干扰素α治疗肝细胞癌的再认识

干扰素（IFN）是多功能的细胞因子，有抑制增殖、抗病毒、抑制血管生成和免疫调节的作用。IFN家族包括α、β、γ三大类，目前在肝病和肿瘤治疗中应用较多的是IFNα。[第一段]     

甲胎蛋白应答在肝细胞癌治疗中的预后价值

肝细胞癌（HCC）是最常见的肝脏恶性肿瘤。因其恶性程度高、预后差,准确评估患者的治疗效果及预后情况至关重要。尽管目前影像学是肝癌预后评估的标准方法,但其仍存在诸多局限性。甲胎蛋白是重要的肝癌肿瘤标志物,广泛的应用于肝癌的筛查、诊断及预后评价。总结了甲胎蛋白应答在评判肝癌患者预后的相关文献。整体上,甲胎蛋白应答在肝癌患者接受射频消融、肝动脉化疗栓塞、钇90放射性栓塞、索拉菲尼等分子靶向药物、全身化疗、肝动脉灌注化疗或同步放化疗等治疗后具有良好的预后价值。     

甲胎蛋白对丙型肝炎患者中肝细胞癌检测特征的系统回顾和分析

据AnnsInternMed 2 0 0 3年 7月第 139卷第 1期报道 :为确定甲胎蛋白 (AFP)对丙型肝炎病毒 (HCV)感染患者中肝细胞癌检测的特征 ,作者对 196 6年至 2 0 0 2年 12月美国MEDLINE数据库中的有关文章进行了分析。论文的纳入标准为报告了AFP对HCV阳性肝细胞癌检测的敏感性和特异性 ;剔除标准为患者肝炎病因不清或被研究者中超过 5 0 %的人无HCV感染。对 5项符合纳入标准的研究进行了分析 ,仅有 1项研究采用公认的金标准 ,3项采用病例对照研究者可能过高地估计了诊断的正确度。采用最常用的诊断肝细胞癌试验的阳性域值 (AFP >2 0 μg/…     

甲胎蛋白应答评价索拉非尼联合卡瑞利珠单抗治疗晚期肝细胞癌的效果分析

目的 探讨甲胎蛋白(AFP)应答在索拉非尼联合卡瑞利珠单抗治疗晚期肝细胞癌中的临床疗效及安全性。方法 选取2020年9月—2022年2月于新疆医科大学第一附属医院接受索拉非尼联合卡瑞利珠单抗治疗的48例晚期肝细胞癌患者的临床资料,按照治疗后AFP应答水平进行分组：应答组(治疗6～8个月时,与基础AFP比较,AFP下降率>20%,n=32);无应答组(治疗6～8个月时,与基础AFP比较,AFP下降率≤20%,n=16)。计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ²检验。绘制生存曲线,行Cox单因素/多因素回归分析得到与OS相关的独立危险因素。比较两组患者无进展生存时间、总生存期与治疗效果。结果 两组患者中均未观察到达到临床缓解的病例。AFP应答组的客观有效率(21.88%vs 0)和疾病控制率(84.38%vs 43.75%)均高于无应答组(χ²值分别为2.530、6.668,P值分别为0.112、0.010)。应答组无进展生存期(9.9个月)、总生存期(13.8个月)均高于无应答组(6.8个月、11.1...     

甲胎蛋白的生物学功能

甲胎蛋白(AFP)不仅是肝细胞癌诊断的重要标志物,还在肝癌细胞的生长、增殖及凋亡等过程中发挥着重要的生物学作用.除了胞外的配体结合和运输功能,以及作为生长调控因子刺激肿瘤细胞生长外,细胞内的AFP还可以通过和转录因子或一些关键蛋白之间发生相互作用而作为信号分子参与对下游基因的转录调控或对信号通路产生影响.这些为我们研究...     

