Hepatobiliary & Pancreatic Diseases International最新文献_第10页

The outcomes and mechanisms of chronic hepatitis B complicated by metabolic dysfunction-associated steatotic liver disease 慢性乙型肝炎合并代谢功能障碍相关脂肪变性肝病的结局和机制

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-05-02 DOI: 10.1016/j.hbpd.2025.04.007

Mao-Ping Li , Kai-Zhong Luo

Background

In recent years, the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, given the substantial global prevalence of chronic hepatitis B (CHB), instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios. Both conditions can lead to liver fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). However, the intricacies of the dual etiology, consequential outcomes, and associated risks of CHB concurrent with MASLD are still not fully understood.

Data sources

A literature search was conducted on PubMed for articles published up to March 2024. The search keywords included nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic hepatitis B, liver fibrosis, hepatocellular carcinoma, nuclear factor erythroid 2-related factor 2, and oxidative stress.

Results

This review examined recent studies on the interplay between MASLD and CHB. The coexistence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus (HBV) replication. Conversely, individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD. Nevertheless, these observations do not necessarily indicate universally positive outcomes. Indeed, MASLD and CHB may synergistically act as “co-conspirators” to exacerbate clinical manifestations, particularly liver fibrosis and HCC.

Conclusions

As our understanding of the interaction between steatosis and HBV infection becomes clearer, we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD. These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.

背景：近年来，肥胖和代谢综合征患病率的上升导致越来越多的个体发展为代谢功能障碍相关的脂肪变性肝病（MASLD）。此外，鉴于慢性乙型肝炎（CHB）在全球的普遍流行，MASLD与CHB共存的实例在临床场景中变得越来越普遍。这两种情况都可能导致肝纤维化、肝硬化和潜在的肝细胞癌（HCC）。然而，CHB合并MASLD的双重病因、后果和相关风险的复杂性仍未完全了解。数据来源：在PubMed上进行文献检索，检索截止到2024年3月发表的文章。搜索关键词包括非酒精性脂肪性肝病、非酒精性脂肪性肝炎、慢性乙型肝炎、肝纤维化、肝细胞癌、核因子2相关因子2和氧化应激。结果：本文回顾了最近关于MASLD和CHB相互作用的研究。这些条件的共存可能促进乙型肝炎表面抗原从血清中清除，并阻碍乙型肝炎病毒（HBV）的复制。相反，与仅患有NAFLD的个体相比，同时患有CHB的个体往往表现出较低的高甘油三酯血症发生率和血清甘油三酯水平降低。然而，这些观察结果并不一定表明普遍的积极结果。事实上，MASLD和CHB可能协同起“同谋”作用，加剧临床表现，特别是肝纤维化和HCC。结论：随着我们对脂肪变性与HBV感染之间相互作用的了解越来越清楚，我们可以更好地评估并发CHB和MASLD患者发生晚期肝病的风险。这些见解将有助于探索潜在的潜在机制，并可能为改善患者预后提供建议。

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引用次数: 0

Sodium butyrate ameliorates liver fibrosis in metabolic dysfunction-associated steatohepatitis rats via miR-155-5p/SOCS1/PDGF signaling pathway 丁酸钠通过miR-155-5p/SOCS1/PDGF信号通路改善代谢功能障碍相关脂肪性肝炎大鼠肝纤维化。

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-04-30 DOI: 10.1016/j.hbpd.2025.04.006

Lei-Jie Huang , Meng-Yu Wang , Feng-Zhi Xin, Rui-Xu Yang, Jing Zeng, Tian-Yi Ren, Jian-Gao Fan

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease worldwide. Recently, short-chain fatty acids (SCFAs), as metabolites of intestinal flora, have been found to participate in the progression of MASLD. Sodium butyrate (NaB), one of the most important SCFAs, shows therapeutic potentials in MASLD and its mechanisms have not been fully understood. The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis (MASH) associated fibrosis as well as the underlying mechanisms.

