HCV-infected Hemodialysis Patients Research Articles

Occult hepatitis C virus infection in hemodialysis patients who achieved a sustained virological response to directly acting antiviral drugs: is it a concern?

PurposeHepatitis C virus infection is a major health problem in hemodialysis patients. Occult HCV infection is defined as the presence of HCV-RNA in hepatocytes or peripheral blood mononuclear cells without the detection of HCV-RNA in the serum. We aimed to evaluate the prevalence and predictors of occult HCV infection among hemodialysis patients after treatment with direct-acting antiviral agents.MethodsThis research is a cross-sectional study that included 60 HCV patients maintained on regular HD patients who achieved 24 weeks of sustained virological response after treatment with direct-acting antiviral agents. Real-time PCR was performed to detect HCV-RNA in peripheral blood mononuclear cells.ResultsHCV-RNA was detected in peripheral blood mononuclear cells of three patients (5%). Occult HCV infection cases were treated by Interferon/ribavirin before direct-acting antiviral agents and two of them had raised pre-treatment alanine aminotransferase levels. Logistic regression analyses revealed that high pre-treatment viral load and raised pre-treatment alanine aminotransferase were associated with an increased risk of occult HCV infection with p value of 0.041 and 0.029, respectively.ConclusionsOccult HCV infection in hemodialysis patients who achieved sustained virological response after treatment with direct-acting antiviral agents may occur, and this may necessitate dual testing for HCV in both serum and peripheral blood mononuclear cells to ensure viral clearance.Clinical trials registrationClinicalTrials.gov NCT04719338.

Study the response of Qurevo (ombitasvir, paritaprevir, and ritonavir) in end-stage renal disease patients with hepatitis C virus

BackgroundOut of the 185 million people infected with hepatitis C virus (HCV) worldwide according to the World Health Organization (WHO), Egypt had the highest prevalence of HCV reaching 13% of its population with an estimated number of 12 million people. The prevalence of HCV infection among hemodialysis (HD) patients ranged from 6 to 60%. HD patients have an increased overall mortality risk if they have chronic HCV when compared to those without HCV infection. Treatment of HCV with the new direct-acting antiviral agent (DAA) therapy Qurevo “ombitasvir/paritaprevir/ritonavir” with ribavirin in ESRD was approved in many countries compared to traditional HCV treatment that faced restrictions in the setting of chronic kidney disease (CKD).Aim of the studyTo evaluate the efficacy and safety of Qurevo/ribavirin regimen in HCV-infected HD patients.Patients and methodsA prospective cohort study evaluated the outcome of 12-week ombitasvir (NS5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir with ribavirin combination therapy for 50 HCV-infected HD patients, over a period of 15 months from December 2016 to February 2018. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) and after 24 weeks of therapy (SVR24).ResultsThe SVR12 rate was 96% (48/50); 2 patients (4%) were non-responders to treatment at SVR12, and another 2 (4%) were relapsers after SVR12. As regards the adverse events, the most frequent were fatigue/asthenia in 44 patients (88%) and worsening anemia (Hb dropped to < 10 g/dl) in 42 patients (84%). GIT upset occurred in 10 patients (20%), sleep disorders in 8 patients (16%), decreased appetite in 8 patients (16%), respiratory distress in 6 patients (12%), headache and dizziness in 6 patients (12%), and muscle spasms in 4 patients (8%). Itching (pruritus) occurred in 3 patients (6%). Death occurred in 4 patients (8%) after SVR24 most probably not due to DAA but may be due to myocardial infarction, pulmonary edema, severe hypotension on hemodialysis sessions, and shock due to blood loss in retroperitoneal hematoma following peritoneal dialysis not related to DAA therapy. Hepatic decompensation, hypersensitivity (angioedema), teratogenicity, and drug interactions did not occur in any patient (0%). Other events occurred in 11 patients (22%). They were parenchymal liver changes in ultrasound at the end of therapy after being normal before therapy (in 3 patients), thrombocytopenia, increased alkaline phosphatase, hiccough, deterioration of hypertension, urinary tract infection, lower limb cellulitis, vaginal bleeding, and chest infection (in 1 patient each). SVR12 was achieved in 100% of patients who had to stop or modify the ribavirin dose; this means that ribavirin absence did not affect the SVR in these patients.ConclusionOur results confirm the efficacy of Qurevo “ombitasvir/paritaprevir/ritonavir” with ribavirin combination therapy in ESRD patients (on regular hemodialysis) with HCV infection with anemia as the most frequent adverse event.

