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Background: Controversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease., Study Aims and Design: A systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out., Results: Fifteen studies were eligible (n=356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n=7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p=0.0016) and between-study heterogeneity was found (p-value by Q test=0.004). Aggregation of studies comparing treated vs untreated cohorts (n=8, n=333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p=0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p=0.02) and HBV infection (p=0.0001) increase among HCV-infected individuals., Conclusions: Antiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing., (Copyright © 2019. Published by Elsevier España, S.L.U.)

The management of hepatitis C virus (HCV)-induced glomerular disease remains unsatisfactory despite novel advances in antiviral and immunosuppressive therapy. Recent evidence highlighted the role of ribavirin, a drug provided with immunomodulatory properties, in the treatment of glomerular diseases associated with chronic HCV. We administered low-dose ribavirin (200 mg/day or 200 mg twice a week or 200 mg thrice weekly) in a prospective fashion to a group of patients with HCV-associated glomerular disease (n = 7). Ribavirin monotherapy was given in most (n = 6) patients and was accompanied by erythropoietin therapy in all. The primary endpoint was reduction of 24-h proteinuria after treatment ended; the secondary end-points were decrease in serum creatinine and amelioration of urinary abnormalities. We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Many patients (n = 6) had inactive HCV infection as they had shown HCV RNA clearance from serum after antiviral therapy with direct-acting antivirals. Some patients (n = 4) had membranoproliferative glomerulo- nephritis, the diagnosis being confirmed by kidney histology in three cases; others (n = 2) received diagnosis of diabetic glomerulosclerosis, confirmed in one by kidney biopsy. We observed consistent reduction of 24-h proteinuria in two individuals after ribavirin therapy; another patient reported disappearance of microscopic hematuria. We found severe AE (hemolytic anemia) in three patients which required discontinuation of ribavirin treatment in two patients, one required hospitalization. Other AEs were cutaneous rash (n = 1), dyspepsia (n = 1), and fatigue (n = 1). Low-dose ribavirin was able to give consistent reduction of 24-h proteinuria in two patients; tolerance to ribavirin was unsatisfactory. We need further studies aimed to expand our knowledge on ribavirin therapy of HCV-associated glomerular disease. The low incidence of the disease hampers the conduction of clinical trials on this aim.

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., (© 2018 Steunstichting ESOT.)

Introduction: Hepatitis C virus (HCV) infection leads to important morbidity and mortality through liver disease and extra-hepatic manifestations. Recent evidence suggests the role of HCV in developing chronic kidney disease (CKD); also, HCV adversely affects cardiovascular (CV) disease both in the general population and in patients with CKD. Areas covered: All-oral, interferon-free direct-acting antiviral agents (DAAs) are currently available; anti-HCV regimens based on DAAs are provided with high efficacy and safety and short treatment duration. However, some difficult-to-treat populations still exist including patients with CKD and those who failed previous DAA regimen. Expert commentary: Two DAAs regimens (elbasvir/grazoprevir and glecaprevir/pibrentasvir) are now recommended for the treatment of HCV in patients with advanced CKD, these combinations have shown great efficacy, according to two multicenter phase-3 trials (C-SURFER and EXPEDITION-4). These trials reported a minimal impact of baseline resistance-associated substitutions (RASs) on treatment outcomes. The sofosbuvir/velpatasvir/voxaliprevir combination has been recommended as the first-line option for DAAs failures, on the basis of the results given by two randomized clinical trials involving patients who had been previously received DAA-containing regimens (POLARIS 1-4 studies). It has been suggested that clinicians should consider RASs upon the introduction of DAA-based antiviral therapy.

Hepatitis C virus infection is still common among patients with chronic kidney disease, particularly within Dialysis Units all over the world. Although the full extent of HCV transmission in dialysis units is unknown, outbreaks of HCV infection continue to occur all over the world. Evidence has been accumulated in the last decade suggesting that HCV plays consistent activity at hepatic and extra-hepatic level. A recent systematic review of the medical literature with a meta-analysis of clinical studies retrieved 15 longitudinal studies (n=2,299,134 patients) ; we found a significant relationship between anti-HCV positive serologic status and higher frequency of CKD; the summary estimate for adjusted hazard risk with HCV across the surveys, 1.54 (95% CI, 1.26; 1.87) (P<0.0001). The advent of direct-acting antiviral agents has revolutionized the therapy of HCV, including patients with advanced chronic kidney disease. Two regimens based on DAAs have been recently approved for the antiviral therapy of HCV in patients with CKD stage 4/5: elbasvir/grazoprevir and glecaprevir/pibrentasvir. Such regimens have been provided with high efficacy and safety, according to the results given by C-SURFER and EXPEDITION-4, respectively. Sofosbuvir, a non-structural 5B polymerase inhibitor, is the backbone of many anti-HCV drug regimens, and has significant renal excretion. As a result, the use of sofosbuvir is not recommended in patients with an eGFR <30 mL/min/1.73m². In summary, recent studies have shown that several combinations of DAAs are currently available for CKD patients, including those with CKD stage 4/5. These drugs have reported high efficacy and satisfactory tolerability, regardless of HCV genotype or renal impairment. We need to improve the screening for HCV and the access to DAAs in patients with CKD stage 4/5., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: The evidence in the medical literature on the treatment of hepatitis C virus-associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety., Aims: We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus-associated glomerular disease., Methods: In the first phase of the study, patients with hepatitis C virus-associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively)., Results: We enrolled 25 consecutive patients with hepatitis C virus-associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers ( n = 2) and nonresponders ( n = 3) with some benefit. Among patients on interferon-based regimens ( n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers ( n = 3) were successfully managed with immunosuppressive agents in two patients., Conclusion: Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus-related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.

