HCV-related Chronic Liver Disease Research Articles

Mitochondrial DNA copy number in Hepatitis C virus-related chronic liver disease: impact of direct-acting antiviral therapy

Hepatitis C virus (HCV) infection can regulate the number and dynamics of mitochondria, and is associated with a prominent hepatic mitochondrial injury. Mitochondrial distress conveys oxidative damage which is implicated in liver disease progression. The present study was conducted to assess the change of mitochondrial DNA (mtDNA) copy number in patients with HCV-related chronic liver disease and the impact of direct-acting antiviral (DAA) therapy. Whole blood mtDNA copy number was measured using real-time quantitative polymerase chain reaction at baseline and 12 weeks after the end of therapy in 50 treatment-naïve HCV-infected patients who achieved sustained viral response (SVR) after DAA therapy and 20 healthy controls. Whole blood mtDNA copy number appeared significantly lower in HCV-infected patients before therapy compared to healthy subjects (P < 0.001). Post-treatment, there was significant increase of mtDNA copy number in HCV-infected patients at SVR12 compared to the pre-treatment values (P < 0.001), meanwhile it didn’t differ significantly between HCV-infected patients after therapy and healthy subjects (P = 0.059). Whole blood mtDNA copy number correlated inversely to the serum bilirubin in HCV-infected patients (P = 0.013), however it didn’t correlate significantly to the serum aminotransferases, viral load or fibrosis-4 score (P > 0.05). In conclusion, chronic HCV infection has been associated with a prominent mitochondrial injury which could mediate a progressive liver disease. The improved mtDNA content after DAA therapy highlights a possible potential of these drugs to alleviate mitochondrial damage in HCV-related liver disease.

Farnesoid X receptor in chronic liver diseases: an immunohistochemical study

ABSTRACT Chronic hepatitis C virus (HCV) related liver diseases are still an ongoing cause of hepatic failure despite the effective role of direct-acting anti-viral agents. Farnesoid X receptor (FXR) agonists have a potential therapeutic effect on the management of chronic liver diseases (CLD). However, data regarding FXR protein expression in human CLDs are limited and conflicting. We aimed to assess the immunohistochemical expression of FXR in HCV-related chronic hepatitis and cirrhosis in comparison with metabolic-associated fatty liver disease (MAFLD) and normal liver tissue. The expression of FXR was low both in hepatocytes and bile ducts of HCV-related chronic hepatitis and cirrhosis (p = .001, respectively). In addition, a significantly low expression of FXR was observed in HCV-related hepatitis and cirrhosis groups compared to MAFLD in hepatocytes (p < .001, for both) and bile ducts (p = .004 and p = .018). FXR expression in HCV-related cirrhosis was significantly associated with compensated liver function (p = .032) and low inflammatory activity (p = .022). FXR expression decreases in HCV-related CLDs. There was some evidence that FXR expression could protect against post-hepatitis cirrhosis.

Plasma Pattern of Extracellular Vesicles Isolated from Hepatitis C Virus Patients and Their Effects on Human Vascular Endothelial Cells.

Hepatitis C virus (HCV) patients are at increased risk of cardiovascular disease (CVD). In this study, we aimed to evaluate the role of extracellular vesicles (EVs) as pathogenic factors for the onset of HCV-related endothelial dysfunction. Sixty-five patients with various stages of HCV-related chronic liver disease were enrolled in this case series. Plasma EVs were characterized and used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, and reactive oxygen species (ROS) release. The results showed that EVs from HCV patients were mainly of endothelial and lymphocyte origin. Moreover, EVs were able to reduce cell viability and mitochondrial membrane potential of HUVEC, while increasing ROS release. Those harmful effects were reduced by the pretreatment of HUVEC with the NLR family pyrin domain containing 3 (NLRP3)/AMP-activated protein kinase and protein kinase B blockers. In conclusion, in HCV patients, we could highlight a circulating pattern of EVs capable of inducing damage to the endothelium. These data represent a novel possible pathogenic mechanism underlying the reported increase of CVD occurrence in HCV infection and could be of clinical relevance also in relation to the widespread use of antiviral drugs.

