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A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue.Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level2-fold the upper limit of normal in addition to HBVr).Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P.001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment.Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients.gov no: NCT04405011.

Background: Hepatitis C Virus (HCV) infection represents a global problem, and it is related to both hepatic and extra-hepatic manifestations (e.g., xerophthalmia). New direct-acting antivirals (DAAs), IFN-free treatments, are commonly used to manage HCV infection. However, the impact of new DAAs on dry eyes (xerophthalmia) is lacking. In this study, we evaluated its incidence in HCV patients and the effect of DAAs on this manifestation. Methods: We performed an observational open-label non-randomized study in HCV patients from 01 April 2018 to 01 June 2020. Results : Patients who satisfied the inclusion criteria underwent clinical and laboratory evaluation, Schirmer's test, and Break-up time test. Enrolled patients were divided in two groups: Group 1: HCV patients with xerophthalmia: 24 patients (16 male and 8 female), HCV-RNA 2,685,813 ± 1,145,698; Group 2: HCV patients without xerophthalmia: 35 patients (19 male and 16 female), HCV-RNA 2,614,757 ± 2,820,433. The follow-ups (3 and 6 months after the enrollment) documented an improvement in both eyes’ manifestations and HCV-infection (HCV-RNA undetected). Conclusion: In conclusion, in this study, we reported that xerophthalmia could appear in HCV patients, and DAAs treatment reduces this manifestation without the development of adverse drug reactions.

BACKGROUND: Increasing direct-acting antiviral (DAA) treatment uptake is key to eliminating HCV infection as a public health threat in Canada. People living with human immunodeficiency virus (HIV) and hepatitis C (HCV) co-infection face barriers to HCV treatment initiation. We sought to identify interventions that could support HCV treatment initiation based on patient and HCV care provider perspectives. METHODS: Eleven people living with HIV with a history of HCV infection and 12 HCV care providers were recruited for this qualitative descriptive study. Participants created ranked-ordered lists of potential interventions during nominal groups ( n = 4) and individual interviews ( n = 6). Following the nominal group technique, transcripts and intervention lists underwent thematic analysis and ranking scores were merged to create consolidated and prioritized lists from patient and provider perspectives. RESULTS: Patient participants identified a total of eight interventions. The highest-ranked interventions were multidisciplinary clinics, HCV awareness campaigns and patient education, nurse- or pharmacist-led care, peer involvement, and more and better-prepared health professionals. Provider participants identified 11 interventions. The highest-ranked were mobile outreach, DAA initiation at pharmacies, a simplified process of DAA prescription, integration of primary and specialist care, and patient-centred approaches. CONCLUSION: Participants proposed alternatives to hospital-based specialist HCV care, which require increasing capacity for nurses, pharmacists, primary care providers, and peers to have more direct roles in HCV treatment provision. They also identified the need for structural changes and educational initiatives. In addition to optimizing HCV care, these interventions might result in broader benefits for the health of HIV–HCV co-infected people.

BackgroundIn 2017, Tayside, a region in the East of Scotland, rapidly scaled-up Hepatitis C Virus (HCV) outreach and treatment among People Who Inject Drugs (PWID) using novel community care pathways. AimsWe aimed to determine treatment outcomes for PWID during the scale-up against pre-determined targets; and assess re-infection, mortality, and post-treatment follow up.Methods HCV treatment was delivered in community pharmacies, drug treatment centres, nurse-led outreach clinics, prisons, and needle exchanges, alongside conventional hospital care. We retrospectively analysed clinical outcomes and compared pathways using logistic regression models.ResultsOf 800 estimated HCV-infected PWID, 718 (90%) were diagnosed. 713 treatments commenced among 662 (92%) PWID, delivering 577 (81%) Sustained Virologic Responses (SVR). SVR was 91% among those who attended for testing. Forty-six individuals were treated more than once. Needle exchanges and community pharmacies initiated 49% of all treatments. Regression analyses implied pharmacies had superior follow-up, but there was no difference in likelihood of achieving SVR in community pathways relative to hospital care. Re-infection occurred 39 times over 256.57 person years (PY), yielding a rate of 15.20 per 100 PY (95% CI 10.81–20.78). 54 deaths occurred (29 drug related) over 1,553.04 PY, yielding a mortality rate of 3.48 per 100 PY (95% CI 2.61–4.54). Drug-related mortality was 1.87 per 100 PY (95% CI 1.25–2.68).ConclusionsRapid HCV treatment scale-up to PWID in community settings, whilst maintaining high SVR, is achievable. However, other interventions are required to minimise re-infection; reduce drug-related deaths; and improve post-SVR follow-up testing regionally.

Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.

