Direct-acting Antiviral Agents Regimens Research Articles

Weight Gain and Increased Body Mass Index in Patients with Hepatitis C after Eradication Using Direct-Acting Antiviral Therapy in Taiwan.

Few studies have reported weight gain in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral agents (DAAs). This retrospective cohort study identified factors associated with substantial weight gain after DAA treatment in Taiwan. This study involved patients treated using DAAs at the Chiayi and Yunlin branches of Chang Gung Memorial Hospital from 1 January 2017 to 31 October 2020. Body weight data were collected at the start of DAA therapy and 2 years after the confirmation of a sustained virologic response. We performed multiple logistic regression to evaluate the clinical and laboratory parameters associated with a large body mass index (BMI) increase (≥5%). The mean BMI was 25.56 ± 4.07 kg/m2 at baseline and 25.77 ± 4.29 kg/m2 at the endpoint (p = 0.005). A considerable reduction in fibrosis-4 (FIB-4) score was a significant predictor of a large BMI increase (OR: 1.168; 95% CI: 1.047-1.304, p = 0.006). By contrast, older age (OR: 0.979; 95% CI: 0.963-0.996, p = 0.013) and a higher baseline BMI (OR: 0.907; 95% CI: 0.863-0.954, p < 0.001) were associated with a reduced risk of a large increase in BMI at the endpoint. In summary, a larger BMI increase was closely associated with a younger age, lower baseline BMI, and higher FIB-4 score reduction. Notably, differences in DAA regimens did not affect outcomes. Future studies are needed to elucidate the long-term effects and metabolic outcomes associated with this body weight change and investigate the exact underlying mechanisms.

Next-generation sequencing analysis of hepatitis C virus resistance-associated substitutions in direct-acting antiviral failure in South Korea.

We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles. Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed. ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree. ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.

Acute hepatitis C virus infection and direct-acting antiviral drugs: Perfect combination to eliminate the epidemic?

Early diagnosis and treatment of incident cases of hepatitis C virus (HCV) infection is fundamental to eliminate HCV in HIV-positive patients. From January 2016 to December 2019, we attended 40 episodes of acute HCV infection (AHC) in 35 subjects (9 reinfections) who were coinfected with HIV. The patients were treated with direct-acting antiviral agents (DAAs) in seven hospitals in Andalusia, Spain. All were men who have sex with men (MSM), mean age was 42.9 (±8.3) years and median time of HIV infection was 46.6months (IQR: 20.4-67.2). All received antiretroviral therapy and had undetectable HIV viral load (except 2 with 65 and 68 copies/mL); median CD4 count was 632 cells/mm3 (IQR: 553-896). Over half (74.3%) also had another concomitant sexually transmitted infection, syphilis (48.6%) being the most common. AHC was asymptomatic in 32 cases (80%). Genotypic distribution was G1a 65%, G4 32.5% and G1b 3%. Median time to DAA was 6weeks (IQR: 4.3-18.3) and median baseline HCV RNA was 6.1 Log (IQR: 5.6-6.5). DAA regimens were SOF/LDV (19 episodes), SOF/VEL (14), ELB/GZV (5) and GLP/PIB (2). All presented sustained viral response and none discontinued due to adverse effects. In conclusion, early treatment with DAA in AHC patients proved effective and safe. It could be an excellent strategy to eliminate HCV infection in HIV-coinfected MSM.

Additional Inhibition of Wnt/β-Catenin Signaling by Metformin in DAA Treatments as a Novel Therapeutic Strategy for HCV-Infected Patients.

Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). Although HCV clearance has been improved by the advent of direct-acting antiviral agents (DAA), retrospective studies have shown that the risk of subsequent HCC, while considerably decreased compared with active HCV infection, persists after DAA regimens. However, either the mechanisms of how chronic HCV infection causes HCC or the factors responsible for HCC development after viral eradication in patients with DAA treatments remain elusive. We reported an in vitro model of chronic HCV infection and determined Wnt/β-catenin signaling activation due to the inhibition of GSK-3β activity via serine 9 phosphorylation (p-ser9-GSK-3β) leading to stable non-phosphorylated β-catenin. Immunohistochemical staining demonstrated the upregulation of both β-catenin and p-Ser9-GSK-3β in HCV-induced HCC tissues. Chronic HCV infection increased proliferation and colony-forming ability, but knockdown of β-catenin decreased proliferation and increased apoptosis. Unexpectedly, Wnt/β-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3β-mediated β-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/β-catenin signaling for HCV-infected patients.

