Non-cirrhotic Hepatitis C Virus Research Articles

Is there a connection between neurocognitive profile in treatment naïve non-cirrhotic HCV patients and level of systemic inflammation?

Hepatitis C virus (HCV) infection is a progressive, systemic disease which leads to the development of end-stage liver disease. In 70% of patients, HCV infection is followed by the development of extrahepatic manifestations (EHM). A common EHM is HCV associated neurocognitive disorder (HCV-AND), characterized by neuropsychological changes in attention, working memory, psychomotor speed, executive function, verbal learning, and recall. The aim of this study is to examine the correlation between the neurocognitive profile and routine, available laboratory parameters of inflammation, liver function tests, grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia in treatment naïve non-cirrhotic HCV patients. This is a single-center exploratory study in which we examined 38 HCV + treatment naïve patients. The complete blood count and hematological parameters of systemic inflammation, liver function tests, biopsy confirmed grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia caused by chronic HCV infection were observed. In the study, we used a battery of neuropsychological tests assessing multiple cognitive domains: executive functions, verbal fluency, delayed memory, working memory and learning, and one measure for visuo-constructive performance. Before the Bonferroni correction for multiple comparisons, the results show significant correlations between the scores in the neurocognitive variables and the single measures of inflammation, liver function parameters, and mixed cryoglobulinemia. It has not found a statistically significant correlation between systemic inflammation and neurocognitive variables. After the Bonferroni adjustment, no correlations remained significant. Certainly, the obtained results can be a recommendation for additional validation through future research.

Study of MicroRNA 203 and Its Target Genes (Survivin, Cyclin-D) in Circulating Liver Cancer Stem Cells in Patients with Chronic Hepatitis C with and without HCC

Abstract Background Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality, infecting more than 180 million people worldwide. Chronic viral infection is one of the most common causes of hepatic fibrosis, distortion of the hepatic architecture, and ultimate progression to cirrhosis of the liver. HCV infection inflames the liver which, if unmanaged, will inevitably result in fibrosis and then progress to cirrhosis which has many co-morbid complications such as hepatocellular carcinoma (HCC). HCC is an aggressive tumor usually involving late stage liver cancers when diagnosed. Although significant progress regarding the treatment options for HCC has been made in recent years, poor prognosis remains a problem because of late diagnosis and drug resistance, making recurrence almost inevitable. Objective to compare level of miRNA 203 and its target genes (Survivin, Cyclin-D) in circulating liver cancer stem cells in patients with chronic hepatitis C with and without H.C.C. Patients and Methods This study was conducted in co-operation between Gastroenterology and Hepatology Department, Ain-Shams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute “between” April 2021 to October 2021.It included total participants of 80 divided to 4 GrousGroup A (HCV group): twenty patients infected with HCV without liver cirrhosis.Group B (LC group): twenty patients infected with HCV with liver cirrhosis.Group C (HCC group): twenty patients infected with HCV with HCC.Control group: twenty normal populations. Results our study demonstrated that the level of miRNA 203 showed statistically significant difference between all study groups with lowest level was found in HCC group and highest level was in control group with statistically significant decrease in HCC group than LC and other groups. The study also demonstrated that circulating level of Survivn shows significant increase in HCC group than other study groups. With no significant changes in its level between non HCC groups (Control, HCV and LC groups).The circulating Cyclin D level showed significant increase in HCC group than other study groups, With statistically significant increase in its level in LC group than control and non-cirrhotic HCV group. The study markers (miRNA 203, Survivn and Cyclin D) showed no significant relation between their levels in HCC patients and AFP level. Also, no significant relation was established between (miRNA 203, Survivn and Cyclin D) and PVT, number of focal lesions, largest diameter of the lesion or BCLC. Conclusion miRNA 203 level in circulating CSCs showed significant changes according to the stage of HCV related disease with lowest level is seen in HCC patients.Survivin level in circulating CSCs showed significant increase in HCC patients with no significant difference between other groups, and this indicates that changes in its level is highly specific for malignant transformation.Cyclin D level in circulating CSCs showed significant increase in HCC patiens than other study groups, with increase in its level in LC patients than control and non-cirrhotic HCV patients, and this indicates that the changes in its level start with cirrhosis process. No relation was established between (circulating miRNA 203, Survivn and Cyclin D) and AFP, PVT, number of focal lesions, largest diameter of the lesion or BCLC.