Background: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Chronic HCV infection is associated with development of insulin resistance and therefore type 2 Diabetes mellitus (T2DM), it is also associated with hepatic steatosis and hypocholesterolemia. The treatment by Direct Acting Antivirals (DAAs) leads to sustained virological response (SVR) in almost all infected patients and decreases liver-related as well as all-cause mortality in these patients. The evidence for the effect of DAAs therapy on T2DM is quite conflicting. Some studies agreed with the glucometabolic amelioration induced by the Sustained Virological Response (SVR) but other studies disagreed with this hypothesis. The aim of the work was to evaluate glucose and Lipid Profile changes in hepatitis C patients at 12 weeks post treatment (SVR12) by Direct Acting Antivirals Therapy. Methods: This prospective study was carried out on 80 chronic HCV infected patients who are treatment naïve and subjected to HCV DAAs treatment (Daclatasvir + Sofosbuvir for 12 weeks +/- Ribavirin or any DAA available) with 100% SVR rate at 12 weeks with no relapse. All patients are subjected to assessment of Fasting blood glucose, HbA1C and assessment of Lipid profile; Total cholesterol, Triglycerides, HDL, LDL at baseline (pretreatment) and at end of treatment then they are followed up at SVR12. Results: Average HbA1C, fasting blood glucose has significantly decreased in group A diabetic patients from baseline to end of treatment and to SVR12, Average Total Cholesterol, LDL has significantly increased in group A and B from baseline to end of treatment and to SVR12 respectively. Average Triglycerides has significantly decreased from baseline to end of treatment in group A and B and to SVR12 in group A only. Average HDL has significantly increased only in group B non-diabetics from baseline to end of treatment and to SVR12. Conclusions: Successful clearance of HCV viremia (SVR12) with DAAs treatment has been associated with significant Improvement or decrease of HbA1c and Fasting plasma glucose levels in diabetic chronic HCV infected patients, and has been associated with Rise in the Lipid profile; Total Cholesterol, LDL, HDL (non-diabetics only) while it decreases Triglycerides in both diabetic and non-diabetic chronic HCV infected patients.

Background: Management of chronic infection with hepatitis C virus (HCV) with direct acting antivirals (DAAs) agents achieves high virological response. Recently, there is a matter of controversy about occurrence of hepatocellular carcinoma (HCC) following those agents. Objective: This study aimed to evaluate the efficacy of alpha fetoprotein (AFP) in development of HCC following DAAs therapy. Patients and methods: two hundred patients with chronic HCV infection who were eligible for DAAs therapy were recruited. Those patients were followed up for one year following therapy to detect development of HCC. Patients were grouped into either with normal AFP (100 patients) or high AFP (100 patients). Results: Majority (84%) of patients were males with overall mean age of 43.87±12.76 years. There were no significant differences between both groups of patients as regard baseline data. With exception of 4% of patients, all of them reached the sustained virological response (SVR). Frequency of HCC detection was higher among those patients with high AFP (9 (9%) vs 1 (1%); P< 0.001). We found that liver cirrhosis; FIB-4, APRI and AFP were predictors for HCC. AFP had the best diagnostic accuracy for prediction of HCC following DAAs Conclusion: Patients who received DAAs for HCV infection should be regularly screened for development of HCC.

The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P

Introduction: Sofosbuvir/velpatasvir is a combination of direct-acting antivirals with pangenotypic activity for treatment of chronic hepatitis C virus infection. It was approved in 2020 for use in...

The Hepatitis C virus (HCV) has a major impact on public health and is thought to be responsiblefor 25% of hepatocellular carcinoma (HCC) and 27% of cirrhosis cases worldwide.Recent direct-acting antivirals (DAAs) for hepatitis C have the potential to reduce this diseaseburden, but there are increased worries about HCC incidence in HCV patients receivingDAAs. This work assessed the HCC incidence in HCV patients treated with DAAs and its relationship to Hepatic Fibrosis Stage.The study included 400 chronic HCV patients equally divided into two groups: chronicHCV patients who did not receive anti HCV medication (control group) and chronic HCV patientswho received different DAAs treatment regimens. There was a highly significant differencebetween both groups as regards hepatic fibrosis stages before DAAs therapy. The DAAreceiving group had highly statistically advanced hepatic fibrosis when compared to the controlgroup. After eighteen months of follow up, the DAA receiving group had a significantlylower incidence of HCC when compared to the control group (5.5% versus 11% respectively,p-value 0.04).

Background & Aims: There is high proportion of geriatric patients who acquired chronic hepatitis C virus infection. There is a shortage in evidence- based data as regards direct-acting antivirals in this group of patients. The aim was to assess safety, efficacy, and tolerability of direct acting antiviral drugs in Egyptian geriatric patients. Methods: This prospective study was performed on 177 patients with chronic hepatitis C and administrated different regimens of direct acting antivirals. Patients were divided into two groups: Group I: patients below 65 years old (N = 143), and Group II: patients > 65 years old (N = 34). Pretreatment history taking, baseline characteristics, and investigations were done for both groups. Follow up was made to detect treatment efficacy and adverse effects. Results: Geriatric group were found to have more comorbidities (diabetes mellitus, hypertension, and cardiomyopathy); also liver cirrhosis. Minor adverse effects occurred in both groups without significant difference included fatigue, insomnia, headache, and dizziness. Vomiting, diarrhea, and skin rash occurred in group II more than group I. Leucopenia, thrombocytopenia, jaundice, and significant anemia occurred without significant difference between both groups. Eighteen patients (25%) of 72 patients who took ribavirin had to reduce ribavirin dose or to stop it. The overall treatment response in the entire study was 97.7% without significant difference between both groups. Conclusion: Direct acting antivirals are recommended regardless the age. These drugs are effective and tolerable in elderly patients. Attention to other comorbidities, drug-drug interactions, and follow up are recommended.

Through the discovery of direct-acting antiviral therapies over the last decade, Hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease and is a risk factor for progression of chronic kidney disease, is associated with higher morbidity and mortality in dialysis patients and leads to worse allograft and patient outcomes in kidney transplant recipients. Clinical trial and real-world data of direct acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease including patients with chronic kidney disease, end-stage kidney disease, and kidney transplant recipients.