Natural history of hepatitis C virus infection in a large national seroconversion cohort in the direct-acting antiviral agent era: Results from ERCHIVES.

Hepatitis C virus (HCV) natural history studies are limited by not knowing the time of infection, small numbers and non-representative populations. No studies are available from the direct-acting antiviral agents (DAA) era. We created the largest known cohort of persons with HCV with a known window of seroconversion in the DAA era. We compared the annual cumulative incident events and incidence rate/1000 person-years of follow-up for liver cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC) and mortality from the time of seroconversion among untreated and those treated and attaining a sustained virologic response (SVR). Among 12,881 persons in the final analyses, 10,417 had never been treated for HCV, 2464 (23.6%) were treated with a DAA regimen and 1836 (74.5%) attained SVR. After 9years of follow-up, cirrhosis was diagnosed in 17.4% of untreated and 13.6% of the SVR group. Overall, 29.5% in the untreated versus 3.5% in the SVR group died. Incidence rates/1000 person-years of follow-up (95% CI) for untreated versus SVR group were 22.7 (21.6, 23.9) versus 19.5 (17.0, 21.9) for cirrhosis (p=0.03), 0.1 (0.03, 0.2) versus 0.07 (-0.07, 0.2) for HCC (p=0.74) and 35.4 (34.0, 36.8) versus 4.53 (3.4, 5.7) for mortality (p<0.0001). After excluding those with alcohol-related diagnoses at baseline, the difference in cirrhosis was not statistically significant. Cirrhosis and mortality occur early and steadily increase over the first decade after acquiring HCV infection, while HCC is rarely observed. Those treated with a DAA regimen have sharply lower cirrhosis and mortality rates, particularly among those without alcohol abuse or dependence.

Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C patients with genotype-2 infection after completed treatment.

Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype-2 (GT-2) patients in Taiwan. However, there is limited real-world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real-world efficacy in CHC GT-2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT-2 patients who were treated with SOF-based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non-SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT-2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.

Efficacy and Safety of Sofosbuvir-Based Direct-Acting Antiviral Agents Treatment for Patients with Genotype 3/6 Hepatitis C Virus Infection.

Aims The aim is to evaluate the efficacy and safety of Sofosbuvir- (SOF-) based direct-acting antiviral agents (DAAs) treatment for patients with genotype (GT) 3/6 hepatitis C virus (HCV) infection. Methods Patients infected with GT 3/6 HCV and treated with SOF-based DAAs were enrolled in this prospective, open, single-center, and real-world study. Drugs included Sofosbuvir (SOF), Velpatasvir (VEL), Daclatasvir (DCV), and Ribavirin (RBV). The treatment regimens included SOF + RBV for 24 weeks, SOF + DCV ± RBV for 12/24 weeks, and SOF/VEL ± RBV for 12 weeks. Results A total of 54 patients were included. Age was 42.5 ± 10.4 years. Baseline HCV RNA was 6.29 ± 0.89log10 IU/mL. The numbers of GT 3a, 3b, and 6a patients were 10, 12, and 32, respectively. The numbers of chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis patients were 39, 9, and 6, respectively. In patients with chronic hepatitis C and liver cirrhosis, sustained virological response 12 weeks after the end of treatment (SVR12) was 97.4% and 96.7%, respectively, and rapid virological response (RVR) was 75.0% and 57.1%, respectively. SVR12 of GT3a, GT3b, and GT6a was 100%, 83.3%, and 97%, respectively. ALT normality rate in chronic hepatitis group is higher than that in cirrhosis group at 4 weeks of treatment (89.7% versus 60.0%, p = 0.033) and at 12 weeks after EOT (94.9% versus 66.7%, p = 0.021). The overall incidence rate of adverse events was 44.4%, with fatigue being the most common (13.0%). Conclusion SOF-based DAAs regimen can achieve ideal SVR12 for Chinese patients with both GT3a and GT6a HCV infection. The tolerance and safety of SOF-based DAAs regimen are good.