Response of Daclatasvir and Sofosbuvir in Treatment-Naïve, HCV Genotype 3, Non-Cirrhotic Pakistani Population: 1 Year Follow-Up Experience

using daclatasvir and sofosbuvir in treatment-naive, non-cirrhotic HCV genotype 3 Pakistani population. Methodology: From January 2017 to February 2019, HCV patients who met the inclusion criteria were included in this open-label, non-randomized, uncontrolled observational trial at HBS General Hospital in Islamabad. A 12-week course of oral daclatasvir and sofosbuvir therapy was administered to each participant. Each patient got 400mg of sofosbuvir and 60mg of daclatasvir. Treatment outcomes included sustained virological response (SVR12 and SVR24), rapid virological response (RVR), and end-of-treatment response (ETR) as primary and secondary respectively. Results: There were 105 participants in the study, of which 72.3% were male and 27.6% were female. RVR for male was 92% (p=0.002), while it was 89.65% for female (p=0.004). 96.05% of the male and 93.1% of the female achieved ETR (p=0.002). Both 93.1% of female and 93.4% of male had SVR12 (p=0.001). A single male patient experienced relapse after achieving SVR12 (p=060). SVR24 rates for male and female were 92.1% (p=0.003) and 93.1%, (p=0.003) respectively. The combination therapy was well-tolerated, with the primary side effect being fatigue (36% in males, 44% in females). Conclusion: The combination therapy of daclatasvir and sofosbuvir demonstrated both safety and efficacy in treating treatment-naïve, non-cirrhotic individuals with HCV genotype 3 in Pakistan. The study underscores the potential of direct-acting antiviral agents in addressing the challenge of HCV infections.

Impaired anti-HBV vaccine response in non-cirrhotic chronic HCV is not overcome by double dose regimen: randomized control trial

Introduction and ObjectivesSome studies suggest chronic HCV infection diminishes responses to the anti-HBV vaccine. We evaluated the efficacy of double versus standard dose HBV vaccination among HCV patients without cirrhosis. Patients and Methods141 adults with untreated chronic HCV were randomized to HBV vaccination with double dose (40μg) or standard dose (20μg) at 0, 1 and 6 months; 70 healthy HCV-negative patients given standard dose served as controls. Vaccine response was defined by anti-HBs ≥10 mIU/mL. Results128 patients (60 double, 68 standard doses) completed the study. Patients were of median age 52 years, 61% female, 60% fibrosis <2 of 4, and 76% genotype 1 with median 6-log 10 IU/mL HCV RNA. Overall seroprotection rate was 76.7% (95% CI: 65-87) in the 40μg versus 73.5% (95% CI: 63-84) in the 20μg dose HCV-positive groups (p =0.68) and 91.2% (95%CI:84-99) in HCV-negative controls (p =0.011 and 0.003, respectively). In multivariate logistic regression, vaccine dose (double vs. standard dose) was not associated with vaccine response (OR=0.63, p =0.33). Of 32 HCV-infected patients who were non-responders to 3- doses, 25 received the fourth dose of vaccine. The fourth dose seroconversion rate for the 40μg and 20μg groups were 45.5% and 21.4%, respectively. ConclusionsIn HCV-infected patients without cirrhosis, impaired responses to HBV vaccination cannot be overcome by the use of double dose HBV vaccination, but adding a fourth dose of vaccine for non-responders may be an effective strategy. Other adjuvant measures are needed to enhance seroconversion rates in these patients. Trial registerU 1111-1264-2343 (www.ensaiosclinicos.gov.br)