Background: Direct-acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled-up in England since 2017. To assess early impacts, we described trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self-reported treatment access.Methods: Bio-behavioural data from an annual, national surveillance survey of PWID (2011 to 2018) estimated trends in viraemic prevalence among HCV antibody-positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection.Findings: Between 2011 and 2016, viraemic prevalence among antibody-positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p

Globally, 13% of all hepatitis C virus (HCV) infections are caused by genotype 4 (GT4), which consists of 17 subtypes with various levels of susceptibility to anti-HCV therapy. This genotype is endemic in the Middle East and Africa and has considerably spread to Europe lately. The molecular features of HCV-GT4 infection, as well as its appropriate therapeutics, are poorly characterized as it has not been the subject of widespread basic research. As such, in this review, we aim to gather the current state of knowledge of this genotype with a particular emphasis on its heterogeneity, sequence signatures, resistance-associated substitutions, and available in vivo and in vitro models used for its study. We urge developing more cell-culture models based on different GT4 subtypes to better understand the virology and therapeutic response of this particular genotype. This review may raise more awareness about this genotype and trigger more basic research work to develop its research tools. This will be critical to design better therapeutics and help to provide adequate guidelines for physicians working with HCV-GT4 patients.

Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.

Background and Aim: Cirrhotic patients have lower response rates to DAAs with increased frequency of adverse events. This study aims to evaluate the value of HCVcAg as an early predictor of SVR to DAAs in cirrhotic patients to justify the treatment and avoid side effects. Patients and Methods: This prospective cohort study was conducted on 85 treatment-naive HCV cirrhotic patients who had fulfilled the inclusion and exclusion criteria of the National Treatment Protocol of chronic HCV infection. HCVcAg detection was done on 10th day of treatment. Predictivity of HCVcAg for SVR was assessed in terms of specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy rates. ROC curve was conducted to assess predictivity of HCVcAg as well. Results: SVR12 was (91.76%). HCVcAg was negative in 79 patients; 78 of them achieved SVR, while it was positive in 6 patients; all of whom did not achieve SVR. HCVcAg had sensitivity, specificity, PPV, NPV and accuracy rates of 100%, 98.73%, 85.71%, 100% and 98.82% respectively in prediction of SVR. With AUC of 0.929. There was a positive strong significant correlation between HCVcAg and SVR12 (r = 0.898, P = 0.015). Conclusion: HCVcAg is a sensitive, specific, accurate, easily available, and affordable on- treatment predictor of SVR in cirrhotic patients with chronic HCV with possible future treatment regimen modification to improve efficacy and tolerability in difficult to treat cirrhotic patients.

Objective:Direct acting antivirals (DAA) is a class of antivirals that hasbeen extensively used in chronic hepatitis C virus (HCV) patients over the past 6 years.Despite the excellent therapeutic benefits of DAA, there is a knowledge gap regardingthe safety of this class. Several reports of possible renal toxicity associated with DAAadministration can be found in the literature. The aims of this study are: to assess therenal safety of DAA used for the treatment of chronic HCV infection and to quantify the odds ofdeveloping renaltoxicityin patients withchronicHCV viralinfection. Study Design: Disproportionalityanalysiswasusedtodetectsignalsofpotentialsideeffects. Place andDuration: Amman –Jordan,One year study since September 2017 to march 2018. Methods: The method that was applied in the current study is obtaining the data from United States (US) food and drug administration(FDA)adverseeventreportingsystem(FAERS).DatabetweenJuly,2014andSeptember,2017werecombinedandexplored.Disproportionalityanalysiswasconducted to reports from chronic HCV patients to explore possible association betweenDAA administrationand renalsideeffects. Results: This study showed that a total of 3,837,418 safety reports were available in the period between July,2014 and September, 2017. Patients with chronic HCV infection represent 22,022 cases.When considering all DAA as drug of interest, the use of DAA alone or in combinationwith interferon and/or ribavirin did not increase the risk of having renal side effects.Exploring individual DAA demonstrated a significant association between the incidenceofrenalsideeffectsandtheadministrationoftelapreviranddasabuvir.ConsideringrenalsideeffectsindividuallyshowedasignificantassociationbetweenDAAadministrationand chronickidney disease. Conclusions: In this study, we reported a significant association between DAA administration andchronic kidney disease and between telaprevir or dasabuvir and renal side effect. Thesefindings are used for hypothesis generation rather than testing.

