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Cambodia has experienced exponential economic growth in recent years and is expected to graduate from least developed country (LDC) status within the next decade. Membership of the World Trade Organization (WTO) will require Cambodia to grant product and process patents for pharmaceuticals upon LDC graduation. This study aims to measure the impact of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) on the price of HIV and hepatitis C medicine in Cambodia once it graduates from LDC status and is obliged to make patents available for pharmaceutical products and processes. Using scenarios based on likely outcomes of accession to the TRIPS Agreement, it measures the impact on the price of the HIV treatment program and compares that impact with the hepatitis C treatment program. Graduation from LDC status would be expected to result in a modest increase in the cost of the antiretroviral (ARV) treatment program and very large increases in the cost of the direct acting antivirals (DAA) treatment program. If annual treatment budgets remain constant, patent protection could see 1,515 fewer people living with HIV able to access ARV treatment and 2,577 fewer people able to access DAA treatment (a drop in treatment coverage of 93%). [ABSTRACT FROM AUTHOR]

Introduction: In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitis C (HCV) in patients with cirrhosis. We used data from the Chronic Hepatitis Cohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. Methods: Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12 weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with p value < 0.05. Results: The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159 had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-week and 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. Conclusion: An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) remains a public health concern given its global prevalence and potential complications including hepatocellular carcinoma (HCC). Current therapies, including nucleos(t)ide analogs (NA) and interferons (IFN), are effective in chronic treatment of HBV but rarely provide a functional cure due to inadequate host response and the presence of viral DNA. Therefore, novel therapies that enhance the innate immune response while suppressing DNA transcription may provide definitive treatment of HBV. In this review, the authors provide a brief overview of commonly used agents and their efficacy in treatment of HBV. Newer therapies with direct antiviral agents such as bepirovirsen (antisense oligonucleotide (ASO)) and entry inhibitors such as bulevirtide have shown efficacy in reducing viral load but demonstrate further reductions in conjunction with immune modulators such as therapeutic vaccines. Combination therapy is far superior to monotherapy alone, necessitating the need for both immunomodulators and direct antiviral agents in chronic treatment of HBV. Therapies that target covalently closed circular (cccDNA) with immunomodulators like therapeutic vaccines have shown promising results and may ultimately achieve functional cure. However, therapies need to be evaluated in the context of the patient, considering both financial and socioeconomic factors. [ABSTRACT FROM AUTHOR]

The efficacy and safety of 12 weeks of therapy with sofosbuvir/ledipasvir in three patients aged 5–10 years are presented. All three children suffered from comorbidities, including chronic kidney disease in two. All participants achieved a sustained virologic response 12 weeks after the end of treatment. No adverse effects were reported during or after the treatment, and the compliance was good. Decisions on starting treatment in children below 6 years of age should be made individually, taking compliance into consideration. The adjustment of formulation and dosing of medication during treatment is necessary in young children. Further research with larger groups of patients is needed to confirm our findings.

Objectives: Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct‐acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre‐ or post‐treatment. Materials and Methods: This case–control preliminary study enrolled three equal groups: Group (I): untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. Results: The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and the healthy ones. Conclusions: Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition. [ABSTRACT FROM AUTHOR]

Objective To learn the situation of the evolution process of HCV virus population and the selection pressure of HCV NS5B in intravenous drug users (IDUs) in Guangdong. Methods 141 blood samples from hepatitis C virus (HCV) RNA-positive blood donors and 58 from HCV patients in Guangdong were randomly collected for HCV NS5B sequence amplification, combined with HCV NS5B sequences from blood donors and IDUs obtained by sequencing previously(between 2009 and 2011). Homology analysis was performed by Molecular Evolutionary Genetics Analysis (MEGA) software, evolutionary analysis were performed by Bayesian Evolutionary Analysis Sampling Trees (BEAST) software package. Selection pressure analysis was performed on sequences isolated from IDUs by Datamonkey online software package with Mixed Effects Model Evolution (MEME) method, and the population expansion of species were analyzed using Tajima and Fu neutrality test by Arlequin software. Results The comparison results of internal homology among different subtypes of IDUs in this group were as follows : HCV-3b had the highest homology (97%), followed by HCV-3a (96%), HCV-6a (95%) and HCV-1b (94%); HCV evolution rate analysis showed that HCV-1b had the fastest evolution rate [2.17E-03 substitutions/site/year (y/y/y)], followed by HCV-3b (2.12E-0 y/y/y), HCV-3a (1.58E-03 y/y/y) and HCV-6a (1.28E-03 y/y/y). The analysis on effective population of HCV: 1980~1990 was rapid growth period for HCV-6a, 1990~1995 period for HCV-1b, and 2000~2007 period for HCV-3a. HCV population genetic characteristics was as follows: HCV-1b, 3a, 3b and 6a experienced population expansion, among which 3a and 3b were the most obvious. As to the analysis of HCV selection pressure, two positive selection sites (235 and 243)were found in the 339 nucleotide fragment of the NS5B sequence in injecting drug users, but mutation only occurred at position 316 [mutation rate 1.24% (14/1 130)] among 5 direct antiviral drug (DAA) sites in this gene. Conclusion The evolution of HCV-3b in Guangdong has showed an obvious trend of population expansion, with a high proportion and homology especially in the local IDUs. HCV-3b should be the focus of HCV prevention and control in this region. Given that the positively selected sites of the HCV NS5B gene region of IDUs in Guangdong are non-DAA binding sites, DAA is expected to demonstrate a good effect on these patients.

