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Background and Study Aims: Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications., Patients and Methods: Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment., Results: Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups., Conclusions: Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background & Aims: The safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs) have been established in several real-world trials; however, some reports have claimed an association between DAAs and hepatocellular carcinoma (HCC) occurrence or aggressive behavior. We aimed to prospectively examine differences in de-novo HCC tumor behavior and overall survival (OS) in DAAs-treated versus HCV-untreated patients as measured by BCLC progression during a two-year follow-up period., Methods: This multicenter cohort study recruited 523 patients with de-novo HCV-related HCC. After exclusion criteria were applied, 353 patients were placed into; Group 1, including 236 patients without a history of DAAs therapy, and Group 2 including 117 patients with de-novo HCC developed after receiving DAAs. Patients were then stratified in each group according to BCLC staging (Liver, 2018). All patients received standard of care management and were followed until death or a maximum of 2 years., Results: No statistically significant differences were observed between the two groups regarding tumor characteristics (number and size of lesions) and criteria for aggressiveness upon presentation. Among all BCLC stages, DAAs treated patients showed significantly lower baseline Fib4 values than DAA untreated patients in BCLC-0 stage (4.1 vs 7.7, p 0.019). No statistically significant differences were evident in HCC progression in the different BCLC stages at 12 and 24 months follow up periods (p 0.0718 and 0.279 respectively). Significantly better survival was recorded in Group 1 compared to Group 2 patients for BCLC stages C and D (p = 0.003 and 0.01, respectively)., Conclusion: HCC may develop at an earlier stage of liver disease after DAAs therapy. No defensive role was found for DAAs treatment in delaying HCC progression that occurs after viral eradication., .

Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs.

Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.

Background: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV., Research Design and Methods: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein., Results: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01)., Conclusion: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.

