Hepatocellular carcinoma screening in cirrhotic patients is worth it in Australia

Background & Aims: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate the association between TLR3 gene polymorphism and HCV-related hepatocellular carcinoma in Egypt. Methods: This work was conducted on 70 individuals; fifty HCV cirrhotic patients were included in two groups; with HCC (30 patients) and without HCC (20 patients) compared with a group of 20 apparently healthy controls. All of the studied individuals underwent clinical-laboratory evaluation. TLR3 gene single-nucleotide polymorphism (SNP) (+1234C/T) was tested by polymerase chain reaction- restriction fragment length polymorphism. Results: This study reported that the prevalence of TLR3 +1234TT genotype was significantly increased in cirrhotic patients with HCC than without HCC, while it was not detected at all among the controls. When analyzing the TLR3 SNP +1234C/T with different clinical parameters in HCC patients, there was a significant association between+1234C/T SNP; namely TT genotype and each of the hepatic focal lesions᾽ number, size and the patients᾽ higher Okuda and BCLC stages. No association could be detected between TLR3 SNP and the age, sex, Child-Pugh grades, MELD score or AFP of the studied HCC cases. Conclusion: TLR3 gene SN P +1234C/T could be a novel risk factor for the HCV-related HCC among the Egyptian population.

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Genetic Determinants in a Critical Domain of NS5A Correlate with Hepatocellular Carcinoma in Cirrhotic Patients Infected with HCV Genotype 1b

Viruses ◽

10.3390/v13050743 ◽

2021 ◽

Vol 13 (5) ◽

pp. 743

Author(s):

Mohammad Alkhatib ◽

Velia Di Maio ◽

Valentina De Murtas ◽

Ennio Polilli ◽

Martina Milana ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariable Analysis ◽

Viral Fitness ◽

Cellular Proteins ◽

Genetic Determinants ◽

Hcv Genotype ◽

Genotype 1B ◽

Oncogenic Pathways ◽

Cirrhotic Patients ◽

Cycle Regulation

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and β-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.

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Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients

BMC Gastroenterology ◽

10.1186/s12876-021-01761-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kung-Hao Liang ◽

Ming-Wei Lai ◽

Yang-Hsiang Lin ◽

Yu-De Chu ◽

Chih-Lang Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Characteristic Curve ◽

Alpha Fetoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Interleukin 17 ◽

Medical Need ◽

Tumor Tissues ◽

Resected Tumor ◽

Cirrhotic Patients ◽

A Prospective Study

Abstract Background Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. Methods We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. Results IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893–0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: $${\text{R}} = (2.6914)*{\text{IL-17}} + (0.3909)*{\text{AFP}} - (0.80812875)*{\text{IL-17}}^{2} + (0.10288876884)*{\text{IL-17}}^{2} *{\text{AFP}}.$$ R = ( 2.6914 ) ∗ IL-17 + ( 0.3909 ) ∗ AFP - ( 0.80812875 ) ∗ IL-17 2 + ( 0.10288876884 ) ∗ IL-17 2 ∗ AFP . Conclusions The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

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

Egyptian Liver Journal ◽

10.1186/s43066-021-00122-7 ◽

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.

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Tumor size may influence the prognosis of solitary hepatocellular carcinoma patients with cirrhosis and without macrovascular invasion after hepatectomy

Scientific Reports ◽

10.1038/s41598-021-95835-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bin-yong Liang ◽

Jin Gu ◽

Min Xiong ◽

Er-lei Zhang ◽

Zun-yi Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Staging System ◽

Prognostic Impact ◽

Term Survival ◽

Long Term Survival ◽

Before And After ◽

Cirrhotic Patients ◽

Curative Hepatectomy

AbstractHepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

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