Hepatoma Research最新文献

英文中文

Immunotherapy biomarkers for HCC: contemporary challenges and emerging opportunities. 肝癌免疫治疗生物标志物:当代挑战和新机遇

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2022.58

Sandi Kwee, Xin Chen

Clinical management of advanced unresectable HCC has indelibly changed with the advent of immune checkpoint inhibitor (ICI) antibody therapy. The CheckMate-040 multi-cohort trial first demonstrated the effectiveness of an anti-PD1 antibody (nivolumab) in patients with clinically advanced HCC previously treated with sorafenib, reporting an approximately 20% overall objective response rate in such patients [1] . Another anti-PD1 agent, pembrolizumab, demonstrated similar response rates in its phase 2 trial [2] , and both agents subsequently received accelerated regulatory approval for second-line systemic treatment of HCC. The CheckMate-040 trial later showed up to a 32% objective response rate in patients treated with nivolumab plus ipilimumab (an antibody targeting CTLA-4), leading to approval of this combination regimen for second-line therapy [3] . With regards to first-line treatment of locally advanced or metastatic and/or unresectable HCC, the IMbrave150 phase 3 randomized trial associated the combination of bevacizumab plus atezolizumab (an anti-PD-L1 antibody) with improved overall survival over first-line sorafenib, with an objective response rate of 30% (95%CI: 25%–35%) and median duration of response of 18.1 months based on a recent extended efficacy and safety analysis of the trial [4] . Although remarkable for the setting of advanced HCC, these findings congruously show that most patients eligible to receive ICI therapy will not experience an objective benefit and that predictive biomarkers of treatment response will be necessary to optimize the risk-benefit ratio of immunotherapy treatment in this setting. Notable efforts had been made to identify predictive biomarkers within the cohorts of these and other HCC immunotherapy trials. In the Keynote-040 trial, tumor PD-L1

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引用次数: 0

Histopathology of hepatocellular carcinoma - when and what 肝细胞癌的组织病理学-何时和什么

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2021.106

D. Gisder, A. Tannapfel, I. Tischoff

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

本综述的主题是肝细胞癌(HCC)何时需要进行肝脏活检，以及您将获得哪些信息。如果在临床上，影像学检查后HCC的鉴别诊断被建议，活检已经成为非肝硬化肝脏HCC的强制性诊断确认，在确定的治疗干预之前，以及在姑息治疗概念中。在肝病变伴非特征性造影剂摄取的情况下，应立即进行活检以确认HCC的诊断。诊断HCC后，评估治疗策略。此外，活检，或手术治疗的情况下，切除的组织，向我们展示了HCC的不同亚型，脂肪性肝炎亚型是最常见的，而富含淋巴细胞的亚型是最不常见的。根据WHO分级系统或Edmonson and Steiner分级系统确定HCC的组织学分级。通过活检，HCC可与肝内胆管癌或合并肝细胞-胆管癌或其他恶性肿瘤转移相鉴别，尤其是胃肠道转移。总之，活组织检查是HCC诊断的基础。

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引用次数: 7

Advances in Y-90 radioembolization for the treatment of hepatocellular carcinoma Y-90放射栓塞治疗肝癌的研究进展

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2021.122

A. Woerner, G. Johnson

Hepatocellular carcinoma remains a prominent cause of cancer-related mortality globally. Transarterial yttrium-90 radioembolization is a versatile therapy and plays an important role in the treatment of hepatocellular carcinoma. This review summarizes the establishment of radioembolization in the hepatocellular carcinoma treatment paradigm, treatment considerations across cancer stages, and recent advances in evidence.

肝细胞癌仍然是全球癌症相关死亡的主要原因。经动脉氚-90放射栓塞是一种多功能的治疗方法，在肝细胞癌的治疗中起着重要的作用。本文综述了肝细胞癌放射栓塞治疗模式的建立、不同癌症分期的治疗考虑以及证据的最新进展。

引用次数: 4

Promise and pitfalls of new viral biomarkers for hepatocellular carcinoma risk prediction in patients with chronic hepatitis B 慢性乙型肝炎患者肝细胞癌风险预测新病毒生物标志物的前景与缺陷

