Detection Of Hepatocellular Carcinoma In Patients Research Articles

Dual-tracer PET/CT in the management of hepatocellular carcinoma

Background & AimsCombined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron emission tomography-computed tomography (PET-CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. MethodsWe retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET-CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET-CT in diagnosing HCC were evaluated. A Multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. ResultsDual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with an estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n=273, κ=0.822; 95% CI 0.803-0.864). ConclusionsDual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.• Impact and implications• Dual-tracer PET-CT detected 12% more disease in HCC patients undergoing staging than CT or MRI, resulting in change in treatment in 8% of cases and a cost saving of US$495 per patient.• It is also able to accurately detect HCC in high-risk cases where CT or MRI are equivocal or normal.• Dual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Diagnostic performance of US LI-RADS in hepatocellular carcinoma surveillance

BackgroundLiver cirrhosis and chronic infection with hepatitis B virus are major risk factors for hepatocellular carcinoma (HCC). Guidelines recommend ultrasound (US) surveillance for population at risk of HCC. The US Liver Imaging Reporting and Data System (LI-RADS) aims at standardization of interpretation, reporting, and management recommendations for US surveillance examinations. The aim of this study is to assess the diagnostic accuracy of US LI-RADS in early HCC detection in patients at risk.ResultsThis retrospective study included patients with surveillance US between January 2018 and January 2020 who had a contrast-enhanced CT or MRI of the liver within 1 month from the date of US examination. Visualization scores and US categories were assigned according to the US LI-RADS lexicon. A total of 264 participants were eligible for the study. HCC was diagnosed in 33 participants. The US-3 category had a 39.4% sensitivity and 93.5% specificity for HCC detection. The US-2 category had a 45.4% sensitivity and 87% specificity for HCC detection. The visualization score C showed the highest number of HCC (19/33) and had the highest false-negative rate (76%, 13 of 17).ConclusionsBoth US-2 and US-3 categories showed high specificity and low sensitivity for HCC detection in the setting of surveillance of patients at high risk. Visualization score C had the highest risk for HCC and the highest rate of false-negative results. Intense surveillance by contrast-enhanced CT or MRI might be beneficial for patients with limited visualization scores B and C.

Risk factors associated with late hepatocellular carcinoma detection in patients undergoing regular surveillance.

Hepatocellular carcinoma (HCC) has a very poor prognosis with a 5-year survival rate of < 20%; hence, early diagnosis is crucial. Despite regular checkups for high-risk groups of HCC, there are a few cases in which it is discovered as a late-stage HCC. Therefore, this study aimed to investigate the characteristics of patients with delayed HCC detection during regular surveillance. Between January 2010 and December 2020, we analyzed patients with newly diagnosed HCCs who underwent HCC surveillance by ultrasound or computed tomography scan at least twice and were followed up for more than 1 year for hepatitis B, hepatitis C, and chronic liver disease. The mean age of 223 HCC patients was 70 years, of which 152 were male, accounting for 68.1%. Among them, 196 patients (87%) were diagnosed with Barcelona clinic liver cancer stage 0 or A, while 27 (13%) were diagnosed with Barcelona clinic liver cancer stages B and C. When classified according to the TNM criteria, 154 patients (69%) were in stage I, and 69 (31%) were in stage II or higher. Multivariate analysis was performed to identify the risk factors for patients diagnosed with late-stage HCC. The Child-Turcotte-Pugh (CTP) score was identified as a highly significant factor (P = .002, HR 1.547, 95% CI 1.177-2.032), whereas the presence of cirrhosis, body mass index, and sex had no significant effect. We found that in patients with chronic liver disease who were screened regularly, those with higher CTP scores were more likely to be diagnosed with HCC in the late-stages. Therefore, although the presence of cirrhosis is also important for HCC surveillance, careful attention is needed in patients with high CTP scores.

Comparison of a multitarget blood test to ultrasound and alpha-fetoprotein for hepatocellular carcinoma surveillance: Results of a network meta-analysis.

