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2026年欧洲肝病学会年会（EASL 2026）于2026年5月27日在西班牙•巴塞罗那正式开幕。作为全球肝病学领域的学术盛会，本届大会汇聚国际顶尖专家学者，共同探讨肝病学、胃肠病学、移植外科及传染病学等领域的最新研究进展与临床实践突破。

大会设置前沿学术报告、高互动性研讨会及专题论坛，为与会者提供深度交流与专业提升的高端平台。为及时传递大会精华内容，肝胆相照平台将全程跟踪报道，本篇精选遗传代谢性肝病领域热点研究进行整理，以传递大会的最新动态和精彩看点。

01 OS-056

CAM2029治疗多囊肝病的有效性与安全性：IIb期POSITANO研究

Efficacy and safety of CAM2029 in patients with polycystic liver disease: phase 2b POSITANO study

作者：Marie C. Hogan, Frederik Nevens, Arun Jesudian, K. Rajender Reddy, Richard Taubert, Jonel Trebicka, Peter Almgren, Ulrika Axling, Peter Jönsson, Fredrik Tiberg, Joost P.H. Drenth

研究背景与目的▼

生长抑素类似物（如奥曲肽、兰瑞肽）在研究者发起的临床试验中，已被证实可缩小多囊肝病患者的肝脏体积，但该疗效尚未在随机对照临床试验中得到验证。CAM2029是一款采用流体晶体技术研发的新型皮下注射长效奥曲肽缓释制剂，患者可使用自动注射笔自行给药，使用便捷。本文报道Ⅱb期POSITANO研究（临床试验编号：NCT05281328）53周核心阶段结果，评估CAM2029用于多囊肝病患者的疗效与安全性。

Background and aims：Somatostatin analogues (SSAs; eg octreotide and lanreotide) have indicated efficacy in reducing liver volume in investigator-driven clinical trials in polycystic liver disease (PLD) but efficacy has not yet been established in randomised clinical trials. CAM2029 is a novel subcutaneous, extended-release octreotide depot, based on the FluidCrystal® technology, designed for convenient administration by patients using an autoinjector pen. Here we report the 53-week (W) core phase results of the Phase 2b POSITANO (NCT05281328) study evaluating CAM2029 in patients with PLD.

研究方法▼

本研究核心阶段为为期53周的双盲、随机、安慰剂对照试验，入组存在临床症状、身高校正后总肝脏体积≥1800毫升/米的多囊肝病患者。受试者分为三组：CAM2029 10毫克每周给药组、CAM2029 10毫克每两周给药组、安慰剂组。

主要终点：对比CAM2029组与安慰剂组，受试者从基线至第53周身高校正后总肝脏体积的变化差值。

次要终点：采用全新研发的多囊肝病症状评分量表评估患者相关症状变化、肝脏囊肿总体积变化及用药安全性。

Method：In this single-center, open-label RCT (February 2022-March 2025), we randomly (1:1) assigned 194 adult patients (aged 18–60 years) with ACLF (European Association for the Study of the Liver-Chronic Liver Failure Consortium [EASL CLIF-C] Grades 1–3b) to receive SMT plus 5 sessions of TPE (97 patients) or SMT alone (97 patients). The primary outcome was all-cause mortality at 28 days. Secondary outcomes included 90-day mortality, changes in prognostic scores and resolution of organ failures, infections and adverse events.

研究结果▼

本研究共纳入71例受试者（CAM2029组48例，安慰剂组23例）。受试者平均年龄54.1岁，女性占比85.9%，身高校正后总肝脏体积中位数为3070毫升/米。CAM2029组与安慰剂组试验完成率分别为87.2%、87.0%。

研究达到主要终点：自基线至第53周，CAM2029组与安慰剂组相比，身高校正后总肝脏体积的相对治疗差值为4.3%（95%置信区间：0.1~8.4，P=0.0443），差异具有统计学意义。

CAM2029可抑制肝脏囊肿总体积增长，两组相对治疗差值达8.7%（95%置信区间：1.8~15.2，P=0.0159），差异有统计学意义。

从基线至第53周，CAM2029组患者多囊肝病症状评分有所改善，但两组间无显著差异（相对治疗差值：2.7，95%置信区间：−5.2~10.5，P=0.5041）。