The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4-5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.

The frequency of hepatitis C virus infection remains high in renal transplant recipients and plays a detrimental role on survival in this population. According to the latest evidence, the adjusted relative risk of mortality and graft loss for anti-HCV seropositive versus anti-HCV negative renal transplant recipients was 1.85 with a 95% confidence interval (CI) of 1.49 ; 2.31 (P < 0.0001) and 1.76 (95% CI, 1.46 ; 2.11) (P < 0.0001), respectively. Interferon-based regimens have been recommended for the treatment of hepatitis C after renal transplantation only in selected circumstances because of an increased risk of acute rejection due to the immuno-stimulatory properties of interferon. Limited data exist on the treatment of HCV with direct-acting antiviral agents among kidney transplant recipients. To date, the most important evidence comes from the European multicenter study where a large cohort (n=114) of patients with glomerular filtration rate of 40 mL/min/1.73m² received an interferon-free, ribavirin-free combination of direct-acting antivirals (Ledipasvir/Sofosbuvir) for 12 or 24 weeks. A high efficacy [SVR12 rate, 100% (114/114) ] was found even if three serious adverse were observed ; all were determined to be treatment related, one patient interrupted permanently treatment. Also, single-center single-arm observational studies have reported high efficacy and safety of sofosbuvir-based combinations for the treatment of HCV after renal transplant. A decline in through levels of calcineurin inhibitors after completion of antiviral therapy has been found in many patients; an enhanced metabolism of calcineurin inhibitors associated with resolution of liver injury has been suggested. An effective and safe therapy for HCV in kidney transplant recipients might improve the current suboptimal utilization of HCV-positive kidney donors and provide many patients with end-stage renal disease access to HCV-infected donor kidneys., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions.

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., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The medical literature on mono-therapy with pegylated interferon for chronic hepatitis C in dialysis patients is mostly based on small clinical studies and the efficacy and safety of such approach is still unclear. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to evaluate the efficacy and safety of mono-therapy with pegylated interferon of chronic hepatitis C in patients on regular dialysis. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). The random-effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Twenty-four clinical studies (N = 744 unique patients) were retrieved; five (21%) being randomized controlled trials. The summary estimate for sustained viral response and drop-out rate was 0.40 (95% confidence interval [CI], 0.35; 0.46) and 0.14 (95% CI, 0.09; 0.20), respectively. The most frequent side-effects requiring discontinuation of treatment were hematological (31/83 = 37%) and gastrointestinal (9/31 = 10.8%). Meta-regression analysis showed a detrimental role of ageing on the frequency of sustained virological response (P = 0.01); drop-out rate was greater in diabetics (P < 0.005). Important heterogeneity was seen with regard to drop-out rate only. In summary, pegylated interferon monotherapy of hepatitis C in dialysis patients resulted unsatisfactory in terms of efficacy and safety. Studies with novel direct-acting antiviral agents in combination with pegylated interferon and ribavirin for the treatment of hepatitis C virus in dialysis population are under way., (© 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Introduction: Hepatitis C virus (HCV) infection has been associated with a large spectrum of glomerular lesions in both native and transplanted kidneys. The most common HCV-associated renal disease is type I membranoproliferative glomerulonephritis usually, but not invariably, in the context of type II mixed cryoglobulinemia (MC). HCV infection is also the major cause of MC, a systemic vasculitis characterized by involvement of small and, less frequently, medium-sized vessels. Conflicting data exist on the treatment of HCV-associated glomerular disease., Areas Covered: This review examines the drugs used for management of HCV-related kidney disease and discusses current and new strategies. All literature concerning treatment of HCV-associated kidney disease has been retrieved by electronic (Medline) and manual searches., Expert Opinion: Various approaches have been recommended for the treatment of HCV-related glomerular disease, including immunosuppressive therapy (corticosteroids, cytotoxic agents and mAbs) and antiviral therapy. These regimens should be considered according to the level or proteinuria and kidney failure. Immunosuppressive agents are recommended in patients with nephrotic syndrome and/or rapidly progressive kidney failure. Antiviral treatment based on IFN and/or ribavirin or triple antiviral therapy (PEGylated-IFN/ribavirin/telaprevir or boceprevir) has been adopted in patients with moderate proteinuria and slow loss of kidney failure; however, the number of patients enrolled was small. Some patients with HCV-related cryoglobulinemic glomerulonephritis have been treated with rituximab but some issues about its role remain to be clarified. The antiviral treatment of HCV-related glomerular disease is expected to improve in the near future with new agents provided with greater efficacy and safety. However, the affordability of these drugs remains a pivotal issue, particularly in low-income countries.

