Chronic Hepatitis C Virus Patients Research Articles

Hepatitis C Virus (HCV) Eradication With Interferon-Free Direct-Acting Antiviral-Based Therapy Results in KLRG1+ HCV-Specific Memory Natural Killer Cells.

Direct acting antiviral therapies rapidly clear chronic hepatitis C virus (HCV) infection and restore natural killer (NK) cell function. We investigated NK-cell memory formation following HCV clearance by examining NK-cell phenotype and responses from control and chronic HCV patients before and after therapy following sustained virologic response at 12 weeks post therapy (SVR12). NK-cell phenotype at SVR12 differed significantly from paired pretreatment samples, with an increase in maturation markers CD16, CD57, and KLRG1. HCV patients possessed stronger cytotoxic responses against HCV-infected cells as compared to healthy controls; a response that further increased following SVR12. The antigen-specific response was mediated by KLRG1+ NK cells, as demonstrated by increased degranulation and proliferation in response to HCV antigen only. Our data suggest that KLRG1+ HCV-specific memory NK cells develop following viral infection, providing insight into their role in HCV clearance and relevance with regard to vaccine design.

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.

Changes in clinical, biochemical, immunological and integrative parameters in patients with chronic hepatitis C virus infection according to the virus genotype and the grade of activity

The aim of this study is to determine the features of the course of chronic hepatitis C virus (CHCV) infection and the dependence of changes in integrative indicators of endogenous intoxication, nonspecific immunoreactivity and inflammation on the virus genotype and the grade of activity. Materials and methods. In total, 287 CHCV patients were examined and their inpatient and outpatient medical cards were analyzed. The study included 55 healthy individuals. In addition to the general group, which included all the patients, the examined people were divided into groups, depending on the grade of activity (minimal activity – 210 people, moderate – 68, expressed – 9) and the virus genotype (1b – 150 people, 2 – 19, 3a – 102). Clinical and laboratory examination was performed according to the protocol. The integrative indices of severity, nonspecific reactivity, indices of inflammation and intoxication activity were also calculated. The statistical processing of the obtained results was carried out by Microsoft Office Excel 2010 and IBM SPSS Statistic 23 computer software. Results. The groups were sex- and age-representative. The 1b genotype (52.30 %), moderate liver fibrosis (F2 – 31.25 %) and minimal activity (73.17 %) were the most frequently encountered in patients with CHCV. The most frequent clinical manifestations were asthenovegetative syndrome (81.88 %) and heaviness in the right hypochondrium (64.76 %). Patients with CHCV caused by different virus genotypes had evenly distributed clinical data (P > 0.05), with the exception of the 1b genotype patients who were diagnosed with telangiectasia 1.3 times more frequently than in the total sample; and liver enlargement were 1.5 times (P 0.05); IIS with genotype 3a was 1.7 times lower compared with all patients (P < 0.05). The ELR indicator did not change in all grades of activity and did not differ from those of healthy individuals. In patients with moderate activity, IA was higher than in the comparison group and NI was lower than in the total group (P < 0.05). Abdominal ultrasound, regardless of the group, most frequently revealed liver enlargement (76.26% of persons) and an increase in its echogenicity (82.35 %). Conclusions. Chronic hepatitis C virus patients were dominated by asthenovegetative syndrome, feeling of heaviness in the right hypochondrium, liver enlargement, increase in lymphocyte count, ESR, transaminase activity. Telangiectasia in genotype 1b and liver enlargement in genotype 2 were less frequent. Laboratory changes were accompanied by leukocytopenia, erythrocytopenia, anemia and thrombocytopenia, an increase in total protein content, ALT, AST and GGT activity. In chronic hepatitis C virus, the entropy indexes of leukocyte formula, RC, Ilimph, AI, ILG and IL ESR were increased. Positive ANAs were significantly more frequently identified than AMAs.