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2022.06

K. Zhou, N. Terrault

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

©作者2022。开放获取本文遵循知识共享署名4.0国际许可协议(https://creativecommons.org/licenses/by/4.0/)，该协议允许不受限制地使用、共享、改编、分发和复制，以任何媒介或格式，用于任何目的，甚至商业目的，只要您适当地注明原作者和来源，提供知识共享许可协议的链接，并注明是否进行了更改。

引用次数: 0

Association of human leukocyte antigen-DR-DQ-DP haplotypes with the risk of hepatitis B virus-related hepatocellular carcinoma 人白细胞抗原dr - dq - dp单倍型与乙型肝炎病毒相关肝细胞癌风险的关系

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2021.133

Yifan Chen, Jiansheng Lin, Yang Deng, Wenbin Liu, Zishuai Li, Xinyu Zhou, Shiliang Cai, R. Pu, Jianhua Yin, X. Tan, Jun Zhao, Xue Han, G. Cao

Aim: Genetic polymorphisms of human leukocyte antigen (HLA) class II molecules are associated with chronic hepatitis B virus (HBV) infection. We aimed to investigate the impacts of HLA-II haplotypes on viral evolution and the risks of HBV-caused liver diseases. Methods: HLA-DR-DQ-DP haplotypes were estimated in 1210 healthy controls, 296 HBV clearance subjects, 301 asymptomatic hepatitis B surface antigen carriers, 770 chronic hepatitis B patients, 443 HBV-related liver cirrhosis (LC) patients, and 1037 HBV-related hepatocellular carcinoma (HCC) patients. HBV mutations were determined by sequencing. The associations of HLA-DR-DQ-DP haplotypes with viral mutations and the risks of liver diseases were assessed by multivariate logistic regression. Results: Compared to HBV-free subjects, the haplotypes CCAACG, CCGACG, TCAATA, and TCGATA were associated with decreased HCC risk, with an odds ratio (OR) [95% confidence interval (CI)] of 0.62 (0.40-0.95), 0.60 (0.39-0.92), 0.73 (0.54-0.98), and 0.58 (0.42-0.78), respectively. CCAACG, CCGACG, and TCAATA were significantly associated with decreased frequencies of the HCC-risk HBV mutations: preS1 deletion, APOBEC-signature HBV mutations in the core promoter and preS regions, A51C/T, G104C/T, and G146C/T. TCGATA and TTAACG were associated with increased LC risk, with an OR (95%CI) of 1.54 (1.03-2.30) and 2.23 (1.50-3.33), respectively. However, TCGATA and TTAACG were not consistently associated with the cirrhosis-risk HBV mutations. Conclusion: CCAACG, CCGACG, and TCAATA are inversely associated with HCC risk, possibly because they are involved in creating an immune microenvironment attenuating the generation of HCC-risk HBV mutations. TCGATA and TTAACG might predispose the polarity of immunity towards Th17 isotype related to LC.

目的:人白细胞抗原(HLA)ⅱ类分子遗传多态性与慢性乙型肝炎病毒(HBV)感染相关。我们的目的是研究HLA-II单倍型对病毒进化和hbv引起的肝脏疾病风险的影响。方法:对1210名健康对照者、296名HBV清除者、301名无症状乙型肝炎表面抗原携带者、770名慢性乙型肝炎患者、443名HBV相关肝硬化(LC)患者和1037名HBV相关肝癌(HCC)患者进行HLA-DR-DQ-DP单倍型检测。通过测序确定HBV突变。通过多变量logistic回归评估HLA-DR-DQ-DP单倍型与病毒突变和肝脏疾病风险的关系。结果:与无hbv的受试者相比，单倍型CCAACG、CCGACG、TCAATA和TCGATA与HCC风险降低相关，比值比(OR)[95%可信区间(CI)]分别为0.62(0.40-0.95)、0.60(0.39-0.92)、0.73(0.54-0.98)和0.58(0.42-0.78)。CCAACG、CCGACG和TCAATA与hcc风险HBV突变频率降低显著相关:preS1缺失、核心启动子区和preS区apobecc特征HBV突变、A51C/T、G104C/T和G146C/T。TCGATA和TTAACG与LC风险增加相关，OR (95%CI)分别为1.54(1.03-2.30)和2.23(1.50-3.33)。然而，TCGATA和TTAACG与肝硬化风险HBV突变并不一致相关。结论:CCAACG、CCGACG和TCAATA与HCC风险呈负相关，可能是因为它们参与创造免疫微环境，减弱HCC风险HBV突变的产生。TCGATA和TTAACG可能使免疫倾向于与LC相关的Th17同型。

