Liver Transplantation in Short Telomere-Mediated Hepatopulmonary Syndrome Following Bone Marrow Transplantation Using HCV Positive Allografts: A Case Series.
Liver Transplantation in Short Telomere-Mediated Hepatopulmonary Syndrome Following Bone Marrow Transplantation Using HCV Positive Allografts: A Case Series.
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DOI：
10.1002/lt.26109
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发表时间：
2021-12
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影响因子：
--
通讯作者：
Gurakar A
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文献类型：
--
作者：
Oseini AM;Hamilton JP;Hammami MB;Kim A;Oshima K;Woreta T;Rizkalla N;Pustavoitau A;Merlo C;Nguyen MC;King EA;Wesson RN;Garonzik-Wang J;Ottmann S;Philosophe B;Cameron AM;Armanios M;Gurakar A
短端粒综合征（STSs）是最常见的早衰疾病；端粒酶和其他端粒维持基因的突变是其病因的基础。(1)它们的生物学特征是端粒较短，导致衰老和细胞凋亡，导致器官衰竭。大多数STSs为常染色体显性，但也存在x连锁、新生和隐性形式。在70%-80%的STSs中可识别出14个基因的突变，其中端粒酶逆转录酶基因TERT突变占近一半。(1)终末期肝病是继特发性肺纤维化（IPF）和再生障碍性贫血之后第三常见的退行性并发症。(2)再生障碍性贫血多见于儿童和青壮年，IPF多见于成人，肝脏疾病多见于中等年龄人群。另一方面，肺纤维化（PF）在40岁以后的绝大多数病例中表现出来。(1)肝脏病变有2种主要表现。第一种，非肝硬化门脉高压伴肝肺综合征（NCPH-HPS），通常在儿童/年轻成人中诊断，通常与结节性再生增生（NRH）相关。(2) HPS是这类患者的主要表现，门静脉高压的其他并发症很少见。(2)第二种是隐源性肝硬化（伴或不伴HPS），出现在IPF之前或与IPF同时发生的老年人中。(3)肝脏疾病的最佳管理，特别是在存在这些综合征合并症的情况下，仍不清楚。最近，低强度造血干细胞移植（HSCT）治疗再生障碍性贫血方案的成功揭示了STS的自然历史，几乎所有HSCT幸存者都发展为HPS。然而，肝移植（LT）在这些患者中的作用仍然未知，特别是考虑到肺易损和实质性PF加剧的可能性，以及鳞状癌和骨髓增生异常综合征的相对风险增加。(4)考虑到终末期肝病模型（MELD）评分较低，对于需要肝移植的患者来说，寻找合适的供体仍然是一个挑战。HPS患者有资格获得MELD例外点，以改善移植的可及性；然而，这通常是在疾病的后期阶段，有长期低氧血症的后遗症的风险。为确保这些患者及时接受肝移植，公共卫生服务（PHS）指定缩写：AML，急性髓性白血病；AVN，无血管坏死；巨细胞病毒、巨细胞病毒;DAA，直接作用抗病毒；DDLT，病变供肝移植；DKC1，先天性角化不良1基因（x连锁）；DLCO：一氧化碳扩散能力；FISH，荧光原位杂交；丙型肝炎病毒；HPS，肝肺综合征；造血干细胞移植；IPF，特发性肺纤维化；IST，免疫抑制疗法；终末期肝病模型MELD；MDS，骨髓增生异常综合征；核酸检测；NCPH，非肝硬化门静脉高压症；NRH，结节性再生增生；PF，肺纤维化；公共卫生服务；短端粒综合征；SVR，持续病毒学反应；TERT，端粒酶逆转录酶基因
Short telomere syndromes (STSs) are the most common premature aging disorders; mutations in telomerase and other telomere maintenance genes underlie their etiology.(1) Their biology is defined by short telomere length which provokes senescence and apoptosis, leading to organ failure. The majority of STSs are autosomal dominant, but X-linked, de novo, and recessive forms exist. Mutations in 14 genes are identifiable in 70%-80% of STSs, with the mutant telomerase reverse transcriptase gene, TERT, accounting for nearly half the cases.(1) End-stage liver disease is the third most common degenerative complication after idiopathic pulmonary fibrosis (IPF) and aplastic anemia.(2) While aplastic anemia generally manifests in children and young adults, and IPF is adult-onset, liver disease presents in intermediate age groups. Pulmonary fibrosis (PF) on the other hand manifests in the vast majority of cases after the fourth decade.(1) Liver disease has 2 primary manifestations in STS. The first, noncirrhotic portal hypertension with hepatopulmonary syndrome (NCPH-HPS), is usually diagnosed in children/younger adults and often in association with nodular regenerative hyperplasia (NRH).(2) HPS is the predominant manifestation in this subset of patients while other complications of portal hypertension are rare.(2) The second is cryptogenic cirrhosis (with or without HPS), present in older adults preceding or co-occurring with IPF.(3) The optimal management of liver disease, especially in the presence of these syndromic comorbidities, remains unclear. Recent success of reduced intensity hematopoietic stem cell transplantation (HSCT) regimens for aplastic anemia has uncovered the natural history of STS with nearly all HSCT survivors developing HPS. However, the role of liver transplantation (LT) in these patients remains unknown, especially given the pulmonary vulnerability and potential for exacerbation of parenchymal PF, as well as increased relative risk of squamous cancers and myelodysplastic syndromes.(4) For patients requiring LT, finding suitable donors remains a challenge, given the low Model for End-Stage Liver Disease (MELD) score at initial presentation. Patients with HPS are eligible for MELD exception points to improve access to transplantation; however, this is often in later stages of the disease, risking the sequelae of prolonged hypoxemia. To ensure timely LT for these patients, public health service (PHS)-designatedAbbreviations: AML, acute myeloid leukemia; AVN, avascular necrosis; CMV, cytomegalovirus; DAA, direct-acting antiviral; DDLT, diseased donor liver transplant; DKC1, dyskeratosis congenita 1 gene (X-linked); DLCO, diffusion capacity for carbon monoxide; FISH, fluorescence in situ hybridization; HCV, hepatitis C virus; HPS, hepatopulmonary syndrome; HSCT, hematopoietic stem cell transplantation; IPF, idiopathic pulmonary fibrosis; IST, immunosuppressive therapy; MELD, Model for End-Stage Liver Disease; MDS, myelodysplastic syndrome; NAT, nucleic acid test; NCPH, noncirrhotic portal hypertension; NRH, nodular regenerative hyperplasia; PF, pulmonary fibrosis; PHS, public health service; STS, short telomere syndrome; SVR, sustained virological response; TERT, telomerase reverse transcriptase gene.
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影响因子：
2.6
作者：
Ting, Peng-sheng;Hamilton, James Peter;Chen, Po-Hung
通讯作者：
Chen, Po-Hung
影响因子：
9.6
作者：
Gorgy, Amany I.;Jonassaint, Naudia L.;Armanios, Mary
通讯作者：
Armanios, Mary
影响因子：
20.3
作者：
Schratz, Kristen E.;Haley, Lisa;Armanios, Mary
通讯作者：
Armanios, Mary
DOI：
10.1073/pnas.0804280105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Alder, Jonathan K.;Chen, Julian J. -L.;Armanios, Mary Y.
通讯作者：
Armanios, Mary Y.