Ultrasound‐based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt‐HBT). We compared performance of mt‐HBT against ultrasound with or without alpha‐fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clinicaltrials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt‐HBT diagnostic performance was derived from a clinical validation study. A network meta‐analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty‐one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound‐alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%–60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%–82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt‐HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%–37.7%) and similar to ultrasound with AFP (−3.3%; 95% CrI, −22.3%–17.4%). Pairwise posterior probabilities suggested a preference for mt‐HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood‐based mt‐HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP. Mt‐HBT could be a comparable alternative to existing methods for HCC surveillance in patients who are at risk.

Liver Cancer-Specific Isoform of Serine Protease Inhibitor Kazal for the Detection of Hepatocellular Carcinoma: Results from a Pilot Study in Patients with Dysmetabolic Liver Disease.

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6–39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7–18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease.

Early detection of hepatocellular carcinoma using cfDNA signatures from cirrhotic patients with nodules.

4113 Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Early detection of HCC patients is related to favorable survival. Nodules in liver cirrhosis (LC) are at higher risk of developing into HCC. There is an urgent clinical need for development of an accurate and affordable non-invasive method for early HCC diagnosis among LC patients with nodules. Methods: We have previously shown that the genome-wide HIFI (5-Hydroxymethylcytosine/motIf/ Fragmentation/nucleosome footprInt) method held a solid diagnostic value in differentiating HCC from LC. In this study, we leverage this knowledge to diagnose early HCC (BCLC 0/A) in cirrhotic nodules using copy number variation (CNV) to replace 5-Hydroxymethylcytosine to simplify NGS protocol and decrease cost. The updated method generates a score that reflects the presence of tumor-derived cfDNA in 10 ml blood via low coverage (2x) whole-genome sequencing (WGS). We applied it in a retrospective cohort (validation set 1, n = 171) and a prospective cohort (validation set 2, n = 156), both of which involved patients with newly diagnosed early stage HCC (BCLC 0/A) as well as individuals with cirrhotic nodules. Results: The updated method showed excellent performance for early HCC detection both in the validation set 1 (84 HCC and 87 cirrhotic nodules; AUC: 0.951, 82.1% sensitivity at 90.8% specificity) and validation set 2 (71 HCC and 85 cirrhotic nodules; AUC: 0.958, 81.7% sensitivity at 91.8% specificity) (Table). The AUC values for distinguishing early HCC from cirrhotic nodules could reach 0.951 (80.9% sensitivity at 91.0% specificity) and 0.947 (74.7% sensitivity at 92.1% specificity) among patients with AFP &lt; 400 μg/L and those with nodular size &lt; = 2 cm, respectively. More importantly, our model also maintained consistent performance in detecting very early stage HCC (BCLC 0) with AUC of 0.941 (74.7% sensitivity at 91.3% specificity). Conclusions: These findings provide an accurate, affordable, excellent clinical potential model integrating four cfDNA molecular signatures for detecting early stage HCC from cirrhotic nodules using low-coverage WGS of plasma cfDNA samples. [Table: see text]

Liver cancer-specific isoform of serine protease inhibitor Kazal for the detection of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

Introduction. Surveillance of patients at risk of hepatocellular carcinoma (HCC) development mainly relies on ultrasound, while the role of serum biomarkers is still a matter of debate. Recent evidence highlighted a remarkable diagnostic accuracy of liver cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) for the detection of HCC in patients with cirrhosis of viral etiology.