Sofosbuvir and Ribavirin Combination Therapy Response in Various Hepatitis C Virus Genotypes in Peshawar, Khyber Pakhtunkhwa

Background: Approximately 3% of the population worldwide is infected with Hepatitis C Virus (HCV). Different regimens have been used to treat HCV, each of which has its side effects and efficacy. Sofosbuvir, a direct-acting antiviral drug, has replaced all previous regimens with the highest response rate. However, its response is not fully covered in Pakistan, especially Khyber Pakhtunkhwa. Objectives: The study aimed to examine the response to Sofosbuvir and Ribavirin combination therapy in chronic HCV patients infected with various HCV genotypes. Methods: This study was conducted in Tertiary Care Hospitals, Peshawar, Pakistan. The patients were enrolled from January 2016 to March 2017. A total of 80 patients (57 naïve and 23 non-responder) were enrolled in this study. The age range was 16 - 70 years, and the mean age was 36 ± 2 years. Genotyping, biochemical profile, PCR tests, and liver ultrasounds were done for all of the enrolled subjects at the start and end of therapy. All patients were given direct-acting antiviral drugs for six months and then, the end of treatment response was noted. Results: A total of 80 subjects with HCV infection took part in the study, including 57 (71.25%) treatment-naïve and 23 (28.75%) treatment non-responding patients. The end of therapy response was reported after 24 weeks of treatment. Among the 80 patients, 72 (90%) patients achieved the end of therapy response. The highest end of therapy response (100%) was noted in genotype 1 and mixed genotypes and patients with normal liver ultrasound. The lowest end of therapy response (70%) was found in un-type genotype and patients with an abnormal texture of liver ultrasound. The end of therapy response rate was higher in females than in males. Conclusions: In the current study, the minimal response was found in un-type genotypes and genotypes that did not respond to INF, as compared to treatment-naïve subjects. Further research is needed to understand the relevant host and viral factors, with particular attention to relapsed patients and non-responders that are difficult to treat in the Pakistani population.

Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection.

Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. Twelve weeks' regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).

CXCL9 chemokine level is associated with spontaneous clearance and sustained virological response in Egyptian Chronic Hepatitis C patients receiving direct acting antivirals.

Chronic Hepatitis C virus (HCV) infection is associated with progressive liver inflammation which in turn leads to cirrhosis and finally causes hepatocellular carcinoma (HCC). By different escape mechanisms, the virus succeeds to evade the innate and acquired immune responses to establish chronic infection. This study aimed to evaluate the level of chemokine CXCL9 and its correlation with some biochemical parameters in different subjects of HCV patients. A total of 83 persons participated in this study including healthy subjects without both HCV antibodies and HCV RNA (22.9%), HCV treated responders accomplished SVR post treatment, with HCV antibodies and absence of HCV RNA (24.1%), spontaneous or natural clearance patients, with positive HCV antibodies and negative HCV RNA without treatment (26.5%) and chronic HCV-patients, with both positive HCV antibodies and HCV RNA with no treatment (26.5%). HCV RNA was quantitated by real time PCR and serum CXCL9 level was measured by ELISA commercial kit pre-coated with human MIG/CXCL9 antibody. Assessment of biochemical and hematological parameters was carried out. Data showed that, the level of CXCL9 was significantly increased in chronic individuals (627.1 pg/ml) (P< 0.001) than spontaneous clearance (107.76 pg/ml) and responder subjects (117.28 pg/ml) (P⩽ 0.05). No correlation has been found between CXCL9 level and viral load. Furthermore, CXCL9 levels correlated variably with some biochemical and hematological parameters according to each subject. Serum Chemokine CXCL9 level is associated with spontaneous clearance of HCV and response to HCV treatment, which may be identified as a predictive marker among HCV patients.

Direct-acting antivirals restore systemic redox homeostasis in chronic HCV patients

Chronic hepatitis C therapy has completely changed in the last years due to the availability of direct-acting antivirals (DAAs). Removing the virus may be not enough since chronic infection deeply modifies immune system and cellular metabolism along decades of inflammation. Oxidative stress plays a significant role in maintaining systemic inflammation during chronic HCV infection. Other than removing the virus, effective therapy could counteract oxidative stress. This study investigated the impact of DAA treatment on circulating markers of oxidative stress and antioxidant defence in a cohort of patients affected by chronic hepatitis C. To this, an observational study on 196 patients who started therapy with DAA for HCV-related hepatitis was performed. Patients were assessed at baseline, 4 weeks after the initiation of therapy (4wks), at the end of treatment (EoT), and 12 weeks after the EoT (SVR12). Circulating oxidative stress was determined by measuring serum hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and 8-hydroxydeoxyguanosine (8-OHdG). Antioxidant status was evaluated by measuring the enzymatic activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in peripheral blood mononuclear cells. We observed a reduction of serum 8-OHdG at 4wks, while the circulating level of both HNE- and MDA-protein adducts diminished at EoT; all these markers persisted low at SVR12. On the other side, we reported an increase in the enzymatic activity of all the antioxidant enzymes in PBMC at EoT and SVR12. Taking into account circulating 8-OHdG and antioxidant enzyme activities, patients with high fibrosis stage were those that had the most benefit from DAA therapy. To conclude, this study indicates that treatment with DAAs improves the circulating redox status of patients affected by chronic hepatitis C. This positive impact of DAA therapy may be related to its effectiveness on cutting down viremia and pro-inflammatory markers.

