Hepatitis C Virus Infected Patients Research Articles

Common molecular basis for MASH and hepatitis C revealed via systems biology approach

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is characterized by liver inflammation and damage caused by a buildup of fat in the liver. Hepatitis C, caused by hepatitis C virus (HCV), is a disease that can lead to liver cirrhosis, liver cancer, and liver failure. MASH and hepatitis C are the common causes of liver cirrhosis and hepatocellular carcinoma. Several studies have shown that hepatic steatosis is also a common histological feature of liver in HCV infected patients. However, the common molecular basis for MASH and hepatitis C remains poorly understood.MethodsFirstly, differentially expressed genes (DEGs) for MASH and hepatitis C were extracted from the GSE89632, GSE164760 and GSE14323 datasets. Subsequently, the common DEGs shared among these datasets were determined using the Venn diagram. Next, a protein-protein interaction (PPI) network was constructed based on the common DEGs and the hub genes were extracted. Then, gene ontology (GO) and pathway analysis of the common DEGs were performed. Furthermore, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. After the MASH and hepatitis C cell model was treated with predicted drug, the expression levels of the signature genes were measured by qRT-PCR and ELISA.Results866 common DEGs were identified in MASH and hepatitis C. The GO analysis showed that the most significantly enriched biological process of the DEGs was the positive regulation of cytokine production. 10 hub genes, including STAT1, CCL2, ITGAM, PTPRC, CXCL9, IL15, SELL, VCAM1, TLR4 and CCL5, were selected from the PPI network. By constructing the TF-gene and miRNA-gene network, most prominent TFs and miRNAs were screened out. Potential drugs screening shows that Budesonide and Dinoprostone may benefit patients, and cellular experiments showed that Budesonide effectively inhibited the expression of genes related to glycolipid metabolism, fibrosis, and inflammatory factors.ConclusionWe extracted 10 hub genes between MASH and hepatitis C, and performed a series of analyses on the genes. Molecular docking and in vitro studies have revealed that Budesonide can effectively suppress the progression of MASH and hepatitis C. This study can provide novel insights into the potential drug targets and biomarkers for MASH and hepatitis C.

Prevalence of hepatitis C virus hypervariable region 1 insertions and their role in antibody evasion.

Chronic hepatitis C virus (HCV) infection afflicts around 50 million people globally, causing ~250,000 deaths yearly. An effective vaccine needs to overcome high viral diversity and HCV's ability to evade neutralizing antibodies (NAbs). Rapid antigenic drift in the N-terminal motif of envelope protein E2, named hypervariable region 1 (HVR1), is critically involved in NAb evasion via an incompletely understood mechanism involving viral entry factors. The canonical length of HVR1 is 27 amino acids, but insertions of 2-4 amino acids was described in patients infected with genotype 1b. We aimed at determining whether HVR1 insertions may be underreported due to extreme HVR1 variability. We observed a 0.7% HVR1 insertion prevalence in routine NGS patient contigs. Thus, we performed direct sequence analysis of E1E2 sequences from 131 HCV infected patients. Interestingly, we observed that 3% of patients harbored viruses (genotype 1a, 2b, 3a) with dominant HVR1 insertions. Insertion of longer non-canonical HVR1s into HCV cell culture recombinants frequently caused loss of fitness. However, culture-viable viruses with HVR1 insertions were fully viable in vivo. Interestingly, in adapted genotype 1b recombinants with HVR1 insertions, we found internal HVR1 deletions, that increased antibody sensitivity, which surprisingly correlated more with reduced LDLr than reduced SR-BI dependency, indicating a role of LDLr in NAb evasion. Conversely, HVR1 insertions had no effect on receptor dependency, however, they modulated epitope-specific NAb sensitivity. HVR1 insertion prevalence and NAb sensitivity modulation indicate they represent a mechanism by which HCV evades emerging NAbs during infection.

