HCV-induced Liver Cirrhosis Research Articles

Exploring the prognostic significance of blood carnitine and acylcarnitines in hepatitis C virus-induced hepatocellular carcinoma

BackgroundHepatic energy metabolism is intricately linked with the metabolic changes associated with HCV infection and hepatocellular carcinoma (HCC). This study investigated the potential of carnitine and acylcarnitines as markers for monitoring the development and progression of HCC in the context of HCV-induced liver cirrhosis. Blood samples from patients with chronic liver cirrhosis due to HCV (n = 55) and from those with HCC (n = 90) were analyzed, alongside samples from healthy control subjects (n = 25), utilizing liquid chromatography coupled with mass spectrometry.ResultsPrincipal component analysis revealed distinct metabolic clustering patterns, segregating HCC and HCV patients into separate groups. Pairwise comparisons showed significantly elevated acylcarnitine levels in both HCV and HCC patients when compared to the control group (p = 0.001). Importantly, there was no significant difference between HCV and HCC groups, although linear trend analysis indicated an increasing linear trend that reached its peak in the HCC group, signifying a notable relationship with disease severity (p = 0.001).ConclusionThe observed carnitine and acylcarnitine levels in HCV and HCC patients offer crucial clinical insights, suggesting their potential as valuable diagnostic and prognostic markers.

Vitamin D receptor rs3782905 and vitamin D binding protein rs7041 polymorphisms are associated with hepatocellular carcinoma susceptibility in cirrhotic HCV patients

BackgroundThe severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are associated with genetic variations within vitamin D receptor (VDR) in several populations. This study aims to determine the significance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection and their effect on the progression of liver cirrhosis to carcinogenesis.MethodsSingle nucleotide polymorphisms (SNPs) VDR (rs2228570, rs3782905), and DBP rs7041 were genotyped using restriction fragment length-PCR (RFLP-PCR) technique and VDR rs11568820 was genotyped using single strand polymorphism PCR (SSP PCR). These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls).ResultThe VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly higher in HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are higher in HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported.ConclusionAmong the four investigated SNPs, there are associations between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. These SNPs are considered as risk factors in HCV induced liver cirrhosis and HCC. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. Future research with a larger sample size of subjects with HCV infection is advised, because chronic liver disease induced by HCV infection is the primary cause of HCC in Egypt. We recommend screening of these SNPs for prediction of LC and HCC development in HCV infected patients, which may improve the used therapeutic protocol. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.

Evaluation of the Novel PAP Score and Other Fibrosis Scores as Non-Invasive Alternative for Upper GI Endoscopy in Detection of Large Esophageal Varices in HCV-Induced Liver Cirrhosis

Evaluation of the Novel PAP Score and Other Fibrosis Scores as Non-Invasive Alternative for Upper GI Endoscopy in Detection of Large Esophageal Varices in HCV-Induced Liver Cirrhosis

Elevated Serum Vinculin in Patients with HBV/HCV-Associated Liver Cirrhosis and Hepatocellular Carcinoma: A Pilot Study.

The stiffness of the extracellular matrix (ECM) controls many cellular processes, such as migration and differentiation. Cells detect stiffness through adhesion structures termed focal adhesions (FAs). Vinculin, an actin-binding FA protein, plays a pivotal role in FA-mediated mechanotransduction. This study aimed to explore the role of vinculin in the development of HBV/HCV-induced hepatocellular carcinoma (HCC). Vinculin levels in a total number of 100 serum samples from patients with HBV/HCV-induced liver cirrhosis and HCC, as well as healthy controls, were analyzed using an enzyme-linked immunosorbent assay (ELISA). In patients with HCC and liver cirrhosis, the serum vinculin levels were significantly greater than in controls (503.8±242.2 and 728.4±1044.8 vs 77.7±36.1 respectively, p<0.001). However, results showed no link between serum vinculin and the clinicopathological features of HCC. Patients with HBVor HCV-induced liver cirrhosis and HCC have significantly higher serum levels of vinculin than do controls. This might point to a potential role for vinculin in the development of HCC. More research into how this protein affects the development of HCC at the molecular level could lead to better clinical treatments and the development of new molecular therapies.