Methods

Male Sprague-Dawley rats were randomly assigned to three groups: (i) control group, standard chow for 24 weeks; (ii) HFD group, high-fat and high-cholesterol diet (HFD) for 24 weeks; and (iii) HFD + NaB group, HFD for 24 weeks and NaB gavage for the last 16 weeks. Body weight, liver index (liver weight/body weight × 100%), serum parameters, and liver histology were analyzed to evaluate MASH and fibrosis severity. AML12, RAW264.7 and LX2 cell lines were used for in vitro study.

Results

Compared to MASH rats with fibrosis induced by 24-week HFD, NaB intervention alleviated the degree of hepatic steatosis, inflammation, hepatocyte ballooning, and fibrosis. Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats, and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1 (SOCS1) in both hepatocytes and hepatic stellate cells (HSCs) were blunted when they were treated with NaB. Furthermore, NaB also significantly decreased the production of platelet-derived growth factor-BB (PDGF-BB), a pro-fibrotic mediator, in hepatocytes. NaB treatment on AML12 cells markedly impaired the proliferation ability of co-cultured LX2 cells. Moreover, NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.

Conclusions

NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats. NaB might be a potential agent for the treatment of fibrosis in patients with MASH.

背景：代谢功能障碍相关脂肪变性肝病（MASLD）是世界范围内慢性肝病的主要原因之一。最近，短链脂肪酸（SCFAs）作为肠道菌群的代谢物被发现参与了MASLD的进展。丁酸钠（NaB）是最重要的scfa之一，在MASLD中显示出治疗潜力，其机制尚未完全了解。本研究旨在探讨NaB对代谢功能障碍相关脂肪性肝炎（MASH）相关纤维化的影响及其潜在机制。方法：雄性Sprague-Dawley大鼠随机分为3组：(i)对照组，标准喂养24周；（ii） HFD组，高脂高胆固醇饮食（HFD） 24周；（iii） HFD + NaB组，HFD第24周，NaB灌胃后16周。分析体重、肝脏指数（肝脏重量/体重× 100 %）、血清参数和肝脏组织学来评估MASH和纤维化严重程度。采用AML12、RAW264.7和LX2细胞系进行体外研究。结果：与24周HFD诱导纤维化的MASH大鼠相比，NaB干预可减轻肝脂肪变性、炎症、肝细胞球囊化和纤维化程度。进一步的机制研究表明，添加NaB可显著降低MASH大鼠肝脏和血清中miR-155-5p的水平，并且在NaB处理后，miR-155-5p对肝细胞和肝星状细胞（hsc）中细胞因子信号传导1 （SOCS1）抑制因子的抑制作用减弱。此外，NaB还显著降低肝细胞中促纤维化介质血小板衍生生长因子- bb （PDGF-BB）的产生。NaB对AML12细胞的处理显著降低了共培养LX2细胞的增殖能力。此外，NaB干预或miR-155-5p模拟物也会干扰LX2细胞中细胞外调节的蛋白激酶信号传导。结论：NaB干预通过miR-155-5p/SOCS1/PDGF信号通路抑制hsc活化，从而缓解MASH大鼠的纤维化。NaB可能是治疗MASH患者纤维化的潜在药物。

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引用次数: 0

Fluid therapy in acute pancreatitis comparing balanced solutions and normal saline: A systematic review, meta-analysis and trial sequential analysis 比较平衡溶液和生理盐水对急性胰腺炎的液体治疗：一项系统回顾、荟萃分析和试验序列分析。

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-04-22 DOI: 10.1016/j.hbpd.2025.04.002

Lin Gao , Hsiang-Wei Wang , Zi-Rui Liu , Yi-Zhen Xu , Lu Ke , Wei-Qin Li , John A Windsor

Background

Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pancreatitis (AP), with normal saline (NS) and lactate Ringer’s (LR) used most often. Evidence based recommendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials (RCTs). We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions (BS) versus NS on patient-centered clinical outcomes in AP.

Methods

From four databases searched up to October 2024, we included only RCTs of adult patients with AP that compared the use of BS (including LR, acetate Ringer’s, etc.) with NS. The primary outcome was the disease advances from AP to moderately severe and severe AP (MSAP/SAP). Trial sequential analyses (TSA) were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence.

