Rapid Virological Response Research Articles

Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis

BackgroundPrevious studies suggested, variations in the IL28B gene can serve as predictors of sustained and rapid virological responses (SVR and RVR) in the treatment of HCV with pegylated interferon and ribavirin (pegINF-RBV) among HCV-HIV co-infected patients. Here, we explored the correlation between IL28B variants (rs12979860, rs8099917 and rs12980275) and treatment response for HCV among co-infected individuals using meta-analysis. MethodsRelevant studies were retrieved from PubMed, EBSCO, ISI Web of Knowledge, Cochrane databases, and the role of IL28B variants on SVR and RVR in co-infected patients treated with pegINF-RBV was evaluated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fixed- and random-effects models. ResultsForty-three studies consisting 3499 patients who achieved SVR/RVR and 4308 non-responders were included in our study. The CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, were associated with SVR in the recessive model for all HCV genotypes: rs12979860, OR = 3.18 [95% CI (2.66, 3.79)]; P < 0.0001; rs8099917, OR = 3.6`9 [95% CI (2.74, 4.97)]; P < 0.0001; rs12980275, OR = 2.97 [95% CI (2.26, 3.89)]; P < 0.0001. Significant association of rs12979860 CC genotype with RVR was also found: OR = 2.31 [95% CI (1.54, 3.57)]; P < 0.0001. Stratification analysis of HCV genotypes revealed similar trends of association with the rs12979860 CC genotype for HCV-1, HCV-1/4 and HCV-4, but no association was found for HCV-2/3 and HCV-3. ConclusionsOur meta-analysis suggests that the CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, are strong predictors for SVR, and the rs12979860 CC genotype has significant RVR predictive value in HCV-HIV co-infected patients treated with pegINF-RBV.

Safety and Efficacy of Antiviral Therapy of Chronic Hepatitis C in Chronic Kidney Disease and Hemodialysis Patients

Background and Aims: To assess the efficacy and tolerability of sofosbuvir-based antiviral therapy for viral hepatitis C (HCV) patients with chronic kidney disease and on maintenance hemodialysis.&#x0D; Methods: We retrospectively reviewed all treated patients with HCV from January 2015 to November 2020. They were treated either with standard Interferon/Ribavirin or with Sofosbuvir combined to Daclatasvir or to Ledipasvir. We evaluated the sustained virologic response at 12 weeks (SVR12). Data were analyzed using SPSS 20.00.&#x0D; Results: Out of 61 patients, the mean age of our patients was 56,8±12,56 years and 42,6% were males. Six patients had eGFR&lt; 60 ml/mn/1,73 m2 (9,8%) and 26 patients were on maintenance hemodialysis (42,6%). The majority had genotype 1 and overall SVR12 was 70,1% with a rate of 75% in the Sofosbuvir-regimen subgroup. The adverse events were minor. On multivariate analysis, genotype, viral load and rapid virologic response were independent factors that significantly predicted treatment success.&#x0D; Conclusion: Sofosbuvir-based regimen appears to be safe and efficious in patients with chronic kidney disease and on maintenance hemodialysis, especially in countries with limited resources.

Treatment for chronic hepatitis E virus infection: A systematic review and meta-analysis.

Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty‐four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta‐analysis of 395 patients showed a pooled SVR rate of 78% (95‐CI 72%–84%) after ribavirin treatment. Twenty‐five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon‐alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon‐alpha increases the risk of transplant rejection and should therefore be administered with great caution.

Efficacy and safety of ledipasvir/sofosbuvir in 5,028 Mongolian patients infected with genotype 1 hepatitis C virus: A multicenter study.

Background/AimsLedipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients.MethodsBetween 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12).ResultsMost patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA >6×106 IU/mL (n=866; 17.2%), or liver stiffness >9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%).ConclusionsLDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.

Incidence and Impact of Persistent Viremia on SVR Rates in Patients Receiving Direct-Acting Antiviral Therapy.

Rates of persistent viremia (PV) while on direct-acting antiviral therapy were low (5.7%) in a real-world cohort of 983 patients. High sustained virologic response rates were achieved both in patients with PV (92.9%) and those with rapid virologic response (96.5%), without significant differences.

