Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.

'Real-life' experience with direct-acting antiviral agents for HCV after kidney transplant.

INTRODUCTIONS AND OBJECTIVES: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a 'real-life' setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV. MATERIAL AND METHODS: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. RESULTS: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvir-based regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four drop-outs obtained SVR. CONCLUSIONS: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a 'real-life' clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C Virus Infection in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2018 Clinical Practice Guideline.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population. Methods: The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification. Recommendation: The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.

Management of hepatitis C virus infection in patients with chronic kidney disease: position statement of the joint committee of Italian association for the study of the liver (AISF), Italian society of internal medicine (SIMI), Italian society of infectious and tropical disease (SIMIT) and Italian society of nephrology (SIN).

Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation.

Impact of hepatitis C virus and direct acting antivirals on kidney recipients: a retrospective study.

Hepatitis C virus (HCV) in kidney transplanted patients (KTx-p) carries a high risk for a worse outcome. This retrospective study evaluates the impact of HCV and of the new direct acting antivirals (DAAs) on patient and graft outcomes in KTx patients. Forty (6.5%) of the 616 KTx-p, who received a kidney transplantation (KTx) in our Centre had antibodies against HCV: 13 were positive for HCV RNA and received DAAs (Group A); 11 were HCV RNA positive and did not receive any treatment (Group B; n = 11); 16 were negative for HCV RNA (Group C). All Group A patients had HCV RNA negativity after 12 weeks of treatment, and 12 (92.30%) achieved a sustained virological response (SVR). Only two patients, who had proteinuria greater than 500 mg/day showed a worsening of proteinuria after antiviral therapy in Group A. Liver enzyme elevation and death were significantly more frequent in Group B than other groups. Our results support the notion that active HCV infection negatively affects kidney recipients and that DAA have a high safety and efficacy profile after KTx with no significant negative effect on allograft function, particularly in well-functioning renal grafts.

The epidemiology of HCV infection in patients with advanced CKD/ESRD: A global perspective.

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.

Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline: welcoming advances in evaluation and management.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.

Association Between Hepatitis C Virus and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION AND AIM: The role of hepatitis C virus infection as a risk factor for the development and progression of chronic kidney disease in the general population remains unclear. MATERIAL AND METHODS: A systematic review of the published medical literature was performed to assess whether positive anti-HCV serologic status is associated with higher frequency of chronic kidney disease in the adult general population. We used a random-effects model to generate a summary estimate of the relative risk of chronic kidney disease (defined by lowered glomerular filtration rate or detectable proteinuria) with HCV across the published studies. Meta-regression and stratified analysis were also carried out. RESULTS: Forty studies were eligible (n = 4,072,867 patients), and separate meta-analyses were conducted according to the outcome. Pooling results of longitudinal studies (n = 15 studies, n = 2,299,134 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HCV across the surveys, 1.54 (95% CI, 1.26; 1.87) (P < 0.001). Between-study heterogeneity was observed (Q value by Chi-squared [χ2] test 500.3, P < 0.0001). The risk of chronic kidney disease related to HCV, in the subset of surveys from Asia was 1.45 (1.27; 1.65) (P < 0.001) (no heterogeneity). According to our meta-regression, ageing (P < 0.0001) and duration of follow-up (P < 0.0001) increased the risk of chronic kidney disease among HCV-positive subjects. We observed a relationship between anti-HCV positive serologic status and frequency of proteinuria, adjusted effect estimate of proteinuria with HCV among surveys was 1.633 (95% CI, 1,29; 2.05) (P < 0.001) (n = 10 studies; 315,404 unique patients). However, between-studies heterogeneity was noted (P value by Q test < 0.0001). CONCLUSION: An association between HCV infection and increased risk of chronic kidney disease in the general population exists. The mechanisms underlying such association are currently under active investigation.

Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.

Hepatitis C and Its Metabolic Complications in Kidney Disease.

