Treatment issues surrounding hepatitis C in renal transplantation: a review

Hepatitis C infection is prevalent in candidates for and recipients of solid organ transplants. In the renal transplant population, HCV infection has been shown to decrease long-term patient and graft survival. The outcomes of HCV in recipients of other solid organ transplants are yet to be established and prospective studies will be needed in the future. In the absence of effective and safe antiviral treatment for HCV infection in renal, heart, and lung transplant recipients, the management of these patients remains a challenge and has led to an increased focus on identifying and treating hepatitis C in patients prior to transplantation. Interferon-based therapy for HCV prior transplantation appears to improve outcomes after transplantation. On the other hand, post-transplant interferon therapy is associated with an increased risk of graft rejection. Given the paucity of information on HCV treatment in solid organ transplant recipients, there is a great need for large-scale, multi-centre randomized controlled trials to determine the optimal approach to HCV infection in this population. This article will summarize the current peer-reviewed literature focusing on the efficacy of amantadine, ribavirin and both standard and pegylated interferon in the treatment of chronic hepatitis C in renal, transplant recipients.     

A concise review of hepatitis C in heart and lung transplantation

Hepatitis C (HCV) infection is prevalent in recipients of, and candidates for, solid organ transplants. The outcomes of HCV infection in cardiac and lung transplant recipients have yet to be clearly established, and future prospective studies are needed. In the absence of safe and effective antiviral treatment for HCV infection in heart and lung transplant recipients, the management of these patients remains a challenge and must be considered on an individual basis. Interferon therapy for HCV before transplantation appears to improve outcomes; however, post-transplant interferon therapy in the cardiac and pulmonary transplant setting may be associated with an increased risk of graft rejection. Given the paucity of information regarding HCV treatment in these transplant recipients, and with appropriate concerns that graft loss from rejection may not be amenable to a second transplant (given the scarcity of suitable cadaveric organs), multicentre, randomized controlled trials are needed to determine the optimal approach for treatment of HCV infection in this population.     

Hepatitis C virus and liver transplantation.

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.     

Viral hepatitis in solid organ transplantation other than liver

Transplantation is the best treatment for end-stage organ failure. Hepatitis virus infections, mainly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections still constitute a major problem because they are common in allograft recipients and are a significant cause of morbidity and mortality after transplantation. Recently, hepatitis E virus infection has been added as an emergent cause of chronic hepatitis in organ transplantation. The prevalence of HBV and HCV infections has markedly decreased in patients who are candidates for transplantation since the introduction of screening, hygiene and prevention measures, including systematic screening of blood and organ donations, use of erythropoietin, compliance with universal hygiene rules, segregation of HBV-infected patients from non-infected patients and systematic vaccination against HBV. A liver biopsy is preferable to non-invasive biochemical and/or morphological tests of fibrosis to evaluate liver fibrosis before and even after transplantation. Treatment with entecavir or tenofovir is indicated in HBV-infected dialyzed patients who have moderate or severe disease (≥A2 or F2 on the Metavir scale) in preparation for renal transplantation. Due to the risks of severe reactivation, fibrosing cholestatic hepatitis or histological deterioration after transplantation, systematic use of nucleoside or nucleotide analogues shortly before or at the time of transplantation is recommended (tenofovir or entecavir are preferable to lamivudine) in all patients, whatever the baseline histological evaluation. In HCV-infected dialyzed patients who are not candidates for renal transplantation, the indication for antiviral therapy is limited to significant fibrosis (fibrosis ≥2 on the Metavir scale). Treatment must be proposed to all candidates for renal transplantation, whatever their baseline histopathology, and interferon-α should be used as monotherapy. After transplantation, interferon-α is contraindicated but may be used in patients for whom the benefits of antiviral treatment clearly outweigh the risks, especially that of allograft rejection. All cirrhotic patients, notably after solid organ transplantation, should be screened for hepatocellular carcinoma. Sustained suppression of necro-inflammation may result in regression of cirrhosis, which in turn may lead to decreased disease-related morbidity and improved survival. Finally, due to the high mortality after renal transplantation, active (namely without sustained viral suppression) cirrhosis should be considered a contraindication to kidney transplantation, but an indication to combined liver-kidney transplantation; on the contrary, inactive (namely with sustained viral suppression) compensated cirrhosis may permit renal transplantation alone. Organ transplantations other than kidney (cardiac or pulmonary transplantations) involve the same diagnosis and therapeutic issues.     