Results

Six RCTs were identified and included, involving 260 patients treated with BS and 298 patients with NS. Patients who received the BS had less MSAP/SAP [odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.29 to 0.85, P = 0.01, I² = 0%; 5 studies, 299 patients], reduced the need of ICU admission (OR = 0.60, 95% CI: 0.39 to 0.93, P = 0.02, I² = 0%; 5 studies, 507 patients) and shorter length of hospital stay [mean difference (MD) = -0.88, 95% CI:-1.48 to -0.28, P = 0.004, I² = 0%; 6 studies, 558 patients; confirmed by TSA with high certainty] compared with those who received NS. The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias, imprecision and inconsistency.

Conclusions

BS, compared with NS, was associated with improved clinical outcomes in patients with AP. However, given the moderate to low quality of evidence for most of the outcomes assessed, further trials are warranted.

背景：等渗晶体液被推荐为急性胰腺炎（AP）液体治疗的首选，其中最常用的是生理盐水（NS）和乳酸林格液（LR）。基于证据的液体类型建议是相互矛盾的，通常来自小型单中心随机对照试验（rct）。因此，我们进行了系统回顾和荟萃分析，比较平衡溶液（BS）和NS对AP患者中心临床结果的影响。方法：从四个数据库检索到2024年10月，我们只纳入了成年AP患者的rct，比较BS（包括LR，醋酸林格等）与NS的使用。主要转归是AP进展为中重度和重度AP （MSAP/SAP）。采用试验序贯分析（TSA）来控制i型和ii型错误，采用分级推荐评估、发展和评价（GRADE）来评估证据质量。结果：确定并纳入6项随机对照试验，涉及260例BS患者和298例NS患者。接受BS的患者MSAP/SAP较低[比值比(OR) = 0.50, 95 %置信区间（CI）： 0.29 ~ 0.85, P = 0.01, I2 = 0 %；5项研究，299例患者]，减少了ICU住院需求(OR = 0.60, 95 % CI: 0.39 ~ 0.93, P = 0.02, I2 = 0 %；5项研究，507例患者)和更短的住院时间[平均差异(MD) = -0.88, 95 % CI:1.48 ~ -0.28, P = 0.004, I2 = 0 %；6项研究，558例患者；与接受NS治疗的患者相比。由于存在偏倚、不精确和不一致的风险，大多数临床结果的证据被评为中等至低。结论：与NS相比，BS与AP患者的临床结果改善相关。然而，鉴于大多数评估结果的证据质量为中等至低，进一步的试验是有必要的。

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引用次数: 0

Adiponectin alleviates inflammatory response in metabolic dysfunction-associated steatohepatitis by inhibiting NLRP3 inflammasome-mediated hepatocyte pyroptosis 脂联素通过抑制NLRP3炎性小体介导的肝细胞焦亡，减轻代谢功能障碍相关脂肪性肝炎的炎症反应。

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-04-21 DOI: 10.1016/j.hbpd.2025.04.004

Tie-Xiong Wu , Hua-Zhen Pang , Xu-Dong Liu , Li Liu , Yan-Fang Tang , Xue-Fei Luo , Xiao-Ke Ran

Background

Activation of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasomes induced by pyroptosis is crucial in metabolic dysfunction-associated steatohepatitis (MASH) progression. Adiponectin possesses an anti-inflammatory role in various liver diseases. This study aimed to evaluate the effects of adiponectin on MASH.

Methods

Adiponectin-mediated anti-inflammatory mechanisms, effects on pyroptosis-related proteins, and activation of NLRP3 inflammasomes were investigated using methionine-choline-deficient (MCD)-induced MASH murine model and in vitro models. The degree of MASH inflammation in liver tissue of C57BL/6J mice was assessed using histopathology. Enzyme-linked immunosorbent assay was performed to measure levels of inflammatory factors [interleukin-18 (IL-18), IL-1β, and tumor necrosis factor-α (TNF-α)] in mice serum and culture medium. Western blot and quantitative polymerase chain reaction were performed to analyze the expression of pyroptosis-related genes and proteins in liver tissues of mouse model and in vitro models. Macrophage recruitment in vitro was evaluated using co-culture of upper and lower chambers.