INTRODUCTION: Evidence has been accumulated during the last decade showing that HCV infection plays an important activity at hepatic and extra-hepatic level. Chronic HCV is associated with a large spectrum of extra-hepatic manifestations including lympho-proliferative diseases and metabolic abnormalities (such as insulin resistance and fatty liver disease). MATERIAL AND METHODS: We have performed an extensive review of the medical literature regarding the increased risk of cardiovascular and kidney disease that has been observed in various groups of HCV-infected patients. The potential link between such increased risk and the metabolic consequences of chronic HCV infection has been explored. RESULTS: According to a systematic review with a meta-analysis of longitudinal studies (n = 9 clinical observational studies; n = 1,947,034 unique patients), we found a strong relationship between positive anti-HCV serologic status and increased incidence of chronic kidney disease in the adult general population, the summary estimate for adjusted hazard ratio was 1.43 (95% confidence intervals, 1.23; 1.63, P = 0.0001) (random-effects model) in anti-HCV positive patients. In another meta-analysis of clinical observational studies (n = 145,608 unique patients on long term dialysis; n = 14 observational studies), anti-HCV sero-positive status was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all-cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25; 1.47 (P < 0.01) in anti-HCV positive patients on maintenance dialysis. An updated and stratified analysis (n = 4 studies, n = 91,916 patients on maintenance dialysis) resulted in an adjusted HR for cardiovascular mortality among anti-HCV positive patients of 1.21 (95% CI, 1.06; 1.39) (P < 0.01); the homogeneity assumption was not rejected. The mechanisms underlying such relationships remain unclear; it has been suggested that HCV promotes atherogenesis through direct and indirect mechanisms. CONCLUSIONS: Clinical trials are under way to assess whether the clearance of HCV RNA from serum by direct-acting antiviral drugs reduces all cause or disease-specific (cardiovascular) mortality among patients on maintenance dialysis.

Association between hepatitis B virus and chronic kidney disease: a systematic review and meta-analysis.

 Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease. AIM: To evaluate the effect of infection with HBV on the risk of chronic kidney disease in the general population. MATERIAL AND METHODS: We conducted a systematic review of the published medical literature to determine if hepatitis B infection is associated with increased likelihood of chronic kidney disease. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis B virus across the published studies. Meta-regression and stratified analysis were also conducted. RESULTS: We identified 16 studies (n = 394,664 patients) and separate meta-analyses were performed according to the outcome. The subset of longitudinal studies addressing ESRD (n = 2; n = 91,656) gave a pooled aHR 3.87 (95% CI, 1.48; 6.25, P < 0.0001) among HBV-infected patients and no heterogeneity was recorded. In meta-regression, we noted the impact of male (P = 0.006) and duration of follow- up (P = 0.007) upon the adjusted hazard ratio of incidence of chronic kidney disease (including end-stage renal disease). No relationship occurred between HBV positive status and prevalent chronic disease (n = 7, n = 109,889 unique patients); adjusted odds ratio, were 1.07 (95% CI, 0.89; 1.25) and 0.93 (95% CI, 0.76; 1.10), respectively. CONCLUSIONS: HBV infection is possibly associated with a risk of developing reduced glomerular filtration rate in the general population; no link between HBV sero-positive status and frequency of chronic kidney disease or proteinuria was noted in cross-sectional surveys.

New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant.

The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing HCV treatment, particularly for chronic kidney disease patients who have a heavy burden of comorbidities.

Hepatitis C virus increases the risk of kidney disease among HIV-positive patients: Systematic review and meta-analysis.

Kidney disease has become an important co-morbidity among human immunodeficiency virus-infected patients as they live longer in the era of highly effective antiretroviral therapy. It remains unclear how co-infection with hepatitis C virus impacts on the trajectory of kidney disease among HIV-infected patients. To evaluate the effect of co-infection with HCV on the risk of kidney disease in HIV-infected populations. We conducted a systematic review of the published medical literature to determine if hepatitis C co-infection is associated with increased likelihood of chronic kidney disease in HIV-positive adults. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis C virus across the published studies. Meta-regression and stratified analysis were also conducted. We identified 19 studies (146,151 unique patients with HIV) and separate meta-analyses were performed according to the outcome. Aggregation of longitudinal studies (n = 8, 105,462 unique patients) showed a relationship between HCV infection and increased risk of reduced glomerular filtration rate among HIV-infected individuals, the summary estimate for adjusted hazard ratio was 1.64 (95%CI, 1.28; 2.0, P < 0.001) in HIV-HCV co-infected individuals compared with those having HIV mono-infection. No between-studies heterogeneity was noted (P-value by Q test = 0.08). HCV positive serology was an independent risk factor for proteinuria; adjusted effect estimate, 1.23 (95% confidence interval, 1.18; 1.28, P = 0.001) (n = 6 studies; 26,835 unique patients). In meta-regression, we noted the impact of ageing (P = 0.0001) upon the adjusted hazard ratio of incidence of reduced glomerular filtration rate among HCV-HIV co-infected patients; a negative association between frequency of males (P = 0.001) and the adjusted hazard ratio of prevalence of low glomerular filtration rate was found. Hepatitis C co-infection is associated with a significant increase in the risk of reduced glomerular filtration rate and/or detectable proteinuria among HIV-infected individuals.

