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Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p

BackgroundRecurrent respiratory papillomatosis is a potentially life-threatening condition characterised by the growth of exophytic lesions within the larynx and trachea. The principal aim of management is maintenance of an adequate airway by surgical debulking. Several adjuvant therapies have been used to varying effect to reduce the burden of this disease and increase the interval between debulking procedures. The most severe cases present in children aged under three years, who are therefore most likely to need adjuvant therapies. The current evidence base on adjuvant treatments relating to children who present aged under three years has been reviewed.MethodsA literature review of articles in Cochrane, PubMed and Embase databases was carried out. Given the rarity of the condition in this age group, all the literature relates to case reports and case series.Results and conclusionThe following adjuvant therapies have been used in children who presented under three years of age: quadrivalent human papilloma virus vaccine, intralesional cidofovir, pegylated interferon, alpha-interferon, cimetidine and cetuximab.

Background: For Interleukin 28b Single nucleotide poly-morphism (SNP) rs8099917, the favourable T allele is asso-ciated with a higher SVR after PEG-IFN alpha/RBV therapy while the G allele is a risk factor for non-response. Aim of Study: To assess the value of Interleukin 28b (SNP) rs8099917 as a predictor of SVR. Patients and Methods: This study is a retrospective con-trolled study and was performed on a total number of 240 patients who were treated by PEG-IFN alpha/RBV for 48 weeks and (SNP) rs8099917 was done for the all patients. Results: TT genotype was more prevalent in SVR group than TG and GG genotypes. Conclusion: IL-28b single nucleotide polymorphism (SNP) rs8099917 is a strong pretreatment predictor of response to pegylated interferon and ribavirin therapy in egyptian patients chronically infected with HCV genotype 4.

This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the direct‐acting antiviral effect on intracellular processes, which can then be integrated with the viral kinetics within the host while accounting for the interindividual variability between patients. This should allow an exploration of the treatment effect within the entire chronic HCV‐infected population.

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first-line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment-experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first-line direct-acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.

Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.

Objective: The purpose behind this study was to determine the frequency of erectile dysfunction in patients receiving pegylated interferon and ribavirin for the treatment of chronic hepatitis C. Study Design: Prospective observational study. Setting: Department of Gastroenterology and Hepatology, Medical Unit III, Services Hospital, Lahore. Period: Six months from 10st July 2017 to 9th January 2018. Materials and Methods: We have evaluated a total of 130 patients through a consecutive sampling technique who were admitted or visited Out-Patient-Department (OPD) with an underlying diagnosis of hepatitis C virus infection and advise to take anti viral regime (Pegylated interferon and ribavirin combination therapy) for HCV treatment and followed after 12 weeks and 24 weeks for erectile dysfunction. Results: A total of 130 patients with HCV infection were included. The overall mean age of the patients was 37.4±9.6 years. The overall frequency of erectile dysfunction was 83.07%. Among them, equal percentage of patients at 12 and at week 24 did not have erectile dysfunction (N = 76, 58.5%). While severe erectile dysfunction was surprisingly more common at week 12 (14.61%, N = 19) than at week 24 (13.07%, N = 17) of treatment. Significant association of severe erectile dysfunction was only observed at week 12 in age group 40 – 60 years (p

Background Direct-Acting agents (DAAs) target and inhibit essential viral replication proteins. They have revolutionized the treatment of Hepatitis C virus (HCV) infection reaching high levels of sustained virologic response. However, the detection of basal resistance-associated substitutions (RASs) to DAAs in naïve patients could be important in predicting the treatment outcome in some patients exhibiting failures to DAA-based therapies. Therefore, the aim of this work was to evaluate the presence of RASs as minority variants within intra-host viral populations, and assess their relationship to response to therapy on a multiple times relapser patient infected chronically with HCV. Case presentation A male HCV infected-patient with a genotype 1a strain was evaluated. He had previously not responded to dual therapy (pegylated interferon-α plus ribavirin) and was going to start a direct-acting agent-based therapy (DAAs). He showed no significant liver fibrosis (F0). Viral RNA was extracted from serum samples taken prior and after therapy with DAAs (sofosbubir/ledipasvir/ribavirin). NS5A and NS5B genomic regions were PCR-amplified and the amplicons were sequenced using Sanger and next-generation sequencing (NGS) approaches. RASs were searched in in-silico translated sequences for all DAAs available and their frequencies were determined for those detected by NGS technology. Sanger sequencing did not reveal the presence of RASs in the consensus sequence neither before nor after the DAA treatment. However, several RASs were found at low frequencies, both before as well as after DAA treatment. RASs found as minority variants (particularly substitutions in position 93 within NS5A region) seem to have increased their frequency after DAA pressure. Nevertheless, these RASs did not become dominant and the patient still relapsed, despite perfect adherence to treatment and having no other complications beyond the infection (no significant fibrosis, no drug abuse). Conclusions This report shows that some patients might relapse after a DAA-based therapy even when RASs (pre- and post-treatment) are detected in very low frequencies (

Background The progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus (HCV) infection who underwent pegylated interferon plus ribavirin (PR) regimen and achieved a sustained virological response 24 weeks post-treatment (SVR24). Methods Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma (HCC), progression of liver disease (increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates (AIRs) of these adverse events were analyzed, and the risk factors were also examined. Results In total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68% (95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05% (95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease (AIR: 6.17% vs. 1.42%, P = 0.039). Conclusions The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.