Cognitive Impairment, Extrapyramidal Manifestations, and their impact on Quality of Life in Patients with HCV-Related Chronic Liver Diseases

Cognitive Impairment, Extrapyramidal Manifestations, and their impact on Quality of Life in Patients with HCV-Related Chronic Liver Diseases

Clinical study on the efficacy of hepatitis B vaccination in hepatitis C virus related chronic liver diseases in Egypt

BackgroundChronic hepatitis B (HBV) and C virus (HCV) infections represent significant public health issues internationally. HBV vaccination has high sero-conversion rates in patients with mild to moderate chronic liver disease but has reduced efficacy in advanced stages. Aimto evaluate the efficacy of hepatitis B vaccination in HCV-related chronic liver disease and identify possible factors that may contribute to hypo-responsiveness in those patients. MethodsOur study was a retrospective observational clinical study carried out at the tropical medicine department. It was conducted on 500 individuals (400 chronic HCV patients and 100 healthy controls). Individuals were divided into 5 groups: A (control group), B (cirrhotic patient not receiving treatment), C (chronic hepatitis patients receiving treatment), D (cirrhotic patients receiving treatment), and E (HCC patients receiving treatment). All individuals were subjected for comprehensive history taking, clinical examination, laboratory investigations, and assessment of anti-HBs titer. ResultsThere is an inverse relationship between the level of anti-HBs Abs and the duration of vaccine. Diabetes and presence of cirrhosis have statistically significant relationship with serum anti-HBs Abs titer (P = 0.007). Oral DAAs therapy is associated with reduced response to HBV vaccine (only 31.75% of the patients were protected). ConclusionHCV infection and its complications significantly impair HBV vaccine response. Levels of anti-HBs Abs decline progressively with increasing duration from the last dose in immunization schedule of HBV vaccine. Diabetes and presence of cirrhosis being the main risk factors for vaccine hypo-responsiveness, also oral DAAs therapy is associated with reduced response to HBV vaccine.

Hepatitis C active viremia over time in an ED-based testing programme: Impact, disparities and surveillance tool.

Hepatitis C virus (HCV) surveillance is a critical component of a comprehensive strategy to prevent and control HCV infection and HCV-related chronic liver disease. The emergency department (ED) has been increasingly recognized as a vital partner in HCV testing and linkage. We sought to consider active RNA HCV viremia over time in patients participating in an ED-based testing programme as a measure of local HCV surveillance and as a barometer of ED-testing programme impact. We performed a retrospective analysis of individuals participating in our ED-based HCV testing programme between 2015 and 2021. Chi-square tests were used to compare the demographic characteristics of HCV antibody positive tests with active viremia to those without active viremia. Cox proportional hazard models were used to estimate the trend in active viremia risk over time in the overall study population as well as in key subpopulations of interest. Of 5456 HCV antibody positive individuals, 3102 (56.8%) had active viremia. In the overall study population, we found that the risk of active viremia decreased by 4.8% per year during the study period (RR: 0.95, 95% CI: 0.93-0.97|p < .0001). Baby boomers experienced a 9% decrease in active viremia risk per year over the study period while non-baby boomers only had a 2% decrease in risk per year (p=.0009). Compared with insured patients, uninsured patients had a smaller decrease in risk of active HCV viremia per year (p=.003). No significant differences in the risk of active viremia over time were observed for gender (p=.4694) or by primary care provider status (p=.2208). In conclusion, this ED-based testing and linkage programme demonstrates significantly decreased active HCV viremia over time. It also highlights subpopulations, specifically non-baby boomers and uninsured patients, who may benefit from focused interventions to improve access to and adoption of definitive HCV care.

Hepatocytes infected with hepatitis C virus change immunological features in the liver microenvironment.