Abstract Background Hepatocellular carcinoma (HCC) incidence and mortality vary by race/ethnicity and both are higher in Black patients than in Whites. For HCC surveillance, all cirrhotic patients are advised to undergo lifelong twice‐annual abdominal imaging. We investigated factors associated with surveillance and HCC incidence in a diverse HCC risk group, cirrhotic patients recently cured of hepatitis C virus (HCV) infection. Methods In this observational cohort study, all participants (n = 357) had advanced fibrosis/cirrhosis and were cured of HCV with antiviral treatment. None had Liver Imaging Reporting and Data System (LI‐RADS) 2–5 lesions prior to HCV cure. Ultrasound, computed tomography, and/or magnetic resonance imaging were used for surveillance. Results At a median follow‐up of 40 months [interquartile range (IQR) = 28–48], the median percentage of time up‐to‐date with surveillance was 49% (IQR) = 30%–71%. The likelihood of receiving a first surveillance examination was not significantly associated with race/ethnicity, but was higher for patients with more advanced cirrhosis, for example, bilirubin [odds ratio (OR) = 3.8/mg/dL, p = 0.002], private insurance (OR = 3.4, p = 0.006), and women (OR = 2.3, p = 0.008). The likelihood of receiving two or three examinations was significantly lower for non‐Hispanic Blacks and Hispanics versus non‐Hispanic Whites (OR = 0.39, and OR = 0.40, respectively, p

IntroductionA scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL.MethodsThis study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications.ResultsThe stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years.DiscussionA stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

The introduction of safe and highly effective direct acting antivirals (DAAs) has significantly improved hepatitis C virus (HCV) treatment outcomes after transplant. The solid organ transplant community has sought to identify strategies aimed at increasing the donor pool including the utilization of HCV‐viremic organs in HCV‐negative recipients. We will review the existing literature to evaluate DAA use for the treatment of HCV viremia post‐liver transplant in patients who receive HCV‐viremic allografts. A PubMed search was conducted and references for each study were also reviewed to identify additional articles. Randomized controlled trials, cohort studies, case series, and case reports were included if: published in English language, evaluated DAA treatment outcomes after liver only or simultaneous liver‐kidney transplantation with HCV‐viremic allografts in HCV‐negative recipients, and had full‐text article availability. Our review included 16 studies and 2 case reports. The majority of liver transplant recipients were treated with a pangenotypic DAA for 12 weeks with a heterogeneous median time to initiation (range 1.7–118 days). Sustained virologic response was assessed in 253 liver transplant patients with 99.6% achieving cure with minimal DAA‐attributed adverse drug events. There were 23 reported episodes of rejection, 12 deaths, and 1 graft loss among all studies. Treatment with DAA after transplantation of HCV‐viremic livers into HCV‐negative recipients appears to be safe and effective; however, long‐term outcomes remain unknown. Transplant pharmacists play a key role in the development of center‐specific protocols to optimize post‐transplant outcomes in this unique patient population. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatitis C virus (HCV) infection results in hepatocytic injury with elevation of both alanine aminotransferase (ALT) and aspartate aminotransferase (AST). It remains to be determined if direct-acting antiviral treatment can terminate hepatocytic injury following virologic response. To this end, we evaluated the pattern and predicting factors of ALT and AST normalization during and after direct-acting antiviral treatment with sustained virologic response at 12 weeks (SVR12). Methods: Single-center retrospective study on 115 HCV-infected patients who achieved SVR12 was performed. Results: At treatment week 2, 100% and 45.9% showed decline in HCV RNA to

Simple Summary: Hepatitis C virus (HCV) therapy lowers risk of liver cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate immune response and pathogenesis of disease. We evaluated soluble markers of interferon signaling and liver cirrhosis, plasma miRNAs and other non-coding RNAs throughout HCV therapy prior to diagnosis of liver cancer to understand factors involved in the early stages of the cancer pathogenesis. Our results of the absence of cancer pathway suppressive miRNAs, in combination with serum immune biomarkers, may help enhance ability to identify patients at high risk for liver cancer and provide timely treatments. Background: Hepatitis C virus (HCV) therapy lowers risk of hepatocellular carcinoma (HCC). Little is known about factors driving/preceding HCC in treated persons. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate host response and pathogenesis of disease. We investigated plasma levels of these RNAs and select serum markers before, during, and after HCV therapy, preceding HCC. Methods: Of 187 DAA treated HCV patients where therapy oriented longitudinal sampling was performed at a time without HCC diagnosis, 9 were subsequently diagnosed with HCC within 2 years of therapy. They were matched with 7 patients not diagnosed with HCC over the same time period. RNASeq was performed on plasma, and serum was assessed for biomarkers of inflammation by ELISA. Results: HCC diagnosis was 19 months (6–28) after therapy start in the HCC group. 73 and 63 miRs were differentially expressed at baseline (before DAA therapy) and 12 weeks after DAA therapy comparing HCC and non-HCC groups. Several lncRNA- showed differential expression as well. Several miRNA suppressors of cancer-related pathways, lncRNA- and mRNA-derived stabilized short RNAs were consistently absent in the plasma of patients who developed HCC. Serum IP10, and MCP-1 level was higher in the HCC group 12 weeks after therapy, and distinct miRNAs correlated with IP10 and MCP-1. Finally, in a focused analysis of 8 miRNAs best associated with HCC we observed expression of mi576 and mi-5189 correlation with expression of a select group of PBMC mRNA. Conclusions: These results are consistent with complex interplay between RNA-mediated host immune regulation and cancer suppression, strikingly skewed 12 weeks following therapy, prior to HCC diagnosis. [ABSTRACT FROM AUTHOR]

The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV‐associated symptoms and functional well‐being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well‐being using the disease‐specific HCV‐PRO instrument. Survey assessments were administered at baseline, early post‐treatment (median = 6 months) and late post‐treatment (median = 21 months). Constrained longitudinal linear mixed‐effects models were used to evaluate within‐treatment change and between‐treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post‐treatment, 5 out of 6 symptoms and functional well‐being significantly improved (all p's <.05). In the LDV/SOF arm, mean changes ranged from −3.73 for nausea to −6.41 for fatigue and in the EBR/GZR, mean changes ranged from −2.19 for cognitive impairment to −4.67 for fatigue. Change of >3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well‐being that were sustained during the late post‐treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well‐being up to two years after SVR. [ABSTRACT FROM AUTHOR]