Can successful treatment by direct-acting antivirals improve depression in chronic HCV patients?

Depression is the most common extrahepatic neuropsychiatric manifestation in chronic hepatitis C (CHCV) and is due to direct neuropathogenic mechanisms. Our aim is to evaluate the effect of viral clearance by directly acting antivirals (DAAs) on depression in CHCV patients. One hundred fifty chronic HCV patients eligible for DAAs were assessed for depression using the Beck depression inventory (BDI) scale at baseline, 1 and 3 months after end of treatment (EOT). BDI ≥10 reliable in detecting depression in CHCV. All included patients received Sofosbuvir/Dacltasvir ± Ribavirin for 12 weeks and all achieved sustained virological response (SVR). Baseline BDI of all included patients was 10 ± 5 then decreased to 5.3 ± 5 and 3.5 ± 4.5 at 1 and 3 months after EOT (P = 0.001), respectively. After EOT, 20 patients (13.3%) had BDI >10 which were 11.35 ± 6.5 and 13.3 ± 3.2 at 1 and 3 months (SVR), respectively. A comparison between patients with high and low BDI after EOT showed that patients with persistent high score were older (60.6 ± 9.5vs 52.2 ± 10.6, P = 0.001) and included higher percentage of females (50% vs 22.3%, P = 0.01). Also high BDI patients had higher baseline FIB4 (3 ± 1.6 vs 2 ± 1.3, P = 0.006) and included more patients with significant fibrosis (40% vs 17.7%, P = 0.05), as well as lower baseline hemoglobin (13.6 ± 1.5 vs 14.4 ± 1.65, P = 0.04). Depression associated with CHCV improves after successful treatment with DAAs; however, it may persist in elderly females with significant fibrosis and low hemoglobin.

The Gamma-glutamyl Transpeptidase to Platelet Ratio (GPR) Predict Significant Liver Fibrosis and Cirrhosis in Chronic Egyptian HCV Patients

Background and aim: Non- invasive parameters of liver fibrosis are being widely incorporated and adopted in clinical practice, of them, 2 ratios APRI and FIB-4 were proposed and applied. The gamma-glutamyl transferase -to- platelet ratio (GPR) was developed and investigated as available test that is useful in predicting liver fibrosis stages in chronic HBV patients. We aimed to estimate the diagnostic performance of GPR compared to APRI in assessing different fibrosis stages estimated by ultrasound based Transient Elastography in chronic HCV Egyptian patients. Methods: This prospective study was conducted on 90 treatment-naive chronic HCV patients. Fibrosis stages were assessed by Transient Elastography. Serum aspartate transferase, alanine transferase, gamma-glutamyl transferase and platelets were estimated. APRI and GPR formulas were calculated. Results: GPR was significantly different with fibrosis stage (p value F3) from non-significant fibrosis (< F3) was significant with GPR AUC was 0.97 while APRI AUC was 0.86. GPR at cutoff point 0.31 has sensitivity 92 %, specificity 88%, PPV 86 % and NPV 91 %. While, APRI at cutoff 0.26 has sensitivity 81 % and specificity 78 %. Conclusion: The GPR represents a simple, non-invasive, inexpensive model for assessment of liver fibrosis. The GPR is a more accurate model than APRI to stage liver fibrosis in chronic HCV patients in Egypt.

Indeterminate Prediction of Hepatitis C Virus Genotype by Commercial Real-Time Polymerase Chain Reaction Assay Resolving by Sequencing to Avoid the Consequence of Inaccurate Typing.

