Hepatocellular Carcinoma In Liver Cirrhosis Patients Research Articles

MiR-3651 Participates in the Growth Cycle of Hepatocellular Carcinoma Cells and Promotes the Malignant Metastasis via the PI3K/AKT/mTOR Signalling Pathway.

Objective Hepatocellular carcinoma (HCC) shows a growing incidence over the past few years, and clinical efforts are made to search for more effective novel diagnosis and therapy regimen for it to improve its outcome. This study probed into the association of miR-3651 with the PI3K/AKT/mTOR pathway to offer a more detailed reference to the follow-up exploration of novel diagnosis and therapy methods of HCC. Methods Totally, 83 patients with HCC treated in our hospital between Apr. 2017 and Aug. 2018, 100 patients with simple liver cirrhosis (LC), and 94 normal persons over the same time span were enrolled, and serum miR-3651 in them was quantified to understand the predictive and prognostic significance of miR-3651 for HCC. In addition, with purchased human HCC cell strains (HepG2), the impacts of miR-3651 on the invasion as well as proliferation of HepG2 were determined using the MTT and Transwell assays, and the PI3K/AKT/mTOR pathway and autophagy-associated proteins in HepG2 were quantified via WT. Results Serum miR-3651 was found to be higher in HCC patients than in LC patients and normal persons, and it presented a sensitivity and specificity of 57.14% and 94.00%, respectively, in forecasting the occurrence of HCC in LC patients. The decrease of miR-3651 in HCC patients after therapy was strongly bound up with patients' prognosis, and its increase implied an increased risk of death. In in vitro assays, HepG2 presented higher miR-3651 expression than HL-7702, and upregulated miR-3651 intensified the invasion and proliferation of HepG2, while silencing miR-3651 gave rise to opposite results. Additionally, the PI3K/Akt/mTOR pathway in HepG2 presented an obvious activation state, and its activation was further intensified after increase of miR-3651, while its activation was suppressed after silence of miR-3651. Moreover, HepG2 presented notably downregulated autophagy-associated proteins, and the increase of miR-3651 further suppressed the autophagy process, but with the intervention of BEZ235, the impacts of miR-3651 were completely reversed. Conclusion miR-3651 intensifies the growth and invasion of HCC cells through activating the PI3K/AKT/mTOR signalling pathway, which is probably a breakthrough in the future diagnosis and therapy of HCC.

Abstract No. 340 ▪ FEATURED ABSTRACT Artificial intelligence-mediated multidisciplinary approaches for hepatocellular carcinoma early diagnosis

Cirrhosis is a crucial risk factor for hepatocellular carcinoma (HCC), with over 90% of HCC patients having underlying cirrhosis. An integrated multidisciplinary surveillance approach including artificial intelligence (AI) mediated quantitative image analysis, transcriptomics, and proteomics biomarkers will improve the early diagnosis of HCC in liver cirrhosis patients.

Serum microRNA expression profiling identifies serum biomarkers for HCV-related hepatocellular carcinoma.

The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential. The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC. Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC. Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects. The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis.

Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals

BackgroundDirect-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. AimsThe aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. MethodsIn 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. ResultsMedian LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was −26.7% (IQR: −38.4% −13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (−18.0% vs −28.9% p = 0.005). At multivariate analysis, ∆LS lower than −30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. ConclusionOur results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment.

FABP1 Polymorphisms Contribute to Hepatocellular Carcinoma Susceptibility in Chinese Population with Liver Cirrhosis: A Case-Control Study.

Purpose: Single nucleotide variations in the liver fatty acid binding protein (L-FABP, FABP1) gene lead to changes in cellular signaling pathways and lipid metabolism. FABP1 polymorphisms were associated with some liver diseases, like steatotic hepatocellular carcinoma. However, the association between FABP1 rs1545224 and rs2241883 polymorphisms and hepatitis B virus-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) has not been reported. We performed this study to explore their relationship.Methods: One thousand individuals (250 healthy controls, 250 chronic HBV (CHB), 250 LC, and 250 HCC patients) were recruited. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to assess the difference in allele and genotype frequencies. Cochran-Armitage trend test was used to evaluate the cumulative effect. Significant difference would be defined when the P value was less than 0.05.Results: The distribution of rs1545224 GG, AG and AA genotypes in healthy controls or CHB carriers was not significant when compared to LC or HCC patients (P>0.05). LC patients carrying at least one A allele are more likely to develop HCC in contrast with those with G allele (P<0.05). After adjustment for confounders, meaningful results were only seen in the comparison between rs1545224 AG+AA genotype carriers and GG genotype carriers among the LC patients (P<0.05). Rs2241883 polymorphism did not influence the risk of developing LC or HCC in healthy and CHB individuals, nor did it influence the risk of HCC in LC patients (P>0.05).Conclusions: Taken together, FABP1 rs1545224 polymorphism might increase HCC risk in LC patients, indicating that FABP1 rs1545224 polymorphism may be related to the process of developing HCC in Chinese patients with LC.

Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection.

The identification of new high-sensitivity and high-specificity markers for hepatocellular carcinoma (HCC) is essential. We aimed at identifying serum microRNAs (miRNAs) as potential biomarkers for early detection of HCC on top hepatitis C virus (HCV) infection. We investigated serum expression of 13 miRNAs in 384 patients with HCV-related chronic liver disease (192 with HCC, 96 with liver cirrhosis (LC), and 96 with chronic hepatitis C (CHC)) in addition to 96 healthy participants enrolled as a control group. The miRNA expression was performed using real-time quantitative PCR-based SYBR Green custom miRNA arrays. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of miRNA panels for early detection of HCC. Using miRNA panel of miR-122, miR-885-5p, and miR-29b with alpha fetoprotein (AFP) provided high diagnostic accuracy (AUC = 1) for early detection of HCC in normal population while using miRNA panel of miR-122, miR-885-5p, miR-221, and miR-22 with AFP provided high diagnostic accuracy (AUC = 0.982) for early detection of HCC in LC patients. However, using miRNA panel of miR-22 and miR-199a-3p with AFP provided high diagnostic accuracy (AUC = 0.988) for early detection of HCC in CHC patients. We identified serum miRNA panels that could have a considerable clinical use in early detection of HCC in both normal population and high-risk patients.

Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside/nucleotide analog therapy.

Some patients develop hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy even if alanine aminotransferase (ALT) or hepatitis B virus (HBV) DNA levels are sufficiently reduced. The aim of this study is to identify the risk factors of development of HCC during NA therapy. Six hundred and two patients were analyzed who were continuously receiving NA for chronic HBV infection. The patients who developed HCC previously or within 1 year of therapy were excluded. In the patients studied, the median duration of therapy was 90 months. A total of 492 patients had chronic hepatitis (CH) and 110 had liver cirrhosis (LC). In 602 patients, the rate of normalization of ALT, loss of serum HBV DNA and development of HCC were 90.4%, 55.4%, and 6.1%, respectively. The significant risk factors of development of HCC were LC status and duration of therapy. The annual incidence of HCC in LC patients was 2.53%/year, compared with 0.34%/year in CH patients. When the relation between the incidence of HCC and the response to therapy was evaluated, in patients with normalization of ALT level, loss of HBV DNA by real-time polymerase chain reaction or hepatitis B e-antigen seroconversion, the incidences of HCC was reduced to some extent. However, none of the patients who achieved hepatitis B surface antigen (HBsAg) seroclearance during NA therapy developed HCC. LC status was the significant risk factor of development of HCC during NA therapy. However, none of the patients who showed HBsAg seroclearance developed HCC. The ultimate goal of therapy for reduced risk of HCC may be HBsAg seroclearance.

Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations

To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis. We investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ(2) test and unconditional logistic regression analysis. In the HCC group, genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The differences in genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ(2) = 15.441, P = 0.000; χ(2) = 11.983, P = 0.001; P = 0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC occurred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P = 0.000). Unconditional logistic regression analysis revealed that patients infected by genotype C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P = 0.013, 95%CI: 1.540-39.264). Genotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.

A simultaneous monitoring of Lens culinaris agglutinin A-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients.

To elucidate the risk factors for developing hepatocellular carcinoma (HCC) during the follow-up of patients with liver cirrhosis (LC), outpatients with LC were examined periodically by means of serum biochemical assessments, ultrasonography, and computed tomography. Risk factors for HCC were statistically analyzed. We also examined an efficacy of Lens culinaris agglutinin A-reactive profiles of alpha-fetoprotein (AFP-L3%) and des-gamma-carboxy prothrombin (DCP) value using a highly sensitive DCP determination kit (ED036) for the early recognition of HCC. The AFP-L3% and the ED036 value were retrospectively determined with stored serum samples. HCC was diagnosed in 21 of the 78 patients with LC during the follow-up period (mean follow-up period: 42 months). The estimated cumulative incidence of HCC was 25% with 3 years and 48% with 5 years. The most significant risk factor for the development of HCC in LC patients was found to be the mean serum AFP concentration from the year before the HCC detection (p=0.02). At the time of the recognition of HCC, the positive rates of the tumor markers were: serum AFP concentration 14%, serum DCP value 5%, AFP-L3% was 33%, and that of ED036 43%. The positive rate in collaborative use of AFP-L3% and ED036 was 67%. The simultaneous determination of the AFP-L3% and the ED036 value was shown to be effective for the early detection of HCC.