Development and validation of a new and rapid molecular diagnostic tool based on RT-LAMP for Hepatitis C virus detection at point-of-care

PurposeGlobally, it is estimated that 1.0 million individuals are newly infected by Hepatitis C virus (HCV) every year, and nearly 50 million people live with a chronic infection, according to World Health Organization. To overcome underdiagnosis of HCV infection among hard-to-reach populations, it is essential to develop new rapid and easy-to-use molecular diagnostic systems. In this work, we have developed a pangenotypic diagnostic tool based on Loop-Mediated Isothermal Amplification (LAMP), coupled to a direct sample lysis procedure for molecular detection of HCV at point-of-care (POC). MethodsProcedure validation was performed using 129 different samples from HCV infected patients (116 serum samples, and 13 fresh blood samples), 27 individuals who tested negative for HCV but positive for HIV, and 11 healthy donors. Serum was collected, lysed for 10 min at room temperature, and assayed by RT-LAMP. To achieve this, a set of 9 LAMP-primers was used for the first time. Parallel RT-qPCR assays were conducted for HCV to both validate the procedure and quantify viral loads. ResultsHCV was detected by RT-LAMP in 109/116 HCV positive serum samples, and in 11/13 positive blood samples in less than 40 min. Compared to RT-qPCR results, our RT-LAMP procedure showed a sensitivity of 94 %, 100 % specificity, and a limit of detection of 3.26 log10 IU/mL (10–20 copies per reaction). ConclusionsWe have developed an accurate system, more affordable than the current available rapid tests for HCV. Since no prior RNA purification step from capillary blood is required, we strongly recommend our RT-LAMP system as a valuable and rapid tool for the molecular detection of HCV at POC.

Meta-Analysis of the Effectiveness of Sofosbuvir-Based Regimens in Treating Hepatitis C Genotype 3

Hepatitis C virus (HCV) is an RNA virus with seven primary genotypes. It is highly prevalent in Pakistan, especially genotype 3. HCV infection can progress to a chronic state with further complications. Direct-acting antiviral agents (DAAV) were introduced in 2014 as a treatment option, some of which include Sofosbuvir (SOF), Daclatasvir (DCV), Velpatasvir (VEL) and Ribavirin (RV). This meta-analysis was performed to outline the treatment response and efficacy of DAAV in HCV infected patients. We systematically searched PubMed, Web of Science, MEDLINE, and Google Scholar for studies from January 2019 to December 2023. The studies selected met the criteria of patients having chronic HCV infection (genotype 3) and either compensated cirrhosis or decompensated chronic liver disease. Treatment regimens with DAAV specifically were included. The primary outcomes [sustained viral response (SVR), rapid virological response (RVR), end-of-treatment response (ETR)] were highlighted to assess treatment response. The studies proved that the use of direct-acting antiviral agents in different combinations was very effective against HCV infection with minimal side-effects.

Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis.

Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy

BackgroundGlobally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy.MethodsThis prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied.ResultsA total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction.ConclusionPretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Cytokines in hepatitis C-infected patients with or without opioid maintenance therapy.

Both chronic hepatitis C virus (HCV) infection and opioids cause altered blood levels of cytokines. Previous studies have investigated levels of selected groups of cytokines in patients on opioid maintenance treatment. Little is known about the levels of multiple cytokines in patients with chronic HCV infection on opioid maintenance treatment. Our aim was to investigate the cytokine profile in patients with active HCV infection with and without opioid maintenance treatment. We conducted a cross-sectional study in an out-patients population included upon referral for antiviral hepatitis C infection treatment. The level of 27 cytokines was measured in serum using multiplex technology. Patients were interviewed using a modified version of the European addiction severity index. Data pertaining to weight, height, current medication, smoking habits, allergies, previous medical history and ongoing withdrawal symptoms were collected. Non-parametric testing was used to investigate differences in levels of cytokines between the two groups. A 3-model hierarchical regression analysis was used to analyse associations between cytokines and confounding variables. Out of 120 included patients, 53 were on opioid maintenance treatment. Median duration of opioid treatment was 68.4 months. There were no demographical differences between the two groups other than age. IL-1β was lower and eotaxin-1 higher in the group on opioid maintenance treatment than in the non-opioid group. No other inter-group differences in the remaining cytokine levels were found. In HCV infection patients, the impact of chronic opioid administration on peripheral circulating cytokine level is minimal.

