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Liu CH, Kao JH. Pan-genotypic direct-acting antivirals for patients with hepatitis C virus infection and chronic kidney disease stage 4 or 5. Hepatol Int 2022; 16:1001-1019. [PMID: 35876967 PMCID: PMC9309604 DOI: 10.1007/s12072-022-10390-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/03/2022] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) infection is a major health problem with significant clinical and economic burdens in patients with chronic kidney disease (CKD) stage 4 or 5. Current guidelines recommend pan-genotypic direct-acting antivirals (DAAs) to be the first-line treatment of choice for HCV. This review summarizes the updated knowledge regarding the epidemiology, natural history, public health perspectives of HCV in patients with CKD stage 4 or 5, including those on maintenance dialysis, and the performance of pan-genotypic DAAs in these patients. The prevalence and incidence of HCV are much higher in patients with CKD stage 4 or 5 than in the general population. The prognosis is compromised if HCV patients are left untreated regardless of kidney transplantation (KT). Following treatment-induced HCV eradication, patient can improve the health-related outcomes by maintaining a long-term aviremic state. The sustained virologic response (SVR12) rates and safety profiles of pan-genotypic DAAs against HCV are excellent irrespective of KT. No dose adjustment of pan-genotypic DAAs is required across CKD stages. Assessing drug-drug interactions (DDIs) before HCV treatment is vital to secure on-treatment safety. The use of prophylactic or preemptive pan-genotypic DAAs in HCV-negative recipients who receive HCV-positive kidneys has shown promise in shortening KT waiting time, achieving excellent on-treatment efficacy and safety, and maintaining post-KT patient and graft survival. HCV elimination is highly feasible through multifaceted interventions, including mass screening, treatment scale-up, universal precautions, and post-SVR12 reinfection surveillance.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, 7 Chung-Shan South Road, Taipei, 10002 Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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2
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Yeh H, Chiang CC, Yen TH. Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges. World J Gastroenterol 2021; 27:4104-4142. [PMID: 34326614 PMCID: PMC8311541 DOI: 10.3748/wjg.v27.i26.4104] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/17/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.
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Affiliation(s)
- Hsuan Yeh
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
| | - Chun-Cheng Chiang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
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3
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Progress in hepatitis C virus management in chronic kidney disease. Curr Opin Nephrol Hypertens 2021; 30:493-500. [PMID: 34054074 DOI: 10.1097/mnh.0000000000000729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW The current review highlights advances in the use of direct-acting antiviral (DAA) agents in the treatment of hepatitis C virus (HCV) in chronic kidney disease (CKD) stages G4-5, end-stage renal disease, and kidney transplantation. The use of DAA to facilitate kidney transplantation of HCV negative recipients with kidneys from HCV-infected donors and in the management of HCV-related cryoglobulinemia are also reviewed. RECENT FINDINGS DAA treatment results in rates of viral clearance (sustained virological response or SVR) of 90-100% in all studied CKD populations, comparable to SVR rates in the general population. DAA treatment allows safe and effective transplantation of HCV viremic kidneys into uninfected recipients. SUMMARY The high SVR results achieved with DAA allow successful treatment of previously under-treated CKD populations, and encouraged innovative interventions such as the use of HCV-infected donor kidneys to uninfected kidney transplant recipients.
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Toyoda H, Kikuchi K, Tsuruta Y, Hiraoka A, Tsuji K, Tanaka J. Utility of serological tumor biomarkers for surveillance of hepatocellular carcinoma in patients undergoing dialysis. Nephrol Dial Transplant 2021; 36:1097-1103. [PMID: 33009910 DOI: 10.1093/ndt/gfaa165] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 05/19/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Patients undergoing dialysis are at risk of hepatocellular carcinoma (HCC) and preferably should undergo HCC surveillance. We investigated the utility of HCC tumor markers for HCC surveillance in patients undergoing dialysis. METHODS Three serum markers specific for HCC, namely alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), were measured in dialysis patients with and without a diagnosis of HCC (n = 60 and 507, respectively). The predictive value of each marker and that of a diagnostic score (GALAD score) based on patient age and gender as well as the same three markers were evaluated by receiver-operating characteristic (ROC) analysis, as well as sensitivity and specificity. RESULTS AFP, DCP and the GALAD scores showed high predictive values for HCC, with areas under the ROC curve of >0.85. This effectiveness remained when focusing on small HCC (≤3 cm or ≤2 cm) or early-stage HCC (Stage I), as well as after propensity score matching of background characteristics of HCC and non-HCC patients. In particular, DCP and GALAD score had excellent predictive abilities for HCC. CONCLUSIONS Measuring serum tumor markers for HCC can serve as a complement to imaging studies in the surveillance of HCC in patients undergoing dialysis, and reduce the likelihood of advanced HCC at detection and diagnosis.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kan Kikuchi
- Division of Nephrology, Shimoochiai Clinic, Tokyo, Japan
| | | | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Weinfurtner K, Reddy KR. Hepatitis C viraemic organs in solid organ transplantation. J Hepatol 2021; 74:716-733. [PMID: 33212088 DOI: 10.1016/j.jhep.2020.11.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
Although rates of organ donation and solid organ transplantation have been increasing over the last few decades, demand for organs still greatly exceeds supply. Several strategies have been utilised to increase organ supply, including utilisation of high-risk (e.g. HCV antibody-positive) donors. In this context, organs from HCV antibody-positive donors have been used in recipients with chronic HCV since the early 1990s. Recently, transplantation of HCV-viraemic organs into HCV-naïve recipients has garnered significant interest, owing to the development of safe and highly effective direct-acting antivirals and increased experience of treating HCV in the post-transplant setting. Preliminary studies based largely in the US have shown excellent outcomes in kidney, liver, heart, and lung transplantation. This practice has the potential to significantly increase transplantation rates and decrease waitlist mortality; however, intentionally transmitting an infectious disease to recipients has important practical and ethical implications. Further, the generalisability of the US experience to other countries is limited by significant differences in HCV-viraemic donor populations. This review summarises the current data on this practice, discusses barriers to implementation, and highlights areas that warrant further study.
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Affiliation(s)
- Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
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Morishita A, Ogawa C, Moriya A, Tani J, Yoneyama H, Fujita K, Oryu M, Senoo T, Takaguchi K, Masaki T. Clinical outcomes of hepatitis C virus elimination using glecaprevir and pibrentasvir in hemodialysis patients: A multicenter study. Hepatol Res 2020; 50:557-564. [PMID: 31883211 DOI: 10.1111/hepr.13482] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/24/2019] [Accepted: 12/26/2019] [Indexed: 12/22/2022]
Abstract
AIM The incidence of hepatitis C 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. METHODS This study was a retrospective, six-center study conducted in Japan, in which 24 hemodialysis patients with HCV genotype 1-2 treated with glecaprevir/pibrentasvir were recruited. Blood examinations were performed at end of treatment (EOT), and at 3, 6, and 12 months post-treatment during the 12-month follow-up period. RESULTS 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. CONCLUSIONS HCV elimination using glecaprevir/pibrentasvir treatment might be a major breakthrough for the control of anemia in hemodialysis patients.
