慢性乙型肝炎合并代谢性疾病罹患肝细胞癌的风险分析

肝细胞癌是全球第五大常见肿瘤，发病率高且早期诊断率低，往往预后较差。慢性乙型肝炎是我国肝细胞癌发生的最重要病因，随着乙肝疫苗的广泛接种及抗乙肝病毒药物的应用，乙肝病毒感染相关肝癌有下降趋势。近年来，代谢性疾病逐渐成为肝细胞癌重要病因。该文对慢性乙型肝炎患者合并代谢相关性疾病罹患肝细胞癌的风险分析作一综述，以期为临床监测和早期干预肝细胞癌提供参考。     

慢性乙型肝炎相关性肝细胞癌的危险因素研究进展

慢性乙型病毒性肝炎是我国肝癌的最主要病因，肝癌的早筛早治有利于改善患者的预后。目前还没有可以直接诊断的早期标志物，因此对慢性乙型肝炎患者发生肝细胞癌的危险因素研究，具有重要意义。本篇综述主要总结了慢性乙型肝炎进展至肝癌的危险因素。慢乙肝患者在HBsAg阴转后仍需监测肝癌的发生。     

《慢性乙型肝炎防治指南(2015年版)》解读之:HBV感染相关HCC的随访监测

<正>《慢性乙型肝炎防治指南(2015年版)》在2010年版基础上做了很多更新,但是针对HBV感染者原发性肝细胞癌(hepatocellular carcinoma,HCC)发生的监测、筛查、防控、管理等方面尚有许多内容有待明了。慢性肝炎患者规范的随访和监测对于HCC的早诊断、早治疗、提高生存率、改善预后起着决定性作用[1]。但对于数量众多、病情表现和遗传背景各异的HBV感染者,如何     

甲胎蛋白对肝衰竭肝细胞再生及预后判定价值的研究

甲胎蛋白(alpha fetoprotein,AFP)作为肿瘤标志物,临床上主要用于原发性肝癌、生殖腺胚胎癌、胃癌、胰腺癌等的诊断参考指标。我国最新的《慢性乙型肝炎防治指南》就明确提出AFP明显升高往往提示肝细胞癌(HCC),可用于监测HCC的发生。但AFP升高也可提示大量肝细胞坏死后的肝细胞     

基于5-hmC的液体活检在早期肝细胞癌诊断中的应用价值

正原发性肝癌是我国最常见的恶性肿瘤之一,居癌症相关死亡原因的第二位,近年来发病率持续增长,严重威胁我国人民的生命健康~([1])。肝细胞癌(HCC)是原发性肝癌的主要病理类型,占原发性肝癌的85%～90%~([1])。HCC的早期发现、诊断及治疗是改善患者生存预后的关键。我国85%以上的HCC与慢性HBV感染有关,因此在慢性乙型肝炎(CHB)、肝硬化(LC)患者中进行HCC筛查和监测是实现HCC早诊断的最有效途径~([1-2])。目前临床上用于HCC检测和诊断的血液学指标主要有血清甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)、异常凝血酶原(DCP)等,其中AFP为肝癌诊断和疗效监测中最常用且重要的     

抗病毒治疗时代慢性乙型肝炎患者发生肝细胞癌的风险评估及管理

慢性乙型肝炎病毒（HBV）感染是我国肝细胞癌（HCC）发生的主要原因。口服抗病毒药物已被证实能够明显降低慢性乙型肝炎（CHB）患者肝硬化、HCC的发生风险,但并不能完全消除HCC的发生。因此,准确评估CHB患者HCC发生风险,开展规范化的HCC筛查,对于早期诊断HCC、改善患者预后至关重要。近年来,医学研究者们建立了多...     

抗病毒治疗的慢性乙型肝炎患者中,抗血小板治疗与肝细胞癌发生风险的关系

【据《Hepatology》2017年11月报道】题：抗病毒治疗的慢性乙型肝炎患者中,抗血小板治疗与肝细胞癌发生风险之间的关系（作者Lee M等） 临床前研究表明,抗血小板治疗对肝细胞癌有保护作用。然而,该治疗能否降低慢性乙型肝炎患者发生肝细胞癌的风险尚无定论。     

慢性乙型肝炎抗病毒治疗近况

我国是乙型肝炎病毒(HBV)感染的高发区,慢性乙型肝炎表面抗原(HBsAg)携带率为9.57％。根据推算,慢性乙型肝炎患者约3 000万人。慢性乙型肝炎可以引起肝硬化、肝细胞癌。对慢性乙型肝炎的治疗,目前仍以综合治疗为主,其迄今尚缺乏特效病因治疗方法。从病     

慢性乙肝病毒感染者血清血管内皮生长因子的研究

目的:检测慢性乙型肝炎病毒感染患者血清中血管内皮生长因子(VEGF)的水平,探讨其临床意义.方法:采用双抗体夹心ELISA法对50例肝细胞癌、40例乙型肝炎肝硬化、36例乙型肝炎肝纤维化、40例慢性乙型肝炎患者血清中VEGF进行检测,并以43例健康者作为对照.同时采用全自动生化分析仪检测所有人员的肝功能常规指标.结果:慢性乙型肝炎、肝纤维化、肝硬化、肝细胞癌组患者血清VEGF浓度明显高于正常对照组(P＜0.01,P＜0.05,P＜0.05,P＜0.05),同时四组患者之间比较,差异均有统计学意义(P＜0.05).四组患者血清VEGF水平与肝功能指标AST、ALT无相关性,与GGT成正相关(r=0.337,P＜0.05).结论:VEGF与慢性乙型肝炎病毒感染者病情密切相关,可作为病情发展动态监测的指标.VEGF与GGT联合检测,可显著提高肝细胞癌的检出率.     

