Rapid Virological Response Research Articles

High efficacy and safety of direct-acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha-fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well-tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.

Meta-Analysis of the Effectiveness of Sofosbuvir-Based Regimens in Treating Hepatitis C Genotype 3

Hepatitis C virus (HCV) is an RNA virus with seven primary genotypes. It is highly prevalent in Pakistan, especially genotype 3. HCV infection can progress to a chronic state with further complications. Direct-acting antiviral agents (DAAV) were introduced in 2014 as a treatment option, some of which include Sofosbuvir (SOF), Daclatasvir (DCV), Velpatasvir (VEL) and Ribavirin (RV). This meta-analysis was performed to outline the treatment response and efficacy of DAAV in HCV infected patients. We systematically searched PubMed, Web of Science, MEDLINE, and Google Scholar for studies from January 2019 to December 2023. The studies selected met the criteria of patients having chronic HCV infection (genotype 3) and either compensated cirrhosis or decompensated chronic liver disease. Treatment regimens with DAAV specifically were included. The primary outcomes [sustained viral response (SVR), rapid virological response (RVR), end-of-treatment response (ETR)] were highlighted to assess treatment response. The studies proved that the use of direct-acting antiviral agents in different combinations was very effective against HCV infection with minimal side-effects.

Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide

Background & AimsBulevirtide is a first-in-class entry inhibitor antiviral treatment for chronic hepatitis D. The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with pegylated-interferon (Peg-IFN) are unknown. MethodsWe used mathematical modelling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks. ResultsThe efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, whereas Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% prediction interval [PI] = [79.7–95.0]), compared with 56.1% (95% PI = [46.4–66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5–13.2]) with bulevirtide compared with 18.8% (95% PI = [11.6–29.0]) with bulevirtide + Peg-IFN. Mathematical modelling suggests that after 144 weeks of treatment, the rates of viral cure could be 42.1% (95% PI = [33.3–52.6]) with bulevirtide and 66.7% (95% PI = [56.5–76.8]) with bulevirtide + Peg-IFN. ConclusionsIn this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment. Impact and implicationsBulevirtide has been approved for chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of Peg-IFN and bulevirtide in patients with CHD. Clinical trials are now warranted to confirm those predictions.

Assessment of ubiquitin specific Peptidase-18 gene in peripheral blood of chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C virus (HCV) infection remains one of the leading causes of liver complications globally. Ubiquitin Specific Peptidase-18 (USP18) is a ubiquitin-specific protease that cleaves interferon-stimulated gene 15 (ISG15) from ISGylated protein complexes and is involved in regulating interferon responsiveness. To study the effect of direct-acting antivirals (DAAs) on the USP18 gene using qPCR, 132 participants were recruited and classified into different groups based on treatment duration. USP18 expression was raised compared to rapid virologic response (RVR) and early virologic response (EVR) groups with P = 0.0026 and P = 0.0016, respectively. USP18 was found to be 7.36 folds higher in naïve patients than those with RVR and sustained viral response (SVR). In RVR and SVR groups where patients had cleared HCV RNA after treatment with direct-acting antiviral agents (DAA) therapy, the expression of USP18 was found to be low, with a fold change of 1.3 and 1.4 folds, respectively. Expression of USP18 was significantly higher in the non-RVR group than in the RVR group. In the No EVR group, gene expression was significantly higher than in the EVR group. It is concluded that targeting HCV proteins using DAAs can cause USP18 expression to be normalized more effectively. Moreover, USP18 is a vital marker indicating treatment resistance and distinguishing responders from non-responders during DAA therapy.

Recurrence Rate of Early Hepatitis C Virus Infection After Renal Transplantation Following Successful Treatment of Patients on Dialysis With Direct-Acting Antiviral Agents.