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

Introduction The risk of hepatocellular carcinoma persists in some patients despite achieving sustained virologic response with current interferon‐free direct‐acting antiviral therapy for hepatitis C. The subject of an even higher carcinoma risk in this context has been reported and is currently being debated. The quest for understanding this paradox relative to the dynamics of inflammatory biomarkers in cirrhosis patients receiving antiviral therapy thus remains a subject of importance. Objective Here, we aimed at evaluating the effects of direct‐acting antiviral therapy‐induced hepatitis C cure on plasmatic markers of systemic inflammation measured before, during and after treatment. Specifically, soluble immune mediator phenotype associations that impact the odds of hepatocellular carcinoma development and the related changes that arise upon direct‐acting antiviral‐mediated hepatitis C clearance in cirrhosis patients was investigated. Methods Employing multiplex technology that measured up to 91 circulating biomarker proteins, we profiled the plasma soluble immune mediator concentrations of cirrhosis patients who developed posttreatment hepatocellular carcinoma and their respective negative controls, before and after direct‐acting antiviral treatment. Results Elevated pretherapy concentrations of specific soluble immune mediators including MCP‐3, GDNF, CDCP1, IL‐17C, IL‐17A, signalling lymphocytic activation family 1, CCL11, FGF‐5, LIF‐R, interleukin 10 (IL‐10), IL‐10RA, IL‐15RA, beta NGF, CCL28, CCL25 and NT‐3 distinguished patients who developed posttreatment hepatocellular carcinoma relative to those that did not. Particularly, GDNF, FGF‐5 and IL‐15RA displayed independent predictive biomarker attributes for delineating carcinoma emergence regardless of de novo or recurrence groupings. Upon successful therapy, the elevated pretherapy soluble immune mediator establishment of the patients who eventually developed hepatocellular carcinoma stayed largely unperturbed whereas a panel of some 38 soluble immune mediators in the posttherapy carcinoma‐free patients experienced significant ameliorations. Conclusions These results have considerable implications for delineating potential hepatocellular carcinoma emergence before initiating direct‐acting antiviral therapy for hepatitis C in cirrhosis patients. They provide preliminary contribution to unravelling cases where the benefit of direct‐acting antiviral therapies would be superior to the risk of developing carcinoma., Key Summary Established knowledge on this subject Current interferon (IFN)‐free direct‐acting antivirals (DAAs) are effective at eliminating hepatitis C virus (HCV), but risks of residual liver disease and development of hepatocellular carcinoma persists.The hepatic inflammation that occurs during chronic hepatitis C causes systemic changes in blood soluble immune mediators (SIMs) that impact carcinogenetic processes involved in the growth, invasion and metastasis of hepatocellular carcinoma (HCC).DAA‐induced HCV cure does not lead to a complete immunological restitution of the altered soluble inflammatory compartment in chronic hepatitis C. Significant and/or new findings of this study An elevated pre‐therapy plasma profile of an extended repertoire of SIMs in cirrhosis was associated with HCC development post‐DAA therapy.Successful DAA therapy did not alter the baseline elevated plasma SIM profile of cirrhosis patients that developed post‐therapy HCC contrary to its effect in those that remained HCC‐free.

Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection can cause hepatitis B virus (HBV) reactivation in HBV/HCV co-infected patients. Cancer patients undergoing immunosuppressant treatment or chemotherapy are at risk for HBV reactivation. To our knowledge, no prospective studies have examined the risk of HBV reactivation during DAA treatment for HCV infection in cancer patients with HBV/HCV co-infection. Here, we report the results of one such study. In a prospective observational study, we enrolled HCV-infected cancer patients undergoing DAA treatment at The University of Texas MD Anderson Cancer Center between January 2015 and March 2018. Data regarding demographics, cancer history, and prior HCV treatment history were collected. Patients were assessed for HBV status before DAA treatment and for HBV-related outcomes, including HBV reactivation, hepatitis flare, and HBV-associated hepatitis, during DAA treatment. Demographic and treatment variables were analyzed using descriptive statistics. One hundred sixty-six patients were analyzed. Forty-eight patients received systemic chemotherapy within 6 months before to 6 months after treatment with DAAs. Ledipasvir plus sofosbuvir was the most common DAA regimen, administered to 88 patients (53%). Fifty-one patients (31%) had past HBV infection, and 4 (2.4%) had chronic HBV infection. No patient experienced HBV reactivation, hepatitis flare, or HBV-associated hepatitis induced by DAA treatment. In HCV-infected cancer patients, DAA treatment is safe regardless of whether patients have past or chronic HBV infection. However, HBV screening is still recommended before the initiation of and during DAA treatment, as is anti-HBV prophylactic treatment in selected cases.

To compare the ultrasound (US) and pulse shear wave elastography (pSWE, Elast PQ®) methods with transient elastography (TE), clinical scores and laboratory tests, during the follow-up of HCV patients receiving direct-acting antiviral drugs (DAA). Our prospective study from June 2016 to December 2017 included 22 consecutively enrolled HCV-positive patients (59.7 ± 12.3 years, 11 male) which were subjected to antiviral therapy. All patients underwent B-mode ultrasound, color-Doppler, pSWE and TE five times: before therapy (T0), at the end of therapy (post-Tx), and at 12, 24, 48 weeks post-therapy. The liver stiffness (LS) values obtained with pSWE and TE and the data coming from US assessment and clinical evaluation were compared. We obtained a statistically significant reduction of LS values (kPa) measured by pSWE, between T0 (14.3 ± 9.3), post-Tx (11.8 ± 10.5), 12 weeks (7.5 ± 3.3), 24 weeks (8 ± 3.8) and 48 weeks (8.5 ± 4.6) (p = 0.02). The reduction of kPa measured by TE was not significant between T0 (14.7 ± 9.3), post-Tx (12 ± 9.5), 12 weeks (11.6 ± 7.7), 24 weeks (10.3 ± 6) and 48 weeks (10.8 ± 7.5) (p > 0.05). Multivariate baseline analysis showed significant independent association among measurement of TE stiffness with cirrhosis, type of vein hepatic flow and showed significant independent association between delta-pSWE measurement (difference between stiffness measurements at the baseline and 12 months after treatment) with staging of fibrosis (p = 0.006) and sustained virologic response after 12 weeks of treatment (SVR12, p = 0.017). The pSWE method has shown better ability than TE to identify a reduction in LS. Therefore, pSWE allow to evaluate stiffness reduction in HCV patient during DAA treatment follow-up, which is related to SVR12.