Doylestown Plus and GALAD Demonstrate High Sensitivity for HCC Detection in Patients With Cirrhosis

Hepatocellular carcinoma (HCC) surveillance is associated with early tumor detection and improved survival in patients with cirrhosis.1 Surveillance is performed using semiannual abdominal ultrasound with or without α-fetoprotein (AFP); however, this strategy misses more than one-third of HCC at an early stage.2 These data highlight a need for novel surveillance strategies with higher accuracy for early HCC detection. GALAD and Doylestown Plus are novel biomarker panels that combine multiple biomarkers with patient demographic and clinical characteristics; both demonstrated promising accuracy in phase II case-control studies;3,4 however, case-control studies can overestimate biomarker performance, highlighting a need for phase III cohort and nested case-control studies.5 Our study aimed to compare multiple biomarkers (including AFP, GALAD, and Doylestown Plus) in a nested case-control study of patients with cirrhosis.

Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents

In the US, hepatocellular carcinoma (HCC), primarily associated with hepatitis C virus (HCV) infection, is the fastest rising cause of cancer-related death. Wider use of highly effective direct-acting antiviral agents (DAAs) substantially reduces the burden of chronic HCV infection, but the subsequent impacts with HCV-associated HCC remain unknown. To assess projected changes in the incidence rate of and surveillance burden for HCC in the era of DAA treatment for HCV. This decision analytical model study was performed from January 2019 to February 2020, using an individual-level state-transition simulation model to simulate disease progression, screening, and different waves of antiviral treatments for HCV in the US from 2012 to 2040. Current clinical management for chronic HCV infection. Model outcomes were projected temporal trends and age distribution of incident HCC cases and candidates for HCC surveillance among patients with viremia and patients with virologically cured HCV. The simulation model projected that the annual incidence of HCC among patients with viremia and patients with virologically cured HCV will continue increasing to 24 000 (95% uncertainty interval [UI], 18 000-31 000) cases until 2021. In patients with virologically cured HCV, incident HCC cases are projected to increase from 1000 (95% UI, 500-2100) in 2012 to the peak of 7000 (95% UI, 5000-9600) in 2031 with a subsequent decrease to 6000 (95% UI, 4300-8300) by 2040. The proportion of incident HCC cases that occur in individuals with virologically cured HCV is estimated to increase from 5.3% in 2012 to 45.8% in 2040. The number of candidates for HCC surveillance in the population with virologically cured HCV is projected to increase from 106 000 (95% UI, 70 000-178 000) in 2012 to the peak of 649 000 (95% UI, 512 000-824 000) in 2030 and decrease to 539 000 (95% UI, 421 000-687 000) by 2040, while the proportion of all candidates for surveillance who are virologically cured is estimated to increase from 8.5% to 64.6% during the same period. The average age of HCC incidence and surveillance candidates is estimated to increase from 55 in 2012 to 72 and 71, respectively, by 2040. The results of this study suggest that the burden of HCC will shift from patients with viremia to patients with virologically cured HCV, and to older populations. Appropriate management may be warranted for early detection of HCC in patients who may no longer be receiving specialty care for liver conditions.

Clinical relevance of increased serum preneoplastic antigen in hepatitis C-related hepatocellular carcinoma.

BACKGROUNDThe prognosis of hepatocellular carcinoma (HCC) patients remains poor despite advances in treatment modalities and diagnosis. It is important to identify useful markers for the early detection of HCC in patients. Preneoplastic antigen (PNA), originally reported in a rat carcinogenesis model, is increased in the tissues and serum of HCC patients.AIMTo determine the diagnostic value of PNA for discriminating HCC and to characterize PNA-positive HCC.METHODSPatients with hepatitis C virus (HCV)-related hepatic disorders were prospectively enrolled in this study, which included patients with hepatitis, with cirrhosis, and with HCC. A novel enzyme-linked immunosorbent assay was developed to measure serum PNA concentrations in patients.RESULTSSerum PNA concentrations were measured in 89 controls and 141 patients with HCV infections (50 hepatitis, 44 cirrhosis, and 47 HCC). Compared with control and non-HCC patients, PNA was increased in HCC. On receiver operating characteristic curve analysis, the sensitivity of PNA was similar to the HCC markers des-γ-carboxy-prothrombin (DCP) and α-fetoprotein (AFP), but the specificity of PNA was lower. There was no correlation between PNA and AFP and a significant but weak correlation between PNA and DCP in HCC patients. Importantly, the correlations with biochemical markers were completely different for PNA, AFP, and DCP; glutamyl transpeptidase was highly correlated with PNA, but not with AFP or DCP, and was significantly higher in PNA-high patients than in PNA-low patients with HCV-related HCC.CONCLUSIONPNA may have the potential to diagnose a novel type of HCC in which glutamyl transpeptidase is positively expressed but AFP or DCP is weakly or negatively expressed.

