Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey.
Department of Gastroenterology, Hacettepe University, Ankara, Turkey.
Clin Gastroenterol Hepatol. 2014 May;12(5):863-9. doi: 10.1016/j.cgh.2013.09.021. Epub 2013 Sep 26.
BACKGROUND & AIMS: For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH.
We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58).
Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes).
In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.
对于具有自身免疫性肝炎（AIH）特征的原发性胆汁性肝硬化（PBC）患者，单用熊去氧胆酸（UDCA）或联合免疫抑制治疗存在争议。对于与初始治疗反应或结局相关的因素知之甚少。我们对符合巴黎标准的 PBC-AIH 患者的治疗策略和结局相关因素进行了回顾性分析。
我们分析了来自 5 个国家 7 个中心的 88 例 PBC-AIH 患者的数据。一线治疗包括单用 UDCA（n=30）或 UDCA 联合免疫抑制治疗（n=58）。
接受 UDCA 单药一线治疗的患者中，37%的患者未对治疗产生应答。严重界面肝炎与治疗无应答独立相关（P=0.024；比值比，0.05；95%置信区间，0.004-0.68）。对于既往未接受治疗或对 UDCA 无应答的患者，UDCA 联合免疫抑制治疗有效率为 73%。存在晚期纤维化与 UDCA 联合免疫抑制治疗无应答相关（P=0.003；比值比，0.13；95%置信区间，0.03-0.48）。二线免疫抑制剂（环孢素、他克莫司和霉酚酸酯）使对初始免疫抑制无应答的患者中有 54%生化缓解。4 例 PBC-AIH 患者接受了肝移植。5 例患者在随访期间死亡（3 例死于与肝脏相关的原因）。
在一项对 PBC-AIH 患者进行的大型回顾性研究中，单用 UDCA 对大多数伴有严重界面肝炎的患者未能产生生化应答；这些患者需要额外的免疫抑制治疗。对于对常规免疫抑制无应答的患者，二线免疫抑制剂对控制疾病活动有效。