Association of PNPLA3 (rs738409) & TM6SF2 (rs58542926) and ATG16L1 (rs2241880) genetic variants with susceptibility to hepatocellular carcinoma in a group of Egyptian patients with HCV-induced liver cirrhosis

Association of PNPLA3 (rs738409) & TM6SF2 (rs58542926) and ATG16L1 (rs2241880) genetic variants with susceptibility to hepatocellular carcinoma in a group of Egyptian patients with HCV-induced liver cirrhosis

Interplay between TGF-b1 and miRNA-122 biomarkers in hepatocellular carcinoma progression in patients with chronic hepatitis C.

Hepatocellular carcinoma (HCC) is a highly lethal malignancy and clinically validated medications have not yet been developed since there are no reliable diagnostic and prognostic biomarkers. Based on bioinformatics tools, TGF-b1 gene was the first target gene of miRNA-122, therefore this study was intended to assess the potential interconnection between TGF-b1 and miRNA-122 as a diagnostic and prognostic biomarker in the progression of HCC in patients with chronic hepatitis C (CHC) genotype (4). In this study, 100 people were included and split into two groups; group I: CHC patients without HCC that were classified into patients CHC without cirrhosis and CHC cirrhotic patients, group II: CHC patients with HCC, and healthy volunteers as control. The expression of miRNA-122 and TGF-b1 genes were analyzed using Real-Time PCR. An upregulation of miRNA-122 gene in cirrhotic and HCC patients compared to both chronic HCV non-cirrhotic, and cirrhotic patients, while, a decrease in expression of TGF-b1 was found in cirrhotic patients compared to HCV non-cirrhotic patients. Although significantly downregulated in HCC patients. Regression analysis indicated that the expression levels of miRNA-122 and TGF-b1 could be regarded as important indicators of the alterations in cirrhotic and HCC patients versus HCV non-cirrhotic patients, also with the chances of HCC versus cirrhosis patients. Our data indicated an interaction between miRNA-122 and TGF-b1, regulated gene expression and recommended the use of these parameters as noninvasive predictive biomarkers and therapeutic targets for HCV induced liver cirrhosis and HCC.

Retraction Note: The interaction between microRNA-152 and DNA methyltransferase-1 as an epigenetic prognostic biomarker in HCV-induced liver cirrhosis and HCC patients.

Retraction Note: The interaction between microRNA-152 and DNA methyltransferase-1 as an epigenetic prognostic biomarker in HCV-induced liver cirrhosis and HCC patients.

Value of Serum miRNA-96-5p and miRNA-99a-5p as Diagnostic Biomarkers for Hepatocellular Carcinoma.

PurposeCirculatory microRNAs (miRNAs) have the potential to be employed as markers for cancer detection and as prognostic tools for disease management. As a result, our goal was to explore the effectiveness of serum miRNA-96-5p and miRNA-99a-5p as diagnostic tools in hepatocellular carcinoma (HCC).Patients and methodsBlood samples were collected from 55 patients with HCV-induced HCC, 55 patients with HCV-induced liver cirrhosis, and 55 healthy controls. The expression levels of miRNA-96-5p and miRNA-99a-5p were measured using quantitative RT-PCR.ResultsmiRNA-96-5p expression levels were increased in HCC patient sera, while miRNA-99a-5p levels were reduced. According to ROC curve analysis, using a combination of circulating miRNA-96-5p, miRNA-99a-5-, and alpha-fetoprotein (AFP) improves the accuracy of diagnoses for HCC, with an area under the curve (AUC) of 0.97, compared to AUCs of 0.82, 0.86, and 0.73, respectively, for the individual biomarkers. Furthermore, the present data suggested that higher serum miRNA-96-5p levels were linked to larger tumors and metastasis, whereas lower serum miRNA-99a-5p levels were exclusively linked to HCC metastasis.ConclusionUsing miRNA-96-5p and miRNA-99a-5p in combination with AFP increased both sensitivity and specificity for the diagnosis of HCC. Furthermore, serum levels were linked to tumor size and metastasis. These findings suggested that serum miRNA-96-5p and miRNA-99a-5p could be used as non-invasive biomarkers for the diagnosis of HCC.