In this study, we investigated the use of direct-acting antivirals (DAAs), medical expenses and clinical outcomes since the initiation of national health insurance coverage in Taiwan.This was a retrospective observational study. We obtained claims data from Taiwan's National Health Insurance Research Database in 2017. Patients diagnosed with hepatitis C with at least two physician visits or one hospitalization were included in the study. Cases were divided into three groups based on the treatment type: traditional treatment (interferon, INF), new drug treatment (DAA) and INF-experienced (INF followed by DAA). We compared the distributions of various cases based on individual demographic variables, hospital type and comorbidities. Trends in medical expenses by treatment type were estimated. We also analyzed clinical outcomes, including rehospitalization and liver function disorders, using a survival analysis method.Among patients with hepatitis C, the DAA group had a significantly higher proportion of females, a higher mean age and greater disease severity than the INF group. The growth rate of medical expenses was significantly lower in the DAA group. In addition, compared to the INF group, the DAA group and INF-experienced group had significantly lower rehospitalization rates, and the DAA group had a significantly lower risk of liver function disorders. Furthermore, the longer a patient received any form of treatment, the lower was their chance of rehospitalization and liver function disorders.In conclusion, our results confirmed that insurance coverage of DAAs led to better clinical outcomes than INF, and this may reduce increases in medical expenses and the risks of rehospitalization and liver function disorders.Interferon for hepatitis C has low efficacy with serious side effects, while the efficacy of new oral drugs (direct-acting antivirals, DAAs) is high. DAAs were approved for listing in Taiwan in December 2013, and they have been covered by National Health Insurance since January 2017. Little is known about DAA-related real-world evidence following the coverage of DAAs in Taiwan, including drug utilization, expenditures and safety.This study explored three important issues related to DAAs: drug utilization, medical expenses and clinical outcomes following the insurance coverage by using the National Health Insurance Database. Cases were divided into three groups based on the treatment type: traditional treatment (interferon, INF), new drug treatment (DAA) and INF-experienced (INF followed by DAA). After the adjustment of various personal and hospital factors, the DAA group and INF-experienced group had significantly lower rehospitalization rates, and the DAA group had a significantly lower risk of liver function disorders, compared to the interferon group. There was a lower chance of rehospitalization and lower liver function disorder rates with longer treatment.

Drug resistance is prevalent across many diseases, rendering therapies ineffective with severe financial and health consequences. Rather than accepting resistance after the fact, proactive strategies need to be incorporated into the drug design and development process to minimize the impact of drug resistance. These strategies can be derived from our experience with viral disease targets where multiple generations of drugs had to be developed to combat resistance and avoid antiviral failure. Significant efforts including experimental and computational structural biology, medicinal chemistry, and machine learning have focused on understanding the mechanisms and structural basis of resistance against direct-acting antiviral (DAA) drugs. Integrated methods show promise for being predictive of resistance and potency. In this review, we give an overview of this research for human immunodeficiency virus type 1, hepatitis C virus, and influenza virus and the lessons learned from resistance mechanisms of DAAs. These lessons translate into rational strategies to avoid resistance in drug design, which can be generalized and applied beyond viral targets. While resistance may not be completely avoidable, rational drug design can and should incorporate strategies at the outset of drug development to decrease the prevalence of drug resistance.

Introduction: Objectives: Elderly cases have not been adequately representedin clinical trials with respect to chronic hepatitis C treatment. Extremely limited realworld data is available on new direct-acting antivirals in elderly patients. Herein, weaim to evaluate real-world data on new direct-acting antivirals used in the treatmentof chronic hepatitis C virus.Materials and Method: Medical records of 122 patients who started treatmentwith new direct-acting antivirals between January 2018 and December 2019 owingto chronic hepatitis C virus infection were analyzed retrospectively. Patients weredivided into two age groups: those younger than 65 years and those aged 65 andolder. Sustained virological response at 12 week rates were compared between thetwo groups. Sustained virological response at 12 week treatment efficacy analyseswere performed with both modified intention to tract and per protocol.Results: Sustained virological response in the 12th week post treatment wassimilar in both elderly patients and younger patients. Per protocol analysis was97.6% (42/43) vs. 100% (56/56) and modified intention to tract analysis was 91.3%(43/45) vs. 91.8% (56/61), respectively. The most common genotype of patientsaged 65 years and older were 1b 80%, and the most common genotype of patientsyounger than 65 years was 1b 57%.Conclusion: In the present study, Sustained virological response rates weresimilar in elderly patients compared to younger patients; however, very limitedinformation is available on the effectiveness and safety of new, recently approveddirect-acting antivirals in the elderly population.

Summary Background Despite the availability of effective and well-tolerated direct acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a substantial number of HCV patients remain untreated. Novel strategies targeting HCV patients with poor adherence are urgently needed to enable HCV elimination. Methods We implemented a physician-operated HCV hotline (HCV-Phone) that was promoted within the patient community and referral networks. Previously diagnosed HCV patients were contacted via the HCV-Phone and offered low-barrier access to DAA therapy. Patients/referring physicians could directly call or send messages to the HCV-Phone. The HCV-Phone related and unrelated visits as well as DAA treatment initiations throughout 2019 were documented. Patients were followed until October 2020. This study analyzed treatment initiation, adherence to scheduled visits and outcomes in patients in whom management was assisted by the HCV-Phone. Results Out of 98 patient contacts via the HCV-Phone 74 attended treatment assessment at our clinic. While 15 (20%) patients were HCV-RNA negative and 1 (1%) patient did not initiate therapy, 58 patients were recruited for DAA therapy via the HCV-Phone. A total of 21 additional patients who started DAAs without HCV-Phone assistance required the use of the HCV-Phone infrastructure later on during treatment, resulting in a total of 79 HCV-Phone related DAA therapies. The poor adherence of patients previously diagnosed with HCV at our clinic is underlined by the long duration from HCV diagnosis to DAA therapy of median 37.0 months (IQR 2.7–181.1 months). A total of 55 (70%) HCV patients achieved a sustained virological response (SVR), 5 (6%) discontinued therapy, 1 (1%) had a reinfection, while 10 (13%) and 8 (10%) patients were lost during DAA therapy or follow-up, respectively. Conclusion The implementation of a physician-operated phone hotline for patients with HCV infection facilitated treatment initiation in an HCV population with poor adherence. Mainly due to losses to follow-up, the SVR rate remained suboptimal with 70%.