The advent of direct-acting anti-viral (DAA) drugs is dramatically changing the treatment of hepatitis C virus (HCV) in patients with intact kidney function ('cure rates' >90% and infrequent adverse events). The information on efficacy and safety of DAAs for HCV therapy in patients with renal failure is limited. We have reviewed the available evidence regarding efficacy and safety of numerous DAAs (boceprevir, telaprevir, sofosbuvir, simeprevir, grazoprevir, elbasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, ledispavir, daclatasvir, asunaprevir, beclabuvir) in treating HCV-infected patients with renal impairment and/or end-stage renal disease. The major limitation of this review is the paucity of published data and its reliance on abstracts and product monographs. Preliminary data suggest that combination antiviral therapy (grazoprevir and elbasvir) is provided with great efficacy in patients with HCV genotype 1 and chronic kidney disease stage 4 or 5 including those on intermittent dialysis, SVR12, 99% (114/115), according to a per-protocol analysis. In another trial, patients with HCV genotype 1 and chronic kidney disease stage 4 or 5 were given the 3D regimen; an interim evaluation reported that all patients completing treatment to date had viral response (100%, 14/14) but data on sustained viral response are under evaluation. Treatments were generally well tolerated.

Interferon-based therapy remains the gold standard for hepatitis C in patients with chronic kidney disease; however, due to the high rate of IFN-induced rejection after transplant, treatment of HCV-infected kidney transplant recipients is recommended only in particular circumstances. We report the case of a 45-year-old Caucasian female with chronic hepatitis C (genotype 1b) who returned to hemodialysis following the complete functional loss of her kidney transplant. She started combination antiviral therapy with peg-IFN-α2a (135 mcg sc weekly) plus ribavirin (200 mg daily) nine months after the re-initiation of hemodialysis. Antiviral therapy was neither effective nor safe; ribavirin was stopped at week 38 due to hemolytic anemia; on-treatment HCV breakthrough was observed at week 48; and acute rejection occurred after four months of IFN-based therapy. Diagnosis of acute allograft rejection was suspected on the grounds of clinical, radiographic, and laboratory data. Allograft nephrectomy was then performed and histology showed acute-on-chronic rejection. This is an uncommon case of IFN-associated kidney rejection in an allograft recipient who had functional loss of her graft and had returned to hemodialysis. In view of the risk of rejection of renal allograft, and the limited efficacy of IFN-based treatment of hepatitis C, physicians should be aware of effective treatment with oral anti-viral agents and avoid the use of IFN in patients on maintenance dialysis with failed renal allograft.

Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long-term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long-term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta-regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long-term dialysis; such approach should be considered the current standard of care for HCV-infected individuals on regular dialysis., (© 2014 John Wiley & Sons Ltd.)

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., (© 2014 Wiley Periodicals, Inc.)

Mixed cryoglobulinemia (MC), the most common extrahepatic manifestation of HCV, may lead to renal involvement ranging from mild urinary abnormalities to nephritic syndrome, eventually evolving to renal failure requiring renal replacement therapy. HCV eradication with pegylated interferon (PEG-IFN) and ribavirin (RBV) is the only curative treatment for MC-related membranoproliferative glomerulonephritis. The addition of directly acting antivirals (DAAs) to PEG-IFN and RBV has significantly improved sustained virological response rates in HCV genotype 1 patients. Safety and efficacy of this regimen in patients with membranoproliferative glomerulonephritis has not been proved yet. Here, we report the case of a woman with HCV-1-related cryoglobulinemic membranoproliferative glomerulonephritis presenting with severe nephritic syndrome and rapidly progressive renal failure, who received successful treatment with the DAA telaprevir in conjunction with PEG-IFN and RBV. Triple therapy was safe and effective, leading to HCV eradication and complete resolution of acute renal failure.

Hepatitis C virus (HCV) remains the most common cause of liver damage in patients with kidney disease, including those on long-term dialysis. The natural history of HCV in patients on regular dialysis is not fully elucidated, but an adverse effect of HCV on survival has been noted; a novel meta-analysis of observational studies (14 studies including 145,608 unique patients) showed that the summary estimate for adjusted relative risk (all-cause mortality) was 1.35 with a 95% confidence interval of 1.25-1.47. The adjusted RR for liver disease-related death and cardiovascular mortality among maintenance dialysis patients was 3.82 (95% CI, 1.92-7.61) and 1.26 (95% CI, 1.10-1.45), respectively. It has been recommended that the decision to treat HCV in patients with chronic kidney disease be based on the potential benefits and risks of therapy, including life expectancy, candidacy for kidney transplant, and comorbidities. A pooled analysis including 494 dialysis patients on monotherapy with conventional interferon reported a summary estimate for sustained viral response and dropout rate of 39% (95% CI, 32-46) and 19% (95% CI, 13-26), respectively. All renal transplant candidates (dialysis dependent or not) with HCV should be assessed for antiviral treatment given the increased risk of progressive liver disease with immunosuppressive therapy, the increased life expectancy compared to other HCV-positive patients on dialysis, and the inability to receive interferon after transplant. Current guidelines support monotherapy with standard interferon in these patients, but modern antiviral approaches (that is, dual therapy with peg-IFN plus ribavirin) in a well-controlled setting may be an appropriate alternative.

Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia. Evidence on HCV-related mixed cryoglobulinemia in the non-transplantation setting exists even if its appropriate management remains unclear. The cornerstone of treatment for symptomatic HCV-associated mixed cryoglobulinemia is antiviral therapy but little is known about its activity. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to assess efficacy and safety of combination antiviral therapy for symptomatic HCV-associated mixed cryoglobulinemia in non-immunosuppressed individuals. The random effects model of DerSimonian and Laird was used, with heterogeneity and sensitivity analyses. The primary outcome was sustained virological response (as a measure of efficacy), and the secondary outcome was the rate of patients stopping (or dose reducing) antiviral agents (as a measure of tolerability). Ten clinical studies (300 unique patients) were identified; the rate of baseline kidney involvement ranged between 4% and 39%. The summary estimate of frequency of sustained viral response was 0.42 with a 95% confidence interval (CI) of 0.31; 0.54 (random effects model). Significant heterogeneity occurred (P = 0.00001; I(2) = 77.6%). Stratified analysis showed higher efficacy in those studies using combination therapy with pegylated-than conventional IFN; the summary estimate of sustained viral response being 0.52 (95% CI, 0.40; 0.63) and 0.32 (95% CI, 0.15; 0.49), respectively. There was good association between viral and clinical response, weighted K 0.634 (95% CI, 0.455; 0.814), by a meta-analysis at individual level on a subset of reports (n = 3; 74 unique patients). The summary estimate of frequency of patients stopping (or dose reducing) antiviral agents was 0.15 (95% CI, 0.08; 0.21); no heterogeneity occurred (P = 0.05; I(2) = 51%). In summary, combination antiviral therapy (pegylated IFN plus ribavirin) gives satisfactory response in more than the half of patients with symptomatic mixed cryoglobulinemia associated with HCV. HCV-related mixed cryoglobulinemia is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed to evaluate efficacy and safety of antiviral therapy in non-immunosuppressed individuals., (Copyright © 2013 Wiley Periodicals, Inc.)

Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia (MC). Consistent evidence exists on HCV-MC in the non-transplantation setting but information on HCV-related cryoglobulinemia after solid organ transplantation is limited, particularly after liver transplantation (LT). We report on a 48-year-old man who developed HCV-associated cryoglobulinemic vasculitis with recurrent hepatitis after liver transplant. One year after transplant for HCV-positive 
cirrhosis, he presented severe cutaneous manifestations, and biopsy-proven cryoglobulinemic membrano-proliferative glomerulonephritis (MPGN). HCV RNA clearance occurred within a few weeks of antiviral therapy; sustained viral response (SVR) was obtained by one year of anti-HCV combination therapy (eight months of pegylated IFN/ribavirin and four months of standard IFN/ribavirin). SVR was linked to complete remission of skin, liver, and kidney abnormalities. Tolerance to the pegylated IFN/ribavirin regimen was not excellent due to the occurrence of lobar pneumonia with anemia; thus, peg-IFN was replaced by recombinant IFN, with a favorable outcome. Clinical and viral remission persisted over a 48-month follow-up. HCV-associated mixed cryoglobulinemia flareups following LT were successfully managed with combined antiviral therapy. HCV-related MC is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed at evaluating the efficacy and safety of anti-HCV therapy after solid organ transplantation or in the non-transplantation setting.

Background: Hepatitis C virus infection is associated with a variety of extrahepatic disorders such as membrano-proliferative glomerulonephritis, which is generally due to cryoglobulinemia. 
, Setting: We describe the case of one liver transplant recipient who received antiviral therapy (subcutaneous administration of peg-IFN-alpha-2a 180 mcg weekly and oral ribavirin 200 mg thrice a day) 
for HCV-related membrano-proliferative glomerulonephritis. He presented normal kidney function, non-nephrotic proteinuria (2 g/24 h) and mild hematuria.
, Results: Urinary abnormalities disappeared within a few weeks after the initiation of antiviral therapy; however, combination antiviral therapy was not able to obtain viral clearance. After 11 months, IFN-therapy was interrupted and the patient continued low-dose ribavirin monotherapy (200 mg once per day) for one additional year- remission of proteinuria (<0.3 g/24 h) and hematuria persisted with intact kidney function. Although other mechanisms cannot be excluded, we suggest that ribavirin therapy was critically implicated in the remission of urinary abnormalities in our patient. The existing literature on the association between HCV-associated glomerulonephritis and therapy with ribavirin is reviewed. 
, Conclusions: Antiviral therapy may be effective in patients with HCV-induced glomerulonephritis. 
Further evidence is needed to evaluate efficacy and safety of ribavirin monotherapy for HCV-related glomerulonephritis.

