Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Aliment Pharmacol Ther. 2011 Aug;34(3):335-43. doi: 10.1111/j.1365-2036.2011.04727.x. Epub 2011 Jun 12.
Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment.
To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes.
Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression.
Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001).
Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.
在接受泼尼松龙和硫唑嘌呤（AZA）治疗的自身免疫性肝炎患者中，有 20%出现治疗失败。目前尚无既定的二线治疗方法。
评估霉酚酸酯在自身免疫性肝炎和重叠综合征患者对 AZA 不耐受或 AZA 无反应后的二线治疗效果。
纳入荷兰自身免疫性肝炎组队列中的连续患者，该队列由 661 例自身免疫性肝炎或重叠综合征患者组成，这些患者对 AZA 不耐受或 AZA 无反应，过去或现在使用过霉酚酸酯。霉酚酸酯治疗的主要终点是生化缓解。次要终点是生化反应（无缓解）、治疗失败和疾病进展的预防。
共纳入 45 例接受霉酚酸酯治疗的患者。在 AZA 无反应组中，自身免疫性肝炎的缓解或应答率分别为 13%和 27%，而在 AZA 不耐受组中分别为 67%和 0%（P=0.008）。在重叠综合征中，缓解或应答率分别为 57%和 14%，在 AZA 无反应组中为 63%和 25%，在 AZA 不耐受组中为 25%和 13%（无统计学差异）；有 33%的患者出现副作用，有 13%的患者停止使用霉酚酸酯。总体上有 38%的患者治疗失败；在自身免疫性肝炎 AZA 无反应组中这一比例为 60%。失代偿性肝硬化、肝移植和死亡仅见于自身免疫性肝炎 AZA 无反应组（P<0.001）。
霉酚酸酯在大多数对 AZA 不耐受和 AZA 无反应的自身免疫性肝炎和重叠综合征患者中诱导缓解或缓解，无论对 AZA 是否不耐受或无反应。在 AZA 无反应的自身免疫性肝炎中，霉酚酸酯的疗效较差。