Pakistan is ranked second highest after Egypt in hepatitis C virus (HCV) infection. Accurate typing is mandatory to be compliant with the World Health Organization strategy to eliminate HCV infection in 2030. We characterized the HCV genotypes using Abbott real-time polymerase chain reaction assay and indeterminate samples were sequenced. We also investigated the distribution of HCV genotype among different age groups and gender in chronic HCV patients. One thousand thirteen samples were tested for HCV genotyping using Abbott real-time HCV genotyping assay. RNA extraction from plasma was done using the m2000sp platform. The amplification and detection of genotypes was done on m2000rt instrument. The lower limit of detection assay is 500 IU/mL. The indeterminate genotypes were analyzed by sequencing of the NS5B region. We found genotype 1 in 1.68%, genotype 1b in 0.89%, genotype 1a in 0.79%, genotype 2 in 0.6, genotype 3 in 94.37%, genotype 4 in 0.4%, genotype 5 in 0.09%, and indeterminate genotype result were found in 1.18%. Abbott assay could not identify 12 samples of genotype 3 (1.18%) and gave the indeterminate result. It also fails to assign some of the samples of genotype 1 into 1a and 1b. The indeterminate genotypes were resolved by sequencing followed by phylogenetic analysis. Genotype 3 is the predominant genotype and significantly higher in females as compared with males. Genotype 1a is more common in males than in females. Indeterminate HCV genotypes on sequencing analysis identify as genotype 3a and likewise subtype of genotype1 as 1a.

Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score: A new simple score for diagnosis of HCC

Background and Study AimsThe risk of hepatocarcinogenesis depends on background liver factors, of which fibrosis is a major determinant. Serum markers and scores are of increasing importance in non-invasive diagnosis of hepatic fibrosis. Our aim was to predict the occurrence of hepatocellular carcinoma (HCC) using a non-invasive fibrosis score calculated using routine patient data. Patients and mthodsOur retrospective study included 1,291 hepatitis C related-HCC Egyptian patients (Group 1) recruited from the multidisciplinary HCC clinic, Faculty of Medicine, Cairo University in the period between February 2009 and June 2016 and 1072 chronic hepatitis C-naïve patients (Group 2) with advanced fibrosis (≥F3) and cirrhosis (F4). King score, Fibro Q score, Aspartate aminotransferase-to-platelet ratio index (APRI), AST to ALT ratio (AAR), LOK score, Göteborg University Cirrhosis Index (GUCI), Fibro-α and Biotechnology Research Center (BRC) scores were calculated for all patients. Regression analysis and receiver operating characteristics (ROC) were used to calculate the sensitivity, specificity and predictive values for significant scores with the best cut-off for predicting HCC. A regression equation was used to calculate predicted probabilities of HCC using the following variables; age, gender, haemoglobin, international normalised ratio (INR), albumin and alpha fetoprotein. The appropriate score cut-off points yielding optimal sensitivity and specificity were determined by ROC curve analysis. ResultsThere was a highly significant difference between the two groups for all calculated scores (P = 0.0001). Our new score, the Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score (Logit probability of HCC = − 2.524 + 0.152*age – 0.121*Hb − 0.696*INR – 1.059*Alb + 0.022*AFP + 0.976*Sex. Male = 1, Female = 0), with a cut-off of 0.559 was superior to other scores for predicting HCC, having a sensitivity of 90% and specificity of 80.6%. ConclusionThe HMC-CU score is a promising, easily calculated, accurate, cost-effective score for HCC prediction in chronic HCV patients with advanced liver fibrosis.

Depression-free after Interferon-α exposure indicates less incidence of depressive disorder: A longitudinal study in Taiwan