Background Coadministration of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection and first generation anticonvulsants is currently not recommended due to a drug-drug interaction that could potentially lead to subtherapeutic DAA levels and subsequent treatment failure. Currently, there is limited data evaluating this interaction and timely treatment of HCV infection with DAAs is imperative to prevent liver-related morbidity and mortality. Methods A retrospective case series evaluating clinical cure of chronic HCV infection, defined as sustained virologic response (SVR) 12 weeks after completion of DAA therapy, in patients from three inner-city clinics who remained on first generation anticonvulsants during the treatment course. Results A total of five patients received standard dose DAAs for treatment of chronic HCV infection while being maintained on first generation anticonvulsants. The most common HCV genotype was 1a (80%), followed by 1b (20%). The majority of patients were treated with glecaprevir/pibrentasvir (80%) for eight weeks and one patient was treated with ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant regimens consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. All five patients achieved sustained virologic response (SVR) despite this drug-drug interaction. Conclusion Although every effort to prevent concomitant use of DAAs and potent inducers should be made, clinical cure may still be achieved in patients whom cannot avoid this coadministration.

© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan=99%, UK=78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2-3years after interferon-based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon-based therapy suggests that failure to achieve SVR is associated with long-term decline in liver function and, in contrast, patients who do achieve SVR can expect long-term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course.

BACKGROUND: Direct-acting antivirals (DAAs) are expected to improve outcomes for patients with hepatitis C virus (HCV) infection after liver transplantation (LT). We aim to evaluate trends in post-LT outcomes with availability of DAAs. METHODS: We retrospectively evaluated US adults transplanted from January 1, 2002, to March 31, 2018, using the United Network for Organ Sharing Registry, stratified by pre-DAA (January 1, 2002– to December 31, 2013) vs. post-DAA (January 1, 2014–, to March 31, 2018) eras. Adjusted multivariate Cox regression analyses and competing risk models evaluated likelihood of graft failure, death, and retransplantation (re-LT). RESULTS: Among 97,147 patients, 30.2% had HCV infection and 19.4% had hepatocellular carcinoma (HCC). Of all patients, 31.9% experienced graft failure, 27.1% died after LT, and 4.7% underwent re-LT. The post-DAA era experienced lower likelihood of graft failure (hazard ratio [HR] = 0.69, p

Hepatitis C Virus (HCV) is recognized as a prominent medical concern, being a common cause of cirrhosis, a risk factor for hepatocellular carcinoma, and a leading indication for liver transplantati...

Whether patients with advanced hepatocellular carcinoma (aHCC) benefit from hepatitis C virus (HCV) eradication is uncertain. We aimed to investigate whether a survival benefit was conferred by HCV eradication in aHCC patients. This retrospective cohort study enrolled 168 HCV‐infected aHCC patients from April 2013 to January 2019. All patients were treated with sorafenib. Endpoints included overall survival (OS), progression free survival (PFS), and time to liver decompensation. Patients with undetectable HCV RNA exhibited reduced aspartate aminotransferase and alpha fetoprotein levels, as well as an attenuated proportion of aHCC at initial diagnosis but increased albumin and mean sorafenib daily dosing. Patients with undetectable HCV RNA exhibited significantly longer OS compared to patients with detectable or unknown HCV RNA, which was an independent factor of OS (HR: 0.56, 95% CI: 0.350‐0.903, P = .017). Patients with undetectable HCV RNA also presented a trend for longer PFS (HR 0.68, 95% CI: 0.46‐1.00, P = .053). The survival benefit was considered with respect to the significantly prolonged time to Child‐Pugh B scores in patients with undetectable HCV RNA (HR 0.59, 95% CI: 0.38‐0.92, P = .020). Patients with detectable HCV RNA at sorafenib initiation who further received direct acting antiviral therapy also had significantly longer OS (HR 0.11, 95% CI: 0.02‐0.81, P = .030) and PFS (HR 0.23, 95% CI: 0.06‐0.99, P = .048). In conclusion, abolishing HCV viremia preserves liver function and confers a survival benefit in advanced HCC patients on sorafenib treatment.

Background: Liver-related mortality is considered the most common cause of death in HIV/HCV-co infected individuals. Accordingly, treatment of HCV infection in HIV/HCV-co infected individuals is a priority to manage such major health burden. Objectives: To evaluate the safety and efficacy of treatment of chronic HCV by DDAs in HCV-HIV co-infected Egyptian patients. Patients and methods: It is an observational study that included 22 patients; only 18 HCVHIV co-infected patients completed the study [14 males (77.8 %) and 4 females (22.8 %)]. Their ages ranged from 21 to 46 years with a mean age of 32.89 years. Half of them married and 72% of them working. 61% of them are smokers and IV addicts. Patients were divided into two groups according to HIV PCR. Group I included 12 Patients with HIV PCR > 50 copies/mm and group II that included 6 patients with HIV PCR < 50 copies mm. Results: The rates of a sustained virologic response (SVR) at post-treatment week 12 (SVR 12) were high [17/18 (94.4%)]. The most common adverse events were fatigue (66.7%), headache (50%) and there was a high safety profile on using direct-acting antivirals (DAAs) and no patient discontinued treatment because of adverse events. No serious adverse events or mortality was reported. In addition, AST & ALT were significantly decreased at end of treatment and 12 weeks after treatment. Otherwise there were no significant changes in both hematological and chemistry labs. Conclusions: Daclatasvir plus sofosbuvir for 12 weeks resulted in a high rate of sustained virologic response in patients co infected with HIV and HCV with high safety profile after treatment completion.