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Affiliation(s)
- Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kanoji, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Makoto Oryu
- Department of Internal Medicine, Kagawa Saiseikai Hospital, Takamatsu, Japan
| | - Tomonori Senoo
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
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7
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Zjacic Puljiz D, Mestrovic A, Zaja I, Tonkic A, Grgurevic I, Duplancic D, Delic Jukic IK, Ljutic D, Puljiz Z. Impact of hemodialysis on liver stiffness measured with real-time two-dimensional shear wave elastography. Wien Klin Wochenschr 2019; 133:96-101. [PMID: 31781940 DOI: 10.1007/s00508-019-01577-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 10/30/2019] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND AIMS The impact of hemodialysis on liver stiffness is still unclear. The aim of the study was to assess liver fibrosis by real-time two-dimensional shear wave elastography (RT 2D-SWE) and to quantify the influence of net fluid withdrawal on liver stiffness during one hemodialysis session. The second aim was to investigate the influence of systolic blood pressure and time spent on dialysis (in years) on liver stiffness measurements. METHODS This before/after hemodialysis (HD) study in a group of end stage renal disease (ESRD) patients was carried out with patients on regular HD. Measurements of liver stiffness were done using RT 2D-SWE directly before and after a hemodialysis session. RESULTS In this study 27 patients with mean age 69.4 ± 14.75 years were included. Mean net fluid withdrawal volume per session was 2874.07 ± 778.35 ml. Mean pre-HD and post-HD liver stiffness measurements were 8.15 kPa (95% confidence interval, CI 7.61-8.68) and 6.70 kPa (95% CI 6.10-7.30 kPa), respectively. Mean liver stiffness reduction was 1.448 ± 1.14 kPa. The amount of fluid removed correlated with the decline in liver stiffness values after HD (ρ = 0.523, P = 0.003). There was a positive but statistically not significant correlation between time spent in HD and liver stiffness (ρ = 0.151, P = 0.623) CONCLUSION: Liver stiffness significantly declined after one session of HD. The change in liver stiffness was strongly correlated with the amount of net fluid withdrawal. Random liver stiffness measurements (LSM) by RT 2D-SWE does not precisely show the degree of fibrosis, Furthermore, it is presumed that postdialysis liver stiffness values likely reflect the real degree of liver fibrosis.
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Affiliation(s)
| | - Antonio Mestrovic
- Department of Gastroenterology, University Hospital Split, 21 000, Split, Croatia
| | - Ivan Zaja
- Department of Gastroenterology, University Hospital Split, 21 000, Split, Croatia
| | - Ante Tonkic
- Department of Gastroenterology, University Hospital Split, 21 000, Split, Croatia.
| | - Ivica Grgurevic
- Department of Gastroenterology, University Hospital Dubrava, Zagreb, Croatia
| | - Darko Duplancic
- Department of Cardiology, University Hospital Split, Split, Croatia
| | | | - Dragan Ljutic
- Department of Nephrology and Dialysis, University Hospital Split, Split, Croatia
| | - Zeljko Puljiz
- Department of Gastroenterology, University Hospital Split, 21 000, Split, Croatia
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8
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Nkansah C, Serwaa D, Osei-Boakye F, Owusu-Ampomah R. Seroprevalence and trend of hepatitides among blood donors in a district hospital in Ghana: a nine-year retrospective, descriptive cross-sectional study. J Immunoassay Immunochem 2019; 41:71-83. [PMID: 31635519 DOI: 10.1080/15321819.2019.1682601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Hepatitis infections are among the greatest threats to human existence and survival and hence poses a serious public health challenge in blood donation. This study aimed to determine the prevalence and trend of hepatitis infections among voluntary blood donors at Nkenkaasu District Hospital. A retrospective study of voluntary blood donors' records from January 2010 to December 2018 was conducted. Data on the donors' age, sex and serum HBsAg and Hepatitis C virus results were retrieved from the Laboratory's register and analyzed with SPSS version 16.0. Out of the 3306 total donors, the seroprevalence of hepatitis C infection was 11.7% and hepatitis B infection was 10.3%. Only 1.4% of the donors were co-infected with both pathogens and 82.7% had no infection. Rhesus blood group had a significant association with Hepatitis B (P = 0.005). As at 2010, both hepatitis infections had the same prevalence (73), from 2011 to 2018 both showed inconsistent trends. The relatively high seroprevalence of hepatitis infections identified from the study poses a greater threat to blood safety. Extensive screening of blood donors using standard techniques is highly recommended to ensure that recipients receive safe blood.
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Affiliation(s)
- Charles Nkansah
- Department of Medical Laboratory Technology, Faculty of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.,Clinical Laboratory Department, Nkenkaasu Government Hospital, Nkenkaasu, Ghana
| | - Dorcas Serwaa
- Pan African University (PAULESI), Department of Obstetrics and Gynecology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Felix Osei-Boakye
- Department of Medical Laboratory Technology, Faculty of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.,Clinical Laboratory Department, Mankranso District Hospital, Mankranso, Ghana
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9
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Abstract
BACKGROUND The prevalence and clinical epidemiological profile of hepatitis C virus (HCV) infection have changed over time. AIM This study aimed to evaluate these changes in renal transplant recipients (RTx) comparing two different decades. MATERIALS AND METHODS RTx with HCV referred to RTx from 1993 to 2003 (A) and from 2004 to 2014 (B) were studied retrospectively. The demographic and clinical characteristics and different outcomes were compared between groups A and B. Variables that were statistically different were tested for inclusion in a multivariate Cox proportional hazard model predicting patient survival within the group. RESULTS Among 11 715 RTx, the prevalence of HCV was 7% in A and 4.9% in B. In the more recent period (B), the mean age was older (46.2 vs. 39.5 years), with more males (72 vs. 60.7%), larger number of deceased donors (74 vs. 55%), higher percentage of previous RTx (27 vs. 13.7%), less frequent history of blood transfusion (81 vs. 89.4%), lower prevalence of hepatitis B virus coinfection (4.7 vs. 21.4%), and higher percentage of cirrhotic patients (13 vs. 5%). Patients of group B more frequently underwent treatment of HCV (29 vs. 9%), less frequently used azathioprine (38.6 vs. 60.7%) and cyclosporine (11.8 vs. 74.7%), and more frequently used tacrolimus (91 vs. 27.3%). In the outcomes, graft loss showed no difference between periods; however, decompensation was more frequent (P = 0.007) and patients' survival was lower in the more recent period (P = 0.032) compared with the earlier one. CONCLUSION The profile of RTx with HCV has changed over the last 20 years. Despite a decrease in the prevalence of HCV, new clinical challenges have emerged, such as more advanced age and a higher prevalence of cirrhosis.
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10
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Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int 2019; 22 Suppl 1:S61-S70. [PMID: 29694723 DOI: 10.1111/hdi.12643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus (HCV) infection is prevalent in patients with kidney disease including transplant candidates and recipients. It is associated with increased morbidity and mortality in end-stage renal disease patients and also increases the risk of allograft rejection and decreases allograft and patient survival post-transplant. Newly developed direct acting antivirals have revolutionized the way HCV is treated. Whether patients are treated before or after kidney transplantation, the cure rates with direct acting antivirals are >90%. Great debate has formed revolving the optimal timing to treat kidney transplant candidates. On the one hand, treatment before transplantation decreases early post-transplant complications related to HCV. On the other, postponing treatment until after transplantation opens the possibility of transplanting a kidney from a HCV positive donor, which is associated with shorter waiting time and improved organ utilization by expanding the organ donor pool. Most patients living in an area where waiting time is reduced by accepting an HCV positive kidney would benefit by the strategy of treatment post-transplantation, but this decision needs to be individualized in a patient-by-patient basis given that there are special circumstances (i.e., severe HCV-related extrahepatic manifestations, availability of live donors, etc.) in which treatment before transplant might be preferred.
