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 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.

scholarly journals A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Naga P. Chalasani ◽  
T.S. Ramasubramanian ◽  
Abhik Bhattacharya ◽  
Marilyn C. Olson ◽  
David K. Edwards V ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Protein Markers ◽  
Methylated Dna

scholarly journals Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Hiraoka ◽  
Takashi Kumada ◽  
Toshifumi Tada ◽  
Joji Tani ◽  
Kazuya Kariyama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Hazard Analysis ◽  
Progression Free Survival ◽  
Significant Prognostic Factor ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Free Survival ◽  
Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

scholarly journals Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?

2022 ◽  
Vol 23 (1) ◽  
pp. 500
Author(s):  
Francesco Paolo Russo ◽  
Alberto Zanetto ◽  
Elisa Pinto ◽  
Sara Battistella ◽  
Barbara Penzo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Viral Hepatitis ◽  
Chronic Viral Hepatitis ◽  
Virological Suppression ◽  
Risk Patients ◽  
Related Liver Disease ◽  
Direct Acting ◽  
Cell Signaling Pathways

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death. Although the burden of alcohol- and NASH-related HCC is growing, chronic viral hepatitis (HBV and HCV) remains a major cause of HCC development worldwide. The pathophysiology of viral-related HCC includes liver inflammation, oxidative stress, and deregulation of cell signaling pathways. HBV is particularly oncogenic because, contrary to HCV, integrates in the cell DNA and persists despite virological suppression by nucleotide analogues. Surveillance by six-month ultrasound is recommended in patients with cirrhosis and in “high-risk” patients with chronic HBV infection. Antiviral therapy reduces the risks of development and recurrence of HCC; however, patients with advanced chronic liver disease remain at risk of HCC despite virological suppression/cure and should therefore continue surveillance. Multiple scores have been developed in patients with chronic hepatitis B to predict the risk of HCC development and may be used to stratify individual patient’s risk. In patients with HCV-related liver disease who achieve sustained virological response by direct acting antivirals, there is a strong need for markers/scores to predict long-term risk of HCC. In this review, we discuss the most recent advances regarding viral-related HCC.

scholarly journals Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

2015 ◽  
Vol 21 (3) ◽  
pp. 279 ◽  
Author(s):  
Chansik An ◽  
Youn Ah Choi ◽  
Dongil Choi ◽  
Yong Han Paik ◽  
Sang Hoon Ahn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Rate ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Early Stage ◽  
Chronic Liver

scholarly journals External validation of an algorithm combining multi‐analyte blood tests (FibroTest‐LCR1‐LCR2) to identify subjects at risk of hepatocellular carcinoma in patients with chronic liver disease

GastroHep ◽  
2019 ◽  
Vol 1 (3) ◽  
pp. 146-153
Author(s):  
Valentina Peta ◽  
Marianne Ziol ◽  
Françoise Imbert‐Bismut ◽  
Angela Sutton ◽  
Denis Monneret ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
External Validation ◽  
Chronic Liver ◽  
Blood Tests

Liver resection for multifocal hepatocellular carcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Peter Tae Wan Kim ◽  
Jihyun Jang ◽  
Sandra Fischer ◽  
Paul David Greig ◽  
Steven Gallinger ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Liver Resection ◽  
Chronic Liver Disease ◽  
Early Stage ◽  
Chronic Liver ◽  
Term Survival ◽  
Liver Resections ◽  
Common Etiology ◽  
Multifocal Disease

355 Background: Liver resection for multifocal hepatocellular carcinoma (HCC) is controversial. This study was conducted to outline our institution’s experience with liver resection for multifocal HCC. Methods: A retrospective review of patients who underwent liver resections from 1992 to 2011 for histologically confirmed hepatocellular carcinoma was performed. Multifocal disease was defined as more than 1 histologically proven HCC found in the liver resection specimens. Results: Of the 386 liver resections performed for HCC, 47 were performed for multifocal disease. Mean age was 60+11 years, and most patients (92%) had chronic liver disease. Hepatitis B was the most common etiology (60%), followed by hepatitis C (26%), and other etiologies (15%). Most patients were Child’s class A (89%). Most patients had intermediate Barcelona Clinic Liver Cancer (BCLC) stage (stage B) tumors (81%) and a minority of patients had early stage tumors (BCLC stage A, 19%). Major hepatectomy (>2 segments) was performed in 87% with an in hospital mortality of 6.4%. Major complications (Clavien-Dindo scale >3) occurred in 4 patients (9%). Median length of stay was 7 days and the rate of liver failure was 4.3%. Mean tumor number was 3+2 and the size of the largest lesion was 5+3 cm. Cirrhosis was present in 51% of patients. Majority of tumors were moderately differentiated (60%) and vascular invasion was present in 42%. The recurrence rate was 57% and the liver was the most common site of recurrence (81%). Treatment of recurrences occurred in 74% of patients: ablation (33%), chemotherapy (11%), transarterial chemoembolization (11%), resection (7.4%), sorafenib/radiation (7.4%) and transplantation (3.7%). Median disease free interval was 8 months and the overall survival was 18 months Conclusions: Liver resection for multifocal HCC can be performed safely in patients with chronic liver disease. Long term survival can be achieved in these patients and it should be considered as an option.

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