Effectiveness of direct-acting antivirals in maintenance hemodialysis patients complicated with chronic hepatitis C.

Hepatitis C virus (HCV) infection is very common in maintenance hemodialysis patients, causing high morbidity and mortality. This study aimed to evaluate the effectiveness and adverse events of direct-acting antivirals (DAAs) in maintenance hemodialysis patients complicated with chronic hepatitis C in real-world clinical practice.In this retrospective observational study, hemodialysis patients with chronic hepatitis C infection in the Third Central Hospital of Tianjin outpatient were screened, and appropriate treatment plans were selected accordingly. Totally 25 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks or 24 weeks were included. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indexes and adverse reactions during the treatment process were also assessed.A total of 25 cases met the eligibility criteria and provided informed consent. Except for 1 patient who discontinued the treatment due to gastrointestinal bleeding, the remaining 24 cases completed the treatment cycle with 100% rapid virologic response (RVR) and 100% SVR12, with no serious adverse reactions recorded.Maintenance hemodialysis patients complicated with chronic hepatitis C in Chinese real-world setting tolerate DAAs very well, with a viral response rate reaching 100%.

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.

The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease.

Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated. This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level < 10.5g/dL. Hemodialysis patients received ritonavir-boosted paritaprevir/ombitasvir. KTx patients received sofosbuvir/daclatasvir. CKD patients with eGFR > 30mL/min/1.73 m2 received sofosbuvir/daclatasvir. Those with eGFR < 30mL/min/1.73 m2 received ritonavir-boosted paritaprevir/ombitasvir; 64 non-anemic patients also received ribavirin therapy. Mean age of CKDs was 49.1years, 43.2years for HDs, and 45.2years for KTx patients. Most were male; body-mass index was ~ 23.8. Anemia did not affect the efficacy of DAAs in hemodialysis, CKD, or KTx patients. Most patients achieved a rapid virologic response (RVR), and a 12- and 24-week sustained viral response. Worsening of anemia among the non-anemic group was mostly related to ribavirin therapy in hemodialysis patients (11/16 patients). Acute kidney injury in CKDs occurred more frequently within the anemic group (59.5%) compared to the non-anemic group (32.1%). For KTx, graft impairment was more common among the anemic group (7/40) compared to the non-anemic group (2/85). Hemoglobin levels of < 10.5g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD.

Effectiveness and safety of sofosbuvir/velpatasvir combination ± ribavirin in the treatment of Chinese adults with chronic hepatitis C virus infection

Objective: To understand the effectiveness and safety sofosbuvir/velpatasvir (SOF/VEL) combination ±ribavirin in the treatment of chronic hepatitis C virus (HCV) infection in China. Methods: A total of 96 Chinese adults with chronic HCV infection who were treated with SOF/VEL combination ± ribavirin for 12 weeks between July 2018 and February 2020 were selected. HCV RNA, routine blood test, liver, kidney and coagulation function, abdominal Color Doppler ultrasound or CT and liver stiffness were detected at baseline, 4 weeks of treatment, end of treatment and 12 weeks of follow-up. Adverse events and laboratory abnormalities during the treatment were recorded. A t-test was used to compare the measurement data between the two groups, and the analysis of variance was used for multiple group comparison. Results: A total of 93 cases (96.9%) achieved sustained virological response (SVR12), of which 3 cases had relapsed. 88 cases (91.7%, 88/96) had achieved rapid virological response (RVR). 96 cases (100%) had achieved virological response by the end of treatment (EOT). In patients with decompensated liver cirrhosis, the average baseline Child-Pugh score and Model for End-Stage Liver Disease score was 7.4±1.0, and 11.4±1.7, respectively. Among them, 12 cases of the SOF/VEL combined with RBV treatment had achieved SVR12 (100%) at 12 weeks, while only 3 of the 5 cases of single-tablet regimen of SOF/VEL had achieved SVR12 (60%). There was no significant difference between creatinine levels and baseline during or 12 weeks after treatment. The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 6.3% (5/79), while that in patients with decompensated cirrhosis was 35.3% (6/17). The most common adverse events were hyperbilirubinemia, fatigue and anemia. There were no serious adverse events, deaths or discontinuation of treatment due to adverse events. Conclusion: SOF/VEL combination ± ribavirin in the treatment of various common genotypes of chronic hepatitis C, compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma has higher SVR12 in China, and the tolerance and safety are good.

