scholarly journals The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Cirrhosis ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Serum Samples ◽  
Disease Etiology ◽  
Risk Patients ◽  
Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

Algorithm for blood-based panel of methylated DNA and protein markers to detect early-stage hepatocellular carcinoma with high specificity.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4577-4577 ◽  
Author(s):  
Naga P. Chalasani ◽  
Abhik Bhattacharya ◽  
Adam Book ◽  
Brenda Neis ◽  
Kong Xiong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Disease ◽  
Early Stage ◽  
Lasso Regression ◽  
Protein Markers ◽  
Disease Etiology ◽  
Methylated Dna ◽  
Risk Patients ◽  
Higher Sensitivity

4577 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Though biannual ultrasound surveillance with or without alpha-fetoprotein (AFP) testing is recommended for at-risk patients, its sensitivity for early-stage HCC detection is suboptimal. We therefore evaluated performance of a biomarker panel incorporating methylated DNA markers (MDMs) and proteins for early HCC detection in at-risk patients with chronic liver disease. Methods: In an international, multicenter, case-control study, blood specimens were collected from patients with HCC per AASLD criteria and controls matched for age and liver disease etiology. All patients had underlying cirrhosis or chronic HBV infection. Whole blood was collected in cell-free DNA stabilizing and serum-separation tubes and shipped to a central laboratory for processing. The levels of 5 MDMs, AFP, and AFP-L3 were assessed along with age and sex. We used 537 samples in a 5-fold validation for developing a LASSO regression algorithm to classify samples as HCC positive or negative. Model robustness was tested by perturbing the data in silico and analyzing results with the predictive algorithm. Algorithm performance was compared to AFP alone and the GALAD score (Gender, Age, AFP-L3, AFP, and DCP). Results: The study included 136 HCC cases (81 early-stage—BCLC stage 0/A) and 401 controls. With specificity set at 89%, we developed a model using sex, AFP, and 3 MDMs (HOXA1, TSPYL5, B3GALT6) with higher sensitivity (70%) for early-stage HCC compared to GALAD (54%) or AFP (31% at 20 ng/mL or 52% at ≥7.7 ng/mL) (Table). The AUC for the HCC marker panel was 0.91 (95% CI 0.89 – 0.94) compared to GALAD (0.88; 95% CI 0.85 – 0.91) or AFP (0.84; 95% CI 0.81 – 0.87). The panel performed similarly in viral (AUC = 0.94) and non-viral (AUC = 0.89) etiologies. Conclusions: The robust algorithm based on novel blood-based biomarkers presented here provides higher sensitivity for early-stage HCC compared to other available blood-based biomarkers and, therefore, could significantly impact HCC clinical management and patient outcomes. Further clinical studies to validate the algorithm are ongoing. Clinical trial information: NCT03628651 . [Table: see text]

scholarly journals The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reham A. Aboelwafa ◽  
Walid Ismail Ellakany ◽  
Marwa A. Gamaleldin ◽  
Marwa A. Saad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis C ◽  
Early Stage ◽  
Group Iii ◽  
Real Time Quantitative Pcr ◽  
Early Stages ◽  
Group I ◽  
Egyptian Patients ◽  
Cirrhotic Patients

Abstract Background Hepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR. Results Levels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls. Conclusion Serum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

scholarly journals The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3740
Author(s):  
Chunye Zhang ◽  
Ming Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Early Stage ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Diagnostic Methods ◽  
T Cell Therapy ◽  
Nonalcoholic Fatty Liver

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

scholarly journals Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

2020 ◽  
Vol 9 (3) ◽  
pp. 765
Author(s):  
Chung-Man Moon ◽  
Sang Soo Shin ◽  
Suk Hee Heo ◽  
Yong Yeon Jeong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Lactate Dehydrogenase ◽  
Enzymatic Activity ◽  
Viral Hepatitis ◽  
Potential Risk ◽  
Early Stage ◽  
Liver Parenchyma ◽  
Cirrhotic Liver ◽  
1H Mrs

Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60–80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60–80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.

scholarly journals Improving the Detection of Hepatocellular Carcinoma using serum AFP expression in combination with GPC3 and micro-RNA miR-122 expression

2019 ◽  
Vol 14 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Jian Li ◽  
Sun Qiyu ◽  
Tiezheng Wang ◽  
Boxun Jin ◽  
Ning Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Operating Characteristic ◽  
Early Stage ◽  
Roc Curves ◽  
Micro Rna ◽  
Serum Samples ◽  
Serum Alpha Fetoprotein ◽  
Laboratory Investigations ◽  
Chronic Hcv ◽  
Positive Controls

AbstractEarly diagnosis of hepatocellular carcinoma (HCC) greatly improves the survival and prognosisfor patients. In this study weevaluate the diagnostic promise of combining serum alpha-fetoprotein (AFP) expression with two potential biomarkers, serum glypican-3 (GPC3) and expression of the micro-RNA miR-122 for hepatitis C virus (HCV) related early-stage HCC. For this study serum samples from 47 patients with early-stage HCC, 54 chronic HCV (CH) carriers, 35 patients with liver cirrhosis (LC) and 54 health controls (HC) were collected. In addition to routine laboratory investigations, serum AFP, GPC3 and miR-122 were measured in all patients and healthy controls. Receiver operating characteristic (ROC) curves were used to present sensitivity and specificity for the biomarkers. The three markers were all significantly elevated in the serum samples from HCC patients. ROC curves showed the three markers had similar diagnostic capacities for distinguishing early-stage HCC from HCV-positive controls (LC + CH). In order to distinguish early-stage HCC from high-risk LC patients, the expression of miR-122 was superior to GPC3. Combination of the three markers as a panel showed a better diagnostic performance than any of the single markers (P <0.05). Overall, this study revealed that serum expression of GPC3 and miR-122 may be useful biomarkers to combine with serum AFP expression for the diagnosis of HCV related early-stage HCC.