MO831: Hepatitis Virus Infection in End-Stage Kidney Disease Patients Treated by Haemodialysis in Romania After 5 Years of Active Antiviral Therapy, Revisited

Abstract BACKGROUND AND AIMS After 5 years from the previous national prospective observational study and a modern antiviral program, we aimed to re-evaluate the prevalence of hepatitis virus infection and its impact in end-stage kidney disease (ESKD) patients treated with haemodialysis (HD) in Romania. METHOD A total of 1516 ESKD patients (909 men and 608 women, median age 60.1 ± 12.9 years) treated with chronic HD in twelve centres from all the historical regions of Romania have been assigned to this study. Data regarding their HBs Ag and anti-HCV antibodies were recorded. RESULTS HBsAg was positive now in 5% (n = 76) patients and it was significantly lower than in 2015 (9.5%, n = 57), P = 0.0001, anti-HCV antibodies were detected in 11.5% (175) versus 27.3% (n = 164), P &amp;lt; 0.0001; and 1.5% (n = 24) versus 5% (n = 30) were positive for both HBV and HCV infection, P &amp;lt; 0.0001. When we split the cohort between the historical regions of Romania (Moldavia 426 patients, Muntenia 321 patients, Transylvania 769 patients), in Moldavia (Eastern Romania), the prevalence of both HBV and HCV infection was significantly lower than 2015 (4.2% versus 16.8%; P &amp;lt; 0.001, respectively for HCV 20% versus 42.9%; P &amp;lt; 0.0001). The prevalence of HBV infection in Muntenia region was 3.1% versus 9.9% in 2015 (P = 0.003), but Muntenia recorded a significant decrease in the prevalence of HCV infection in haemodialysis patients from 2015 until now (9.6% versus 36.4%, P &amp;lt; 0.001). Data from Transylvania are similar, there are no significant differences in terms of HBV infection (3.7% versus 4.7% in 2015; P = 0.455) but the prevalence of HCV infection is significantly &amp;lt;2015 (7.6% versus 13.9%; P = 0.001). CONCLUSION This study shows that the systematically nationwide applied measures for significant reduction of infection risk and antiviral therapy significantly decreased HV infection prevalence in HD patients in Romania.

Updated Evidence on the Epidemiology of Hepatitis C Virus in Hemodialysis.

Prevalence rates of HCV infection are decreasing in hemodialysis units of most developed countries; however, nosocomial transmission of HCV continues to occur in the hemodialysis setting, not only in the emerging world. According to the Dialysis Outcomes and Practice Patterns Study (DOPPS, 2012–2015), the prevalence of HCV among patients on regular hemodialysis was 9.9%; in incident patients, the frequency of HCV was approximately 5%. Outbreaks of HCV have been investigated by epidemiologic and phylogenetic data obtained by sequencing of the HCV genome; no single factor was retrieved as being associated with nosocomial transmission of HCV within hemodialysis units. Transmission of HCV within HD units can be prevented successfully by full compliance with infection control practices; also, antiviral treatment and serologic screening for anti-HCV can be useful in achieving this aim. Infection control practices in hemodialysis units include barrier precautions to prevent exposure to blood-borne pathogens and other procedures specific to the hemodialysis environment. Isolating HCV-infected hemodialysis patients or using dedicated dialysis machines for HCV-infected patients are not currently recommended; reuse of dialyzers of HCV-infected patients should be made, according to recent guidelines. Randomized controlled trials regarding the impact of isolation on the risk of transmission of HCV to hemodialysis patients have not been published to date. At least two studies showed complete elimination of de novo HCV within HD units by implementation of strict infection control practices without isolation practices. De novo HCV within hemodialysis units has been independently associated with facility HCV prevalence, dialysis vintage, and low staff-to-patient ratio. Antiviral treatment of HCV-infected patients on hemodialysis should not replace the implementation of barrier precautions and other routine hemodialysis unit procedures.