Evaluation of Articular Manifestations in Hepatitis C Virus Infected Patients and its Association with Liver Fibrosis: A Cross-sectional Study from Rural Indian State of Manipur

Introduction: Hepatitis C Virus (HCV) is the main culprit for liver diseases worldwide. In Manipur its incidence is increasing, mainly due to blood borne transmission through intravenous drugs users. Among the extrahepatic manifestations of HCV infection-arthropathy (joint pain, swelling and stiffness) is most common. Exact mechanism of arthropathy are not well elucidated but are probably connected with the participation of the immune system and due to the replicating virus in the affected tissues, organ systems. Aim: To determine the articular manifestations in HCV infected patients and to study the association between articular manifestations and liver fibrosis. Materials and Methods: This cross-sectional study enrolled 100 hepatitis C infected patients above 18 years of age who attended Medicine OPD, gastroenterology and liver clinic or admitted in the General Medicine wards, Regional institute of Medical Sciences (RIMS), Imphal, Manipur, India. Blood samples were collected for Complete Blood Count, Erythrocyte Sedimentation Rate, C Reactive Protein, Liver function test, Renal function test, HCV, Rheumatoid Factor (RF), Antinuclear Antibody (ANA), anti-ds DNA. Ultrasound (USG) whole abdomen and X-rays of involved joints were done when indicated. Markers for liver stiffness/fibrosis, {Aspartate Aminotransferases (AST) to Platelet Ratio Index (APRI)} score, The fibrosis-4 (FIB-4) score and AST/Alanine Transaminase (ALT) ratio were calculated and compared. The Statistical Package for Social Sciences(SPSS) (IBM) version 21.0 was used for statistical analysis. Chi-square and Fischer’s-exact test were used. Results: A total of 100 hepatitis C infected patients were enrolled in the present study. Majority of the study subjects were males (63%) under 40 years of age (69%). Eighty-four (84%) patients were intravenous drug users. Joint pain, swelling and stiffness was present in 37 (37%), 31 (31%) and 24 (24%), respectively. Around 36 (36%), 45 (45%) and 29 (29%) of the participants had significant fibrosis with respect to FIB 4 score, APRI and USG finding, respectively. Conclusion: The prevalence of joint pain was 37% in this study. Females and younger age group were more associated with articular manifestation. The present study concluded that patient with articular manifestation were seen to have significant fibrosis with respect to FIB 4 score, APRI and USG finding, AST/ALT.

Evaluation of liver fibrosis by non-invasive markers (transient elastography vs. APRI, FIB-4, and FORNS) in chronic hepatitis C virus carriers in a low-income country

Abstract Background: The interest in evaluating hepatic fibrosis stems from the fact that the risk of developing cirrhosis following hepatitis C virus (HCV) infection is estimated at 10%–20%. The aim of this study was to identify feasible, accessible, and affordable non-invasive methods other than transient elastography (TE) in the evaluation of liver fibrosis in a resource-limited country. Materials and Methods: This was a cross-sectional analytical study conducted over 24 months in two health facilities in Douala, Cameroon. All chronically infected HCV patients who had undergone a TE were enrolled. In this study, TE was considered the gold standard for evaluating hepatic fibrosis. Other non-invasive markers considered were the aspartate transaminase to platelet ratio (APRI) index, fibrosis-4 (FIB-4), and FORNS scores. The sensitivity (Se), specificity (Sp), positive predictive value, and negative predictive value of each marker to determine significant fibrosis and cirrhosis were calculated for different thresholds, and the best Se/Sp ratio evaluated by the area under the receiving operating characteristic curve. Results: One hundred eighty-four patients were enrolled. The mean age was 56.2 ± 10.6 years with a female predominance. There was a positive correlation between TE and the FIB-4 score, the APRI score, and the FORNS score. The threshold values to predict significant fibrosis for the FIB-4, APRI, and FORNS score were 2, 0.5, and 7.6, respectively. The threshold values to predict cirrhosis for the FIB-4, APRI, and FORNS scores were 3.2, 1.3, and 9.6, respectively. Conclusion: The FIB-4 score is the best at predicting significant fibrosis, while the APRI and FIB-4 scores are the best at predicting cirrhosis in hepatitis C patients when compared to TE as the gold standard.

Cytokine polymorphisms and genotypic susceptibility of HCV infection in ribavirin response to peg interferon.

Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.