CAM2029整体耐受性良好，安全性特征与其他注射用生长抑素类似物一致。两组绝大多数不良事件为1~2级。CAM2029组最常见不良事件为腹泻（68.1%）、注射部位瘙痒（42.6%）、注射部位疼痛（40.4%）及腹痛（36.2%）。

Results：Seventy-one patients were randomised (CAM2029 combined n = 48; placebo n = 23). Mean age was 54.1 years, 85.9% were female and median htTLV was 3070 mL/m. Treatment was completed by 87.2% for CAM2029 combined and 87.0% for placebo. The primary endpoint was met, with a statistically significant estimated relative treatment difference in htTLV from baseline to W53 of 4.3% (95% confidence interval [CI]: 0.1, 8.4; p = 0.0443) between CAM2029 and placebo. CAM2029 reduced total liver cyst volume growth, with an estimated relative treatment difference from baseline to W53 of 8.7% (95% CI: 1.8, 15.2; p = 0.0159) between CAM2029 and placebo. CAM2029 improved PLD-S score from baseline to W53; however, no significant difference was observed between CAM2029 and placebo (estimated relative treatment difference: 2.7; 95% CI: −5.2, 10.5; p = 0.5041). CAM2029 was well tolerated, with a safety profile consistent with other injectable SSAs. Most adverse events (AEs) were grade 1–2 for both CAM2029 and placebo. The most frequent AEs with CAM2029 were diarrhoea (68.1%), injection site pruritus (42.6%), injection site pain (40.4%) and abdominal pain (36.2%).

研究结论▼

CAM2029能够抑制多囊肝病患者肝脏总体积及肝脏囊肿体积的增长，具备成为多囊肝病治疗药物的潜力，值得开展进一步研究。目前该研究仍在推进，后续将开展最长120周的开放标签延伸试验，评估CAM2029长期用药效果。

Conclusion: CAM2029 reduced total liver and liver cyst volume growth, supporting further evaluation as a potential PLD treatment. The study is ongoing to evaluate long-term CAM2029 treatment in an open-label extension period up to 120 weeks.

02 OS-057

胆碱硫钼酸盐可稳定经治肝豆状核变性患者的肝脏病变，并改善其神经症状与生活质量

Tiomolibdate choline stabilizes liver disease and improves neurological symptoms as well as quality-of-life in treatment-experienced Wilson disease patients

作者：Valentina Medici, Aftab Ala, Karl Heinz Weiss, Edward J. Gane, Zoe Mariño, Chandler Robinson, Andrew Cittadine, Declan Tuffy, George Boon Bee Goh, Marina Berenguer, Thomas Sandahl, Fred Askari

研究背景与目的▼

肝豆状核变性（WD）是一种罕见的常染色体隐性遗传病，以体内铜过量蓄积为特征，可造成肝脏、神经系统损伤，并伴随精神异常。胆碱硫钼酸盐（TMC，研发代号ALXN1840） 为每日一次口服药物，对铜离子具有极高结合亲和力。既往研究证实，该药可纠正肝豆状核变性患者的铜代谢失衡，避免铜超载引发的毒性损害。本项Ⅱ期研究针对既往接受过规范治疗的肝豆状核变性患者开展，评估胆碱硫钼酸盐对患者肝脏病变及临床症状的改善效果。

Background and aims：Wilson disease (WD) is a rare autosomal recessive disorder characterized by excess copper (Cu) accumulation resulting in hepatic and neurologic damage as well as psychiatric symptoms. Tiomolibdate choline (TMC; ALXN1840), a once-daily oral agent with extremely high affinity for binding Cu, has been shown to improve Cu balance and prevent toxic effects of Cu overload in WD patients. A Phase 2 study was conducted in treatment-experienced WD patients to evaluate the effect of TMC on both liver pathology and clinical symptoms of WD.