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Affiliation(s)
- Abraham Cohen-Bucay
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA.,Division of Nephrology and Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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11
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Dejman A, Ladino MA, Roth D. Treatment and management options for the hepatitis C virus infected kidney transplant candidate. Hemodial Int 2019; 22 Suppl 1:S36-S44. [PMID: 29694726 DOI: 10.1111/hdi.12646] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
A substantial body of literature has unequivocally established that prevalent hepatitis C virus infection in chronic kidney disease (CKD), end stage renal disease (ESRD) and kidney transplant recipients is associated with a negative impact on patient survival. As a consequence of remarkable work that explained the details of the hepatitis C virus (HCV) genome, a class of drugs referred to as the direct-acting antiviral (DAA) agents were developed that targeted specific key sites in viral replication. Large clinical trials in the HCV-infected general population followed soon after that demonstrated cure rates exceeding 95%. Treatment paradigms have been further refined and expanded to populations of patients that were initially excluded from the large pivotal trials. This includes the CKD and ESRD patients for whom there are now safe and effective DAAs available as well. In this context, the focus of decision making has shifted from initially demonstrating safety and efficacy to now identifying which patient should receive therapy and at what point in their CKD/ESRD journey. The specific issue of timing of treatment is particularly relevant to the HCV-infected ESRD patient who is being considered for kidney transplantation. The option of treating with DAAs prior to the transplant or alternatively delaying therapy and treating in the posttransplant period will be influenced by several factors, including patient preference, the extent of liver injury, the availability of a living or deceased donor, and more recently the option of transplanting a kidney from HCV-positive donor. The latter has been associated with the advantage of shortened waiting times and expansion of the organ donor pool. The optimal timing and choice of therapy will be the result of a decision that has been individualized for each patient as a consequence of a process of clear communication involving the patient, primary care physician, nephrologist, gastroenterologist (GI)/hepatologist, and local transplant center.
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Affiliation(s)
- Adriana Dejman
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Marco A Ladino
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - David Roth
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida, USA
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12
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Abstract
Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.
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Affiliation(s)
- Abraham Cohen-Bucay
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.,Nephrology Department, American British Cowdray Medical Center, Mexico City, 05300, Mexico
| | - Craig E Gordon
- Division of Nephrology, Tufts Medical Center, Boston, MA, 02111, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, MA, 02118, USA
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13
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Cottone C, Bhamidimarri KR. Evaluating CKD/ESRD patient with hepatitis C infection: How to interpret diagnostic testing and assess liver injury. Semin Dial 2019; 32:119-126. [PMID: 30599462 DOI: 10.1111/sdi.12760] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Chronic hepatitis C (CHC) is the most common cause of infection related deaths in USA according to Central Disease Control and Prevention (CDC) report in 2016. Hepatitis C is a blood borne virus and is common in chronic kidney disease (CKD) and in hemodialysis (HD) dependent patients. A majority of patients with CHC could remain asymptomatic and are still undiagnosed. Early detection of CHC and linkage of infected patients to care for evaluation and treatment is the standard of care as emphasized by Kidney Disease Improving Global Outcome (KDIGO) and American Association for the Study of Liver Disease- Infectious Disease Society of America (AASLD-IDSA) practice guidelines. Historically, the management of hepatitis C virus (HCV)-infected CKD patients, including those on dialysis and in the peri-transplant setting, was a challenge. However, the evolution of various liver assessment tools, HCV tests, therapies and treatment strategies in the recent years has catalyzed a paradigm change in this area. This review provides an update on evaluating methodology, diagnostic tests and the various assessment tools for liver fibrosis pertaining to the CKD/HD patient infected with HCV.
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Affiliation(s)
- Claudia Cottone
- Department of Internal Medicine, Chicago Medical School at Northwestern Medicine - McHenry Hospital, McHenry, Illinois
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14
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Fabrizi F, Messa P. The epidemiology of HCV infection in patients with advanced CKD/ESRD: A global perspective. Semin Dial 2018; 32:93-98. [PMID: 30536715 DOI: 10.1111/sdi.12757] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver disease in patients with chronic kidney disease (CKD) is most commonly due to hepatitis C virus (HCV) and contributes to increased rates of mortality. Among the pre-dialysis population, the estimated prevalence of anti-HCV positivity is based on few, limited-size studies. In hemodialysis patients however, HCV remains very prevalent despite large declines in seropositivity rates in dialysis facilities in developed countries after preventive measures were adopted in the 1990s. Recent surveys indicate that the HCV seropositivity prevalence ranges from 1.4%-28.3%, and 4.7%-41.9%, among maintenance dialysis patients in developed and developing countries respectively. Although the full extent of dialysis unit-associated HCV transmission is unknown, outbreaks continue to occur, regardless of health system infrastucture. According to US Centers for Disease Control data, over 50% of health care-associated HCVoutbreaks reported from 2008 to 2015 occurred within dialysis facilities. Strict adherence to infection control procedures and routine serologic screening plays a pivotal role in preventing transmission of HCV within hemodialysis units, even in the setting of low HCV prevalence. With the advent of directly acting antivirals, cure of HCV-infected patients on maintenance hemodialysis will help reduce transmission within units and further lower the frequency of HCV infection.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milan, Italy
| | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milan, Italy.,University School of Medicine, Milan, Italy
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15
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Maduell F, Belmar L, Ugalde J, Laguno M, Martínez-Rebollar M, Ojeda R, Arias M, Rodas L, Rossi F, Llovet LP, González LN, Mallolas J, Londoño MC. Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 42:164-170. [PMID: 30293914 DOI: 10.1016/j.gastrohep.2018.07.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 07/23/2018] [Accepted: 07/29/2018] [Indexed: 12/13/2022]
Abstract
INTRODUCTION In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. PATIENTS AND METHODS This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. RESULTS All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. CONCLUSION HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.
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Affiliation(s)
- Francesc Maduell
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Lara Belmar
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Jésica Ugalde
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Montserrat Laguno
- HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - María Martínez-Rebollar
- HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Raquel Ojeda
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Marta Arias
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Lida Rodas
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Florencia Rossi
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Laura-Patricia Llovet
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | | | - Josep Mallolas
- HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Maria-Carlota Londoño
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
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16
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Butt AA, Ren Y, Puenpatom A, Arduino JM, Kumar R, Abou-Samra AB. Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study. Aliment Pharmacol Ther 2018; 48:35-43. [PMID: 29797514 DOI: 10.1111/apt.14799] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 03/08/2018] [Accepted: 04/18/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era. AIM To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. METHODS We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity. RESULTS Among 13 663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4-5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4-5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4-5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%-38% of persons with baseline eGFR ≥60 mL/min/1.73 m2 , but in only 0%-6% with CKD4-5. Grade 3/4 anaemia was more frequent in persons with CKD4-5, but ribavirin co-administration did not appear to affect this. CONCLUSIONS SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.
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Affiliation(s)
- A A Butt
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.,Weill Cornell Medical College, New York, NY, USA.,Weill Cornell Medical College, Doha, Qatar.,Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Y Ren
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
| | | | | | - R Kumar
- Merck & Co., Inc., North Wales, PA, USA
| | - A-B Abou-Samra
- Weill Cornell Medical College, New York, NY, USA.,Weill Cornell Medical College, Doha, Qatar.,Department of Medicine, Hamad Medical Corporation, Doha, Qatar
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17
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HEPATIC ENZYMES CHANGES IN CHRONIC KIDNEY DISEASE PATIENTS- A NEED FOR MODIFIED REFERENCE VALUES. ACTA ACUST UNITED AC 2018. [DOI: 10.14260/jemds/2018/439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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18
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Diagnostic Accuracy of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis 4 Scores in Predicting Advanced Liver Fibrosis in Patients with End-stage Renal Disease and Chronic Viral Hepatitis: Experience from Pakistan. J Transl Int Med 2018; 6:38-42. [PMID: 29607303 DOI: 10.2478/jtim-2018-0008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.
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19
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Fabrizi F, Messa P, Martin P. Transmission of hepatitis C virus infection in hemodialysis: Current concepts. Int J Artif Organs 2018; 31:1004-16. [DOI: 10.1177/039139880803101204] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A variety of epidemiological data provides evidence for the occurrence of nosocomial transmission of hepatitis C virus (HCV) infection to hemodialysis (HD) patients. The most important factor implicated in HCV transmission between patients treated in the same dialysis unit is cross-contamination from supplies and surfaces as a result of failure of staff to follow infection control procedures. Parts of the HCV genome are highly variable and lend themselves to fingerprinting of each isolate using nucleic acid testing (NAT) and sequencing. This approach has permitted investigation of possible transmission routes within HD units. A systematic review of molecular virology papers revealed transmission of HCV via internal fluid pathways of the dialysis machines in a minority of reports only. Dialyzer reuse was not identified as a risk factor for HCV acquisition in multicenter databases. No randomized controlled trials exist on the impact of isolation on the risk of transmission of HCV to hemodialysis patients. A Belgian prospective multicenter study showed a reduction from 1.4% to 0% in the annual incidence of seroconversion for HCV without any isolation measures, by implementation of strict infection control procedures designed to prevent transmission of blood-borne pathogens, including HCV. However, an isolation policy for HCV-infected dialysis patients should be considered in dialysis units where nosocomial transmission of HCV persists despite reinforcement and audit of hygienic precautions for hemodialysis. Routine audit precautions (general and for dialysis machines) are recommended on a regular basis within HD units.