Usefulness of the SAF score to characterize NAFLD/NASH in non-cirrhotic HCV patients

BackgroundThe SAF score (steatosis, activity, and fibrosis) has been developed for the assessment of the histological severity of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the usefulness of the SAF score in a homogenous cohort of Egyptian patients with chronic HCV infection (CHC) without any alcohol consumption and without cirrhosis. We performed a prospective cross-sectional study including 70 consecutive Egyptian patients with chronic HCV infection to assess the usefulness of the SAF score to characterize NAFLD/NASH in non-cirrhotic HCV patients. The inclusion criteria included positive serum anti-HCV IgG antibody and positive HCVRNA, absence of treatment, and absence of cirrhosis (fibrosis score < F4). Patients were divided into two groups: with metabolic syndrome (MS) and without metabolic syndrome (non-MS). All patients were exposed to thorough history taking, full clinical examination, and laboratory and ultrasound assessment. Histopathologic evaluation of the liver biopsy for the assessment of steatosis, activity, grade, and fibrosis stage was assessed by 2 pathologists with experience in liver diseases.ResultsWe found that the degree of fibrosis increases with aging. Liver biopsies from CHC patients with metabolic syndrome (MS) exhibited a significantly higher stage of fibrosis than biopsies from those without MS; however, the grade of inflammation did not differ significantly between the two groups. No significant correlation was found between the SAF score and the body mass index (BMI) or serum HCV RNA. No significant relation between SAF score, fibrosis, and MS. No significant relation was found between the MS and the level of HCV viremia.ConclusionWe concluded that steatosis was associated with the fibrosis stage, independently of MS. This suggests that in this population, steatosis might be more related to HCV infection than to NAFLD and that fibrosis progression might be related, at least in part, to the steatosis process, i.e., virus-associated fatty liver disease (VAFLD).

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation.

Simple SummaryHepatocellular carcinoma (HCC) is a disease of poor prognosis. The early diagnosis of HCC will restrain the disease progression and thus improve patients’ quality of life. We aimed in this study to define a panel of microRNAs (miRNAs) that could facilitate the early prognosis of HCC focal lesions in the cirrhotic livers of patients previously infected with hepatitis C virus (HCV). A minimally invasive technique was used to measure the differential expression of isolated miRNAs from the serum of 201 HCV infected and HCV-HCC patients. We suggest that a panel of five serum miRNAs (miR-150, miR-199a, miR-224, miR-424, and miR-3607) might provide a potentially promising tool in the prognosis of HCC disease in cirrhotic HCV patients.Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.

Outcomes and Predictors of Non-Responsiveness in Treatment of Naïve and Non-Cirrhotic Patients with HCV Genotype 3 Infection – A Third World Perspective

Objective: To assess the clinical outcome in treatment naïve and non-cirrhotic patients with HCV genotype 3 infection after treatment with Sofosbuvir with declastasvir and valpatasvir (in case of non-responsiveness).&#x0D; Methods: Study included 263 participants. The inclusion criteria were HCV genotype 3 infection confirmed through PCR, age above 18 years, treatment naïve and non-cirrhotic. HCV PCR below the threshold of quantification at 12th week of treatment was defined as SVR12 (sustained virological response). The patients were started on a fixed dose generic combination of declastasvir 60 mg and Sofosbuvir 400 mg and PCR was performed at 12, 24 and 48 weeks. PCR positive patients at 24 weeks were given valpatasvir with Sofosbuvir.&#x0D; Results: There were 162 males and 101 females. PCR performed at 12 weeks showed that 251 patients (95.4%) became PCR negative and 12 (4.56%) remained positive. Repeat PCR of these 12 patients started on valpatasvir and Sofosbuvir at 48 weekswas negative. The treatment was well tolerated by all.Probability of positive HCV PCR at 12 weeks decreases by 0.73 with one unit increase in the hemoglobin, whereas one unit increase in TLC reduces the probability of HCV PCR at 12 weeks, positive by 0.001.&#x0D; Conclusion: The combination of Sofosbuvir and declastasvir is a cheap and effective treatment strategy for treatment naïve and non-cirrhotic HCV genotype 3 infections. Those not responding will achieve PCR negativity with a 6 month therapy of Sofosbuvir and valpatasvir combination. A high hemoglobin level and high total leucocyte count are predictors of good treatment response.