Background:: Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Of those infected, 70% (55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death. Objective:: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects. Methods:: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation. Results:: We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings. Conclusion:: Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy.

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. Methods Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). Results SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. Conclusion Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

The pegylated interferon plus ribavirin combination therapy has been used as the primary treatment for chronic hepatitis C (CHC) but fails to produce a sustained viral response (SVR) in many patients. In recent years, the treatment of CHC has been rapidly changing because of the introduction of direct-acting antivirals (DAAs), which have a high cure rate. However, retreatment of patients after failure of the first DAA therapy is difficult. We report two rare cases of CHC that showed acquired SVR with other DAA combinations after failure to daclatasvir and asunaprevir.

Background Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-α on the activity of serotonergic receptors 5-HT1A and 5-HT2A, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. Methods The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-α2a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery–Asberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. Results Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (β = −0.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery–Asberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). Limitations This study had an open-label design in a population receiving naturalistic treatment. Conclusion The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a.

HCV genotype 4 dominates the HCV epidemic in Egypt. Drug resistance was the most serious side effect that reflects bad clinical outcome. Several studies had demonstrated that baseline serum interferon-γ-inducible-protein 10 (IP-10) levels and interleukin 28B polymorphisms were associated with the resistance to the standard of care pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy and development of post-treatment relapse. Our purpose was to assess the predictive value of combining IP-10 levels and IL28B genotypes to PEG-IFNα/RBV therapy response in Egyptian chronic HCV infection patients with genotype 4. Ninety Egyptian patients chronically infected by HCV genotype-4 treated with pegylated interferon alpha and ribavirin (PEG-IFNα/RBV) therapy were enrolled. Serum IP-10 levels were determined by enzyme linked immunosorbent assay pre- and post- treatment. IL-28B (rs12979860 and rs8099917) polymorphisms were performed by PCR-RFLP in all patients. Overall, 38 patients (42.2%) achieved sustained virologic response (SVR) and 52 (57.8%) patients have non-viral response (NVR). Pretreatment serum IP-10 mean levels were significantly lower in patients who achieved SVR than in NVR (P

Hsuan-Wei Chen,1 Yi-Lin Chiu,2 Tsai-Yuan Hsieh,1 Peng-Jen Chen,1 Tien-Yu Huang,1 Hsuan-Hwai Lin,1 Yu-Lueng Shih,1 Jung-Chun Lin1 1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Biochemistry, National Defense Medical Center, Taipei, TaiwanCorrespondence: Jung-Chun LinDivision of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Sec 2, Cheng-Kung Road, Neihu 114, Taipei, TaiwanTel +886-2- 87927409Fax +886-2- 87927139Email doc10506@gmail.comBackground: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans.Methods: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus.Findings: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders.Conclusion: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.Keywords: cytokines, interferon-α, PBMCs, VDR signaling, vitamin D

Background Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. Methods We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κβ ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. Results A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/μL, and 86.6% had HIV-1 RNA Conclusions SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.

Background/Aims: We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treat ment in patients with chronic hepatitis C (CHC). Methods: Our study was a multi-center, randomized controlled trial in 11 hos pitals. CHC patients were randomly assigned (1:1) to two groups namely, PEG-IFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU dai ly) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). Results: One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients complet ed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). Conclusions: Vitamin D supplement did not increase SVR in treatment naive pa tients with CHC irrespective of genotype.

