乙型肝炎病毒感染血清学标志与慢性感染自然史研究进展

乙型肝炎（乙肝）病毒（Hepatitis B Virus,HBV）感染的血清学标志主要有乙肝病毒表面抗原、乙肝病毒表面抗体、乙肝病毒e抗原（Hepatitis B e Antigen,HBeAg）、乙肝病毒e抗体和乙肝病毒核心抗体。慢性HBV感染自然史复杂、多样,与初次感染年龄、HBV载量、基因型、突变位点、HBeAg状态、丙氨酸氨基转移酶（Alanine Aminotransferase,ALT）水平、丙型肝炎病毒和／或丁型肝炎病毒合并感染及宿主免疫状态等有关。慢性HBV感染过程可分免疫耐受期、免疫清除期、低或无病毒复制期和病毒恢复活性期。部分HBeAg阴性、ALT高水平和HBV脱氧核糖核酸高滴度（〉10^5拷贝／ml）患者,可出现肝硬化、肝细胞癌和肝功能衰竭等肝脏相关综合征。现有证据表明,合理使用抗HBV药物可减少后遗症发生率和病死率。     

Impact of pathological response after preoperative transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma: a multicenter propensity score matching analysis

BackgroundTo study the influence of pathological responses (PR) after transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion (MVI) and early recurrence in hepatocellular carcinoma (HCC) patients.MethodsBetween 2013 to 2015, consecutive HCC patients who underwent liver resection with “curative” intent at three hospitals were enrolled in this study. Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI, early recurrence rates and patterns of recurrence before and after propensity score matching (PSM).ResultsOf 1,970 patients, 737 patients who received preoperative TACE were divided into three groups according to the areas of PR: ≥90% (n=226), 60–90% (n=447), and <60% (n=64). PR ≥90% was an independent protective factor of incidences of MVI [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.082–0.245, P<0.001) and early recurrence (HR, 0.742; 95% CI, 0.561–0.963, P=0.032); while PR<60% was an independent risk factor of incidences of MVI (OR, 6.076; 95% CI, 3.004–11.728, P<0.001) and early recurrence (HR, 1.428; 95% CI, 1.095–1.929; P=0.009). Furthermore, patients with PR <60% were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.ConclusionsThis study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence. Patients with PR <60% were at significantly higher risks of having more MVI, early and multiple tumor recurrences     

肝脏硬度、层粘连蛋白及AFP值对HBV相关HCC的诊断价值

目的 评估血清甲胎蛋白（alpha-fetoprotein,AFP）、肝脏弹性（也称为硬度）测量值（liver stiffness measurement,LSM）、层粘连蛋白（laminin,LN）检测在HBV相关性肝细胞性肝癌（hepatocellular carcinoma,HCC）诊断中价值。方法 采用回顾性研究方法,纳入2013年10月至2021年3月在延安大学附属医院及延安市第二人民医院就诊的HBV感染者,行上腹部增强MRI或增强CT等检查诊断为肝硬化和肝癌的患者。检查肝纤维化四项LSM及AFP值等指标。采用统计学方法分析两组各指标的差异,Logistic单因素及多因素分析筛选诊断HCC有价值的指标。结果 两组透明质酸（hualuronic acid,HA）、Ⅳ型胶原蛋白（collagen Ⅳ,CⅣ）、Ⅲ型前胶原（procollagen type Ⅲ,PCⅢ）、LN、AFP及LSM水平差异,均有统计学意义（P均<0.05）。多因素分析显示,AFP、LN、LSM是HCC的独立危险因素（P均<0.05）。并经ROC曲线分析发现均有诊断价值,AFP的ROC曲线下面积为...     

Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1^st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1^st- and 2^nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.     

榭皮黄酮通过抑制Traf6/NF-κB信号转导通路增强5-氟尿嘧啶对HepG2的化疗作用

目的 研究榭皮黄酮（quercetin,Qu）影响肝癌细胞HepG2对5-氟尿嘧啶（5-fluorouracil,5-FU）的敏感性及Traf6/NF-κB信号转导通路。方法 体外培养HepG2细胞,取对数期细胞进行后续实验,将细胞分为对照组（不含任何药物的培养基孵育细胞24 h）、单独Qu组（含40μg/ml Qu的培养基孵育细胞24 h）、单独5-FU组（含50μmol/L 5-FU的培养基孵育细胞24 h）、Qu+5-FU联合处理组（含40μg/ml Qu和50μmol/L 5-FU的培养基共同孵育细胞24 h）、单独Traf6抑制剂C25-140组（2μmol/L C25-140的培养基孵育细胞8 h）、C25-140+Qu+5-FU组（C25-140预处理细胞8 h,然后含40μg/ml Qu和50μmol/L 5-FU的培养基共同处理细胞24 h）。采用CCK8法检测细胞活力,采用倒置显微镜记录细胞克隆数,采用流式细胞术检测细胞凋亡率,采用Western blot检测剪切的半胱氨酸蛋白酶-7(cleaved-caspase 7,Cle-caspase 7)、Clecaspa...     

