Choi Shinjie, Kim Yeji, Park Sunwoo, Ahn Jeong Eun, Kim Lia, Shin Minsoo, Lee Kyung Jae, Moon Jin Soo, Ko Jae Sung
Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Pediatrics, Korea University Ansan Hospital, Ansan, Korea.
Pediatr Gastroenterol Hepatol Nutr. 2025 Jul;28(4):245-255. doi: 10.5223/pghn.2025.28.4.245. Epub 2025 Jul 7.
The aim of this study was to elucidate the genetic variants associated with progressive familial intrahepatic cholestasis (PFIC), a rare class of disorders driven by pathogenic monogenic variants in bile acid transporters. Furthermore, the long-term clinical outcomes of PFIC patients were evaluated.
A retrospective cohort study was conducted at Seoul National University Hospital and included pediatric patients diagnosed with PFIC and confirmed by genetic testing between January 2000 and October 2024. Genetic testing, encompassing either single-gene testing or a neonatal cholestasis 34-gene panel, was performed for all patients.
Six patients were identified, including five with PFIC2, classified as bile salt export pump deficiency, and one with PFIC3, classified as multidrug resistance protein 3 deficiency. The median age of symptom onset was 3 months. The genetic analyses revealed no widely known variants associated with PFIC. However, a novel frameshift variant (c.589dup, p.(Glu197GlyfsTer8)) was detected in the gene. Additionally, a missense variant (c.3812T>A, p.(Ile1271Asn)) was commonly identified in the same gene. All patients ultimately underwent liver transplantation; two patients who developed hepatocellular carcinoma (HCC) were diagnosed at a median age of 1.6 years. Notably, all patients survived without recurrence after transplantation, with a median follow-up duration of 12.0 years.
This study is the first documented case of PFIC3 in a Korean child. Genotype is not associated with the risk of developing HCC. Given the early diagnosis of HCC observed in some patients, routine surveillance for HCC is strongly recommended in all patients with PFIC2.
本研究旨在阐明与进行性家族性肝内胆汁淤积症（PFIC）相关的基因变异，PFIC是一类由胆汁酸转运蛋白中的致病性单基因变异驱动的罕见疾病。此外，还评估了PFIC患者的长期临床结局。
在首尔国立大学医院进行了一项回顾性队列研究，纳入了2000年1月至2024年10月期间诊断为PFIC并经基因检测确诊的儿科患者。对所有患者进行了基因检测，包括单基因检测或新生儿胆汁淤积症34基因检测板。
共鉴定出6例患者，其中5例为PFIC2型，归类为胆盐输出泵缺乏症，1例为PFIC3型，归类为多药耐药蛋白3缺乏症。症状出现的中位年龄为3个月。基因分析未发现与PFIC相关的广为人知的变异。然而，在该基因中检测到一个新的移码变异（c.589dup，p.(Glu197GlyfsTer8)）。此外，在同一基因中还常见一个错义变异（c.3812T>A，p.(Ile1271Asn)）。所有患者最终均接受了肝移植；2例发生肝细胞癌（HCC）的患者诊断时的中位年龄为1.6岁。值得注意的是，所有患者移植后均存活且无复发，中位随访时间为12.0年。
本研究是韩国儿童中首例记录的PFIC3病例。基因型与发生HCC的风险无关。鉴于在一些患者中观察到HCC的早期诊断，强烈建议对所有PFIC2患者进行HCC的常规监测。