HLA-G 3'UTR haplotype analyses in HCV infection and HCV-derived cirrhosis, hepatocellular carcinoma and fibrosis.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Chronic HCV infection is also an important cause of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV has the capacity to evade immune surveillance by altering the host immune response. Moreover, variations in immune-related genes can lead to differential susceptibility to HCV infection as well as interfere on the susceptibility to the development of hepatic fibrosis, cirrhosis and HCC. The human leucocyte antigen G (HLA-G) gene codes for an immunomodulatory protein known to be expressed in the maternal-foetal interface and in immune-privileged tissues. The HLA-G 3' untranslated region (3'UTR) is important for mRNA stability, and variants in this region are known to impact gene expression. Studies, mainly focusing in a 14bp insertion/deletion polymorphism, have correlated HLA-G 3'UTR with susceptibility to viral infections, but other polymorphic variants in the HLA-G 3'UTR might also affect HCV infection as they are inherited as haplotypes. The present study evaluated HLA-G 3'UTR polymorphisms and performed linkage disequilibrium test and haplotype assembly in 286 HCV infected patients who have developed fibrosis, cirrhosis or HCC, as well as in 129 healthy control subjects. Haplotypes UTR-1, UTR-2 and UTR-3 were the most observed in HCV+ patients, in the frequencies of 0.276, 0.255 and 0.121, respectively. No statistically significant difference was observed between HCV+ and control subjects, even when patients were grouped according to outcome (HCC, cirrhosis or fibrosis). Despite that, some trends in the results were observed, and therefore, we cannot rule out the possibility that variants associated to high HLA-G expression can be involved in HCV infection susceptibility.

Seroprevalence and Genotypic Distribution Patterns of Hepatitis C Virus among Infected Patients from Sulaimaniyah Province: Iraq

Background: The hepatitis C virus (HCV) is a prevalent cause of liver illness. The virus displays a high degree of genetic variability, with documented geographical differences in genotype predominance.&#x0D; &#x0D; Objective: This study aimed to determine the prevalence of HCV genotypes among people who lived in Sulaimaniyah province, Kurdistan region of Iraq.&#x0D; &#x0D; Patients and Methods: Blood samples were collected from 229 individuals identified as having a confirmed positive HCV antibody and who had been referred to the Public Health Laboratory in Sulaimaniyah city by medical professionals for genotyping from July 2021 to December 2022. Following the extraction of the viral RNA, a PCR-based genotyping kit was used to identify the HCV genotype.&#x0D; &#x0D; Results: The most prevalent genotype was GT1a (31.6%), followed by GT1 and GT4 (23.6%) and then GT1b (7.9%). Mixed genotypes were observed in 10.4% of samples. Males were affected mainly by HCV (58.5%) than females (41.5%). The frequency of GT1a was higher in males (32.1%) compared to females (30.5%). On the other hand, males exhibited a more excellent distribution of GT4 and GT1 than females, while GT1b and GT5 were observed more in females than males. Among mixed genotypes, GT5 or 6 was the most prevalent infection type (no.=8, 3.5%), while GT1a, 3 reported the lowest rate (no.=1, 0.4%).&#x0D; &#x0D; Conclusion: This study assesses the HCV genotype distribution among infected HCV patients in Sulaimaniyah, which is distinct from the prevalent distribution in Iraq and Middle Eastern Arab nations, but it is equivalent to the distribution worldwide.

Viral hepatitis increases the risk of cholangiocarcinoma: a systematic review and meta-analysis.

Whether viral hepatitis increases the risk of cholangiocarcinoma (CCA) has been controversial. The reasons for the differences between previous research results may be related to the differences in sample size, region, living environment and course of disease. A meta-analysis is needed to clarify the correlation between them and select the key population for early screening of CCA. Meta-analysis was used to explore the relationship between viral hepatitis and the risk of CCA, so as to provide evidence for the prevention and treatment of CCA. We systematically searched EmBase, SinoMed, PubMed, Web of Science China National Knowledge Infrastructure, and Wanfang databases. The quality of the included literature was evaluated using the Newcastle Ottawa Scale. Before merging the effect quantities, the data was first subjected to heterogeneity testing. Heterogeneity testing was evaluated using I2 (the proportion of heterogeneity variation to overall variation). Subgroup analysis was used to identify sources of heterogeneity in this study. The effect odds ratio (OR) of various studies was extracted or calculated for consolidation. Beta's rank correlation, Egger's Law of Return and funnel plot were used to test publication bias. Conduct subgroup analysis based on the regions included in the literature. A total of 2,113 articles were retrieved, and a total of 38 articles were included in the meta-analysis. There are 29 case-control studies and 9 Cohort study, including 333,836 cases and 4,042,509 controls. The combined risk estimate of all studies showed a statistically significant increased risk of CCA, extrahepatitis and intrahepatitis incidence with hepatitis B virus (HBV) infection (OR =1.75, OR =1.49, and OR =2.46, respectively). The combined risk estimate of all studies showed a statistically significant increased risk of CCA, extrahepatitis and intrahepatitis incidence with hepatitis C virus (HCV) infection (OR =1.45, OR =2.00, and OR =2.81, respectively). The research points of HCV and CCA were asymmetric, indicating that there may be publication bias in the study of HCV and CCA. HBV and HCV infection could increase the risk of CCA. Therefore, in clinical practice, attention should be paid to CCA screening and early prevention of HBV and HCV infected patients.

