多囊性肝病(PLD)是在三种遗传疾病中观察到的罕见疾病,包括常染色体显性多囊性肝病(ADPLD),常染色体显性多囊肾病(ADPKD),常染色体隐性遗传性多囊肾病(ARPKD)。PLD通常不会损害肝功能,当增大的肝脏压迫邻近器官或增加腹内压力时,晚期PLD会出现症状。目前,PLD的诊断主要基于影像学,除了复杂的病例,基因检测是不需要的。此外,基因检测可能有助于预测患者的预后,对患者进行基因干预分类,并进行早期治疗。尽管潜在的遗传原因和机制尚未完全了解,以前的研究认为原发性纤毛病或纤毛发育受损是主要原因。首先,PLD的发生是由于纤毛发生缺陷和内质网质量控制无效。具体来说,与纤毛发生直接相关的基因的功能突变丧失,例如Pkd1、Pkd2、Pkhd1和Dzip1l,在ADPKD和ARPKD中可导致肝和肾的膀胱形成。此外,涉及内质网质量控制和蛋白质折叠的基因的功能缺失突变,贩运,和成熟,比如PRKCSH,Sec63,ALG8,ALG9,GANAB,SEC61B,可损害多囊毒素1(PC1)和多囊毒素2(PC2)的产生和功能,或促进其降解并间接促进孤立的肝囊形成或同时的肝和肾囊形成。最近,研究表明,LRP5的突变会损害经典的Wnt信号,会导致肝囊肿形成。PLD目前由生长抑素类似物治疗,经皮介入,手术开窗术,切除,和肝移植。此外,基于潜在的分子机制和信号通路,几种研究性治疗方法已用于临床前研究,其中一些已经显示出有希望的结果。本文就临床表现、并发症,患病率,遗传基础,和PLD的治疗,并解释了治疗的研究方法和未来的研究方向,这对对PLD感兴趣的研究人员和临床医生是有益的。
Polycystic liver disease (PLD) is a rare condition observed in three genetic diseases, including autosomal dominant polycystic liver disease (
ADPLD), autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). PLD usually does not impair liver function, and advanced PLD becomes symptomatic when the enlarged liver compresses adjacent organs or increases intra-abdominal pressure. Currently, the diagnosis of PLD is mainly based on imaging, and genetic testing is not required except for complex cases. Besides, genetic testing may help predict patients\' prognosis, classify patients for genetic intervention, and conduct early treatment. Although the underlying genetic causes and mechanisms are not fully understood, previous studies refer to primary ciliopathy or impaired ciliogenesis as the main culprit. Primarily, PLD occurs due to defective ciliogenesis and ineffective endoplasmic reticulum quality control. Specifically, loss of function mutations of genes that are directly involved in ciliogenesis, such as Pkd1, Pkd2, Pkhd1, and Dzip1l, can lead to both hepatic and renal cystogenesis in ADPKD and ARPKD. In addition, loss of function mutations of genes that are involved in endoplasmic reticulum quality control and protein folding, trafficking, and maturation, such as PRKCSH, Sec63, ALG8, ALG9, GANAB, and SEC61B, can impair the production and function of polycystin1 (PC1) and polycystin 2 (PC2) or facilitate their degradation and indirectly promote isolated hepatic cystogenesis or concurrent hepatic and renal cystogenesis. Recently, it was shown that mutations of LRP5, which impairs canonical Wnt signaling, can lead to hepatic cystogenesis. PLD is currently treated by somatostatin analogs, percutaneous intervention, surgical fenestration, resection, and liver transplantation. In addition, based on the underlying molecular mechanisms and signaling pathways, several investigational treatments have been used in preclinical studies, some of which have shown promising results. This review discusses the clinical manifestation, complications, prevalence, genetic basis, and treatment of PLD and explains the investigational methods of treatment and future research direction, which can be beneficial for researchers and clinicians interested in PLD.