Background/aims: Interferon treatment of malignant or viral diseases can be accompanied by various side-effects including nephro-toxicity., Methods: We report on a 68-year-old Caucasian male who received dual therapy with pegylated interferon 2a plus ribavirin for chronic hepatitis C., Results: After three months of antiviral therapy, the patient developed acute kidney failure (serum creatinine up to 6 mg/dL) with mild proteinuria (500 mg daily) and haematuria. Immediate immunosuppressive therapy with high-dose intravenous steroids did not improve kidney function. Kidney biopsy was consistent with acute tubular necrosis without glomerular abnormalities. He started long-term peritoneal dialysis (four regular exchanges) to provide both dialysis adequacy and ascites removal. Kidney function gradually improved over the following months (serum creatinine around 2 mg/dL) and peritoneal dialysis was continued with two exchanges daily. The temporal relationship between the administration of the drug and the occurrence of nephro-toxicity, and the absence of other obvious reasons for acute tubular necrosis support a causative role for pegylated interferon; benefit on kidney disease was noted after withdrawal of antiviral agents. An extensive review of the literature on acute tubular necrosis associated with interferon-based therapy, based on in vitro data and earlier case-reports, has been made. The proposed pathogenic mechanisms are reviewed., Conclusions: Our case emphasizes the importance of monitoring renal function during treatment of chronic hepatitis C with antiviral combination therapy as treatment may precipitate kidney damage at tubular level.

The efficacy and safety of antiviral therapy in patients with acute hepatitis C on long-term dialysis remains unclear, although a number of small clinical studies have been published addressing this issue. We evaluated the efficacy and safety of interferon therapy in chronic dialysis patients with acute hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR, as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eight clinical studies (173 unique patients), three (37.5%) being controlled clinical trials (CCTs). Among CCTs, the viral response was much more common in study (patients on antiviral therapy) than control (patients who did not receive therapy) groups; the pooled odds ratio of SVR being 27.06, 95% Confidence Intervals (95% CI), 9.26; 79.1 (P = 0.00001). No difference in the dropout rate between study and control patients was shown, odds ratio = 0.920 (95% CI, 0.367; 1.92), NS. Pooling all study results (n = 8 studies) demonstrated that the summary estimate for SVR and dropout rate was 58% (95% CI, 38; 77) and 9% (95% CI, 4; 14), respectively. The most frequent side-effects requiring interruption of the treatment were flu-like symptoms (n = 4, 18%), followed by haematological changes and loss to follow-up. A strong relationship between increasing age and reported dropout rate was recognized (P = 0.001). The studies were heterogeneous with regard to SVR but not to dropout rate. Our meta-analysis of CCTs showed that the viral response after antiviral therapy was more common than the spontaneous viral clearance in dialysis patients with acute hepatitis C. Pooled analysis demonstrated that IFN-based therapy of acute hepatitis C in dialysis populations gives SVR in around one half of patients. These results support IFN-based therapy for acute hepatitis C in patients on maintenance dialysis., (© 2012 Blackwell Publishing Ltd.)

We describe the case of a 51-year-old woman with HCV-associated cryoglobulinemic glomerulonephritis (GN). She presented mild deterioration of kidney function, non-nephrotic proteinuria, and active urinary sediment. Kidney biopsy showed features of membranoproliferative changes with some sclerosis. Sustained viral response (SVR) was obtained by 6 months of antiviral therapy (peg-IFN-α2a plus ribavirin). SVR was linked with improvement of kidney function and remission of proteinuria. Clinical and virological remission persists over a 25-month follow-up. This case report emphasizes efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis--preliminary but encouraging results exist. We identified by systematic review of the literature 9 studies (156 unique patients); the pooled estimate of frequency of sustained virological response after IFN-based therapy was 0.49 (95% confidence interval, CI: 0.21, 0.77; p < 0.0005; random effects model). Heterogeneity was found (I(2) = 98.9%, p < 0.0001). Two possible regimens should be considered for the treatment of HCV-associated cryoglobulinemic GN according to the clinical presentation. Immunosuppressive therapy is recommended for HCV-related kidney disease having aggressive course, and recent evidence supports rituximab (RTX) use with a reduced exposure to corticosteroids. We identified six studies (66 unique patients) on RTX therapy for HCV-associated kidney disease; at the end of RTX therapy, the pooled estimate of the mean decrease in proteinuria was 1.4 g/24 h (95% CI: 0.75, 2.05, p < 0.001); The p test for heterogeneity gave a value of 0.94 (I(2) = 0). Several questions related to RTX use remain. HCV-induced GN is uncommon among CKD patients of developed countries, and this clearly hampers prospective controlled clinical trials aimed to evaluate efficacy and safety of antiviral or immunosuppressive therapy in this population., (Copyright © 2013 S. Karger AG, Basel.)

