Rapid Virological Response Research Articles

HCV core antigen is a useful predictor during pegylated-interferon/ribavirin therapy in patients with hepatitis C virus genotype 1b

Enzyme immunoassays for quantifying hepatitis C virus (HCV) core antigen (Ag) have been proposed as an alternative to HCV RNA detection. The present study aimed to investigate the early kinetics of serum HCVcAg and its usefulness in predicting virological responses.The clinical data of 135 patients with chronic hepatitis C treated with pegylated interferon alpha (PEG-IFN-α) and ribavirin was retrospectively collected. The patients were grouped according to their treatment outcomes as follows: sustained virological response (SVR), nonsustained virological response (N-SVR), and relapse.Higher HCVcAg and HCV RNA levels were observed in patients in the N-SVR group than in the other groups at baseline. HCVcAg better predicted rapid virological response (RVR) compared with HCV RNA and had a predictive value similar to that of HCV RNA for SVR and early virological response. In the relapse group, HCV RNA decreased to 0 after 48 weeks, whereas HCVcAg was still detectable, indicating that HCVcAg more sensitively predicted relapse in antiviral therapy than HCV RNA.For patients treated with PEG-INF-α and ribavirin, HCVcAg may more sensitively predict relapse than HCV RNA.

Pharmacokinetics of Daclatasvir, Sofosbuvir, and GS-331007 in a Prospective Cohort of Hepatitis C Virus-Positive Kidney Transplant Recipients.

Limited data exist on the pharmacokinetic profile of novel direct-acting antivirals in kidney transplant recipients. Daclatasvir is primarily eliminated through the biliary route and sofosbuvir through the renal route; here, we report the pharmacokinetic profile of combined treatment with these compounds in a prospective study of hepatitis C virus (HCV)-positive kidney transplant recipients (EudraCT: 2014-004551-32). In this study, plasma samples of 16 HCV-positive kidney transplant recipients receiving daclatasvir and sofosbuvir were collected at 4 time points at days 1, 7, 14, 21, 56, and 84 after start of treatment. Inclusion criteria were stable graft function and an estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m. Daclatasvir, sofosbuvir, and GS-331007 (inactive metabolite of sofosbuvir) plasma concentrations were determined using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. All patients showed a rapid virological response with HCV RNA below the detection limit 21 days after the start of therapy (medium time to viral clearance). No difference of the areas under the concentration-time curve (AUC) of daclatasvir, sofosbuvir, and GS-331007 was observed between patients with an eGFR below or ≥60 mL/min. For GS-331007, no relevant changes of trough levels were observed over time. Mean GS-331007 trough levels were 339.5 ± 174.9 ng/mL in patients with an eGFR ≥60 mL/min and 404.3 ± 226 ng/mL in patients with an eGFR <60 mL/min at day 7 (P = 0.52). At day 84, GS-331007 trough levels were 357.8 ± 200.8 and 404.2 ± 70.2 ng/mL in patients with an eGFR ≥60 mL/min and in patients with an eGFR <60 mL/min, respectively (P = 0.51). The accumulation ratios of renally eliminated GS-331007 for AUC and Cmax did not significantly differ between the 2 eGFR groups at day 7. An impaired eGFR (30-60 mL/min) does not lead to a dose accumulation of daclatasvir, sofosbuvir, and GS-331007. This study provides the rationale for future studies investigating the pharmacokinetic profile of sofosbuvir-based HCV treatment in kidney transplant recipients with an eGFR <30 mL/min.