Hepatitis C virus and kidney disease

Hepatitis C virus (HCV) infection remains frequent in patients on renal replacement therapy and has an adverse impact on survival in infected patients on chronic hemodialysis as well as renal transplant (RT) recipients. Nosocomial spread of HCV within dialysis units continues to occur. HCV is also implicated in the pathogenesis of renal dysfunction often mediated by cryoglobulins leading to chronic kidney disease as well as impairing renal allograft function. The role of antiviral therapy for hepatitis C in patients with renal failure remains unclear. Monotherapy with conventional interferon (IFN) for chronic hepatitis C is probably more effective in dialysis than in non-uraemic patients but tolerance is lower. Limited data only are available about monotherapy with pegylated interferon and combination therapy (pegylated IFN plus ribavirin) for chronic HCV in the dialysis population. Clinical experience with antiviral therapy for acute HCV in dialysis population is encouraging. Interferon remains contraindicated post-RT because of concerns about precipitating graft dysfunction. Sustained viral responses obtained by antiviral therapy in renal transplant candidates are durable after renal transplantation and may reduce HCV-related complications after RT (post-transplant diabetes mellitus, HCV-related glomerulonephritis, and chronic allograft nephropathy).     

Hepatitis C infection in transplantation

This review emphasizes the role of HCV in the transplant setting. Prolonged HCV infection results in end-stage liver disease and as such represents a common indication for liver transplantation. Recurrence of infection is almost universal after transplantation in those with viremia before transplantation. Acquired disease is uncommon but nevertheless important, particularly in organ populations in whom screening for infection is not routine. The natural history of post-transplantation disease suggests that the effect on graft or patient survival is minor, at least during short-term follow-up. Long-term follow-up is needed, as well as more detailed study of the factors contributing to severity of post-transplantation disease. Kidney transplant recipients are commonly infected with HCV prior to transplantation. HCV infection after transplantation is associated with an increased risk of liver disease and infectious complications, but its effect on survival is still controversial. Similarly, observations in recipients of other solid organ transplants, such as heart and lung, and bone marrow patients suggest that HCV infection usually is not a major cause of mortality in the first 5 to 10 years of follow-up. Many issues still need to be addressed. The most important is the identification of factors that contribute to disease progression. Finally, effective therapies to eradicate infection and prevent disease progression are awaited.     

Hepatitis C in non-hepatic solid organ transplant candidates and recipients:A new horizon

Hepatitis C virus(HCV) infection is estimated to affect 130-150 million people globally which corresponds to2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to nonhepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon(IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals(DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant(LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.     

Hepatitis C Virus Treatment in Non-Liver Organ Transplantation Programs

Purpose of Review

Solid organ transplantation is the treatment of choice for many patients with end organ damage. Hepatitis C (HCV) infection is prevalent among solid organ candidates and recipients and remains to be a significant source of morbidity and mortality for this population. New therapies are currently available for this population. In the following review, we will outline HCV treatment strategies in non-liver transplantation candidates and recipients.

Recent Findings

Direct-acting antivirals (DAAs) have drastically modified the treatment landscape of HCV. New DAA agents have been studied in patients with chronic diseases, transplantation candidates, and transplantation recipients.

Summary

The safety and efficacy of DAAs in patients awaiting liver transplantation and liver transplantation recipients has provided us with guidance on how to use them effectively for patients who received or are awaiting non-liver solid organ transplantations.

     

Spontaneous clearance of hepatitis C after liver and renal transplantation

Spontaneous clearance of hepatitis C virus (HCV) is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.     

Management of hepatitis C virus infection in liver transplantation

Because of graft reinfection and recurrence of the primary disease in the graft, patients who undergo transplantation due to cirrhosis caused by chronic hepatitis C virus (HCV) infection have a poorer long-term prognosis than non-HCV-infected transplant recipients. Apart from antiviral therapy, which can occasionally eradicate HCV infection before transplantation, there are no effective measures to prevent graft reinfection. Pre-transplantation antiviral therapy, however, is of limited applicability with currently available drugs. After liver transplantation, 2 options can be used to prevent graft loss due to HCV progression: early treatment in the first 4-6 weeks when there is still no evidence of histological injury and treatment of established HCV infection. Early antiviral therapy is limited not only by its scarce applicability but also by poor tolerability and limited effectiveness (sustained virological response in approximately 20-30% of patients). Treatment of established HCV infection, especially in patients with evidence of disease progression in biopsy, is the most cost-effective alternative with an efficacy of around 35-45% when pegylated interferon combined with ribavirin is used. Adverse effects, such as cytopenia and even induction of rejection, are the main limitation and lead to premature withdrawal in 30% of patients.     