血清甲胎蛋白异质体对肝细胞癌的诊断意义

目的探讨甲胎蛋白异质体（AFP-L3）对肝细胞癌的诊断意义。方法采用电化学发光法和亲和吸附离心管法检测135例肝细胞癌和116例慢性肝炎和肝硬化患者血清AFP和AFP-L3。结果肝细胞癌患者血清AFP和AFP-L3阳性率明显高于良性肝病患者,差别有统计学意义（P〈0.001）;血清AFP-L3阳性与肿瘤大小无相关性（P〉0.05）。结论甲胎蛋白异质体在肝细胞癌的诊断中具有重要的价值。     

甲胎蛋白疫苗在肝癌中的研究进展

肝细胞癌(HCC)是世界上第五大恶性肿瘤,严重危害了人类的健康,常用的治疗效果并不理想,病死率仍居高不下,因此,迫切需要一种有效的辅助治疗,提高患者生存率。甲胎蛋白(AFP)作为诊断HCC最常用的肿瘤标志物,研究表明,AFP可诱导肝癌患者自身T细胞,其免疫原性抗原表位为研究AFP肝癌疫苗提供了新思路。目前已研制出多种AFP疫苗,如树突状细胞疫苗、DNA疫苗、多肽疫苗,且已成功应用到HCC小鼠模型以及Ⅰ期/Ⅱ期临床试验中,效果明确,现对AFP肝癌疫苗的分子机制、类别以及应用前景进行讨论。     

促肝细胞生长素治疗甲胎蛋白升高症28例

1 资料与方法 1.1 病例选择 28例患者均为1997年2月～1999年5月的住院病人,查血清AFP升高(>31μg/L),经彩色多普勒或/和CT检查均排除肝内占位性病变,其中慢性乙型肝炎17例,慢性丙型肝炎4例,肝炎后肝硬变7例。 1.2 诊断标准 参照1995年5月北京第5次全国传染病寄生虫病学术会议制订的《病毒性肝炎防治方案》(试行)。 1.3 治疗方法 PHGF 80～120mg/日,加入10％葡萄糖液250ml,静脉点滴,疗程30～90天。辅以肌苷、维生素C和复合维生素B口服。     

干扰素治疗后甲胎蛋白水平可预测肝细胞癌的发生

<正>【据《Clin Gastroenterol Hepatol》2013年12月报道】题:干扰素治疗后甲胎蛋白水平可预测肝细胞癌的发生(作者Oze T等)慢性HCV感染的患者应用干扰素(IFN)治疗结束后24周,缺乏持续病毒学应答(SVR)是肝细胞癌(HCC)的重要危险因素。尽管已经知道许多治疗前的因素可以影响HCC的发生率,但是对治疗后的因素(在IFN治疗过程中发生许多改变)知之甚少。研究者进行了一项前瞻性研究,收集2002至2008年在日本医院应用Peg–IFN+利巴韦林治疗的、无HCC病史的2659位慢性丙型()()     

原发性肝癌患者血清表皮生长因子与甲胎蛋白的相关研究

研究表皮生长因子 (EGF)在原发性肝癌患者中的含量变化及与甲胎蛋白的相关关系 ,以探讨表皮生长因子在原发性肝癌发生、发展过程中的作用和意义。采用放射免疫方法测定 30例原发性肝癌患者和 4 8例健康体检人群的血清表皮生长因子和甲胎蛋白 (AFP)。结果发现原发性肝癌组患者EGF含量明显低于健康对照组且有显著性差异 ;经相关分析血清EGF与AFP含量间无相关性关系 (r =0 16 4 3,P >0 0 5 )。表明EGF含量变化在肝癌早期诊断方面有一定的临床价值 ,同时与AFP无相关关系 ,也说明了两者在肝癌发生机制中的不同作用     

Combined use of AFP,PIVKA-II,and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients

Objective: As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3). Material and methods: This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence. Results: Most patients were men (n?=?431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n?=?467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728–0.801) for AFP; 0.823 (95% CI, 0.791–0.854) for PIVKA-II; and 0.755 (95% CI, 0.718–0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691–0.816) for AFP, 0.701 (95% CI, 0.630–0.771) for PIVKA-II, and 0.670 (95% CI, 0.596–0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851–0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704–0.841) for early HCC diagnosis. Conclusion: Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.     