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引用次数: 1

Safety and efficacy of DEM-TACE performed with drug-eluting microspheres smaller than 300 μm in patients with HCC and TIPS 小于300 μm的药物洗脱微球在HCC和TIPS患者中进行DEM-TACE的安全性和有效性

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2021.143

P. Lucatelli, Simone Zilahi De Gyurgyokai, G. De Rubeis, R. Argirò, Simone Ciaglia, B. Rocco, F. Ferri, S. Parisse, M. Forlino, A. Cannavale, F. Basilico, P. Nardis, M. Corona, V. Cantisani, C. Catalano

Aim: Safety and efficacy evidence of drug-eluting-microspheres trans-arterial chemoembolization (DEM-TACE) in patients with hepatocellular carcinoma (HCC) and trans-jugular intrahepatic portosystemic shunt (TIPS) is lacking. The aim of this retrospective study was to report the safety and efficacy of DEM-TACE procedures performed with microspheres smaller than 300 μm in patients with HCC and TIPS in a high-volume transplant center. Methods: Embolization was standardized by initiating DEM-TACE with microspheres smaller than 100 μm, and if stasis was not achieved, adjunctive embolization with 100-300 or 200 μm microspheres was administered. With regards to efficacy, the oncological response was evaluated and categorized according to mRECIST criteria at 1, 3-6, 9-12, and 15-18 months. Reporting the safety profile, detailed laboratory analysis was performed before, at 36-48 h, and 30-60 days after the procedure. Adverse events (AEs) were recorded; post-embolic syndrome was defined as the onset of fever/nausea/pain after the procedure. Late onset hepatobiliary complications were evaluated by follow-up imaging with computed tomography or magnetic resonance (CT/MR). Results: From December 2007 to November 2020, 17 HCC patients (25 HCC nodules) with patent TIPS underwent 20 DEM-TACE. Embolization was performed only with microspheres smaller than 100 μm in 3/20 DEM-TACE (15%); adjunctive embolization with 100-300 or 200 μm microspheres was required in 17/20 DEM-TACE (85%). Reported early AEs were post-embolic syndrome (9/20; 45%) all of grade 1-2, late AEs were asymptomatic acute liver bile duct injury (2/20; 10%), and in one case we observed hepatic abscess (1/20; 5%) resulting in death due to sepsis. With regards to efficacy, the oncological response was evaluated and categorized according to mRECIST criteria. Complete response (CR) at 1, 3-6, 9-12, and 15-18 months was 52%, 50%, 50%, and 50%, respectively. Objective response (CR + partial response) at 1, 3-6, 9-12, and 15-18 months was 95%, 71%, 70%, and 50%, respectively. Conclusion: DEM-TACE with drug-eluting-microspheres smaller than 300 μm can be performed in appropriately selected patients with TIPS.

目的:药物洗脱-微球经动脉化疗栓塞(DEM-TACE)治疗肝细胞癌(HCC)和经颈静脉肝内门静脉分流术(TIPS)的安全性和有效性尚缺乏证据。本回顾性研究的目的是报告在大容量移植中心HCC和TIPS患者中使用小于300 μm的微球进行DEM-TACE手术的安全性和有效性。方法:用小于100 μm的微球启动DEM-TACE进行标准化栓塞，如果不能达到止血效果，则使用100-300或200 μm微球辅助栓塞。在疗效方面，根据mRECIST标准在1、3-6、9-12和15-18个月对肿瘤反应进行评估和分类。在手术前、手术后36-48小时和30-60天进行了详细的实验室分析。记录不良事件(ae);栓塞后综合征定义为手术后出现发热/恶心/疼痛。通过计算机断层扫描或磁共振(CT/MR)随访评估迟发性肝胆并发症。结果:2007年12月至2020年11月，17例TIPS专利HCC患者(25例HCC结节)行了20次DEM-TACE。在3/20 DEM-TACE中，仅使用小于100 μm的微球进行栓塞(15%);17/20例DEM-TACE患者(85%)需要100-300或200 μm微球辅助栓塞。报告的早期ae为栓塞后综合征(9/20;45%) 1-2级、晚期ae均为无症状急性肝胆管损伤(2/20;10%)， 1例观察到肝脓肿(1/20;5%)，导致败血症死亡。在疗效方面，根据mRECIST标准对肿瘤反应进行评估和分类。1、3-6、9-12和15-18个月的完全缓解(CR)分别为52%、50%、50%和50%。1、3-6、9-12和15-18个月时的客观缓解(CR +部分缓解)分别为95%、71%、70%和50%。结论:药物洗脱微球小于300 μm的DEM-TACE可用于适当选择的TIPS患者。