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Affiliation(s)
- F. Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milano - Italy
- Center for Liver Diseases, School of Medicine, University of Miami, Miami, Florida - USA
| | - P. Messa
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milano - Italy
| | - P. Martin
- Center for Liver Diseases, School of Medicine, University of Miami, Miami, Florida - USA
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20
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Li Vecchi M, La Spada E, Li Vecchi V, Montalto G. Hepatitis C Virus Infection in Hemodialyzed Patients. Int J Artif Organs 2018; 30:100-7. [PMID: 17377904 DOI: 10.1177/039139880703000204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in non-infected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders. Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.
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Affiliation(s)
- M Li Vecchi
- Department of Nephrology, University of Palermo, Palermo, Italy
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21
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Epidemiology of hepatitis C virus among hemodialysis patients in the Middle East and North Africa: systematic syntheses, meta-analyses, and meta-regressions. Epidemiol Infect 2017; 145:3243-3263. [PMID: 28988562 PMCID: PMC9148758 DOI: 10.1017/s0950268817002242] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We aimed to investigate hepatitis C virus (HCV) epidemiology among hemodialysis (HD) patients in the Middle East and North Africa (MENA). Our data source was an HCV biological measures database populated through systematic literature searches. Descriptive epidemiologic syntheses, effects meta-analyses and meta-regressions, and genotype analyses were conducted. We analyzed 289 studies, including 106 463 HD patients. HCV incidence ranged between 0 and 100% as seroconversion risk, and between 0 and 14·7 per 1000 person-years as incidence rate. The regional pooled mean estimate was 29·2% (95% CI: 25·6–32·8%) for HCV antibody positive prevalence and 63·0% (95% CI: 55·4–70·3%) for the viremic rate. Region within MENA, country income group, and year of data collection were associated with HCV prevalence; year of data collection adjusted odds ratio was 0·92 (95% CI: 0·90–0·95). Genotype diversity varied across countries with four genotypes documented regionally: genotype 1 (39·3%), genotype 2 (5·7%), genotype 3 (29·6%), and genotype 4 (25·4%). Our findings showed that one-third of HD patients are HCV antibody positive and one-fifth are chronic carriers and can transmit the infection. However, HCV prevalence is declining. In context of growing HD patient population and increasing HCV treatment availability, it is critical to improve standards of infection control in dialysis and expand treatment coverage.
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22
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Toyoda H, Hiraoka A, Tada T, Michitaka K, Takaguchi K, Tsuji K, Itobayashi E, Takizawa D, Hirooka M, Koizumi Y, Ochi H, Joko K, Kisaka Y, Shimizu Y, Tajiri K, Tani J, Taniguchi T, Toshimori A, Fujioka S, Kumada T. Characteristics and Prognosis of Hepatocellular Carcinoma in Japanese Patients Undergoing Dialysis. Ther Apher Dial 2017; 21:465-472. [PMID: 28880488 DOI: 10.1111/1744-9987.12563] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 04/09/2017] [Accepted: 04/17/2017] [Indexed: 02/05/2023]
Abstract
Patients with end-stage renal disease who are undergoing dialysis may be at high risk of developing hepatocellular carcinoma (HCC). We investigated the characteristics and prognosis of HCC in patients undergoing dialysis in Japan. Patients characteristics, progression of HCC at diagnosis, and survival rates after diagnosis were compared between 108 HCC patients undergoing dialysis and 526 non-dialysis patients followed up at liver center. The comparisons were also performed after adjusting for patient age, gender, platelet count, and etiology using propensity-score matching. HCC was more advanced in patients undergoing dialysis than in non-dialysis controls. The 3- and 5-year survival rates of patients undergoing dialysis were 56.3% and 38.3%, respectively, which were lower than those of non-dialysis controls (66.5% and 52.7%, respectively, P = 0.0026). The results were the same after propensity score matching (P = 0.0014). In Japan, HCC was more advanced at diagnosis in patients undergoing dialysis in comparison to HCC in patients at liver centers, resulting in a lower survival rate after diagnosis.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Daichi Takizawa
- Department of Gastroenterology, Isesaki Municipal Hospital, Isesaki, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabolism, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabolism, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Koji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | | | - Yuko Shimizu
- Department of Gastroenterology, Ozu City Hospital, Ozu, Japan
| | - Kazuto Tajiri
- Department of Gastroenterology and Hematology, University of Toyama, Toyama, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Kagawa University, Takamatsu, Japan
| | - Tatsuya Taniguchi
- Department of Gastroenterology and Oncology, Tokushima University School of Biomedical Sciences, Tokushima, Japan
| | - Akiko Toshimori
- Department of Internal Medicine, Saiseikai Imabari Hospital, Imabari, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
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Potential Hepatoprotective Role of Galectin-3 during HCV Infection in End-Stage Renal Disease Patients. DISEASE MARKERS 2017; 2017:6275987. [PMID: 28487598 PMCID: PMC5405569 DOI: 10.1155/2017/6275987] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Revised: 02/24/2017] [Accepted: 02/26/2017] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus infection (HCV), one of the greatest causes of liver disease, is a frequent complication in patients with end-stage renal disease (ESRD) on dialysis. ESRD is defined as decreased glomerular filtration and also accompanied by impaired function of the immune system. Galectin-3 is a β-galactoside-binding lectin, involved in various biological processes including pathogenesis of chronic renal disease. The aim of our study was to estimate disease severity in ESRD HCV+ patients and analyze the serum concentrations of IL-1β, IL-4, IL-23, and IL-6; anti-HCV antibodies; and galectin-3. Also, we attempted to determine potential correlation between galectin-3 level and parameters of disease severity ALT and AST. Our results showed decreased levels of ALT and AST (p = 0.00), demonstrating less liver destruction in ESRD HCV+ patients in comparison to HCV+ patients. Increased levels of IL-6 (p = 0.03) implicate a hepatoprotective role of IL-6 in these patients. Also, level of galectin-3 (p = 0.00) in the serum of ESRD HCV+ patients was higher than that of HCV+ patients. This alteration was accompanied with negative correlation between galectin-3 and AST and ALT, respectively (p = 0.029; p = 0.033). The presence of increased systemic levels of IL-6 and Gal-3 in ESRD HCV+ patients may be an attempt to counteract or limit ongoing proinflammatory processes and to downregulate chronic inflammation, suggesting the new aspects of HCV infection in ESRD patients.
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Aggarwal A, Yoo ER, Perumpail RB, Cholankeril G, Kumari R, Daugherty TJ, Lapasaran AS, Ahmed A. Sofosbuvir Use in the Setting of End-stage Renal Disease: A Single Center Experience. J Clin Transl Hepatol 2017; 5:23-26. [PMID: 28507922 PMCID: PMC5411352 DOI: 10.14218/jcth.2016.00060] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 01/10/2017] [Accepted: 01/21/2017] [Indexed: 12/20/2022] Open
Abstract
Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15 treatment courses, patients completed the designated treatment duration. One patient was treated twice and developed SVR-12 with the retreatment. One patient was lost to follow-up and counted as a non-responder. Premature discontinuations were not due to DAA-related adverse effects. There were no reports of severe adverse effects or drug interactions. Conclusion: We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.