Background: Conflicting studies were proposed either suggested or denied the relationship between early hepatocellular carcinoma (HCC) recurrence and the use of direct-acting antivirals (DAAs) for chronic hepatitis C management., Aim of the Study: To evaluate HCC recurrence rate post-DAAs and potential predictive factors.Study This prospective cohort study included all HCC patients achieved complete response attending our multidisciplinary HCC clinic, Cairo University, from November 2013 to February 2018. Group I (60 patients) who received DAAs after HCC ablation and group II (273 patients) who were DAAs-untreated. We studied factors that could play a role in HCC recurrence., Results: The sustained virological response rate was 88.3% among DAA-treated patients. HCC recurrence rate was 45% in the post-DAA group vs. 19% in the non-DAAs group; P < 0.001. Mean survival was significantly higher in the post-DAA group (34.23 ± 16.16 vs. 23.92 ± 13.99 months respectively; P value <0.001). There was a significant correlation between HCC recurrence rate and age, male gender, mean size of tumors and time interval between complete HCC ablation and occurrence of HCC recurrence., Conclusion: Our study reports high rate of HCC recurrence post-DAA therapy in patients treated with transarterial chemoembolization but not in those treated with curative measures. DAA therapy after curative treatment for HCC led to significantly earlier HCC recurrence, which correlated with specific clinic-pathologic features in our prospective single-institution study. However, future independent prospective randomized studies are warranted to evaluate this correlation which may lead to a change in the current standard-of-care approach to patients with hepatitis C virus-related HCC., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Study Aims: The clinical value of the cell-free DNA (cf-DNA) integrity index as a diagnostic biomarker of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) was investigated and correlated with alpha-fetoprotein (AFP)., Patients and Methods: This case-control study was conducted on 160 patients with HCV genotype 4-related liver cirrhosis. Group 1 consisted of 80 patients with HCC, including 40 patients naïve to direct-acting antivirals (DAAs) and 40 patients who received DAAs and achieved sustained virological response. Group 2 comprised 80 patients with cirrhosis without HCC. Plasma cf-DNA integrity index using ALU 115 and ALU 247 sequences was assessed using SYBR Green-based real-time polymerase chain reaction (RT-PCR). The cf-DNA integrity index was calculated as the ratio of Q247/Q115 where Q115 and Q247 are the ALU-qPCR results obtained using ALU 115 and ALU 247, respectively., Results: Patients with HCC had significantly lower plasma cf-DNA integrity index than those with liver cirrhosis. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those who did not. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve of 0.965 and 0.886 for detecting HCC using the cf-DNA integrity index and AFP, respectively. The combination of the cf-DNA integrity index and AFP improved the sensitivity from 81.6% to 94.7%, positive predictive value from 93.4% to 94.7%, negative predictive value from 84.4% to 94.9%, and accuracy from 88.4% to 94.8%., Conclusion: The cf-DNA integrity index can predict the occurrence of HCV genotype 4-related HCC. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those without previous DAAs. The combination of the cf-DNA integrity index and AFP provides better HCC prediction accuracy., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Considered as one of the most recurrent types of liver malignancy, Hepatocellular Carcinoma (HCC) needs to be assessed in a non-invasive way. The objective of the current study is to develop prediction models for Chronic Hepatitis C (CHC)-related HCC using machine learning techniques., Methods: A dataset, for 4423 CHC patients, was investigated to identify the significant parameters for predicting HCC presence. In this study, several machine learning techniques (Classification and regression tree, alternating decision tree, reduce pruning error tree and linear regression algorithm) were used to build HCC classification models for prediction of HCC presence., Results: Age, alpha-fetoprotein (AFP), alkaline phosphate (ALP), albumin, and total bilirubin attributes were statistically found to be associated with HCC presence. Several HCC classification models were constructed using several machine learning algorithms. The proposed HCC classification models provide adequate area under the receiver operating characteristic curve (AUROC) and high accuracy of HCC diagnosis. AUROC ranges between 95.5% and 99%, plus overall accuracy between 93.2% and 95.6%., Conclusion: Models with simplistic factors have the power to predict the existence of HCC with outstanding performance., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, particularly in Egypt. The role of apoptosis in tumorigenesis has been well-documented and resistance to apoptosis is a hallmark of cancer. Several studies discussed the association between death receptor 4 (DR4) genetic variants and HCC risk., Aim: To study the possible link between DR4 gene polymorphisms and the susceptibility to HCC., Methods: Genotyping of DR4-C626G, -A683C, and DR4-A1322G single nucleotide polymorphisms (SNP) was determined by polymerase chain reaction assay for 100 de novo HCV-related HCC patients, 100 chronic hepatitis C-related liver cirrhosis patients, and 150 healthy controls., Results: DR4-A1322G polymorphic genotypes (AG and GG) were significantly higher in HCC and cirrhotic patients than controls. The AG genotype conferred two-fold increased risk of HCC (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.56-3.51) and the risk increased to three-fold for the GG genotype (OR, 3.51; 95%CI, 2.33-5.28). The frequency of DR4-C626G and -A683C SNPs in HCC and cirrhotic patients were not significantly different from the controls. Combined genotype analysis showed that coinheritance of the polymorphic genotypes of DR4-C626G and -A1322G conferred nine-fold increased risk of HCC (OR, 9.34; 95%CI, 3.76-23.12). The risk increased to be 12-fold when DR4-A683C and -A1322G variants were coinherited (OR, 11.9; 95%CI, 4.82-29.39). Coexistence of the variant genotypes of the three SNPs conferred almost 10-fold increased risk of HCC (OR, 9.75; 95%CI, 1.86-51.19)., Conclusions: The G allele of DR4 -A1322G could be considered as a novel independent molecular predictor for HCV-related HCC in the Egyptian population., (© 2019 Wiley Periodicals, Inc.)

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver-related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon-free direct-acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old., (© 2018 Wiley Periodicals, Inc.)

Introduction: Scarce reports have commented on hepatocellular carcinoma (HCC) behavior after direct-acting antivirals (DAAs)., Aim: To analyze differences in tumor behavior between patients with hepatitis C virus (HCV)-induced HCC and were either treated or not using DAAs., Patients and Methods: This case-control study includes patients with HCV-related HCC who received generic DAAs (group I) and all non-DAA treated patients with HCC who presented to our clinic during the same period (group II). Patient and tumor characteristics, treatment types and outcome were compared between the two groups., Results: Group I included 89 patients and group II included 207 patients. No significant difference was detected between groups regarding HCC number or size. Group I showed a more infiltrative HCC pattern, whereas group II had more circumscribed and delineated lesions. The incidence of portal vein thrombosis and significant lymphadenopathy was significantly higher in group I (P=0.03 and 0.03, respectively). Serum levels of α-fetoprotein were significantly higher in group I (P=0.02). These factors significantly affected the response to HCC management (P=0.03). Incidence of complete responses were 47.2 and 49.8% for groups I and II, respectively, whereas incomplete responses were 12.4 and 25.1%, respectively. Supportive treatment was applied to 40.4% in group I and 25.1% in group II., Conclusion: HCC behavior was more aggressive in DAA-treated patients regarding portal vein thrombosis, malignant lymphadenopathy, and HCC imaging characteristics, which affected the chance of ablation and the treatment response.