Almost all patients achieved sustained virological response (SVR) by direct-acting antivirals (DAA) therapy, but it is not clear as to what extent DAA therapy affects changes in liver fibrosis after achieving SVR. In this study, we investigated the changes of liver stiffness by magnetic resonance elastogaraphy (MRE) during DAA therapy. A total of 308 patients were enrolled in the study. Liver stiffness was measured twice before and after DAA treatment using MRE and time-course change of liver stiffness was investigated. The median (interquartile range) values for liver stiffness were 4.2 (3.2-6.1) kPa at baseline and 3.3 (2.6-4.8) kPa at SVR, demonstrating a significant improvement (p < 0.01). 44% of patients had no improvement in liver stiffness despite achieving SVR. In patients with advanced fibrosis (lower level of albumin or histological fibrosis stage F4), it was difficult to improve liver stiffness. Except for albumin, there were no blood tests associated with non-improvement in liver stiffness, making these cases difficult to predict. In conclusion, despite obtaining SVR, improvement in liver stiffness could not be obtained in some cases, especially in patients with advanced fibrosis. In these patients, liver stiffness must be followed even if SVR is obtained. This article is protected by copyright. All rights reserved.

The cost‐effectiveness of the second‐generation direct‐acting antivirals (DAA) has received considerable attention; however, their effect on wider societal costs has remained relatively unexplored. The aim of this study was to investigate the effect the new drugs have on sick leave compared to older treatment paradigms. This retrospective study utilized Swedish registry data to identify three cohorts: (a) patients treated with ribavirin and/or peginterferons (peg‐IFN) during 2005‐2011; (b) patients treated with the first generation of DAAs and ribavirin and/or peg‐IFN 2011‐2013; and (c) patients treated with the new generation of DAAs 2014‐2018. Individual‐level data on sick leave and early retirement were used to compare days away from work the year prior to the year following treatment initiation. A difference‐in‐difference model was estimated to test for differences between the cohorts adjusting for age and gender. Days away from work prior to treatment initiation was similar in the cohorts: 106, 85 and 94 days in cohorts 1 to 3. After treatment initiation, the number of days away from worked increased in cohort one and two to 150 and 140 days, while it remained similar in cohort three (88 days). The monetary value of the avoided sick leave was 7000‐10 000 €. In conclusion, patients treated with second‐generation DAAs without peg‐IFN had fewer days of sick leave in the year following treatment initiation compared to older treatments. Some caution is advised when interpreting the absolute figures due to potential heterogeneity between cohorts as they were treated at different points in time.

Chronic hepatitis C virus (HCV) is common in the Department of Corrections (DOC). Telemedicine is an effective way to treat HCV. The goal of this report was to demonstrate high SVR rate in DOC patients using telemedicine irrespective of the HCV genotype (GT) and DAAs used. Demographic, clinical and laboratory data were prospectively collected. A total of 870 DOC patients were evaluated and completed HCV therapy June 2015-December 2019 with SVR data were included. The mean age was 50 years, 90% were male, 63% were Caucasian, the majority (79%) had GT 1, 92% were treatment naive, and 80% had advanced fibrosis (FIB-4 ≥ 3.25 and/or transient elastography ≥ 9.5 kPa). The overall SVR was 97% and was similar among all DAAs irrespective of age, sex, race, HIV status, fibrosis level, GT, ribavirin use, prior treatment experience or DAA duration. We conclude that HCV treatment in the DOC through telemedicine is achievable and highly effective with overall SVR 97%, irrespective of the underlying GT or DAA regimen used and can eliminate HCV in this microenvironment and reduce the overall burden of HCV.

AIM We analyzed the impact of hepatitis C virus eradication by direct-acting antiviral (DAA) therapy on the risk of development of hepatocellular carcinoma (HCC), prognosis, and portal hypertension in patients with liver cirrhosis. METHODS The rate of HCC development and overall survival after achievement of sustained virological response (SVR) in 173 DAA-treated compensated cirrhosis patients without HCC history were retrospectively compared with that of 125 cirrhosis patients who achieved SVR by interferon (IFN)-based therapy or that of 85 cirrhosis patients who failed to respond to anti-HCV therapy. Changes in esophagogastric varices (EGV) and incidence of portosystemic encephalopathy were analyzed in 87 consecutive cirrhosis patients. RESULTS The cumulative HCC development rates at 1, 3, and 5 years were 2%, 7%, and 7% for the DAA-SVR group, significantly lower than the 3%, 7%, and 18% for the non-SVR group (log-rank, P