Results

MASH developed in MCD diet mice [metabolic dysfunction-associated steatotic liver disease (MASLD) activity score = 6] but not in methionine-choline-sufficient (MCS) diet mice (MASLD activity score = 3). Compared to MCS-fed mice, MCD-fed mice showed increased serum levels of aspartate aminotransferase, IL-18, IL-1β, and TNF-α and higher MASLD activity score (P < 0.001). Adiponectin inhibited these increases (P < 0.05) and suppressed mRNA and protein levels of NLRP3, gasdermin-D (GSDMD), and GSDMD-N in liver tissues (P < 0.05). In vitro, lipopolysaccharide (LPS)/palmitic acid (PA) increased the levels of IL-18, IL-1β, and TNF-α, mRNA expressions of CASP1 and GSDMD, and production of CASP1, NLRP3, GSDMD, and GSDMD-N (P < 0.01). Adiponectin reduced the levels of these inflammatory factors and downregulated the mRNA expression and protein generation of pyroptosis-related markers (P < 0.05). HepG2 cells pretreated with LPS/PA recruited more J774A.1 cells (P < 0.001) and increased inflammatory factor secretion by J774A.1 cells (P < 0.001). Adiponectin inhibited this recruitment and reduced inflammatory factor secretion (P < 0.001).

Conclusions

Adiponectin inhibits hepatocyte pyroptosis by reducing the production and activation of NLRP3 inflammasomes, CASP1, and GSDMD, thus improving the inflammatory response in MASH and possibly delaying or reversing MASLD progression.

背景：焦亡诱导NLRP3 （NOD-， LRR-和pyrin结构域蛋白3）炎症小体的激活在代谢功能障碍相关脂肪性肝炎（MASH）进展中至关重要。脂联素在多种肝脏疾病中具有抗炎作用。本研究旨在探讨脂联素对MASH的影响。方法：采用蛋氨酸胆碱缺乏（MCD）诱导的MASH小鼠模型和体外模型，研究脂联素介导的抗炎机制、对焦解热相关蛋白的影响以及NLRP3炎症小体的激活。采用组织病理学方法评价C57BL/6J小鼠肝组织MASH炎症程度。采用酶联免疫吸附法测定小鼠血清和培养基中炎症因子[白细胞介素-18 （IL-18）、IL-1β和肿瘤坏死因子-α (TNF-α)]的水平。采用Western blot和定量聚合酶链反应分析小鼠模型和离体模型肝组织中焦热相关基因和蛋白的表达。采用上下腔共培养法评价巨噬细胞体外募集情况。结果：MCD饮食小鼠（代谢功能障碍相关脂肪变性肝病（MASLD）活动评分= 6）发生MASH，而蛋氨酸-胆碱充足（MCS）饮食小鼠（MASLD活动评分= 3）没有发生MASH。与mcs相比，mcd小鼠血清中天冬氨酸转氨酶、IL-18、IL-1β和TNF-α水平升高，MASLD活性评分升高（P < 0.001）。脂联素抑制了肝组织NLRP3、GSDMD和GSDMD- n mRNA和蛋白水平的升高（P < 0.05）。在体外实验中，脂多糖(LPS)/棕榈酸（PA）增加了IL-18、IL-1β和TNF-α水平，增加了CASP1和GSDMD mRNA的表达，增加了CASP1、NLRP3、GSDMD和GSDMD- n的产生（P < 0.01）。脂联素可降低上述炎症因子水平，下调热死相关标志物mRNA表达和蛋白生成（P < 0.05）。LPS/PA预处理的HepG2细胞募集了更多的J774A。J774A增加了炎性因子的分泌（P < 0.001）。1个细胞（P < 0.001）。脂联素抑制这种募集并减少炎症因子的分泌（P < 0.001）。结论：脂联素通过减少NLRP3炎性小体、CASP1和GSDMD的产生和激活来抑制肝细胞焦亡，从而改善MASH的炎症反应，可能延缓或逆转MASLD的进展。