Ropeginterferon Alfa-2b administered every two weeks for patients with genotype 2 chronic hepatitis C

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

Induction of Combination Therapy for the Management of Hepatitis C: An Observational Study.

Background and objectiveHepatitis C infection is prevalent in Pakistan. The purpose of this study was to observe the therapeutic effects of conventional interferon in combination with ribavirin among treatment-naive hepatitis C patients.MethodsThis descriptive cross-sectional study of hepatitis C combination therapy was conducted at our institute after approval. All the patients received treatment with conventional interferon (5-MU three times weekly) and ribavirin (1000mg/day) for four weeks. A follow-up for the rapid virological response (RVR) was done in the fourth week of treatment. ResultsThe mean age of the patients was 37.43. There was a gradual decrease in RVR with increasing age after four weeks of treatment. ConclusionThe combination therapy showed good RVR in the fourth week among all hepatitis C patients.

HIV seronegativity in children, adolescents and young adults living with perinatally acquired HIV: A cross-sectional study in Thailand.

IntroductionEarly initiation of combination antiretroviral therapy (ART) with long‐term viral suppression may lead to seronegativity in grown‐up children with perinatally acquired HIV (PHIV). This study aimed to determine the frequency and associated factors of seronegativity in Thai children, adolescents and young adults with PHIV.MethodsA cross‐sectional HIV serological study was performed in children, adolescents and young adults two years or older who were receiving ART with undetectable HIV‐RNA for at least one year from August 2018 to August 2019. Medical records were extracted for multivariate analysis of independent factors for seronegativity.Results and discussionOf 110 patients, 50 male, median (range) age was 18.4 (4.8 to 26.6) years, 8 (7.3%) were seronegative, and 1 (0.9 %) was inconclusive. The seronegative group had a younger median (range) age at ART initiation: 3.0 (1.0 to 12.0) versus 40.0 (2.0 to 207.0) months, p = 0.045; and shorter median (range) duration from ART initiation to viral suppression: 16.8 (7.2 to 42.0) versus 55.2 (6.0 to 214.8) months, p = 0.036. Multivariate analysis identified younger age at ART initiation (aOR 0.69, 95% CI 0.49 to 0.98, p = 0.038) and shorter time to viral suppression after ART initiation (aOR 0.94, 95% CI 0.89 to 0.99, p = 0.019) as independent factors associated with HIV seronegativity. Of the infants who initiated ART < 3 and between three and six months of age, 50% and 26.7% became seronegative respectively.ConclusionsHIV seronegativity was observed in children and adolescents with PHIV who initiated ART early in infancy and had rapid and sustained virological response. Awareness of this phenomenon will help avoid inappropriate treatment interruption on the basis of negative antibody testing.

Rapid virologic response in chronic hepatitis C genotype 1: Evaluation of pretreatment factors in patients

Background and study aimsRapid virologic response (RVR) is defined as undetectable hepatitis C virus (HCV) RNA in serum after 4 weeks of treatment for chronic hepatitis C (CHC). Paritaprevir/ritonavir/ombitasvir (PRO) and/or dasabuvir (D), with or without ribavirin [PRO (D) ± ribavirin], which are direct-acting antivirals (DAAs), is the currently approved treatment regimen for CHC genotype 1; this regimen can also be used in patients with end-stage renal failure (ESRF). In this study, we aimed to evaluate the effect of pretreatment factors on RVR in patients treated with PRO (D) ± ribavirin. Patients and methodsThis study included 60 patients with CHC genotype 1 who were treated with PRO (D) ± ribavirin and achieved RVR. Patients’ demographic data; baseline HCV RNA levels; HCV genotype information; biochemical, histologic, and radiologic results; and previous treatment history were recorded. Patients were categorized into two groups: virologic responses achieved in the first week (group 1) and in the first to the fourth week (group 2). Pretreatment factors were compared between the groups. ResultsPatients in group 1 who achieved ultraRVR (undetectable HCV RNA after 1 week of treatment) had significantly lower mean pretreatment HCV RNA levels and lower prevalence of ESRF than patients in group 2. ConclusionsRVR has been indicated to be a robust positive predictor of sustained virologic response. We concluded that some pretreatment factors such as low HCV RNA level and absence of ESRF might lead to faster RVR and shorter treatment duration with DAAs for CHC.

