化反应（p=0.07）。在KaplanMeier分析中，G等位基因的纯合性与无失代偿的存活率降低相关（p=0.006），肝硬化事件(代偿失调，肝移植,肝细胞癌；p=0.001）和治疗患者的肝脏相关死亡或肝移植（p=0.011）。
■AIH患者的PNPLA3I148M变异与诊断时晚期疾病的风险增加以及无肝硬化事件和肝脏相关死亡或肝移植的生存率降低相关。不管MASLD的存在。这表明PNPLA3I148M变体作为一种新的AIH生物标志物具有潜在的作用，可以识别疾病进展风险增加的患者。