Efficacy and Safety of Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C Virus Infection: A Real-World Single-Center Experience in Tianjin, China.

ObjectiveToward the limited real-world data concerning the treatment response to brand direct-acting antiviral agents (DAAs) therapy, we proposed to evaluate the efficacy and safety of DAAs for the treatment of chronic hepatitis C virus (HCV) in mainland China.MethodsIn this retrospective, single-center, cohort study, all HCV-infected adult patients treated with brand DAA drugs covered by Tianjin local health insurance (Apr 2018–Sept 2019) and responding to other specific inclusion criteria were recruited. The five available DAA regimens included sofosbuvir + ribavirin (SOF + RBV), elbasvir/grazoprevir (EBR/GZR), ombitasvir/paritaprevir/ritonavir/dasabuvir (OBV/PTV/r/DSV) ± RBV, daclatasvir + asunaprevir (DCV + ASV), and SOF + DCV ± RBV. Demographic, virologic, clinical, and adverse effects data obtained during and after DAAs treatment were collected. We evaluated the rate of sustained virological response at 12 weeks post-treatment (SVR12), the incidence of adverse effects, and assessed the factors associated with SVR12.ResultsFour hundred ninety-four patients finished the treatment and completed the 12-week post-treatment follow-up. The overall SVR12 rate was estimated at 96.96%. SVR rates greater than 95% were achieved in most of the HCV genotypes with the exception of GT1a (0%), GT3a (93.33%), and GT3b (88.24%). SVR12 for patients treated with DCV + ASV, EBR/GZR, OBV/PTV/r/DSV ± RBV, SOF + DCV ± RBV, and SOF + RBV for 12 or 24 weeks was 86.67%, 100%, 98.11%, 97.56%, and 95.06%, respectively. Subjects with compensated cirrhosis (92.73%) and prior treatment experience (77.78%) had significantly lower SVR rates when compared to chronic hepatitis C (98.15%) and treatment-naive (97.69%) groups. In Tianjin, the available DAA regimens were generally well-tolerated, and not a single serious adverse event was reported.ConclusionIn this large real-life single-center HCV cohort from China, oral DAAs were highly effective and well-tolerated. Further and larger-scale studies are needed to evaluate their clinical safety and efficacy.

Hepatocellular carcinoma occurs frequently and early after treatment in HCV genotype 3 infected persons treated with DAA regimens

BackgroundThere are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known.MethodsWe prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy.ResultsA total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen.ConclusionIn a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC.

Cost-Effectiveness Analysis of Direct-Acting Antiviral Agents for Occupational Hepatitis C Infections in Germany.

Around 1% of the world’s population is infected with hepatitis C. The introduction of new direct-acting antiviral agents (DAAs) in 2014 has substantially improved hepatitis C treatment outcomes. Our objective was to evaluate the long-term cost effectiveness of DAAs in health care personnel (HP) with confirmed occupational diseases in Germany. A standardised database from a German statutory accident insurance was used to analyse the cost-effectiveness ratio for the DAA regimen in comparison with interferon-based triple therapies. Taking account of the clinical progression of the disease, a Markov model was applied to perform a base case analysis for a period of 20 years. The robustness of the results was determined using a univariate deterministic sensitivity analysis. The results show that treatment with DAAs is more expensive, but also more effective than triple therapies. The model also revealed that the loss of 3.23 life years can be averted per patient over the 20 years. Compared to triple therapies, DAA treatment leads to a higher sustained virologic response (SVR). Although this results in a decrease of costs in the long term, e.g., pension payments, DAA therapy will cause greater expense in the future due to the high costs of the drugs.

Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma.

The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm (p < 0.001), but diminished in the DAA arm (p = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 104 person-years, log-rank p = 0.042) and III (5259 vs. 3278 per 104 person-years, log-rank p = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.