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Affiliation(s)
- Avin Aggarwal
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Eric R. Yoo
- Department of Medicine, University of Illinois College of Medicine, Chicago, IL, USA
| | - Ryan B. Perumpail
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Radhika Kumari
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Tami J. Daugherty
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | | | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
- *Correspondence to: Aijaz Ahmed, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite #210, Stanford, CA 94304, USA. Tel: +1-650-498-5691, Fax: +1-650-498-5692, E-mail:
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25
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Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev 2017; 16:523-541. [PMID: 28286108 DOI: 10.1016/j.autrev.2017.03.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 02/26/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.
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Affiliation(s)
- Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Dario Roccatello
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Klinik für Rheumatologie Oberarzt, Ratzeburger Allee 160 (Haus 40), 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room, 32 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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The Prevalence of HCV Infection in Hemodialysis Population and Compared ELISA and PCR Methods for Detecting of HCV Infection. Nephrourol Mon 2017. [DOI: 10.5812/numonthly.45144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Equal 3-Year Outcomes for Kidney Transplantation Alone in HCV-Positive Patients With Cirrhosis. Int Surg 2016; 100:142-54. [PMID: 25594655 DOI: 10.9738/intsurg-d-13-00231.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Kidney transplantation alone in clinically compensated patients with cirrhosis is not well documented. Current guidelines list cirrhosis as a contraindication for kidney transplantation alone. This is an Institutional Review Board-approved retrospective study. We report our experience with a retrospective comparison between transplants in hepatitis C virus-positive (HCV(+)) patients without cirrhosis and HCV(+) patients with cirrhosis. All of the patients were followed for at least a full 3-year period. All of the deaths and graft losses were recorded and analyzed using Kaplan-Meier methodology. One- and three-year cumulative patient survival rates for noncirrhotic patients were 91% and 82%, respectively. For cirrhotic patients, one- and three-year cumulative patient survival rates were 100% and 83%, respectively (P = NS). One- and three-year cumulative graft survival rates censored for death were 94% and 81%, and 95% and 82% for the noncirrhosis and cirrhosis groups, respectively (P = NS). Comparable patient and allograft survival rates were observed when standard kidney allograft recipients were analyzed separately. This study is the longest follow-up document in the literature showing that HCV(+) clinically ompensated patients with cirrhosis may undergo kidney transplantation alone as a safe and viable practice.
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 105] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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Mogahed EA, Abdelaziz H, Helmy H, Ghita H, Abdel Mawla MA, Hassanin F, Fadel FI, El-Karaksy H. Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis. J Interferon Cytokine Res 2016; 36:681-688. [PMID: 27656950 DOI: 10.1089/jir.2016.0019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 μg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.
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Affiliation(s)
- Engy A Mogahed
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Hanan Abdelaziz
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Heba Helmy
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Haytham Ghita
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | | | - Fetouh Hassanin
- 3 Faculty of Pharmacy, Misr International University , Cairo, Egypt
| | - Fatina I Fadel
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Hanaa El-Karaksy
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
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Isnard Bagnis C, Cacoub P. Hepatitis C Therapy in Renal Patients: Who, How, When? Infect Dis Ther 2016; 5:313-27. [PMID: 27388502 PMCID: PMC5019972 DOI: 10.1007/s40121-016-0116-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Indexed: 02/07/2023] Open
Abstract
Renal patients are overexposed to hepatitis C virus (HCV) infection. Hepatitis C virus infection may induce renal disease, i.e., cryoglobulinemic membrano-proliferative glomerulopathy and non-cryoglobulinemic nephropathy. Hepatitis C virus impacts general outcomes in chronic kidney disease, dialysis or transplanted patients. Hepatitis C virus infection is now about to be only part of their medical history thanks to new direct acting antiviral drugs exhibiting as much as over 95% of sustained virological response. All HCV-infected patients potentially can receive the treatment. Control of the virus is associated with better outcomes in all cases, whatever the severity of the hepatic or renal disease. This article focuses on HCV-induced renal diseases, the reciprocal impact of HCV infection on the renal outcome and renal status in liver disease, use of new direct-acting antiviral drugs with dosage adaptations and the most recent safety data.
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Affiliation(s)
- Corinne Isnard Bagnis
- Department of Nephrology AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. .,UPMC Univ Paris 06, Paris, France.
| | - Patrice Cacoub
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 75005, Paris, France.,INSERM, UMR_S 959, 75013, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.,Sorbonne University, UPMC Univ Paris 06, UMR 7211, Paris, France
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Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol 2016; 51:741-7. [PMID: 26872889 DOI: 10.1007/s00535-016-1174-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 01/18/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis. METHODS The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction. RESULTS The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups. CONCLUSIONS The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.
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Nazario HE, Ndungu M, Modi AA. Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min. Liver Int 2016; 36:798-801. [PMID: 26583882 DOI: 10.1111/liv.13025] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 11/06/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Treating chronic hepatitis C (CHC) in patients with end-stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC-infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR) <30 ml/min is unknown. We evaluated the safety and efficacy of sofosbuvir and simeprevir in this special patient population. METHODS All (n = 17) patients in the analysis had ESRD on HD or GFR <30 ml/min. All received sofosbuvir 400 mg daily and simeprevir 150 mg daily, without ribavirin for 12 weeks. Safety and efficacy data were collected; including SVR4 and SVR12 data for all patients after completing therapy. RESULTS In this 17 patient cohort, eight (47%) were cirrhotic, four (24%) had stage three liver fibrosis and 13 (76%) were genotype 1A. All 17 have completed 12 weeks of therapy. Treatment was overall well tolerated with no treatment discontinuations reported. Four (24%) patients reported mild adverse events (AE). These AEs were insomnia (n = 2), headache (n = 1), nausea (n = 1) and worsening anaemia requiring blood transfusion (n = 1). All 17 patients reached post-treatment week-12 follow-up, and achieved SVR12 or virological cure (100% SVR12). CONCLUSIONS Daily, full dose of sofosbuvir plus simeprevir for 12 weeks of therapy appears to be well tolerated in patients with ESRD on HD or GFR <30 ml/min. Most common AEs resembled those of healthier CHC patients without significant renal impairment. The cure rates obtained in this cohort treated with sofosbuvir and simeprevir are dramatically superior to any previous treatment regimen studied & published in this special patient population.
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Affiliation(s)
- Hector E Nazario
- Division of Hepatology, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA
| | - Milka Ndungu
- Division of Hepatology, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA
| | - Apurva A Modi
- Division of Hepatology, Liver Consultants of Texas, Baylor All Saints Medical Center, Fort Worth, TX, USA
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Cacoub P, Comarmond C, Domont F, Savey L, Desbois AC, Saadoun D. Extrahepatic manifestations of chronic hepatitis C virus infection. Ther Adv Infect Dis 2016; 3:3-14. [PMID: 26862398 DOI: 10.1177/2049936115585942] [Citation(s) in RCA: 115] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, and Inflammation Immunopathology Biotherapy Department (DHU i2B), Paris, France
| | | | | | - Léa Savey
- Sorbonne Universités, UPMC Univ Paris 06, and Inflammation Immunopathology Biotherapy Department (DHU i2B), Paris, France
| | | | - David Saadoun
- Sorbonne Universités, UPMC Univ Paris 06, and Inflammation Immunopathology Biotherapy Department (DHU i2B), Paris, France
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Zhang K, Wang L, Lin G, Li J. Is Anti-Hepatitis C Virus Antibody Level an Appropriate Marker to Preclude the Need for Supplemental Testing. Intervirology 2016; 58:310-7. [PMID: 26785210 DOI: 10.1159/000441474] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 10/04/2015] [Indexed: 12/09/2022] Open
Abstract
OBJECTIVES In the present study, we aimed to determine whether signal-to-cutoff (S/Co) ratios of reactive anti-HCV samples could be used as a basis for avoiding the need for supplemental testing in our study population. METHODS We analyzed 901 anti-HCV-positive sera from 8 institutions in China. The Ortho VITROS anti-HCV assay and Monolisa Plus anti-HCV version 2 were used as screening assays to detect anti-HCV antibodies. Recombinant immunoblot assay (RIBA) and quantitative tests for HCV RNA were performed to validate confirmed HCV infection status. RESULTS Receiver operating characteristic curve analyses demonstrated that 41.5% (114/275) of true-positive samples with S/Co ratios ≤3.0 would be missed and the negative predictive value was 63.9 and 87.06%, using real-time polymerase chain reaction (RT-PCR) and RIBA as supplemental testing, respectively. 29.8% (90/302) of those who tested positive by RIBA samples were missed when only RT-PCR was used as supplemental testing. CONCLUSIONS We determined that very low anti-HCV levels (S/Co ≤3.0), as determined by chemiluminescence immunoassay, was not an appropriate marker to preclude the need for supplemental testing in our study population. A screening strategy employing a secondary HCV antibody assay using different HCV antigens from the first assay as the supplemental testing method should be studied further. The immunoblot assay, as a supplemental testing method, is still necessary.