EFFICIENCY OF DAA ON HCV-INFECTED KIDNEY TRANSPLANT PATIENTS AT CHO RAY HOSPITAL – VIETNAM

Purposes:To evaluate the efficiency of DAA (Direct Antiviral Agent), in particular sofosbuvir, ledipasvir in Hepatitis C treatment for patients with kidney transplants. Take note in the side effects and drug interactions during the treatment processes. Method:Intervention, prospective, cohort, case studies, non-randomized, open on to all kidney transplant cases with chronic Hepatitis C tested positive HCV RNA (+); the patients from the cases above had agreed to be the research’s subjects from 11/2015 to 8/2018 at Cho Ray hospital. Two regimens Sofosbuvir/Ribavirin and Sofosbuvir/Ledipasvir have been used for treatments, which depend on HCV genotype and liver cirrhosis levels. Results:In 440 patients who had been observed after kidney transplants, 44 cases anti HCV (+), 29 cases HCV RNA(+) and 4 cases HBV/HCV Confection. There were 15 cases with chronic Hepatitis C participated in study. Males made up 66.6% of the group with the average age 49± 7.06 yrs. There were 6.7% of them not taking full-course treatments. 80% of the patients were infected with only C virus, while 20% of the patients were co-infected with B and C virus. 40% of them had histories of previous blood transfusions. The ratio of patients with elevated liver enzymes was 33.3%. Genotype 1 (a and b) was 33.3%, genotype 2 was 6.7%, genotype 6 was 53.3% and 6.7% unidentifiable genotype. There were 2 cases which were treated with Sofosbuvir/Ribavirin regimen and 13 cases which were treated with Sofosbuvir/Ledipasvir regimen. Rapid virologic response (RVR) is 100%. Sustained virologic response (SVR) within 12 weeks and 24 weeks is 100%. Relapse ratio 0%. In regimen using Sofosbuvir / Ledipasvir, the side effects are mild and transient, including skin irritation, digestive disorders which account for 7.7%. In regimen using Sofosbuvir / Ribavirin, side effects including severe anemia, fatigue, loss of appetite related to Ribavirin occur in 50% of cases (1/2) which lead to stopping treatment termination after 10 weeks and being replaced with treatment regimens using sofosbuvir / daclatasvir with good results. No major interactions are recorded when being used simultaneously with immunosuppressive drugs such as Prograf, Sandimmum Neoral, Mycophenolate Mofetil, Prednisone in this research. No renal failure occurs. Liver enzymes are improved during and after treatment. There is improvement scale of fibroscan after treatment. Conclusion: Sofosbuvir/ Ledipasvir regimen have proven their effectiveness in treating chronic Hepatitis C genotype 1, 2 and 6 on kidney-transplanted patient, with RVR at 100%, SRV 12 and SRV 24 at 100%. Sofosbuvir/ ribavirin regimen have proven to be effective in eliminating virus and be economical in treating chronic hepatitis C genotype 2, however, the anemia side effect of ribavirin need to be considered in case it become serious and now the first-line regimens are Sofosbuvir/daclatasvir or sofosbuvir/ Velpatasvir. There is improvement of hepatic fibrosis after treatment DAA.

Efficacy and Safety of Glecaprevir/Pibrentasvir in Combination Therapy in Chronic Hemodialysis Patients with Genotype 2 Hepatitis C Virus Infection

Background: Glecaprevir (nonstructural protein 3/4A protease inhibitor) and Pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-antiviral regimen, was evaluated for safety and efficacy in chronic hemodialysis patients with genotype 2 hepatitis C virus infection. Methods: In this prospective, observational, single-center study at Masuko Memorial Hospital, between November 2017 and December 2018, a total of 8 HD patients with an HCV infection genotype 2 received G/P combination therapy. Age was an average of 67.1 (61 - 75) years and there were four men and two women. It was FIB4 INDX an average of 2.67 (1.5 - 3.34) before the start of therapy. It was quantity of HCV RNA an average of 4.43 (2.1 - 6.5). HCV RNA levels were measured by real-time RCR-based method (COBAS AmpiPrep/COBAS TaqMan HCV Test. 4 cases 12 weeks were 2 cases eight weeks for dosing period. Patients were excluded if they had evidence of hepatocellular carcinoma. This study was approved by the ethics committee of our hospital, while we obtained written consent from the participants after providing a thorough explanation of the contents and methods of this study. Results: 6 patients were available for total dose internal use. As for the HCV RNA of the fourth week, (100%) HCV RNA became negative after administration start of therapy. Rapid virologic response (RVR) achieved all cases. 5 patients achieved 12-week sustained virologic response (SVR12) and were following up the 1 patient. The itching appeared in two cases (33%), but there was symptom improvement in nalfurafine hydrochloride use treatment, and treatment continuation was possible. Conclusion: It is thought that G/P can be given to the HD patients’ safety, but we will accumulate a case in future, and it is thought to be necessary to examine utility and safety.