Introduction: Steatosis is a documented feature of chronic hepatitis C (CHC). There is an association between steatosis decrease and fibrosis progression. The association between steatosis and advanced fibrosis versus hepatocellular carcinoma (HCC) development has not been precisely evaluated. The controlled attenuation parameter (CAP) was applied as an immediate and efficient process to detect and quantify hepatic steatosis with adequate accuracy., Aims: The aim of this study was to assess the difference in liver steatosis between patients with hepatitis C virus-related advanced hepatic fibrosis versus HCC., Patients and Methods: This cross-sectional study included 130 patients with HCC, attending the multidisciplinary HCC clinic, Cairo University, and 54 patients with CHC between October 2015 and June 2016. Clinical and laboratory characteristics were recorded. Liver stiffness and CAP were obtained by using the FibroScan 502, touch., Results: All included patients had genotype 4. The mean CAP value was significantly lower in HCC (209.5±57.1 dB/m) versus CHC (259.9±54.9 dB/m). Receiver operating characteristic curve revealed an area under the curve of 0.75 for the differentiation between groups. At a cutoff value of 237 dB/m, sensitivity was 72.3%, specificity was 70.7%, positive likelihood ratio was 2.5, and negative likelihood ratio was 0.4 in the differentiation between CHC versus HCC. Logistic regression analysis revealed an odds ratio of 6.4 for the diagnosis of HCC with CAP of less than 237 dB/m. Multivariate analysis, controlling for age, sex, BMI, triglycerides, and cholesterol levels, revealed a significantly increased odds for HCC diagnosis (odds ratio: 4.3, P=0.006)., Conclusion: The progression of CHC is associated with a decrease in steatosis, particularly toward advanced fibrosis and HCC. Steatosis reduction less than 237 dB/m is likely to be associated with HCC.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence., (© 2018 Wiley Periodicals, Inc.)

Background: Elastography point quantification (ElastPQ) is a newly noninvasive method incorporated into a conventional ultrasound system for staging of liver fibrosis in patients with chronic liver diseases., Aim: The aim was to evaluate ElastPQ reproducibility and its accuracy in staging of liver fibrosis in hepatitis C virus (HCV) patients in comparison with transient elastography (TE) and fibrosis scores [FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI)] using liver biopsy as a reference standard and also to predict the sensitivity and specificity of ElastPQ as well as proposing a cut-off for advanced fibrosis., Patients and Methods: A single-center, cross-sectional study enrolled 72 chronic HCV patients. Baseline demographic and laboratory data were recorded. ElastPQ and TE were performed. Fibrosis scores were calculated. The performance of ElastPQ was compared with that of TE and noninvasive methods (FIB-4, APRI) using liver biopsy as a reference standard using receiver operating characteristic curve analysis., Results: ElastPQ is a valuable diagnostic tool for the diagnosis of F≥1, F≥2, and F≥3, with area under the receiver operating characteristic curve of 0.79, 0.74, and 0.83, respectively. The best cut-off values for ElastPQ were 4.9, 6.6, and 10.7 kPa for mild fibrosis, significant fibrosis, and advanced fibrosis, respectively. ElastPQ correlated positively with all other fibrosis indices (TE, APRI, and FIB-4) as well as liver biopsy. Area under the curve for the diagnosis of advanced fibrosis (F3/F4) using ElastPQ was 0.83 at a cut-off value of 10.7 kPa (P<0.01)., Conclusion: ElastPQ is a promising noninvasive US-based method for assessing liver fibrosis in HCV-related chronic liver disease patients with good diagnostic performance comparable to that of liver biopsy and TE.

Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. The aim of the study was to compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. Six hundred and fifty two treatment naïve chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests including complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. AFP was correlating significantly with LSM, FIB-4, and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis, and cirrhosis were 0.897, 0.931, and 0.955, respectively, for equations (scores) containing AFP, LSM, and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929, and 0.959, respectively, for equations (scores) containing AFP, LSM, and APRI. The study shows that combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis., (© 2018 Wiley Periodicals, Inc.)

Introduction: Currently, direct-acting antivirals (DAAs) are considered the ideal choice for the treatment of chronic HCV patients due to their proven efficacy (SVR> 90%), and minimal adverse effects. Egypt launched a large treatment program aimed at providing treatment coverage for Egyptian HCV- infected patients. Areas covered: This review covers the treatment and prevention efforts made by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with the available model of care for HCV patients in Egypt, in addition to the barriers that prevent elimination of HCV from Egypt. Expert commentary: Egypt could provide a model for establishing the largest HCV management system aimed at eliminating HCV from the country with the highest worldwide prevalence. Despite the huge efforts and achieved results in combating the HCV epidemic in Egypt, certain improvements are needed in order to attain HCV elimination, such as the development of an enhanced screening program working in parallel to the present treatment options.