Effect of direct-acting antiviral medications on α-fetoprotein, IL-10, and VEGF as predictors of HCC in HCV-infected hemodialysis patients

Background Hepatitis C virus (HCV) is considered one of the major causes of chronic liver disease in Egypt. HCC is a common complication of liver cirrhosis; it is the most common malignant neoplasm among Egyptian males and the second one in Egyptian females. The aim of the current study is to investigate the effect of our national DAA treatment protocol on the serum levels of IL-10, and VEGF in HCV infected hemodialysis patients. Patients and methods This study was carried out in Alexandria, Egypt. 85 subjects were enrolled in this study and divided into three groups. The first group was the control group, it included 25 healthy subjects, the second group included 50 hemodialysis patients infected with chronic HCV G4, they received DAAs therapy for 12 weeks, and the third group comprises 10 HCV chronic hemodialysis patients with HCC. Results Sustained viral response (SVR12) had been achieved in 43 patients (86%) in group two. There was a clear increase in the serum level of IL 10, and VEGF in HCV+HD and HCV+HD+HCC from control (P&lt;0.001) Logistic regression analysis showed that serum IL10, and VEGF could be utilized as predictor marker of (HCV+HD and HCV+HD+HCC) group from control and for HCV+HD from control ROC analysis detected 90% sensitivity and 92 % specificity to discriminate between healthy subjects and HCV+HD+HCC group. Conclusion Study demonstrated that high levels of IL-10 and VEGF in both HCV+HD and HCV+HD+HCC (higher levels) patients. Attainment of SVR12 with combination of ombitasvir paritaprevir, and ritonavir plus ribavirin in HCV+HD is potential without major side effects, and it was achieved regardless the serum levels of IL-10 or VEGF.

Aminotransferase-to-platelet ratio index and Fibrosis-4 index score predict hepatic fibrosis evaluated by transient hepatic elastography in hepatitis C virus-infected hemodialysis patients.

This study aimed to evaluate the performance of aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 index (FIB-4) in chronic kidney disease stage 5D HCV-infected patients compared to transient hepatic elastography (TE) as the gold standard. Hemodialysis HCV-infected patients submitted to TE (FibroScan, Echosens, Paris, France) had APRI and FIB-4 calculated. Based on the best area under receiver operating characteristic curve (AUROC) for significant fibrosis and cirrhosis, APRI and FIB-4 cutoffs were determined and their performances were compared. Seventy patients were included. Both APRI and FIB-4 showed good performance for identifying significant fibrosis [AUROC = 0.73, 95% confidence interval (CI) 0.61-0.83 and 0.79, 95% CI 0.68-0.88; P < 0.05] and cirrhosis [AUROC = 0.82, 95% CI 0.71-0.90 and 0.85, 95% CI 0.75-0.93; P < 0.05]. APRI ≤ 0.25 excluded significant fibrosis with negative predictive value (NPV) of 81.8% and APRI > 0.61 confirmed it with a positive predictive value (PPV) of 81.8%. Similarly, NPV for FIB-4 ≤ 0.60 regarding significant fibrosis was 90.9%. NPV for cirrhosis for APRI ≤ 0.42 or FIB-4 ≤ 1.40 was 97%. However, APRI > 0.73 or FIB-4 > 2.22 showed a modest PPV of 60 and 70% to confirm cirrhosis, respectively. APRI and FIB-4 are simple, non-expensive scoring systems with good accuracy to assess fibrosis in HCV-infected hemodialysis patients, mainly excluding both significant fibrosis or cirrhosis and may be an alternative to TE in the evaluation of this population.

Hepatitis C core antigen testing to diagnose active hepatitis C infection among haemodialysis patients

BackgroundHepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost.MethodsWe conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.ResultsWe recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients.ConclusionsAlthough HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

Clinical outcomes of hepatitisC virus elimination using glecaprevir and pibrentasvir in hemodialysis patients: A multicenter study.