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.

The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P < 0.001 and P = 0.011, respectively). Systemic inflammatory marker (IL6) showed significant decrease in cirrhotic patients (P = 0.001). While, IL6 level did not change significantly in non-cirrhotic group (P = 0.061). Also at SVR, noninvasive liver fibrosis indices have been reduced significantly in the two groups (P < 0.001). HCV clearance by new DAA treatment improves the vascular endothelial dysfunction in Egyptian HCV infected patients with different levels of liver fibrosis and with no risk factors for endothelial dysfunction or CVD.

Role of circulating microRNA-21 and microRNA-215 in the diagnosis of hepatitis C related hepatocellular carcinoma.

Several micro ribonucleic acids (miRNAs) are deregulated in hepatocellular carcinoma (HCC). Others are linked to clinical pathological features of HCC. The goal of this study was to investigate whether miRNA-21 and miRNA-215 gene expression could be used as a non-invasive diagnostic tool to diagnose HCC. The gene expression of mature miRNA -21 and miRNA -215 in serum was analysed retrospectively using singleplex TaqMan two-step stem-loop quantitative real-time reverse-transcription PCR in 40 patients with HCC, 40 with chronic hepatitis C virus (HCV) with cirrhosis and 40 apparently healthy controls. Expression of miRNA -21 was significantly more down regulated in patients with HCC than in those with non-cirrhotic HCV (P = 0.007; odds ratio = 5; 95% confidence interval 1.6-15.4). The receiver operating curve analysis of the ability of miRNA-21 expression to discriminate between HCC and non-cirrhotic HCV revealed an area under the curve of 0.712 with 70% sensitivity and 68% specificity at a cut-off of ≤ 1.4468. Thus, the expression level of miRNA -21 could discriminate HCC from non-cirrhotic HCV. Significant positive correlation was observed between expression levels of microRNA-21 and miRNA -215 (r = 0.783, p < 0.001), but no association was observed between expression level of miR-215 and HCC or chronic HCV (p = 0.474). MiRNA-21 may be a useful, non-invasive tool for diagnosing HCC. Non-cirrhotic HCV patients have five times the risk of developing HCC when the miRNA -21 level ≤ 1.4468.

Hepatectomy outcomes in patients with hepatitis C virus-related hepatocellular carcinoma with or without cirrhosis

Although hepatocellular carcinoma (HCC) is rare in hepatitis C virus (HCV) patients without cirrhosis, little is known about the postoperative results of these patients. We performed this study to compare the outcomes of cirrhotic and non-cirrhotic HCV patients with solitary treatment-naïve HCC and to assess ability of non-invasive markers to predict prognosis in these patients. Two hundred seven adult hepatectomy patients with HCV-related HCC were prospectively identified at our institution between July 2005 and May 2019. One hundred sixteen (56%) hepatectomy patients had HCC in a non-cirrhotic liver. The non-cirrhotic group had better liver function than the cirrhotic group. Consistently, the FIB-4 grade, ALBI grade, and APRI were higher in the cirrhotic group than in the non-cirrhotic group. The cumulative disease-free survival rates and patient survival rates in the non-cirrhotic group were significantly better than in the cirrhotic group. HCC recurrence is related to major liver resection (LR) and alpha-fetoprotein (AFP) > 40 ng/mL, death is related to long hospitalization, and AFP > 40 in multivariate analysis. APRI was the only predisposing factor for HCC recurrence in non-cirrhotic patients in multivariate analysis. The FIB-4 grade, ALBI grade, and the presence of cirrhosis were not related to HCC recurrence or patient survival in multivariate analyses. The non-cirrhotic group had a higher survival than the cirrhotic group after curative LR, although the difference was not significant in multivariate analysis. The factors influencing HCC recurrence and patient survival were different in the cirrhotic and non-cirrhotic groups.