Recombinant Hepatitis B Vaccine Adjuvanted With AS04 in Dialysis Patients: A Prospective Cohort Study.

BACKGROUND/AIMS: Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination, including to hepatitis B vaccine. A recombinant HB vaccine containing a new adjuvant system AS04 (HBV-AS04) has been recently developed; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis. All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospectively included. METHODS: Patients received four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 0,1,2, and 3. Anti-HB surface antibody concentrations were measured at intervals of 1, 2, 3, 4, and 12 months. Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine. RESULTS: 102 patients were enrolled and 91 completed the study. At completion of the vaccination schedule, using per-protocol analysis, 76 of 91 (84%) had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations (GMCs) of 385.25 mIU/mL. The sero-protection rate at month 12 was 84% (48/57) with lower GMCs (62.74 mIU/mL, P<0.0001). Multivariate analysis revealed a detrimental role of age on the immune response to HB-AS04 vaccine (F Ratio, 4.04; P<0.04). Tolerance to HBV-AS04 was good and only minor side-effects were observed. CONCLUSIONS: HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present. Prospective studies with HBV-AS04 on larger study groups and with longer follow-ups are under way.

Pegylated interferon (alone or with ribavirin) for chronic hepatitis C in haemodialysis population.

BACKGROUND/AIMS: Hepatitis C virus infection remains prevalent among patients undergoing long-term haemodialysis and has a detrimental impact on survival in this population. Antiviral therapy for chronic hepatitis C in haemodialysis patients is still a challenge to clinicians. The aim of the current study is to evaluate the efficacy and safety of therapy with pegylated interferon, alone or combined with ribavirin, for chronic hepatitis C among patients undergoing long-term hemodialysis. METHODS: We conducted a retrospective, multicenter cohort trial with monotherapy (pegylated interferon) (n=21) or combined antiviral therapy (pegylated interferon plus ribavirin) (n=5) for chronic hepatitis C in patients undergoing long-term haemodialysis. RESULTS: Sustained virological response was obtained in eleven (42%) patients. Seven (26.9%) patients interrupted prematurely the antiviral treatment due to serious side-effects, the most frequent cause of treatment withdrawal being hematological (n=3). HCV RNA load was lower in responder than non-responder patients, 5.44 (3.45; 6.36) vs. 5.86 (4.61; 6.46) log10 copies/mL, even if the difference was not significant (P=0.099). Blood transfusion requirement was greater in patients on combined antiviral therapy than those on pegylated interferon alone, 100% (5/5) vs. 0% (0/21), P=0.0001. No difference in sustained viral response occurred between patients on combined antiviral therapy and those on pegylated interferon monotherapy [40% (2/5) vs. 42.8% (9/21), P=0.90]. CONCLUSIONS: Results from this study showed that pegylated interferon alone or with ribavirin is unsatisfactory in terms of efficacy and safety. Prospective trials based on interferon-free regimens (i.e., sofosbuvir plus ribavirin or sofosbuvir plus daclatasvir) are under way in patients with hepatitis C receiving long-term hemodialysis.

