Role of C11-FDG dual-tracer PET-CT scan in metastatic screening of hepatocellular carcinoma-a cost-effectiveness analysis

Background:We aimed to identify predictive factors for positron emission tomography(PET)-detected hepatocellular carcinoma(HCC)metastasis and a cost-effective approach to preoperative PET-computed tomography(CT)for detecting metastasis.Methods:Clinicopathological and survival data of HCC patients having PET-CT with 18F-fludeoxyglucose(FDG)and 11C-acetate(ACT)following contrast-enhanced CT/magnetic resonance imaging(MRI)for preoperative tumor staging were reviewed.Binary logistic regression was performed to identify predictive factors for PET-detected metastasis.A cost-benefit analysis model was built for the incurred costs and the impact of PET-CT findings on treatment strategy was studied.Results:Totally 152 patients were analyzed.Dual-tracer PET-CT detected metastasis in 17 patients(11%).By multivariate analysis,alpha-fetoprotein(AFP)≥400 ng/mL[relative risk(RR):4.30,95%confidence interval(CI):1.41-13.15,P=0.011]and bilobar disease(RR:3.94,95%CI:1.24-12.52,P=0.014)were independent predictive factors for PET-detected metastasis.PET-CT findings altered the treatment strategy for 12 patients(7.9%);three partial hepatectomies,eight episodes of transarterial chemoembolization(TACE)and one episode of ablation were avoided,with an estimated cost-saving of US$91,000,$150,000 and$10,600 respectively.Had the PET-CT been performed only for patients with AFP≥400 ng/mL or bilobar disease(n=74),metastasis would have been confirmed in 14 patients(18.9%),and the cost-saving per patient was estimated at US$1,070.Conclusions:Dual-tracer PET-CT is cost-effective and useful for preoperative HCC staging in patients with AFP≥400 ng/mL or bilobar disease.Its routine use in preoperative workup for all HCC patients is not recommended.Unilobar disease with AFP<400 ng/mL can achieve good negative predictive value for PET-detected metastasis.Screening patients with either factor can avoid unnecessary procedures and is thus cost-effective for preoperative HCC workup.

Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk:Results From a German Multicenter Retrospective Cohort Study

Background and Aims:Hepatocellular carcinoma(HCC)surveillance in patients at risk is strongly recommended and usually performed by ultrasound(US)semiannually with or without alfa-fetoprotein(AFP)measurements.Quality pa-rameters except for surveillance intervals have not been strictly defined.We aimed to evaluate surveillance success and risk factors for surveillance failure.Methods:Patients with≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively analyzed.Surveillance success was defined as HCC detection within Milan criteria.Results:Only 47%of 156 patients,median age 63(interquartile range:57-70)years,56%male,and 96%with cirrhosis,received recom-mended surveillance modality and interval.Surveillance fail-ure occurred in 29%and was significantly associated with lower median model for end-stage liver disease(MELD)score odds ratio(OR)1.154,95%confidence interval(CI):1.027-1.297,p=0.025)and HCC localization within right liver lobe(OR:6.083,95%CI:1.303-28.407,p=0.022),but not with AFP≥200μg/L.Patients with surveillance failure had sig-nificantly more intermediate/advanced tumor stages(93%vs.6%,p<0.001),fewer curative treatment options(15%vs.75%,p<0.001)and lower survival at 1 year(54%vs.75%,p=0.041),2 years(32%vs.57%,p=0.019)and 5 years(0%vs.16%,p=0.009).Alcoholic and non-alcoholic fatty liver disease(OR:6.1,95%CI:1.7-21.3,p=0.005)and ascites(OR:3.9,95%CI:1.2-12.6,p=0.021)were in-dependently associated with severe visual limitations on US.Conclusions:US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related outcomes.Lower MELD score and HCC lo-calization within right liver lobe were significantly associated with surveillance failure.

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 and diagnosis of hepatocellular carcinoma: A systematic review

BACKGROUND Hepatocellular carcinoma (HCC) appears in most of cases in patients with advanced liver disease and is currently the primary cause of death in this population.Surveillance of HCC has been proposed and recommended in clinical guidelines to obtain earlier diagnosis,but it is still controversial and is not accepted worldwide.AIM To review the actual evidence to support the surveillance programs in patients with cirrhosis as well as the diagnosis procedure.METHODS Systematic review of recent literature of surveillance (tools,interval,cost-benefit,target population) and the role of imaging diagnosis (radiological non-invasive diagnosis,optimal modality and agents) of HCC.RESULTS The benefits of surveillance of HCC,mainly with ultrasonography,have been assessed in several prospective and retrospective analysis,although the percentage of patients diagnosed in surveillance programs is still low.Surveillance of HCC permits diagnosis in early stages allows better access to curative treatment and increases life expectancy in patients with cirrhosis.HCC is a tumor with special radiological characteristics in computed tomography and magnetic resonance imaging,which allows highly accurate diagnosis without routine biopsy confirmation.The actual recommendation is to perform biopsy only in indeterminate nodules.CONCLUSION The evidence supports the recommendation of performing surveillance of HCC in patients with cirrhosis susceptible of treatment,using ultrasonography every 6 mo.The diagnosis evaluation of HCC can be established based on noninvasive imaging criteria in patients with cirrhosis.

