Abstract：
OBJECTIVE: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement.
METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022.
RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%).
RESULTS: After a median 40 months\' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy.
CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.
METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022.
RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%).
RESULTS: After a median 40 months\' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy.
CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.
摘要：
目的：肝脏受累预示成人预后不良。我们的目的是表征临床特征，肝功能检查,放射学发现，分子概况,成人朗格汉斯细胞组织细胞增生症（LCH）合并肝脏受累的治疗方法和结果。
方法：我们对北京协和医院（北京，中国）2001年1月至2022年12月。
结果：在445名新诊断为LCH的成年人中，90例患者在诊断时肝脏受累，22例患者复发。中位年龄为32岁(范围，18-66岁）。在112名可评估的患者中，108人进行了完整的肝功能测试，包括丙氨酸转氨酶,天冬氨酸转氨酶,碱性磷酸酶(ALP),γ-谷氨酰转肽酶(GGT),总胆红素和白蛋白.63.0%的ALP升高，86.1%的GGT升高；14.8%的胆红素升高。54例患者的下一代测序显示频繁的BRAFN486_P490（29.6％），BRAFV600E（18.5%），和MAP2K1（14.8%）。
结果：经过中位40个月的随访（范围1-168个月），3年无进展生存率（PFS）和总生存率分别为49.7%和86.6%。在多变量分析中，≥3次异常肝功能检查（HR3.384，95％CI1.550-7.388，P=.002）与PFS较差相关；免疫调节药物治疗（HR0.073，95％CI，0.010-0.541，P=.010）与PFS优于化疗相关。
结论：总之，GGT和ALP升高在LCH肝脏受累的成人中很常见.大于等于3个异常肝功能测试预测不良结果。与化疗相比，免疫调节药物治疗与良好的无进展生存期相关。
方法：我们对北京协和医院（北京，中国）2001年1月至2022年12月。
结果：在445名新诊断为LCH的成年人中，90例患者在诊断时肝脏受累，22例患者复发。中位年龄为32岁(范围，18-66岁）。在112名可评估的患者中，108人进行了完整的肝功能测试，包括丙氨酸转氨酶,天冬氨酸转氨酶,碱性磷酸酶(ALP),γ-谷氨酰转肽酶(GGT),总胆红素和白蛋白.63.0%的ALP升高，86.1%的GGT升高；14.8%的胆红素升高。54例患者的下一代测序显示频繁的BRAFN486_P490（29.6％），BRAFV600E（18.5%），和MAP2K1（14.8%）。
结果：经过中位40个月的随访（范围1-168个月），3年无进展生存率（PFS）和总生存率分别为49.7%和86.6%。在多变量分析中，≥3次异常肝功能检查（HR3.384，95％CI1.550-7.388，P=.002）与PFS较差相关；免疫调节药物治疗（HR0.073，95％CI，0.010-0.541，P=.010）与PFS优于化疗相关。
结论：总之，GGT和ALP升高在LCH肝脏受累的成人中很常见.大于等于3个异常肝功能测试预测不良结果。与化疗相比，免疫调节药物治疗与良好的无进展生存期相关。