The incidence of hepatitisC virus (HCV) infection is much higher in hemodialysis patients than that in healthy individuals. The prognosis of hemodialysis patients with HCV infection is poorer than that without HCV infection. Therefore, antiviral intervention is pivotal for HCV infection in hemodialysis patients. Recent evaluations of the pangenotypic regimen of glecaprevir/pibrentasvir show that it is highly effective and safe for HCV-infected hemodialysis patients. However, a few reports showed that the effect of HCV elimination by glecaprevir/pibrentasvir improved liver dysfunction or anemia. The aim of the present study was to determine clinical outcomes after HCV elimination using the glecaprevir/pibrentasvir regimen in HCV-infected hemodialysis patients. This study was a retrospective, six-center study conducted in Japan, in which 24 hemodialysis patients with HCV genotype1-2 treated with glecaprevir/pibrentasvir were recruited. Blood examinations were performed at end of treatment (EOT), and at 3, 6, and 12months post-treatment during the 12-month follow-up period. The overall sustained virologic response rate was 100% (24/24). During the DAA treatment period, adverse events were observed in 20.8% of patients (5/24), and pruritus was the most frequently observed in 12.5% (3/24). Interestingly, we observed an improved control of anemia after EOT with a significant increase in hemoglobin levels. In addition, total bilirubin was diminished, and platelet counts and albumin, total cholesterol, and alpha-fetoprotein levels remained unchanged after EOT in hemodialysis patients. Furthermore, erythropoietin concentration was not increased after EOT. HCV elimination using glecaprevir/pibrentasvir treatment might be a major breakthrough for the control of anemia in hemodialysis patients.

Level of health behaviours of HCV infected patients treated with dialysotherapy

Introduction. Hepatitis C virus (HCV) infection is one of the greatest epidemiological risks worldwide (3% infected globally). Dialysis patients are the group at high risk of infections transmitted via blood, are often infected with HCV virus, and suffer from acute or chronic hepatitis. Anti-health behaviours enhance the process of liver fibrosis. The objective of the study was recognition of the level of health behaviours in HCV-infected haemodialysis patients. Materials and Method. The study included 149 adult patients on dialysis infected with HCV, hospitalized in two dialysotherapy centres: the Military Medical Institute and Clinical Hospital in Warsaw. In the study there also participated family members and acquaintances of students of the Higher School in Radom. The study was conducted during the first half of 2017 by a diagnostic survey, using research instrument Health Behaviours Inventory (HBI) according to Z. Juczyński. The questionnaire concerned: eating habits, prophylactic behaviours, everyday health practice, and positive psychological attitude.Results. 73.8% of respondents presented a high level of health behaviours (7–10 sten scores), mediocre - 19.5% (5–6 sten scores), and low – 6.7% (1–4 sten scores). The highest mean value evidencing health promoting life style of the patients was observed with respect to prophylactic behaviours (4.0±0.4), while eating habits and health practices were on the level 3.9±0.4-0.5. The lowest value indicating the least pro-health behaviours concerned positive psychological attitude (3.7±0.4). Conclusions. The overall rate of health behaviours of dialysed HCV patients was high. The dominant category was prophylactic behaviours, whereas the lowest results were obtained with respect to positive psychological attitude. The respondents infected with HCV for longer than 10 years, mainly males, those aged 60-84, with primary vocational education, living in rural areas, and non-active occupationally, had the greatest needs for psychotherapy. It is necessary to provide psychological support for dialysis patients infected with HCV.