Hepatitis B virus (HBV) infection persists among patients with renal insufficiency in the industrialized world. A variety of therapeutic options are now available for the treatment of chronic hepatitis B infection, including potent new nucleos(t)ide analogs, along with standard and pegylated interferon. We report on a patient with aggressive hepatitis B and renal insufficiency who was successfully treated with nucleoside analogs (mostly entecavir monotherapy) for two years. He received intense immunosuppression for severe myopathy of lower limbs, probably related to vasculitis. HBV DNA (at the beginning, > 1 x 10(8) IU/mL) was no longer detectable in serum after a few months of antiviral therapy, while HBeAg and HBsAg seroconversion occurred with ALT normalization. Clinical signs of vasculitis disappeared. Five months after discontinuation of entecavir therapy, he remained HBsAg negative with detectable anti-HBs antibody in serum. We conclude that nucleos(t)ide analogs can offer excellent response in selected patients with renal insufficiency and hepatitis B-related liver disease. Prospective, controlled clinical trials are needed to confirm these encouraging results.

The efficacy and safety of combined interferon (IFN) plus ribavirin in patients on long-term dialysis and chronic hepatitis C remains unclear, although a number of small clinical trials have addressed this issue. We evaluated the efficacy and safety of combination antiviral therapy (conventional or pegylated interferon plus ribavirin) in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 10 clinical studies (151 unique patients), one (10%) of which was a controlled clinical trial. Most (97.4%) patients were on long-term haemodialysis. The summary estimate for SVR and drop-out rate was 56% [95% Confidence Intervals (95% CI) 28-84] and 25% (95% CI, 10-40), respectively. The most frequent side effects requiring interruption of treatment were anaemia (26%) and heart failure (9%). These results occurred irrespective of type of interferon (conventional or peg-IFN, peg-IFNalfa-2a or alfa-2b), trial design (controlled or cohort study), or clinical characteristics of patients (naïve, nonresponders or relapsers). The studies were heterogeneous with regard to SVR and drop-out rate. Combination antiviral therapy (interferon plus ribavirin) gives encouraging results in terms of efficacy and safety among dialysis patients even if the limited number of patients enrolled in our meta-analysis hampers definitive conclusions., (© 2010 Blackwell Publishing Ltd.)

The efficacy and safety of pegylated interferon monotherapy in patients with chronic renal failure and chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. A systematic review of the literature with a meta-analysis of clinical trials was performed in order to assess efficacy and safety of initial pegylated interferon monotherapy in chronic renal failure patients with chronic hepatitis C. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). The random effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Sixteen clinical trials (254 unique patients) were identified, five (31%) being controlled studies; the majority (15/16 = 94%) regarded patients on long-term dialysis. The summary estimate for sustained virological response and drop-out rate was 33% [95% Confidence Intervals (95%CI) 24-43] and 23% (95%CI, 14-33), respectively. The most frequent side-effects requiring interruption of treatment were haematological (18%) and gastrointestinal (14%). In the group of controlled clinical trials, the summary estimate for sustained viral response and drop-out rate was 38% (95% CI, 18-59), and 15% (95% CI, 3-26), respectively. The studies were heterogeneous with regard to sustained virological response and drop-out rate. Pegylated IFN does not provide an added benefit in terms of virological response in comparison with standard IFN monotherapy. Tolerance to pegylated-IFN monotherapy was unsatisfactory. Prospective trials are in progress to assess the optimal antiviral therapy for chronic hepatitis C in dialysis patients.

The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is type I membranoproliferative glomerulonephritis (MPGN) in patients with type II mixed cryoglobulinemia. The principal clinical manifestations of glomerular disease in HCV-infected patients are the presence of proteinuria and microscopic hematuria with or without impaired kidney function. Various approaches have been tried for the treatment of HCV-associated glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Limited data exist regarding antiviral treatment of HCV-associated glomerulonephritis, whereas immunosuppressive agents have been suggested for cryoglobulinemic kidney disease. A recent meta-analysis of controlled clinical trials (CCTs) suggested that standard interferon (IFN) doses were more effective than immunosuppressive agents in lowering proteinuria of patients with HCV-related cryoglobulinemic glomerulonephritis (odds ratio 3.86; 95% confidence interval, 1.44-10.33; p=0.007). However, data for follow-up were not given. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. Preliminary studies with rituximab therapy of HCV-related cryoglobulinemic glomerulonephritis have given encouraging results, even if a point of caution is important, because rituximab use may be associated with activation of various infections, including HCV.