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.

Present and future possibilities for early diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) represents the fifth most common cancer in the world,and the third most frequent oncological cause of death.The incidence of HCC is on the increase.HCC typically develops in patients with chronic liver diseases,and cirrhosis,usually with viral etiology,is the strongest predisposing factor.Nowadays HCC diagnosis is a multistage process including clinical,laboratory,imaging and pathological examinations.The prognosis of HCC is mostly poor,because of detection at an advanced,non-resectable stage.Potentially curative treatment(surgery) is limited and really possible only for cases with small HCC malignancies.For this reason,more effective surveillance strategies should be used to screen for early occurrence of HCC targeted to the population at risk.So far,the generally accepted serological marker is α-fetoprotein(AFP).Its diagnostic accuracy is unsatisfactory and questionable because of low sensitivity,therefore there is a strong demand by clinicians for new HCC-specific biomarkers.In this review,we will focus on other biomarkers that seem to improve HCC diagnosis,such as AFP-L3,des-γ-carboxyprothrombin,α-l-fucosidase,,γ-glutamyl transferase,glypican-3,squamous cell carcinoma antigen,a new generation of immunoglobulin M-immunocomplexes,and very promising geneexpression profiling.

Screening for hepatocellular carcinoma: summary of current guidelines up to 2018

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related to worldwide death with a great geographical variation. To be eligible for curative therapy at the time of diagnosis is important. However, the majority of cases are diagnosed at late stages. This can be achieved with applicable screening modalities. Until now, many organizations around the world have developed guidelines according to their own evidence-based data for screening of HCC. The purpose of this article is to review the screening modalities of HCC to assist gastroenterologists and providers involved in the management of HCC.

原发性肝癌基层筛查与健康监测管理的研究进展

当前我国原发性肝癌(以下简称肝癌)的发病率和死亡率较高,经济和疾病负担沉重,对肝癌风险人群进行规范的筛查与健康监测管理是有效降低肝癌相关负担的重要措施。目前我国基层慢性肝病患者缺乏肝癌筛查与监测必要性的认知,依从性较差,现有的筛查工具灵敏度欠佳、成本效益较低。本文从我国慢性肝病人群肝癌发生风险的评估分层、基层筛查和肝癌高危人群的加强筛查与长期监测现状等方面探讨中国人群肝癌基层筛查与健康管理策略,为我国人群肝癌筛查与早诊、早治工作的规范开展提供参考,以期提升我国基层人群肝癌筛查覆盖率及防控效果。

慢性乙型肝炎病毒感染者肝细胞癌筛查和监测

肝细胞癌是我国常见恶性肿瘤,疾病负担十分沉重。筛查和监测是提高肝细胞癌患者早诊早治和生存率的有效措施。慢性乙型肝炎病毒感染是我国肝细胞癌的主要病因,有必要制定专门的筛查和监测策略。中国肝炎防治基金会组织国内有关专家,参考国内外相关指南,并结合当前研究进展和临床实践经验共同讨论后达成一致意见,旨在为规范开展慢性乙型肝炎病毒感染者肝细胞癌的筛查和监测提供参考,进而改善我国肝细胞癌的防控效果和患者预后。

慢性乙型肝炎病毒感染者肝细胞癌筛查和监测

肝细胞癌是我国常见恶性肿瘤,疾病负担十分沉重。筛查和监测是提高肝细胞癌患者早诊早治和生存率的有效措施。慢性乙型肝炎病毒感染是我国肝细胞癌的主要病因,有必要制定专门的筛查和监测策略。中国肝炎防治基金会组织国内有关专家,参考国内外相关指南,并结合当前研究进展和临床实践经验共同讨论后达成一致意见,旨在为规范开展慢性乙型肝炎病毒感染者肝细胞癌的筛查和监测提供参考,进而改善我国肝细胞癌的防控效果和患者预后。

非酒精性脂肪性肝病患者肝癌筛查的必要性及可行性

原发性肝癌的发病率和死亡率与日俱增,严重影响公众健康。其中慢性肝病,尤其是肝硬化,是导致肝癌的主要病因和危险因素。随着对病毒性肝炎的有效防治,以及肥胖、糖尿病等代谢综合征的发病率迅速增长,非酒精性脂肪性肝病已成为最常见的慢性肝病原因,因此对非酒精性脂肪性肝病患者进行肝癌筛查刻不容缓。现综述概括总结了非酒精性脂肪性肝病及其相关性肝癌的流行病学特征、高危因素,以及筛查监测手段,进而探讨肝癌筛查的必要性及可行性。