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Affiliation(s)
- Kuo Zhang
- National Center for Clinical Laboratories, Beijing Hospital, Beijing, PR China
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Lack of impact of hepatitis C virus infection on graft survival after kidney transplantation--a Portuguese single-center experience. Transplant Proc 2016; 47:926-32. [PMID: 26036487 DOI: 10.1016/j.transproceed.2015.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis C virus infection (HCV) is a common problem among kidney transplant (KT) recipients. The long-term burden of HCV infection on graft survival after kidney transplantation is controversial. METHODS We performed a retrospective study including all renal transplant recipients with HCV infection (n = 34) compared with a control group (n = 80). The prevalence of HCV infection was 2.7%. The median follow-up period was 134 months (11 years). Graft survival and associated risk factors were assessed by means of Cox proportional hazard analysis. RESULTS We found that HCV-positive patients remained on dialysis for longer periods (P = .001) and received transplants at a younger age (P = .03). Actuarial graft survival rates at 1, 5, and 10 years after KT were, respectively, 94.1%, 78.1%, and 66.9%, in the HCV-positive group and 94.9%, 89.1%, and 80.4% in the HCV-negative group. Graft survival did not differ significantly between groups (P = .154). A higher incidence of major cardiovascular disease among HCV-positive patients (P = .004) was noted. Multivariate analysis showed that HCV infection was not an important risk factor for graft loss (adjusted hazard ratio, 2.810; 95% confidence interval, 0.925-8.541; P = .069). Among the HCV-positive population, immunosuppression with cyclosporine or azathioprine conveyed better graft survival. CONCLUSIONS Our findings suggest that the long-term impact of HCV infection on graft survival after KT is not significant. KT remains a safe and effective modality of renal replacement in HCV-infected patients with end-stage renal disease.
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Abou Rached A, El Khoury L, El Imad T, Geara AS, Jreijiry J, Ammar W. Incidence and prevalence of hepatitis B and hepatitis C viruses in hemodialysis patients in Lebanon. World J Nephrol 2016; 5:101-107. [PMID: 26788469 PMCID: PMC4707162 DOI: 10.5527/wjn.v5.i1.101] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Revised: 08/09/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the incidence and the prevalence of hepatitis B and C viral infections in patients on hemodialysis (HD) across Lebanon.
METHODS: We reviewed the data registry at the Lebanese Ministry of Public Health where records of monthly hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) serology are reported from 60 affiliated HD centers across Lebanon. All patients who were on HD or who started HD between October 2010 and July 2012 were included in the study. Patients from seven HD centers were excluded due to inadequate and incomplete results reporting. During the selected period, HBsAg and HCV serology were available for 3769 patients from 53 HD centers distributed at all Lebanese governorates. The prevalence was calculated by dividing the number of patients with positive HBsAg or HCV serology to the total number of patients. The Incidence was calculated by dividing the number of newly acquired infection to number of patients-years (p-y). Incidence rates at different governorates were compared to each other using two tailed Z test and a P value of < 0.05 was considered significant.
RESULTS: Sixty out of 3769 HD patients were found to have positive HBS Ag and 177 out of 3769 were positive for HCV Antibodies. The prevalence of hepatitis B virus (HBV) and HCV in HD patients across Lebanon was 1.6%, and 4.7%, respectively. The comparison of prevalence according to geographic distribution could not be done accurately due to the frequent shift of patients between dialysis centers at different governorates. The incidence rate was 0.27 per 100 p-y for HBV and 0.37 per 100 p-y for HCV. There was no significant difference concerning the incidence of HBV between HD centers at different governorates (all P values > 0.1), but this difference was highly significant concerning the incidence rates of HCV which occurred predominantly in the southern centers (1.47 per 100 p-y) with a P value of 0.00068 and 0.00374 when compared to Mount Lebanon (0.21 per 100 p-y) and the Northern centers (0.19 per 100 p-y), respectively.
CONCLUSION: The incidence rate of HBV and HCV is very low in the Lebanese HD centers and their prevalence is decreasing over the last two decades.
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Mikolajczyk AE, Aronsohn AI. Current Management of Chronic Hepatitis B and C in Chronic Kidney Disease. Adv Chronic Kidney Dis 2015; 22:352-60. [PMID: 26311596 DOI: 10.1053/j.ackd.2015.06.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 06/18/2015] [Accepted: 06/22/2015] [Indexed: 12/15/2022]
Abstract
The landscape of therapeutic options for hepatitis B and C has changed drastically over the course of 2 decades. There are now novel, effective, well-tolerated, oral antiviral agents being used to successfully control chronic hepatitis B (HBV) infections and cure chronic hepatitis C (HCV) infections. However, patients with CKD were rarely included in the Phase II and III randomized trials for these medications. This paucity of data and the high prevalence of comorbidities associated with CKD pose distinct challenges to physicians treating chronic hepatitis B virus and hepatitis C virus infections in the setting of kidney insufficiency/failure. Thus, this review will attempt to summarize the current data regarding novel antiviral therapies for HBV and HCV in the CKD population.
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Prabhu RA, Nair S, Pai G, Reddy NP, Suvarna D. Interventions for dialysis patients with hepatitis C virus (HCV) infection. Cochrane Database Syst Rev 2015; 2015:CD007003. [PMID: 26287983 PMCID: PMC9208657 DOI: 10.1002/14651858.cd007003.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39% with side effects necessitating treatment discontinuation in 20%. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. OBJECTIVES We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. SEARCH METHODS We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. SELECTION CRITERIA Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. MAIN RESULTS Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity.One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95% CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias.Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 µg/week versus 90 µg/week) and PEG interferon alpha-2b (1 µg/kg versus 0.5 µg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences.Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second.No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. AUTHORS' CONCLUSIONS Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.