Hepatitis C virus (HCV) infection remains frequent in patients with chronic kidney disease and the detrimental role of HCV on survival is well-established in this population. Several authors have reported on efficacy and safety of antiviral therapy for hepatitis C in this polulation but there is no clear consensus on management. To evaluate efficacy and safety of antiviral therapy for hepatitis C in patients with chronic kidney disease, we performed a systematic review of the published medical literature and completed a meta-analysis of controlled clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 13 studies including 539 unique patients; 10 (76.9%) concerned patients on maintenance dialysis. Only prospective, controlled clinical trials were included. Pooling of study results showed a significant increase of viral response in study (patients treated with antiviral therapy) than control patients (patients who did not receive therapy), the pooled odds ratio (OR) of failure to obtain a sustained viral response was 0.081 [95% confidence intervals (CI), 0.029-0.230], P = 0.0001. The pooled OR of drop-out rate was significantly increased in study vs control patients, OR = 0.389 (95% CI, 0.155-0.957), P = 0.04. The studies were heterogeneous with regard to viral response and drop-out rate. In the subset of clinical trials (n = 6) involving only dialysis patients receiving interferon (IFN) monotherapy for chronic HCV, there was a significant difference in the risk of failure to obtain a sustained viral response (study vs control patients), OR = 0.054 (95% CI, 0.019; 0.150), P = 0.0001 (random-effects model). No significant (NS) heterogeneity was found (Q = 14.604, P = 1.0). No difference in the drop-out rate between study and control patients was shown, OR = 0.920 (95% CI, 0.367; 2.311), NS. This result being homogeneous (Q = 3.639, P = 0.388). Our meta-analysis showed that the viral response was greater in patients with chronic kidney disease who received antiviral therapy than controls. No difference in the drop-out rate between study and control patients occurred in the subgroup of dialysis patients on IFN monotherapy. These results support IFN-based therapy for hepatitis C in patients on maintenance dialysis., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.)

One of the major advances in the management of patients on regular dialysis has been the control of the spread of hepatitis B virus (HBV) infection in dialysis units. The rate of HBsAg positive patients on regular dialysis in the developed world is currently low, but outbreaks of HBV continue to occur. The diffusion of HBV in dialysis units in developing countries is higher, although available information is not abundant. There are limited data on the natural history of HBV in the dialysis population; they support a detrimental effect of HBV on survival in dialysis patients. The HBV viral load in HbsAg-positive dialysis patients appears low and stable over time and numerous mechanisms have been posited to explain it. Several assays for detecting HBV DNA in serum are available but they should not be used for purposes of routine screening within dialysis units. The epidemiology and clinical significance of occult HBV infection in the dialysis population needs to be addressed adequately - this remains an area of active research. Recent recommendations for the management of HBsAg chronic carriers on maintenance dialysis have been issued. No controlled trials for the treatment of hepatitis B with either interferon or lamivudine in dialysis patients are currently available.

The efficacy of monotherapy with interferon (IFN) (conventional or pegylated IFN) in dialysis patients with chronic hepatitis C remains unclear, although a number of clinical trials have been published addressing this issue. The aim of the study was to evaluate the efficacy and safety of monotherapy by conventional or pegylated IFN in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (SVR; as a measure of efficacy), and the secondary outcome was drop-out rate (as a measure of tolerability). We used the random-effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 28 clinical trials (645 unique patients), of which six (21.4%) had a controlled design. In the group of trials based on conventional IFN, the summary estimate for SVR and drop-out rate was 39% [95% confidence interval (CI) 32-46] and 19% (95% CI 13-26) respectively. The summary estimate for SVR rate in patients with the hepatitis C virus genotype 1 was 33% (95% CI 19-47). In the subset of trials using pegylated IFN, the summary estimate for SVR and drop-out rate was 31% (95% CI 7-55) and 27% (95% CI 1-52) respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms, and gastrointestinal and haematological changes. A relationship between age and drop-out rate was found, even if no statistical significance was reached (P = 0.064). The studies were heterogeneous with regard to SVR and drop-out rate. No publication bias was observed. One-third of dialysis patients with chronic hepatitis C were successfully treated with conventional or pegylated IFN monotherapy. Preliminary evidence does not support additional benefit due to monotherapy with pegylated IFN on the viral response in the chronic kidney disease (CKD) population. Tolerance to IFN monotherapy was unsatisfactory, particularly to pegylated IFN. The optimal antiviral treatment of chronic hepatitis C in dialysis populations is currently under active investigation.

Background: A relationship between hepatitis C virus (HCV) infection and chronic glomerulonephritis (GN) has been asserted on the grounds of epidemiological and experimental data. Although this suggests a role for an antiviral approach to HCV-associated GN instead of the more conventional immunosuppressive (or supportive) therapy, the optimal management of HCV related glomerulonephritis remains controversial., Objective: To compare antiviral with immunosuppressive therapy for HCV-associated GN., Design: Meta-analysis of controlled clinical trials (CCTs) of the two treatments (antiviral versus immunosuppressive) of HCV-associated GN., Methods: We used the fixed or random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. The rate of proteinuria and serum creatinine decrease after therapy for HCV-associated GN were regarded as the most reliable outcome end-points., Results: We identified six studies involving 145 unique patients with HCV-associated GN. Pooling of study results demonstrated that proteinuria decreased more commonly after IFN than corticosteroid therapy (OR 1.92 (95% CI, 0.39; 9.57), NS), P-test for heterogeneity, 0.06 (I2=52.9%). In a sensitivity analysis including only CCTs using standard IFN-doses, OR was 3.86 (95% CI, 1.44; 10.33, (P=0.007)), P-test for heterogeneity, 0.18 (I2=35.9%). No improvement of serum creatinine after IFN compared to immunosuppressive therapy was noted (OR, 0.59 (95% CI, 0.21; 1.65), NS), P-test for heterogeneity, 0.76 (I2=0%). Only three CCTs gave information on the rate of proteinuria decrease over follow-up (OR, 5.08 (95% CI, 0.69; 37.31), NS). A few major side effects were noted after IFN administration., Conclusions: Our meta-analysis indicates that standard IFN-doses were more effective than immunosuppressive therapy in lowering proteinuria of patients with HCV-related glomerulonephritis. However, no significant improvement in serum creatinine was seen by IFN or steroid therapy across the studies. Also, information on proteinuria recurrence after the completion of antiviral therapy was not sufficient. Prospective, randomized trials based on combined antiviral therapy (pegylated IFN plus ribavirin) with adequate dose and follow-up are required to assess the efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis.