Hepatocellular carcinoma surveillance and appropriate treatment options improve survival for patients with liver cirrhosis

2010 ◽  
Vol 46 (4) ◽  
pp. 744-751 ◽  
Author(s):  
Yuan-Hung Kuo ◽  
Sheng-Nan Lu ◽  
Chao-Long Chen ◽  
Yu-Fan Cheng ◽  
Chih-Yun Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Treatment Options ◽  
Appropriate Treatment ◽  
Hepatocellular Carcinoma Surveillance

New advances in the diagnosis and management of hepatocellular carcinoma

BMJ ◽  
2020 ◽  
pp. m3544 ◽  
Author(s):  
Ju Dong Yang ◽  
Julie K Heimbach
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Early Stage ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Long Term Outcomes ◽  
Stage Disease

ABSTRACT Hepatocellular carcinoma is one of the leading causes of cancer related death in the world. Biannual surveillance for the disease in patients with cirrhosis and in high risk carriers of hepatitis B virus allows early stage cancer detection and treatment with good long term outcomes. Liver ultrasonography and serum α fetoprotein are the most commonly used surveillance tests. If suspicious results are found on the surveillance test, multiphasic computed tomography or magnetic resonance imaging should be undertaken to confirm the diagnosis of hepatocellular carcinoma. If radiologic tests show inconclusive results, liver biopsy or repeat imaging could be considered for confirmation of hepatocellular carcinoma. Management of the disease is complex. Patients should be evaluated by a multidisciplinary team, and the selection of treatment should consider factors such as tumor burden, severity of liver dysfunction, medical comorbidities, local expertise, and preference of patients. Early stage hepatocellular carcinoma is best managed by curative treatment, which includes resection, ablation, or transplantation. Patients with intermediate stage disease often receive locoregional treatment. Systemic treatment is reserved for patients with advanced disease. Several positive, phase III, randomized controlled trials have expanded the systemic treatment options for advanced hepatocellular carcinoma with promising long term outcomes, especially trials using combination treatments, which could also have eventual implications for the treatment of earlier stage disease.

scholarly journals Sub-Classification of Cirrhosis Affects Surgical Outcomes for Early Hepatocellular Carcinoma Independent of Portal Hypertension

2021 ◽  
Vol 11 ◽  
Author(s):  
Er-lei Zhang ◽  
Jiang Li ◽  
Jian Li ◽  
Wen-qiang Wang ◽  
Jin Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Surgical Outcomes ◽  
Early Stage ◽  
Surgical Mortality ◽  
Tumor Capsule ◽  
B Virus ◽  
Independent Risk Factors

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p &lt;0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.

Serum Dickkopf-1 as a diagnostic & prognostic marker for Hepatocellular Carcinoma

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Enas Mahmoud Foda ◽  
Khaled Amr Mansour ◽  
Walaa Mohamed Hashem ◽  
Nancy Zakaria Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Prognostic Marker ◽  
Early Stage ◽  
Serum Levels ◽  
University Hospitals ◽  
Post Intervention ◽  
Curative Therapy ◽  
Diagnostic Role ◽  
Dickkopf 1

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading reason of cancer-associated deaths around the world.The poor outcome of patients with HCC is attributed to late detection, with more than two-thirds of patients diagnosed at advanced stages of the disease. However, a considerable improvement in survival has been observed (5-year survival up from 40% to 70%) when patients are diagnosed at an early stage and receive potentially curative therapy in the form of liver transplantation, surgical resection, or tumor ablation. Objective Evaluate levels of serum Dickkopf-1, & its significance as a diagnostic & prognostic marker for Hepatocellular Carcinoma. Aim of the work assess the possible diagnostic role of serum DKK1 compared to alpha- fetoprotein which is the slandered marker used for diagnosis of HCC.also DKK1 act as prognostic marker for Hepatocellular Carcinoma. Pateints and Methodes This study had been carried out on 45 subjects diveded into 2 groups,first group include 30 pateints with liver cirrhosis,and second group 15 pateints with HCC.In this group of patients DKK1 was withdrawn before TACE & 3 months post intervention, age range 25-73 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from March 2019 till January 2020.They were distributed as 25 males and 20 females. There were 13 pateints with child A,17 pateints with child B, & 15 pateints (20%) with child C. Results In this study, the serum levels of serum DKK1 were highest in patients with HCC compared to those with liver cirrhosis. Also DKK1 values significally decreased after intervention(TACE). Conclusion Serum DKK1 act as a diagnostic marker for HCC and its level significally decrease after TACE

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