Virological Response to Sofosbuvir-Based Treatment in Renal Transplant Recipients With Hepatitis C in Pakistan.

Direct-acting antiviral agents have recently been recommended in renal transplant recipients. Considering our previous encouraging responses with combined sofosbuvir and ribavirin in renal transplant recipients and the availability of daclatasvir, we aimed to evaluate the effectiveness and safety of sofosbuvir-based direct-acting antiviral agents in our population. All renal transplant recipients who received sofosbuvir-based direct-acting antivirals from August 2015 to March 2018 were included in our study. Patients were treated with sofosbuvir and ribavirin for 24 weeks or with combined sofosuvir, daclatasvir, and ribavirin for 12 weeks. Patient demographics and baseline laboratory parameters were collected. Rapid virologic response, end of treatment response, and sustained virologic response at 12 weeks were analyzed. Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 20.0, IBM Corporation, Armonk, NY, USA). In our study group of 79 patients, mean age was 36.5 ± 10.2 years and 60 were men (78.5%). Fiftysix patients (70.9%) were treatment naive; of the remaining patients, 20 received interferon before transplant and 3 were treated with sofosbuvir and ribavirin after renal transplant. Genotype 1 was observed in 42 patients (53.2%), whereas mixed genotype (1 and 3) was shown in 10 patients (12.6%). Sixty-two patients (78.5%) received sofosbuvir and ribavirin, and 17 patients (21.5%) received sofosbuvir, daclatasvir, and ribavirin. End of treatment response was achieved in 78 recipients (98.1%). Anemia was observed in 13 patients (16.4%). Hepatitis C virus was successfully eradicated in renal transplant recipients who received a combination of sofosbuvir plus ribavirin or sofosbuvir, daclatasvir, and ribavirin. These combinations were effective and well tolerated in our study population, even in those with mixed genotype, with no major adverse events.

Treatment With Grazoprevir/Elbasvir for Renal Transplant Recipients With Chronic Hepatitis C Virus Infection and Impaired Allograft Function.

BackgroundDirect-acing antiviral agents are highly efficient treatment options for chronic hepatitis C virus (HCV) infection after renal allograft transplantation. Treatment options for patients with impaired graft function remain limited. Therefore, we assessed the effectiveness and safety of grazoprevir/elbasvir therapy for patients with chronic HCV infection and impaired renal allograft function.MethodsEleven renal allograft recipients with therapy-naïve HCV genotype (GT) 1a, 1b, or 4 were treated with the fixed-dose combination of elbasvir/grazoprevir without ribavirin for 12 weeks. All recipients exhibited impaired graft function with an average glomerular filtration rate lower than 30 mL/min per 1.73 m2. Clinical data were retrospectively reviewed for renal and liver function parameters. Patients were closely monitored for trough levels of immunosuppressive agents, viral load, laboratory values, and potential adverse effects.ResultsSeven (64%) patients exhibited a rapid virologic response within 4 weeks (HCV GT1a, n = 2; HCV GT1b, n = 5). The other 4 patients exhibited a virologic response within 8 weeks (HCV GT1b, n = 3; HCV GT 4, n = 1). All patients exhibited a sustained virologic response at week 12 after the end of treatment. Clinical measures of liver function improved substantially for all patients. Few adverse effects were reported. Impaired renal allograft function and proteinuria remained stable. For most patients, only moderate adjustments to the tacrolimus dosage were necessary for maintaining sufficient trough levels.ConclusionsThis treatment appears to be safe and effective for renal transplant recipients with impaired allograft function and is a promising treatment option for eradicating HCV infection in this patient population.