Usefulness of Circulating Methylated p16 as a Noninvasive Molecular Biomarker for Hepatitis C-Related Hepatocellular Carcinoma with Normal Serum Alpha-Fetoprotein Levels.

BackgroundScreening of hepatocellular carcinoma (HCC) is challenged especially in patients with normal alpha-fetoprotein (AFP) levels. Aberrant p16 methylation has been implicated in HCC.Objectives and AimsThis study aimed to assess serum methylated p16 (MP16) expression levels and to evaluate MP16 diagnostic performance in HCC detection among HCV-infected Egyptian patients with normal AFP levels.MethodsMP16 levels were quantified using real-time PCR in 230 serum samples (30 healthy controls, 95 with HCV-HCC, 40 with chronic hepatitis C “CHC” and 65 with HCV cirrhosis). Diagnostic performance of MP16 for diagnosis of HCC was done using receiver operator characteristic curve analysis.ResultsSerum MP16 levels were significantly higher in HCC than CHC, cirrhosis, and healthy subjects and significantly higher in HCC with normal AFP levels than those with higher AFP. ROC curves revealed promising diagnostic performance for MP16 in discriminating HCC with normal AFP levels from non-HCC cases. This predictive ability improved by combining MP16 and AFP (AUC of 0.872 with 100% sensitivity, 76.5% specificity, 79.1% positive predictive value, 100% negative predictive value, and 87.5% accuracy).ConclusionMP16 can be a potential noninvasive molecular biomarker for HCC detection in patients with hepatic mass(es) and normal AFP levels especially in those where liver biopsy and radiological imaging cannot be done.

Clinical utility of serum chromogranin A as a marker of hepatocellular carcinoma in chronic hepatitis patients

<br><b>Background</b><br>Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer deaths accounting for about 745 000 deaths per year globally. HCC is often diagnosed at an advanced stage where effective therapies are lacking.<br><b>Aim</b><br>Is to investigate the role of serum chromogranin A (CgA) as a marker for detection of HCC in patients with HCC complicating chronic hepatitis and correlate its serum levels with alpha fetoprotein (AFP).<br>This study was conducted on 90 HCC patients (group I), 30 patients with hepatic cirrhosis (group II), and 30 age-matched and sex-matched healthy-controls (group III). Group I was further subdivided into group Ia (30 patients) with HCC complicating chronic hepatitis B, and group Ib (60 patients) with HCC complicating chronic hepatitis C. All participants included in the study were subjected to full history taking and clinical examination, laboratory investigations, including complete blood count, liver-function tests, renal-function tests, and viral markers. Serum AFP and serum CgA levels were also determined.<br><b>Results</b><br>Our results revealed that there was a highly significant elevation (<i>P</i> < 0.01) in the median serum CgA in hepatitis-B virus -related HCC (200 ng/ml) and hepatitis-C virus-related HCC (190 ng/ml) when compared with the control group (30 ng/ml) and when compared with cirrhotic group (60 ng/ml) with no significant difference between the median serum CgA in hepatitis-B virus -related HCC and hepatitis-C virus-related HCC (<i>P</i> > 0.05). A highly significant positive correlation between chromogranin and AFP (<i>P</i> < 0.01) was found in HCC patients. On the other hand, no significant correlations were found between chromogranin and complete blood count, kidney functions, and liver-function tests in patient groups. Diagnostic reliability testing revealed that for CgA, the best cutoff for discriminating HCC patients was 100 ng/ml at which the sensitivity was 77.78%, the specificity 93.3% with positive predictive value 94.59% and negative predictive value 73.68%. Regarding the combination between CgA and AFP, it showed a sensitivity of 97.78% and a specificity of 86.67%.<br><b>Conclusion</b><br>Serum CgA is a promising sensitive and specific tumor marker for identification of HCC. Addition of serum CgA to the current standard tests will improve the sensitivity and accuracy of diagnosis of HCC patients and thus could allow them to benefit from earlier treatment.<br>