EXPLOSION OF HEPATITIS B AND C VIRUSES AMONG HEMODIALYSIS PATIENTS AS A RESULT OF HEMODIALYSIS CRISIS IN YEMEN

The United Nations considers the situation in Yemen to be the worst humanitarian crisis in the world. In the midst of this, the fastest-spreading viral infection among HD patients was recorded. Therefore, this cohort study based in HD unit was conducted in Dhamar Hospital to estimate the outbreak of hepatitis B and C viruses among dialysis patients during the dialysis crisis in Yemen. All the patients who continuous go through hemodialysis from January 2018 to December 2018 and they were free from HBV/HCV infections at the start of the study (January 2018) were included. Patients who were discontinued from dialysis before the end of the year due to death or relocation were excluded from the study. Patients were tested for anti-HCV antibodies and hepatitis B surface antigen (HBsAg) at study start (January 2018) then at the end of the follow up (December 2018). The individual’s data were collected in a pre-designed questionnaire including; demographic data of HD frequency, and laboratory results. The study included 202 patients, 20 (9.9%), 18 (8.9%) and 6 (2.97%) were found to be infected with HCV, HBV and Co-HBV/HCV infection respectively. There was significant association between rise of HCV rate and younger patient age, and high frequency of dialysis. In conclusion, the prevalence of HBV and HCV infection and HBV / HCV infection in hemodialysis patients in our surroundings one year after HD was extremely common and lead to disaster for HD patients. This catastrophe is due to the lack or limited availability of materials and tools for dialysis and laboratory materials for virus tests due to the unfair siege on Yemen from Saudi Arabia and the United Arab Emirates and the closure of Sana'a airport, which is the only entrance to medicines.&#x0D; Peer Review History: &#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 5.5/10&#x0D; Average Peer review marks at publication stage: 8.5/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Mohammed Sadeg Abdullah Al-Awar&#x0D; Affiliation: Physiology &amp; Histopathology Queen Arwa University and Amran University, Yemen&#x0D; E-mail: momed.sadeg@gmail.com&#x0D; &#x0D; Name: Dr. Heba-Tallah Ahmed Mohamed Moustafa &#x0D; Affiliation: Heliopolis University Cairo, Egypt&#x0D; E-mail: anasweety2003@yahoo.com&#x0D; Comments of reviewer(s): &#x0D;

Factors Correlating to the Development of Hepatitis C Virus Infection in Hemodialysis Patients-Findings Mainly from Asiatic Populations: A Systematic Review and Meta-Analysis.

Hemodialysis is an effective replacement therapy for chronic renal failure patients. In recent decades, the number of hemodialysis patients has grown rapidly and some measures for preventing blood-borne diseases have been implemented, but hepatitis C virus (HCV) infection remains a significant problem. The meta-analysis published in 2009 on HCV infection-related factors was based on localized study objects, and some additional studies have been published since 2009; however, the contribution of these factors remains under dispute. Our study pooled the odds ratios (ORs) or mean standard deviations (MDs) with 95% confidence intervals (CIs) and analyzed sensitivity using Review Manager 5.1 software (5.1 version Copenhagen: The Nordic Cochrane Centre; 2011) by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Spearman correlation analysis was performed using the SPSS package. In our meta-analysis, 1715 HCV-infected hemodialysis patients and 7093 non-HCV-infected hemodialysis patients from 44 studies were analyzed. The pooled ORs with 95% CIs were: histories of blood transfusion, 4.30 (3.11, 5.96); weekly hemodialysis times > 2, 6.00 (3.25, 11.06); kidney transplantation, 5.80 (3.95, 8.52); hemodialysis units > 2, 6.90 (2.42, 19.68); shared hemodialysis devices, 5.00 (2.35, 10.65); and drug addiction, 4.73 (1.54, 14.47). The pooled MDs with 95% CIs were duration of hemodialysis (months) 27.48 (21.67, 33.30). There was a positive correlation between duration of hemodialysis and the HCV infection rate (p < 0.01). Hemodialysis patients, especially from Asia, with shared hemodialysis devices, hemodialysis units > 2, blood transfusion, kidney transplantation, and drug addiction were at increased risk of HCV infection. The HCV infection rate increased with the duration of hemodialysis. High-risk hemodialysis patients should be monitored and receive timely screening.

Safety and efficacy of glecaprevir and pibrentasvir in Japanese hemodialysis patients with genotype 2 hepatitis C virus infection.