Treatment of Chronic Hepatitis C Genotype 3 With Ledipasvir and Sofosbuvir: An Observational Study

Sofosbuvir/ledipasvir (SOF/LED) is recommended for treatment of genotypes 1, 4, 5 and 6. Despite some preliminary data from the ELECTRON-2 trial regarding use of SOF/LED combination in chronic hepatitis C genotype 3, there are no guidelines recommending this combination in such patients. We conducted this study to evaluate the efficacy of the overall sustained virologic response at 12 weeks (SVR 12) and safety of SOF/LED in chronic hepatitis C genotype 3 infection in our population. It was a prospective, hospital-based observational study. All patients with chronic hepatitis C genotype 3 treated with SOF/LED were divided into two groups: patients with cirrhosis and without cirrhosis. Patients without cirrhosis received SOF/LED (90/400mg) for 12 weeks; however, patients with cirrhosis received treatment for 24 weeks. We enrolled 104 patients with chronic hepatitis C over a period of 24 months. Of the total, 66 were women (63.5%) and 38 were men (36.5%). The average age was 40 years (range: 18-76 years). Of 104 patients, 86 (82.7%) were of genotype 3, 15 (14.9%) were of genotype 1 and 3 (2.9%) were of genotype 4. Ninety-two (88%) were noncirrhotic and 12 (11.5%) were cirrhotic. Ninety-five (95.2%) were treatment naïve. Among genotype 1 and 4, all patients achieved rapid virologic response and SVR 12. Of 86 genotype 3 patients, 78 (90.6%) were noncirrhotic and 8 (9.3%) were cirrhotic. Among genotype 3 patients without cirrhosis, 75 (96%) achieved SVR 12 while6 (75%) with cirrhosis achieved SVR 12. All patients tolerated the combination well; however, some patients experienced nausea (26%), headache (25%) and fatigue (21%). No patient had to discontinue therapy due to adverse drug reactions. Single tablet LED and SOF combination is safe and effective in genotype 3 patients without cirrhosis even without ribavirin. Being effective in genotype 3, the combination can be used as a pangenotypic drug in patients without cirrhosis.

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues.

Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited. To ascertain serum HBV RNA kinetics during long-term NA treatment and identify associated factors. We enrolled 76 HBeAg-positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Baseline serum HBV RNA was 8.5±1.0 log10 copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, -0.207 log10 copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, -0.071 log10 copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P=0.044), low baseline HBsAg (OR, 0.525, P=0.001) and rapid virological response (RVR) (OR, 0.624, P=0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P=0.043) and greater decline (OR, 0.966, P=0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49-66.40) months. RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.

P1384EFFECT OF ANEMIA ON EFFICACY AND SAFETY OF CHRONIC HEPATITIS C TREATMENT AMONG RENAL PATIENTS USING DIRECT ACTING ANTI-VIRUS

