Liver Biopsy is Indicated Before Attempting Treatment Withdrawal in Children with AIH: Commentary by the ESPGHAN HepCom.
Liver Biopsy is Indicated Before Attempting Treatment Withdrawal in Children with AIH: Commentary by the ESPGHAN HepCom.
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患有 AIH 的儿童在尝试停止治疗之前需要进行肝活检：ESPGHAN HepCom 的评论。
DOI：
10.1097/mpg.0000000000003858
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发表时间：
2023
影响因子：
2.9
通讯作者：
Samyn M
中科院分区：
文献类型：
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作者：
Samyn M
JPGN·第77卷，第3期，2023年9月致编辑肝脏活检的信函(11/24)，19名从儿科向成人肝病服务过渡后由成人肝病专家酌情决定停止治疗的患者中有63%(12/19)。后一组中停止治疗的标准没有具体说明。有兴趣知道没有接受过基线诊断肝活检的患者是否包括在这一队列中。停药前年龄较大和疗程较长与无复发相关。2例复发患者治疗效果不佳，需要肝移植。在50名患者中，没有尝试停止治疗的主要原因是肝酶波动或患者/医生偏好。作者继续将他们的结果与6个历史队列进行比较，这些队列包括40名儿童，其中至少有10名儿童根据包括组织学在内的严格标准考虑停止治疗。停止治疗的成功率在45%到87%之间，只有2个队列报告的成功停止治疗的比率低于或接近于作者目前的队列。作者提出了一种更温和的方法来治疗儿童自身免疫性肝炎，其基础是持续正常的血清转氨酶活性(正常的ALT和GT；1年)，没有组织学，以及额外的标准正常的丙种球蛋白/免疫球蛋白G和低或阴性的自身抗体效价(5)。参考美国肝病研究协会(AASLD)的指导方针，他们指出，在考虑停止成人治疗时，肝脏组织学“不再是强制性的”。指南中的确切措辞略有不同，“≥患者在停药前进行肝组织检查是首选的，但成人不是强制性的，儿童是必需的”和“儿童仍强烈建议停药前进行肝活检，以确保炎症的消退”(6)。此外，欧洲肝脏研究协会(EASL)的指导方针建议如下：“在血清转氨酶和免疫球蛋白水平完全正常化(生化缓解)后，治疗应继续至少三年和至少24个月。较长时间的治疗可能会降低复发的频率，因此可以考虑。对于首发症状严重且对诱导治疗耐受性低的患者，建议在停药前进行肝活检，因为组织学结果可预测纤维化进展和复发。在组织学疾病持续活跃的患者中，免疫抑制治疗不应该停止，因为复发几乎是肯定的“，并且”在维持治疗期间或治疗减少后自身免疫性肝炎活动的爆发需要增加免疫抑制的剂量，并阻止完全停药“(7)。Maggiore等人建议使用ALT水平是正常上限(ULN)的0.5倍作为考虑停止治疗的标准，该研究涉及288名患有自身免疫性肝炎的成年人，其中28人停止治疗(8)。然而，所有继续缓解的成人(15，54%)在停药时ALT水平和免疫球蛋白G水平均为<；0.5ULN和<；12g/L，而不仅仅是ALT水平<；0.5ULN。此外，在Maggiore等人报告的儿童中，ALT水平的值似乎并不是特别有帮助，因为在11名没有复发的儿童中有10名的血清ALT活性为<；0.5ULN，而在13名复发的儿童中也有7名。
JPGN• Volume 77, Number 3, September 2023 Letters to the Editor liver biopsy (11/24), and 63% of 19 who discontinued treatment at the discretion of the adult hepatologist following transition from pediatric to adult hepatology services (12/19). The criteria for discontinuing treatment in the latter cohort were not specified. It would be of interest to know whether patients who had not undergone a baseline diagnostic liver biopsy are included in this cohort. Older age at and longer duration of treatment before withdrawal were associated with absence of relapse. In 2 patients relapse was not treatment responsive requiring liver transplantation. The main reasons for not attempting to discontinue treatment in 50 were fluctuating liver enzymes or patient/physician preference. The authors go on to compare their results with 6 historical cohorts of> 40 children with at least 10 children considered for withdrawal of treatment based on stringent criteria including histology. The percent of successful withdrawal of treatment varied between 45% and 87% with only 2 cohorts reporting lower or similar rates of successful withdrawal of treatment than that of the authors’ current cohort. The authors suggest a softer approach to treatment withdrawal in children with autoimmune hepatitis based on lasting normal serum transaminase activity (normal ALT> 1 year) without histology and additional criteria of normal gamma globulins/immunoglobulin G and of low or negative autoantibody titers (5). Referring to the American Association for the Study of Liver Diseases (AASLD) guidelines they state that liver histology is “no longer mandatory” when considering discontinuation of treatment in adults. The exact wording in the guidance is slightly different “liver tissue examination prior to drug withdrawal in individuals with≥ 2 years of biochemical remission is preferred but not mandatory in adults and required in children” and “prewithdrawal liver biopsy is still strongly advised in children to ensure resolution of inflammation”(6). In addition, the European Association for the Study of the Liver (EASL) guidelines recommend the following:“treatment should be continued for at least three years and for at least 24 months after complete normalisation of serum transaminases and IgG levels (biochemical remission). Longer treatments may decrease the frequency of relapse and may therefore be considered. For patients with severe initial presentation and low tolerance of induction treatment, performance of a liver biopsy prior to treatment withdrawal is advisable as histological findings are predictive of fibrosis progression and relapse. In patients with continued histological disease activity (> 3), immunosuppressive treatment should not be discontinued, as relapse is almost certain to occur” and “flares of autoimmune hepatitis activity during maintenance therapy or following treatment reduction require increased doses of immunosuppression and preclude complete drug withdrawal”(7).Maggiore et al suggest using ALT levels< 0.5 times the upper limit of normal (ULN) as a criterion to consider treatment discontinuation referring to a study in 288 adults with autoimmune hepatitis including 28 in whom treatment was discontinued (8). However, all adults who remained in remission (15, 54%) had both ALT levels< 0.5 ULN and immunoglobulin G levels< 12 g/L at the time of withdrawal of treatment and not only ALT levels< 0.5 ULN. Moreover, the value of ALT levels< 0.5 ULN does not appear to be particularly helpful in the children reported by Maggiore et al, as the serum ALT activity at the time of treatment withdrawal was< 0.5 ULN in 10 of 11 children who did not relapse but also in 7 of 13 children who did relapse.