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作者：Tran Tram T，et al.
翻譯：楊涓
譯者簡介：女，博士，重慶醫科大學附屬第一醫院中西醫結合科主治醫師。畢業於天津中醫藥大學中西醫結合婦科專業，現任重慶市醫師協會風濕免疫科醫師分會第一屆委員會免疫相幹生殖疾病學組委員，承擔重慶市衛生局科研課題1項，發表SCI及CSCD論好康篇。擅長常見、多發風濕性疾病病的診治，能夠熟練處理風濕病危重症，擅長中西醫結合婦科內分泌疾病及不孕症的診治。
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【摘要】
孕婦肝臟疾病的診治是胃腸病醫生的常見且時常困擾臨床的診治。挑戰在於在臨床管理決策中必須考慮準媽媽和未出生胎兒的安全性。該實踐指南為孕婦肝病的常見診斷和治療挑戰提供了基於證據的方法。
自身免疫性肝炎
31.患有自身免疫性肝炎（AIH）的孕婦應繼續接受皮質類固醇和/或硫唑嘌呤（AZA）治療（強烈建議，證據水平很低）。
32.原發性膽汁性肝硬化（PBC）孕婦應繼續接受熊去氧膽酸（UDCA）治療（強烈建議，證據水平很低）。
盡管總體上有一些針對這些疾病的治療方法的系統評價，但尚未發表有關懷孕期自身免疫性肝炎）（AIH），原發性膽汁性肝硬化（PBC）或威爾遜氏病（WD）治療的系統評價或meta分析。
對於患有慢性肝病的女性，成功懷孕的關鍵似乎是在懷孕之前、期間和之後均進行有關生育能力和肝病最佳管理的適當咨詢。在這種情況下，治療慢性肝病的藥物管理難點就在於治療劑量，有效性和安全性。討論的局限性在於有關在肝病和懷孕情況下，特定藥物的數據很少。然而，在回顧藥物治療、慢性肝病和懷孕的交集時，一個顯而易見的原則就是，健康的母親能有最佳的機會生一個健康的嬰兒和最佳的孕婦結局。
因此，在考慮懷孕的患有慢性肝病（如AIH，PBC或WD）的女性中，建議把慢性肝病控制在最佳狀態。除了治療方案帶來的益處和風險外，還必須考慮在懷孕期不治療肝病的風險，以及隨之而來的對母嬰健康的風險。
很難區分孕婦肝臟疾病潛在的影響和針對這些疾病的治療對孕婦或胎兒並發症風險的潛在影響。
此外，由於諸如先天性畸形等不良事件非常少見，因此可用數據僅限於病例報告。孕期這些肝病治療的有效性和安全性方面的數據有限，這種局限性常常導致這些肝病在孕期的治療依賴於其他疾病過程（如炎症性腸病，自身免疫性疾病或器官移植）在孕期治療的推斷數據。必須認識到這種推斷的局限性，將這些結論推廣到孕期肝病患者時要格外小心。
自身免疫性肝病（AIH）與胎兒早產和流產的風險增加有關，AIH活動度控制欠佳會導致不良結局，尤其是在懷孕前或懷孕期間沒有或停止AIH治療的情況下（123）。
盡管以往一直認為AIH在懷孕期處於靜止狀態，但近期數據表明AIH可能在懷孕期初次出現，圍產期暴發的風險>20％，產後暴發的風險高達30-50％（124,125）。AIH的治療是基於使用皮質類固醇和/或硫唑嘌呤（AZA）的免疫抑制作用，而AIH的最新實踐指南建議對孕婦進行潑尼松單藥治療（126）。
一項AIH治療的系統評價認為，皮質類固醇±AZA適於誘導，而對於AIH維持治療，皮質類固醇+ AZA或AZA單一療法優於皮質類固醇單一療法（127）。但是，目前尚無關於懷孕期AIH治療的系統評價或薈萃分析。在缺乏此類數據的情況下，重要的是要考慮到懷孕期間AIH發作可能比控制和預防AIH發作所需的藥物治療潛在風險更不利於新生兒結局。
一項基於人群的研究對> 51,000例接受皮質類固醇（懷孕C類藥物）治療的孕婦進行了研究，結果顯示唇腭裂或其他嚴重不良事件的發生沒有增加（127）。傳統上，皮質類固醇單藥療法在懷孕期間用於AIH發作的治療，因為AZA是懷孕D類藥物，其使用受到限制（127）。
一些AZA相幹動物研究發現，使用超藥理劑量和非口服給藥門路（例如腹膜內或皮下給藥）與四肢畸形、腭裂、骨骼畸形和造血抑制有關，從而引發擔憂。然而，據報導，在少數病例報告中，在懷孕期間使用AZA來治療AIH是安全的（128-136）。目前尚未對懷孕期AIH中的AZA治療進行系統研究。
但是，已經在炎性腸病中系統地研究了懷孕期使用AZA的情況，該研究涉及3,000例AZA暴露的懷孕與早產有關，但先天畸形或LBWs的發生卻沒有增加（137）。關於AZA在其他自身免疫性疾病和炎性腸病中的研究中，有早產的分散報告，但先天畸形、自然流產或感染的風險沒有增加，這證明了AZA在孕期的可接受性不斷增加（138-142）。
越來越多的證據表明AZA在懷孕期間的安全性，以及在懷孕期間實現和維持AIH疾病控制的重要性，證明了AIH持續治療對優化母體和胎兒結局至關重要。用皮質類固醇和AZA進行治療以控制母親AIH病情的潛在好處似乎遠遠大於母親和胎兒與治療相幹的不良事件的潛在小風險。
原發性膽汁性肝硬化：
先前的一些文獻表明，原發性膽汁性肝硬化（PBC）患者的懷孕結局較差（143）。由於懷孕懷孕，因此關於PBC和懷孕的研究數量非常有限。然而，最近一些研究報導了良好的母嬰結局（144）。PBC與分娩後的疾病發作有關（144，145）。熊去氧膽酸（UDCA）是懷孕B類藥物，通常推薦用於PBC（146）。
懷孕期間使用UDCA治療PBC的研究非常有限，尤其是在孕早期（147,148）。與AIH的情況類似，懷孕期間UDCA的潛在風險與治療對母嬰結局的潛在積極作用相比顯得更小。
越來越多的證據表明，UDCA用於其他疾病（如懷孕期肝內膽汁淤積症）的孕間是安全的，並且不太可能進行關於PBC懷孕期間UDCA的有效性和安全性的大規模研究，因此建議在PBC患者孕期繼續使用UDCA似乎是謹慎的做法（149,150）。
附原文
Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both
the expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver
disease in pregnant women.
Autoimmune hepatitis
31. Pregnant women with autoimmune hepatitis (AIH) should be continued >
32. Pregnant women with primary biliary cirrhosis (PBC) should be continued >
There are no published systematic reviews or meta-analysis >
The key for successful pregnancy outcomes in women with chronic liver disease appears to be appropriate counseling regarding fertility and optimal management of the liver disease before, during,
and after the pregnancy. The most challenging issue in this setting is the management of medications used for the treatment of the underlying chronic liver disease with regard to dosing,
effectiveness, and safety. Limiting the discussion is the paucity of data >