BackgroundIFN-α-induced depression in patients undergoing hepatitis C virus (HCV) treatment provides powerful support for the inflammation hypothesis of depression. Most studies have focused on the occurrence of depressive symptoms, but there has been no study yet in depression-free HCV patients receiving IFN-α. We hypothesized that HCV patients who did not develop depression after IFN-α exposure might have a lower incidence of depressive disorders after the IFN-α treatment. MethodsWe conducted a twelve-year population-based cohort study of chronic HCV patients who received IFN-α therapy. The data were obtained from the Taiwan National Health Insurance Research Database. The study cohort was patients without any depressive disorder nor antidepressant use before and during IFN-α therapy. They were matched randomly by age, sex income and urbanization at a ratio of 1:4 with the control cohort of HCV patients without IFN-α therapy. The follow-up started after the last administration of IFN-α, and the primary outcome was the incidence of depressive disorders after IFN-α therapy. ResultsA total of 20,468 depression-free subjects were identified from records of HCV patients receiving IFN-α therapy. Patients without IFN-α-induced depression were associated with a significantly lower incidence (per 10,000 person-years) of new-onset depressive disorders (126.8, 95% Confidential Interval [CI] of 118.5–135.6) as compared to the control cohort (145.2, 95% CI of 140.0–150.6) (p < 0.001). After adjusting for age, sex, income, urbanization and comorbid diseases, the crude hazard ratio for the incident depressive disorder was 0.87 (95% CI, 0.80–0.87) and the adjusted hazard ratios was 0.79 (95% CI, 0.72–0.87) for IFN-α-induced depression-free subjects as compared to the controls. DiscussionOur study indicates that IFN-α treated depression-free patients have a lower risk for depressive disorders. This hypothesized mechanism might derive from an IFN-α-induced resilience factor as yet to be defined. ConclusionsOur study might suggest a new possibility for a new pharmacological strategy against depression.

Cost-effectiveness of increased screening and treatment of chronic hepatitis C in Korea

Background Given a hepatitis C virus (HCV) elimination goal by 2030, World Health Organization (WHO) guidelines recommend scaling up HCV screening and treatment with highly-effective direct-acting antivirals (DAAs). This study investigated the cost-effectiveness of various screening and treatment strategies for chronic HCV patients in South Korea in patients aged over 40 as compared to currently screening only high-risk patients. Methods A published Markov disease progression model was used with a screening/treatment decision-tree to model different screening and treatment strategies for Korean HCV patients (aged over 40) from a national payer perspective over a lifetime time horizon. The screening strategies included “screen-all” (upfront only: “once”; or upfront and age 65: “twice”) or a “high-risk only” screening strategy followed by treatment. Treatment strategies included either ledipasvir/sofosbuvir (LDV/SOF), SOF + ribavirin (SOF + RBV; in GT2 only), or glecaprevir/pibrentasvir (GLE/PIB). Model inputs were sourced from published literature and costing databases and validated by Korean hepatologists. Results Regardless of treatment strategy, a “screen all twice” scenario led to the lowest rates of advanced liver disease events compared to “screen all once” and “high-risk only” screening scenarios. In this screening scenario, treatment with LDV/SOF for GT1/2 dominates (i.e. is more effective and less4costly) LDV/SOF in GT1 and SOF + RBV in GT2, while GLE/PIB is not cost-effective relative to LDV/SOF (₩105,124,920/QALY) at a willingness-to-pay threshold of 1xGDP per capita. Conclusion Screening all South Korean patients twice followed by LDV/SOF treatment is cost-effective as compared current high-risk screening. Adopting this strategy can help achieve WHO HCV elimination goals.

Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt

BackgroundThe scale of HCV problem in Egypt prioritized the development of a national control strategy that employs the use of locally manufactured generic direct-acting antivirals (DAAs). Achieving sustained virologic response in chronic HCV patients is the key for preventing fibrosis progression and ultimately its resolution. Objective(s)To evaluate impact of generic DAAs on liver fibrosis in chronic HCV patients using some non-invasive biomarkers (NIBMs). MethodsA total of 280 chronic HCV patients (18 treatment experienced and 262 naive) were enrolled and received the standard of care. All patients were clinically evaluated before starting treatment and at 4, 12 and 24 weeks of treatment. ResultsThe sensitivity and the specificity of the tested NIBMs for predicting cirrhosis versus liver ultrasound ranged between 75.0-79.6% and 59.4–67.2% respectively. All NIBMs showed significant linear decline during the treatment and follow up periods among responders but tended to fluctuate in values toward an increase among non-responders. In cox regression analysis, normal baseline ALT, AST, total serum cholesterol, serum albumin, WBCS, prothrombin activity and early stages of liver fibrosis predicted improvement in liver fibrosis by 1.5–2 folds. The mean probability of recovery at 1, 3, 6 months varied between the different scores and ranged from 0.059 to 0.637, 0.125–0.741, 0.538–0.951 respectively. ConclusionThe results provide prognostic data on the improvement in liver fibrosis over the treatment course and follow up periods without the need for a liver biopsy. Early detection and management of HCV infection should be emphasized to maximize the benefits of the treatment.