Hepatitis C Virus Infection Increases the Risk of Developing Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND RATIONALE: Chronic kidney disease and hepatitis C virus are prevalent in the general population worldwide, and controversy exists about the impact of HCV infection on the development and progression of kidney disease. DESIGN: A systematic review of the published medical literature was made to assess whether positive anti-HCV serologic status plays an independent impact on the development of chronic kidney disease in the adult general population. We used a random-effects model to generate a summary estimate of the relative risk of chronic kidney disease (defined by reduced glomerular filtration rate or detectable proteinuria) with HCV across the published studies. Meta-regression and stratified analysis were also conducted. RESULTS: Twenty-three studies (n = 2,842,421 patients) were eligible, and separate meta-analyses were performed according to the outcome. Pooling results of longitudinal studies (n = 9; 1,947,034 unique patients) demonstrated a relationship between positive HCV serologic status and increased incidence of chronic kidney disease, the summary estimate for adjusted hazard ratio was 1.43 (95% confidence interval 1.23; 1.63, P = 0.0001), and between-studies heterogeneity was noted (P value by Q test <0.0001). The risk of the incidence of chronic kidney disease associated with HCV, in the subset of Asian surveys, was 1.31 (95% confidence interval 1.16; 1.45) without heterogeneity (P value by Q test = 0.6). HCV positive serology was an independent risk factor for proteinuria; adjusted odds ratio, 1.508 (95% confidence intervals 1.19; 1.89, P = 0.0001) (n = 6 studies; 107,356 unique patients). CONCLUSIONS: HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population.

Novel evidence on hepatitis C virus-associated glomerular disease.

A large spectrum of renal pathology is associated with hepatitis C virus (HCV). According to novel evidence, occult HCV infection (HCV-RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) could be involved in the pathogenesis of glomerular nephropathy among patients negative for conventional markers of HCV. Additional studies with appropriate size and technology are in progress to confirm the relationship between occult HCV and glomerular disease, which has multiple implications from the clinical standpoint.

Treatment of hepatitis C after kidney transplant: a pooled analysis of observational studies.

Various authors have given IFN-based therapy for hepatitis C among renal transplant recipients but the efficacy and safety of this approach remains unclear. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to assess efficacy and safety of antiviral therapy (IFN-based therapy) in renal transplant recipients with hepatitis C virus infection. The primary outcomes were sustained virological response (as a measure of efficacy) and/or drop-out rate (as a measure of tolerability). The random-effects model of DerSimonian and Laird was used, with heterogeneity and sensitivity analyses. Sixteen studies (187 unique patients) were identified, one being controlled study. The summary estimate for sustained virological response and dropout rate was 0.34 (95% confidence intervals: 0.27, 0.42) and 0.32 (95% CI: 0.21, 0.44), respectively. The studies were heterogeneous with regard to dropout rate but not to sustained viral response. The most common side-effect requiring interruption of treatment was graft dysfunction (n = 27; 51%). Stratified analysis reported a higher rate of drop-outs in those studies based on IFN monotherapy (pooled event rate, 0.43; 95% CI: 0.25, 0.63). Meta-regression analysis showed an inverse relationship between reference year (P = 0.019), length of IFN therapy (P = 0.029) and drop-out rate. IFN-based therapy has inadequate safety and tolerance after renal transplantation. The reasons for the high rate of graft dysfunction after IFN have not been fully elucidated. Antiviral treatment of hepatitis C among kidney graft recipients continues to be a challenge to transplant physicians.

Recent advances on hepatitis C virus in dialysis population.

Hepatitis C virus (HCV) infection remains common among patients undergoing regular dialysis and good evidence supports the detrimental role of HCV on survival in patients undergoing maintenance dialysis. According to an updated meta-analysis of clinical studies (n=15; 195,370 unique patients on maintenance dialysis), the summary estimate for adjusted relative risk (all-cause mortality) with anti-HCV across the published studies was 1.32 with a 95% Confidence Intervals of 1.24; 1.42, homogeneity assumption was not rejected. Various mechanisms support the excess death risk of HCV-infected patients on regular dialysis, in addition to liver disease-related mortality. The adjusted relative risk for cardiovascular mortality among HCV-infected patients on regular dialysis was 1.26 (95% Confidence Intervals, 1.10; 1.45); the increased cardiovascular mortality in anti-HCV positive patients has been associated in part to malnutrition and chronic inflammation. The current standard of care for HCV in dialysis population is combined antiviral therapy (pegylated interferon plus ribavirin) with a rate of viral response of around 60%. Triple therapy with telaprevir proved to be effective and safe in dialysis patients with HCV but only anecdotal evidence exists. Antiviral treatment of HCV-infected patients on maintenance dialysis could lead to cure the liver damage and the extrahepatic complications. The future availability of all-oral interferon/ribavirin free regimens for antiviral treatment of HCV will help nephrologists to improve survival in this high-risk group.