Until recently, interferon-free anti-hepatitis C virus (HCV) therapy for genotype 2 (GT2) HCV-infected hemodialysis patients was an unfulfilled medical need. Recent clinical trials of glecaprevir and pibrentasvir (G/P) for hemodialysis patients showed high efficacy and safety; however, the number of GT2 HCV-infected patients, especially Asian patients, was limited and most of them were treated with a 12-week regimen. In this prospective multicenter study, we aimed to investigate the efficacy and safety of G/P in Japanese hemodialysis patients with GT2 HCV infection. Twenty-seven Japanese hemodialysis patients with GT2 HCV infection who were started on with 8- or 12-week G/P regimen between November 2017 and June 2018 were included and followed up for around 12weeks after treatment completion. Among the 27 included patients, 13 non-liver cirrhosis (LC) and direct-acting antivirals (DAAs)-naïve patients were treated with 8weeks of G/P and 14 patients with LC (n = 13) or history of failure of DAAs (n = 1) were treated with a 12-week regimen. The overall sustained virological response at 12weeks after treatment completion (SVR 12) was 96.3% (26/27). All patients with 8weeks of treatment achieved SVR12. Two patients discontinued the therapy at 2 and 11weeks after treatment initiation. The patient who discontinued at 2weeks due to pruritus alone failed to respond to G/P. No patients experienced lethal adverse events during the therapy, and the most common adverse event was pruritus. An 8- or 12-week G/P regimen is highly effective and safe in GT2 HCV-infected hemodialysis patients.

2223. Effect of Direct-Acting Antivirals in Hemodialysis Patients with HCV: Real-Life Data

BackgroundHepatitis C virus (HCV) infection is widespread in hemodialysis patients worldwide. Studies of the effectiveness of new generation DAAs in the treatment of HCV infection in hemodialysis patients are limited.We investigated the effectiveness of DAAs in hemodialysis patients with HCV infection.MethodsTwenty-three HCV-positive treatment naïve or experienced (IFN/pegIFN±RBV) hemodialysis patients were enrolled.Three patients were excluded for not attending follow-ups regularly, and the data for 20 patients were included. Patients’ demographic, virological, and genotypic characteristics, liver fibrosis status, DAAs started, and sustained virological responses at the 12th week (SVR12) were recorded. DAA regimens based on the treatments patients were using and potential drug interactions.Patients completing treatment were followed for 12 weeks for SVR.ResultsThe mean age of the patients was 57.8 (±10.5). Ninety percent were men; 55% were treatment-experienced and 45% were treatment naïve. Ninety percent were noncirrhotic and 10% had compensated cirrhosis. Of the treatment-experienced patients, 45.5% were nonresponder and 54.5% were relapsed (Table 1). Eighteen patients with Genotype 1b were treated with paritepravir-ritonavir-ombitasvir-dasabuvir(ProD) for 12 weeks, one patient with Genotype 4 received ProD+ribavirin for 12 weeks, and one patient with Genotype 2 received sofosbuvir+ribavirin for 24 weeks. HCVRNA was negative on the 4th week in 85% of patients, and was negative in all patients on the 12th week, apart from the patient receiving the sofosbuvir+ribavirinregimen. At the end of treatment, HCVRNA was negative in all patients, and the SVR12 rate was 100%. Patients’ treatment responses were independent of previous treatments, liver fibrosis status, and hemodialysis duration. No marked side effects or complications were observed, apart from sleeplessness in one patient (Table 1).ConclusionOur study data confirm that new generation DAAs in hemodialysis patients provide high SVR and are well tolerated, as in patients other than those with chronic kidney disease. Achieving cure in hemodialysis patients is important in terms of preventing cross-contamination and of global elimination of HCV. Disclosures All authors: No reported disclosures.

Rationale for treatment of hepatitis C virus infection in end-stage renal disease patients who are not kidney transplant candidates.

Hepatitis C virus (HCV) infection is a common problem in patients treated with maintenance hemodialysis (HD) and is associated with an increased morbidity and mortality and lower quality of life. The major causes of HCV-associated mortality are liver and cardiovascular-related death. HCV-infected HD patients have a higher prevalence of inflammation-related metabolic and vascular diseases, leading to high rates of cardiovascular mortality in patients with end-stage renal disease. In the current era of highly effective direct-acting antiviral regimens, HCV treatment may also confer hepatic, cardiovascular and other morbidity and mortality benefits even to dialysis-dependent patients who do not qualify for kidney transplantation. Currently, the most accepted regimens in this patient population include elbasvir/grazoprevir and glecaprevir/pibrentasvir.

Current Status of Hepatitis C Virus-Infected Maintenance Hemodialysis Patients in Japan.