研究方法▼

本研究为多中心、开放标签Ⅱ期临床试验，入组既往接受标准治疗≥1年的肝豆状核变性患者，单用胆碱硫钼酸盐治疗48周并评估疗效。分别在基线、治疗第48周对患者肝脏功能、神经功能及生活质量进行评估；进入延伸期的患者在第96周再次复查。

所有受试者于基线及第48周接受肝脏穿刺活检，检测肝脏铜含量、肝纤维化分期及脂肪变性程度。采用统一肝豆状核变性评分量表（UWDRS）、临床总体印象量表（CGI） 评估神经功能与整体临床状态，使用欧洲五维健康量表（EQ5D）英国健康指数评价生活质量。

Method：This open-label, multicenter Phase 2 trial evaluated the efficacy of TMC monotherapy through 48 weeks in treatment-experienced (≥1 year on standard of care) WD patients. Hepatic, neurologic, and quality-of-life assessments were performed at Baseline and Week 48; patients in the extension period had assessments repeated at Week 96. Liver biopsy was performed at Baseline and Week 48 to assess the impact of TMC on hepatic Cu concentration, stage of fibrosis, and grade of steatosis. Neurologic and clinical outcomes were assessed by the Unified WD Rating Scale (UWDRS) and Clinical Global Impression (CGI) scale. Quality of life was assessed by the EuroQoL 5-Dimensions (EQ5D) UK Health Index.

研究结果▼

研究共纳入29例患者，既往中位治疗时长为13.8年（四分位距：10.9年），其中23例患者进入试验延伸期。

治疗第48周时，多数患者肝脏病变得到改善或维持稳定：非酒精性脂肪肝活动度评分（NAS）改善/稳定比例达71%，非酒精性脂肪性肝炎临床研究协作组（NASH CRN）肝纤维化评分改善/稳定比例为67%。瞬时弹性检测提示肝脏硬度显著下降，平均降幅1.19千帕（标准差2.15千帕，P=0.0122）。第48周时肝脏铜含量较基线无统计学差异。

第48周时，患者统一肝豆状核变性评分、临床总体印象量表评分及欧洲五维健康指数均出现显著改善，且该疗效持续至第96周。

Results：Twenty-nine WD patients were enrolled with a median [IQR] prior treatment duration of 13.8 years [10.9]; 23 continued in the extension period. At Week 48, the majority of patients showed improvement or stabilization in hepatic pathology, including Non-alcoholic Fatty Liver Disease Activity Score (NAS; 71% improved or stabilized) and Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) fibrosis score (67% improved or stabilized). There was a statistically significant improvement in liver stiffness by transient elastography (mean [SD] −1.19 kPa [2.15]; p = 0.0122). Hepatic Cu concentration was not statistically different at Week 48. Statistically significant improvements in UWDRS, CGI, and EQ5D UK Health Index were observed at Week 48 and persisted through Week 96.

研究结论▼

对于长期接受过多种治疗的肝豆状核变性患者，使用胆碱硫钼酸盐治疗最长2年，可改善或稳定肝脏相关指标，同时显著缓解神经症状、提升整体临床状态。肝脏铜含量保持稳定，提示该药可有效调控体内铜水平。提高用药剂量或延长治疗时长，或可进一步降低肝脏铜含量。上述结果证实，胆碱硫钼酸盐是治疗肝豆状核变性的有效选择。

Conclusion:  TMC treatment for up to 2 years resulted in improvement or stabilization of parameters of liver pathology as well as improvement in neurologic and clinical outcomes in heavily pretreated patients. Stability in hepatic Cu concentration indicates effective Cu control by TMC. Higher doses and/or a longer treatment period may lead to reductions in liver Cu. These results support TMC’s role as a valuable treatment option for WD patients.

03 THU-254

巴西人群肝豆状核变性的基因突变谱与临床表型分析

Genotypic spectrum and clinical presentation of Wilson disease in a Brazilian cohort

作者：Maria Chiara Chindamo, Ida Vanessa Schwartz, Gabriel Quintana, Paulo Sgobbi, Thais Guaraná, Vivian Rotman, Cibele Franz, Luciana Agoglia, Renata Perez

研究背景与目的▼

肝豆状核变性（WD）是由ATP7B基因致病突变引发的常染色体隐性遗传病。目前全球已报道该基因变异型超2700种，但针对巴西人群的变异分布及基因型-表型关联研究仍较为匮乏。明确地区性基因突变特征，有助于提升疾病诊断准确率并降低诊疗成本。本研究分析巴西肝豆状核变性患者队列中ATP7B基因变异的发生频率，并探究其与临床表型的相关性。

Background and aims：Wilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in the ATP7B gene. Although more than 2700 variants have been described worldwide, data on their distribution and genotype–phenotype association in Brazilian populations remain limited. Identifying regional variant patterns may improve diagnostic accuracy and cost-effectiveness. We evaluated the frequency of ATP7B variants in a Brazilian WD cohort and their association with clinical phenotypes.