Introduction: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC., Methods: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment., Results: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03)., Conclusions: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

Background: Chronic hepatitis C virus (HCV) is a worldwide health problem that can lead to liver cirrhosis, liver cell failure and numerous subsequent complications such as hepatocellular carcinoma. Till the near past, pegylated interferon was the standard of care therapy. However, it was associated with suboptimal success rates and many side effects. Thereafter, direct antiviral agents (DAA) appeared and played the key role in management of HCV. One of those recent DAAs is ravidasvir., Summary: It is a potent NS5A inhibitor that was formerly known as PPI-668. It is produced by the cooperation of Presidio pharmaceuticals and Pharco International pharmaceutical company. Since its first production, it has been enrolled in different successive clinical trials. Phase 1 and 2 trials confirmed its safety and tolerability and its great efficacy in suppressing viral loads in short periods. It has a pangenotypic activity with favorable pharmacokinetic properties. Ravidasvir inhibits the replication of HCV variants that develop resistance mutations for different DAA classes. Even more, HCV variants that had reduced susceptibility to ravidasvir are completely susceptible to other DAA. Finally, a large multicenteric registrational phase 3 clinical trial that included large percentages of difficult to treat patients (such as cirrhotic and interferon experienced patients) has been fully accomplished and proved great SVR12 rates., Conclusion: Ravidasvir is a potent new NS5A inhibitor with excellent safety and tolerability in management of genotype 4 HCV patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background & Aims: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy., Methods: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy., Results: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%)., Conclusion: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Hepatitis C virus (HCV) is sialotropic. The pathogenesis of sicca manifestations in patients with chronic HCV infection is not fully understood. We aimed to detect changes in magnetic resonance sialography (MRS) of HCV patients with and without vasculitis., Method: We studied 32 HCV patients (19 female, mean age 48.8 ± 10.3 years) and 20 age- and gender-matched healthy controls. Half of the patients had vasculitis. Demographic, clinical and serological data were prospectively evaluated. In patients with vasculitis, the disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). MRS was performed on all patients and controls., Results: Abnormal MRS was found in 25% of patients, (6/16 and 2/16 in patients with and without vasculitis, respectively). Among patients with vasculitis, those with abnormal MRS had longer disease duration, higher leukocytic and lymphocytic counts and more frequent cryoglobulinemia (P < 0.01, P < 0.001, P < 0.001 and P < 0.008, respectively), while BVAS scores were not significantly different., Conclusion: Among HCV patients with vasculitis, longer disease duration and cryoglobulinemia were associated with abnormal findings on MRS. To confirm our results, we propose larger-scale, multicentre studies with longer evaluation periods., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Introduction: During the last few years, treatment of hepatitis C virus (HCV) revolutionized with the appearance of direct antiviral agents especially for patients with HCV genotypes 1 and 4 infections. Elbasvir (NS5A inhibitor) and grazoprevir (NS3/4A protease inhibitor) are newly developed drugs that are presented in fixed dose combination tablets. Areas covered: This review covers the mechanism of action, pharmacokinetic and pharmacodynamics properties, clinical uses, safety and efficacy of elbasvir/grazoprevir in managing a wide variety of easy and difficult to treat populations (such as presence of cirrhosis, treatment experienced, co-infection with HIV and patients with inherited blood disorders). Expert commentary: Elbasvir/grazoprevir combination showed great efficacy with high rates of sustained virological response rates in genotypes 1 and 4 HCV infection. In addition, it retained a good safety profile and is generally well tolerated.

Immunoregulatory cytokines have an influence on hepatitis C virus (HCV) infection outcome. This study aimed to determine whether single nucleotide polymorphisms (SNP) in IFN- γ and IL-10 genes are associated with susceptibility and/or are markers of prognosis regarding chronic hepatitis C outcomes. IFN γ (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 75 HCV genotype 4 patients with different disease severities (chronic hepatitis, n=25, liver cirrhosis and hepatocellular carcinoma (HCC) on top of liver cirrhosis, n=50) and 25 healthy participants using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFN γ and IL-10 genes were detected between patients and controls or between patientgroups. No significant difference in the frequency of IL-10 SNP at position -1082 or IFN-γ at position +874T/A was found between chronic HCV genotype 4 and with progression of disease severity in liver cirrhosis or HCC. In conclusion; interferon-γ and interleukin-10 gene polymorphisms are not predictors of disease progression in patients with chronic hepatitis C (Genotype-4).