Complete recovery using interferon therapy in Japanese hepatitis C virus (HCV)-infected dialysis patients is difficult to achieve because >70% of the HCV genotypes observed in Japan are type 1. In 2016, new direct-acting antiviral drugs against HCV genotype 1 were reported to be effective and safe for HCV-infected hemodialysis patients. Although new direct antiviral therapy has become available, no large-scale studies evaluating the status of HCV infection in Japanese hemodialysis patients have been conducted since 2007. Therefore, we conducted a questionnaire survey to determine the current status of HCV infection in patients. Our results indicated that the HCV antibody prevalence was 5.02%, and HCV RNA prevalence was 72.3%. Genotype testing revealed that 62.1% of patients had HCV genotype 1. New direct antiviral therapy may improve the survival of Japanese HCV-infected dialysis patients.

Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan.

Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV). Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events. Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n=2), rash (n=1), and HCC (n=1); all of these achieved SVR12. This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).

A COMPARATIVE STUDY OF EFFICACY BETWEEN THIRD GENERATION ELISA AND FOURTH GENERATION TRI-DOT TEST TO DETECT SEROPREVALENCE OF HEPATITIS-C INFECTION IN PATIENTS ON HAEMODIALYSIS

Introduction: The detection of anti-HCV antibodies is based on the use of third generation Enzyme Immunoassay (EIA) that detects antibodies directed against various HCV epitopes. HCV TRI-DOT test is a rapid, protein A immunofiltration assay for the qualitative detection of anti HCV antibodies in serum or plasma with a sensitivity of 100% and specificity of 91.5%. The study was conducted to compare the efficacy between 3rd generation ELISA and 4th generation TRI-DOT test to detect the seroprevalence of HCV and to assess the risk factors associated with HCV infection in the patients who are on haemodialysis. Material and Methods: The study was conducted to compare the efficacy between 3rd generation ELISA and 4th generation TRI-DOT test to detect the seroprevalence of HCV and to assess the risk factors associated with HCV infection in the patients who are on haemodialysis. Sera of 150 adult CRF patients on &gt;2 months haemodialysis tested by TRIDOT test and then by ELISA. Demographic data of all included patients reviewed for risk factors. Statistical analysis was performed by the SPSS program for Windows, version 17.0. Results: Out of 150 cases, 17 were found seropositive for HCV by TRI-DOT test and 16 were found seropositive for HCV by ELISA. One hundred and one patients were males and 49 were females. Maximum positive patients fell in 36-55 years age group. Duration of haemodialysis, mean blood transfusion, number of dialysis centre changed found almost double in HCV reactive patients than in non reactive. Sensitivity of HCV TRI-DOT is 100% and specificity is 99.3%, positive predictive value is 94.1% and negative predictive value is 100% in comparison of ELISA. Conclusion: Seroprevalence of Hepatitis C in haemodialysis patients in our institute is 10.7%. Risk factors for HCV infection in haemodialysis patients included duration of haemodialysis, number of haemodialysis centre changed, number of blood transfusion unit transfused, male gender and middle age. The sensitivity of HCV TRI-DOT is equal to HCV ELISA but the specificity is slightly less.

Bacteremia in Hemodialysis Patients With Hepatitis C

BackgroundHepatitis C virus (HCV) infection and bacteremia are common comorbidities in hemodialysis patients. A specific relationship between HCV infection and bacteremia has not been defined; however, there is evidence of immune compromise in both HCV-infected and uremic patients, suggesting that this group may be at higher risk for infection. MethodsWe investigated risk factors and mortality associated with bacteremia in HCV-infected hemodialysis patients from the United states Renal Data system. ResultsDuring the 4-year study period, HCV was present in 2.1% of 355,084 patients initiating hemodialysis. When compared with the total population, the rate of bacteremia was significantly higher in patients with HCV (38.3% versus 21.8%). The adjusted relative risk (RR) for bacteremia was higher in HCV versus all patients (relative risk, 95% confidence interval [CI]) in the presence of methicillin-resistant Staphylococcus aureus infection (2.64, CI: 2.58-2.70 versus 2.32, CI: 2.27-2.38), HIV (1.93, CI: 1.85-2.02 versus 1.86, CI: 1.77-1.95) urinary tract infection (1.79, CI: 1.77, 1.82 versus 1.64, CI: 1.61-1.67) and cirrhosis (1.49, CI: 1.451.54 versus 1.29, CI: 1.25-1.34). The hazard ratio (95% CI) for death was higher in HCV versus all patients at 1.69 (CI: 1.58-1.81) versus 1.54 (CI: 1.53-1.56). ConclusionsThese data indicate that several clinical covariates increase the risk of bacteremia in hemodialysis patients, with the magnitude of that risk being further increased by HCV infection. Improving outcomes in HCV-infected hemodialysis patients will likely be dependent on aggressive diagnosis and treatment of both HCV and bacteremia.