Background: The presence of direct-acting antiviral (DAA) has improved the treatment of HCV infection and making it more preferable than Pegylated-interferon (PegIFN) and Ribavirin (RBV) based treatment. However, treatment with all DAA combination regimen is limited and expensive in low health care affordability country including Indonesia. The appearance of generic sofosbuvir (SOF) facilitate the utilization of SOF plus PegINF with or withour RBV combination. Therefore, in this study we assessed the efficacy of SOF+RBV and SOF+RBV+PegINF combination for treatment of chronic hepatitis C infections patient with genotype 1 in Indonesia.Method: We performed retrospective study comprising 128 patients in Cipto Mangunkusumo Hospital with chronic hepatitis C, genotype 1, infection. 36 patients was treated with PegINF+SOF+RBV and 92 patients was treated with SOF+RBV with the duration of therapy was 12 and 24 weeks in both arms. The primary endpoint was sustained virologic response after treatment completion (SVR12).Results: In the end of treatment, 99.2% patients achieved undetected HCV RNA in 12 weeks and 24 weeks duration of therapy (100% in PegINF+SOF+RBV group and 98.9% in SOF+RBV group). The SVR12 of PegINF+SOF+RBV reach 100% meanwhile The SVR12 of SOF+RBV reach 88%. No different in SVR12 between cirrhotic and non-cirrhotic patient in PegINF+SOF+RBV group while in SOF+RBV group, the SVR12 was lower in cirrhotic patients (82.9%) compared to non-cirrhotic patients (92.2%). In multivariate analysis, HIV co-infection is associated with lower SVR12 in SOF+RBV group.Conclusion: 12 weeks and 24 weeks of PegINF+SOF+RBV and SOF+RBV is effective in the treatment of genotype 1 chronic hepatitis C infection.

Background: Neopterin is a proinflammatorymarker which participates in cell-mediated immunity, and its elevated concentrations declare the presence of interferon-γ in body fluids. In thisstudy, neopterin concentrations were determined in patients with chronic hepatitis C virus (HCV)to assess whether its plasma level can be used to predict the response to antiviral therapy by pegIFNγ combined with ribavirin before starting the treatment. Materials and Mehtods: A total of 54 subjects (all males with an average age of 46.12± 9.89) were included in this study. Neopterin levels were evaluatedby Enzyme-linked immunosorbent assay (ELIZA) in HCV patients treated with peylated interferon combined with ribavirin. Liver function tests (Aspartate aminotransferase, Alanine aminotransferase), albumin and creatinine concentrations were also estimatied. Results: Mean and median pretreatment neopterin levelsshowed no statistically difference between patients with sustained virological response (cured)and non-responders (relapsed) where the concentrations in both groups were≥16 nmol/L.On the other hand, a positive correlation was observed between neopterin level and creatinine at (p ≤ 0.05). Conclusion: Our study suggests that the pretreatment level of neopterin might not be used in routine clinical practice as a marker to predict the response to antiviral therapy in HCVpatients.

Background Direct-acting antivirals (DAAs) are entering the hepatitis C virus (HCV) treatment landscape in Hong Kong, prompting the need for cost–effectiveness evaluations of these interventions to enable optimal use of healthcare resources. Aims This study aimed to compare the cost–effectiveness of DAAs to standard-of-care pegylated interferon plus ribavirin (RBV) in treatment-naïve patients without significant liver fibrosis and to compare different DAAs in patients who are treatment-experienced and/or have advanced liver disease. Methods A Markov model was constructed to evaluate cost–effectiveness over a lifetime time horizon from the payer perspective. The target population was treatment-naïve and treatment-experienced HCV genotype 1 patients, stratified by degree of liver fibrosis. The model consists of 16 health states encompassing METAVIR fibrosis score (F0–F4), treatment success or failure, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death. The proportions of patients achieving sustained virologic response were obtained from clinical trials. Other inputs were obtained from published and local data. The primary outcome was incremental cost–utility ratio for each DAA versus pegylated interferon + ribavirin and among different DAAs. Results In treatment-naïve F0–2 HCV patients, all DAAs were cost-effective in genotype 1a and daclatasvir + asunaprevir, elbasvir/grazoprevir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir were cost-effective compared to pegylated interferon + ribavirin in genotype 1b. In genotypes 1a and 1b, treatment-experienced patients, and F3–4 patients, elbasvir/grazoprevir was the least costly DAA and economically dominant over most other DAAs. Conclusions DAAs can be a cost-effective option for the treatment of genotype 1 HCV patients in Hong Kong, and elbasvir/grazoprevir is cost-effective.

Background: Worldwide, more than one million people die each year from hepatitis C virus (HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Objective: Studying the benefit of adding sofosbuvir to pegylated interferon and ribavirin in chronic hepatitis C patients not responding to interferon and ribavirin as regards virological response and liver fibrosis regression. Patients and methods: A prospective study was conducted in cooperation with AL-AgouzaPoliceHospital. The enrolled patients were classified into two groups: Group (A): one hundred and fifty naive patients with chronic HCV infection, and group (B): one hundred and fifty patients with chronic HCV infection who were non responders to prior treatment with pegylated interferon and ribavirin after at least 6 months of this treatment. Enrolled patients were treated using interferon (IFN) based regemin that included Pegylated INF alpha + ribavirin (weight based; 1200 mg if ≥ 75 Kg or 1000 if < 75 Kg of body weight) + sofosbuvir (400 mg/day for 12 weeks) according to National Committee for Control of Viral Hepatitis (NCCVH) hepatitis C treatment protocol update, May 2015. PCR was done 4 weeks after starting treatment (RVR), at the end of treatment (ETR), 12, 24, 48 weeks after the end of treatment to assess virological response in both groups. Fibroscan was done before treatment and 12-24 weeks after the end of treatment to assess liver fibrosis. Results: Of the 300 patients included, SVR12 was achieved in 275 patients (92%), SVR24 and SVR48 in 267 patients (89%). There was a statistically significant difference between both studied groups as regards SVR12, SVR24 and SVR48 where group (A) showed better virological response than group (B). Regression of fibrosis was achieved in both groups, and there was a statistically significant difference as regards pre-treatment and post-treatment fibroscan score in both groups. Conclusion: Adding Sofosbuvir to Interferon and Ribavirin in retreating chronic hepatitis C patients not responding to Interferon and Ribavirin improved the response of treatment and caused regression of liver fibrosis.