Treatment of Chronic Hepatitis C Infection Among Egyptian Kidney Transplant Recipients: A Pilot Study.

Chronic hepatitis C infection incidence and prevalence are high in Egypt and represent a major health burden. Hepatitis C virus infection can affect graft outcomes in kidney transplant recipients. Treatment of hepatitis C virus infection among this special group was difficult during the interferon era; however, with advances in direct-acting antivirals, treatment outcomes have become more promising. This is a pilot, observational, single-center, one arm study that included 50 kidney transplant recipients seen at the Mansoura (Egypt) Urology and Nephrology Center. Patients were consented to receive a sofosbuvir-based regimen as all had creatinine clearance of greater than 30 mL/min/1.73 m2. All patients achieved rapid virologic responses 4 weeks after starting treatment. Forty-nine of 50 patients achieved 12-week and 24-week sustained viral responses. Six patients had increased serum creatinine levels. Four graft biopsies were performed. Anemia was the most common adverse effect among the patients who were maintained on ribavirin. Treatment of chronic hepatitis C infection has become easier and safe with the advance of new direct-acting antivirals.

Safety and efficacy of DCV-based DAAs therapy for chronic HCV infection in China

Objective: To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients. Methods: An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups. Results: Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred. Conclusion: DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.

CDR3 repertoire diversity of CD8+ T lymphocytes in patients with HCV

T cell receptors (TCR) diversity is known to serve as a defining hallmark of the antigen-reactive T cell repertoire. Complementarity determining region 3 (CDR3) was the most important region for the recognition of peptide-major histocompatibility complex (MHC) complexes and represented the diversity of TCR repertoire. In this study, we detected the CDR3 spectratypes by complexity scoring system to assess TCR repertoire diversity and further analyzed the correlation of CDR3 score with CD8+ T cell function and with the prognosis of chronic hepatitis C virus (HCV)-infected patients. The results demonstrated that CDR3 score was related to CD8+ T cell function and prognosis by analyzing the clinical indicators such as viral load (VL), rapid virologic response (RVR), early virologic response (EVR) and sustained virologic response (SVR). Importantly, we found that Vβ27, a member of CDR3 subfamily, might play an important role in the clearance of HCV. These findings indicate that TCR diversity maybe serve as a biomarker to predict the clinical parameters of HCV-infected patients.

Eradication of Hepatitis C in Renal Transplant Recipients With Sofosbuvir Based Direct Acting Antiviral Agents in Resources Sparse Country

Introduction: Treatment of Hepatitis C is revolutionized but these novel agents are neither widely available nor recommended in renal transplant recipients (RTRs).We aimed to evaluate the effectiveness and safety of sofosbuvir (SOF) based regimen with or without daclatasavir (DAC) in RTRs; the only available agents in Pakistan. Methods: All RTRs receiving direct acting antiviral agents from August 2015 to 2018 were enrolled in the study. Patients' demographics and baseline laboratory parameters and virologic reponse were analyzed Results: A total of 85 recipients were enrolled with the mean age was 37.6 ±10 years and majority (79.5%) was men. Eighteen patients were treatment experienced to interferon before transplant. Genotype 1 and mix genotype was documented in 39.8 % and 11.4 %, respectively. Fifty three patients (80.3%) were prescribed SOF and RBV for 6 months and 13 (18.8%) received SOF, DAC and RBV combination for 3 months. At the time of study, 64 patients completed their treatment course. Rapid virologic response was achieved in 57 patients (89.1 %). End-of treatment response was achieved in 61 patients (95.3 %). At the time of writing, SVR 12 and 24 was achieved in 48 and 21 patients, respectively. Anemia was noted in 11 patients (17.8 %) requiring RBV dose modification. Ascites resolved in 2 patients after treatment Conclusion: Studies and case reports in RTRs have demonstrated the effectiveness of sofosbuvir-based regimens for HCV eradiation with no allograft rejection1-3. Kamar et al,2documented 100% SVR12 in 25 RTRs; 3 patients received SOF with RBV while other 3 were prescribed SOF with DAC combination. Xue Y et al,3 documented 100 % SVR 12 in 6 RTRs treated with 12 weeks of SOF and DAC combination. Here we report, successful eradication of HCV in RTRs using a combination of sofosbuvir with ribavirin and sofosbuvir, daclatasavir and ribavarin. This combination was effective and well tolerated in our study population even with mixed genotype (i.e., 1 and 3) with no major adverse events.

