scholarly journals In Egyptian Patients with Hepatocellular Carcinoma the role of MicroRNA-215

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S136-S137
Author(s):  
H A Ali

Abstract Introduction/Objective MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs which are make a contribution in the regulation of gene expression and protein translation, and they play vital roles in differentiation, cell growth, and the development of diverse types of cancers. Methods/Case Report Our research was done in hepatology and gastroenterology department at the National Liver Institute, Menoufia University. It included 135 patients and 60 healthy subjects serving as control group. We have 3 groups: Group I (Control) This group included 60 apparently healthy individuals. They were 32 males and 28 females, whose ages ranged from 39 to 67 years old (mean ±SD= 51.67 ± 6.40 years). Group II (Cirrhosis) This group included 75 patients with liver cirrhosis due to chronic HCV infection. They were 41 males and 34 females whose ages ranged from 41 to 68 years old (mean ±SD= 54±6.73 years). Group III (HCC) Sixty patients with HCC were included. They were 35 males and 25 females, whose ages ranged from 41 to 70 years old (mean ±SD= 53.97±6.15 years). Laboratory Investigations Complete blood count (CBC), Liver tests: aspartate transaminase (AST) and alanine transaminase (ALT), serum albumin, total and direct bilirubin, alkaline phosphatase and INR were measured. Serum creatinine was also measured. The analysis of serum alpha fetoprotein (AFP) (ng/ml) was done. Chronic HCV infection was diagnosed by detection of HCV antibody and HCV RNA by real time PCR. Anti-HCV antibody was detected by means of a third generation enzyme immunoassay. Quantification of HCV RNA level was performed by means of COBAS Taqman 84 (Roche) real time HCV RNA Assay with lower detection limit 15 IU/ml. Results (if a Case Study enter NA) In control group, miRNA-215 ranged from 1.60 to 21.30 with a median value of 6.89. In cirrhotic patients group, it ranged from 0.70 to 14.65 with a median value of 2.85. In patients with HCC group, it ranged from 0.03 to 10.95 with a median value of 0.52 (pg/ml). MiRNA-215 and AFA mean levels showed a statistically significant difference (p <0.001) between the three studied groups. Conclusion In conclusion, MicroRNA-215 was proved to be significantly lower in HCC patients compared to cirrhotic patients and control group. This marker might be used as a potential serologic marker for HCC and a complementary diagnostic tool in monitoring cirrhotic patients for detection of HCC.

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
William W. Thompson ◽  
Mohammed A. Khan ◽  
Jay Soh ◽  
Lauren Canary ◽  
Michael Blank ◽  
...  

ObjectiveUsing data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters, we sought to assess the relationship between mental health outcomes and chronic hepatitis C infection after adjusting for important confounders. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in fee-for-service plans were included in the analysisIntroductionHepatitis C virus (HCV) infection is a leading cause of liver disease-related morbidity and mortality in the United States and HCV incidence has been increasing. Mental illness may impact the likelihood of initial HCV infection, progress and adherence to treatment along the hepatitis C care cascade, and risk of subsequent reinfection for those cured of hepatitis C. The relationship between HCV infection and mental illness is not well understood and many studies have lacked sufficient sample size to adjust for important confounders. We sought to explore the association between chronic HCV infection and mental illness after adjusting for important confounders.MethodsWe obtained data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. These data consist of inpatient and outpatient service claims for persons with employer-sponsored health insurance coverage and their dependents. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in a fee-for-service plan were included in the analysis. Chronic HCV infection was defined by a positive HCV RNA test result. Controls without chronic HCV infection had a negative HCV antibody test result and no positive HCV antibody or RNA test result in the preceding or following year. The index date was defined by the date of the earliest positive HCV RNA or negative HCV antibody test. Demographic characteristics were obtained from the MarketScan® enrollment tables. All enrollees in the study population were at least 18 years old during the year of the index date. The analysis sample was restricted to persons who were identified as receiving outpatient prescription drug claims data feeds. We estimated adjusted odds ratios (OR) for the association between mental illness (ICD-9 code 295 or 296) and HCV RNA status. Multivariate models included age (18-44, 45-64, 65+ years), sex, region, and an adjusted Charlson Comorbidity Index which excluded liver disease and hepatocellular carcinoma.ResultsWe identified 2,847 individuals with chronic HCV infection (HCV RNA+) and 57,418 controls who were HCV antibody negative. With respect to age, 83% of HCV RNA+ individuals were aged 45-64 years while only 43% of the HCV antibody negative individuals were in the same age range. Similarly, for sex, 62% and 40% of HCV RNA+ individuals and controls, respectively, were male. For unadjusted analyses, age, sex, region, comorbid conditions, and mental illness (OR= 2.25 [95% CI; 1.52 - 3.34]) were all statistically associated with HCV RNA+. For the multivariate adjusted models, these same variables remained statistically significant. For the multivariate model, individuals with a mental illness were more likely to be HCV RNA+ relative to HCV antibody negative controls. (OR= 1.95 [95% CI; 1.30 - 2.93]).ConclusionsThis study demonstrated a strong association between mental illness and HCV chronic infection after adjusting for important confounders including other comorbid conditions. A growing body of research suggests that persons with mental illness are at increased risk for contracting and transmitting HCV due to high rates of substance use and high-risk sexual behavior among infected persons as well as high rates of sexual victimization. HCV prevention efforts should be directed toward individuals with mental illness or seeking treatment for mental illness. 