Background and aim Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. Methods The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naive to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. Results ALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. Conclusions ALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

BACKGROUND To assess the effects of eradication of hepatitis C virus (HCV) on cardiovascular risk (CVR) and preclinical atherosclerosis in HIV/HCV-coinfected patients. SETTING Prospective cohort study. METHODS We assessed serum lipids, 10-year Framingham CVR scores, pulse wave velocity, carotid intima-media thickness, and biomarkers of inflammation and endothelial dysfunction (BMKs) at baseline and 96 weeks (wk) after initiation of anti-HCV therapy (Rx) in HIV/HCV-coinfected patients. RESULTS A total of 237 patients were included. Anti-HCV therapy comprised pegylated interferon and ribavirin plus 1 direct-acting antiviral in 55.2%, pegylated interferon and ribavirin in 33.8%, and all-oral direct-acting antiviral in 11.0%. A total of 147 (62.0%) patients achieved sustained viral response (SVR). Median increases in low-density lipoprotein cholesterol in patients with and without SVR were 14 mg/dL and 0 mg/dL (P = 0.024), respectively. Increases in CVR categories were found in 26.9% of patients with SVR (P = 0.005 vs. baseline) and 8.1% of patients without SVR (P = 0.433). This resulted in a significant interaction between SVR and CVR over time (P < 0.001). No significant effect of SVR was observed for pulse wave velocity (P = 0.446), carotid intima-media thickness (P = 0.320), and BMKs of inflammation and endothelial dysfunction. CONCLUSIONS In coinfected patients, eradication of HCV had no effect on markers of preclinical atherosclerosis and BMKs of inflammation and endothelial dysfunction but was associated with a clinically relevant rise in serum low-density lipoprotein cholesterol. Evaluation of CVR should be an integral part of care after the cure of chronic hepatitis C in patients with HIV.

Background: Chronic Hepatitis C (CHC) is a common progressive healthcare challenge that leads to liver cirrhosis, liver failure, and hepatocellular carcinoma. The optimum therapy was a combination of pegylated interferon and ribavirin, which was associated with moderate response and severe side effects. Sofosbuvir revolutionized CHC treatment, especially in combination with other antiviral agents. Objective: The aim of this study was to compare and evaluate the safety and efficacy of sofosbuvir/ daclatasvir versus sofosbuvir/ledipasvir for the treatment of non-cirrhotic naïve patients with chronic Hepatitis C Virus (HCV) genotype 4 infection for 12 weeks. Method: One hundred CHC genotype 4 patients (70 females, 30 males) were recruited from the hepatology clinic at the Beni-Suef general hospital. Patients were randomly allocated into two groups that received a 12 weeks treatment of either sofosbuvir 400 mg/daclatasvir 60 mg or sofosbuvir 400 mg/ledipasvir 90 mg. The sustained virological response 12 weeks post-treatment (SVR12) (HCV RNA < Lower Limit of Quantification (LLOQ)) was determined to evaluate efficacy. The clinical laboratory tests and any reported adverse effects starting from the administration of the first dose till 30 days after the last dose were assessed to evaluate safety. The main outcome measure was the assessment of the safety, efficacy and compliance of sofosbuvir/ daclatasvir versus sofosbuvir/ledipasvir for the treatment of non-cirrhotic naïve CHC genotype 4 patients for 12 weeks. : The main outcome measure was the assessment of the safety, efficacy and compliance of sofosbuvir/ daclatasvir versus sofosbuvir/ledipasvir for the treatment of non-cirrhotic naïve CHC genotype 4 patients for 12 weeks. Results: SVR12 was achieved by 98% and 96% of patients receiving sofosbuvir plus ledipasvir and sofosbuvir plus daclatasvir, respectively. The most common adverse events reported were headache, and fatigue. No patients discontinued treatment due to adverse events. Conclusion: The findings from this study suggest that the 12 weeks treatment regimens of sofosbuvir plus daclatasvir and sofosbuvir plus ledipasvir were both efficacious and well-tolerated in patients with HCV genotype 4 infection. Impact on Practice: In this paper, we report on the most recent approaches in the treatment of Hepatitis C genotype 4 patients in Egypt. This is significant because this article focuses on comparing the efficacy and tolerability of the most commonly used antiviral drugs in Egypt.