Role of different direct-acting antiviral drugs on hepatitis C virus-associated mixed cryoglobulinemia in Egyptian patients

BackgroundSeveral extrahepatic manifestations have been reported and mixed cryoglobulinemia is a clonal disorder of B cells which is strongly associated with hepatitis C virus (HCV).New regimens of direct-acting antiviral agents (DAAs) have recently been approved for the treatment of genotype 4 HCV which offer improved results of sustained virologic response (SVR) in the treatment-naive and previously treated patients.AimTo assess the prevalence of cryoglobulinemia for evaluating the efficacy of DAA therapy on it.Patients and methodsPatients received one of the following regimens: sofosbuvir, daclatasvir±ribavirin, or sofosbuvir plus ledipasvir±ribavirin follow-up for 24 weeks after treatment.ResultsA total of 132 patients were involved in our study: 65 men and 67 women. Cryocrit-positive patients clinically presented with clinical manifestations in 32 (53.3%) patients out of the 60 patients. After 12 weeks of DAAs treatment, there was a significant reduction in cryoprecipitate level and rheumatoid factor (RF) level with improvement of glomerular filtration rate, basal C4, and clinical improvement of purpura, Raynaud’s phenomenon, and this was the same when 38 patients continued treatment for 24 weeks. However, comparing 12 and 24-week therapy showed significant improved difference in cryoprecipitate level but improved glomerular filtration rate, basal C4, and decreased level of RF, proteinuria, purpura, and peripheral neuropathy although it did not reach statistical significanceConclusionCryocrit-positive patients were old age, cirrhotics with long duration of HCV. There is significant improvement of both laboratory and clinical parameters of cryoglobulinemia after SVR12 and more significant after SVR24. There is no significant difference in using different DDA regimen with or without ribavirin on the SVR at either 12 or 24 weeks. So, we advise basal laboratory and clinical parameters of mixed cryoglobulinemia before designing treatment regimens of HCV patients in Egypt.

P.446 Baclofen for alcohol use disorder: Mechanisms, results and safety

The advent of direct-acting antiviral agents (DAAs) has transformed the hepatitis C virus (HCV) therapeutic landscape in terms of efficacy and safety, with a cure rate of more than 90%. However, an important potential for drug-drug interactions (DDIs) is expected with these combinations, particularly in patients with other comorbidities (e.g. HIV co-infection, cardiovascular diseases). Each DAA can be a substrate, an inhibitor and/or an inducer of metabolic enzymes and drug efflux transporters. DAAs can act as both victims and perpetrators of DDIs and can sometimes increase the risk and/or intensity of side effects or limit the efficacy of treatment. Therefore, knowledge and management of DDIs with DAAs should be considered a key issue of HCV therapy. This review describes the pharmacokinetic profile of currently used and recommended DAA regimens and summarizes available data regarding DDIs to optimize HCV treatment in clinical practice.

953 Sustained Decline of Noninvasive Fibrosis Index Values in Patients With Chronic Hepatitis C (CHC) With Sustained Virologic Response (SVR) After Receiving Direct-Acting Antiviral Agents (DAAs)