Impact of Hepatitis C Virus Infection and Treatment on Mortality in the Country of Georgia, 2015-2020.

Mortality related to hepatitis C virus (HCV) infection is a key indicator for elimination. We assessed the impact of HCV infection and treatment on mortality in the country of Georgia during 2015-2020. We conducted a population-based cohort study using data from Georgia's national HCV Elimination Program and death registry. We calculated all-cause mortality rates in 6 cohorts: (1) Negative for anti-HCV; (2) anti-HCV positive, unknown viremia status; (3) current HCV infection and untreated; (4) discontinued treatment; (5) completed treatment, no sustained virologic response (SVR) assessment; (6) completed treatment and achieved SVR. Cox proportional hazards models were used to calculate adjusted hazards ratios and confidence intervals. We calculated the cause-specific mortality rates attributable to liver-related causes. After a median follow-up of 743 days, 100 371 (5.7%) of 1 764 324 study participants died. The highest mortality rate was observed among HCV infected patients who discontinued treatment (10.62 deaths per 100 PY, 95% confidence interval [CI]: 9.65, 11.68), and untreated group (10.33 deaths per 100 PY, 95% CI: 9.96, 10.71). In adjusted Cox proportional hazards model, the untreated group had almost 6-times higher hazard of death compared to treated groups with or without documented SVR (adjusted hazard ratio [aHR] = 5.56, 95% CI: 4.89, 6.31). Those who achieved SVR had consistently lower liver-related mortality compared to cohorts with current or past exposure to HCV. This large population-based cohort study demonstrated the marked beneficial association between hepatitis C treatment and mortality. The high mortality rates observed among HCV infected and untreated persons highlights the need to prioritize linkage to care and treatment to achieve elimination goals.

Transcriptional Analysis of TP53 Gene in Chronic Hepatitis C Patients Treated with Sofosbuvir, Daclatasvir, Pegylated Interferon, and Ribavirin.

Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies.

Prevalence and Genotypes of Hepatitis C Infection Among Hemodialysis Patients in Bushehr, Iran.

To investigate the prevalence, genotype distribution, and risk factors of hepatitis C virus (HCV) infection among patients undergoing regular hemodialysis in Bushehr province in southern Iran. All chronic hemodialysis patients from the cities of Dashtestan, Genaveh, and Bushehr participated in this study. Enzyme-linked immunosorbent assay was used to detect anti-HCV antibodies. Molecular detection of HCV infection was performed by semi-nested reverse transcription polymerase chain reaction assay, targeting 5' untranslated region and core region of the genome, and sequencing. Of 279 hemodialysis patients, 15 (5.4%) were positive for anti-HCV antibodies, and two (0.7%) patients had HCV viremia with genotype 3a. The hemodialysis patients had a significantly higher seroprevalence of HCV than the control group (p =0.007). Patients with Arab ethnicity had significantly higher anti-HCV seroprevalence compared to those with Fars ethnicity (p =0.026). Anti-HCV seropositivity was not statistically associated with the patients' sex, age group, place of residence, level of education, duration of hemodialysis, or history of blood transfusion. Considering the high seroprevalence of HCV in hemodialysis patients, regular screening of these patients for HCV infection and prompt treatment of those found infected are recommended.