Assessment of efficacy and safety of PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C

Patients with chronic hepatitis C‐associated liver disease are of an older age in southern Taiwan. PEGylated interferon‐based therapy could reduce the risk of cirrhosis and hepatocellular carcinoma and improve survival. We assessed the efficacy and safety of combination therapy with PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C. A total of 88 consecutive patients with chronic hepatitis C treated with combination therapy were analyzed retrospectively to identify factors associated with a sustained virological response (SVR). These patients were divided into two groups according to age: elderly patients ≧ 60 years (n = 43) and patients 50 to 59 years (n = 45). We compared baseline characteristics, adherence 80/80/80, dose modification, discontinuation, and adverse events profiles between these two groups. We further compared virological response rates stratified by genotype. The factors associated with an SVR were determined by total patients and different age groups. In the intent‐to‐treat analysis, the SVR rate was 61.8%. The SVR rate of elderly patients tended to be superior to that of total patients. Patients aged ≧ 60 years had a higher proportion of concomitant chronic disease, dose modification, clinical events with anorexia, depression, leucopenia, and anemia than those aged 50 to 59 years. Total patients with genotype 1 tended to have a lower SVR rate than nongenotype 1 (P = 0.067). Total patients with nongenotype 1 had a significantly higher rapid virological response (RVR) rate than genotype 1 (P = 0.009). In patients aged ≧ 60 years, the relapse rate of genotype 1 was higher than that of nongenotype 1 (P = 0.034). After stratification by HCV genotype 1, high viral load, and achievement of an RVR, the SVR rates remained similar between the two groups. The most strongly predictive factors of an SVR of total patients were the achievement of an RVR (OR: 49.744; 95% CI: 6.979‐354.574; P &lt; 0.001), followed by breakthrough (OR: 0.018; 95% CI: 0.002‐0.195; P = 0.001). The factor mostly predictive of an SVR in age ≧ 60 years group was achievement of an RVR (OR: 12.779; 1.430‐114.180; P = 0.023). Elderly patients had a greater frequency of adverse events. Genotype 1 is independently associated with lower SVR and RVR rates and high relapse rates. Attainment of an RVR is the most powerful predictor of SVR in elderly patients.

Patients with chronic hepatitis C receiving sofosbuvir and ribavirin-based treatment, with or without interferon in Zhejiang, China: An observational study.

Hepatitis C virus (HCV) is one of the most important virus as the cause of liver disease in China. The aim of the present study was to explore whether sofosbuvir and ribavirin-based treatment can cure patients with chronic hepatitis C in eastern China. We examined a cohort of HCV-monoinfected patients and 9 patients agreed to participate in our treatment and research. The patients were diagnosed with chronic hepatitis C with or without cirrhosis. Nine patients including 4 female and 5 male met the requirements for selection and were willing to participate in this experiment. Sofosbuvir and ribavirin-based treatment with or without interferon was given to the patients. Viral loads, cytokines, and chemokines were recorded during treatment and after treatment. After 2 weeks of sofosbuvir and ribavirin-based treatment, the viral load of patients decreased to limits of detection. Eight patients were cured. Patients had rapid virological response (RVR) with undetectable viral load at week 4 and sustained virological response (SVR). The interferon-inducible protein-10 (IP-10) decreased after the treatment. However, the patient with cirrhosis failed, as the virus reappeared during SVR4. At the same time, the IP-10 dramatically increased as the relapse of the HCV virus. In summary, the IP-10 has the potential to be the biomarker for the prognostic of HCV.