Recurrence of hepatitis C virus after organ transplant has dreadful complications. An excellent response has been shown with direct-acting antiviral agents in transplant recipients. Although a sustained virological response is considered as the virological cure, it requires patients to be on dialysis for 3 months more before undergoing renal transplant, thus increasing the risk of hepatitis C virus reinfection and associated complications. We aimed to determine hepatitis C virus recurrence in renal transplant recipients who had achieved endof-treatment response before transplant. Per our institutional dialysis protocol, patients who do not achieve rapid virological response are treated with 6 months of direct-acting antiviral agents. All patients who achieve end-of-treatment response are then referred for renal transplant. Our study included kidney transplant recipients who were treated with directacting antiviral agents and had a hepatitis C virus polymerase chain reaction test 3 months after renal transplant. We obtained demographic and clinical data of patients and used SPSS version 20.0 for statistical analyses. Our study included 48 transplant recipients; most were males (81.1%) with mean age of 28.7 ± 9.4 years. All patients received sofosbuvir, daclatasvir, and ribavirin combination before transplant. Most patients (70%) received treatment for 3 months. The polymerase chain reaction test for hepatitis C virus was conducted after a mean of 8.3 ± 3.3 months posttransplant. Laboratory parameters showed total bilirubin of 3.6 ± 17.5 mg/day, alanine aminotransferase of 51.5 ± 80.2 IU/L, and gammaglutamyltransferase of 133.9 ± 220 IU/L. Two recipients (4.2%) had posttransplant recurrence of hepatitis C virus infection. To our knowledge, this study is the first to document excellent response of direct-acting antivirals in renal transplant recipients who had been referred early for transplant. Thus, dialysis patients can undergo transplant after achieving end-oftreatment response.

Assessment of Serum Interleukin-35 Levels in Iraqi Patients with Hepatitis C Virus Infection

Background: It is unclear how IL-35 contributes to chronic hepatitis C virus (HCV) infection. Objective: To evaluate the association of IL-35 with the viral load in HCV infections. Methods: Fifty patients were included, and their age and sex were matched with 50 healthy subjects. Seven ml of venous blood was obtained and tested for anti-HCV antibodies using the ELISA kit, quantitative measurement of HCV RNA by PCR, and estimation of serum levels of IL-35. Results: The HCV viral RNA titers ranged from 165 to 55595000 copies/mL and were positive for anti-HCV antibodies. The control group was negative. The serum level of IL-35 in the patients was significantly lower than in the controls. The correlation coefficient for HCV viral loads and IL-35 in patients is equal to 0.114. The serum IL-35 level was highest in the age group of 30–39 years. The HCV patients on treatment have a mean viral load equal to 406,3051.90 copies/ml and a mean IL-35 level equal to 151.98 ng/ml; those without treatment have a mean viral load equal to 765,525.94 copies/ml and an IL-35 level equal to 165.09 ng/ml. The gender distribution of HCV viral load revealed non-significant differences. Conclusion: Most of the HCV patients did not achieve rapid or sustained virologic responses after treatments. Serum IL-35 was significantly reduced and shows a weak positive correlation with HCV viral load. Older HCV patients usually had lower serum IL-35 levels.

Sofosbuvir and Velpatasvir Regimen Outcome for Chronic Hepatitis C Patients With End-Stage Renal Disease Undergoing Hemodialysis.