It is difficult to discriminate between the potential impact of underlying maternal liver diseases and therapies for these diseases, >
Moreover, because adverse events such as congenital malformations are very rare, available data are limited to case reports and case series. The limited data >
AIH is associated with an increased risk of fetal prematurity and loss, with worse outcomes with inadequate AIH activity control, especially in the absence of or discontinuation of AIH treatment
before or during pregnancy (123). Although AIH was historically thought to be quiescent during pregnancy, more recent data suggest that AIH may have an initial presentation during pregnancy, an
intrapartum fl are risk of >20% and postpartum flare risk of up to 30–50% (124,125). Treatment for AIH is based >
Corticosteroids, pregnancy category C drugs, have been studied in a population-based study of >51,000 corticosteroid-exposed pregnancies, with no increase in orofacial cleft defects or other
significant adverse events (127). Corticosteroid monotherapy has traditionally been used for the management of AIH flares during pregnancy because AZA is a pregnancy category D drug, which has
limited its use (127). Concerns regarding AZA arose from animal studies using suprapharmacologic doses and nonoral delivery routes such as intraperitoneal or subcutaneous dosing, associated with
limbic malformations, cleft palate, skeletal anomalies, and hematopoietic suppression. However, utilization of AZA during pregnancy for treatment of AIH has been reported to be safe in a limited
number of case reports and series (128–136). AZA treatment in AIH during pregnancy has not been studied systematically. However, utilization of AZA during pregnancy has been studied systematically in
inflammatory bowel disease with 3,000 AZA-exposed pregnancies showing an association with preterm births but no increase in congenital abnormalities or LBWs (137).
Studies of AZA in other autoimmune diseases and inflammatory bowel disease have found scattered reports of preterm births but no increased risk of congenital abnormalities, spontaneous abortions,
or infections supporting the growing evidence regarding the acceptability of AZA during pregnancy (138-142). The mounting evidence of AZA’s safety during pregnancy coupled with the importance of
achieving and maintaining AIH disease control during pregnancy supports the mandate that treatment continuation for AIH is critical in optimizing maternal and fetal outcomes.
The potential benefit of treatment with corticosteroids and AZA to keep the mother’s AIH in control appears to be significantly greater than the potentially small risk of treatment-associated
adverse events >
Primary biliary cirrhosis：Older literature suggested poor outcomes of pregnancy in patients with PBC (143). As patients with PBC tend to present at an older age after the usual child-bearing age,
and as women with PBC were discouraged in the past from pursuing pregnancy, there is an extremely limited number of studies >
摘自
Tran, Tram T， Ahn, Joseph， Reau, Nancy S. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenteroladvanceonlinepublication,2February2016;doi: 10.1038/ajg.2015.430
>「前沿傳遞」免疫性肝病孕婦如何用藥物（美國胃腸學會臨床指南）