良性肝病甲胎蛋白异常者5年随访

探讨AFP升高的良性肝病患者原发性肝癌发生率。对AFP升高的 16 4例良性肝病患者追踪随访 5年 ,每 3个月一次检测AFP、肝功能、B超等。 8例急性肝炎及 6例重型肝炎均无恶变 ,而肝硬化恶变为 14 6 % (7/48) ,明显较慢性肝炎 3 9% (4/10 2 )高 (P <0 0 5 ) ,AFP动态观察中 ,一过升高型、反复波动型、持续低浓度型、稳定上升型发生恶变分别为 0 % (0 /36 )、4 2 % (1/2 4 )、6 9% (7/10 1)、10 0 % (3/3)。对AFP升高的慢性肝病患者 3个月一次的追踪随访 ,可早期发现原发性肝癌。     

TAE术前后外周血肝癌播散细胞的变化及随访观察

目的研究原发性肝癌患者 TAE 术前后外周血中微转移变化情况,并评价 AFP mRNA 的预后诊断价值。方法应用巢式 RT-PCR 方法,检测32例肝癌患者 TAE 术前后外周血中 AFP mRNA 的表达,并对其预后进行随访观察。结果 32例 TAE 患者术前 AFP mRNA 阳性21例,阳性率为65.6％;术后 AFP mRNA 阳性23例,阳性率为71.9％。其中21例术前阳性者依然全部阳性,未发现有转阴性;11例阴性患者中有2例转为阳性。随访观察发现 AFP mRNA 阳性患者肝内、肝外转移发生率和 AFP mRNA 阴性患者差异显著(p<0.01)。结论 TAE 可能促使原发性肝癌发生血道播散。检测肝癌患者外周血中的 AFP mRNA,是一种灵敏预后诊断方法。     

Effects of interferon therapy on development of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis: A meta-analysis of randomized controlled trials

Aim: The role of interferon (IFN) therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)‐related cirrhosis remains controversial. This meta‐analysis aimed to determine whether IFN therapy reduced the incidence of HCC in HCV‐related cirrhotic patients. Methods: We performed a meta‐analysis including eight randomized controlled trials (RCT) (a total of 1505 patients) to assess the effect of IFN therapy on prevention of HCC in patients with HCV‐related cirrhosis. The pooled odds ratios (OR) were calculated using a random or fixed effects model. Results: Our results showed that IFN therapy significantly decreased the overall HCC incidence in HCV‐related cirrhotic patients (OR, 0.29; 95% confidence interval [CI], 0.10–0.80; P = 0.02). HCC risk in patients who failed to achieve sustained virological response (SVR) in the initial IFN‐based treatment was also reduced by maintenance IFN therapy (OR, 0.54; 95% CI, 0.32–0.90; P = 0.02). Subgroup analysis indicated that IFN therapy decreased HCC incidence in HCV‐related cirrhotic patients during long‐term follow up (>48 months) evidently (OR, 0.25; 95% CI, 0.09–0.67; P = 0.006). However, subgroup analysis of four RCT with short‐term follow up (≤48 months) did not demonstrate the significant difference in HCC incidence between IFN‐treated cirrhotic patients and controls (OR, 0.78; 95% CI, 0.39–1.55; P = 0.48). Conclusion: The present study suggested that IFN therapy could efficiently reduce HCC development in patients with HCV‐related cirrhosis; this effect was more evident in the subgroup of patients with long‐term follow up (>48 months). Patients who received maintenance IFN therapy had a lower risk of HCC than controls.     

Alpha-Fetoprotein (AFP) and AFP-L3 Is Most Useful in Detection of Recurrence of Hepatocellular Carcinoma in Patients after Tumor Ablation and with Low AFP Level

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6–8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.     