International audience; Current treatments against chronic hepatitis B (CHB) include pegylated interferon alpha (Peg-IFNα) and nucleos(t)ide analogs (NAs), the latter targeting the viral retrotranscriptase, thus inhibiting de novo viral production. Although these therapies control infection and improve the patient's quality of life, they do not cure HBV-infected hepatocytes. A complete HBV cure is currently not possible because of the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Current efforts are focused on achieving a functional cure, defined by the loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA levels in serum, and on exploring novel targets and molecules that are in the pipeline for early clinical trials. The likelihood of achieving a long-lasting functional cure, with no rebound after therapy cessation, is higher using combination therapies targeting different steps in the hepatitis B virus (HBV) replication cycle. Novel treatments and their combinations are discussed for their potential to cure HBV infection, as well as exciting new technologies that could directly target cccDNA and cure without killing the infected cells.

Summary Objectives The advent of direct-acting antivirals (DAAs) has revealed high rates of sustained virological response at 12 weeks (SVR 12) in Hepatitis C (HCV) treatment. Since the introduction of DAAs, in our centre, 42% of patients treated for HCV are HIV co-infected. Our study aimed to identify the SVR 12 rates between this group and HCV mono-infected patients. Methods Retrospective data analysis of HCV mono-infection and HIV-HCV co-infection patients between 1st July 2015 and 30th November 2018, who had a SVR at 12 weeks post treatment. Co-infected patients were only referred for HCV treatment if they had well controlled HIV. Patients treated with Pegylated Interferon and Ribavirin were excluded. Results During this period, 724 patients were treated for HCV and had data on SVR 12. Of those, 303 (41.8%) were co-infected with HIV. The SVR 12 was achieved in 386 (91.6%) of the HIV negative patients and 288 (95%) of the HIV positive patients (χ²= 3.10 p = 0.078). Cirrhotic patients had poorer SVR 12 in both groups (90% in co-infection and 88.4% in HCV mono-infection). Conclusions Our results demonstrate a higher SVR 12 in co-infected patients compared to patients with HCV mono-infection. We hypothesise that adherence to HIV treatment could increase compliance and success of HCV treatment.

Background: Immunomodulatory properties of interferon (IFN) have been documented. It may induce autoimmune diseases such as autoimmune thyroiditis with hypo- or hyperthyroidism. In addition, it may impair thyroid hormone synthesis through affecting iodide organification in thyroid gland.Purpose: The aim of this study was to describe thyroid function tests disturbances in children with chronic hepatitis C (CHC) receiving pegylated interferon-alpha (PEG IFN-α) plus ribavirin.Methods: Fifty children with CHC virus infection who received combined pegylated interferon-alpha with ribavirin were selected. Other 50 apparently healthy children of matched age and sex (considered as control group) were selected. All children (100) were subject to liver function tests, virological studies, and follow-up of thyroid function test during and after the treatment course.Results: Our study showed that 28% of children received combined PEG IFN-α plus ribavirin showed subclinical hypothyroidism. After 24 weeks treatment with combined therapy of IFN plus ribavirin, the mean level of thyroid stimulating hormone (TSH) was 3.23±88 mU/mL, while TSH was 1.16± 0.77 mU/mL before starting treatment. On the other hand, mean TSH was 1.09±0.92 mU/mL in normal control group.Conclusion: This study revealed an association between subclinical thyroid dysfunction and treatment with IFN-alpha and ribavirin in children. Further studies on larger number of patients and longer follow-up duration are recommended for further confirmation.

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.

Background Georgia has one of the highest HCV prevalence in the world and launched the world’s first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia. Methods Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed. Results Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05–1.15]) and genotype 3 (RR = 1.14, CI [1.11–1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93–0.98]), receiving treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR = 0.85, CI [0.81–0.91]; RR = 0.86, CI [0.82–0.92]; RR = 0.88, CI [0.85–0.91] and RR = 0.92, CI [0.87–0.98], respectively) were less likely to achieve SVR. Conclusions Georgia’s real world experience resulted in high overall response rates given that most patients had severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs, significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.