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Affiliation(s)
- Ravindra A Prabhu
- Kasturba Medical College and Hospital Manipal, Manipal UniversityDepartment of NephrologyPO Box 7 Madhav NagarManipalKarnatakaIndia576104
| | - Sreekumar Nair
- Manipal UniversityDepartment of Statistics6th Floor, Health Sciences Library BuildingMadhav NagarManipalKarnatakaIndia576 104
| | - Ganesh Pai
- Kasturba Medical College, Manipal UniversityDepartment of GastroenterologyMadhav NagarManipalKarnatakaIndia576104
| | - Nageswara P Reddy
- Kasturba Medical College, Manipal UniversityDepartment of NephrologyMadhavnagar StreetManipalKarnatakaIndia576104
| | - Deepak Suvarna
- Kasturba Medical College, Manipal UniversityDepartment of GastroenterologyMadhav NagarManipalKarnatakaIndia576104
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Kao HH, Chen KS, Lin CL, Chang JJ, Lee CH. Utilization of Signal-to-Cutoff Ratio of Hepatitis C Virus Antibody Assay in Predicting HCV Viremia among Hemodialysis Patients. Nephron Clin Pract 2015; 130:127-33. [PMID: 26065912 DOI: 10.1159/000430988] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 04/28/2015] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a common cause of acute and chronic hepatitis among the hemodialysis population. To prevent cross infection between hemodialysis patients during the hemodialysis procedure, routine screening of anti-HCV antibody is recommended. However, a reactive anti-HCV EIA test is not equal to active HCV infection. An expensive RT-PCR study is required to confirm HCV viremia. This will significantly increase the cost burden because payment for each hemodialysis treatment is very low in Taiwan. Thus, it is useful to identify parameters that could predict HCV viremia among anti-HCV-reactive patients. In this study, we examined the usefulness of signal-to-cut (S/CO) ratio of anti-HCV antibody in discriminating HCV viremia from non-viremia among the anti-HCV-reactive hemodialysis population. MATERIALS AND METHODS In a cross-sectional measurement of anti-HCV antibody among 369 chronic hemodialysis patients, 44 showed reactive and 9 grey zone reaction for anti-HCV. These 53 patients underwent further blood tests for the measurement of AST, ALT and HCV RNA (by RT-PCR). The results of RT-PCR were used as a dependent variable. Then, S/CO ratios of anti-HCV, serum AST, ALT levels, age and duration of hemodialysis were used as independent variables to undergo ROC curve and logistic regression analysis. RESULTS Thirty-six of the 53 reactive and grey zone patients were positive for HCV RNA in the RT-PCR study. Patients who were positive for HCV RNA had a higher S/CO ratio (p < 0.01), higher AST and ALT levels (p < 0.01), and longer duration on hemodialysis (p < 0.05) than those negative for HCV RNA. Logistic regression revealed that only S/CO ratio was a significant predictor for HCV viremia (p = 0.004). ROC curve analysis showed that S/CO ratio had a highest area under curve (0.967, p < 0.001), followed by ALT (0.826, p < 0.001), AST (0.778, p = 0.001), duration on hemodialysis (0.606, p = 0.215) and age (0.426, p = 0.386) in discriminating HCV viremia from non-viremia. Using a cutoff S/CO ratio of 65, we can confirm HCV viremia with a diagnostic specificity of 100%, sensitivity of 80.1% and positive predictive value of 100%. CONCLUSION S/CO ratio is a useful indicator in predicting HCV viremia among anti-HCV-reactive hemodialysis patients. Patients with an S/CO ratio >65 can be regarded as those with active HCV infection. Alternatively, patients with reactive anti-HCV but with an S/CO ratio <65 should receive further RT-PCR test.
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Affiliation(s)
- Hao-Hsi Kao
- Division of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC
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Orăşan OH, Sava M, Iancu M, Cozma A, Saplonţai-Pop A, Sarlea Ţărmure S, Lungoci C, Orăşan RA, Patiu IM, Dumitraşcu DL. Serum hyaluronic acid in chronic viral hepatitis B and C: a biomarker for assessing liver fibrosis in chronic hemodialysis patients. Int Urol Nephrol 2015; 47:1209-17. [PMID: 26025064 DOI: 10.1007/s11255-015-1017-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 05/19/2015] [Indexed: 12/31/2022]
Abstract
PURPOSE Serum hyaluronic acid (sHA) is studied as a noninvasive marker of liver fibrosis (F) in chronic B and C viral hepatitis in general population but less in end-stage renal disease patients undergoing hemodialysis. METHODS We evaluated sHA as a noninvasive biomarker of F in a multicenter prospective, transversal, and observational study which included 52 end-stage renal disease patients with chronic B (14) and C (38) viral hepatitis (age 55.57 ± 14.46 years, dialysis vintage 132.59 ± 86.02 months). RESULTS Of the noninvasive tests analyzed, only sHA, APRI, and FIB4 index were able to differentiate patients with F1 (sHA p = 0.006; APRI p = 0.031; FIB4 p = 0.016). No statistically significant differences were found between sHA and APRI, ASAT/ALAT ratio, and FIB4 index in detecting F1 a (p > 0.02). sHA seemed to be more efficient than APRI, ASAT/ALAT ratio, and FIB4 index, having the highest estimated AUC value. The sHA threshold value for F1 was equal to 33.46 ng/mL, with the following estimated values of the performance indicators: Se 88.46 % and Sp 50 %. sHA was the only noninvasive test of the studied tests that could determine F2 (p = 0.002), with a threshold value of 80.24 ng/mL (Se 63 %, Sp 88 %), and F3 (p = 0.008), with a threshold value of 88.54 ng/mL (Se 60 %, Sp 84 %). None of the studied noninvasive tests could determine F4. CONCLUSIONS In patients with chronic B and C viral hepatitis undergoing hemodialysis, sHA may be a useful biomarker for the liver fibrosis grades: F1-mild, F2-moderate, and F3-severe, but it does not differentiate between chronic hepatitis (F1-F3) and liver cirrhosis (F4).
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Affiliation(s)
- Olga Hilda Orăşan
- 4th Medical Department, University of Medicine and Pharmacy, Cluj-Napoca, Romania,
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Scotto G, Aucella F, Grandaliano G, Martinelli D, Querques M, Gesuete A, Infante B, Carri PD, Massa S, Salatino G, Bulla F, Fazio V. Hepatitis E in hemodialysis and kidney transplant patients in south-east Italy. World J Gastroenterol 2015; 21:3266-3273. [PMID: 25805933 PMCID: PMC4363756 DOI: 10.3748/wjg.v21.i11.3266] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Revised: 11/04/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the serovirological prevalence and clinical features of hepatitis E virus (HEV) infection in end-stage renal failure patients and in the healthy population.
METHODS: HEV infection is a viral disease that can cause sporadic and epidemic hepatitis. Previous studies unexpectedly showed a high prevalence of HEV antibodies in immunosuppressed subjects, including hemodialysis (HD) patients and patients who had undergone kidney transplant. A cohort/case-control study was carried out from January 2012 to August 2013 in two hospitals in southern Italy (Foggia and S. Giovanni Rotondo, Apulia). The seroprevalence of HEV was determined in 801 subjects; 231 HD patients, 120 renal transplant recipients, and 450 health individuals. All HD patients and the recipients of renal transplants were attending the Departments of Nephrology and Dialysis at two hospitals located in Southern Italy, and were included progressively in this study. Serum samples were tested for HEV antibodies (IgG/IgM); in the case of positivity they were confirmed by a Western blot assay and were also tested for HEV-RNA, and the HEV genotypes were determined.
RESULTS: A total of 30/801 (3.7%) patients were positive for anti-HEV Ig (IgG and/or IgM) and by Western blot. The healthy population presented with a prevalence of 2.7%, HD patients had a prevalence of 6.0%, and transplant recipients had a prevalence of 3.3%. The overall combined HEV-positive prevalence in the two groups with chronic renal failure was 5.1%. The rates of exposure to HEV (positivity of HEV-IgG/M in the early samples) were lower in the healthy controls, but the difference among the three groups was not statistically significant (P > 0.05). Positivity for anti-HEV/IgM was detected in 4/30 (13.33%) anti-HEV Ig positive individuals, in 2/14 HD patients, in 1/4 transplant individuals, and in 1/12 of the healthy population. The relative risk of being HEV-IgM-positive was significantly higher among transplant recipients compared to the other two groups (OR = 65.4, 95%CI: 7.2-592.7, P < 0.001), but the subjects with HEV-IgM positivity were numerically too few to calculate a significant difference. No patient presented with chronic hepatitis from HEV infection alone.
CONCLUSION: This study indicated a higher, but not significant, circulation of HEV in hemodialysis patients vs the healthy population. Chronic hepatitis due to the HEV virus was not observed.