The efficacy and safety of 12 weeks of therapy with sofosbuvir/ledipasvir in three patients aged 5–10 years are presented. All three children suffered from comorbidities, including chronic kidney disease in two. All participants achieved a sustained virologic response 12 weeks after the end of treatment. No adverse effects were reported during or after the treatment, and the compliance was good. Decisions on starting treatment in children below 6 years of age should be made individually, taking compliance into consideration. The adjustment of formulation and dosing of medication during treatment is necessary in young children. Further research with larger groups of patients is needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: The kidney is a major component of extrahepatic manifestations of hepatitis C virus (HCV) clinical syndrome and the risk of chronic kidney disease (CKD) is more than 20% higher in patients with HCV infection than in seronegative individuals. Introduction of direct acting antivirals (DAA) represented a transforming point in the treatment of HCV. Patients and Method: Retrospective cohort study of 118 adult HCV infected patients with normal baseline kidney functions and eGFR >60 ml/min were included. Patients coinfected with HBV and those with impaired kidney functions at beginning of treatment were excluded. Patients were divided into 3 groups according to their DAA-combination treatment regimen. Patients’ eGFR were measured at baseline, at the end of treatment and one year later. Results: Our results showed that patients who received sofosbuvir/daclatasvir/ribavirin, their pre-treatment eGFR mean±SD was (86.156±16.37). Post treatment eGFR showed an insignificant change after end of treatment (84.736± 17.41) and 1 year after treatment (82.06± 18.07). Those who received sofosbuvir/daclatasvir, their pretreatment eGFR mean ±SD was (94.606 ±19.32). Post treatment eGFR showed an insignificant change after end of treatment (89.396 ±18.39) and 1 year after treatment (89.176±20.27). As for patients who received sofosbuvir/simeprevir, their pretreatment eGFR mean ± SD was (92.716 ± 15.11). Post treatment eGFR showed an insignificant change after end of treatment (88.366 ±16.27) and 1 year after treatment (89.016± 15.72). Conclusion: The new direct antiviral agents like sofosbuvir, daclatasvir and simeprevir are safe regarding glomerular filtration rate in patients with normal renal function. However, the treated patients need careful monitoring of kidney function tests during the period of treatment. [ABSTRACT FROM AUTHOR]

Background: Prisons provide a key strategic opportunity to upscale hepatitis C testing and treatment in a high prevalence setting and are crucial for elimination efforts., Methods: A decentralized, statewide nurse-led model of care offering hepatitis C treatment for people in prison was implemented in Victoria, Australia in 2015. The program provides hepatitis C care to all 14 adult prison sites in the jurisdiction. We prospectively evaluated treatment uptake between 1 November 2015 and 31 December 2021. Data on all people in prison treated were recorded in a clinical database. The primary outcomes were i) total number of people in prison with hepatitis C treated; ii) total number of DAA treatment courses., Results: 3,133 DAA treatment courses were prescribed to 2,768 people in prison. The proportion of total Victoria DAA prescriptions the program was responsible for increased from 6% in 2016 to a peak of 23% in 2020. Of those treated, median age was 39 years, 91% were male and 9% had cirrhosis. Few (20%) had previously engaged in hepatitis C care in the community and at first treatment course in prison, only 6% had previously accessed hepatitis C treatment. Complete follow up data were available for 1,757/2,768 (63%) treated, with 1,627/1,757 (93%) achieving SVR12., Conclusions: A decentralized, nurse-led, statewide model of care was highly effective in treating large numbers of people in prison with hepatitis C and achieved high rates of SVR12. Nurse-led prison programs are playing a crucial role in eliminating hepatitis C as a public health threat in Australia., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The advent of highly effective and well-tolerated direct-acting antiviral (DAA) therapy has made it more feasible to transplant HCV virus-infected organs into HCV-negative recipients. This case report presents the outcomes of four patients who underwent multi-visceral transplantation (MVT) from HCV NAT-viremic donors, with one recipient also requiring a kidney transplant. All recipients received post-transplant direct-acting antiviral (DAA) therapy with sofosbuvir/velpatasvir (SOF/VEL-Epclusa). By the fourth week of therapy, none of the recipients exhibited detectable viral loads, and all achieved sustained virologic response at 12 weeks (SVR-12). Allograft function for HCV D+/R- recipients remained excellent throughout follow-up. One recipient died from post-transplant lymphoproliferative disorder (PTLD) and another developed end-stage renal disease (ESRD); both outcomes were ostensibly unrelated to HCV-donor status. The other two patients are progressing well without any evidence of allograft rejection., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Abstract Background Chronic hepatitis C (CHC) virus is associated with insulin resistance and diabetes which have been linked to progressive liver fibrosis and sustained virologic response (SVR) to antiviral treatment. Resistin is a polypeptide hormone belonging to adipokines that may contribute to the development of obesity, insulin resistance, and metabolic syndrome. Also, the link between resistin and insulin resistance in patients with chronic hepatitis C and the effect of new direct acting antivirals on them seems unclear at present. The aim of this study is to evaluate the role of Resistin in detecting Insulin Resistance and their impact on response to direct acting antiviral in chronic hepatitis C patients. Results The Study was prospective Cohort clinical study, in Hepatology outpatient clinic at Ain Shams University Hospitals .This study was performed on 40 Egyptian patients who have Chronic viral hepatitis C, divided into 3 groups: GROUP I includes: 20 patients with Chronic viral hepatitis C on Sofosbovir- Daclatasvir before start of treatment and Sustained viral response after 12 weeks [SVR 12]. GROUP II includes: 20 patients with Chronic viral hepatitis C and non-responders before start of 2nd line of treatment and SVR 12. GROUP III includes: 10 subjects not infected with HCV as control group. The following investigations were done: body mass index calculation, Laboratory investigations including CBC, complete hepatic function tests, FIB-4 calculation, fasting serum insulin, HOMA-IR and serum Resistin level at baseline and re-assessed 12 weeks post end of treatment. Fasting serum Insulin, HOMA-IR and Resistin level were statistically significant higher in both naïve & relapser chronic HCV infected patients than in control group (p value 1800 ng/ml had 38.89 % sensitivity, 86.36 % specificity, 70 % PPV, 63.3 % NPV (with an overall accuracy of 57.1 %) in predicting absence of liver cirrhosis based on FIB-4. And at a cutoff value ≥2400 ng/ml had 93.55% sensitivity, 33.3% specificity, 82.9% positive predictive value, and 60% negative predictive value with an overall accuracy of 62.4% in prediction of significant insulin resistance among chronic HCV patients. Conclusion Serum Resistin level was significantly up regulated in patients with chronic HCV, with significant reduction in its level after achievement of SVR. Resistin has the potential to be a biomarker for screening of insulin resistance among chronic HCV patients.