Diminished survival due to hepatitis B has been observed after renal transplantation (RT). Lamivudine, a second-generation nucleoside analogue, has been approved for the treatment of chronic hepatitis B virus (HBV) infection in patients with normal renal function. Numerous clinical experiences with lamivudine after RT have been recently published. Despite numerous shortcomings, all of these reports have shown encouraging results. The rate of clearance of HBV viremia ranged between 67% and 100%, and the frequency of ALT normalization was between 50% and 100% with lamivudine use. Even patients with fibrosing cholestatic hepatitis, a serious form of HBV-related liver disease with ominous course, have been successfully treated with lamivudine. Lamivudine therapy significantly improved the survival of HBsAg positive renal allograft recipients. However, numerous issues concerning the treatment of hepatitis B after RT remain unclear: the optimal time to initiate lamivudine, the appropriate duration of antiviral therapy after RT, and the role for pre-transplantation liver biopsy. Also, the management of lamivudine resistance remains a concern for physicians. Clinical trials are under way.

Recent evidence has shown that anti- HCV-positive serologic status is significantly linked to lower patient and graft survival after renal transplant, but conflicting results have been given on this point. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on all-cause mortality and graft loss after RT. The relative risk of all-cause mortality and graft loss was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effect pooled estimates for mortality and graft loss with HCV across the published studies. We identified eighteen observational studies involving 133 530 unique renal transplant recipients. The summary estimate for adjusted relative risk ( aRR) of all-cause mortality was 1.85 with a 95% confidence interval ( CI) of 1.49; 2.31 ( P < 0.0001); heterogeneity statistics, R i = 0.87 ( P-value by Q-test = 0.001). The overall estimate for adjusted RR of all-cause graft loss was 1.76 (95% CI, 1.46; 2.11) ( P < 0.0001), heterogeneity statistics, R i = 0.65 ( P-value by Q-test = 0.001). Stratified analysis did not change meaningfully these results. Meta-regression showed that living donor rate had a favourable influence on patient ( P = 0.031) and graft survival ( P = 0.01), whilst diabetes mellitus having a detrimental role on patient survival ( P = 0.001). This meta-analysis of observational studies supports the notion that HCV-positive patients after RT have an increased risk of mortality and graft loss. Further studies are in progress to understand better the mechanisms underlying the relationship between HCV and mortality or graft dysfunction after renal transplant. [ABSTRACT FROM AUTHOR]

Background: The discrepancy between the number of potential available kidneys and the number of patients listed for kidney transplant continues to widen all over the world. The transplant of kidneys from hepatitis C virus (HCV)-infected donors into HCV naïve recipients has grown recently because of persistent kidney shortage and the availability of direct-acting antiviral agents. This strategy has the potential to reduce both waiting times for transplant and the risk of mortality in dialysis. Aim: We made an extensive review of the scientific literature in order to review the efficacy and safety of kidney transplant from HCV-viremic donors into HCV naïve recipients who received early antiviral therapy with direct-acting antiviral agents (DAAs). Results: Evidence has been rapidly accumulated on this topic and some reports have been published (n = 11 studies, n = 201 patients) over the last three years. Various combinations of DAAs were administered—elbasvir/grazoprevir (n = 38), glecaprevir/pibrentasvir (n = 110), and sofosbuvir-based regimens (n = 53). DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT. The sustained virological response (SVR) rate was between 97.5% and 100%. A few severe adverse events (SAEs) were noted including fibrosing cholestatic hepatitis (n = 3), raised serum aminotransferase levels (n = 11), and acute rejection (n = 7). It remains unclear whether the AEs were related to the transmission of HCV, the use of DAAs, or kidney transplant per se. It appears that the frequency of AEs was greater in those studies where DAAs were not given in the very early post-kidney transplant phase. Conclusions: The evidence gathered to date encourages the expansion of the kidney donor pool with the adoption of HCV-infected donor organs. We suggest that kidney transplants from HCV-viremic kidneys into HCV-uninfected recipients should be made in the context of research protocols. Many of the studies reported above were externally funded and we need research generating “real-world” evidence. The recent availability of pangenotypic combinations of DAAs, which can be given even in patients with eGFR < 30/min/1.73 m2, will promote the notion that HCV-viremic donors are a significant resource for kidney transplant.