Pre-existing resistance associated polymorphisms to NS3 protease inhibitors in treatment naïve HCV positive Pakistani patients.

Chronic Hepatitis C Virus (HCV) infection is still a major health issue especially in endemic areas where fewer direct-acting virals (DAAs) are treatment options. Some HCV variants are associated with resistance and it reduces DAAs success where pre-existing variants prevail. In this study, we investigated resistance-associated polymorphisms (RAPs) in the HCV NS3 region from DAAs naïve Pakistani patients. 277 chronic HCV treatment naïve patients infected with genotype 1a, 3a and 3b were selected from various clinical centers in the capital city of Khyber Pakhtunkhwa province Pakistan. All the patients were included in this study after taking informed consent. HCV NS3 region was amplified and Sanger sequencing was performed to analyze RAPs to NS3 protease inhibitors. Of the total 29.24% (81/277) patients had detected with known RAPs viz V36A/G/L, T54S, V55A/D/I, Q80K/R, S122G/T/R, R155K/T/I, V158I, D168T/Q, and I170V. Among HCV-1a subjects overall RAPs found were 26.09% (12/46) and most prevalent substitutions were V36A/G (10.87%, 5/46) and R155K/T/I (8.70%, 4/46). Of the total HCV-3a infected patients, 30.95% were observed with RAPS. Ammon these, the most frequent substitutions were Q80R (13.69%, 23/168) followed by V36L (18.33%, 14/168) and V55I (5.95%, 10/168). Among HCV-3b patients, 26.98% were found with RAPs and S122R and Q80R were the dominant variants detected in 17.46 (11/63) and 12.70% (8/63) patients respectively. All these substitutions were associated with Boceprevir, Simeprevir, Telaprevir, and Paritaprevir. Single substitution in one sequence was found in 18.77% (52/277) and multiple in 10.46% (29/277). More than one RAP was frequent in HCV-3a sequences. Natural RAPs are common in chronic HCV patients infected with genotype 1a, 3a and 3b, the most prevalent subtypes in Pakistan. High prevalence of HCV NS3 RAPs suggested a large scale study of the NS3 gene before the introduction of NS3 protease inhibitors in Pakistan.

Improvement of platelet in thrombocytopenic HCV patients after treatment with direct-acting antiviral agents and its relation to outcome

Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84–127) × 103/mm3 vs. 120 (87–153) × 103/mm3(P = <0.0001) but remained unchanged thereafter to SVR24. Among responders, the platelet count significantly increased at SVR24 compared to baseline (P = <0.0001) but in relapsers, there was improvement in platelet count that didn’t reach statistical significance (P = 0.9). Logistic regression analysis showed that higher Child-Pugh score and more advanced fibrosis at baseline were significant predictors of decreasing of platelet count and development of severe TCP at SVR24. Among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis, the platelet count improved after treatment with DAAs regardless to treatment response.

Elevated mean platelet volume to platelet ratio predicts advanced fibrosis in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is an important health problem that can cause liver cirrhosis and hepatocellular carcinoma. Recently, novel inflammatory markers from complete blood count have been used as a precursor of many clinical conditions. In this study, we investigated the role of hemogram parameters in predicting advanced liver fibrosis in chronic HCV patients. Patients who underwent percutaneous liver biopsy due to chronic HCV infection between 01.01.2011 and 01.08.2019 were included in this study. Liver biopsies were evaluated according to Ishak method. Patients were classified into those with mild fibrosis (F ≤ 2) and advanced fibrosis (F ≥ 3). Hemogram parameters of these groups were compared and their efficacy in predicting severe fibrosis was investigated. Of the 81 chronic HCV patients, 38 cases were in the mild fibrosis group and 43 cases were in the severe fibrosis group. Mean platelet volume, mean platelet volume to lymphocyte ratio, mean platelet volume to platelet ratio, and red cell distribution width to platelet ratio of the severe fibrosis group were significantly higher than those of the mild fibrosis group (P < 0.05 for all). In the ROC curve analysis, mean platelet volume to platelet ratio showed the biggest area under the curve in the prediction of advanced fibrosis. Mean platelet volume to platelet ratio may be an easy and practical biomarker to gain a preliminary insight into advanced fibrosis in chronic HCV patients.