Abstract Background and Aim The primary objective of this study was to determine whether the characteristics of patients prescribed direct acting antiviral (DAA) medicines have changed since initial listing of the medicines on the Australian Pharmaceutical Benefits Scheme (PBS). Methods A cross‐sectional study was conducted using data from MedicineInsight, an Australian database of general practice electronic health records, from March 2016 to August 2018. We compared sociodemographic, comorbidity, and clinical characteristics of patients aged at least 18 years who were prescribed at least one DAA in the first 4 months of PBS listing in 2016 with those prescribed at least one DAA in 2018. Results There were 2251 eligible adult patients prescribed a DAA during the study period, 62% were men and 59% were aged 50 years and older. Patients prescribed DAA medicines initially were older (aged ≥50 years: 67.9% vs 49.3%; P 1 (20.4% vs 8.9%; P

Background: Hepatocellular carcinoma (HCC) incidence and mortality vary by race/ethnicity and both are higher in Black patients than in Whites. For HCC surveillance, all cirrhotic patients are advised to undergo lifelong twice‐annual abdominal imaging. We investigated factors associated with surveillance and HCC incidence in a diverse HCC risk group, cirrhotic patients recently cured of hepatitis C virus (HCV) infection. Methods: In this observational cohort study, all participants (n = 357) had advanced fibrosis/cirrhosis and were cured of HCV with antiviral treatment. None had Liver Imaging Reporting and Data System (LI‐RADS) 2–5 lesions prior to HCV cure. Ultrasound, computed tomography, and/or magnetic resonance imaging were used for surveillance. Results: At a median follow‐up of 40 months [interquartile range (IQR) = 28–48], the median percentage of time up‐to‐date with surveillance was 49% (IQR) = 30%–71%. The likelihood of receiving a first surveillance examination was not significantly associated with race/ethnicity, but was higher for patients with more advanced cirrhosis, for example, bilirubin [odds ratio (OR) = 3.8/mg/dL, p = 0.002], private insurance (OR = 3.4, p = 0.006), and women (OR = 2.3, p = 0.008). The likelihood of receiving two or three examinations was significantly lower for non‐Hispanic Blacks and Hispanics versus non‐Hispanic Whites (OR = 0.39, and OR = 0.40, respectively, p < 0.005 for both) and for patients with higher platelet counts (OR = 0.99/10,000 cells/µl, p = 0.01), but higher for patients with private insurance (OR = 2.8, p < 0.001). Incident HCC was associated with higher bilirubin (OR = 1.7, p = 0.02) and lower lymphocyte counts (OR = 0.16, p = 0.01). Conclusions: Contrary to best practices, HCC surveillance was associated with sociodemographic factors (insurance status and race/ethnicity) among patients cured of HCV. Guideline‐concordant surveillance is needed to address healthcare disparities. [ABSTRACT FROM AUTHOR]

Background/Aim: Recent advances in antiviral treatment have achieved a sustained viral response (SVR) in over 95% of hepatitis C virus (HCV) infections. HCV elimination is suggested to improve several lifestyle-related factors; however, few studies have focused on dietary habit-/appetite-related factors. Patients and Methods: HCV-infected patients who received Daclatasvir/Asnaprevir (DCV/ASV) therapy were enrolled, and the changes in appetite-related molecules after antiviral therapy were assessed with a multiple cytokine-measuring system. Results: Among 119 HCV-infected patients who received DCV/ASV treatment, 104 (87.3%) achieved an SVR. In the SVR group, DCV/ASV treatment improved several liver-related variables at 24 weeks after the completion of therapy. In patients with an SVR, the values of glucagon-like peptide 1 (GLP-1) and leptin were significantly increased at 24 weeks after completing directacting antiviral therapy. However, no significant change was observed in non-SVR patients, regardless of the receipt of direct-acting antiviral treatment. Conclusion: Gastrointestinal hormones related to the dietary habit and/or appetite may be influenced by HCV elimination. [ABSTRACT FROM AUTHOR]

Ekta Gupta,1 Reshu Agarwal,1 Aayushi Rastogi,2 Nitiksha Rani,1 Ankur Jindal3 1Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India; 2Department of Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India; 3Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, IndiaCorrespondence: Ekta GuptaDepartment of Clinical Virology, Institute of Liver and Biliary Sciences, Sector D1, Vasant Kunj, New Delhi, 110070, IndiaTel + 91 11 46300000Fax + 91 11 26123501Email ektagaurisha@gmail.comPurpose: Limited literature on the prevalence of baseline resistance associated substitutions (BL-RAS) among HCV–HIV co-infected patients and their association with treatment outcomes is available especially from India. Hence, the present study aimed to study naturally occurring RAS among non-cirrhotic HCV–HIV co-infected patients and their impact on the response to anti-HCV therapy.Patients and Methods: In this retrospective study, archived blood samples of 80 HCV–HIV co-infected patients, before anti-HCV therapy initiation, were tested for substitutions at the drug acting sites (NS5a and NS5b) in the HCV genome by direct PCR sequencing.Results: BL-RAS were seen in 19 (23.7%) patients. As well as BL-RAS, all patients were given sofosbuvir (SOF) 400 mg+ daclatasvir (DCV) 60 mg for 12 weeks. Overall, sustained virological response (SVR) was achieved in 63 (78.8%) patients, in 13 with BL-RAS and in 50 without BL-RAS. All the SVR failure cases (n=17) were retreated with SOF (400 mg) +DCV (60 mg)+ ribavirin (RBV) for 24 weeks. SVR was eventually attained in 14 (82.3%) patients, in 4/6 (66.6%) with BL-RAS and in 10/11 (91%) without BL-RAS. On univariate analysis, age more than 30 years (OR: 11.6; 95% CI: 3.0– 45.5, p-value< 0.001) and female gender (OR: 8.6; 95% CI: 1.1− 69, p-value < 0.009) were found to be significant factors associated with the attainment of SVR.Conclusion: BL-RAS are common in HCV–HIV co-infected patients. The existence of BL-RAS, however, did not affect the attainment of SVR among non-cirrhotic, treatment naive HCV–HIV co-infected patients.Keywords: HCV–HIV co-infection, drug resistance, direct acting antiviral, resistance associated substitutions

BackgroundNew highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed.MethodsPROP UP is a multi-center prospective observational study that plans to enroll 1600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12weeks post-treatment (T4), 12months post-treatment (T5).Outcomes(1) Changes in side effects, functioning, pre-existing conditions, and out-of-pocket costs during therapy (T1 vs T2/T3); (2) Medication adherence in relation to a history of mental health/substance abuse, treatment regimens, pill burden, reasons for missed doses, and cure rates; (3) Short term impact of cure on functioning and amelioration of symptoms (T1 vs T4); (4) Long-term treatment harms or benefits of cure on symptoms, side effects, pre-existing conditions, and functioning (T1 vs T5). Similarities between regimens will be examined where comparisons are appropriate and meaningful.ConclusionPROP UP complements previous clinical trials by focusing on patient-reported outcomes in a representative sample of patients treated in clinical practice, by collaborating with a patient engagement group, by characterizing the experiences of vulnerable subgroups, and by investigating long-term harms and benefits of treatments. PROP UP is designed to provide novel and detailed information to support informed decision-making for patients and providers contemplating HCV treatment (PCORI CER-1408-20,660; NCT02601820).