Background and Aim Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. Methods A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients’ plasma using methylation-specific polymerase chain reaction (MSP). Results Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients’ response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P

Background Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in Methods A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment. Results SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction. Conclusions DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

Genetic polymorphisms within the interferon λ (IFN-λ) chromosomal region, mainly rs12979860 of IFN-λ4 gene (IFNL4), are known as associated with spontaneous hepatitis C virus (HCV) resolution and sustained viral response to therapy with pegylated interferon- α and ribavirin. Strong linkage disequilibrium of IFNL4 rs12979860 with IFNL4 rs368234815, which is casually associated with HCV spontaneous and therapeutical eradication, at least partially explains favorable HCV outcomes attributed to major homozygosity in rs12979860. Effects of IFN-based antiviral treatment are associated with pretreatment expression of the IFN-λ1 receptor, expression of hepatic IFN-stimulated genes, production of IFN- λ4, and preactivation of the JAK-STAT signaling. Nowadays direct-acting antivirals (DAAs) became a potent tool in the treatment of hepatitis C, but IFN-λs are still under investigation as potential antivirals and might be an option in HCV infection (DAA resistance, recurrent viremia, adverse effects). : Patients with altered immunocompetence are especially prone to infections. In uremic subjects, polymorphisms within the IFN-λ chromosomal region associate with spontaneous HCV clearance, similarly like in the non-uremic population. Circulating IFN-λ3 shows a positive correlation with plasma titers of antibodies to surface antigen of hepatitis B virus (anti-HBs), which are crucial for protection against hepatitis B virus. More efficient anti-HBs production in the presence of higher IFN-λ3 levels might occur due to IFN-λ3-induced regulation of indoleamine 2,3-dioxygenase (IDO) expression. IFN-stimulated response element is a part of IDO gene promoter. It is worth further investigation whether IDO gene, circulating IDO, genetic polymorphisms within the IFN-λ region, and circulating IFN-λ3 act in concordance in immunological response to hepatotropic viruses.

Worldwide and national efforts are directed against eradication of HCV. The introduction of direct-acting antivirals (DAAs) has changed dramatically the outcome of HCV treatment. In spite of the Food and Drug Administration approval of the oral drugs sofosbuvir (SOF) and ledipasvir (LED) for the treatment of HCV in adolescents more than or equal to 12 years old, sufficient real-world experience is still lacking. The aim of this study was to assess the safety and efficacy of the generic SOF/LED fixed-dose combination 400/90 (400 mg SOF + 90 mg LED) for the treatment of adolescents and children (9–12 years) with chronic hepatitis C (CHC). In this prospective observational study, 100 cases of genotype 4 CHC were recruited consecutively from those fulfilling the inclusion and exclusion criteria. All cases received the generic fixed-dose combination SOF/LED (400/90), one tablet daily for 12 weeks. All clinical, laboratory, and virologic characteristics were evaluated at base line, and week (W) 2, 4, 8, and 12 of therapy and W12 post-treatment (SVR12). Recruited children (9–12) and adolescents weighed 28–83 and 31–90 kg, respectively. Eighty cases were naive and 20 cases were pegylated interferon/ribavirin treatment-experienced. Very rapid virologic response (vRVR) at W2 was 96%, while at W4 response rate was 100% and maintained till the end of treatment and at W12 post-treatment (SVR12). All reported side effects were mild and did not lead to treatment termination and disappeared at W12 post-treatment. The generic SOF/LED fixed-dose combination is safe and effective in children, 9–12 years, and adolescents with vRVR rate of 96%, 100% EOT response and SVR12.

Chronic hepatitis C (CHC) treatment modalities dramatically evolve, however some patients still suffer treatment failure with sever aggressive side effects. Accordingly personalizing antiviral treatment becomes an urgent cornerstone in treatment path. Inflammation is one of the hallmarks of viral infection. Besides it is one of the main factors interfering with drug response. Accordingly, this study focused on studying some inflammatory markers interfering with antiviral response in different CHC patients. A cohort of 157 genotype 4 (G4) Egyptian CHC patients treated with sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) plus ribavirin (RBV) were enrolled. Single nucleotide polymorphism (SNP) within chemerin gene (rs17173608) was analyzed by quantitative real-time PCR (qRT-PCR). Serum chemerin, serum IL-6 and serum alpha-fetoprotein (AFP) were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrosis grade, serum AFP, serum IL-6 and serum chemerin levels were found to be significant univariant predictors of SOF, Peg- IFNα-2a and RBV response at (p < 0.01). Moreover, G/G Chemerin (rs17173608) genotype was also proved to be associated with treatment failure (OR=17.067- 95% CI =6.684-43.575- p < 0.001) in Egyptian CHC G4 patients. Combining all predictors in Multiple stepwise regression analysis concluded that higher serum chemerin levels and G/G Chemerin rs17173608 genotype formulated the strongest predictive model with a significant prediction capacity expressed by area under the receiving operating curve (AUROC) 0.881(95% CI = 0.832–0.931) with specificity of 77.1%, sensitivity of 80.2% and accuracy of 78.9%. Chemerin is a vital pretreatment predictor of anti-HCV drug response as it accurately predicts SOF, Peg- IFNα-2a and RBV different outcomes in naive Egyptian CHC G4 patients.