Background Patients on hemodialysis (HD) are most likely to contract hepatitis C (HCV) infection, which is associated with significant morbidity and disease progression. Direct-acting antivirals (DAAs) are safe and tolerable in chronic kidney disease (CKD) with a 90-100% cure rate, and limited data exist regarding their efficacy in end-stage renal disease (ESRD), particularly for HDpatients in South Asia. The study aimed to assess the outcome of a 12-week sofosbuvir (SOF) and velpatasvir (VEL) treatment regimen on ESRD patients with chronic HCV infection undergoing HDin the Pakistani Asian population. Methodology This prospective cohort study was conducted between January 2022 and January2023 at the outpatient nephrology and gastroenterology clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan. This study included a total of 220 ESRD patients fulfilling the inclusion criteria, aged 20-55 years, who had been undergoing weekly HD sessions for at least two years, with acquired HCV infection. Data on demographic and clinical characteristics were collected through patient interviews. Laboratory and dialysis profiling was executed to assess ESRD and discover the underlying cause by ultrasound abdomen, blood pressure measurement by sphygmomanometer, random blood sugarfor diabetes, and taking note of the duration and frequency of dialysis. HCV RNA PCR was done at selected intervals to evaluate the virological response to treatment. Sustained virological response (SVR), liver cirrhosis status, and number of weekly HD sessions were compared at one year of SOF/VEL regimen. Results The mean age of patients with ESRD was 41.8 with a standard deviation (SD) of 9.3 years, and HCV diagnosis was 1.3 years with SD of 0.4 years; 52.7% (n=116) were males, 47.3% (n=104) were females, 75% (n=165) were urban dwellers, and 93.6% (n=206) were married.CKD that requires dialysis was caused mainly by hypertension (78, 35%), diabetes mellitus type 2 (52, 24%), bilateral small kidney disease (40, 18%), and others (34, 16%). One hundred and six (48.2%) received dialysis thrice weekly, 83 (37.7%) twice, and 31 (14.1%) once weekly. The study monitored the rapid virological response (RVR) at four weeks of SOF/VEL regimen in 89.5% of ESRD patients, observed end-of-treatment response (ETR) at 12 weeks in 93.2%, and noted 91.4% SVR response at one year. Only four (1.8%) relapses were observed in the study, which was statistically insignificant. The status of liver cirrhosis showed a 50% improvement, decreasing from 40% to 20%. The frequency of weekly HD sessions decreased from thrice to twice-thrice a week. Conclusion The prevalence of contracting HCV is high among CKD and dialysis ESRD patients. All-oral DAA therapy has revolutionized HCV treatment with co-morbidities. Renal functions improved after the SOF/VEL regimen for chronic HCV infection in ESRD patients undergoing HD, with the number of weekly dialysis sessions reduced and SVR reaching 91.4%. Thus, a single-tablet, pan-genotypic DAA regimen of SOF/VEL for 12 weeks is safe, effective, and tolerable regardless of the underlying etiology of ESRD, complications of cirrhosis, HCV genotype, or previous treatment exposure. The successful treatment of HCV and achieving SVR lowers the risk of ESRD complications, improves extra-hepatic manifestations, and greatly enhances survival. Further studies are warranted after the availability of other DAAs to confirm findings with no limitations.

Expression Profiling of the Tripartite Motif Family Genes in Chronic Hepatitis C Patients.

Hepatitis C virus (HCV) is one of the most prevalent pathogens which causes significant morbidity and mortality in 2% of the world's population. Several interferon-stimulated genes (ISGs) are involved in HCV clearance by interacting with the viral proteins. Among these ISGs, the tripartite motif (TRIM) family genes are elevated during HCV infection. This study aims to evaluate the expression of three TRIM family genes in chronic hepatitis C patients, distributed among different groups, including TRIM11, TRIM14, and TRIM25. A total of 242 participants were recruited in this study, including 182 infected patients, 37 naïve individuals, and 23 control individuals. Out of 182 infected patients, 100 achieved sustained virologic response (SVR), 61 achieved rapid virologic response (RVR), and 21 patients developed hepatocellular carcinoma (HCC), showing no response to the given treatments. Our results indicate highest expression levels of TRIM mRNA transcripts in the RVR group with the highest increase of 7.5 folds in TRIM25, 6.68 folds in TRIM14, followed by the data from patients of the SVR group. The elevation was also evident in other groups, i.e., SVR and HCC, in different patterns among all the three TRIM genes. In addition to elevation in expression levels, a linear correlation is observed between the TRIM mRNAs and viral loads of HCV. These results showed the potential role of TRIM family genes in HCV restriction.