Abstract Background Treatment of chronic hepatitis C virus infection with direct acting antiviral therapy results in viral elimination in over 90% of cases. The duration of treatment required to achieve cure differs between individuals and relapse can occur. We asked whether cellular and transcriptional profiling of peripheral blood collected during treatment could identify biomarkers predictive of treatment outcome. Methods We analyzed peripheral blood collected during treatment of genotype 1 HCV with 24 weeks of sofosbuvir and weight-based or low dose ribavirin in a trial in which 29% of patients relapsed. Changes in host immunity during treatment were assessed by flow cytometry and whole blood gene expression profiling. Differences in expression of immune-relevant transcripts based on treatment outcome were analyzed using the Nanostring Human Immunology V2 panel. Results Multiple cellular populations changed during treatment, but pre-treatment neutrophil counts were lower and natural post-treatment killer cell counts were higher in patients who relapsed. Pre-treatment expression of genes associated with interferon-signaling, T-cell dysfunction, and T-cell co-stimulation differed by treatment outcome. We identified a pre- and post-treatment gene expression signature with high predictive capacity for distinguishing treatment outcome, but neither signature was sufficiently robust to suggest viability for clinical use. Conclusions Patients who relapse after hepatitis C virus therapy differ immunologically from non-relapsers based on expression of transcripts related to interferon signaling and T-cell dysfunction, as well as by peripheral neutrophil and NK-cell concentrations. These data provide insight into the host immunologic basis of relapse after DAA therapy for HCV and suggests mechanisms which may be relevant for understanding outcomes with currently approved regimens.

Despite the excellent antiviral effects of direct acting antivirals (DAAs) for hepatitis C virus (HCV) infection with subsequent decrease of morbidity and mortality, a small proportion (5%) of the treated patients do not respond to first-line DAAs and have persistent viremia. Rescue therapy for patients with DAA failures is thus mandatory from both clinical and public health perspectives. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), a fixed-dose pangenotypic rescue agent, has been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for retreating HCV patients who fail prior DAA therapies. However, this agent has not been licensed by health authorities of Taiwan. Herein we reported two cases who successfully cleared HCV by using SOF/VEL/VOX plus ribavirin (RBV) after virologic failures to first-line pangenotypic SOF/VEL. Furthermore, we discussed the current unmet medical needs and clinical implications of SOF/VEL/VOX on the perspectives of HCV elimination in Taiwan.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three months after obtaining a sustained viral response (SVR). Materials and Methods: Our study included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibro max prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety and efficacy of Sofosbuvir based Antiviral regimens for chronic hepatitis C virus infected patients with chronic kidney disease stage 3 to stage 5D on haemodialysis. Study Design: Quasi experimental study. Place and Duration of Study: Nephrology Department, Combined Military Hospital Lahore, from Dec 2018 to Dec 2019. Methodology: Fifty patients of chronic kidney disease with stage 3 to stage 5D suffering from chronic hepatitis C were selected. Among them 30 patients were stage 3 to stage 5ND pre-dialysis patients while 20 were patients of End Stage Renal Disease (ESRD) on maintenance haemodialysis. Antiviral treatment consisted of Peg Interferon with Sofosbuvir and Ribavirin, Peg Interferon with Sofosbuvir, Ledipasvir with Sofosbuvir, Velpatsvir with Sofosbuvir and Daclatasvir with Sofosbuvir for 12 weeks. The assessments were conducted at baseline, weeks 2, 4, 8 and 12 on treatment and 12 weeks after treatment. Results: Sustained Virologic Response (SVR) was 96.8% for group treated with Ledipaspavir, Velpatsvir or Declatasvir with Sofosbuvir and 88.9% of patients in Peg IFN/Sofosbuvir/Ribavirin treated group achieved Sustained Virologic Response. Majority (90%) of the participants experienced adverse effects. Two (4%) patient on haemodialysis had treatment discontinuation due to side effects. Dose of Ribavirin was reduced in 4 (8%) patients on haemodialysis during antiviral therapy. Two deaths occurred during the study while on treatment and one death occurred four days after renal transplant. Conclusion: Sofosbuvir based antiviral regimens i.e. Peg Interferon with and without Ribavirin, Ledipasvir, Velpatsvir and Declatasvir for chronic Hepatitis C infected chronic kidney disease patients including haemodialysis patients, are well tolerated, effective and safe for treatment.

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients. [ABSTRACT FROM AUTHOR]

Background and Aim: The primary objective of this study was to determine whether the characteristics of patients prescribed direct acting antiviral (DAA) medicines have changed since initial listing of the medicines on the Australian Pharmaceutical Benefits Scheme (PBS). Methods: A cross‐sectional study was conducted using data from MedicineInsight, an Australian database of general practice electronic health records, from March 2016 to August 2018. We compared sociodemographic, comorbidity, and clinical characteristics of patients aged at least 18 years who were prescribed at least one DAA in the first 4 months of PBS listing in 2016 with those prescribed at least one DAA in 2018. Results: There were 2251 eligible adult patients prescribed a DAA during the study period, 62% were men and 59% were aged 50 years and older. Patients prescribed DAA medicines initially were older (aged ≥50 years: 67.9% vs 49.3%; P < 0.001), and more likely to have liver cirrhosis (14.2% vs 8.4%; P = 0.01) and an aminotransferase to platelet ratio index (APRI) score >1 (20.4% vs 8.9%; P < 0.001) than those prescribed DAA medicines in 2018. A greater proportion of patients in regional/remote (46.5% vs 35.6%; P < 0.001) and socioeconomically disadvantaged areas (44.4% vs 34.5%; P = 0.003) accessed treatment in 2018 compared with 2016. Conclusions: Despite evidence of decreasing uptake of DAA medicines across Australia, this study indicates broadened uptake among younger age groups and those residing in regional/remote and socioeconomically disadvantaged areas since 2016. While uptake of DAA medicines in some population subgroups appears to have improved, continuous efforts to improve uptake across the Australian population are essential. [ABSTRACT FROM AUTHOR]

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.