Serum Beclin 1 and autophagy-related protein-5 and the risk of hepatocellular carcinoma among cirrhotic hepatitis C patients

BackgroundThe most common primary liver cancer in adults is hepatocellular carcinoma (HCC) which is commonly presented with a poor prognosis. Therefore, it is important to explore effective biomarkers and therapeutic targets for HCC patients. Autophagy is involved in the development and prevention of cancer. Mammalian Beclin-1 is needed for an autophagic vesicle in HCC. Autophagy-related protein-5 (ATG5) is an important molecule involved in cell death during autophagy. The objective is to investigate serum ATG 5 and Beclin 1 levels in HCV-induced liver cirrhosis with and without HCC. The study was conducted on 80 individuals classified into 3 groups:Group 1: 30 patients with HCV-induced liver cirrhosis without HCC.Group 2: 30 patients with HCV-induced liver cirrhosis with HCC.Group 3: 20 healthy subjects (control group).ResultsSerum ATG 5 was significantly lower in HCC than liver cirrhosis patients. Serum Beclin 1 was significantly higher in HCC than liver cirrhosis patients. A cutoff value of < 95.7 and > 5.3 of serum ATG5 and Beclin 1 could be suggested for diagnosis of HCC among patients with HCV-related cirrhosis.ConclusionSerum Beclin 1 and ATG 5 could be used as a novel diagnostic marker for HCC. Moreover, scoring of serum BECLIN 1, ATG 5, and cachexia might be a future promising tool to predict the risk of HCC development.

Role of bile acids in the prediction of hepatocellular carcinoma in HCV-induced liver cirrhosis

BackgroundBile acids are essential organic molecules synthesized from cholesterol in the liver and regarded as indicators of hepatobiliary impairment; however, their role in the pathogenesis of hepatocellular carcinoma (HCC) is still unclear. The study aimed to examine the feasibility of bile acids in distinguishing HCC from post hepatitis C virus liver cirrhosis. A UPLC/MS was used to measure 14 bile acids in patients with noncirrhotic HCV disease (n = 50), cirrhotic HCV disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50).ResultsThe progression of liver cirrhosis to HCC was associated with a significant increase in serum bile acids compared to the normal or the noncirrhotic HCV disease (p < 0.05). The fold changes in bile acids concentrations showed a trend that HCC > cirrhotic HCV disease > noncirrhotic HCV disease. Four conjugated acids GCA, GCDCA, GUDCA, and TCDCA steadily increased across the different groups. ROC curves analysis revealed that these bile acids discriminated noncirrhotic liver patients from HCC (AUC 0.850–0.963), with a weaker potential to distinguish chronic liver cirrhosis from HCC (AUC 0.414–0.638).ConclusionThe level of serum bile acid was associated primarily with liver cirrhosis, with little value in predicting the progress of chronic liver cirrhotic disease into hepatocellular carcinoma.

Rapid Decline of Serum Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) in Non-Cirrhotic Patients with Chronic Hepatitis C Infection Receiving Direct-Acting Antiviral Therapy.

Direct-acting antivirals (DAAs) efficiently eradicate the hepatitis C virus (HCV). Low-density lipoprotein (LDL) levels increase rapidly upon DAA treatment. Proprotein convertase subtilisin/kexin 9 (PCSK9) induces degradation of the hepatic LDL receptor and thereby elevates serum LDL. The aim of this study was to determine serum PCSK9 concentrations during and after DAA therapy to identify associations with LDL levels. Serum PCSK9 was increased in 82 chronic HCV-infected patients compared to 55 patients not infected with HCV. Serum PCSK9 was low in HCV patients with liver cirrhosis, but patients with HCV-induced liver cirrhosis still exhibited higher serum PCSK9 than patients with non-viral liver cirrhosis. Serum PCSK9 correlated with measures of liver injury and inflammation in cirrhotic HCV patients. In patients without liver cirrhosis, a positive association of serum PCSK9 with viral load existed. Serum PCSK9 was not different between viral genotypes. Serum PCSK9 did not correlate with LDL levels in HCV patients irrespective of cirrhotic status. Serum PCSK9 was reduced, and LDL was increased at four weeks after DAA therapy start in non-cirrhotic HCV patients. Serum PCSK9 and LDL did not change upon DAA treatment in the cirrhotic group. The rapid decline of PCSK9 after the start of DAA therapy in conjunction with raised LDL levels in non-cirrhotic HCV patients shows that these changes are not functionally related.