#4237 EFFICACY AND TOLERABILITY OF DIRECT-ACTING ANTIVIRALS IN HEMODIALYSIS PATIENTS WITH CHRONIC HEPATITIS C

Abstract Background and Aims Hepatitis C virus (HCV) infection is common in hemodialysis (HD) patients and is associated with increased morbidity and mortality. In recent years major progress in the treatment of HCV infection has been made with the entry into use of direct-acting antivirals (DAA), which target viral proteins, leading to increases in sustained virological response (SVR) and a marked decrease in side effects. The aim of the study was to evaluate the efficacy and frequency of side-effects of DAA therapy in HD patients with HCV infection. Method The multicentric prospective cohort study included 42 HD patients with HCV infection over the last two years. DAAs therapy was administered according to HCV genotype and drug interactions considering guidelines for a period of 12 weeks (for HCV genotype 1: Elbasvir/Grazoprevir or Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir, and for HCV genotype 4: Elbasvir/Grazoprevir or Ombitasvir/Paritaprevir/Ritonavir). The following clinical parameters at weeks 0, 4, 8, 12, and 24 (12 weeks after the completion of treatment with DAA) were analyzed: presence of side effects, PCR HCV titer (ref. range: <12 IU/ml negative), hemoglobin (Hgb-g/L), epoetin dose (IU/kg/week), alanine aminotransferase level (ALT-U/L), and gamma-glutamyl transferase level (GGT-U/L). Before treatment with DAA liver fibrosis score (F0-F4) was defined by Fibroscan and the patients with liver stiffness over 12,5 kPa (Fibrosis score F4) were considered cirrhotic, but only patients with compensated cirrhosis (Child-Pugh score class A) were treated. For statistical analysis chi-square test and combined analysis of variance for repeated measures were performed by IBM SPSS softver. PCR HCV titer was analyzed with logarithmic transformation of data. Results Over the observed period 42 HD patients with HCV infection (25M and 17F) with the average age 56,78±11,6 years and average HD vintage 159±75 months were included in the study. Twenty-six patients (61,9%) were with HCV genotype 1 and 16 patients (38,1%) with HCV genotype 4. Ten patients (23,8%) were with compensated cirrhosis (F4 fibrosis score by Fibroscan). Three patients (7,1%) had mild gastrointestinal side effects and only one patient (2,4%) discontinuated the therapy during the first week due to intolerancy to DAA. All 41 patients (100%) who completed 12 weeks DAA therapy were PCR HCV negative at 4 weeks of treatment and achieved rapid virological response (RVR) and 12 weeks after the completion of treatment and achieved sustained virological response (SVR12) that was statistically significant (p<0.001). In regard to PCR HCV titer before DAA therapy there was no statistically significant difference among HD patients according to cirrhotic status and HCV genotype. There was no statistically significant change of hemoglobin level and epoetin dose in HD patients during the DAA therapy. The ALT and GGT levels statistically significantly decreased at weeks 12 and 24 compared to week 0 in all treated patients with DAA (ALTweek0 = 35,2±21,7; ALTweek12 = 21,8±16,2; ALTweek24 = 23,5±13,1; p<0.001 and GGTweek0 = 53,3±67; GGTweek12 = 18,6±6,8; GGTweek24 = 19,4±11,5; p = 0.042 respectively). The therapy with DAA was equally effective in patients with compensated cirrhosis and in patients without cirrhosis and there was statistically significant decrease of ALT and GGT levels in both groups of patients (p = 0.002 and p<0.05 respectively). In regard to HCV genotype DAA were equally effective in patients with HCV genotype 1 and in patients with HCV genotype 4 and ALT and GGT levels significantly decreased in both groups of patients (p<0.001 and p<0.05 respectively). Conclusion The therapy with DAA in HD patients with HCV infection was extremely effective and SVR12 was achieved in 100% of treated patients. The administered DAA were equally effective in patients with compensated cirrhosis and in patients without cirrhosis, and in patients with HCV genotype 1 and HCV genotype 4. The therapy with DAA was well tolerated, 7,1% of patients had mild side effects and 2,4% of patients discontinuated the therapy due to intolerance.

Response of Daclatasvir and Sofosbuvir in Treatment-Naïve, HCV Genotype 3, Non-Cirrhotic Pakistani Population: 1 Year Follow-Up Experience