{"title":"Adiponectin alleviates inflammatory response in metabolic dysfunction-associated steatohepatitis by inhibiting NLRP3 inflammasome-mediated hepatocyte pyroptosis","authors":"Tie-Xiong Wu , Hua-Zhen Pang , Xu-Dong Liu , Li Liu , Yan-Fang Tang , Xue-Fei Luo , Xiao-Ke Ran","doi":"10.1016/j.hbpd.2025.04.004","DOIUrl":"10.1016/j.hbpd.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div>Activation of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasomes induced by pyroptosis is crucial in metabolic dysfunction-associated steatohepatitis (MASH) progression. Adiponectin possesses an anti-inflammatory role in various liver diseases. This study aimed to evaluate the effects of adiponectin on MASH.</div></div><div><h3>Methods</h3><div>Adiponectin-mediated anti-inflammatory mechanisms, effects on pyroptosis-related proteins, and activation of NLRP3 inflammasomes were investigated using methionine-choline-deficient (MCD)-induced MASH murine model and <em>in vitro</em> models. The degree of MASH inflammation in liver tissue of C57BL/6J mice was assessed using histopathology. Enzyme-linked immunosorbent assay was performed to measure levels of inflammatory factors [interleukin-18 (IL-18), IL-1β, and tumor necrosis factor-α (TNF-α)] in mice serum and culture medium. Western blot and quantitative polymerase chain reaction were performed to analyze the expression of pyroptosis-related genes and proteins in liver tissues of mouse model and <em>in vitro</em> models. Macrophage recruitment <em>in vitro</em> was evaluated using co-culture of upper and lower chambers.</div></div><div><h3>Results</h3><div>MASH developed in MCD diet mice [metabolic dysfunction-associated steatotic liver disease (MASLD) activity score = 6] but not in methionine-choline-sufficient (MCS) diet mice (MASLD activity score = 3). Compared to MCS-fed mice, MCD-fed mice showed increased serum levels of aspartate aminotransferase, IL-18, IL-1β, and TNF-α and higher MASLD activity score (<em>P</em> < 0.001). Adiponectin inhibited these increases (<em>P</em> < 0.05) and suppressed mRNA and protein levels of NLRP3, gasdermin-D (GSDMD), and GSDMD-N in liver tissues (<em>P</em> < 0.05). <em>In vitro</em>, lipopolysaccharide (LPS)/palmitic acid (PA) increased the levels of IL-18, IL-1β, and TNF-α, mRNA expressions of CASP1 and GSDMD, and production of CASP1, NLRP3, GSDMD, and GSDMD-N (<em>P</em> < 0.01). Adiponectin reduced the levels of these inflammatory factors and downregulated the mRNA expression and protein generation of pyroptosis-related markers (<em>P</em> < 0.05). HepG2 cells pretreated with LPS/PA recruited more J774A.1 cells (<em>P</em> < 0.001) and increased inflammatory factor secretion by J774A.1 cells (<em>P</em> < 0.001). Adiponectin inhibited this recruitment and reduced inflammatory factor secretion (<em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Adiponectin inhibits hepatocyte pyroptosis by reducing the production and activation of NLRP3 inflammasomes, CASP1, and GSDMD, thus improving the inflammatory response in MASH and possibly delaying or reversing MASLD progression.</div></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 4","pages":"Pages 433-443"},"PeriodicalIF":3.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges in retrohepatic inferior vena cava reconstruction: The neocava technique 肝后下腔静脉重建的挑战：新腔静脉技术。

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-04-21 DOI: 10.1016/j.hbpd.2025.04.003

Maximilien Roumain , Maxime Foguenne , Lancelot Marique , Olga Ciccarelli , Eliano Bonaccorsi-Riani , Thomas Bidoul , Laurent Coubeau

引用次数: 0

Postoperative regular follow-up in hepatocellular carcinoma: Transforming early detection into survival gains 肝细胞癌术后定期随访：将早期发现转化为生存率提高。

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-04-09 DOI: 10.1016/j.hbpd.2025.04.001