Hepatocellular carcinoma: An Update

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not significantly improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and the limited therapeutic options. The therapeutic options fall into several categories: (i) surgical interventions including tumor resection and liver transplantation, (ii) percutaneous interventions including ethanol injection and radiofrequency thermal ablation, (iii) transarterial interventions including embolization, chemoembolization and selective internal radiotherapy, (iv) external radiation therapy and (v) systemic strategies with cytotoxic agents and molecularly targeted therapies as well as immunotherapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for actual therapeutic recommendations. While surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, &lt;5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% of patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care (BSC). In order to reduce the morbidity and mortality from HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including cytotoxic agents, molecular targeted and immunotherapies is most important. New analytical technologies, including gene expression profiling and proteomic analyses and others, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.

Application value of dynamic contrast-enhanced magnetic resonance imaging and conventional magnetic resonance imaging in evaluation of hepatocellular carcinoma before and after TACE treatment

Objective To compare the application of dynamic contrast-enhanced magnetic resonance imaging (MRI) and conventional MRI in the detection of hepatocellular carcinoma (HCC) lesions before and after transcatheter arterial chemoembolization (TACE) treatment and evaluation of the effect of TACE treatment, thus to judge its application value, and to provide guidance for early clinical diagnosis. Methods Seventy-six patients with HCC who underwent TACE in Pingyang Hospital Affiliated to Wenzhou Medical University from January 2018 to December 2018 were selected in the research.According to the random number table method, 76 patients were randomly divided into control group and study group, with 38 cases in each group.The control group was examined by conventional MRI, while the study group was examined by dynamic enhancement of MRI.The lesions were observed before and after treatment, and Ktrans, Kep and ve of the two groups were recorded before and after treatment.The accuracy, sensitivity and specificity of the two groups were compared. Results Before and after treatment, the total detection rates of the study group (92.05%, 100.00%) were significantly higher than those of the control group (80.85%, 71.43%) (χ2=16.489, 15.246, all P 0.05). After treatment, the Ktrans and Kep values of the two groups were significantly decreased, and the Ktrans[(0.419±0.101)min] and Kep[(1.073±0.237)min] values of the study group were significantly lower than those of the control group [(0.647±0.128)min, (1.158±0.221)min], the differences were statistically significant (t=9.485, 5.642, all P>0.05). There was no statistically significant difference in ve value between the two groups (t=1.025, P>0.05). The accuracy and sensitivity of detection in the study group (92.11%, 97.37%) were significantly higher than those in the control group (81.58%, 84.21%), and the specificity (94.74%) of the study group was significantly lower than that of the control group (97.37%) (χ2=17.186, 14.453, 6.489, all P<0.05). Conclusion Dynamic contrast-enhanced MRI is more effective in the detection of HCC patients before and after TACE treatment.It is convenient to provide guidance for treatment and has higher clinical application value.It is worthy of popularizing. Key words: Liver neoplasms; Chemoembolization, therapeutic; Magnetic resonance imaging; Dynamic enhancement; Conventional magnetic resonance; Quantitative parameters; Curative effect; Application value