Background: Hepatitis C virus (HCV) therapy lowers risk of hepatocellular carcinoma (HCC). Little is known about factors driving/preceding HCC in treated persons. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate host response and pathogenesis of disease. We investigated plasma levels of these RNAs and select serum markers before, during, and after HCV therapy, preceding HCC. Methods: Of 187 DAA treated HCV patients where therapy oriented longitudinal sampling was performed at a time without HCC diagnosis, 9 were subsequently diagnosed with HCC within 2 years of therapy. They were matched with 7 patients not diagnosed with HCC over the same time period. RNASeq was performed on plasma, and serum was assessed for biomarkers of inflammation by ELISA. Results: HCC diagnosis was 19 months (6–28) after therapy start in the HCC group. 73 and 63 miRs were differentially expressed at baseline (before DAA therapy) and 12 weeks after DAA therapy comparing HCC and non-HCC groups. Several lncRNA- showed differential expression as well. Several miRNA suppressors of cancer-related pathways, lncRNA- and mRNA-derived stabilized short RNAs were consistently absent in the plasma of patients who developed HCC. Serum IP10, and MCP-1 level was higher in the HCC group 12 weeks after therapy, and distinct miRNAs correlated with IP10 and MCP-1. Finally, in a focused analysis of 8 miRNAs best associated with HCC we observed expression of mi576 and mi-5189 correlation with expression of a select group of PBMC mRNA. Conclusions: These results are consistent with complex interplay between RNA-mediated host immune regulation and cancer suppression, strikingly skewed 12 weeks following therapy, prior to HCC diagnosis.

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy. Early detection of HCC is extremely important in improving the survival of patients. Alpha-fetoprotein (AFP) was commonly used as a predictor for HCC, but it was associated with low sensitivity and specificity. Thioredoxin (TRX) is a ubiquitous protein that was suggested to be elevated in cases with HCC. Objective: To evaluate the value of serum thioredoxin as a diagnostic marker of HCC versus alpha-fetoprotein in cirrhotic HCV patients. Materials and methods: This study included 96 patients divided into; groups I included, patients with liver cirrhosis, and group II included, patients with HCC on top of a cirrhotic liver. Both groups were successfully undergoing treatment of HCV with direct-acting antiviral (DAAs). Basic data, clinical examination, and laboratory analysis were obtained from all the cases. Human thioredoxin detection was done using Human TRX kits. Results: There is statistically significant increased TRX, AFP, APRI, and FIB4 among hepatocellular carcinoma group versus cirrhotic group. The ROC curve analysis demonstrated that TRX at a cut-off value of 198.19 (IU/ml) has 85.4% sensitivity and 89.6% specificity for differentiating HCC cases from cirrhotic cases with 89.1% PPV, 86% NPV, and AUC equal to 0.841. Both, AFP at a cut-off of 24 (ng/ml) and combined AFP and TRX had 93.8% sensitivity and 97.9% specificity with AUC equal to 0.99 for differentiating HCC cases from cirrhotic cases. Conclusion: Thioredoxin is a novel biomarker that revealed good sensitivity in the prediction of HCC on top of liver cirrhosis especially if combined with AFP. [ABSTRACT FROM AUTHOR]

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

Background: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. Methods: Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. Results: The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6–96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8–99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. Conclusions: SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan. [ABSTRACT FROM AUTHOR]

Abstract Background Almost 1% of Canadians are hepatitis C (HCV)-infected. The liver-specific complications of HCV are established but the extra-hepatic comorbidity, multimorbidity, and its relationship with HCV treatment, is less well known. We describe the morbidity burden for people with HCV and the relationship between multimorbidity and HCV treatment uptake and cure in the pre- and post-direct acting antiviral (DAA) era. Methods We linked adults with HCV at The Ottawa Hospital Viral Hepatitis Program as of April 1, 2017 to provincial health administrative data and matched on age and sex to 5 Ottawa-area residents for comparison. We used validated algorithms to identify the prevalence of mental and physical health comorbidities, as well as multimorbidity (2+ comorbidities). We calculated direct age- and sex-standardized rates of comorbidity and comparisons were made by interferon-based and interferon-free, DAA HCV treatments. Results The mean age of the study population was 54.5 years (SD 11.4), 65% were male. Among those with HCV, 4% were HIV co-infected, 26% had liver cirrhosis, 47% received DAA treatment, and 57% were cured of HCV. After accounting for age and sex differences, the HCV group had greater multimorbidity (prevalence ratio (PR) 1.38, 95% confidence interval (CI) 1.20 to 1.58) and physical-mental health multimorbidity (PR 2.71, 95% CI 2.29–3.20) compared to the general population. Specifically, prevalence ratios for people with HCV were significantly higher for diabetes, renal failure, cancer, asthma, chronic obstructive pulmonary disease, substance use disorder, mood and anxiety disorders and liver failure. HCV treatment and cure were not associated with multimorbidity, but treatment prevalence was significantly lower among middle-aged individuals with substance use disorders despite no differences in prevalence of cure among those treated. Conclusion People with HCV have a higher prevalence of comorbidity and multimorbidity compared to the general population. While HCV treatment was not associated with multimorbidity, people with substance use disorder were less likely to be treated. Our results point to the need for integrated, comprehensive models of care delivery for people with HCV.

Hepatitis C virus (HCV) causes both acute and chronic hepatitis. Following acute HCV infection, chronic infection develops in about %80 of patients. In years, Chronic hepatitis C can progress to cirrhosis, hepatocellular carcinoma (HCC) or may result in liver transplantation. It is one of the most common causes of liver transplantion in the world. Recently, the treatment of CHC has dramatically improved. The success rate of over 90-95% with new developments in treatment, is promising for the future.