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引用次数: 0

The role of minimally invasive surgery in the treatment of HCC 微创手术在HCC治疗中的作用

Hepatoma Research

Pub Date : 2022-01-01 DOI: 10.20517/2394-5079.2022.14

G. Cassese, Ho-Seong Han, Boram Lee, Hae Won Lee, J. Cho, R. Troisi

Liver surgery is the first-line treatment for hepatocellular carcinoma (HCC). Minimally invasive liver resection (MILS) has become an attractive option thanks to reduced intraoperative blood losses, shortened length of hospital stay, and similar oncological outcomes when compared to open liver resection. Nonetheless, the safety of MILS is still debated in challenging situations, such as in cirrhotic patients, difficult tumor locations, multiple or large tumors, and repeat resection. The aim of this review is to discuss current indications of laparoscopic liver resection for HCC treatment in the light of its outcomes, focusing on technical aspects of minimally invasive anatomic liver resection and state of the art of MILS in challenging situations.

肝脏手术是肝细胞癌(HCC)的一线治疗方法。微创肝切除术(MILS)由于术中出血量减少、住院时间缩短以及与开放式肝切除术相似的肿瘤预后，已成为一种有吸引力的选择。尽管如此，在一些具有挑战性的情况下，如肝硬化患者、肿瘤位置困难、多发或大肿瘤以及重复切除，MILS的安全性仍存在争议。本综述的目的是根据其结果讨论目前腹腔镜肝切除术治疗HCC的适应症，重点是微创解剖肝切除术的技术方面和微创解剖肝切除术在挑战性情况下的最新进展。

引用次数: 5

Hepatocellular carcinoma surveillance: current practice and future directions. 肝细胞癌监测：当前实践与未来方向。

Hepatoma Research

Pub Date : 2022-01-01 Epub Date: 2022-03-11 DOI: 10.20517/2394-5079.2021.131

Joseph C Ahn, Yi-Te Lee, Vatche G Agopian, Yazhen Zhu, Sungyong You, Hsian-Rong Tseng, Ju Dong Yang

Hepatocellular carcinoma (HCC) is among the leading causes of cancer incidence and mortality worldwide. Surveillance of individuals with cirrhosis or other conditions that confer a high risk of HCC development is essential for early detection and improved overall survival. Biannual ultrasonography with or without alpha-fetoprotein is widely recommended as the standard method for HCC surveillance, but it has limited sensitivity in early disease and may be inadequate in certain individuals. This review article will provide a comprehensive overview of the current landscape of HCC surveillance, including the rationale and indications for HCC surveillance, standard methods for HCC surveillance, and their strengths/limitations. Alternative surveillance methods such as the role of cross-sectional imaging, emerging circulating biomarkers, as well as the problem of under-utilization of HCC surveillance and surveillance-related harms will also be discussed in this review.

肝细胞癌（HCC）是全球癌症发病率和死亡率的主要原因之一。对肝硬化患者或其他具有 HCC 发病高风险的患者进行监测，对于早期发现和提高总生存率至关重要。一年两次的超声波检查（含或不含甲胎蛋白）被广泛推荐为监测 HCC 的标准方法，但这种方法对早期疾病的敏感性有限，对某些患者可能不适用。这篇综述文章将全面概述目前的 HCC 监测情况，包括 HCC 监测的原理和适应症、HCC 监测的标准方法及其优势/局限性。本综述还将讨论其他监测方法，如横断面成像的作用、新出现的循环生物标记物，以及 HCC 监测利用不足的问题和监测相关的危害。