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.

Spotlight on some psychiatric aspects of hepatitis-C virus patients

Background Hepatitis C viral infection is one of the most burdensome diseases affecting 2–3% of the world population. At least 50% of patients infected with HCV suffer from one psychiatric illness. Aim The aim was to evaluate some psychiatric aspects and life quality in cirrhotic and noncirrhotic hepatitis-C virus (HCV) cases. Patients and methods A case–control study in the Neuropsychiatry Department and Internal Medicine Department in Tanta University Hospital. Patients were divided into 50 cirrhotic HCV patients (group I), 50 noncirrhotic HCV patients, both were nonmedicated (group II), and 30 healthy controls (group III). We used Child–Turcotte–Pugh, Beck Depression Inventory, Taylor's Manifest Anxiety Scale, Mini-Mental State Examination, and Liver Disease Symptom Index 2. Results Beck Depression Inventory showed a statistically significant higher percentage of mild and moderate depressed patients in patient groups (groups I and II) than the control group (group III), unlike between patient groups. Educational level was found to be significant in comparison between depressed and nondepressed groups. Taylor's Manifest Anxiety Scale showed mild and moderate anxiety high percentage in patient groups (groups I and II) than the control group (group III) and this difference was of statistical significance, unlike between patient groups. Mini-Mental State Examination revealed mild cognitive impairment of high percentage in patient groups (groups I and II) than the control group (group III) and this difference of statistical significance, unlike between patient groups. Liver Disease Symptom Index 2 showed strong affection of health-related quality of life in patient groups. Conclusion Psychiatric disorders can occur frequently in HCV patients, with a higher incidence of depression, anxiety, and cognitive impairment. All these psychiatric disorders were found in both cirrhotic and noncirrhotic patients. Also, health-related quality of life was affected in such patients markedly independent of the stage of liver disease.

Hepatitis C Virus Relapse After Ultrashort Direct-Acting Antiviral Therapy Associates With Expression of Genes Involved With Natural Killer-Cell and CD8+ T-Cell Function.

To identify immunologic correlates of hepatitis C virus (HCV) relapse after direct-acting antiviral (DAA) therapy, we quantified select immune transcripts in whole blood from noncirrhotic HCV subjects treated with 4–6 weeks of DAAs. We identified specific markers of natural killer-cell and CD8+ T-cell function (GZMB, PRF1, NKp46) with higher expression in subjects who relapsed. These findings suggest a role for host immunity in HCV eradication with ultrashort DAA therapy.We quantified whole blood immune transcripts in noncirrhotic HCV subjects treated with shortcourse antiviral therapy. Markers of natural killer-cell and CD8+ T-cell function had higher expression in virologic relapsers, suggesting a role for host immunity in HCV eradication.

The Efficacy of Generic Daclatasvir-Sofosbuvir as Pan-Genotypic Regiment for Hepatitis C Virus (HCV) Infected Patients in Bandung Indonesia

Background: Direct-acting antivirals (DAAs) have altered the prognosis of hepatitis C virus (HCV) disease but its access is limited by socioeconomic factors. Generic DAAs with lower prices were available in Indonesia in 2016. The aim of this study was to determine the efficacy of generic daclatasvir-sofosbuvir.Method: We performed an observational study from January to December 2016 in a tertiary care center in Bandung, Indonesia. Data were obtained from medical registry. All study subjects received oral daclatasvir (60 mg, once daily) and sofosbuvir (400 mg, once daily) for 12 weeks for noncirrhotic chronic HCV patients and 24 weeks for cirrhotic chronic HCV patients. The main endpoint criterion was sustained virologic response at post-treatment week 12 (SVR12).Results: We enrolled 32 subjects (20 noncirrhotic, 12 cirrhotic). All noncirrhotic subjects (eighteen were previously untreated patients) and cirrhotic subjects (all were previously untreated patients) achieved SVR12 of 100%. These high rates of SVR12 were observed in all patients with HCV infection regardless of the genotype. ALT normalization was achieved in all patients 12 weeks after therapy. The most common adverse events were fatigue and nausea.Conclusion: Once-daily oral generic daclatasvir-sofosbuvir showed good efficacy and safety. Furthermore, it yielded a high rate of SVR among patients infected with HCV of all genotypes.