Abstract Background and Aims With the advance of new direct acting antiviral, treatment of HCV became safer and easier. Renal impairment makes treatment of HCV more difficult due to poor drug tolerability. Anemia is a common side effect occurring in renal patients. Effect of anemia on the efficacy and safety of these drugs in those particular populations is a point of interest. Method This is a single center cohort study was held in Urology and Nephrology Center, Mansoura, Egypt, including 235 renal patients who were divided into 2 groups according to presence/absence of anemia; hemoglobin below 10.5 g/dL is considered cut-off value: 70 chronic kidney disease patients (CKD) (42 anemic and 28 non-anemic), 40 hemodialysis patients (HD) (24 anemic and 16 non-anemic) and 125 kidney-transplant recipients (KTRs) (40 anemic and 85 non-anemic). Hemodialysis patients received ritonavir-boosted paritaprevir and ombitasvir±ribavirin (OMV/PTV/RTV), KTRs received sofosbuvir and daclatasvir. CKD with eGFR &amp;gt;30 ml/min/1.73m2 received sofosbuvir and daclatasvir. CKD with eGFR &amp;lt;30 ml/min/1.73m2 received OMV/PTV/RTV. All patients were followed-up for 6 months after completing HCV treatment. Results: Demographics: Mean age was 49.17y for CKD, 43.2y for HD and 45.2y for KTRs. Most of them were males with body mass index around 23.8. Out of 235, 22 patients had been previously treated with interferon-IFN- (14 patients showed relapse after primary response on IFN and 8 patients could not tolerate IFN due to severe anemia, leucopenia and recurrent infection) and 7 patients had been co-infected with hepatitis B virus (all patients were cleared from the virus prior to HCV treatment). Efficacy: Rapid virologic response was achieved in all groups. 12-week sustained viral response (SVR-12) among CKD patients was 92.86% in anemic group and 96.42% in no-anemic group (p=91%). SVR-24 was lower in both groups. There were 16 relapse cases among CKD patients (11 in anemic group and 5 in non-anemic group; p value=0.69). Relative Risk for relapse incidence among anemic CKD patients was 1.4 with 95% CI 3.58 to 8.58 (p value: 0.42). Among HD patients, there was only 1 relapse case and it was in anemic group. All KTRs achieved SVR-12 and SVR-24. Safety: Deterioration of kidney function within 1 month from starting DAAs was the major side effect in both groups among CKD patients but it was more profound in anemic group (59.5%) (p value: 0.024). Deterioration of creatinine clearance was more obvious in anemic group (26.7±11.8mL/min, 21.28±12.97mL/min; p value: 0.014). More cases needed hemodialysis either temporary (3 cases) or permanently (13 cases) in anemic group (p value: 0.03 for temporary hemodialysis and 0.005 for permanent hemodialysis). Relative Risk for A/CKD incidence with anemia among CKD patients was 1.85 with 95% CI from 22.94 to 1.98 (p value: 0.04). Anemia was associated with rise of serum creatinine among kidney transplant recipient also. Graft impairment among anemia group was 30% (12 out of 40 patients) in comparison to 3.5% in no-anemia group (3 out of 85 patients); p value: 0.0002. Relative Risk for graft impairment with anemia among KTRs was 8.5 with 95% CI 6.95 to 2.64. Subsequently, drug interruption was more frequent among anemia group in both CKD and KTRS as treatment was suspended during AKI period. Regarding hemodialysis patients, the only difference was that worsening of anemia was more frequent among no-anemia group (p value: 0.0002). Ribavirin resulted in this this difference as no-anemia group received ribavirin while the other group did not receive it. Conclusion Direct-acting anti viral drugs are considered advance in treatment of hepatitis C infection and it is well tolerated by kidney disease patients. However, this particular population needs special care. Correction of anemia before starting DAAs may improve the outcome. Hemoglobin levels below 10.5 g/dL prior to DAAs are associated with rise of serum creatinine among KTRs and CKD patients.

Efficacy and safety of direct-acting antiviral agent regimens in a real-world cohort of adult Chinese patients with chronic hepatitis C virus infection

Background and aimsTo investigate the safety and efficacy of direct-acting antiviral (DAA) regimens in a cohort of Chinese patients with chronic hepatitis C virus (HCV) infection. MethodsA total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accordance with HCV management guidelines. Treatment responses were evaluated 4 weeks after treatment, at the end of treatment (EOT) and 12 weeks post-treatment. Virological responses, biochemical responses, model for end-stage liver disease (MELD) and Child-Pugh (CP) scores were recorded. ResultsA total of 218 patients (98.2%) achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed. The combined number of rapid virological responses for all six regimens was 170/222 (76.6%), and 221/222 (99.6%) had achieved virological responses by the end of treatment. In decompensated cirrhosis patients the baseline mean CP score was 6.8 ± 1.3 and the mean MELD score was 10.1 ± 3.3. Compared with the mean CP score at baseline, the mean score is significantly lower at the end of treatment (5.7 ± 1.3) and 12 weeks post-treatment (5.6 ± 1.0). Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment. The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172 (24.4%), and in patients with decompensated cirrhosis it was 8/22 (36.4%). The most frequently reported adverse events were elevated indirect bilirubin, fatigue and rash. There were no cases of serious adverse events, death or treatment discontinuation because of adverse events. ConclusionDAA regimens were highly effective and well tolerated irrespective of HCV genotype, cirrhosis, liver or kidney transplantation, hepatocellular carcinoma, HCV/hepatitis B virus co-infection, or renal failure.

