Stoelinga Anna E C, Biewenga Maaike, Drenth Joost P H, Verhelst Xavier, van der Meer Adriaan J P, de Boer Ynto S, Bouma Gerd, de Vries Elsemieke S, Verdonk Robert C, van der Berg Aad P, Brouwer Johannes T, Vanwolleghem Thomas, Lammers Wim, Beuers Ulrich, Sarasqueta Arantza Farina, Verheij Joanne, Roskams Tania, Crobach Stijn, Tushuizen Maarten E, van Hoek Bart
Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, the Netherlands.
Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre - location VUmc, Amsterdam, the Netherlands.
JHEP Rep. 2024 Jun 14;6(7):101088. doi: 10.1016/j.jhepr.2024.101088. eCollection 2024 Jul.
BACKGROUND & AIMS: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria.
Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC.
Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9-95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria ( 0.46 and 0.40, respectively) or from AIH ( 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation - not receiving immunosuppression - compared to those with AIH-PBC (65%; 95% CI 52.2-77.8% . 87%; 95% CI 83.2-90.8%; hazard ratio 0.52; 0.043).
In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy.
This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.
自身免疫性肝炎（AIH）和原发性胆汁性胆管炎（PBC）可共存于AIH-PBC中，需要免疫抑制和熊去氧胆酸（UDCA）联合治疗。巴黎标准常用于识别这些患者；然而，最佳诊断标准尚不清楚。我们旨在评估巴黎标准和张标准的应用及临床相关性。
纳入83例临床怀疑为AIH-PBC且接受联合治疗的患者。对组织学进行重新评估。将其特征和长期结局与AIH和PBC患者进行回顾性比较。
17例（24%）接受联合治疗的患者符合巴黎标准。52例患者（70%）符合张标准。与仅符合张标准的患者相比，符合巴黎标准和张标准的患者组织学上更常出现炎症和纤维化。AIH-PBC患者的10年无肝移植（LT）生存率为87.3%（95%CI 78.9-95.7%）。符合或不符合巴黎或张标准的患者与AIH患者之间无差异（分别为0.46和0.40以及0.086）。与AIH-PBC患者相比，PBC且有严重肝脏炎症且未接受免疫抑制的患者无LT生存率显著更低（65%；95%CI 52.2-77.8%对87%；95%CI 83.2-90.8%；风险比0.52；P=0.043）。
在本研究中，不符合巴黎或张标准的AIH-PBC患者常被诊断为AIH-PBC，并通过联合治疗成功治愈，结局相似。PBC且有肝脏炎症的患者无LT生存率比被诊断为AIH-PBC的患者更差。更多患者可能从联合治疗中获益。
本研究表明，接受免疫抑制剂和熊去氧胆酸联合治疗的AIH-PBC变异综合征患者通常不符合巴黎标准。然而，他们对治疗的反应和长期结局与符合诊断标准的患者相当。此外，与被诊断为AIH-PBC的患者相比，PBC且有肝脏炎症其他体征的患者长期结局更差。这些结果表明，更多具有AIH和PBC特征的患者可能从联合治疗中获益。基于我们的结果，我们呼吁该领域专家就AIH-PBC变异综合征的诊断和管理达成更好的共识。