Circulating microRNA-301 as a promising diagnostic biomarker of hepatitis C virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious consequence of persistent hepatitis C virus (HCV) infection and represents one of the most aggressive neoplasms globally. The implication of microRNA-301 (miR-301) in the initiation and progression of different types of cancers has been proved. We aimed to assess circulating microRNA-301 as possible biomarker for the early detection of HCC in patients with chronic HCV infection. miR-301 expression levels were estimated in plasma samples of 42 patients with newly diagnosed HCV-related HCC, 48 chronically HCV infected patients with liver cirrhosis and 40 healthy individuals by reverse transcription-quantitative polymerase chain reaction technique. In comparison with chronically HCV infected patients and healthy controls, miR-301 expression levels were significantly increased in HCC patients (P < 0.001). miR-301 levels distinguished HCC patients from chronic HCV patients, with area under the receiver-operating characteristic curve of 0.89 (95% CI 0.82-0.96), the sensitivity and the specificity were 78.57% and 89.58% respectively. Moreover, miR-301 levels were significantly linked with tumor size (P = 0.014), serum levels of alpha-fetoprotein (AFP) (P = 0.028) and Barcelona Clinic Liver Cancer (BCLC) score (P = 0.003). These results reveal that miR-301 can serve as a promising non-invasive biomarker for diagnosis of HCC in chronically HCV infected patients.

Design of the Texas Hepatocellular Carcinoma Consortium Cohort Study.

The Texas Hepatocellular Carcinoma Consortium cohort study investigates risk factors of hepatocellular carcinoma (HCC) and biomarkers for early HCC detection in patients with liver cirrhosis. Adult patients with liver cirrhosis are enrolled at 5 clinical centers from 3 cities in Texas, with a target of 5,000 patients. Clinical history, risk factor questionnaires, liver imaging, laboratory data, and blood samples were collected at enrollment and at each 6-month follow-up visit. The primary outcome was the development of HCC. Biomarkers were tested in banked blood samples using prospective specimen collection, retrospective blinded evaluation design. We describe study design, eligibility criteria, recruitment, study cores, and sample size and analysis considerations.

High percentage atypical hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs.

Nucleos(t)ide analogs are used for preventing liver cirrhosis in chronic hepatitis B patients, but the risk factors of hepatocellular carcinoma (HCC) in these patients remain unclear. We designed this retrospective cohort study, the aim is to determine the risk factors for HCC development and its image presentation under nucleos(t)ide analogs treatment.In this study, patients were treated with lamivudine (LAM), entecavir 0.5 mg (ETV), or telbivudine (LdT), and followed-up for at least 2 years to detect HCC and its presentation. Assessment of the risk factors for HCC included age, sex, HBeAg, viral load, liver cirrhosis, current and previous medications, and liver function tests.Totally, 396 patients were recruited, and 18 patients developed HCC. The mean time from the treatment to HCC development was 28.5 ± 16.7 months. The clinical characteristics in HCC and no-HCC groups showed significant differences among age (52.8 ± 6.1 vs 47.1 ± 12.6 years, P <.01), baseline alanine transaminase (ALT) levels (161.4 ± 177.3 vs 361.7 ± 496.3, P <.01), and baseline liver cirrhosis (72.2% vs 29.9%, P <.01). In patients aged ≥45 years, the hazard ratio of HCC was 10.2 and liver cirrhosis was 4.1. Majority of HCCs developed in the right liver (14/18), were single numbered (13/18), had tumor size about 1.9 ± 0.7 cm, were classified as T1 (14/18, TNM staging), and the atypical image occupied 88% of the HCC cases.The patients aged ≧45 years on long-term nucleos(t)ide analog therapy, and with baseline liver cirrhosis were at a high risk of HCC. Regular alpha-fetoprotein (AFP) assessment and image study of these patients are the gold standards for early HCC detection in patients with high percentage atypical HCC appearances.