Higher Endogenous Erythropoietin Levels in Hemodialysis Patients with Hepatitis C Virus Infection and Effect on Anemia

Study for influence of chronic Hepatitis C (HCV) on endogenous erythropoietin production and on anemia in dialysis patients remains inconclusive. We hypothesize that chronic hemodialysis patients with co-existing Hepatitis C infection will have higher hemoglobin levels than chronic hemodialysis patients without hepatitis C infection. Secondly, we hypothesize that the higher hemoglobin levels will be associated with higher erythropoietin levels. Therefore we conducted a cross-sectional study of chronic hemodialysis patients with and without hepatitis C infection and evaluated associations with hemoglobin and erythropoietin levels. Our primary outcome was level of hemoglobin. Secondary outcome included association of hemoglobin and erythropoietin levels. 57 chronic hemodialysis patients (33 male, 24 female, mean age 46.05 ± 12.7 years) were included. The mean time spent on hemodialysis was 7.16 ± 6.2 years. None of the patients received any recombinant EPO therapy. Biochemical analyses include ALT, AST, Albumin, C-Reactive Protein, cholesterol levels and complete blood counts. Iron status of patients (transferrin saturation and serum ferritin levels) and parathyroid hormone were measured. Endogenous EPO serum levels were measured by a standardized enzyme-linked immunoassay. 23 of the hemodialysed patients (38.5%) were HCV (+). There was no difference in age, sex, distribution of primary renal diseases, iron status, albumin, C-Reactive-Protein and parathyroid hormone levels between HCV (+) and (-) patients. Mean duration time on dialysis was higher in HCV (+) than HCV (-) patients. Hemoglobin levels were similar between study groups. However serum endogenous erythropoietin levels were significantly higher in HCV (+) patients than HCV (-) patients (19.6 ± 10 mUI/ml vs 7.8 ± 7.7 mUI/ml, p = 0.03). No correlation has been found between the severity of anemia and HCV infection. However, HCV (+) hemodialysed patients had higher serum endogenous erythropoietin levels as compared to HCV (-) patients. Further studies are needed to clarify why high endogenous erythropoietin level does not improve anemia in HCV infected hemodialysis patients.

Hepatitis C infection in hemodialysis patients: A review.

Hepatitis C virus (HCV)-related liver disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) who is treated with dialysis or kidney transplantation (KT). The survival rate for HCV-infected renal transplant recipients is better than that for HCV-infected hemodialysis patients on transplant waiting lists. Early diagnosis and treatment HCV infection prior to KT prevents complications post-transplantation and reduces mortality. In addition to screening for anti-HCV antibodies and detecting HCV RNA, percutaneous liver biopsy is particularly valuable for assessing the stage of liver damage in HCV-infected patients, because the stage of fibrosis is important determining optimal treatment for HCV. Studies have been demonstrated that with conventional interferon (IFN) monotherapy or pegylated IFN monotherapy are similar efficacy and safety in HCV-infected hemodialysis patients. Sustained viral responses (SVRs) with these monotherapies have ranged approximately 30% to 40%. Limited reports support the use of IFN and ribavirin combination therapy as antiviral treatment for ESRD patients or patients on hemodialysis. Ribavirin can be started at low dose and careful monitoring for side effects. Patients that show SVR after treatment are strong candidates for KT. It is also generally accepted that ESRD patients with decompensated cirrhosis and portal hypertension should be referred to the liver transplant team for consideration of combined liver-KT.