Serum microRNA let-7a-1/let-7d/let-7f and miRNA 143/145 Gene Expression Profiles as Potential Biomarkers in HCV Induced Hepatocellular Carcinoma.

Background:Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Which make liver cirrhosis and hepatocellular carcinoma (HCC) major health concerns in Egypt. Circulating microRNAs (miRNAs) have been investigated as biomarkers for malignancies. We investigated miRNA gene expression of Lethal-7 (let-7) cluster: let7-a-1, let-7d-1, let-7f-1 and miRNA (miR)143/145 cluster in sera of HCC patients and chronic HCV patients. Methods:The study included 40 post HCV-Hepatocellular carcinoma patients, 40 chronic HCV patients divided into 2 subgroups, 20 cirrhotic patients and 20 non-cirrhotic patients, and 40 apparently healthy subjects as a control group. Gene expression analysis for studied miRNAs was done using quantitative SYBR Green reverse-transcription Real-Time polymerase chain reaction (PCR). Results:We found that Let-7a-1 gene expression was significantly downregulated in the serum of HCV-HCC patients than in HCV non HCC cirrhotic group and was significantly upregulated in the serum of liver cirrhosis patients than HCV non-cirrhotic group. miR-143 and miR-145 expressions were significantly downregulated in the serum of HCC patients than in control group and miR-143 was significantly downregulated in the serum of non-cirrhotic HCV patients than in control group. Conclusion:The downregulation of serum let-7-a1, miR-143, and miR-145 gene expression may exhibit significant influence on the development of HCC in chronic HCV Egyptian patients and can be used as biomarkers for HCC diagnosis.

Cost-Effectiveness Analysis of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin Regimen for Patients Infected With Chronic Hepatitis C Virus Genotype 1 in Malaysia

ObjectivesThe combination of pegylated-interferon and ribavirin (PegIFN+RBV) is currently the gold standard in treating chronic hepatitis C virus (HCV) patients in Malaysia and is reimbursed by the Malaysian authorities. This analysis evaluated the cost-effectiveness (CE) of the ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin (OBT/PTV/r+DSB±RBV) regimen as compared with the PegIFN+RBV or no treatment in chronic HCV Genotype 1 (GT1) treatment-naïve and treatment-experienced cirrhotic and noncirrhotic patients in Malaysia. MethodsA Markov model based on previously published CE models of HCV was adapted for the Malaysian public healthcare payer perspective, based on good modeling practices. Treatment attributes included efficacy, regimen duration, and EQ-5D treatment-related health utility. Transitional probabilities and health state health utilities were derived from previous studies. Costs were derived from Malaysian data sources. Costs and outcomes were discounted at 3.0% per year. Deterministic and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainties around key variables. ResultsBased on the analysis, patients treated with the OBT/PTV/r+DSB±RBV showed less frequent progression to compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths when compared with standard care (ie, PegIFN+RBV or no treatment). At a price of MYR 1846/day, the OBT/PTV/r+DSB±RBV regimen is cost-effective over PegIFN+RBV and yields better outcomes in terms of life-years (LYs) gained and quality-adjusted life-years (QALYs) at a higher cost, which is still well below the implied willingness to pay threshold of MYR 384 503/QALY. ConclusionThe OBT/PTV/r+DSB±RBV regimen is cost-effective for treatment naïve, treatment experienced, cirrhotic, and noncirrhotic GT1 chronic HCV patients in Malaysia.