引用次数: 0

Tumor microenvironment and immunology of cholangiocarcinoma. 胆管癌的肿瘤微环境和免疫学。

Hepatoma Research

Pub Date : 2022-01-01 Epub Date: 2022-03-10 DOI: 10.20517/2394-5079.2021.140

Massimiliano Cadamuro, Luca Fabris, Xuchen Zhang, Mario Strazzabosco

Cholangiocarcinoma (CCA), an aggressive tumor originating from both intra- and extra-hepatic biliary cells, represents an unmet need in liver oncology, as treatment remains largely unsatisfactory. A typical feature of CCA is the presence of a complex tumor microenvironment (TME) composed of neoplastic cells, a rich inflammatory infiltrate, and cancer-associated fibroblasts and desmoplastic matrix that makes it extremely chemoresistant to traditional chemotherapeutic drugs. In this review, we describe the cell populations within the TME, in particular those involved in the innate and adaptive immune response and how they interact with tumor cells and with matrix proteins. The TME is crucial for CCA to mount an immune escape response and is the battlefield where molecularly targeted therapies and immune therapy, particularly in combination, may actually prove their therapeutic value.

胆管癌（CCA）是一种起源于肝内和肝外胆管细胞的侵袭性肿瘤，是肝脏肿瘤学中尚未满足的需求，因为治疗效果在很大程度上仍不理想。CCA 的一个典型特征是存在复杂的肿瘤微环境（TME），由肿瘤细胞、丰富的炎症浸润、癌症相关成纤维细胞和去瘤基质组成，使其对传统化疗药物具有极强的抗药性。在这篇综述中，我们将描述TME内的细胞群，尤其是那些参与先天性和适应性免疫反应的细胞群，以及它们如何与肿瘤细胞和基质蛋白相互作用。TME是CCA启动免疫逃逸反应的关键，也是分子靶向疗法和免疫疗法（尤其是联合疗法）可能证明其治疗价值的战场。

引用次数: 0

Hepatocellular carcinoma in Hepatitis B and Human Immunodeficiency Virus coinfection in Africa: a focus on surveillance. 非洲乙型肝炎和人类免疫缺陷病毒合并感染中的肝细胞癌:监测重点

Hepatoma Research

Pub Date : 2022-01-01 Epub Date: 2022-10-14 DOI: 10.20517/2394-5079.2022.32

Qian Wan, Chimaobi Anugwom, Hailemichael Desalegn, Jose D Debes

Human immunodeficiency virus (HIV) and hepatitis-B virus (HBV) infections are weighty public health challenges, especially in the African continent. The direct carcinogenic effect of HBV means that it remains a potent cause of early-onset hepatocellular carcinoma (HCC) in Sub-Saharan Africa (SSA), where it causes significant morbidity and mortality. The presence of HIV infection in HBV-infected patients poses a complicating factor, as coinfection has been shown to hasten the progression of liver disease to cirrhosis and HCC, and often resulting in early-age hepatocarcinogenesis with consequent late diagnosis and lower survival. In this review, we discuss this unique conundrum, the epidemiology of HIV-HBV coinfection in SSA, its effect on liver disease and development of HCC, as well as practices and barriers to HCC surveillance in this distinct population. We propose a way forward to curb this considerable health burden focusing on reduction of disease stigma, the need for easy-to-measure biomarkers, and implementation of large prospective studies in this population.

人类免疫缺陷病毒(艾滋病毒)和乙型肝炎病毒(乙肝病毒)感染是重大的公共卫生挑战，特别是在非洲大陆。HBV的直接致癌作用意味着它仍然是撒哈拉以南非洲(SSA)早发性肝细胞癌(HCC)的一个潜在原因，在那里它会导致显著的发病率和死亡率。hbv感染患者中HIV感染的存在是一个复杂的因素，因为合并感染已被证明可加速肝病向肝硬化和HCC的进展，并经常导致早期肝癌发生，因此诊断较晚，生存率较低。在这篇综述中，我们讨论了这一独特的难题，SSA中HIV-HBV合并感染的流行病学，其对肝脏疾病和HCC发展的影响，以及在这一独特人群中进行HCC监测的做法和障碍。我们提出了一种方法来抑制这一巨大的健康负担，重点是减少疾病耻辱感，需要易于测量的生物标志物，并在这一人群中实施大型前瞻性研究。

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引用次数: 1

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