Background: Direct-acting antiviral (DAAs) therapy showed high safety and efficacy profile in patients with chronic hepatitis C (CHC) particularly those with previous or current psychiatric illness. The aim of this study was to evaluate the incidence and potential risk factors of depression and psychological distress following DAAs therapy in CHC euthymic Egyptian patients with no previous or current diagnosis of any psychiatric disorders.Methods: This is a prospective study that included 126 patients diagnosed with chronic hepatitis C virus genotype-4. Patients were candidate for DAAs therapy and were recruited consecutively (convenient sample) from the viral hepatitis center, Department of Endemic medicine, Kasr Al-Ainy Hospitals, Cairo University. Symptom Checklist 90-R, Beck Depression Inventory (BDI) and Structured Clinical Interview for DSM-IV (SCID IV) were performed at baseline and at 12 weeks post-treatment with DAAs.Results: Forty-seven patients were included in the final analysis. Depression severity increased after treatment as BDI scores increased significantly than baseline scores (p= < 0.001). About one third of patients (32%) had moderate to severe depression. All Symptom Checklist-90 scores showed significant increase after treatment.Limitations: Dropout rate of patients for the 12 weeks post-treatment assessment was 33.8%.Conclusion: Depression and psychological distress can occur with DAAs treatments. Close psychosocial assessment and patient monitoring are still needed. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to clarify the features of resistance-associated substitutions (RASs) after failure of multiple interferon (IFN)-free regimens in HCV genotype 1b infections. Methods: A total of 1,193 patients with HCV for whom direct-acting antiviral (DAA) treatment had failed were enrolled from 67 institutions in Japan. The RASs in non-structural protein (NS)3, NS5A, and NS5B were determined by population sequencing. Results: Failure of 1, 2, and 3 regimens was observed in 1,101; 80; and 12 patients, respectively. Among patients with failure of 1 regimen, Y56H and D168V in NS3 were more frequently detected after failure of paritaprevir, whereas D168E was more frequently detected after failure of regimens including asunaprevir. R30H and L31-RAS in NS5A were frequently detected after failure of regimens including daclatasvir. The prevalence of Y93-RAS was high irrespective of the regimen. S282T RAS in NS5B was detected in 3.9% of ledipasvir/sofosbuvir failures. The prevalence of D168-RAS increased significantly according to the number of failed regimens (p

Background: Treatment of chronic hepatitis C virus infection with direct acting antiviral therapy results in viral elimination in over 90% of cases. The duration of treatment required to achieve cure differs between individuals and relapse can occur. We asked whether cellular and transcriptional profiling of peripheral blood collected during treatment could identify biomarkers predictive of treatment outcome.Methods: We analyzed peripheral blood collected during treatment of genotype 1 HCV with 24 weeks of sofosbuvir and weight-based or low dose ribavirin in a trial in which 29% of patients relapsed. Changes in host immunity during treatment were assessed by flow cytometry and whole blood gene expression profiling. Differences in expression of immune-relevant transcripts based on treatment outcome were analyzed using the Nanostring Human Immunology V2 panel.Results: Multiple cellular populations changed during treatment, but pre-treatment neutrophil counts were lower and natural post-treatment killer cell counts were higher in patients who relapsed. Pre-treatment expression of genes associated with interferon-signaling, T-cell dysfunction, and T-cell co-stimulation differed by treatment outcome. We identified a pre- and post-treatment gene expression signature with high predictive capacity for distinguishing treatment outcome, but neither signature was sufficiently robust to suggest viability for clinical use.Conclusions: Patients who relapse after hepatitis C virus therapy differ immunologically from non-relapsers based on expression of transcripts related to interferon signaling and T-cell dysfunction, as well as by peripheral neutrophil and NK-cell concentrations. These data provide insight into the host immunologic basis of relapse after DAA therapy for HCV and suggests mechanisms which may be relevant for understanding outcomes with currently approved regimens. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major health problem all over the world including Egypt. Chronic HCV infection is usually accompanied by decrease of libido and erectile dysfunction. This study aimed to evaluate the efficacy of new oral direct acting antiviral (DAA) therapy on sexual function of male patients with HCV. This study was conducted on 200 male participants divided into two groups, first group included 100 male patients with HCV and the second group included 100 healthy age matched males as a control. Patients received DAA for three months and virological free status was confirmed by polymerase chain reaction. All participants were subjected to full history taking, general examination and local genital examination, assessment of sexual function by a validated Arabic version of the international index of erectile function‐5. Laboratory investigations included liver functions serum testosterone, free testosterone, sex hormone‐binding globulin and bioavailable testosterone. Results of this study showed that patients with HCV suffer from sexual dysfunction than controls that significantly improved after DAA therapy, and this is accompanied by increasing of bioavailable testosterone. It could be concluded that beside its effectiveness in treatment of HCV infection, DAA therapy can improve sexual function in male patients with HCV. [ABSTRACT FROM AUTHOR]

Despite the excellent antiviral effects of direct acting antivirals (DAAs) for hepatitis C virus (HCV) infection with subsequent decrease of morbidity and mortality, a small proportion (5%) of the treated patients do not respond to first-line DAAs and have persistent viremia. Rescue therapy for patients with DAA failures is thus mandatory from both clinical and public health perspectives. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), a fixed-dose pangenotypic rescue agent, has been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for retreating HCV patients who fail prior DAA therapies. However, this agent has not been licensed by health authorities of Taiwan. Herein we reported two cases who successfully cleared HCV by using SOF/VEL/VOX plus ribavirin (RBV) after virologic failures to first-line pangenotypic SOF/VEL. Furthermore, we discussed the current unmet medical needs and clinical implications of SOF/VEL/VOX on the perspectives of HCV elimination in Taiwan. [ABSTRACT FROM AUTHOR]

The paradigm for the treatment of chronic hepatitis C (CHC) has been changed due to the development of direct acting antivirals (DAAs) of hepatitis C virus (HCV). The high sustained virologic response rate and ease of administration makes the DAAs approach ideal to contribute to the complete eradication of HCV. Currently, treatment options for individual patients vary depending on the genotype or subtype of HCV, presence or absence of liver cirrhosis, previous experience of antiviral treatment or resistance associated substitutions. Because of drug avalilability, cost-effectiveness, preference, compliance and greater possibility of desirable effects and presumed patient-important outcomes may vary between countries, treatment options for individual patients are different. The review focuses on the comparing the current treatment options for CHC in other continents with the 2017 Korea Association for the Study of the Liver guidelines.