using daclatasvir and sofosbuvir in treatment-naive, non-cirrhotic HCV genotype 3 Pakistani population. Methodology: From January 2017 to February 2019, HCV patients who met the inclusion criteria were included in this open-label, non-randomized, uncontrolled observational trial at HBS General Hospital in Islamabad. A 12-week course of oral daclatasvir and sofosbuvir therapy was administered to each participant. Each patient got 400mg of sofosbuvir and 60mg of daclatasvir. Treatment outcomes included sustained virological response (SVR12 and SVR24), rapid virological response (RVR), and end-of-treatment response (ETR) as primary and secondary respectively. Results: There were 105 participants in the study, of which 72.3% were male and 27.6% were female. RVR for male was 92% (p=0.002), while it was 89.65% for female (p=0.004). 96.05% of the male and 93.1% of the female achieved ETR (p=0.002). Both 93.1% of female and 93.4% of male had SVR12 (p=0.001). A single male patient experienced relapse after achieving SVR12 (p=060). SVR24 rates for male and female were 92.1% (p=0.003) and 93.1%, (p=0.003) respectively. The combination therapy was well-tolerated, with the primary side effect being fatigue (36% in males, 44% in females). Conclusion: The combination therapy of daclatasvir and sofosbuvir demonstrated both safety and efficacy in treating treatment-naïve, non-cirrhotic individuals with HCV genotype 3 in Pakistan. The study underscores the potential of direct-acting antiviral agents in addressing the challenge of HCV infections.

Transcriptional Analysis of TP53 Gene in Chronic Hepatitis C Patients Treated with Sofosbuvir, Daclatasvir, Pegylated Interferon, and Ribavirin.

Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies.

Preemptive antiviral therapy in lung transplantation from hepatitis C donors results in a rapid and sustained virologic response

ObjectiveThe study objective was to assess the safety and efficacy of a preemptive direct-acting antiviral therapy in lung transplants from hepatitis C virus donors to uninfected recipients. MethodsThis study is a prospective, open-label, nonrandomized, pilot trial. Recipients of hepatitis C virus nucleic acid test positive donor lungs underwent preemptive direct-acting antiviral therapy with glecaprevir 300 mg/pibrentasvir 120 mg for 8 weeks from January 1, 2019, to December 31, 2020. Recipients of nucleic acid test positive lungs were compared with recipients of lungs from nucleic acid test negative donors. Primary end points were Kaplan–Meier survival and sustained virologic response. Secondary outcomes included primary graft dysfunction, rejection, and infection. ResultsFifty-nine lung transplantations were included: 16 nucleic acid test positive and 43 nucleic acid test negative. Twelve nucleic acid test positive recipients (75%) developed hepatitis C virus viremia. Median time to clearance was 7 days. All nucleic acid test positive patients had undetectable hepatitis C virus RNA by week 3, and all alive patients (n = 15) remained negative during follow-up with 100% sustained virologic response at 12 months. One nucleic acid test positive patient died of primary graft dysfunction and multiorgan failure. Three of 43 nucleic acid test negative patients (7%) had hepatitis C virus antibody positive donors. None of them developed hepatitis C virus viremia. One-year survival was 94% for nucleic acid test positive recipients and 91% for nucleic acid test negative recipients. There was no difference in primary graft dysfunction, rejection, or infection. One-year survival for nucleic acid test positive recipients was similar to a historical cohort of the Scientific Registry of Transplant Recipients (89%). ConclusionsRecipients of hepatitis C virus nucleic acid test positive lungs have similar survival as recipients of nucleic acid test negative lungs. Preemptive direct-acting antiviral therapy results in rapid viral clearance and sustained virologic response at 12 months. Preemptive direct-acting antiviral may partially prevent hepatitis C virus transmission.

ОПЫТ ПРИМЕНЕНИЯ ДАСАБУВИРА / ОМБИТАСВИРА / ПАРИТАПРЕВИРА / РИТОНАВИРА У ПАЦИЕНТОВ, НАХОДЯЩИХСЯ НА ГЕМОДИАЛИЗЕ, С ВИРУСНОЙ ИНФЕКЦИЕЙ ГЕПАТИТА С