研究方法▼

研究纳入巴西东南部及南部的肝豆状核变性患者，由孟德利克斯实验室采用二代测序技术，对ATP7B基因全部21个外显子及外显子-内含子连接区进行测序。依据ClinVar数据库标准，将基因变异分为致病变异、可能致病变异、意义未明变异。收集患者人口学资料与临床特征，并结合基因型开展相关性分析。

Method：Next-generation sequencing covering all 21 exons and exon–intron junctions of the ATP7B gene was performed (Mendelics Labs) in WD patients from southeastern and southern Brazil. Variants were classified as pathogenic, likely pathogenic (LP), or variants of uncertain significance (VUS) according to ClinVar. Demographic data and clinical presentation were collected and correlated with genotypes.

研究结果▼

本研究共纳入44例患者，女性占55%，平均年龄29±12岁。临床表型分布：肝损害合并神经症状者占45%，单纯肝损害者占41%，单纯神经精神症状者占7%，无症状患者占7%。

研究共检出33种基因变异：致病变异占61%，意义未明变异占21%，可能致病变异占18%。基因型以复合杂合子最为多见（84%），其次为纯合子（12%）、单纯杂合子（4%）。

人群中高频变异依次为：c.3402delC（18%）、c.3818C>T（14%）、c.2123T>C（11%），这类变异主要与肝脏受累表型相关，可合并或不合并神经损伤。

不同合子类型患者的发病年龄无明显差异：纯合子、复合杂合子、单纯杂合子中位发病年龄分别为19岁、20岁、21岁（P=0.94）。

携带至少1个c.3402delC等位基因的患者，血清铜蓝蛋白水平显著低于其他变异携带者（中位数：3.0 mg/dL vs 7.0 mg/dL，P=0.025），但两组发病年龄无差异（P=0.93）。2号外显子纯合缺失与重度神经系统病变相关。

检出的意义未明变异包括：c.2145C>T（6%）、c.2755C>T（6%）、c.1552T>C（3%）、c.2866-6T>G（3%）、c.2562G>C（3%）、c.4388A>G（3%）、c.3188C>T（3%）。

检出的可能致病变异包括：c.2072G>T（3%）、c.3551T>C（3%）、3~4号外显子缺失（6%）、c.3071_3072delTG（3%）、c.399G>A（3%）、c.3517G>A（3%）。

Results：Forty-four patients were included (55% female; mean age 29 ± 12 years). Combined hepatic and neurological manifestations occurred in 45%, isolated hepatic in 41%, isolated neuropsychiatric in 7%, and 7% were asymptomatic. Thirty-three variants were identified: 61% pathogenic, 21% VUS, and 18% LP. Most patients were compound heterozygous (84%), followed by homozygous (12%) and simple heterozygous (4%). The most frequent variants were c.3402delC (18%), c.3818C>T (14%), and c.2123T>C (11%), predominantly associated with hepatic manifestations, with or without neurological involvement. Age at symptom onset did not differ by zygosity (19, 20, and 21 years for homozygous, compound heterozygous, and simple heterozygous, respectively; p = 0.94). Carriers of at least one c.3402delC allele had lower ceruloplasmin levels compared with other variants (median 3.0 vs 7.0 mg/dL; p = 0.025), without differences in age at symptom onset (p = 0.93). Homozygous deletion of exon 2 was associated with severe neurological disease. VUS included c.2145C>T (6%), c.2755C>T (6%), c.1552T>C (3%), c.2866–6T>G (3%), c.2562G>C (3%), c.4388A>G (3%), and c.3188C>T (3%). LP variants were c.2072G>T (3%), c.3551T>C (3%), exon 3–4 deletion (6%), c.3071_3072delTG (3%), c.399G>A (3%), and c.3517G>A (3%).

研究结论▼

在该巴西患者队列中，c.3402delC、c.2123T>C、c.3818C>T为最常见的基因变异。在确诊肝豆状核变性患者中检出多种意义未明变异。该人群基因异质性显著，难以建立明确的基因型-表型对应关系。

Conclusion: The variants c.3402delC, c.2123T>C, and c.3818C>T were the most prevalent in this Brazilian cohort. Multiple VUS were identified in confirmed WD cases. Marked genotypic heterogeneity was observed, limiting robust genotype–phenotype associations.

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