构建慢性乙型肝炎临床终点事件预测模型的方法学考量

实现慢性乙型肝炎患者临床终点事件的精准预测,确定肝硬化失代偿及肝细胞癌的高危患者,进而加强干预降低相应病死率,具有重要的临床意义。基于目前已发表的慢性乙型肝炎患者临床终点事件的预测模型,主要从方法学角度阐述预测模型构建的思路及基本步骤,以期为乙型肝炎领域预测模型相关研究提供参考。     

Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long?

Hepatitis C virus (HCV) chronic infection is associated with fibrosis progression, end-stage liver complications and HCC. Not surprisingly, HCV infection is a leading cause of liver-related morbidity and mortality worldwide. After sustained virological response (SVR), the risk of developing hepatocellular carcinoma is not completely eliminated in patients with established cirrhosis or with advanced fibrosis. Therefore, lifelong surveillance is currently recommended. This strategy is likely not universally cost-effective and harmless, considering that not all patients with advanced fibrosis have the same risk of developing HCC. Factors related to the severity of liver disease and its potential to improve after SVR, the molecular and epigenetic changes that occur during infection and other associated comorbidities might account for different risk levels and are likely essential for identifying patients who would benefit from screening programs after SVR. Efforts to develop predictive models and risk calculators, biomarkers and genetic panels and even deep learning models to estimate the individual risk of HCC have been made in the direct-acting antiviral agents era, when thousands of patients with advanced fibrosis and cirrhosis have reached SVR. These tools could help to identify patients with very low HCC risk in whom surveillance might not be justified. In this review, factors affecting the probability of HCC development after SVR, the benefits and risks of surveillance, suggested strategies to estimate individualized HCC risk and the current evidence to recommend lifelong surveillance are discussed.     

Screening tests for hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) is rising throughout the world. HCC meets the criteria for which a disease benefits from screening or surveillance: it is an important health problem; those with cirrhosis are the targets for surveillance; there is acceptable treatment if diagnosed early; surveillance using alpha-fetoprotein and ultrasound has been shown to be cost effective; surveillance is widely implemented by health care professionals and accepted by patients; standardized recall procedures exists; and the screening tests must achieve an acceptable level of accuracy in the population undergoing screening. The latter point is the main limitation of surveillance for HCC. In this review we will discuss the currently available tests for the surveillance of HCC.     

Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.     

Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

Surveillance for hepatocellular carcinoma(HCC)is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy.Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments.Repetition of liver ultrasonography(US)every 6 mo is the recommended surveillance program to detect early HCCs,and a positive US has to entrain a well-defined recall policy based on contrast-enhanced,dynamic radiological imaging or biopsy for the diagnosis of HCC.Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance,the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure.Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC.The promotion of specific educational programs for practitioners,clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.     

Surveillance for hepatocellular carcinoma...a hotly debated issue

The question of screening for hepatocellular carcinoma and particularly the surveillance of patients with cirrhosis remains hotly debated. Indeed, even if well defined groups at risk and accurate tools of early diagnosis exist, the impact of screening on the survival improvement has not yet been completely demonstrated. Moreover, the prevalence of hepatocarcinoma and the aetiologies of cirrhosis differ according to regions resulting in recommendations that should be adapted to each country. The purpose of this review is to summarise the data of the literature and to provide adapted recommendation for our country.     

Chronic hepatitis B in 2014: Great therapeutic progress,large diagnostic deficit

This review analyzes progress and limitations of diagnosis, screening, and therapy of patients with chronic hepatitis B infection. A literature review was carried out by framing the study questions. Vaccination in early childhood has been introduced in most countries and reduces the infection rate. Treatment of chronic hepatitis B can control viral replication in most patients today. It reduces risks for progression and may reverse liver fibrosis. The treatment effect on development of hepatocellular carcinoma is less pronounced when cirrhosis is already present. Despite the success of vaccination and therapy chronic hepatitis B remains a problem since many infected patients do not know of their disease. Although all guidelines recommend screening in high risk groups such as migrants, these suggestions have not been implemented. In addition, the performance of hepatocellular cancer surveillance under real-life conditions is poor. The majority of people with chronic hepatitis B live in resource-constrained settings where effective drugs are not available. Despite the success of vaccination and therapy chronic hepatitis B infection remains a major problem since many patients do not know of their disease. The problems in diagnosis and screening may be overcome by raising awareness, promoting partnerships, and mobilizing resources.     

Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study

BACKGROUND: Because hepatic cirrhosis is a major risk factor for hepatocellular carcinoma, recent guidelines by the European Association for the Study of the Liver (EASL) on clinical management of hepatocellular carcinoma recommend periodic ultrasound surveillance of cirrhotic patients with immediate workup for nodules >1 cm; an increase in the frequency of screening is considered sufficient for smaller lesions. AIMS: To determine the actual risk of hepatocellular carcinoma associated with the latter lesions and to assess the role of ultrasound guided-fine needle biopsy in their diagnosis. PATIENTS AND METHODS: Data were analysed for 294 new nodular lesions <20 mm, including 48 that were <10 mm, detected during a prospective multicentre study involving ultrasound surveillance of 4375 patients with hepatic cirrhosis. In the absence of alpha fetoprotein (AFP) levels diagnostic of hepatocellular carcinoma, ultrasound guided-fine needle biopsy was performed (n = 274). AFP and fine needle biopsy diagnoses of malignancies (hepatocellular carcinoma and lymphoma) were considered definitive. Non-malignant fine needle biopsy diagnoses (dysplastic or regenerative nodule) were verified by a second imaging study. Diagnoses of hepatocellular carcinoma based on this study were considered definitive; non-malignant imaging diagnoses were considered definitive after at least one year of clinical and ultrasound follow up. RESULTS: Overall, 258/294 (87.6%) nodules proved to be hepatocellular carcinoma, including 33/48 (68.7%) of those < or =10 mm. Overall typing accuracy of ultrasound guided-fine needle biopsy was 89.4%, and 88.6% for lesions < or =10 mm. CONCLUSIONS: In a screening population, well over half of very small nodules arising in cirrhotic livers may prove to be hepatocellular carcinoma, and approximately 90% of these malignancies can be reliably identified with ultrasound guided-fine needle biopsy.     

An update on cancer risk and surveillance in primary sclerosing cholangitis

Malignancy represents substantial morbidity and mortality in patients with primary sclerosing cholangitis (PSC). This subset of patients has been proven to be at increased risk for developing cholangiocarcinoma, gallbladder carcinoma and colorectal cancer in those with overlapping inflammatory bowel disease. Herein, we review the prevalence of these malignancies and recommend screening tools and current knowledge to reduce the disease burden in this population. Cholangiocarcinoma is the most dominant malignancy affecting PSC patients, with a lifetime risk ranging from 5% to 20%. We advocate for serial US or MRI/MRCP and CA 19‐9 to screen for cholangiocarcinoma. Gallbladder cancer has a lifetime risk around 2% in this population and we agree with annual imaging for lesions as recommended by national guidelines. Patients with PSC and concomitant IBD are at increased risk of colorectal carcinoma from time of diagnosis and therefore should likely undergo annual surveillance. The low rates of hepatocellular cancer and pancreatic cancer indicate surveillance for these malignancies is less advantageous.     

Screening of hepatocellular cancer: Japanese strategy

In Japan, hepatocellular carcinoma ranks as the fourth most common cancer and is responsible for about 40,000 deaths annually. Accordingly, the development of a screening system for its early detection will be linked to early treatment with a view to increasing survival. Algorithms for surveillance of hepatocellular carcinoma established in Japan will be useful for its early detection.     

α-fetoprotein and p53 autoantibodies in patients with chronic hepatitis C

Hepatitis C virus infection is a common cause of chronic liver disease and hepatocellular carcinoma. Recently, mutations in the p53 tumor suppressor gene with generation of circulating autoantibodies to p53 protein have been detected in a significant proportion of patients with different malignancies. Using ELISA methods we assessed α-fetoprotein and anti-p53 as serological screening parameters for hepatocellular carcinoma in 147 consecutive patients with chronic hepatitis C. Liver cirrhosis was histologically diagnosed in 58 patients (39.5%) and a hepatocellular carcinoma confirmed in seven patients (4.8%). Serum α-fetoprotein was raised above 20 ng/ml in 26/147 patients and above 100 ng/ml in 5/147 patients. In 6/7 patients with hepatocellular carcinoma, α-fetoprotein was raised above 20 ng/ml, but only in 3/7 cases above 100 ng/ml, resulting in a sensitivity and specificity of 85.7% and 85.7% (α-fetoprotein>20 ng/ml) and 42.9% and 98.6% (α-fetoprotein>100 ng/ml), for the detection of hepatocellular carcinoma, respectively. Autoantibodies to p53 were detected in 3/7 patients with hepatocellular carcinoma, but in 0/140 patients without malignancy (sensitivity 42.9%, specificity 100%). Screening for hepatocellular carcinoma was improved by combining α-fetoprotein measurement (level>100 ng/ml) with detection for anti-p53 (sensitivity 71.4%, specificity 98.6%). In conclusion, the presence of anti-p53 was highly specific for malignancy and independent of α-fetoprotein status. Further studies including a larger number of patients with hepatitis C virus-related hepatocellular carcinoma are required to investigate whether serological testing for anti-p53 in combination with α-fetoprotein might improve the detection of hepatocellular carcinoma in high-risk patients with liver cirrhosis.