Anna S Griffith,1 Paul H Hayashi,1 Lauren MB Burke,2 Autumn J McRee1 1Department of Medicine, 2Department of Radiology, University of North Carolina at Chapel Hill Hospital, Chapel Hill, NC, USA Abstract: We describe two cases of patients with hepatitis C virus (HCV) treated with direct-acting antiviral (DAA) therapy who had dramatic improvement in hepatocellular carcinoma (HCC) tumor burden with DAA therapy alone. Both patients were diagnosed with HCC on screening magnetic resonance imaging shortly after beginning DAA therapy. Both patients achieved sustained virologic response (SVR) with dramatic improvement in HCC tumor burden on follow-up imaging without HCC treatment. Patients with multifocal or advanced HCC are infrequently treated with antiviral therapy for HCV. As a result, these cases provide unique insight into the ongoing debate regarding the impact of SVR on existing and recurrent HCC. We review the current literature regarding this debate, as well as the theory of immunosurveillance. We postulate that DAA therapy activates CD8+ T cells to induce a T-cell-mediated response and increased immunosurveillance to virus-induced liver cancer. Keywords: hepatocellular carcinoma, hepatitis C virus, sustained virologic response, direct-acting antiviral, T-cell-mediated immunosurveillance

Abstract Background Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. Methods The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy. Results Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Conclusion Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

An editorial is presented on the hepatitis C virus (HCV) infection remains a major health problem for people living with human immunodeficiency virus (HIV). Topics include the million people are living with both HCV and HIV worldwide, and the people living with HIV are 6 times more likely to have HCV infection than those without.

Objective: To assess the safety and efficacy of Sofosbuvir based Antiviral regimens for chronic hepatitis C virus infected patients with chronic kidney disease stage 3 to stage 5D on haemodialysis. Study Design: Quasi experimental study. Place and Duration of Study: Nephrology Department, Combined Military Hospital Lahore, from Dec 2018 to Dec 2019. Methodology: Fifty patients of chronic kidney disease with stage 3 to stage 5D suffering from chronic hepatitis C were selected. Among them 30 patients were stage 3 to stage 5ND pre-dialysis patients while 20 were patients of End Stage Renal Disease (ESRD) on maintenance haemodialysis. Antiviral treatment consisted of Peg Interferon with Sofosbuvir and Ribavirin, Peg Interferon with Sofosbuvir, Ledipasvir with Sofosbuvir, Velpatsvir with Sofosbuvir and Daclatasvir with Sofosbuvir for 12 weeks. The assessments were conducted at baseline, weeks 2, 4, 8 and 12 on treatment and 12 weeks after treatment. Results: Sustained Virologic Response (SVR) was 96.8% for group treated with Ledipaspavir, Velpatsvir or Declatasvir with Sofosbuvir and 88.9% of patients in Peg IFN/Sofosbuvir/Ribavirin treated group achieved Sustained Virologic Response. Majority (90%) of the participants experienced adverse effects. Two (4%) patient on haemodialysis had treatment discontinuation due to side effects. Dose of Ribavirin was reduced in 4 (8%) patients on haemodialysis during antiviral therapy. Two deaths occurred during the study while on treatment and one death occurred four days after renal transplant. Conclusion: Sofosbuvir based antiviral regimens i.e. Peg Interferon with and without Ribavirin, Ledipasvir, Velpatsvir and Declatasvir for chronic Hepatitis C infected chronic kidney disease patients including haemodialysis patients, are well tolerated, effective and safe for treatment. [ABSTRACT FROM AUTHOR]

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Résumé: Les Flavivirus, dont fait partie le virus de la dengue (DENV), sont la cause de maladies qui sont actuellement l'une des préoccupations majeures de l'Organisation mondiale de la santé (OMS). La dengue est la maladie humaine transmise par arthropode la plus répandue dans le monde. Face à l'accroissement du nombre de cas de dengue et de dengue sévère, de l'expansion du territoire de son vecteur dû aux mouvements des populations et au réchauffement climatique, il est important de trouver des mesures pour contrecarrer le virus. À l'heure actuelle, aucun traitement spécifique n'est disponible. Malgré le grand nombre de composés exerçant une activité antivirale in vitro , rares sont ceux qui ont été évalués en études cliniques. Le développement d'antiviraux est une stratégie prometteuse et complémentaire à la production de vaccin. Cette revue introduit la notion d'antiviraux anti-DENV à action directe versus les antiviraux anti-DENV ciblant l'hôte. Elle souligne la nécessité de disposer de multiples antiviraux et la pertinence de maintenir les recherches sur le sujet. Dengue virus (DENV) is part of the Flaviviridae family and has been classify by the Word Health Organization (WHO) as one of the top 10 health concerns. It is the most widespread mosquito-borne human disease. Considering the increasing number of severe dengue, the expansion of the vector territory due to climate change and population movement, it is urgent to find a way to counteract the virus. Indeed, currently there is no treatment available and despite the large number of molecules that proved efficacy in vitro rare are the compounds that have been further evaluated and lead to clinical trials. Development of antiviral is a promising complementary strategy to vaccine production. This review introduces the DENV antivirals and the notions of direct acting antiviral versus host targeted antiviral. It underlines the importance to develop multiple potent antivirals and the relevance to maintain research on this matter. [ABSTRACT FROM AUTHOR]

Background: Egypt had been vexed by the highest load of chronic hepatitis C in the world. It represents a vast market of the new direct-acting anti-viral drugs (DAAs); effectively treating chronic hepatitis C virus (HCV) infection. Objectives: The aim of this study is to detect the occurrence and recurrence of hepatocellular carcinoma (HCC) during the follow-up after antiviral treatment with direct acting antiviral therapy in patients with chronic HCV infection and in patient with chronic HCV prior history of treated hepatocellular carcinoma who achieved complete response. Subjects and methods: This was prospective study including 150 patients with compensated chronic hepatitis C virus infection and 150 patients with compensated chronic hepatitis C virus infection prior history of treated hepatocellular carcinoma. The patients were attending Aswan university hospital and viral hepatitis unit in addition to Viral Hepatitis Unit and were prospectively collected at the end of December 2019. The patients were divided into two groups: Group (A): patients with chronic HCV infection who were treated with direct acting antivirals. Group (B): patients with chronic HCV infection prior history of treated hepatocellular carcinoma who were treated with direct acting antivirals. Results: The results of the study revealed that there was no significant difference between the studied groups as regard time needed for HCC to occur after DAA. Conclusion: Surveillance programs should be widely endorsed during and after DAAs therapy for patients at HCC risk, even for those who had been achieved HCV cure. [ABSTRACT FROM AUTHOR]