Hepatitis C virus (HCV) infection is remarkably efficient in establishing viral persistence, leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC). Direct-acting antiviral agents (DAAs) are promising HCV therapies to clear the virus. However, recent reports indicate potential increased risk of HCC development among HCV patients with cirrhosis following DAA therapy. CD8+ T-cells participate in controlling HCV infection. However, in chronic hepatitis C patients, severe CD4+ and CD8+ T-cell dysfunctions have been observed. This suggests that HCV may employ mechanisms to counteract or suppress the host T-cell responses. The primary site of viral replication is within hepatocytes where infection can trigger the expression of costimulatory molecules and the secretion of immunoregulatory cytokines. Numerous studies indicate that HCV infection in hepatocytes impairs antiviral host immunity by modulating the expression of immunoregulatory molecules. Hepatocytes expressing whole HCV proteins upregulate the ligands of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and transforming growth factor β (TGF-β) synthesis compared to those in hepatocytes in the absence of the HCV genome. Importantly, HCV-infected hepatocytes are capable of inducing regulatory CD4+ T-cells, releasing exosomes displaying TGF-β on exosome surfaces, and generating follicular regulatory T-cells. Recent studies report that the expression profile of exosome microRNAs provides biomarkers of HCV infection and HCV-related chronic liver diseases. A better understanding of the immunoregulatory mechanisms and identification of biomarkers associated with HCV infection will provide insight into designing vaccine against HCV to bypass HCV-induced immune dysregulation and prevent development of HCV-associated chronic liver diseases.

Apelin Association with Hepatic Fibrosis and Esophageal Varices in Patients with Chronic Hepatitis C Virus.

Portal hypertension and esophageal varices complicating hepatitis C virus (HCV)-related chronic liver diseases are some of the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) single-nucleotide polymorphism (SNP), and serum apelin level in patients with chronic HCV, and their association with liver fibrosis and esophageal varices in 112 patients with HCV-related chronic liver disease (40 with liver cirrhosis [LC]/low-grade varices, 33 with LC/high-grade varices, and 39 with fibrotic non-cirrhotic liver/no varices) and 80 healthy control subjects. Real-time polymerase chain reaction was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. The serum apelin level was measured by ELISA. Apelin gene expression was undetectable in the studied samples. The SNP analysis revealed a greater frequency of the C (mutant) allele among patients compared with control subjects (P = 0.012; odds ratio, 3.67). The serum apelin level was significantly greater in patients with LC/varices (median, 31.6 ng/L) compared with patients without LC/varices (median, 2.9 ng/L; P < 0.001). A serum apelin level cutoff value of 16.55 ng/L predicted the presence of varices, with an area under the receiver operating characteristic curve value of 0.786. A positive correlation was found between serum apelin level and grade of liver fibrosis (r = 0.346, P < 0.001) and portal hypertension (r = 0.438, P < 0.001). In conclusion, the apelin rs3761581-C allele may be associated with the progression of HCV-related chronic liver disease and varices formation, and can be considered a potential therapeutic target to control fibrosis progression. The serum apelin level provided an accurate prediction of the presence of esophageal varices.

Effect of direct-acting antiviral drugs on portal circulation hemodynamics in cirrhotic patients infected with HCV

BackgroundLiver cirrhosis (LC) is the most common cause of portal hypertension. In chronic hepatitis C patients who are treated with direct-acting antiviral therapy (DAAS), the progression of cirrhosis can be reversed with treatment. Portal hypertension is also expected to improve with a virological response.AimTo evaluate the effect of direct-acting antiviral therapy on portal circulation hemodynamics in cirrhotic patients infected with HCV.MethodsThis study included 78 consecutive patients with chronic HCV-related liver disease. They were treated by a sofosbuvir-based regimen in combination with daclatasavir. All patients were subjected to routine investigations (complete blood count, liver and renal function tests), hepatitis B surface antigen, α feto protein, PCR of HCV RNA, imaging (abdominal ultrasound and colored Doppler and duplex examination for the assessment portal hypertension) before starting treatment and after 1 year.ResultsThere was a significant improvement in Doppler parameters such as portal vein (PV) diameter, PV velocity, PV cross-sectional area, portal congestive index, splenic vein diameter, and spleen span; the decrease in portal pressure occur in about 55% of the patients; several factors are associated with non-response as a history of bilharziasis, patients from a rural area, presence of splenomegaly and varices, low HB level, low platelet count, and high level of fibrosis.ConclusionSustained virological response to direct-acting antiviral therapy is associated with a reduction in portal pressure in patients with liver cirrhosis and clinically significant portal hypertension.

Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.