The role of IL-4 gene polymorphism in HCV-related hepatocellular carcinoma in Egyptian patients

BackgroundInterleukin-4 (IL-4), a pleiotropic anti-inflammatory cytokine, is produced mainly by activated T helper 2 (Th2). Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer. Alterations influencing IL-4 expression may disturb immune response and may be associated with HCC risk. We aimed to verify role of IL4 gene polymorphism (IL-4-589C/T (rs2243250)) in HCV-related hepatocellular carcinoma in Egyptian patients. IL-4-589C/T (rs2243250) polymorphism was examined in 50 patients with HCC on top of HCV, 40 patients with HCV-induced liver cirrhosis, and 30 healthy controls using the polymerase chain reaction- restriction fragment length polymorphism method.ResultsOverall IL-4 gene polymorphism (IL-4-589C/T (rs2243250)) showed significant difference between hepatocellular carcinoma group versus liver cirrhosis and healthy control groups. TT homozygous genotype was more prevalent in HCC group (24%) versus (5%) in liver cirrhosis and (3.3%) in control. TT homozygous genotype had 10 times more risk of hepatocellular carcinoma versus healthy control group and 6.33 times more risk versus cirrhotic patients group (p value = 0.018 and 0.016 respectively).ConclusionIL-4-589C/T (rs2243250) polymorphism, TT homozygous genetic model, may be a risk factor in HCV-related HCC in Egyptian patients.

Значимость динамики уровня сывороточного маркера фиброза печени WFA+-M2BP у пациентов с хроническим гепатитом С

Objective. To evaluate the role of dynamics of WFA+-M2BP, a serum marker of liver fibrosis, in patients with chronic hepatitis C (CHC). Patients and methods. We examined 56 CHC patients who received antiviral therapy. The severity of liver fibrosis was assessed using indirect elastometry. There were 8 patients with F0 fibrosis, 17 patients with F1 fibrosis, 6 patients with F2 fibrosis, 12 patients with F3 fibrosis, and 13 patients with F4 fibrosis. The level of WFA+-M2BP was measured prior to treatment initiation, then 1 month after treatment initiation, and 3 months after treatment completion. Results. We found that both CHC patients and patients with HCV-induced liver cirrhosis demonstrated a decrease in the serum level of WFA+-M2BP in response to antiviral therapy. Mean levels of WFA+-M2BP in individuals with F3 and F4 fibrosis were significantly higher than those in patients with F0 fibrosis (p &lt; 0.01). Conclusion. Higher grades of liver cirrhosis were associated with higher serum levels of WFA+-M2BP, while antiviral therapy led to a decrease in the concentration of this biomarker. The assessment of WFA+-M2BP dynamics will help to detect early stages of liver fibrosis and also to monitor it in patients receiving antiviral therapy. Key words: chronic hepatitis C, liver cirrhosis caused by HCV, biomarker, WFA+-M2BP, liver fibrosis, antiviral therapy

Association between MICA rs2596542 Polymorphism with the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients.

In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC).

Background and objectives:Hepatocellular carcinoma (HCC) is a potential health problem in Egypt because of the high prevalence of HCV infection. Using alpha-fetoprotein for diagnosis is unsatisfactory especially in early stages. Many studies showed that microRNAs (miRNA) expression may be associated with the development and progression of various types of cancer including HCC and it may serve as biomarkers for diagnosis. This study examined two miRNAs which are miRNA-122 and miRNA-224 if it could serve as biomarkers for diagnosis of HCC. Methods:This study included 20 patients with HCV-induced HCC and 20 patients with HCV-induced liver cirrhosis for comparison. As well as 20 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and determination of serum alpha-fetoprotein. Quantification of plasma miRNA-122 and miRNA-224 was done by real-time quantitative PCR. Results:Our results showed that levels of miRNA-122 were significantly lower in HCC group compared to the cirrhosis group and controls, while levels of miRNA-224 were significantly higher. The levels of both miRNAs have a correlation with tumor size. Moreover, the diagnostic accuracy of miRNA-122 (sensitivity 95%, specificity 81%, p-value <0.001) and of miRNA-224 (sensitivity 85%, specificity 79%, p-value <0.001) in discriminating patients with HCC from patients with liver cirrhosis were higher than that of alpha-fetoprotein (sensitivity 70%, specificity 70%, p-value <0.05). In addition, combining any one of these miRNAs with alpha-fetoprotein will increase the diagnostic accuracy compared to using each marker alone. Conclusion: miRNA-122 and miRNA-224 could serve as biomarkers for the diagnosis of HCC.

The interaction between microRNA-152 and DNA methyltransferase-1 as an epigenetic prognostic biomarker in HCV-induced liver cirrhosis and HCC patients.