XRCC1 Gene Polymorphism Increases the Risk of Hepatocellular Carcinoma in Egyptian Population.

Section TitleSeveral major risk factors for hepatocellular carcinoma (HCC) have been identified, including chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Nevertheless, only a fraction of infected patients develops HCC during their lifetime suggesting that genetic factors might modulate HCC development. X-ray repair cross complementing group1 (XRCC1) participates in the repair pathways of DNA. Aim:to investigate the association between XRCC1 gene polymorphism and HCC in Egyptian chronic hepatitis C patients. Methods:This study was assessed on 40 patients with HCC secondary to chronic HCV infection who were compared to 20 cirrhotic HCV patients and 40- age and gender- matched healthy control group. After collection of relevant clinical data and basic laboratory tests, c.1517G>C SNP of XRCC1 gene polymorphism was performed by (PCR-RFLP) technique. Results:A statistically higher frequency of XRCC1 (CC, GC) genotypes and increased (C) allele frequency in patients with HCC was found in comparison to cirrhotic HCV patients as well as control group. In addition, patients with the XRCC1 (CC, GC) genotypes had significantly higher number and larger size of tumor foci and significantly higher Child Pugh grades. Multivariate analysis showed that the presence of c.1517G>C SNP of XRCC1 gene is an independent risk for the development of HCC in chronic HCV patients with 3.7 fold increased risk of HCC development. In conclusion: XRCC1 gene polymorphism could be associated with increased risk of HCC development in chronic HCV Egyptian patients.

Efficacy and Safety of Omibtasvir, Paritaprevir and Ritonavir Combination with Ribavirin for Treatment of Chronic Hepatitis C Patients

Abstract Background: The highest prevalence of chronic Hepatitis C Virus (HCV) was reported in Egypt. DAAs has been avail-able, with a reported 12 weeks sustained virologic response (12w-SVR) above 95% after treatment for 12 weaks. Aim of Study: Aim of the current study was to evaluate evaluate efficacy of the 2-DAAs combination of ombitasvir, paritaprevir (co-dosed with ritonavir) with ribavirin in treatment of chronic HCV patients and evaluate correlation between virologic failure and risk factors. Patients and Methods: Chronic HCV patients (n=100) were enrolled in the current study. All patients received 25mg ombitasvir, 150mg paritaprevir, and 100mg ritonavir orally once daily plus Ribavirin 600-1000mg) for 12 weaks. Response was assessed 12 weeks after end of treatment by SRT-PCR. Results: The interferon-free regimen of ombitasvir/ pari-taprevir/ritonavir + ribavirin for 12 weeks achieved sustained virologic response in 91% of patients. Conclusion: In conclusion, the 12-week 2-DAA regimen of OBV/PTV/r and DSV achieved an SVR12 rate of 91% in previously untreated patients with HCV infection. Liver Cirrhosis has negative impact on 12 weeks-SVR. Conflict of Interest: The authors have no conflict of interest related to this publication.

Intrafamilial Transmission of Hepatitis C Virus among Household Members of Hepatitis C Virus Patients

Background:Egypt is considered one of the highly endemic countries with Hepatitis C Virus (HCV) infection. Since we are moving into the HCV-free era, it is necessary to acknowledge the most common methods of HCV transmission. Intrafamilial transmission is one important method that hugely contributed to that endemicity. Aim:Our aim is to identify the prevalence of intrafamilial transmission of HCV among household contacts of chronic HCV patients, risk factors, and methods of transmission. Subjects and Methods:In this study, we recruited 807 Household members of 228 chronic HCV patients. Eligible participants were subjected to history taking, clinical examination, and blood testing for HCV antibodies and PCR. Results:We found that HCV infection was more prevalent among older age groups; married; who live in rural residence; and having high crowding index. Among relatives with HCV, parents were the most affected, followed by siblings, then husbands or wives. The longer the duration of contact, the higher the risk of infection. The incidence of HCV infection was significantly higher among patients who did the following activities: Sharing shaving machine and sugar measurement device with HCV-infected family members, sharing towels with family members, and Handshaking/kissing HCV-infected relatives.Conclusions:Intrafamilial transmission of HCV is an undeniable risk factor, which amplified the burden of HCV. Recognition of remarkable modes of intrafamilial transmission would facilitate suppression of infectivity, as a result achieving the ambition of an HCV-free Egypt.