Handgrip strength in prediction of sarcopenia in Chronic HCV patient

Abstract Background HCV is one of the major causes of morbidity and mortality in the world and especially in Egypt. However, there is numerous complications to HCV infection (e.g. liver cirrhosis, ascites, portal hypertension, encephalopathy …. etc.) but there is multiple unseen complication (e.g. sarcopenia, loss of electrolytes, loss of protein …etc.) Objective To evaluate value of handgrip strength in assessment of sarcopenia in HCV related chronic liver disease patients Patients and Methods This study was conducted on 64 adult persons older than 18 years. They were randomly collected from the outpatient clinics at department of internal Medicine in Ain Shams University during the period from June 2018 to August 2019. Results In our study there was a great significance relation between handgrip strength and child score in evaluating nutritional status more than anthropometric parameter. Therefore, even that several methods to evaluate nutritional and functional capacity status in patients with cirrhosis have been tested, they have reported diverse results. Conclusion Our study we can conclude that HGS is a simple, easy to be applied and more accurate method in evaluation of sarcopenia in chronic HCV patients.

Value of Helicobacter pylori Eradication on Platelet Count in chronic Hepatitis C Virus-Infected Patients with thrombocytopenia

Background: Invasive therapies are often needed for sufferers with chronic liver diseases (CLDs). Thrombocytopenia is common hematological abnormality in CLD sufferers. In immune thrombocytopenic purpura (ITP), Helicobacter pylori (HP) infection is linked to a low platelet count, whereas HP eradication is associated to an increase in platelet count. In Egypt, the most common trigger of CLD is infection with the hepatitis C virus. In Egypt HP is common infection happens at a young age. Aim of the work: The impact of Helicobacter pylori eradication on platelet count in HCV-related CLD patients with thrombocytopenia. Patients and methods: A prospective study of 100 patients divided to HP positive and HP negative. Sufferers that checked positive for HP have been given treatment to eliminate the virus. HP eradication was evaluated using a stool test for Helicobacter pylori antigen 6 weeks following the treatment was completed. Platelet counts were used to assess the success of HP eradication after 1, 3, 6, and 9 months of follow-up. Results: HP infection prevalence among HCV patients 65% (65/100) versus 35% (35/100) HP negative. Eradication in HP positive patients after treatment were 46 patients (70.8%) and 19 patients (29.2%) not eradicate. platelets response after HP therapy there were 14 patients (21.5%) with complete response, 20 patients (30.8%) had a partial response, while 31 had no response (47.7%){12 eradicated and 19 not eradicated} Conclusion: Successfully eradicating H. pylori can have an impact on platelet recovery and platelet count maintenance in patients with chronic HCV-infected thrombocytopenia

Correlation of hepatitis C virus-mediated endoplasmic reticulum stress with autophagic flux impairment and hepatocarcinogenesis.

Hepatitis C virus (HCV) infection has been known to use autophagy for its replication. However, the mechanisms by which HCV modulates autophagy remain controversial. We used HCV-Japanese fulminant hepatitis-1-infected Huh7 cells. HCV infection induced the accumulation of autophagosomes. Morphological analyses of monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 transfection showed HCV infection impaired autophagic flux. Autophagosome-lysosome fusion assessed by transfection of mRFP- or GFP-LC3 and immunostaining of lysosomal-associated membrane protein 1 was inhibited by HCV infection. Decrease of HCV-induced endoplasmic reticulum (ER) stress by 4-phenylbutyric acid, a chemical chaperone, improved the HCV-mediated autophagic flux impairment. HCV infection-induced oxidative stress and subsequently DNA damage, but not apoptosis. Furthermore, HCV induced cytoprotective effects against the cellular stress by facilitating the formation of cytoplasmic inclusion bodies as shown by p62 expression and by modulating keratin protein expression and activated nuclear factor erythroid 2-related factor 2. HCV eradication by direct-acting antivirals improved autophagic flux, but DNA damage persisted. In conclusion, HCV-induced ER stress correlates with autophagic flux impairment. Decrease of ER stress is considered to be a promising therapeutic strategy for HCV-related chronic liver diseases. However, we should be aware that the risk of hepatocarcinogenesis remains even after HCV eradication.

