Almasio Piero Luigi, Licata Anna, Maida Marcello, Macaluso Fabio Salvatore, Costantino Andrea, Alessi Nicola, Grimaudo Stefania, Accardi Giulia, Caruso Calogero, Craxi Antonio
Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo, Italy.
Hepat Mon. 2016 Oct 16;16(11):e31681. doi: 10.5812/hepatmon.31681. eCollection 2016 Nov.
Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans.
We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy.
Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was performed in a sub-group of patients.
HLA-DRB107 (RR 5.3, P = 0.0008) and HLA-DRB108 (RR n.c. P = 0.0005) were significantly associated with the risk of PBC development. Patients younger than 45 years had significantly higher alanine aminotransferase (P = 0.038) and alkaline phosphatase levels (P = 0.047) than older cases. In comparison to non-CC rs12979860, patients with CC rs12979860 genotype showed an early histological stage at onset (93.8% vs. 62.5%, P = 0.03). After a mean follow-up of 61 months, three patients died, one underwent liver transplantation and sixteen (21.9%) had progression of the disease. At multivariate analysis, extrahepatic autoimmune disease (P = 0.04), pruritus (P = 0.008) and advanced histological stage (P < 0.0001) were independent risk factors for disease progression.
HLA-DRB107 and HLA-DRB108 alleles increase susceptibility to disease development. At onset, higher biochemical activity was observed in younger patients, whereas rs12979860 CC genotype was associated with milder histological stage. Pruritus and coexistence of extrahepatic autoimmune diseases were significantly associated with poorer prognosis.
原发性胆汁性肝硬化（PBC）的自然病史在来自地中海地区的患者中部分得到了描述，这些患者的遗传背景与北欧人不同。
我们旨在描述意大利南部患者中PBC的遗传易感性和临床病程。
收集了81例连续性PBC患者诊断时的社会人口统计学、临床、生化和组织学数据以及疾病进展情况。所有受试者均接受剂量为15mg/kg的熊去氧胆酸治疗。将HLA II类DRB1等位基因与237名健康对照受试者的等位基因进行比较。在一组患者中对IL28B的rs12979860 C/T和rs80899917 G/T进行IL28B基因分型。
HLA-DRB107（相对风险5.3，P = 0.0008）和HLA-DRB108（相对风险无显著性差异，P = 0.0005）与PBC发生风险显著相关。年龄小于45岁的患者丙氨酸转氨酶（P = 0.038）和碱性磷酸酶水平（P = 0.047）显著高于年龄较大的患者。与非CC型rs12979860相比，rs12979860基因型为CC的患者发病时组织学分期较早（93.8%对62.5%，P = 0.03）。平均随访61个月后，3例患者死亡，1例接受肝移植，16例（21.9%）疾病进展。多因素分析显示，肝外自身免疫性疾病（P = 0.04）、瘙痒（P = 0.008）和晚期组织学分期（P < 0.0001）是疾病进展的独立危险因素。
HLA-DRB107和HLA-DRB108等位基因增加了疾病发生的易感性。发病时，年轻患者的生化活性较高，而rs12979860 CC基因型与较轻的组织学分期相关。瘙痒和肝外自身免疫性疾病的共存与较差的预后显著相关。