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Aguirre Valadez J, García Juárez I, Rincón Pedrero R, Torre A. Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review. Ther Clin Risk Manag 2015; 11:329-38. [PMID: 25767389 PMCID: PMC4354469 DOI: 10.2147/tcrm.s74282] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation.
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Affiliation(s)
- Jonathan Aguirre Valadez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Ignacio García Juárez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Rodolfo Rincón Pedrero
- Department of Nephrology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Aldo Torre
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
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Vidales-Braz BM, da Silva NMO, Lobato R, Germano FN, da Mota LD, Barros EJG, de Martinez AMB. Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil: prevalence, risk factors, genotypes, and viral load dynamics in hemodialysis patients. Virol J 2015; 12:8. [PMID: 25644891 PMCID: PMC4329191 DOI: 10.1186/s12985-015-0238-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 01/02/2015] [Indexed: 01/04/2023] Open
Abstract
UNLABELLED Hepatitis C (HCV) is a serious public health issue, and it is estimated that 3% of the world's population is infected. Patients in hemodialysis units have an increased risk for contracting HCV, and high prevalence rates have been found in hemodialysis units around the world. This study is aimed at determining the prevalence of HCV in patients with terminal chronic renal disease (tCRD) who have been submitted to hemodialysis and peritoneal dialysis in southern Brazil to characterize the most prevalent genotypes, the viral load, and possible risk factors and to assess the validity between the ELISA and RT-PCR detection methods. Of 320 patients from three dialysis units, 318 participated in this study. According to the medical records, 55 patients were reactive to HCV, as determined via ELISA. All 318 samples were submitted to RT-PCR and genotyped using an Abbott Realtime m2000 system. Data obtained through a questionnaire and chemical variables were associated with the HCV. RESULTS The prevalence of HCV was 18.24% (58), and the concordance between the HCV serology and the RT-PCR was 94%. Three patients were diagnosed to be negative for HCV using the ELISA assay but positive when using RT-PCR. Genotype 1 was the most prevalent (46.7%) genotype, within which subtype 1a was the most frequent (74.1%). One of the risk factors associated with HCV infection was the length of time that the patient had been undergoing hemodialysis treatments (p < 0.001). Additionally, the viral load was found to vary when tested before and after hemodialysis (p < 0.001). CONCLUSION The prevalence of HCV in dialysis units continues to remain high, indicating nosocomial contamination. RT-PCR detected the presence of the hepatitis C virus in patients with a non-reactive serology, which highlights the importance of performing molecular tests on dialysis patients. The variation in the viral load in patients submitted to hemodialysis indicates a possible destruction or gripping of viral particles to the dialyzer membrane.
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Affiliation(s)
| | | | - Rubens Lobato
- Federal University of Rio Grande (FURG), Rio Grande, Brazil.
| | | | | | - Elvino J G Barros
- Federal University of Rio Grande do Sul (UFRGS), Porto alegre, Brazil.
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Sartor C, Brunet P, Simon S, Tamalet C, Berland Y, Drancourt M. Transmission of Hepatitis C Virus Between Hemodialysis Patients Sharing the Same Machine. Infect Control Hosp Epidemiol 2015; 25:609-11. [PMID: 15301036 DOI: 10.1086/502448] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AbstractAfter a patient acquired hepatitis C virus (HCV) infection in our unit, we performed epidemiologic and virologic investigations, including genotyping and phylogenetic analyses. The results provided evidence for HCV transmission between two patients sharing the same machine and suggested possible transmission via accidental contamination of the venous pressure monitoring system.
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Affiliation(s)
- Catherine Sartor
- Comité de Lutte Contre les Infections Nosocomiales, Hôpital de la Conception, Marseille, France
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Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 Suppl 5:S165-73. [PMID: 25458776 DOI: 10.1016/j.dld.2014.10.005] [Citation(s) in RCA: 190] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 10/03/2014] [Indexed: 02/09/2023]
Abstract
Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Hepatitis C virus resistance to interferon therapy: an alarming situation. Open Life Sci 2014. [DOI: 10.2478/s11535-014-0352-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
AbstractHepatitis C virus is presently a major public health problem across the globe. The main objective in treating hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). Interferon-α (IFN-α) and pegylated interferon (PegIFN) in combination with Ribavirin (RBV) are the choice of treatment nowadays against chronic hepatitis C. There are several mechanisms evolved by the hepatitis C virus that facilitate the persistence of virus and further lead the patient’s status as non responder. Various factors involved in patient’s lack ofresponse to the therapy include: (1) viral factors, (2) host factors, (3) molecular mechanisms related to the lack of response and (4) social factors. Herein we have made an attempt to summarize all the related predictors of drug resistance in one article so that the future polices can be planned to overcome this obstacle and potential therapies can be designed by considering these factors.
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Sakellariou S, Boletis JN, Sypsa V, Psichogiou M, Tiniakos D, Delladetsima I. Histological features of chronic hepatitis C in haemodialysis patients. Liver Int 2014; 34:e56-61. [PMID: 25234282 DOI: 10.1111/liv.12413] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Accepted: 11/16/2013] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS HCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined. METHODS Sixty-one consecutive liver biopsies from HD patients and 326 from non-uraemic patients with chronic HCV infection were comparatively evaluated. RESULTS Haemodialysis patients with CHC were older than control subjects (P = 0.031), showing a similar HCV genotype distribution (P = 0.328) and lower viral load (P = 0.001). CHC in HD patients was significantly milder according to stage (P = 0.033), grade and its parameters (periportal activity, portal inflammation and lobular activity) (P < 0.001). The frequency of lymphoid aggregates (10.2% vs. 50%, P < 0.001), bile duct lesions (1.7% vs. 22.1%, P < 0.001) and extent of steatosis (P = 0.022) in HD group was significantly reduced. Multivariate analysis showed that non-uraemic patients had 2.3 times higher risk of developing steatosis independently of genotype distribution and age. In HD group, genotype 3, longer HD duration and age at infection were significantly associated with steatosis, while older age at infection correlated with advanced fibrosis. CONCLUSIONS Chronic hepatitis C in HD patients is usually very mild, losing its diagnostic histological features while patient's age and age at infection retain their prognostic significance. The weak inflammatory response, probably because of immunocompromised status and low viral load, may present a beneficial factor in the natural course of the disease.
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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Wang KL, Xing HQ, Zhao H, Liu JW, Gao DL, Zhang XH, Yao HY, Yan L, Zhao J. Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection. World J Gastroenterol 2014; 20:4071-4075. [PMID: 24744598 PMCID: PMC3983465 DOI: 10.3748/wjg.v20.i14.4071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 11/21/2013] [Accepted: 01/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.
METHODS: In total, 19 patients were enrolled in this study, of which 12 received PEG-IFNα-2a 67.5 μg 1 time/wk (Group 1) and 7 received standard interferon α-2b subcutaneously 1.5 × 106 U 3 times/wk (Group 2). The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3. All patients were prospectively followed after the completion of therapy. The efficacy and tolerability of the treatment were evaluated based on the sustained virological response (SVR) and treatment-related drop-out rate.
RESULTS: In Group 1, 11 of the 12 patients completed the treatment. Early virological response (EVR) and sustained virological response (SVR) rates were 83.3% and 91.7%, respectively. One patient withdrew from treatment due to an adverse event (leukopenia). The drop-out rate was 8.3% in this group. In Group 2, 5 of the 7 patients completed the treatment with an EVR and SVR of 85.7% and 71.4%, respectively. Two patients withdrew due to treatment-related adverse events (nausea and depression). In this group, the drop-out rate was 28.6%. In total, 16 of the patients attained EVR, and 15 of them completed the treatment. The SVR rate for the patients who attained EVR was 93.7%. Anemia was the most frequent side effect and was observed in 10/19 patients (55.5%), but could be effectively managed with erythropoietin.
CONCLUSION: Low-dose interferon monotherapy, either with PEG-IFNα-2a or standard interferon α-2b, is an effective treatment option for hemodialysis patients with chronic hepatitis C.
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