Background/Aims This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. Methods This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. Results SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 103 /µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). Conclusions Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

Currently, the only approved hepatitis C virus (HCV) treatment for children aged

Chronic hepatitis D (CHD) results from an infection with the hepatitis B virus and hepatitis D virus (HDV). CHD is the most severe form of human viral hepatitis. Current treatment options consist of interferon alfa, which is effective only in a minority of patients. Study of HDV molecular virology has resulted in new approaches entering clinical trials, with phase-3 studies the most advanced. These include the entry inhibitor bulevirtide, the nucleic acid polymer REP 2139-Ca, the farnesyltransferase inhibitor lonafarnib, and pegylated interferon lambda. This article summarizes the available data on these emerging therapeutics.

Background: Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to predict the impact of EBR/GZR on the incidence of liver and kidney related complications compared with no treatment (NoTx) and pegylated interferon plus ribavirin (pegIFN/RBV) in patients with CKD stage 4/5 in Vietnam. Methods: We developed a mathematical model of the natural history of chronic HCV, CKD, and liver disease. Efficacy of EBR/GZR and pegIFN/RBV were derived from the C-SURFER trial and a meta-analysis, respectively. We calculated lifetime cumulative morbidity and mortality rates, including incidence of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and life expectancy. Results: Estimated lifetime incidence of DC was significantly reduced in patients receiving EBR/GZR (3.47%) compared to NoTx (18.14%) and pegIFN/RBV (9.01%). Estimated incidence of HCC was 1.02%, 21.64%, and 8.90%, and 1.02% in patients receiving EBR/GZR, NoTx, and pegIFN/RBV. EBR/GZR was estimated to extend life expectancy by 4.2 and 2.0 years compared with NoTx and pegIFN/RBV. Conclusions: Our model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV GT1 infection and CKD compared with NoTx or pegIFN/RBV. Keywords: Hepatitis C, Chronic kidney disease, Economics, Elbasvir/grazoprevir

Background Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. Methods Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. Results OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. Conclusions HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.

Chronic hepatitis C (HCV) caused by hepatitis C (HCV) virus, approximately estimated 170-200 million individuals in the world including Pakistan having 10 million HCV infected . The effective available treatment option is a combination of Pegylated interferon (PegIFN) and Ribavirin (RBV) . Recently Genome wide association studies (GAWAS)supporting two single nucleotide polymorphism SNPs adjacent interleukin 28B gene associated with spontaneous and treatment induced clearance of HCV patients. The aim of the present study was to analysis the impact of response associated interleukin 28B(IL28B) single nucleotide polymorphism (SNPs) rs12979860, rs8099917 in different treatment interval with one month (RVR) and after end of treatment (SVR) with Pegylated Interferon(PEG IFN) and Ribavirin in Hepatitis C genotype 3 patients. The present study enrolled 200 HCV RNA positive genotype 3 patients having both SNPs (rs12979860, rs8099917) were analyzed by Real Time Polymerase Chain Reaction (RT-PCR). The frequency distribution of IL28B genotypes were investigated by SNIPs (rs12979860 and rs8099917) in HCV RNA positive genotype 3 patients in Pakistani population

Objective This study aimed to prospectively evaluate cognitive functioning in hepatitis C virus patients before, during, and after interferon alpha and to assess the psychiatric side effects of interferon alpha such as depression and anxiety. Methods A total of 100 chronic hepatitis C virus patients eligible for interferon therapy from the hepatitis outpatient clinic of Assiut University Hospital were included. A full medical and psychiatric assessment was done using the Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A). Cognitive assessment was done using The Mini-Mental State Examination (MMSE), Memory Assessment Scales (MAS), and Wechsler Adult Intelligence Scale (WAIS). Medical, cognitive, and psychiatric assessments were conducted at the start of the study and after starting the treatment at two, four, and six months. Results There was a significant increase in the mean scores of HAM-D (t = 7.739, p Conclusion There were increases in symptoms of depression and anxiety during interferon alpha and ribavirin treatment, which do not correlate with the patients’ cognitive performance. There was a significant improvement in cognitive performance except in verbal memory with the progress of interferon alpha treatment. Years of education, socioeconomic status, and lower quantitative polymerase chain reaction are predictors for better cognitive performance.

