Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Ann Hepatol. 2021 Mar-Apr;21:100260. doi: 10.1016/j.aohep.2020.09.004. Epub 2020 Sep 25.
Genetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear.
We enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.3%]; median age, 53 [14-84] years; 114 with advanced fibrosis [37.5%]) in the patients without hepatocellular carcinoma at diagnosis. Genomic DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) were analyzed. Associations of mortality with patatin-like phospholipase 3 (PNPLA3) and aldehyde dehydrogenase 2 (ALDH2) were analyzed. Finally, a subgroup analysis according to lifestyle-related disease was performed.
During the median 7 years of follow-up, 20 patients (6.4%) died (13 liver-related [4.1%] and 7 non-liver-related deaths [2.2%]). Patients with ALDH2 (non-GG genotype) who had reduced alcohol metabolism tended to have a poor prognosis (p = 0.06). Patients carrying both risk SNPs of PNPLA3 (GG) and ALDH2 (non-GG) had a significantly poor prognosis (p = 0.01). In the subgroup analysis, patients with PNPLA3 (GG) who were non-diabetics (p = 0.06) or non-dyslipidemic (p = 0.03), with ALDH2 (non-GG) who were non-dyslipidemic (p = 0.01) or hypertensive (p = 0.03), also had a poor prognosis. The Cox analysis revealed that ALDH2 (non-GG) was associated with a poor prognosis (Hazard ratio: 4.568, 95% Confidence Interval: 1.294-16.131, p = 0.02) similar to the liver function tests.
Genetic background may affect NAFLD prognosis and ALDH2 SNP could predict the outcome.
遗传背景可能与肝损伤和非酒精性脂肪性肝病（NAFLD）的发生机制有关。然而，其对 NAFLD 长期预后的影响尚不清楚。
我们纳入了 2000 年至 2018 年期间经活检证实的 314 例日本 NAFLD 患者（男性 161 例[51.3%]；中位年龄 53 [14-84]岁；114 例存在晚期纤维化[37.5%]），这些患者在诊断时均无肝细胞癌。从外周血中提取基因组 DNA，并对单核苷酸多态性（SNP）进行分析。分析与死亡率相关的 patatin-like phospholipase 3（PNPLA3）和 aldehyde dehydrogenase 2（ALDH2）的关联。最后，根据生活方式相关疾病进行了亚组分析。
在中位 7 年的随访期间，有 20 例患者（6.4%）死亡（13 例与肝脏相关[4.1%]，7 例与肝脏无关[2.2%]）。ALDH2（非 GG 基因型）患者酒精代谢减少，预后较差（p=0.06）。同时携带 PNPLA3（GG）和 ALDH2（非 GG）风险 SNP 的患者预后显著较差（p=0.01）。在亚组分析中，非糖尿病（p=0.06）或非血脂异常（p=0.03）的 PNPLA3（GG）患者，非血脂异常（p=0.01）或高血压（p=0.03）的 ALDH2（非 GG）患者，预后也较差。Cox 分析显示，ALDH2（非 GG）与不良预后相关（风险比：4.568，95%置信区间：1.294-16.131，p=0.02），与肝功能检查结果相似。
遗传背景可能影响 NAFLD 的预后，ALDH2 SNP 可预测结局。