Alfred Wei Chieh Kow

引用次数: 0

Impact of robotic donor partial hepatectomy on male sexual function: A prospective cohort study 机器人供体部分肝切除术对男性性功能的影响：一项前瞻性队列研究。

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-03-27 DOI: 10.1016/j.hbpd.2025.03.004

Raouf M Seyam , Sultan S Almaiman , Mohamed S Kattan , Said A Kattan , Dieter C Broering , Waleed M Altaweel

引用次数: 0

Adjuvant lenvatinib in combination with transarterial chemoembolization for hepatocellular carcinoma patients with high risk of postoperative recurrence: A multicenter prospective cohort study 辅助lenvatinib联合经动脉化疗栓塞治疗术后复发高危肝癌患者：一项多中心前瞻性队列研究

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-03-26 DOI: 10.1016/j.hbpd.2025.03.001

Jin-Hong Chen , Lu Lu , Xiao-Yun Zhang , Bang-De Xiang , Xiao Xu , Xiang-Cheng Li , Zhi-Yong Huang , Tian-Fu Wen , Liu-Ping Luo , Jing Huang , Jian-Hong Zhong , Zhi-Kun Liu , Chang-Xian Li , Xin Long , Wen-Wei Zhu , Xin Yang , Chao-Qun Wang , Hu-Liang Jia , Ju-Bo Zhang , Yong-Yi Zeng , Lun-Xiu Qin

Background

The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma (HCC). This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization (TACE) as an adjuvant therapy in HCC patients with high risk of recurrence.

Methods

Patients were enrolled from eight hepatobiliary centers in China. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS) and safety. Additionally, propensity score matching (PSM) and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion. The adverse events (AEs) were recorded throughout the study. The study was registered at ClinicalTrials.gov (NCT03838796).

Results

A total of 297 patients were enrolled, with 147 in the LEN + TACE group and 150 in the TACE group. Before PSM, the LEN + TACE group achieved significantly better DFS than the TACE group (19.0 vs. 10.0 months, P = 0.011). PSM analysis identified 111 matched pairs. After PSM, the LEN + TACE group also showed better DFS (19.0 vs. 9.0 months, P = 0.018). Other three propensity score analyses yielded similar DFS benefit tendency. Furthermore, favorable OS was also obtained in the LEN + TACE group before PSM. Lenvatinib related AEs of grade 3 or 4 occurred in 28.6% of the patients in the LEN + TACE group.

Conclusions

Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence, which could significantly prolong DFS and potentially OS with a manageable safety profile.

背景：肝细胞癌（HCC）术后高复发率阻碍了患者的生存。本前瞻性队列研究旨在评估lenvatinib +经动脉化疗栓塞（TACE）作为HCC高复发风险患者辅助治疗的有效性和安全性。方法：患者来自中国8个肝胆中心。主要终点为无病生存期（DFS）。次要终点是总生存期（OS）和安全性。此外，通过倾向得分匹配（PSM）和其他三种倾向得分分析来平衡潜在的基线偏差，以验证结论。在整个研究过程中记录不良事件（ae）。该研究已在ClinicalTrials.gov注册（NCT03838796）。结果：共纳入297例患者，其中LEN + TACE组147例，TACE组150例。PSM前，LEN + TACE组的DFS显著优于TACE组（19.0个月vs 10.0个月，P = 0.011）。PSM分析鉴定出111对配对。PSM后，LEN + TACE组也表现出更好的DFS（19.0比9.0个月，P = 0.018）。其他三种倾向得分分析也产生了类似的DFS获益趋势。此外，LEN + TACE组在PSM前也获得了良好的OS。LEN + TACE组中28.6%的患者发生Lenvatinib相关的3级或4级ae。结论：lenvatinib + TACE可能是一种有希望的HCC复发高风险患者的辅助治疗方法，可以显著延长DFS和潜在的OS，且安全性可控。