Utilization and efficacy of elbasvir/grazoprevir for treating hepatitis C virus infection after liver transplantation.

Recently, elbasvir/grazoprevir combination therapy (EBR/GZR) was reported to have excellent antiviral effects for chronic genotype 1 hepatitis C virus (HCV) infection. However, it has not been recommended for patients with post-liver transplant (LT) HCV re-infections because of a lack of evidence for effectiveness and drug-drug interactions. We report the usage of EBR/GZR in five post-LT HCV re-infected patients with the kinetics of renal function and tacrolimus trough levels during and after therapy. Furthermore, to evaluate the antiviral effects, we examined the HCV kinetics during and after therapy and compared this with other interferon-free therapy in post-LT patients (n = 19). All patients treated with EBR/GZR therapy obtained rapid virologic response and sustained at 12weeks post-treatment. There was no evidence of worsening estimated glomerular filtration rates. Three patients were given tacrolimus as immunosuppressive therapy and its trough levels were controllable with dosage adjustments. One patient developed grade 1 diarrhea 3days after therapy induction. To evaluate the antiviral effects of EBR/GZR therapy for these patients, we compared them to the effects of daclatasvir/asunaprevir combination therapy (n = 8) and sofosbuvir/ledipasvir combination therapy (n = 11). The EBR/GZR combination was not inferior to other therapies in its early phase and late-phase antiviral effects. Although further studies with a larger number of patients are required, we suggest that EBR/GZR therapy is an alternative therapy for patients with post-LT genotype 1 HCV re-infection.

Evaluation of TRIM5 and TRIM22 polymorphisms on treatment responses in Iranian patients with chronic hepatitis C virus infection

The tripartite motif (TRIM)-5 and TRIM22 are involved in innate immune response and show anti-viral activities. The current study aimed at evaluating the association of TRIM5 and TRIM22 polymorphisms with treatment outcomes in patients with chronic hepatitis C virus (CHC). TRIM5 rs3824949 and TRIM22 polymorphisms (rs7113258, rs7935564, and rs1063303) were genotyped using TaqMan polymerase chain reaction (PCR) assay in 425 treatment-naïve CHC patients. Rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) were found in 54.1%, 74.8%, and 67.1% of the patients, respectively. RVR and SVR were associated with TRIM5 rs3824949 (GG), TRIM22 rs1063303 (GC), and TRIM22 rs7113258 (AA), while there was a relationship between TRIM5 rs3824949 (GG) and EVR. TRIM5 and TRIM22 single nucleotide polymorphisms (SNPs) were strongly associated with increased odds of RVR, EVR, and SVR after an interferon-based therapy in patients with CHC.

Daclatasvir and asunaprevir combination therapy for patients with chronic hepatitis C virus genotype 1b infection in real world.

Background/AimsPrevious studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world.MethodsWe enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure.ResultsThe mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure.ConclusionsDCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.

Effectiveness and tolerability of direct-acting antivirals for chronic hepatitis C patients in a Southern state of Brazil

BackgroundThis study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. MethodsThis was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. ResultsA total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p<0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. ConclusionsThe results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.