INTRODUCTION: DAAs for CHC are highly effective at achieving SVR. However, there are limited data on outcomes post-SVR. Our aim was to investigate the temporal effect of DAAs on the outcomes of hepatic fibrosis by non-invasive assessment and incidence of HCC post-SVR. METHODS: Retrospective longitudinal study in adults with CHC who received DAAs between 2014 and 2018 and achieved SVR at 12 weeks (SVR12) and/or 24 weeks (SVR24). Data abstracted included demographic data, pre-treatment fibrosis stage, DAA regimen, clinical and laboratory data post-SVR. Fibrosis level was determined post-SVR using APRI and FIB-4. Co-primary study outcomes were FIB-4 values and APRI values post-SVR, and incidence of hepatocellular carcinoma. ANOVA and two-sample t-test statistical analyses were performed using Microsoft Excel. RESULTS: A total of 532 patients were identified retrospectively. Median age at the end of treatment was 60 (55–65) years, 306 (57.5%) were men, baseline median APRI was 0.92, baseline median FIB-4 was 2.67, and 230/532 (43%) were F4 pre-treatment (Table 1). Hispanics had a higher level of pretreatment fibrosis than non-Hispanics (P &lt; 0.01) and higher BMI than whites and Asians (P &lt; 0.001). We observed a significant sustained reduction in APRI scores post-treatment at SVR12/24, and 1 and 2 years post-SVR and FIB-4 scores at 2 years post-SVR within all fibrosis groups and all races (Tables 2 and 3). Hispanics in our cohort had significantly higher fibrosis levels at 1 and 2 years post SVR compared to blacks and Asians (P &lt; 0.01 and P &lt; 0.05, respectively) but not whites. 159 (70%) women and 224 men (73%) achieved a normal ALT less than 25 or 33. 72% of whites, 67 % of Asians, 81% of blacks, and 76% of Hispanics achieved normal ALT level. 22 (4.14%) patients developed hepatocellular carcinoma (HCC) post-treatment; all had F4 fibrosis prior to treatment initiation. CONCLUSION: In a cohort of HCV patients with high prevalence of advanced fibrosis,treatment with DAAs lead to significant improvement in fibrosis indices, across all initial fibrosis stages and races at 1 and 2 years post-SVR. In our cohort, Hispanics had higher baseline fibrosis levels and BMI yet still had a sustained significant improvement 2 years post-SVR though fibrosis levels still remained higher than Asians and blacks. The risk of HCC post-SVR remains in patients with F4 fibrosis.

Comparative Study between Efficacy of Two Quadruple DAAs Therapy in Treatment of HCV Relapsers

Background: Chronic hepatitis C virus (HCV) is considered as a major cause of liver diseases. The standard treatment of HCV infection is a combination of direct-acting antiviral agents (DAAs). Relapse is defined where HCV RNA remained undetectable at the end of therapy but rebounded to pretreatment levels once DAA therapy was discontinued. Aim of the study: This study was performed to compare efficacy and safety of two quadruple DAAs regimens (Sofosbuvir/Daclatasvir/Simeprevir and Ribavirin Vs. Sofosbuvir/Ombitasvir/ Paritaprevir/ ritonavir - Ribavirin) in treatment of HCV relapsers. Patients and Methods: Retrospective cross-sectional study of 90 experienced patients previously treated with Sofosbuvir and Daclatasvir ± Ribavirin for 3 months and relapsed. The patients were divided into two groups, each group included 45 patients: Group I treated with (Sofosbuvir and Daclatasvir -simeprevir—Ribavirin) while Group II treated with (Sofosbuvir-Ombitasvir/Paritaprevir/ritonavir - Ribavirin). Results: The study showed an excellent response to both regimens of treatment. In group I; the sustained virologic response rates at 24th week were 44/45 (97.8%); 100% (29/29) in non-cirrhotic and 93.8% (15/16) in cirrhotic patients. while group II SVR 24 rates were 93.3% (44/45); 92.9% (26/28) of non-cirrhotic patients, and 94.1% (16/17) of cirrhotic patients. while group II SVR 24 93.3% (44/45) of overall patients, 92.9% (26/28) of non-cirrhotic patients, and 94.1% (16/17) of cirrhotic patients. Additionally, the most common adverse events reported were easy fatiguability, headache, nausea, generalized weakness, photosensitivity - in group I only. Conclusion: It could be concluded that the current combination regimen is well tolerated and achieved excellent SVR rates.

Comparative Study between Efficacy of Two Quadruple DAAs Therapy in Treatment of HCV Relapsers