In hepatitis C virus (HCV) infection viral and host factors can influence therapy outcome to pegylated interferon/ribavirin (PEG-IFN/RBV) and progression of liver fibrosis. Although novel direct-acting antivirals (DAAs) show newly successful treatment of hepatitis C infection, the majority of patients are unable to access this therapy because of cost and so remain untreated. Also, the efficacy of treatment with new therapy may be affected by the presence of resistance-associated substitutions (RASs). This study was designed to describe associations between baseline host and viral factors, progression of liver fibrosis and response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV) in patients with chronic hepatitis C (HCV) genotype 1b. We analyzed pre-treatment of 100 patients with chronic hepatitis C genotype 1b and related it to outcome of therapy. TaqMan assay was used to determine SNP rs12979860 in all patients. In our study there was significant correlation between age and response to therapy. Also, we found associations between a known route of transmission and age, gender, stage of liver fibrosis and therapy outcome. With respect to SNP rs12979860, the frequency of the CC genotype in the group with a sustained virologic response (SVR) was significantly higher than in the group of non-responders (NR). In contrast, there was no correlation between IL28B polymorphism and progression of liver fibrosis.

Background/Purpose: While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment. Methods: 822 Taiwanese CHC patients were enrolled from May–August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed. Results: 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients’ advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%). Conclusion: A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment. Keywords: Hepatitis C, Pegylated interferon, Ribavirin, Direct acting antiviral, Taiwan

Background and aim The prohibitively high cost of direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection remains a barrier to treatment access in Singapore. We aimed to evaluate whether DAA as first-line therapy would be cost-effective for genotype 3 (GT3) HCV patients compared with pegylated interferon and ribavirin (PR). Methods A decision tree analysis was used to compare the costs and outcomes of DAA and PR as first-line therapy. Treatment effectiveness, defined as sustained virological response, was assessed using a retrospective cohort of treated GT3 HCV patients. Direct medical costs were estimated from the payer's perspective using billing information. We obtained health utilities from published literature. We performed extensive one-way sensitivity analyses and probabilistic sensitivity analyses to account for uncertainties regarding the model parameters. Results In base case analysis, first-line therapy with DAA and PR yielded quality-adjusted life years (QALYs) of 0.69 and 0.62 at a cost of USD 54 634 and USD 23 857, respectively. The resultant incremental cost-effectiveness ratio (ICER) (USD 449 232/QALY) exceeded the willingness-to-pay threshold (USD 53 302/QALY). The ICER was robust for uncertainties regarding the model parameters. The cost of DAA is the key factor influencing the cost-effectiveness of HCV treatment. At current price, DAA as first-line therapy is not cost-effective compared with PR, with or without consideration of retreatment. Threshold analysis suggested that DAA can be cost-effective if it costs less than USD 17 002 for a 12-week treatment course. Conclusion At current price, DAA as first-line therapy is not cost-effective compared with PR in GT3 HCV patients in Singapore.

To investigate the efficacy of eltrombopag for the treatment of thrombocytopenia in patients with chronic hepatitis C, a phase II, single-arm, open-label study with a 9-week pre-antiviral phase was conducted, followed by a 48-week antiviral phase and a 24-week follow-up phase. The proportion of patients who achieved a platelet count threshold, the proportion of patients who maintained a platelet count >50,000/µl, sustained virological response (SVR) rates and safety parameters were evaluated. Of the 45 enrolled patients (median age, 59 years; median platelet count, 63,000/µl; 98% with Child-Pugh class A), 43 (96%) achieved the platelet count threshold during the pre-antiviral phase. A total of 13 patients (29%) experienced ≥1 adverse event (AE), of which headache and vomiting were the most common, and 41 patients (mostly receiving eltrombopag 12.5 mg or 25 mg) entered the antiviral phase, of which 36 (88%) maintained the platelet count threshold; no patient platelet count decreased below 25,000/µl. Nine patients (22%) achieved an SVR at the 24-week follow-up. Grade ≥3 AEs occurred in 25 patients (61%). A total of 8 serious AEs occurred in five patients (12%). No mortality, thromboembolic events (TEEs), or cataract progression were reported. Eltrombopag increased the platelet count in chronic hepatitis C virus-infected patients with cirrhosis and thrombocytopenia and enabled them to initiate and complete interferon-based antiviral therapy (NCT01636778; first submitted: July 05, 2012).

Background: Vitamin D deficiency is related to poor clinical outcomes in patients with chronic hepatitis B virus (HBV) infection. Methods: We aimed to investigate the association between the genetic variants in the vitamin D metabolic pathway and the response to pegylated interferon (Peg-IFN) therapy in patients with HBeAg-negative chronic HBV infection. One hundred seven patients treated with Peg-IFN for 48 weeks were selected from 13 specialty hospitals. Eight genotypes of vitamin D cascade genes, including CYP27B1 (rs10877012), DHCR7 (rs12785878), CYP2R1 (rs2060793, rs12794714) and GC (rs4588, rs7041, rs222020, rs2282679), were found. Results: Eighty-two patients (83.7%) were infected with HBV genotype C. Eight patients had compensated liver cirrhosis (8.7%). At 24 weeks after treatment discontinuation, 41 patients (42.3%) achieved sustained treatment response, 53 (55.2%) obtained HBV DNA