Nastasio Silvia, Matarazzo Lorenza, Sciveres Marco, Maggiore Giuseppe
Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy.
Transl Gastroenterol Hepatol. 2021 Apr 5;6:25. doi: 10.21037/tgh.2020.03.10. eCollection 2021.
Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe disease characterized by autoimmune hemolysis associated with acute liver injury, histologically defined by widespread giant cell transformation. It occurs after the neonatal period, most commonly in the first year of life and uniquely affects pediatric patients. It is still poorly understood and likely underdiagnosed, although in recent years there have been advances in the understanding of its pathogenesis and the liver injury is now hypothesized to be secondary to a humoral immune mechanism. Although no laboratory test specific for the diagnosis currently exists, given its severity, it is fundamental to rule out GCH-AHA when evaluating a patient in the first year of life presenting with AHA and/or with acute liver disease of unknown etiology. While GCH-AHA is progressive in nature as other autoimmune liver disorders, it differs significantly from juvenile autoimmune hepatitis (JAIH) in that a cure can be achieved after several years of intensive treatment in a portion of patients. Conventional first line therapy consist of prednisone/prednisolone combined with azathioprine, however, several immunosuppressive drugs, commonly used in the treatment of JAIH have been tried as second line therapy, including cyclosporine, cyclophosphamide, mycophenolate mofetil, 6-mercaptopurine, calcineurin inhibitors, and sirolimus. Intravenous immunoglobulins have also been used in cases of severe liver dysfunction and/or severe anemia allowing for transitory remission. More recently treatment with B-cell depletion has been attempted in some patients and encouraging results have been reported in refractory cases. Although what constitutes optimal treatment has yet to be determined, the recent progress in the understanding of the pathogenetic mechanisms of GCH-AHA have made positive strides, cautiously pointing toward a hopeful prognosis for some of these patients.
巨细胞性肝炎合并自身免疫性溶血性贫血（GCH - AHA）是一种罕见且严重的疾病，其特征为与急性肝损伤相关的自身免疫性溶血，组织学上表现为广泛的巨细胞转化。它发生在新生儿期之后，最常见于生命的第一年，且独特地影响儿科患者。尽管近年来对其发病机制的认识有所进展，目前推测肝损伤继发于体液免疫机制，但人们对它仍知之甚少，且可能存在诊断不足的情况。虽然目前尚无特异性的诊断实验室检查，但鉴于其严重性，在评估1岁以内出现AHA和/或病因不明的急性肝病的患者时，排除GCH - AHA至关重要。与其他自身免疫性肝病一样，GCH - AHA本质上呈进行性，但它与青少年自身免疫性肝炎（JAIH）有显著不同，因为部分患者经过数年强化治疗后可实现治愈。传统的一线治疗包括泼尼松/泼尼松龙联合硫唑嘌呤，然而，几种常用于治疗JAIH的免疫抑制药物已被尝试作为二线治疗，包括环孢素、环磷酰胺、霉酚酸酯、6 - 巯基嘌呤、钙调神经磷酸酶抑制剂和西罗莫司。静脉注射免疫球蛋白也已用于严重肝功能不全和/或严重贫血的病例，可实现短暂缓解。最近，一些患者尝试了B细胞清除治疗，难治性病例已报告了令人鼓舞的结果。尽管最佳治疗方案尚未确定，但对GCH - AHA发病机制的最新认识已取得积极进展，谨慎地为其中一些患者带来了有希望的预后。