Gingival metastasis from primary hepatocellular carcinoma: a case report

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide; however, cases with metastasis to the oral cavity are extremely rare. Herein, we report a 68-year-old man who was diagnosed with HCC. Ten months after surgical removal of the right half of his liver, the patient developed gingival metastasis. Unfortunately, the patient died 4 months after the diagnosis. We discuss treatment options, pathological results, and disease prognosis. When a mandibular gingival mass is found, metastatic tumors should be considered in the differential diagnosis. In this regard, the patient’s medical history and physical examination are valuable indicators for the diagnosis of mandibular gingival metastasis. This case provides a basis for the clinical diagnosis of metastatic HCC involving the oral cavity.     

术前经动脉化疗栓塞对肝细胞癌细胞凋亡的影响

目的 评价术前经导管动脉化疗栓塞(17ACE)对肝细胞癌(HCC)细胞凋亡的影响。资料与方法经手术病理证实的HCC136例，其中行1～5次TACE后Ⅱ期手术切除79例(TACE组)，按治疗方式不同分4组，A组：仅灌注化疗药物ll例，治疗1～4次；B组：化疗药 碘化油栓塞33例，治疗1～5次；C组：化疗药 碘化油 明胶海绵颗粒栓塞23例，治疗1—3次；D组：化疗药 碘化油、无水乙醇、明胶海绵颗粒栓塞12例，治疗1～3次。单纯手术57例(非TACE组)，用TUNEL(terminal deoxynucleotidyl transferase(TdT)-mediated dUTP-digoxigenin nick—end labeling)法检测凋亡细胞，用免疫组织化学检测各标本Bcl-2和Bax蛋白表达。结果 TACE组的A、B、C、D各组HCC细胞凋亡指数及Bax蛋白表达均显著高于非TACE组；而Bcl-2蛋白表达及Bcl-2和Bax蛋白表达比值TACE组的A、B、C、D各组均显著低于非TACE组。结论 术前TACE通过上调Bax蛋白表达，下调Bcl-2蛋白表达及Bcl-2和Bax蛋白表达比值使HCC细胞发生凋亡。     

乙肝肝硬化背景下肝细胞肝癌的MRI 表现：LI-RADS（2014版）定义征象的识别率分析

目的：分析肝硬化背景上肝细胞肝癌（HCC）的 MRI 动态增强表现,探讨2014版肝脏影像报告及数据系统（LI-RADS）所定义的各种征象在 MRI上的识别率。方法：2008年12月－2014年8月共54例乙肝肝硬化患者入组本多中心研究,所有患者均行 MRI平扫和增强扫描、且经病理诊断证实有 HCC。由两位阅片者对 MR 图像进行独立盲法读片,阅片方法遵循LI-RADS流程：对主要征象、次要征象进行评价（出现／未出现）,计算2位阅片者对LI-RADS所定义的各种 MRI征象的识别率。通过Kappa检验来分析两位阅片者对征象识别的一致性。结果：两位阅片者对病灶的3个主要征象（动脉期高强化、“廓清”表现、“包膜”表现）的识别率依次分别为83．3％和85．2％、77．8％和64．8％、51．9％和61．1％,阅片者间的一致性（Kappa值）分别为0．791、0．512和0．589。对于次要征象,大部分征象均有一定的识别率,以T2 WI上稍高信号、扩散受限的识别率最高,分别为90．7％和87．0％、88．9％和90．7％,阅片者间的一致性（Kappa 值）分别为0．813和0．899。结论：基于LI-RADS的诊断标准,平扫及动态增强MR图像上乙肝肝硬化背景上的HCC病灶的主要征象能较多地被识别,且阅片者的一致性较好;次要征象中T2 WI稍高信号和扩散受限的识别率较高,阅片者间的一致性也非常好。     

原发性肝细胞癌放疗抗拒分子机制研究进展

原发性肝细胞癌放疗疗效差异与肿瘤的放疗抗拒密切相关。多种基因及分子通路参与调控原发性肝细胞癌对放疗的抗拒,对原发性肝细胞癌放疗抗拒分子标志物的研究可预测放疗敏感性,对放疗抗拒的逆转研究有重要意义。     

Diagnostic angioscintigraphic evaluation of malignant hepatic tumors before catheter embolization: Determination of shunt,flow distribution,and reflux

Purpose: The aim of this study was to evaluate quantitatively arteriovenous shunts in malignant liver tumors by injection of ^99mTc macroaggregates of albumin (MAA) into the tumor-feeding artery after selective catheterization. Methods: In 40 patients with malignant liver tumors (33 hepatocellular carcinomas and 7 metastases of colorectal cancer), a mean dose of 200 MBq ^99mTc MAA was injected arterially during angiography. The embolized area and the lungs were then visualized using a gamma camera. A dedicated computer program calculated pulmonary shunt rates. Results: The majority of patients (n= 30) with hepatocellular carcinoma showed small shunts varying from 0 to 15%; only 3 of these patients had shunts ranging from 18% to 37%. In patients with colorectal carcinoma metastases (n= 7) the shunt varied from 0 to 3% (2 ± 1%), probably due to a physiological shunt in normal liver tissue in the embolized area. Importantly, the degree of shunt found bore no correlation to the tumor volume or to the pattern of vascularity on angiography. Conclusion: Diagnostic angioscintigraphy is a useful tool for pretherapeutic evaluation of the capacity of an individual tumor to retain particles and to measure extratumoral shunting; these are essential for therapy planning, as they can help to increase the safety and effectiveness of embolization.