Section snippets

Low-to-moderate alcohol consumption is associated with increased fibrosis in MASLD

Marti-Aguado, Calleja and coworkers attempted to evaluate the prevalence and impact of different levels of alcohol consumption on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD). The authors found that obesity, diabetes and alcohol consumption were independently associated with both significant liver fibrosis and at-risk MASH. Low, moderate, and increased alcohol consumption were independently associated with at-risk MASH, while moderate intake and MetALD

Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation

Biliary complications are a major cause of morbidity and mortality in liver transplantation. Esser, Kilpatrick and coworkers investigated the role of the primary cilium, a highly specialised sensory organelle, in post-transplant biliary complications using human biopsies from 7 liver transplant recipients who developed biliary complications and 12 recipients without biliary complications. They generated murine models and used in vitro models of ischaemia, cellular senescence and primary cilia

Differing genetic variants associated with liver fat and their contrasting relationships with cardiovascular diseases and cancer

The numerous observational studies linking MASLD to the increased risk of cardiovascular diseases do not demonstrate causation because of potential selection bias, presence of confounding factors and reverse causation. Ahmed and coworkers conducted a genome-wide association study on 37,358 individuals from the UK Biobank to identify genetic variants associated with liver fat measured by MRI. They performed Mendelian randomisation analyses to investigate the causal relationships between elevated

Parasitic infections leave a durable mark on liver macrophages

Liver macrophages, particularly the tissue-resident Kupffer cell population, fulfill critical roles in fighting infectious diseases. Musrati, Stijlemans and coworkers used a curable mouse model of parasitic infection with the protozoan Trypanosoma brucei to study infection-associated changes in the hepatic macrophage pool. While the acute infection expectedly reshaped the hepatic macrophage pool, it also induced durable changes that persisted after cure. Specifically, the infection induced

Phase Ib/IIa randomised study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination in CHB

Tak WY, and coworkers studied a chimpanzee adenoviral vector (ChAdOx1-HBV) and a modified vaccinia Ankara boost (MVA-HBV) encoding polymerase, core, and S region from a consensus genotype C HBV (named VTP-300) in 55 patients with virally suppressed chronic hepatitis B (CHB) and HBsAg <4,000 IU. VTP-300 alone and in combination with low-dose nivolumab was well tolerated with no treatment-related serious adverse events. VTP-300 monotherapy induced CD4+ and CD8+ T cells and lowered HBsAg in a

Metabolic phenotyping of patients with ACLD for better characterisation of cirrhosis regression

Regression of cirrhosis has been observed in patients with viral and non-viral aetiologies of liver disease in whom the underlying cause of liver injury was effectively suppressed. However, the understanding of the factors contributing to reversibility of fibrosis and cirrhosis is limited. In this case-control pilot study, Mendoza and coworkers aim was to assess clinical factors, perform genotyping of known variants and comprehensive metabolic phenotyping in order to characterise the regression

Histology helps predict more aggressive recurrence after resection of liver cancer

Liver resection remains the preferred therapeutic option for hepatocellular carcinoma in most clinical scenarios where complete tumour elimination is the main objective and liver health status allows it. Tumour recurrence is nevertheless a frequent event, and the biological behaviour of the recurring tumour varies widely. Forner and coworkers retrospectively studied the clinical and pathological features linked to an aggressive recurrence (defined as those beyond Milan criteria) and poor

Patrizia Burra∗ at Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.

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低至中度饮酒与 MASLD 纤维化增加有关

Marti-Aguado、Calleja 及其同事试图评估不同饮酒水平的患病率和对代谢功能障碍相关脂肪性肝病 （MASLD） 严重程度的影响。作者发现，肥胖、糖尿病和饮酒与严重的肝纤维化和高危 MASH 独立相关。低、中和增加的酒精摄入量与高危 MASH 独立相关，而适度摄入量和 MetALD

初级纤毛作为肝移植中胆道损伤、衰老和再生之间的可靶向节点

胆道并发症是肝移植并发症和死亡的主要原因。Esser、Kilpatrick 及其同事使用 7 名出现胆道并发症的肝移植受者和 12 名没有胆道并发症的受者的人体活检，研究了初级纤毛（一种高度专业化的感觉细胞器）在移植后胆道并发症中的作用。他们生成了小鼠模型，并使用 了缺血、细胞衰老和初级纤毛的体外模型

与肝脏脂肪相关的不同遗传变异及其与心血管疾病和癌症的对比关系

许多将 MASLD 与心血管疾病风险增加联系起来的观察性研究并未证明因果关系，因为存在潜在的选择偏倚、混杂因素和反向因果关系。Ahmed 及其同事对来自英国生物样本库的 37,358 人进行了一项全基因组关联研究，以确定与通过 MRI 测量的肝脏脂肪相关的遗传变异。他们进行了孟德尔随机化分析，以研究升高

寄生虫感染在肝脏巨噬细胞上留下持久的印记

肝脏巨噬细胞，尤其是组织驻留的 Kupffer 细胞群，在对抗传染病中发挥着关键作用。Musrati、Stijlemans 及其同事使用原生动物布鲁氏锥虫寄生虫感染的可治愈小鼠模型来研究肝脏巨噬细胞池中与感染相关的变化。虽然急性感染意料之中地重塑了肝脏巨噬细胞池，但它也引起了治愈后持续存在的持久变化。具体来说，感染诱导了

CHB 异源 ChAdOx1-HBV/MVA-HBV 治疗性疫苗接种的 Ib/IIa 期随机研究

Tak WY 及其同事在 55 名病毒抑制的慢性乙型肝炎 （CHB） 和 HBsAg <4,000 IU 患者中研究了编码来自共有基因型 C HBV （命名为 VTP-300） 的黑猩猩腺病毒载体 （ChAdOx1-HBV） 和改良的牛痘安卡拉增强剂 （MVA-HBV） 和 S 区。VTP-300 单独使用和与低剂量 nivolumab 联合使用耐受性良好，无治疗相关的严重不良事件。VTP-300 单药治疗诱导 CD4+ 和 CD8+ T 细胞并降低 HBsAg

ACLD 患者的代谢表型分析有助于更好地描述肝硬化消退的特征

在病毒性和非病毒性肝病病因的患者中观察到肝硬化消退，其中肝损伤的潜在原因得到有效抑制。然而，对导致纤维化和肝硬化可逆性的因素的理解是有限的。在这项病例对照试点研究中，Mendoza 及其同事的目标是评估临床因素，对已知变异进行基因分型和全面的代谢表型，以表征回归

组织学有助于预测肝癌切除术后更具侵袭性的复发

在大多数以完全消除肿瘤为主要目标且肝脏健康状况允许的临床情况下，肝切除术仍然是肝细胞癌的首选治疗选择。然而，肿瘤复发是一个频繁的事件，并且复发性肿瘤的生物学行为差异很大。Forner 及其同事回顾性研究了与侵袭性复发（定义为超出 Milan 标准）和差

Patrizia Burra∗意大利帕多瓦帕多瓦大学医院外科、肿瘤学和胃肠病学系。