Pending the emergence and approval of an effective interferon-free regimen, pegylated interferon will remain an integral part of the treatment of genotype 4 hepatitis C virus (HCV). A new 20 kDa pegylated interferon has been developed in a cost-saving fungal-based system and is commercialized in Egypt at a quarter to a third of the price of conventional pegylated interferon. We hereby test the efficacy and safety of this novel cost-saving interferon. One hundred ninety-three consecutive treatment-naive patients with genotype 4 HCV were treated using the following regimen: subcutaneous 20 kDa pegylated interferon 160 μg once weekly plus oral ribavirin 1,000 or 1,200 mg daily (based on body weight <75 kg or ≥75 kg, respectively) for 48 weeks. A sustained virological response (SVR) of 51% was achieved. Interim responses included rapid virological response (RVR): 54%, early virological response (EVR): 78% (complete EVR: 71%, partial EVR: 7%), and end of treatment response: 63%. The most common adverse events were flu-like symptoms, dyspepsia, anorexia, and pruritus. Treatment-related serious adverse events were encountered in only 2 patients (1%). Discontinuation of treatment due to adverse events occurred in only 13 patients (7%). Multiple logistic regression analyses revealed the following factors as predictors of SVR: RVR (P<0.001), alpha-fetoprotein

Background & Aims: Nitazoxanide has been proposed as a novel therapeutic agent for chronic hepatitis C virus (HCV) potentiating the effect of interferon and improving sustained virological response rates to up to 80% in genotype 4. This is an independent randomized trial to confirm the efficacy of nitazoxanide in the treatment of chronic hepatitis C genotype 4., Methods: This was an open-label trial. Treatment-naive genotype 4 HCV patients were recruited: Group 1 received weekly subcutaneous pegylated interferon 160 μg in addition to weight-based ribavirin (1200 mg if ≥ 75 kg and 1000 mg if <75 kg) for 48 weeks, Group 2 received 4 weeks lead-in therapy by nitazoxanide alone (500 mg bid) followed by triple therapy including nitazoxanide, pegylated interferon and ribavirin for a further 48 weeks., Results: Fifty patients were recruited in each group. Baseline characteristics were similar except for a higher BMI in group 1 (28.5 vs. 26.5, P = 0.01). SVR rates were similar (24/50 (48%) vs. 25/50 (50%) in groups 1 and 2 respectively, P: 0.84). RVR, cEVR and ETR rates were also similar (61% vs. 53% - P:0.4, 70% vs. 72% - P:0.8 and 62% vs. 58% - P:0.6 in groups 1 and 2 respectively). Biochemical response at week 12 was also similar (57% vs. 46% in groups 1 and 2 respectively, P:0.26). Complications were similar except for a higher rate of dyspepsia in the group receiving nitazoxanide (32% vs. 14%, P:0.03)., Conclusion: The addition of nitazoxanide to pegylated interferon and ribavirin does not improve the virological or biochemical response rates in chronic HCV genotype 4., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HCV recurrence represents a universal phenomenon after liver transplantation. In this study Fifty HCV patients who underwent living donor liver transplantation were enrolled and factors that may accelerate HCV reinfection of the allograft such as donor's age and degree of liver steatosis, recipient's age, gender, BMI, MELD score, liver functions, HCV viral load, type of immunosuppressive drug, and genetic polymorphisms of IL28B, OAS, and IL1B were studied. The results of disease-free survival (DFS) rates showed inverse correlation with the recipient's postoperative levels of ALT, AST, ALP (P < 0.001, <0.001, and 0.006 resp.) as well as pre- and postoperative titers of HCV RNA (P < 0.003 and <0.001 resp.). Recipient's IL28B SNP was a significant factor in predicting postoperative DFS (P < 0.025). However, SNPs in OAS and IL1B genes had no apparent correlation with DFS. Cox proportional hazards model revealed that patients with elevated levels of ALT, preoperative viral titers, IL28B CT, and IL28B TT were 8.28, 4.22, 3.35, and 1.36 times, respectively, more likely to develop recurrence. In conclusion IL28B SNP, ALT level, and preoperative HCV titer besides proper choice of immunosuppressant are helpful for predicting posttransplant HCV recurrence and DFS.