We thank Li et al. for their interest in our study on the overlap between primary biliary cholangitis (PBC) and metabolic dysfunction-associated steatotic liver disease (MASLD) [1]. Their letter highlights the role of visceral obesity, measured by computed tomography (CT), as a potential contributor to nonresponse to ursodeoxycholic acid (UDCA) in PBC patients [2]. We appreciate their work emphasising the role of visceral adiposity in MASLD and its relevance to PBC.

In our study, histologically proven hepatic steatosis was a key factor in worse PBC outcomes, including reduced response to UDCA. We agree that visceral fat, as a driver of hepatic steatosis, may play a crucial role [3]. While the authors used CT to quantify visceral adiposity, our study relied on liver biopsies for direct assessment of steatosis and fibrosis. Future studies integrating advanced imaging techniques like CT or MRI with histological data could better explore the interplay between visceral obesity, hepatic steatosis and PBC outcomes.

The authors highlight that visceral adiposity induces systemic inflammation and alters liver-adipose tissue interactions, potentially worsening MASLD and its impact on PBC. This aligns with findings linking visceral adiposity to increased immune-cell infiltration, particularly pro-inflammatory macrophages, which amplify inflammation [4, 5]. Our findings show that steatosis was independently associated with worse prognostic indices and higher liver-related mortality in PBC patients [1]. The systemic effects of visceral fat, including insulin resistance, dyslipidaemia and pro-inflammatory cytokine release, may worsen liver damage in PBC-MASLD overlap cases [5].

Our multivariate analysis adjusted for DM2, BMI, dyslipidaemia and other metabolic risk factors, yet steatosis remained an independent predictor of poor outcomes. It would be valuable to explore whether CT-measured visceral adiposity provides additional prognostic value beyond traditional risk factors and histology. However, both BMI and visceral fat measurements have limitations, as they may not correlate directly with hepatic fat content or liver inflammation. Hepatic fat is a superior biomarker for various conditions and more closely linked to advanced hepatic fibrosis and metabolic complications like insulin resistance, diabetes and increased VLDL-triglyceride secretion [6-8].

Li et al. used CT for visceral fat quantification, while this method provides robust data on adipose tissue distribution; it does not directly measure hepatic steatosis. Incorporating liver fat quantification, through MRI-derived proton density fat fraction or controlled attenuation parameter (CAP) using transient elastography, could further improve understanding of the relationship between visceral adiposity and hepatic outcomes in PBC [9, 10].

We appreciate the authors' suggestion to target visceral obesity as a therapeutic strategy in PBC. Lifestyle interventions, pharmacological approaches targeting visceral adiposity or combined treatments addressing both PBC and MASLD could offer significant benefits. Prospective studies evaluating these interventions are crucial for refining management strategies for PBC patients with metabolic dysfunction.

Finally, the letter by Li et al. highlights the PBC complexity in the context of visceral adiposity and MASLD. Their findings complement ours and emphasise the need for a multidimensional approach to managing PBC patients with metabolic comorbidities. Future collaborative efforts should integrate imaging, histological and clinical data to gain insights into this challenging patient population.

我们感谢 Li 等人对我们关于原发性胆汁性胆管炎 （PBC） 和代谢功能障碍相关脂肪性肝病 （MASLD） 之间重叠的研究的兴趣 [1]。他们的信强调了通过计算机断层扫描 （CT） 测量的内脏肥胖是 PBC 患者对熊去氧胆酸 （UDCA） 无反应的潜在原因 [2]。我们欣赏他们的工作，强调内脏肥胖在 MASLD 中的作用及其与 PBC 的相关性。

在我们的研究中，组织学证实的肝脂肪变性是 PBC 结果恶化的关键因素，包括对 UDCA 的反应降低。我们同意内脏脂肪作为肝脂肪变性的驱动因素，可能起着至关重要的作用 [3]。虽然作者使用 CT 来量化内脏肥胖，但我们的研究依赖于肝活检来直接评估脂肪变性和纤维化。未来的研究将 CT 或 MRI 等先进成像技术与组织学数据相结合，可以更好地探索内脏肥胖、肝脂肪变性和 PBC 结果之间的相互作用。

作者强调，内脏肥胖会诱发全身炎症并改变肝脏-脂肪组织相互作用，可能会使 MASLD 及其对 PBC 的影响恶化。这与将内脏肥胖与免疫细胞浸润增加联系起来的发现一致，特别是促炎巨噬细胞，它放大了炎症 [4， 5]。我们的研究结果表明，脂肪变性与 PBC 患者较差的预后指数和较高的肝脏相关死亡率独立相关 [1]。内脏脂肪的全身效应，包括胰岛素抵抗、血脂异常和促炎细胞因子释放，可能会加重 PBC-MASLD 重叠病例的肝损伤 [5]。

我们的多变量分析调整了 DM2 、 BMI 、血脂异常和其他代谢危险因素，但脂肪变性仍然是不良结局的独立预测因子。探索 CT 测量的内脏肥胖是否提供传统风险因素和组织学之外的额外预后价值将很有价值。然而，BMI 和内脏脂肪测量都有局限性，因为它们可能与肝脏脂肪含量或肝脏炎症没有直接关系。肝脏脂肪是各种疾病的优越生物标志物，与晚期肝纤维化和代谢并发症（如胰岛素抵抗、糖尿病和 VLDL-甘油三酯分泌增加）更密切相关 [6-8]。

Li 等人使用 CT 进行内脏脂肪定量，而这种方法提供了有关脂肪组织分布的可靠数据;它不直接测量肝脏脂肪变性。通过 MRI 衍生的质子密度脂肪分数或使用瞬时弹性成像的受控衰减参数 （CAP） 进行肝脏脂肪量化，可以进一步提高对 PBC 内脏肥胖与肝脏结局之间关系的理解 [9， 10]。

我们感谢作者关于将内脏肥胖作为 PBC 治疗策略的建议。生活方式干预、针对内脏肥胖的药物方法或针对 PBC 和 MASLD 的联合治疗可能会带来显着的好处。评估这些干预措施的前瞻性研究对于完善代谢功能障碍 PBC 患者的管理策略至关重要。

最后，Li 等人的信强调了内脏肥胖和 MASLD 背景下的 PBC 复杂性。他们的发现补充了我们的研究结果，并强调了采用多维方法来管理患有代谢合并症的 PBC 患者的必要性。未来的合作工作应整合成像、组织学和临床数据，以深入了解这一具有挑战性的患者群体。