Abstract. Introduction. Hepatitis C virus is very common in patients on maintenance hemodialysis, resulting in high morbidity and mortality. Currently, new direct antiviral agents lead to a cure of Hepatitis C virus among most patients with a very good safety profile, which has allowed their use in the treatment of patients with Chronic Kidney Disease as well.Aim. To analyze the practical experience of using dasabuvir/ ombitasvir/ paritaprevir/ ritonavir in patients with chronic hepatitis C with history of chronic kidney disease. Material and methods. Treatment with dasabuvir/ ombitasvir/ paritaprevir/ ritonavir was carried out in 11 patients on hemodialysis with chronic hepatitis C. The virologic response was evaluated in 4 and 8 weeks at the end of the treatment, as well as sustained virologic response in 12 and 24 weeks after the start of treatment. Tolerability and safety of the drugs were also evaluated. Laboratory parameters and adverse reactions during treatment were analyzed.Results and discussion. Treatment using dasabuvir/ ombitasvir/ paritaprevir/ ritonavir was tolerated satisfactorily by all patients. There were no undesirable events. All patients completed the treatment cycle with a 100% rapid virologic response and 100% sustained virological response. No serious adverse reactions were registered. Upon follow-up, the hepatitis C virus was again detected in one patient, but of a different genotype.Conclusion. Treatment using dasabuvir/ ombitasvir/ paritaprevir/ ritonavir is effective for patients with chronic hepatitis C of the first genotype of the virus on the background of chronic kidney disease with program hemodialysis. Patients with chronic kidney disease are at high risk of infection and reinfection with parenteral viral hepatitis.

P8.114: Recurrence Rate of Early HCV Infection After Renal Transplantation Following Successful Treatment of Dialysis Patients With Direct Acting Antiviral Agents

Introduction: HCV recurrence after organ transplantation has dreadful complications. Excellent response of direct acting antiviral agents (DAAs) in transplant recipients has been reported in various studies. Although, sustained virological response is considered as the virological cure, but it requires patients to be further 3 months on dialysis before undergoing renal transplant.Thus, increasing risk of HCV re-infection and associated complications. We aim to determine HCV recurrence in renal transplant recipients (RTRs) who has achieved end of treatment response (ETR) before transplant. Methods and Materials: As per institutional protocol dialysis patients who failed to achieve rapid virological response (RVR) were treated with 6 months of DAAs. All patients who have achieved ETR were then referred for transplantation. Kidney transplant recipients who were treatment experience with DAAs and had a HCV PCR done 3 months after transplant was enrolled. Participant’s demographic and clinical data was documented and statistical analysis was performed by SPSS 20.0. Results: In total 40 transplant recipients were included, majority were males (81.1%) with mean age of 28.7 ± 9.4 years. All patients had received sofosbuvir, daclatasavir and ribavirin combination prior to transplant. Majority of patients received treatment for 3 months (70%). Only 5 % of study population did not achieved RVR while all patients achieved ETR. Two patients also had treatment experience with interferon. Post-transplant HCV PCR was conducted at mean duration of 8.3 ± 3.3 months. Laboratory parameters showed Total Bilirubin 3.6 ± 17.5 mg/d, Alanine transaminase 51.5 ± IU/L 80.2 and gamma glutamyl transferase of 133.9 ± 220 IU/L. Post renal transplant HCV recurrence was documented in 2 (5%) recipients. Conclusion: This is first study to document excellent response of DAAs in renal transplant recipients who has been referred early for transplant. Thus, dialysis patients can undergo transplant after achieving end of treatment response.

Comparison of Frequency of Rapid Virological Response in Patients of Hepatitis C being Treated with 25-OH Vitamin D along with Sofosbuvir/Ribavirin with Those Treated with Sofosbuvir/Ribavirin only

Background: Hepatitis C is the leading cause of liver damage that lead to death if left untreated. Sofosbuvir has recently attained enormous success due to high rate of virological response. Recent studies have shown that addition of vitamin D to antiviral therapy improves the efficacy of treatment in patients with Hepatitis C. Objective: To compare the frequency of virological response in hepatitis C patients treated with vitamin D along with sofosbuvir plus ribavirin to those treated with sofosbuvir plus ribavirin only Study Design: Randomized-controlled-trial Place and Duration of Study: Department of Medicine, Pak Emirates Military Hospital, Rawalpindi from 1st November 2017 to 30th April 2018. Methodology: One hundred patients of chronic hepatitis C were included. Patients were randomly divided into two groups; group A receiving vitamin D along with sofosbuvir plus ribavirin and group B receiving sofosbuvir plus ribavirin therapy only. Patients were treated for 6 months and their RVR was monitored. Results: The mean age of patients in combination group was 39.0±12.92 years and in control group were 36.66±13.80years. After 4 weeks, RVR (no HCV RNA detected on PCR) was achieved in 31 (62%) cases in combination group while in 19 (38%) cases there was still HCV RNA present. In control group, RVR could be achieved in 18 (36%) cases while in 32 (64%) cases, RVR could not be achieved. The difference was significant between both groups (p<0.05). Conclusion: The addition of vitamin D can help in achieving RVR in >50% cases within 4 weeks. So addition of vitamin D in standard therapy may help to improve the quality of treatment. Keywords: Rapid virological response, Hepatitis C, 25-OH vitamin D, Sofosbuvir, Ribavirin