Effect of Successful Direct Acting Antivirals Therapy on Liver Stiffness in Patients with Chronic HCV Infection

Background: Achievement of sustained virological response [SVR] and improvement of hepatic fibrosis are the essential goals for therapy of chronic hepatitis C [CHC] with direct acting antivirals [DAAs] therapy. Early detection and management of hepatic fibrosis can significantly improve the prognosis of CHC in clinical practice. Aim of the work: To assess the effect of successful DAAs therapy on liver stiffness in patients with CHC. Methods: This study included 100 patients with chronic HCV-related liver disease. All were treated with Sofosbuvir-based regimen for 12 weeks on outpatient base. HCV treatment applied according to the protocol designed by the Egyptian National Committee for Control of Viral Hepatitis. Follow up continued for 12 weeks [after the end of treatment [EOT]] to estimate effect of successful DAAS therapy on liver stiffness using Shear Wave Elastography [SWE], aminotransferase-to platelet ratio index [APRI] and Fib-4 score before initiation of antiviral therapy, at end of treatment [EOT] and 12 weeks after EOT [SVR12]. Results: Platelets significantly increased, ALT and AST decreased and mean values of APRI, Fib-4 score and Liver stiffness assessment were significantly reduced in all patients at SVR12. Hemoglobin levels significantly reduced in patients receiving ribavirin 12 weeks after EOT. Conclusions: Elimination of HCV after successful DAAS treatment was associated with a significant improvement of the liver stiffness at both EOT and 12 weeks afterwards EOT as evidenced by SWE, Fib-4 score and APRI index

Abstract B114: HCV screening and awareness education are much needed among African American baby boomers in Philadelphia

Abstract Background: African Americans have substantially higher rates of chronic hepatitis C virus (HCV) and HCV-related deaths compared to other ethnic groups. HCV-related chronic liver disease and cirrhosis were among the leading causes of death in baby boomers within African American community. The purpose of this pilot study is to evaluate screening rate, infection history, awareness and knowledge about HCV in African American baby boomers in Philadelphia, Pennsylvania. Methods: In collaboration with church leaders, a total of 138 African Americans aged between 45 to 74 were recruited from African American churches in Philadelphia, PA. Questionnaires were administered face-to-face with voluntary participants. Demographic characteristics, HCV screening, risk factors and family history of liver disease and HCV, awareness and knowledge of HCV were measured. Results: The study sample consisted of 74 (54%) women and 64 (46%) men, with an average age of 62. Two thirds (66%) of the sample had high school or lower education. Most of them had health insurance (91%) and a regular physician to visit (90%). Although 82% of the participants had heard of HCV, only 43% had been tested for it. Of the respondents, 10% reported having family members with liver cancer, with 26% reporting that they did not know about their family history of liver cancer; 9% reported having a family history of HCV infection, and 24% did not know their family history of HCV. The study found that participants had low level of HCV-related knowledge. Less than two-thirds (61%) were able to correctly identify one cause associated with HCV infection, and only 36% knew that there are more people infected with HCV than those with HIV/AIDS. About less than 50% participants correctly identified the means of HCV transmission, including blood transfusion (64%), intravenous drug use (55%), tattooing and body piercing (54%), direct exposure to blood (40%), sharing the razor with an HCV-infected person (35%), sexual activity (36%), and mother-to-child transmission (40%). Furthermore, only 25% knew that 75% to 85% of people with HCV will develop chronic liver disease, and only 21% knew that there was no vaccine for HCV. In terms of risk behaviors, 16% participants had used illegal drug through intravenous/subcutaneous/nasal injection, 16% had received blood transfusion, 5% served in the Vietnam War, 13% had tattoo, 3% received hemodialysis, and 2% had been diagnosed with HIV/AIDS. Conclusions: African American baby boomers present moderate to high risk factors (intravenous drug use, blood transfusion, etc.), yet awareness and knowledge related to HCV family history, transmission, and prevalence remained low. Significant efforts are needed in promoting awareness and education interventions to improve HCV screening in this underserved and vulnerable population. Acknowledgment: This pilot study was supported by faculty research funds from Center for Asian Health, Temple University (PI: Grace Ma). We acknowledge volunteers and community leaders who made this study possible. Citation Format: Grace X. Ma, Lin Zhu, Yin Tan, Fayola Levine, Tamara Gillot, Gina Simoncini, Jennifer Arthur-Lewis, Joanne Rhee, Zhengyu Wei, Olorunseun O. Ogunwobi. HCV screening and awareness education are much needed among African American baby boomers in Philadelphia [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B114.