{"title":"Adjuvant lenvatinib in combination with transarterial chemoembolization for hepatocellular carcinoma patients with high risk of postoperative recurrence: A multicenter prospective cohort study","authors":"Jin-Hong Chen , Lu Lu , Xiao-Yun Zhang , Bang-De Xiang , Xiao Xu , Xiang-Cheng Li , Zhi-Yong Huang , Tian-Fu Wen , Liu-Ping Luo , Jing Huang , Jian-Hong Zhong , Zhi-Kun Liu , Chang-Xian Li , Xin Long , Wen-Wei Zhu , Xin Yang , Chao-Qun Wang , Hu-Liang Jia , Ju-Bo Zhang , Yong-Yi Zeng , Lun-Xiu Qin","doi":"10.1016/j.hbpd.2025.03.001","DOIUrl":"10.1016/j.hbpd.2025.03.001","url":null,"abstract":"<div><h3>Background</h3><div>The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma (HCC). This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization (TACE) as an adjuvant therapy in HCC patients with high risk of recurrence.</div></div><div><h3>Methods</h3><div>Patients were enrolled from eight hepatobiliary centers in China. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS) and safety. Additionally, propensity score matching (PSM) and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion. The adverse events (AEs) were recorded throughout the study. The study was registered at ClinicalTrials.gov (NCT03838796).</div></div><div><h3>Results</h3><div>A total of 297 patients were enrolled, with 147 in the LEN + TACE group and 150 in the TACE group. Before PSM, the LEN + TACE group achieved significantly better DFS than the TACE group (19.0 vs. 10.0 months, <em>P</em> = 0.011). PSM analysis identified 111 matched pairs. After PSM, the LEN + TACE group also showed better DFS (19.0 vs. 9.0 months, <em>P</em> = 0.018). Other three propensity score analyses yielded similar DFS benefit tendency. Furthermore, favorable OS was also obtained in the LEN + TACE group before PSM. Lenvatinib related AEs of grade 3 or 4 occurred in 28.6% of the patients in the LEN + TACE group.</div></div><div><h3>Conclusions</h3><div>Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence, which could significantly prolong DFS and potentially OS with a manageable safety profile.</div></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 3","pages":"Pages 277-285"},"PeriodicalIF":3.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of compliance to postoperative regular follow-up on long-term prognosis after curative resection for hepatocellular carcinoma: A multicenter analysis 遵守术后定期随访对肝细胞癌根治性切除术后长期预后的影响：一项多中心分析。

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-03-18 DOI: 10.1016/j.hbpd.2025.03.003

Lan-Qing Yao , Jin-Bo Gong , Lei Cai , Li-Hui Gu , Ying-Jian Liang , Hong-Wei Guo , Kong-Ying Lin , Zi-Qiang Li , Qi-Xuan Zheng , Ya-Hao Zhou , Ting-Hao Chen , Zhong Chen , Hong Wang , Han Liu , Han Wu , Timothy M Pawlik , Feng Shen , Eric CH Lai , Tian Yang

Background

Despite advances in surgical treatment, high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.

Methods

This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers. Patients were stratified into a regular follow-up group (follow-up every 2–3 months for the first 2 years and every 3–6 months thereafter) and an irregular/no follow-up group. Overall survival (OS), time to recurrence (TTR), and post-recurrence survival (PRS) were compared between the two groups.

Results

Among 1544 patients, 786 (50.9%) underwent regular follow-up during postoperative follow-up. The regular follow-up group had better OS (median: 113.4 vs. 94.5 months, P = 0.010) and PRS (median: 37.9 vs. 16.3 months, P < 0.001) than the irregular/no follow-up group, although TTR was comparable (median: 61.4 vs. 66.2 months, P = 0.161). Furthermore, patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence (41.6% vs. 50.4%, P = 0.013) and were more likely to receive curative treatments for recurrence (56.1% vs. 49.3%, P = 0.061). On multivariate analysis, compliance to regular follow-up was an independent factor associated with better OS [hazard ratio (HR) = 0.777, 95% confidence interval (CI): 0.663–0.910, P = 0.002] and PRS (HR = 0.523, 95% CI: 0.428–0.638, P < 0.001).