A novel machine learning approach for early detection of hepatocellular carcinoma patients

Liver cancer is quite common type of cancer among individuals worldwide. Hepatocellular carcinoma (HCC) is the malignancy of liver cancer. It has high impact on individual’s life and investigating it early can decline the number of annual deaths. This study proposes a new machine learning approach to detect HCC using 165 patients. Ten well-known machine learning algorithms are employed. In the preprocessing step, the normalization approach is used. The genetic algorithm coupled with stratified 5-fold cross-validation method is applied twice, first for parameter optimization and then for feature selection. In this work, support vector machine (SVM) (type C-SVC) with new 2level genetic optimizer (genetic training) and feature selection yielded the highest accuracy and F1-Score of 0.8849 and 0.8762 respectively. Our proposed model can be used to test the performance with huge database and aid the clinicians.

Validation of the Hepatocellular Carcinoma Early Detection Screening (HES) Algorithm in a Cohort of Veterans With Cirrhosis

Early detection of hepatocellular carcinoma (HCC) through surveillance reduces mortality associated with this cancer. Guidelines recommend HCC surveillance every 6 months for patientswith cirrhosis, via ultrasonography, with or without measurement of serum level of alpha fetoprotein (AFP). We previously developed and internally validated an HCC early detection screening (HES) algorithm that included patient's current level of AFP, rate of AFP change, age, level of alanine aminotransferase, and platelet count in a department of Veterans affairs (VA) cohort with active hepatitis C virus-related cirrhosis. HES score was associated with 3.84% absolute improvement in sensitivity of detection of HCC compared with AFP alone, at 90% specificity, within 6 months prior to diagnosis of this cancer. We externally validated the HES algorithm in a cohort of 38,431 patients with cirrhosis of any etiology evaluated at a VA medical center from 2010 through2015. A total of 4804 cases of HCC developed during a median follow-up time of 3.12 years. At 90% specificity, the HES algorithm identified patients with HCC with 52.56% sensitivity, compared to 48.13% sensitivity for the AFP assay alone, within 6 months prior to diagnosis; this was an absolute improvement of 4.43% (P < .0005). In HCC screening, a positive result leads to follow-up evaluation by computed tomography or magnetic resonance imaging. We estimated that the number of HCC cases detected per 1000 imaging analyses was 198.57 for the HES algorithm vs 185.52 for the AFP assay alone, or detection of 13 additional cases of HCC (P < .0005). We validated the HES algorithm in detection of HCC in patients with cirrhosis of any etiology evaluated at VA medical centers. The algorithm offers a modest but useful advantage over AFP alone in HCC surveillance.

Performance of protein induced by vitamin K absence or antagonist-II assessed by chemiluminescence enzyme immunoassay for hepatocellular carcinoma detection: a meta-analysis

Objectives: In the setting of surveillance for hepatocellular carcinoma (HCC) detection, the use of serum biomarkers in addition to ultrasonography (US) is still a matter of debate. Hence, we performed a meta-analysis to evaluate the diagnostic accuracy of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) alone or in combination for HCC detection in patients at risk of tumor development.Materials and methods: We performed a systematic search in PubMed and Scopus database for original articles published in English from 2011 to 2017, investigating the accuracy of PIVKA-II alone or in combination with AFP (reported as area under the curve [AUC]) for HCC detection among patients at risk of tumor development. Furthermore, we focused on studies in which serum PIVKA-II was assessed by highly sensitive chemiluminescence immunoassay (CLEIA).Results: A total of 11 studies (873 patients with HCC and 1244 patients with advanced liver disease/cirrhosis) were included in the meta-analysis. The weighted summary AUC (sAUC) of PIVKA-II and AFP for the discrimination between patients with HCC and those without was 0.791 (0.746–0.837) and 0.767 (0.732–0.803), respectively. The combination of PIVKA-II + AFP results in a sAUC of 0.859 (0.837–0.882). The performance for HCC detection of PIVKA-II + AFP was significantly superior to each biomarker used alone (ΔsAUC = 0.068, p = .032 and ΔsAUC = 0.092, p < .001, respectively).Conclusion: In clinical practice, the use of PIVKA-II + AFP in addition to US examination may improve the effectiveness of surveillance among patients at risk for HCC development.