Correlation of CD81 and SCARB1 polymorphisms on virological responses in Iranian patients with chronic hepatitis C virus genotype 1

The cluster of differentiation 81 (CD81) and scavenger receptor class B member 1 (SCARB1) plays an important role in the entry of hepatitis C virus (HCV). We assessed the correlation of five single nucleotide polymorphisms (SNPs) of CD81 (rs800136, rs2651842, rs2522012, rs800146, and rs708564) and SCARB1 rs10846744 polymorphisms with treatment responses in 395 treatment-naïve patients with chronic HCV (CHC) genotype 1 treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). The frequency of rapid virologic response (RVR), complete early virologic response (cEVR) and sustained virologic response (SVR) were 57.2%, 55.2%, and 58.2%, respectively. RVR, cEVR, and SVR were significantly associated with CD81 rs800136 (CC), CD81 rs2651842 (AA), CD81 rs708564 (TT), and SCARB1 rs10846744 (CC). High rates of RVR, cEVR, and SVR were reported for the CD81 rs800136 (CC), CD81 rs2651842 (AA), and CD81 rs708564 (TT) genotypes when correlated with higher levels of low-density lipoprotein (LDL) and lower levels of high-density lipoprotein (HDL) as well as lower levels of HDL and LDL in the SCARB1 rs10846744 (CC) genotype. In addition, patients with GG genotype had higher fasting blood glucose (FBS) level than those with CC genotype. In conclusion, CD81 and SCARB1 SNPs may serve as powerful predictor factors for treatment responses in CHC patients, and this effect is correlated with serum lipoprotein and FBS levels.

THU-306 - Rapid virological response, as a predictor of sustained virological response of Sofosbuvir and Ribavirin in Korean patients with genotype 2 chronic hepatitis C virus infection

THU-306 - Rapid virological response, as a predictor of sustained virological response of Sofosbuvir and Ribavirin in Korean patients with genotype 2 chronic hepatitis C virus infection

Dolutegravir-based anti-retroviral therapy is effective and safe in HIV\u2013infected paediatric patients

BackgroundTreatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited.MethodsWe describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed. Patients were tested before introduction of DTG, after 1 month and every 3 months in the first 2 years to assess virologic and immunological response, tolerance and development of side effects. Families were asked to report any suspected adverse events.ResultsSix patients (2 male, median age 17 years, range 12–18) were started on DTG-based anti-retroviral regimen due to low adherence to anti-retroviral treatment (ART), multiple drug resistance mutations, or development of ART-related side effects. Within 4–8 weeks after DTG treatment onset, a complete viral suppression and a concomitant increase of CD4+ cell count was observed. Four patients showed a persistent suppression after 2 years of follow-up, and 2 patients at about 1 year. One month after the introduction of DTG, the patient enrolled because of severe dyslipidaemia and hyper-transaminasemia showed a complete normalization of laboratory values. During follow-up (median 24 months, range 9–24) no adverse events were reported and most patients demonstrated a good adherence to treatment.ConclusionsDTG-based treatments demonstrated efficacy and good safety profile in adolescents. All patients demonstrated a rapid virologic and immunological response within 4–8 weeks, with good adherence and absence of side effects.

Qualitative Versus Quantitative PCR in Establishing Response to Chronic Hepatitis C Treatment with Sofosbuvir.

To determine the change in rapid virological response for chronic hepatitis C by qualitative PCR testing after treatment with sofosbuvir. A descriptive study. Memon Medical Institute Hospital, Karachi, from January to September 2016. The study population consisted of patients above 18 years, till 80 years of age, of both genders, having chronic infection with HCV. Patients included were treatment-naive, non-responders or relapsers; and among these categories, both cirrhotic and non-cirrhotic patients were included. Initially, genotyping and quantitative PCR test was done, one at the start of treatment then at 4 weeks that is till rapid virological response (RVR) was elicited. Qualitative testing was compared by Chi-square with quantitative assays simultaneously to check sensitivity by qualitative testing. Out of 106 patients, the mean age of the patients was 46.40 ±14 years. There were 39 (36.8%) males and 67 (63.2%) females. One hundred (94.3%) were infected with genotype 3. One hundred and five (99.05%) patients responded to sofosbuvir with successful achievement of RVR after 4 weeks. One patient did not achieve RVR (0.94%). The sensitivity of qualitative test was 99%. Qualitative analysis is a cost-effective and sensitive method in patients treated with sofosbuvir for confirming RVR, especially in developing countries where patients are self-paying with significant financial constraints.