Conclusions

Compliance to regular follow-up improved OS and PRS after curative resection for HCC, highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.

背景：尽管手术治疗取得了进展，但术后高复发仍然是肝细胞癌（HCC）患者面临的挑战。本研究旨在探讨接受根治性肝细胞癌切除术患者的定期随访依从性与长期肿瘤预后之间的关系。方法：这项多中心研究纳入了2012年1月至2021年12月在12个肝脏手术中心接受早期HCC根治性切除术的患者。将患者分为常规随访组（前2年每2-3个月随访一次，此后每3-6个月随访一次）和不定期/无随访组。比较两组患者的总生存期（OS）、复发时间（TTR）和复发后生存期（PRS）。结果：1544例患者中，786例（50.9 %）在术后随访中接受了常规随访。常规随访组的OS（中位数：113.4个月vs 94.5个月，P = 0.010）和PRS（中位数：37.9个月vs 16.3个月，P < 0.001）优于不规则/无随访组，尽管TTR相当（中位数：61.4个月vs 66.2个月，P = 0.161）。此外，常规随访组患者的肿瘤复发超过米兰标准的发生率较低（41.6 %对50.4 %,P = 0.013），更有可能接受治愈性复发治疗（56.1 %对49.3 %,P = 0.061）。在多因素分析中，定期随访的依从性是较好的OS[风险比(HR) = 0.777, 95 %可信区间（CI）： 0.663-0.910, P = 0.002]和PRS （HR = 0.523, 95 % CI: 0.428-0.638, P < 0.001）的独立因素。结论：术后定期随访可提高HCC根治性切除术后的OS和PRS，突出了术后定期随访对早期发现复发和及时干预的重要性。

{"title":"Impact of compliance to postoperative regular follow-up on long-term prognosis after curative resection for hepatocellular carcinoma: A multicenter analysis","authors":"Lan-Qing Yao , Jin-Bo Gong , Lei Cai , Li-Hui Gu , Ying-Jian Liang , Hong-Wei Guo , Kong-Ying Lin , Zi-Qiang Li , Qi-Xuan Zheng , Ya-Hao Zhou , Ting-Hao Chen , Zhong Chen , Hong Wang , Han Liu , Han Wu , Timothy M Pawlik , Feng Shen , Eric CH Lai , Tian Yang","doi":"10.1016/j.hbpd.2025.03.003","DOIUrl":"10.1016/j.hbpd.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Despite advances in surgical treatment, high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.</div></div><div><h3>Methods</h3><div>This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers. Patients were stratified into a regular follow-up group (follow-up every 2–3 months for the first 2 years and every 3–6 months thereafter) and an irregular/no follow-up group. Overall survival (OS), time to recurrence (TTR), and post-recurrence survival (PRS) were compared between the two groups.</div></div><div><h3>Results</h3><div>Among 1544 patients, 786 (50.9%) underwent regular follow-up during postoperative follow-up. The regular follow-up group had better OS (median: 113.4 vs. 94.5 months, <em>P</em> = 0.010) and PRS (median: 37.9 vs. 16.3 months, <em>P</em> < 0.001) than the irregular/no follow-up group, although TTR was comparable (median: 61.4 vs. 66.2 months, <em>P</em> = 0.161). Furthermore, patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence (41.6% vs. 50.4%, <em>P</em> = 0.013) and were more likely to receive curative treatments for recurrence (56.1% vs. 49.3%, <em>P</em> = 0.061). On multivariate analysis, compliance to regular follow-up was an independent factor associated with better OS [hazard ratio (HR) = 0.777, 95% confidence interval (CI): 0.663–0.910, <em>P</em> = 0.002] and PRS (HR = 0.523, 95% CI: 0.428–0.638, <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Compliance to regular follow-up improved OS and PRS after curative resection for HCC, highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.</div></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 3","pages":"Pages 261-268"},"PeriodicalIF":3.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Meetings and Courses 会议及课程

IF 3.6 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Hepatobiliary & Pancreatic Diseases International

Pub Date : 2025-03-18 DOI: 10.1016/S1499-3872(25)00039-6

引用次数: 0