2020 ◽  
Author(s):  
karim Montasser ◽  
heba Ahmed osman ◽  
Hanan Abozaid ◽  
Abeer M. M. sabry

Abstract Aim: Dysbiosis of gut microbiota favors chronic hepatic inflammation with subsequent hepatic carcinogenesis. The current study aimed to evaluate the role of gut dysbiosis in the development of hepatocellular carcinoma in patients with chronic HCV infection.Methods: This descriptive cross-sectional cohort study carried out on 400 subjects recruited from the Internal Medicine Department and Tropical Medicine and Gastroenterology Department of Helwan and South Valley University Hospitals in Egypt. The study period was from January 2017 till January 2020. The subjects were divided clinically into three groups. Group I: One hundred patients with HCC, evaluated by Child Pugh, TNM and BCLC scoring systems. Group II: 200 chronic hepatitis C virus-infected patients. All patients infected with hepatitis C virus genotype 4. Group III: One hundred healthy control subjects with negative hepatitis marker and normal abdominal ultrasound. PCR of stool Microbiota, complete blood counts, complete liver function tests, INR, HCV antibodies and HBsAg were done for all included subjects. HCV PCR assessment and alpha-fetoprotein (AFP) were done for all patients.Results: No statistically significant difference was detected between HCC patients and control (p-value > 0.05) as regard Bacteroides fragilis & Akkermansia muciniphila. Faecalibacterium prausnitzii was less detected in HCC patients (51%), opposite to 70% of healthy control. With Statistically significant difference (p-value < 0.05). Bifidobacterium was less detected in HCC patients (43%), opposite to (76%) of healthy control. With highly statistically significant difference (p-value < 0.001). Lactobacillus & Enterobacteriaceae was more detected in HCC patients (80%) and (81%), in. Opposite to (36%) and (58%) in healthy control, respectively. With highly statistically significant difference (p-value < 0.001). no significant difference was detected between gut-microbiota and HCC progression with respect to Child or TNM systems. However, a significant difference was detected between number of positive stool isolate of Bacteroid Fragilis and BCLC staging system; where it was isolated from 66.7% of patients with BCLC stage IV opposite to 10.7% of patients with BCLC stage I.Conclusion: A characteristic pattern of Bifidobacterium, Lactobacillus and Enterobacteriaceae species in patients with chronic HCV and HCC was detected. Alteration of gut microbiota may be accused as a predisposing factor for liver disease progression.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pierluca Piselli ◽  
Diego Serraino ◽  
Mario Fusco ◽  
Enrico Girardi ◽  
Angelo Pirozzi ◽  
...  

Abstract Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.


Pathobiology ◽  
1995 ◽  
Vol 63 (5) ◽  
pp. 239-248 ◽  
Author(s):  
Domenico Sansonno ◽  
Vito Cornacchiulo ◽  
Anna Rina Iacobelli ◽  
Pietro Gatti ◽  
Maria Di Stasi ◽  
...  