The necessity for early detection and hence improving the outcome of treatment of hepatocellular carcinoma (HCC) is critical especially in Hepatitis C virus (HCV)-Genotype 4 induced cases. In our current work, we examined the miRNA-152 and DNMT-1 expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients as an attempt to evaluate the potential benefits of these new circulating, noninvasive, prognostic, epigenetic markers for liver cirrhosis and carcinogenesis of Egyptian patients. Eighty subjects were included in this study, divided into two groups; group I (40 patients) were classified into subgroup Ia (CLD without cirrhosis, n = 18) and subgroup Ib (CLD with cirrhosis, n = 22), group II (CLD patients with HCC, n = 20), and control (Healthy volunteer, n = 20). The expression of miRNA-152 and DNMT-1 genes were analyzed using Real-Time PCR. MiRNA-152 showed a persistent and significant downregulation in all diseased groups, which was in consistence with the progression of the disease toward the HCC stage. DNMT-1 showed upregulation in all diseased groups when compared to control and subgroup Ia. The miRNA-152 was shown to correlate inversely with DNMT-1 in subgroup Ia, Ib and group II (r = -0.557, p < 0.01), (r = -0.850, p < 0.001) and (r = -0.544, p < 0.02) respectively. In addition, miRNA-152 and DNMT-1 showed a diagnostic ability to discriminate between cases of cirrhosis and HCC against CLD without cirrhosis (p < 0.01), while DNMT-1 did not, except between HCC and cirrhotic cases. Furthermore, both genes can be considered as predictor and prognostic parameters for cirrhosis (OR = 1.041, p = 0.043) and (OR = 1.039, p = 0.04) respectively, while miRNA-152 alone is proved as a prognostic marker for HCC (OR = 1.003, p = 0.044). Finally, the persistent reverse correlation between miRNA-152 with DNMT-1 prompts their use as noninvasive prognostic biomarkers for HCV induced liver cirrhosis and HCC in HCV Genotype 4 patients.

CDH1 gene as a prognostic biomarker in HCV (genotype 4) induced hepatocellular carcinoma in the Egyptian patients

Patients with hepatocellular carcinoma (HCC) have indigent in prognosis tools due to being diagnosed at the latest stages. It's crucial to identify efficient biomarkers that can get better overall diagnosis and treatment of HCC. In the current work, we examined prototypical type I cadherin (CDH1) expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients as an attempt to evaluate the potential benefits of this new circulating, noninvasive, prognostic, biomarkers for liver cirrhosis and carcinogenesis of Egyptian patients. Eighty subjects were included in this study, divided into two groups; Group I (40 patients) were classified into Group Ia (CLD without cirrhosis, n = 18) and Group Ib (CLD with cirrhosis, n = 22), Group II (CLD patients with HCC, n = 20), and control (Healthy volunteer, n = 20). The expression of CDH1 gene was analyzed by Real-Time PCR. CDH1 showed a persistent and significant downregulation in all diseased groups, which was inconsistency with the progression of the disease toward the HCC stage. In addition, it showed a diagnostic ability to discriminate between cases of HCC against CLD with/without cirrhosis (p < 0.001). Furthermore, CDH1 gene could be considered as a predictor and prognostic parameters for HCC (OR = 0.15, 95% CI 0.033–0.677, p = 0.01), but it was not suitable for use as a predictor for cirrhotic patients. Finally, the gradual decline of CDH1 gene expression with disease progression prompts us to use it as noninvasive prognostic biomarkers for HCV induced liver cirrhosis and HCC in HCV Genotype 4 patients. Abbreviations listUnlabelled TableAASLDAmerican Association for the Study of Liver DiseasesAFPalpha fetoproteinALTalanine aminotrasferaseANAanti-nuclear antibodiesAPRIAST, platelet ratio indexASTaspartate aminotransferaseAUCarea under the ROCCDH1E-cadherin 1CLDchronic liver diseaseCTcomputed tomographyCTthresholdDAAdirect acting antiviralELISAenzyme-linked immunosorbent assayHCChepatocellular carcinomaHCVhepatitis C virusHSCshepatic stellate cellsINRinternational normalized ratioNASHnon-alcoholic steato-hepatitisNPVnegative predictivePCprothrombin concentrationPPVpositive predictive valuePTprothrombin timercorrelation coefficientROCreceiver operating characteristicSPSSstatistical package for social scienceTBRITheodor Bilharz research instituteTSGtumor suppressor genes

Profiling of plasma metabolomics in patients with hepatitis C-related liver cirrhosis and hepatocellular carcinoma.