Effectiveness And Safety Of Direct Acting Antiviral Agents In Thalassaemic Patients With Chronic Hepatitis C.

Pakistan has the highest prevalence of Β-Thalassemia major in children and Chronic Hepatitis C (HCV) infection is a common transfusion transmitted infection. After the emergence of new generations of Antiviral drugs labelled as Direct Acting Antivirals (DAAs), substantial eradication of HCV has been reported as 90-95% with fewer side effects as compared to older regimen of Peginterferon with or without Ribavirin. The main objective of this study was to assess the Rapid virological response (RVR) at 4th week, End of treatment response (ETR) at 12th week and sustained viral response (SVR) at 24th week achieved by using direct acting antiviral and to assess their safety. Retrospective descriptive study was conducted from July 2018 to July 2020 at National Institute of Child Health. All β-thalassemia major paediatric patients with HCV infection and age between 3-14 years were included. Demographic data, liver function test, HCV PCR, and response of antiviral therapy was recorded and analyzed. Safety was determined by adverse effects reported in records and efficacy was documented by clearance of HCV-RNA to see ETR and SVR. Total 21 patients were treated. Mean age was 7.67±3yr and 12 (57%) were male. Mean weight was 19.3±3.2kg. RVR and ETR was achieved in all (100%) and SVR was achieved in 20/21 (95%) patients. Headache in 2(9.5%) and generalized body ache was found in 1 (4.25%) patient. Combined Sofosbuvir and Daclatasvir were found to be effective and safe for treating HCV in Thalassaemia Major Children.

Determination of Risk Factors Associated with the Failure of 12 Weeks of Direct-Acting Antiviral Therapy in Patients with Hepatitis C: A Prospective Study.

Introduction Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy.

Hepatitis C: Epidemiological, Clinical and Therapeutic Aspects in Dakar (Senegal)

Viral hepatitis C is a major public health problem. The aim of our work was to determine the epidemiological, diagnostic and treatment profiles of patients with HCV in Dakar (Senegal). We conducted a retrospective, descriptive, multicentre study between January 1, 2010, and December 31, 2019. We included 26 patients. The mean age of the patients was 53.5 years [28 - 70 years] and 46.2% were males. Of the 26 patients included, 7 (26.9%) were Senegalese, and the majority were from other African countries. Risk factors for contamination found were surgery in 11 patients (42.3%) and blood transfusion in 1 patient (3.8%). The mean viral load was 6.47 log IU/ml [4.26 - 7.26 log IU/ml]. Ten patients were infected by genotype 4. No patients were co-infected with HIV or HBV. Six patients (23.1% of patients) had significant fibrosis, of which five (19.2% of patients) were in the stage of cirrhosis. Twelve patients (46.2%) started treatment. Eleven were treatment-naïve and 1 did not respond to ribavirin-pegylated interferon-based therapy after 48 weeks. Ten cases of antiviral therapy were based on DAA and ribavirin-pegylated interferon in 2 patients. For the patients treated with peginterferon and ribavirin, a rapid virologic response was observed at 12 weeks in one patient, and the other patient was lost to follow-up. Among DAA-treated patients, 7 had sustained virologic responses at 12 weeks, 2 persisted, and 1 was lost to follow-up. Moderate thrombocytopenia and weight loss were observed in one patient receiving peginterferon and ribavirin. In our study, no patient died on treatment and no patients developed de novo HCC during or after DAA therapy. Conclusion: Viral hepatitis C is rare in Senegal. Despite the progress made in the therapeutic management of viral hepatitis C, it remains a challenge in Senegal. Indeed, DAAs are expensive and are not marketed, which makes them inaccessible to most patients.