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics.

Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.

Escalating and sustained immunovirological dissociation among antiretroviral drug-experienced perinatally human immunodeficiency virus-1-infected children and adolescents living in the Central African Republic: A STROBE-compliant study.

Sub-Saharan Africa has the vast majority (∼90%) of new pediatric acquired immunodeficiency syndrome cases worldwide. Biologically monitoring HIV-infected pediatric populations remains challenging. The differential interest of human immunodeficiency virus (HIV)-1 RNA loads and CD4 T-cell counts is debated for the treatment of pediatric acquired immunodeficiency syndrome patients.Long-term antiretroviral treatment (ART) outcomes regarding immunological and virological surrogate markers were longitudinally evaluated between 2009 and 2014 (over 57 months) in 245 perinatally HIV-1-infected children and adolescents born from HIV-infected mothers, treated at inclusion for at least 6 months by the World Health Organization-recommended ART in Bangui, Central African Republic.Patients were monitored over time biologically for CD4 T-cell counts, HIV-1 RNA loads, and drug resistance mutation genotyping.Children lost to follow-up totaled 6%. Four categories of immunovirological responses to ART were observed. At baseline, therapeutic success with sustained immunological and virological responses was observed in 80 (32.6%) children; immunological and virologic nonresponses occurred in 32 (13.0%) children; finally, the majority (133; 54.2%) of the remaining children showed discordant immunovirological responses. Among them, 33 (13.4%) children showed rapid virological responses to ART with an undetectable viral load, whereas immunological responses remained absent after 6 months of treatment and increased progressively over time in most of the cases, suggesting slow immunorestoration. Notably, nearly half of the children (40.8% at baseline and 48.2% at follow-up) harbored discordant immunovirological responses with a paradoxically high CD4 T-cell count and HIV-1 RNA load, which are always associated with high levels of drug resistance mutations. The latter category showed a significant increase over time, with a growth rate of 1.23% per year of follow-up.Our STROBE-compliant study demonstrates the high heterogeneity of biological responses under ART in children with frequent passage from 1 category to another over time. Close biological evaluation with access to routine plasma HIV-1 RNA load monitoring is crucial for adapting the complex outcomes of ART in HIV-infected children born from infected mothers.

A safety and efficacy analysis of direct-antiviral therapy in patients with chronic hepatitis C after renal transplantation.

BackgroundTo explore the safety and efficacy of direct antiviral therapy in patients with hepatitis C virus (HCV) infection after renal transplantation.MethodsWe retrospectively reviewed the medical information of 15 cases of HCV+ patients treated with direct antiviral therapy after renal transplantation in our center. The effectiveness of direct antiviral therapy was evaluated by analyzing the HCV-RNA levels of patients at 1, 4, 12, 24, and 48 weeks before and after antiviral therapy. In addition, parameters including the rejection rate, the blood concentration of anti-rejection drugs, liver function level [alanine aminotransferase (ALT), aspartate transaminase (AST)], estimated glomerular filtration rate (eGFR) and serum creatinine (CREA) levels were used to assess its safety.ResultsA total of 15 patients were enrolled in the study. All patients turned HCV-RNA negative after 12 weeks of direct-antiviral therapy; the serological test of all patients demonstrated an 100% response rate in rapid virological response (RVR) (15/15), 12-week sustained virological response (SVR12), and 24-week sustained virological response (SVR24). In addition, compared to pre-treatment, the liver function within 12, 24, and 48 weeks after treatment was significantly improved. Moreover, eGFR, CREA, and anti-rejection drug concentration remained stable while acute rejection reaction and other obvious side effects were not observed throughout the treatment period.ConclusionsThe direct antiviral therapy was well-tolerated and effective for patients with chronic hepatitis C after renal transplantation.