Machine Learning Prediction Models for Diagnosing Hepatocellular Carcinoma with HCV-related Chronic Liver Disease

Background and ObjectiveConsidered as one of the most recurrent types of liver malignancy, Hepatocellular Carcinoma (HCC) needs to be assessed in a non-invasive way. The objective of the current study is to develop prediction models for Chronic Hepatitis C (CHC)-related HCC using machine learning techniques. MethodsA dataset, for 4423 CHC patients, was investigated to identify the significant parameters for predicting HCC presence. In this study, several machine learning techniques (Classification and regression tree, alternating decision tree, reduce pruning error tree and linear regression algorithm) were used to build HCC classification models for prediction of HCC presence. ResultsAge, alpha-fetoprotein (AFP), alkaline phosphate (ALP), albumin, and total bilirubin attributes were statistically found to be associated with HCC presence. Several HCC classification models were constructed using several machine learning algorithms. The proposed HCC classification models provide adequate area under the receiver operating characteristic curve (AUROC) and high accuracy of HCC diagnosis. AUROC ranges between 95.5% and 99%, plus overall accuracy between 93.2% and 95.6%. ConclusionModels with simplistic factors have the power to predict the existence of HCC with outstanding performance.

Presentations, Causes and Outcomes of Drug-Induced Liver Injury in Egypt

Drug-induced liver injury (DILI) is a frequent cause of liver injury and acute liver failure. We aimed to review all hospitalized DILI cases in a tertiary Egyptian center from January 2015 through January 2016. Cases with elevated alanine aminotransferase more than 3-fold and/or alkaline phosphatase more than 2-fold the upper limit of normal value were prospectively recruited and followed for one year. Drug history, liver biopsy whenever feasible and application of Roussel Uclaf Causality Assessment Method (RUCAM) were the diagnostic prerequisites after exclusion of other etiologies of acute liver injury. In order of frequency, the incriminated drugs were: Diclofenac (31 cases, 41.3%), amoxicillin-clavulanate (14 cases, 18.7%), halothane toxicity (8 cases, 10.7%), ibuprofen (4 cases, 5.3%), Khat (3 cases, 4%), tramadol (3 cases, 4%), Sofosbuvir with ribavirin (2 cases, 2.7%), and acetylsalicylic acid (2 cases, 2.7%) with one offending drug in 93.3% of cases. Forty-four cases (58.7%) were males; while 56 cases (74.7%) had HCV related chronic liver disease. Thirty-two cases (42.7%) presented with pattern of hepatocellular injury, while 23 cases (30.7%) were with cholestasis, and 20 cases (20.7%) with a mixed hepatocellular/cholestatic injury. One case received a transplant (0.75%), 7 cases died (9.3%), 23 cases (30.6%) developed liver decompensation (hepatic encephalopathy and ascites), and 44 cases completely resolved (58.7%). In conclusion, Diclofenac is the commonest offender in DILI occurrence in an Egyptian cohort. Age and prothrombin concentration were the only predictors of unfavorable outcomes of DILI.

Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients

Background and study aimsMicroRNAs (miRNAs), small single stranded RNAs, function in the post-transcriptional regulation of gene expression and incorporated in pathogenesis of HCV related chronic liver disease. This study was designed to evaluate the significance of serum miR-21, miR-223, and miR-885-5p as biomarkers in various clinicopathological stages of HCV related chronic liver disease. Patients and methodsSerum miR-21, miR-223, and miR-885-5p were quantified by quantitative RT PCR in 60 patients with HCV-related liver disease (presumably genotype 4), in addition to 25 healthy controls. HCV patients were classified into: chronic non-cirrhotic HCV (n = 15), HCV related liver cirrhosis (n = 15), and hepatocellular carcinoma (HCC) (n = 30). Results: Serum levels of miR-885-5p in cirrhotic patients ± HCC (n = 45) were significantly higher than the non-cirrhotic patients (n = 15); p = 0.007 and healthy control; p = 0.001. However, no such significance was detected between HCC and non-HCC HCV patients; p = 0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis; AUC 0.85, 87% sensitivity and 80% specificity. On the other hand, HCC patients had significantly higher serum miR-2 1evels than non-HCC patients (non-cirrhotic and cirrhotic groups, n = 30); p = 0.048 and the control group; p = 0.002. ROC could differentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specificity. Both serum bilirubin and albumin showed significant weak correlation with miRNA-885-5p (r = 0.42, p = 0.001) and (r = −0.27, p = 0.04), respectively but no such correlation was observed with serum miRNA-21. In contrast, miRNA-223 showed no significant difference across the studied groups. ConclusionAlong the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC.

584 Apelin Association With Hepatic Fibrosis and Esophageal Varices in Chronic HCV Patients

INTRODUCTION: Portal hypertension (PH) and esophageal varices complicating HCV-related chronic liver disease (CLD) are the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) SNP and serum apelin level in chronic HCV patients, and their association with hepatic fibrosis and esophageal varices. METHODS: 112 patients with HCV related CLD (40 having liver cirrhosis (LC)/low grade varices, 33 with LC/high grade varices and 39 with fibrotic non-cirrhotic liver/no varices), and 80 healthy control subjects were included. Real time PCR was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. Serum apelin level was measured by ELISA. RESULTS: Apelin gene expression was undetectable in studied samples. SNP analysis revealed higher frequency of the C-(mutant)-allele among patients compared to controls (P = 0.012, odds ratio 3.67). Serum Apelin level was significantly higher in patients with hepatic cirrhosis/ varices (median 31.6 ng/L) compared to non-cirrhotic patients/ no varices (median 2.9 ng/L) (P &lt; 0.001). Serum apelin level at cut off value 16.55 ng/L predicted the presence of varices with AUROC 0.786. Positive correlation was found between serum apelin level and grade of liver fibrosis (r=0.346, P &lt; 0.001) and PH (r=0.438, P &lt; 0.001). CONCLUSION: Apelin rs3761581 C-allele may be associated with progression of HCV-related CLD and varices formation, and can be considered as a potential therapeutic target to control fibrosis progression. Serum apelin level provided accurate prediction of the presence of esophageal varices.

Prevalence of prolonged QT interval in patients with HCV-related chronic liver disease

BackgroundHepatitis C virus (HCV) is a common disease in Egypt with a high socioeconomic burden and extra-hepatic manifestations as QT prolongation, but previous studies included mainly patients with advanced liver disease, so in this study, we aimed to delineate the prevalence of QT prolongation in early-stage HCV patients.ResultsThe study included 874 HCV patients with early cirrhosis; in Child’s class A, 57 (6.5%) patients had prolonged QT interval corrected (QTc). There was significant higher proportion of cirrhotic patients in the prolonged QTc group (31.6%) vs. in the normal QTc group (11.5%). QTc was 424.39 ± 36.6 vs. 411.51 ± 32.89 ms in cirrhotic and non-cirrhotic patients, respectively (P, 0.001). There was significant higher proportion of Fibrosis 4 (FIB-4) ≥ 1.45 score in the prolonged QTc (77.2%) vs. in the normal QTc group (56.8%) (P, 0.003). QTc interval was 417.76 ± 34.12 ms in patients with FIB-4 score ≥ 1.45 vs. 406.78 ± 31.95 ms in those with FIB-4 < 1.45 (P, < 0.001). FIB-4 score value of 2.108 predicted prolonged QTc with a sensitivity of 63.2% and a specificity of 64.5% (P, < 0.001). Twenty-four patients of long QTc group sent ECGs after HCV eradication, and 19 patients (79%) showed QTc normalization.ConclusionsHCV is associated with QTc prolongation even in patients with early chronic liver disease stages without significant fibrosis. Also, it is related to the degree of fibrosis and cirrhosis. At a cutoff value of 2.108, FIB-4 score can predict prolonged QTc. HCV eradication is associated with a high incidence of QTc normalization.