Background: Chronic hepatitis C virus (HCV) is considered as a major cause of liver diseases. The standard treatment of HCV infection is a combination of direct-acting antiviral agents (DAAs). Relapse is defined where HCV RNA remained undetectable at the end of therapy but rebounded to pretreatment levels once DAA therapy was discontinued. Aim of the study: This study was performed to compare efficacy and safety of two quadruple DAAs regimens (Sofosbuvir/Daclatasvir/Simeprevir and Ribavirin Vs. Sofosbuvir/Ombitasvir/ Paritaprevir/ ritonavir - Ribavirin) in treatment of HCV relapsers. Patients and Methods: Retrospective cross-sectional study of 90 experienced patients previously treated with Sofosbuvir and Daclatasvir ± Ribavirin for 3 months and relapsed. The patients were divided into two groups, each group included 45 patients: Group I treated with (Sofosbuvir and Daclatasvir -simeprevir—Ribavirin) while Group II treated with (Sofosbuvir-Ombitasvir/Paritaprevir/ritonavir - Ribavirin). Results: The study showed an excellent response to both regimens of treatment. In group I; the sustained virologic response rates at 24th week were 44/45 (97.8%); 100% (29/29) in non-cirrhotic and 93.8% (15/16) in cirrhotic patients. while group II SVR 24 rates were 93.3% (44/45); 92.9% (26/28) of non-cirrhotic patients, and 94.1% (16/17) of cirrhotic patients. while group II SVR 24 93.3% (44/45) of overall patients, 92.9% (26/28) of non-cirrhotic patients, and 94.1% (16/17) of cirrhotic patients. Additionally, the most common adverse events reported were easy fatiguability, headache, nausea, generalized weakness, photosensitivity - in group I only. Conclusion: It could be concluded that the current combination regimen is well tolerated and achieved excellent SVR rates.

Impact of Direct Acting Antiviral Agent Therapy upon Extrahepatic Manifestations of Hepatitis C Virus Infection.

Direct acting antiviral agents (DAAs) have emerged as simple, short, safe, and effective treatments for chronic hepatitis C (CHC) infection. CHC is a systemic disease with frequent and multiple extrahepatic manifestations. The beneficial effects of DAA treatment regimens extend beyond improvement in liver-related outcomes to amelioration of extra hepatic manifestations and are likely to have economic implications. The purpose of this review is to evaluate the effect of DAAs on extra hepatic manifestations of CHC virus infection. Recent studies indicate that DAAs are associated with reduction in all-cause mortality, even in patients without significant hepatic fibrosis. They are also associated with reduction in incident cardiovascular disease and diabetes. DAAs are the mainstay of treatment in HCV-associated cryoglobulinemia and lymphoma. Successful HCV therapy with DAAs also improves patient-related outcomes such as health-related quality of life. DAAs improve extrahepatic manifestations of CHC virus infection. Future studies are needed to evaluate the long-term durability of treatment response and for accounting amelioration of extrahepatic manifestations into the cost effectiveness of DAA regimens.

Transplantation of HCV Viremic Livers into HCV Viremic Recipients Followed by Direct-acting Antiviral Therapy.

Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor.Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression.Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation.Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.

DAA-based treatment for HIV-HCV-coinfected patients: analysis of factors of sustained virological response in a real-life study.

The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and the trend in biochemical parameters and clinical events during and after DAA regimen. We performed a multicentre retrospective cohort study, enrolling all 243 HIV-HCV-coinfected adult patients treated with DAAs between January 2015 and December 2018 in one of the nine participating Infectious Disease Centers in southern Italy, eight in Campania and one in Apulia. Of the 243 patients enrolled, 233 (95.9%) obtained an SVR at 12 weeks (SVR12). Of the 10 patients with non-SVR, 7 were tested for NS3, NS5A and NS5B resistance-associated substitutions (RASs) by sequencing analysis and 6 showed at least 1 major RAS in 1 HCV region (all in NS5A, 2 in NS5B and 1 in NS3). Comparing the 233 patients achieving SVR and the 10 non-achievers, no variable was independently associated with non-SVR. During and after DAA regimen, no modification in the biochemical parameters and clinical events was observed; however, the serum cholesterol and low-density lipoprotein (LDL) levels showed an increase (from 159 ±41.3 mg/dl at baseline to 174 ±44.5 mg/dl at week 12 after stopping treatment, P<0.001, and from 92 ±34.6 mg/dl to 109.4 ±73.7 mg/dl, P=0.002, respectively). The treatment with DAAs led to a high SVR12 rate in HIV-HCV-coinfected subjects, irrespective of epidemiological, clinical or virological characteristics. However, the DAA regimen was associated with an increase in total- and LDL-cholesterol, to be taken into account in the management of HIV infection.