How does scavenger receptor B1 polymorphism (rs4238001) affect the progression of Hepatitis C patients with persistent viral responses?

Aim: Scavenger receptor B1 (SR-B1) is an important glycoprotein that plays an important role in the entry of hepatitis C virus (HCV) to hepatocyte. SR-B1 also acts as a modulator in many situations, such as both the natural and adaptive immune system. The effects of HCV on entry to hepatocyte and response to treatment in SR-B1 mutations were investigated in many studies performed before. We aimed to investigate the effects of SR-B1 polymorphism on liver in patients with noncirrhotic HCV who received pegylated-interferon + ribavirin treatment and had persistent viral response (SVR). Material and Methods: We included naive, non-cirrhosis patients diagnosed with HCV in our clinic between 2008 and 2009. We monitored approximately 53 patients form whom we obtained SVR after treatment and followed up regularly for at least twice a year for ten years. We evaluated ultrasonography, laboratory parameters and calculated non-invasive fibrosis scores (APRI and FIB-4).Results: A total of 91% of patients were genotype 1b and 9% were genotype 1a. 2 patients developed cirrhosis in 4th and 6th year of their follow-up. One of these patients had Wild type SR-B1 rs4238001 (Gly2Ser) (GG) genotype and the other had heterozygous SR-B1 (GA) genotype. We detected no cirrhosis in none of the other 51 patients. We found improvement in APRI and FIB4 scores during follow-up in patients with both wild type and heterozygous SR-B1 genotype. It was more pronounced in the heterozygous SR-B1 group (pretreatment and 10th year values, respectively 0.82±0.65, 0.38±0.24 for APRI, 1.79±1.12, 1.31±0.65 for FIB-4) (p 0.05). Conclusion: The improvement of noninvasive fibrosis scores of SR-B1 mutations in non-cirrhotic HCV patients with SVR was more prominent in the group with heterozygous mutations. Although no difference was detected between SR-B1 mutations in terms of risk of cirrhosis progression and HCC development, larger studies are needed in this direction.

Prognostic value of serum autotaxin in liver cirrhosis and prediction of hepatocellular carcinoma

BackgroundAutotaxin is a lysophospholipase D related to liver fibrosis; its clinical role in liver cirrhosis is still unknown or limited. In this study we investigate the relation of autotaxin serum levels and prognosis of liver disease and/or prediction of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) patients.Patients and methodsThis observational, prospective case–control study included 180 participants, 60 patients with HCV-related liver cirrhosis, 60 HCV noncirrhotic patients, and 60 healthy controls. They were enrolled from inpatients and clinics of a tertiary-care hospital. Baseline characteristics, serum autotaxin, Child–Turcotte–Pugh and model of end-stage liver disease scores were determined. Abdominal ultrasound and upper gastrointestinal endoscopy were done at the beginning of the study. Cirrhotic patients were prospectively followed up for 6 months.ResultsPatients with liver cirrhosis had the highest level of autotaxin (106±24 μg/ml) compared with noncirrhotic HCV patients (81.9±21 μg/ml) and healthy controls (42.5±11 μg/ml) using one-way analysis of variance test (P=0.000). Spearman’s correlation analysis showed no significant correlation between autotaxin and Child–Turcotte–Pugh score (r=0.02; P<0.70), and model of end-stage liver disease score (r=0.15; P<0.41). At 6 months of follow-up, patients who developed HCC or encephalopathy had significantly higher baseline autotaxin level (141±55 μg/ml; P=0.02, 117±56.6 μg/ml; P=0.000), respectively, than patients who did not (102±34, 90.7±40 μg/ml). Cutoff values of autotaxin for the prediction of HCC and encephalopathy were 95 and 92μg/ml, respectively, with 91 and 92% sensitivity.ConclusionAutotaxin is a sensitive predictor for the development of HCC and encephalopathy in HCV-related cirrhotic patients. However, it was not related to disease severity.

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.