Aim of the studyThe diagnosis of hepatocellular carcinoma (HCC) is usually late, due to the lack of early detection of biomarkers for HCC. Metabolomics analysis has emerged as a useful tool for studying human diseases. The objective of the study was to investigate the differences in plasma metabolites between hepatitis C virus (HCV)-induced cirrhosis and HCC.Material and methods22 subjects with HCV-related liver cirrhosis and 22 subjects with HCC were enrolled. Clinical, routine laboratory and imaging studies were done. Gas chromatography/mass spectrometry (GC/MS) was used for metabolomics analysis of patients’ plasma samples.Results34 known metabolites were detected, of which five metabolites were identified to have the strongest discriminatory power for separation between HCC and cirrhosis groups: octanoic acid (caprylic acid), decanoic (capric acid), oleic acid, oxalic acid and glycine. These are 3 fatty acids (FA), a dicarboxylic acid and a glucogenic amino acid, respectively. No significant correlation was found between the relative intensities of the five metabolites and any of the patient or tumor characteristics (Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, number of focal lesions and size of largest focal lesion). ROC curve analysis was performed and area under the curve (AUC) was calculated, revealing that oleic acid, octanoic (caprylic) acid and glycine had higher positive predictive value than α-fetoprotein.ConclusionsThe study of metabolomics (particularly involving FA) may help define distinct metabolic patterns to distinguish HCV-induced liver cirrhosis from HCC patients. Future research in this field is still needed, particularly concerning HCC treatment strategies which target fatty acid-related metabolic pathways.

Risk scoring systems to predict in-hospital mortality in patients with acute variceal bleeding due to HCV-induced liver cirrhosis

Background: this study was designed to validate and to compare accuracy of the prognostic scores; mainly Child Turcotte Pugh (CTP), creatinine-modified Child Turcotte Pugh (CTP-Cr), MELD, albumin bilirubin score (ALBI), and AIMS65, for the predicting clinical outcomes in cirrhotic Egyptian patients presenting with acute variceal bleeding (AVB). Methods: Retrospective single center study involving 725 patients presenting with AVB due to liver cirrhosis and HCV infection either alone or mixed with HBV infection. In hospital mortality prognostic scores were calculated; mainly CTP, modified CTP-Cr, MELD, ALBI, AIMS65. The endpoint is either patient improvement or death. Results: 725 patients were included over 1-year period. 547 (75%) survived and 178 (25%) died. Patients presented with hematemesis (515/71%), melena (120/16.5%) or hematemesis and melena (90/12.5%). Those with hematemesis for the first time were 241 (33%) and recurrent attacks were 484 (66.8%). The non-survivors had significantly more incidence of shock on presentation, more blood transfused units, history of NSAIDS intake, more ICU admission days and were more likely to be Childs C. Child, modified CTP-Cr, MELD, ALBI and ALMS65 scoring systems showed significant difference between survivors and non-survivors. Conclusion: Liver specific scores (Child, MELD) and gastrointestinal bleeding scoring systems (ALBI, AIMS65) are useful in predicting clinical outcomes of AVB in cirrhotic patients. CTP-Cr score had the highest prognostic capability of in hospital mortality. Presence of active bleeding at time of endoscopy, more complications, old age, shock and higher CPT-Cr score are additional independent predictors of in hospital mortality.

Transforming growth factor-β1 gene polymorphisms with liver cirrhosis risk: A meta-analysis

Although several epidemiological studies have investigated the association of transforming growth factor-β1 (TGF-ß1) gene polymorphisms with the susceptibility to liver cirrhosis (LC), controversial results exist. Consequently, we performed a meta-analysis to accurately evaluate the relationship of TGF-ß1-509C/T and codon 10T/C polymorphisms with the risk of LC introduced by chronic hepatitis B/V virus (HBV/HCV) infection. A total of 9 case-control studies, involving 985 LC patients and 909 controls, were recruited for meta-analysis. The results suggested a significant association between the -509C/T polymorphism and LC risk in the total population. Stratification by ethnicity revealed similar associations in Egyptian and Caucasian populations, but not in Asian populations. Subgroup analyses by different etiologies also showed similar associations in HCV-induced LC, but not in HBV-induced LC. However, the overall data failed to show a significant association between codon 10T/C polymorphism and the risk of LC in the study. We concluded that TGF-ß1-509C/T polymorphism was significantly associated with LC susceptibility, while the codon 10T/C polymorphism seemed to have a limited role in predicting the occurrence of LC induced by HBV/HCV infection.