Virologic outcomes among adults with HIV using integrase inhibitor-based antiretroviral therapy.

Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV). We included adults from the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen containing either InSTI or EFV between 2009 and 2016. We estimated differences in the proportion virologically suppressed up to 7 years of follow-up in observational intention-to-treat and per-protocol analyses. Of 15 318 participants, 5519 (36%) initiated an InSTI-based regimen and 9799 (64%) initiated the EFV-based regimen. In observational intention-to-treat analysis, 81.3% of patients in the InSTI group and 67.3% in the EFV group experienced virologic suppression at 3 months after ART initiation, corresponding to a difference of 14.0% (95% CI 12.4-15.6). At 1 year after ART initiation, the proportion virologically suppressed was 89.5% in the InSTI group and 90.2% in the EFV group, corresponding to a difference of -0.7% (95% CI -2.1 to 0.8). At 7 years, the proportion virologically suppressed was 94.5% in the InSTI group and 92.5% in the EFV group, corresponding to a difference of 2.0% (95% CI -7.3 to 11.3). The observational per-protocol results were similar to intention-to-treat analyses. Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment.

Vitamin D supplementation for chronic liver diseases in adults.

Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver diseases. To assess the beneficial and harmful effects of vitamin D supplementation in adults with chronic liver diseases. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and enquired experts and pharmaceutical companies as to additional trials. All searches were up to November 2020. Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence. We included 27 randomised clinical trials with 1979 adult participants. This review update added 12 trials with 945 participants. We assessed all trials as at high risk of bias. All trials had a parallel-group design. Eleven trials were conducted in high-income countries and 16 trials in middle-income countries. Ten trials included participants with chronic hepatitis C, five trials participants with liver cirrhosis, 11 trials participants with non-alcoholic fatty liver disease, and one trial liver transplant recipients. All of the included trials reported the baseline vitamin D status of participants. Participants in nine trials had baseline serum 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), whilst participants in the remaining 18 trials were vitamin D insufficient (less than 20 ng/mL). Twenty-four trials administered vitamin D orally, two trials intramuscularly, and one trial intramuscularly and orally. In all 27 trials, the mean duration of vitamin D supplementation was 6 months, and the mean follow-up of participants from randomisation was 7 months. Twenty trials (1592 participants; 44% women; mean age 48 years) tested vitamin D3 (cholecalciferol); three trials (156 participants; 28% women; mean age 54 years) tested vitamin D2; four trials (291 participants; 60% women; mean age 52 years) tested 1,25-dihydroxyvitamin D; and one trial (18 participants; 0% women; mean age 52 years) tested 25-hydroxyvitamin D. One trial did not report the form of vitamin D. Twelve trials used a placebo, whilst the other 15 trials used no intervention in the control group. Fourteen trials appeared to be free of vested interest. Eleven trials did not provide any information on clinical trial support or sponsorship. Two trials were funded by industry. We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on all-cause mortality (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.51 to 1.45; 27 trials; 1979 participants). The mean follow-up was 7 months (range 1 to 18 months). We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) (follow-up: 12 months); serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants); myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants); thyroiditis (RR 0.33, 95% CI 0.01 to 7.91; 1 trial; 68 participants); circular haemorrhoidal prolapse (RR 3.00, 95% CI 0.14 to 65.9; 1 trial; 20 participants); bronchopneumonia (RR 0.33, 95% CI 0.02 to 7.32; 1 trial 20 participants); and non-serious adverse events. The certainty of evidence for all outcomes is very low. We found no data on liver-related morbidity such as gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, ascites, or liver cancer. There were also no data on health-related quality of life. The evidence is also very uncertain regarding the effect of vitamin D versus placebo or no intervention on rapid, early, and sustained virological response in people with chronic hepatitis C. Given the high risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, vitamin D supplementation versus placebo or no intervention may increase or reduce all-cause mortality, liver-related mortality, serious adverse events, or non-serious adverse events in adults with chronic liver diseases. There is a lack of data on liver-related morbidity and health-related quality of life. Further evidence on clinically important outcomes analysed in this review is needed.