Background: Hepatitis C virus (HCV) is an important cause of chronic hepatitis with necroinflammation and fibrosis resulting in end stage liver disease and hepatocellular carcinoma. Direct acting antivirals (DAAs) are newer agents that directly interfere with the HCV lifecycle and result in high rates of sustained virologic response (SVR). We evaluated if treatment with DAAs in a real-world setting is as successful in HCV/HIV coinfected patients as it is in HCV monoinfected patients, and if some degree of fibrosis regression can be observed after completion of therapy in both groups. Methods: We retrospectively reviewed data from HCV monoinfected and HCV/HIV coinfected patients who received treatment from 2014-2016 at the East Carolina University Infectious Diseases clinic. The primary outcome was to compare completion and sustained virologic response (SVR) rate at either 12 or 24 weeks between HCV monoinfected patients and HCV/HIV coinfected patients. The secondary outcome was to assess regression of fibrosis at either 12 or 24 weeks after completion of therapy, defined as one METAVIR stage improvement in their FibroSure™, a noninvasive biochemical test to estimate the stage of fibrosis. Results: There were 41 patients in each group. Compared to the coinfected group, patient no show rate was higher in the monoinfected group (p=0.0346). In the HCV monoinfected group, 25 (93%) achieved either SVR 12 or 24. Two patients were non-compliant and had detectable viral load on evaluation at week 12. In the HCV/HIV coinfected group, 37 patients achieved SVR (p=0.0039). One patient in the coinfected group did not complete therapy but achieved SVR. In terms of fibrosis, 12/18 (67%) in the monoinfected group demonstrated improvement in at least 1 Metavir stage and 6/18 (33%) had no change. In the coinfected group, 8/16 (50%) patients demonstrated an improvement in FibroSure™ stage, 5/16 (31%) had no change, and 3/16 (19%) had worsening fibrosis according to FibroSure™ stage, (p=0.4867). Conclusions: In this small, real-world cohort, HCV/HIV coinfected patients treated with DAAs had higher completion and SVR rates than HCV monoinfected patients. Treatment failures in the monoinfected group were all linked to non-adherence, whereas, more coinfected patients achieved SVR, likely related to the fact that they were regularly engaged in routine HIV care. Fibrosis regression based on FibroSure™ was observed more in monoinfected patients than those with coinfection. Although not statistically significant, at least 50% of the patients in each group had regression of fibrosis.

Hepatitis C virus (HCV) is a common infectious disease affecting people worldwide. In the past 10 years, the incidence of HCV has steadily increased in the United States. With the advent of new direct-acting antiviral medications, the treatment of HCV has become important and can cure the infection.

The recent implementation of a scheme to provide universal access to direct-acting antiviral (DAA) medication to treat hepatitis C virus (HCV) places Australia in a unique position to reach global HCV elimination goals. To achieve this, increasing the uptake and success of DAA treatment in general practice settings is essential. This study aims to explore current enablers and residual barriers to HCV treatment in general practice settings in the post-interferon era from both GP and patient perspectives. Semi-structured interviews with 11 GPs and 27 patients were conducted to draw out both challenges and facilitators particularly relevant to DAA uptake and treatment journeys. Key enablers for successful treatment identified by this study included peer-led GP support and skill development, utilisation of electronic reminder systems, trusting relationships with patients and engaging with patients' social and family networks. Barriers related to accessible testing facilities and knowledge and confidence with DAA treatment continue to limit GP-led treatment. Despite a universal access scheme, barriers to DAA prescription in general practice settings remain. These include access to fibrosis testing and GP confidence in DAA prescription. Strengthening peer-led GP skill development and utilisation of electronic reminder systems may help GPs prioritise HCV treatment. Access to fibrosis testing and pathology services with no out-of-pocket costs to patients, particularly in outer-metropolitan areas, should be urgently addressed. This article is protected by copyright. All rights reserved.

Renal transplantation in patients affected by hepatitis C virus (HCV) infection has been a serious problem becauseof the use of immunosuppres-sants. HCV virus may be more aggressive in both the liver and the kidney. Several posttransplantation pathologies are known to be ascribed to the HCV virus.Virus eradication has been historically attempted with interferon (IFN) and ribavirin with poor results. In addition, IFN given posttransplan-tation may cause severe acute rejection.The introduction of direct antiviral agents (DAA) has revolutionized the treatment, and now it is possible to treat renal transplant patients with these agents leading to a HCV-free status in 3 months without the use of IFN.The major problem caused by these agents is their interference with the immunosuppressive agents.The pharmacokinetics of DAA and immunosuppressants often meet the same metabolic pathways and use the same cytochromes or proteic complexes. In some cases, this may lead to high or low immunosuppressant levels with the risk of rejection. In other cases, the DAAs are inter-ested and they may be increase or decrease in a dangerous way. Therefore a strict monitoring is always recommended.

BACKGROUND AND AIM More prospective studies are needed to characterize fibrosis improvement in patients with hepatitis C virus (HCV) who are treated with direct-acting antivirals (DAAs). The aims of this study were to assess changes in elastography scores from baseline to 1-year follow-up in patients with HCV, to identify factors that were independently associated with improvement in fibrosis staging in patients who receive treatment, and to identify factors that were independently associated with no improvement in fibrosis staging among patients who achieved sustained virologic responses (SVR). METHODS Ultrasound elastography and laboratory tests were performed and collected at baseline and at 1-year follow-up for patients who received HCV treatment and for those who did not receive treatment (n = 240). Binomial logistic regression was used to examine factors that were independently associated with improvement in fibrosis staging. RESULTS In patients who achieved SVR, the mean fibrosis score decreased significantly (-1.3) from 7.4 (2.3) before treatment to 6.1 (2.0) after treatment (P = 0.00). In multivariate analysis of patients who received treatment, higher pre-treatment fibrosis stages [odds ratio (OR) = 13.02, P