人外周血AFPmRNA的定性检测和原发性肝细胞癌转移的关系

目的　为探讨人外周血ＡＦＰｍ ＲＮＡ 与肝癌转移之间的关系。方法　采用分子生物学反转录—巢式ＰＣＲ 技术,检测了３８ 例不同肝病患者和９ 例非肝病患者外周血中的ＡＦＰｍ ＲＮＡ。结果　其检出结果分别为：对照组０／９ ;肝硬化组２／１１ ;肝癌未发生转移组２／７ ;局部转移组６／１２ ;远处转移组７／８ 。其中良性组与恶性组之间、肝癌无远处转移与远处转移组之间有显著性差异（ Ｐ＜ ０ ．０１ 及 Ｐ＜ ０ ．０５） 。另外,肝癌患者中,直径＞ ５ ｃｍ 组外周血中ＡＦＰｍ ＲＮＡ 阳性率明显高于直径＜ ５ｃｍ 组（ Ｐ＜ ０ ．０５） 。肝癌患者血清ＡＦＰ＞ ４００ｎｇ／ｍｌ 组外周血中ＡＦＰｍ ＲＮＡ 阳性率具有明显高于ＡＦＰ＜ ４００ｎｇ／ｍｌ组（Ｐ＜ ０ ．０１） 。肝功能分级与外周血中ＡＦＰｍ ＲＮＡ 阳性率无关。结论　人外周血中ＡＦＰｍ ＲＮＡ 的检测具有重要的临床指导意义,可用于预测肝癌远处转移,并为临床治疗提供实验依据     

病毒性肝炎患者血清AFP与临床、病理的关系

目的：探讨肝炎患者AFP水平与临床,病理的关系。方法：临床诊断为病毒性肝炎并经肝穿刺活检的310例患者,常规检测血清TB－ALT,AST,A／G,AFP及肝炎病毒标志,观察异常AFP水平与临床类型,病理类型,有无家族史和病因等的关系。结果：310例肝炎患者中发现AFP异常115例,阳性率为37．1％,急性肝炎,慢性肝炎,慢性重型肝炎患者中均见有AFP异常者,根据病理,急性肝炎患者AFP阳性率最低,慢性肝炎,慢性肝炎肝硬化患者较高,慢性重型肝炎患者阳性率最高,分别为11．7％．34．2％,57．5％和66．7％,按临床表现诊断,阳性率以慢性重型肝炎最高,慢性肝炎最低,而急性肝炎居中,在肝炎病因分类中单纯HBV感染或HBV基础上又有HAV／HEV感染者AFP阳性率较高,为35．3％和62．8％,HBV与HCV双重感染者为27．3％,单一HCV感染者6例中1例AFP阳性,单纯HAV或HEV阳性者未见AFP异常,此外,有肝癌家族史的肝炎患者AFP阳性率为57．9％,高于无肝癌家族史者。结论：肝炎患者AFP异常颇为常见,一旦发现肝炎患者AFP异常时,应考虑患者有HBV感染的背景,或为单纯HBV感染的慢性乙型肝炎,或HBV基础上有HAV或HEV重叠感染者。     

Suppression of hepatocellular carcinoma development in hepatitis C patients given interferon‐based antiviral therapy

The advance of antiviral treatment for chronic hepatitis C has brought a high sustained virological response (SVR) rate. In this review article, the suppressive effect of interferon (IFN)‐based therapy on the development of hepatocellular carcinoma (HCC), risk factors for developing HCC and the characteristics of HCC development after SVR among chronic hepatitis C patients given IFN‐based therapy were studied. The HCC incidence has been revealed to decrease with IFN‐based antiviral therapy, especially in SVR, and the risk factors for developing HCC were older age, advanced liver fibrosis and male sex. α‐Fetoprotein levels at 24 weeks after the end of IFN‐based treatment was associated strongly with HCC incidence irrespective of virological response. In patients with SVR, other risk factors were glucose metabolism disorders, lipid metabolism disorders and alcohol intake. Extra attention to the possibility of HCC incidence should be required for these SVR patients. Antiviral therapy with a combination of HCV‐specific direct‐acting antivirals (DAA) is expected to be utilized in the future. However, it is not known whether DAA‐based treatment can suppress HCC to the level of IFN‐based treatment. Further research is required to clarify this.