2009 ◽  
Vol 23 (6) ◽  
pp. 425-430 ◽  
Author(s):  
Jennifer A Flemming ◽  
David J Hurlbut ◽  
Ben Mussari ◽  
Lawrence C Hookey

BACKGROUND/OBJECTIVE: Liver biopsy has been the gold standard for grading and staging chronic hepatitis C virus (HCV)-mediated liver injury. Traditionally, this has been performed by trained practitioners using a nonimage-guided percutaneous technique at the bedside. Recent literature suggests an expanding role for radiologists in obtaining biopsies using an ultrasound (US)-guided technique. The present study was undertaken study to determine if the two techniques produced liver biopsy specimens of similar quality and hypothesized that at our institution, non-US-guided percutaneous liver biopsies for HCV would be of higher quality than US-guided specimens.METHODS: Liver biopsies from 100 patients with chronic HCV infection (50 consecutive US-guided and 50 consecutive non-US-guided), were retrospectively identified using a hospital histopathology database. All original biopsy slides were coded and prospectively reanalyzed by a single hepatopathologist who was blinded to the technique used in obtaining the biopsy. Additionally, all liver biopsies for chronic HCV infection completed at the centre from 1998 to 2007 were identified and the technique used was recorded. Biopsy quality was determined primarily by the number of complete portal tracts (CPTs) identifiable in the slides. The total length of specimen and the degree of fragmentation were secondary outcome measures.RESULTS: There was a slight difference observed between the US-guided and non-US-guided groups in mean age (46.3 years versus 42.5 years, repectively; P=0.018) but no differences in sex, presence of cirrhosis, bilirubin, creatinine, international normalized ratio, and grade or stage of disease. Biopsies obtained using the US-guided technique produced higher quality specimens than the non-US-guided technique based on our primary outcome of number of CPTs in the biopsy (11.8 versus 7.4; P<0.001). US-guided specimens also were longer (24.4 mm versus 19.7 mm; P=0.001), had less fragmentation (P=0.016), and a higher overall histopathological quality assessment (P=0.026) than the non-US-guided biopsies. However, there was no significant difference between the two groups in the ability to grade and stage the disease (96% US-guided versus 90% in non-US-guided (P=0.20). Over a 10-year period, 763 biopsies for chronic HCV infection were identified with an obvious trend toward the increased use of US-guided technique observed at 2% in 1998 to 85% in 2007.CONCLUSIONS: US-guided liver biopsies for chronic HCV are the most common method of obtaining specimens at the Kingston General Hospital, Kingston, Ontario, and are of higher quality than non-US-guided specimens. However, there is no significant difference in the two techniques in the ability to grade and stage chronic HCV.


2001 ◽  
Vol 45 (2) ◽  
pp. 517-524 ◽  
Author(s):  
Jeffrey M. Jacobson ◽  
Lawrence Feinman ◽  
Leonard Liebes ◽  
Nancy Ostrow ◽  
Victoria Koslowski ◽  
...  

ABSTRACT Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.


2006 ◽  
Vol 80 (15) ◽  
pp. 7364-7374 ◽  
Author(s):  
Kyung-Soo Chang ◽  
Zhaohui Cai ◽  
Chen Zhang ◽  
Ganes C. Sen ◽  
Bryan R. G. Williams ◽  
...  

ABSTRACT Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. The underlying mechanisms of chronic HCV infection and IFN-based therapies, however, have not been defined. Protein kinase R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced antiviral response. In this report, we demonstrate that a subgenomic RNA replicon of genotype 2a HCV replicated efficiently in mouse embryonic fibroblasts (MEFs), as determined by cell colony formation efficiency and the detection of HCV proteins and both positive- and negative-strand RNAs. Additionally, the subgenomic HCV RNA was found to replicate more efficiently in the PKR knockout (PKR−/−) MEF than in the wild-type (PKR+/+) MEF. The knockdown expression of PKR by specific small interfering RNAs significantly enhanced the level of HCV RNA replication, suggesting that PKR is involved in the control of HCV RNA replication. The level of ISG56 (p56) was induced by HCV RNA replication, indicating the activation of PKR-independent antiviral pathways. Furthermore, IFN-α/β inhibited HCV RNA replication in PKR−/− MEFs as efficiently as in PKR+/+ MEFs. These findings demonstrate that PKR-independent antiviral pathways play important roles in controlling HCV replication and mediating IFN-induced antiviral effect. Our findings also provide a foundation for the development of transgenic mouse models of HCV replication and set a stage to further define the roles of cellular genes in the establishment of chronic HCV infection and the mediation of intracellular innate antiviral response by using MEFs derived from diverse gene knockout animals.


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