Prediction of Outcome of Newly Onset Cerebrovascular Stroke in HCV Infected Patients

Chronic Vascular Diseases (CVD) is a major health burden. Hepatitis C Virus (HCV) infection has been implicated in the development of carotid artery atherosclerosis and has recently been associated with poor prognosis in stroke patients. The purpose of this study is to predict the result of de novo cerebrovascular accidents in HCV-infected patients and to look for variables that may predict it. Case control, prospective study had been carried out on two groups, Group (A) of 32 HCV infected patients presented with newly onset cerebrovascular stroke and Group (B) of 32 patients with cerebrovascular stroke without HCV infection. After meticulous history taking and neurological examination for all patients, those presenting with cerebrovascular stroke confirmed by computerized tomography (CT) or Magnetic resonance imaging (MRI) of brain were included in this study. These patients were followed up for 2 weeks and then extended follow up for 3 months was done. The outcome and predictors of prognosis had been documented and estimated statistically. Hb, platelets, albumin, cholesterol, and Na showed significant decreases in the HCV patients than in the free group. However, direct bilirubin, total bilirubin, international normalized ratio (INR), and HbA1C showed significant increases in the case group. Age, National institute of health stroke scale (NIHSS), and Diabetes Mellitus (DM) showed significant increases in poor prognosis in HCV cases, whereas HDL showed a significant decrease. NIHSS, abnormal carotid intima thickness (CIT), and abnormal pulse showed significant increases in control group with poor prognosis. Regarding fate, no significant difference was found between HCV patients and the control group. Regarding prognosis by three-month Modified rankin score (MRS) a significant decrease in the HCV patient group in comparison to the free group. We found there is a significant association between chronic HCV infections and Ischemic Stroke severity and bad prognosis.

Transforming Growth Factor Β as a Marker of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Virus Infection.

The Transforming Growth Factor-beta (TGF-β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role in hepatocarcinogenesis is controversial. To highlight the role of Transforming Growth Factor β as a marker of Hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. Ninety subjects were enrolled in this study, classified into three groups: Group I (chronic HCV group) included 30 patients with chronic HCV infection; Group II (HCC group) include 30 patients having HCC and chronic HCV infection and Group III consisted of 30 age and sex-matched healthy controls. TGF-β was evaluated in all the enrollees and its levels were correlated to liver function and other clinical parameters. TGF-β was found significantly higher in HCC group than in control and chronic HCV (P<0.001). In addition, it was correlated with biochemical and clinical parameters of cancer. Patients with HCC showed increased level of TGF-β compared to chronic HCV infection patients and controls.

Effect of SOF/VEL Antiviral Therapy for HCV Treatment

Liver cirrhosis and hepatocellular carcinoma disease caused by the Hepatitis&nbsp;C virus (HCV) infection. Inside this article, a deterministic model has been formulated and analyzed for the transmission of HCV in the liver cells. We have also considered two types of viral strain (wild and mutant). &nbsp;We have also projected a mathematical model of the effect of Sofosbuvir &nbsp;(SOF) together with Velpatasvir (VEL) antiviral therapy in HCV infected patients. Our analytical and numerical findings reveal that the optimal schedule of treatment for the best result should be obtained by choosing the best strategy depending on the circumstances.

Shear-wave elastography for evaluation of hepatic stiffness in chronic viral hepatitis B and C.

To analyse the consistency between 2D shear-wave elastography (2D-SWE) stiffness and fibrosis in liver biopsy in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. The secondary aim of the study was to analyse the consistency between liver stiffness in 2D-SWE and transient elastography (TE) measurements in patients with chronic hepatitis B and C. The study compared the results of hepatic stiffness assessment with 2D-SWE to available past liver biopsy reports in 153 patients with chronic HBV (n = 51) and HCV (n = 102) infection. In 43 patients with both hepatitides HBV (n = 8) and HCV (n = 35) we performed FibroScan on the same day as 2D-SWE. The appropriate statistical tests were applied for the analysis. Stiffness values analysed in the whole studied population showed a significant positive correlation with a stage of liver fibrosis in biopsy (r = 0.555, p < 0.001). If 2D-SWE was carried out within 24 months since liver biopsy the consistency of the results was 96%, and if the period between procedures exceeded 24 months the consistency was 81%. In 43 patients with both 2D-SWE and TE the coherence (r = 0.872, p < 0.001) and consistency (95%) between these two methods were high. Liver stiffness measured with 2D-SWE showed good consistency with stage of liver fibrosis in liver biopsies, particularly in HCV infected patients, and if the period between procedures did not exceed 24 months.