Successful treatment of hepatitis C after kidney transplantation with combined interferon alpha-2b and ribavirin

The management of acute hepatitis C virus (HCV) infection after renal transplantation (RT) remains controversial, due to the potential risk of interferon-induced graft dysfunction. There is little experience with combined interferon and ribavirin therapy in this group of patients. We treated four consenting RT recipients who developed acute de novo HCV infection with a combination of interferon-alpha 2b and ribavirin. After 48 weeks' treatment, sustained virologic and biochemical remission were achieved in three patients infected with HCV genotypes 1a, 2, and 6a, respectively. The median time from treatment onset to ALT normalization was 8 weeks. The fourth patient was a non-responder infected with genotype 1b. Dose-dependent hemolysis was the most frequent side-effect. No patient developed allograft dysfunction. Our experience indicates that the judicious use of combined interferon and ribavirin can be considered in selected RT recipients with severe acute hepatitis C infection.     

Treatment with pegylated interferon and ribavirin for hepatitis C virus-associated severe cryoglobulinemia in a liver/kidney transplant recipient

End-stage liver disease after hepatitis C virus (HCV) infection is the most common indication for liver transplantation, accounting for over 40% of liver transplants performed. Combined liver/kidney transplantation is being performed more frequently, in part because HCV infection may coexist with conditions that damage the kidney, such as diabetes and cryoglobulinemia. Unfortunately, HCV hepatitis and cryoglobulinemia may recur after liver transplantation and adversely affect graft and patient survival. In immunocompetent patients, interferon (IFN) and ribavirin (RBV) combination therapy is often able to control cryoglobulinemic syndrome. Very little data are available on liver transplant recipients, whereas IFN usually is not indicated in kidney transplant recipients because of early reports of steroid-induced rejection after its administration. Successful treatment of cryoglobulinemia with IFN/RBV in recipients of combined liver/kidney transplant has not been previously reported. We treated 1 recipient of a combined liver and kidney transplant with pegylated-IFN/RBV combination therapy. The patient developed HCV recurrence associated with cryoglobulinemia and severe cutaneous peripheral and neurologic manifestations. Treatment with pegylated-IFN-alpha2b and RBV for 12 months cured the cryoglobulinemic vasculitis and allowed the sustained eradication of HCV with no significant changes in kidney function.     

Transmission of viral hepatitis by kidney transplantation: donor evaluation and transplant policies (Part 1: hepatitis B virus)

Abstract: This two-part article discusses serologic testing of prospective donors for viral hepatitis B and C as part of the comprehensive donor evaluation and reviews of the current policies and practices aimed at preventing donor-to-recipient transmission of hepatitis B and C viruses (HBV, HBC). This second part of the review discusses HCV. Organs procured from HCV-infected donors can transmit the virus to their recipients. Because a number of studies have associated infections with HCV with increased morbidity and mortality among renal transplant recipients, it is important to prevent HCV transmission with renal transplantation. The majority of organ procurement organizations (OPOs) perform routine screening of organ donors for antibodies to HCV (anti-HCV). The prevalence of HCV infection among cadaver organ donors, ascertained based on a positive anti-HCV test by ELISA2, varies worldwide between 1.08% and 11.8%. The use of kidneys from donors negative for anti-HCV by ELISA2 carries negligible or no risk of transmitting HCV infection. The use of organs from anti-HCV-positive donors has been restricted to life-saving transplants (heart, liver or lung) by the majority of OPOs worldwide. However, discarding kidneys from all anti-HCV positive donors would lead to unnecessary waste of organs because not all anti-HCV positive donors are infectious. Recently, the policy of unconditional restriction on the use of kidneys from anti-HCV positive donors has been challenged, and transplantation of organs from anti-HCV-positive donors into anti-HCV-positive recipients has been found to be safe. An even better alternative might be a policy of transplanting kidneys from anti-HCV-positive donors only in HCV RNA-positive recipients. However, until more data become available, these two strategies remain experimental treatments.     

Treatment of hepatitis B and C following nonliver organ transplants

Hepatitis B and hepatitis C virus (HCV) infections are major causes of liver-related morbidity and mortality in recipients of nonliver organ transplantation. The preemptive use of nucleoside analogues has greatly improved the outcome of those hepatitis B surface antigen-positive recipients of transplantation, and pegylated interferon should enable more HCV patients to be successfully treated before and after transplantation.     

Hepatitis B and hepatitis C virus and chronic kidney disease

The most common cause of liver disease in patients with chronic kidney disease (CKD) remains infection by hepatitis B virus (HBV) and/or hepatitis C virus (HCV). The adverse effects of HBV and/or HCV infections upon survival in patients with CKD have been repeatedly confirmed. An excess risk of death in HBsAg positive or anti-HCV antibody-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. A negative impact of HCV infection on survival after renal transplantation has been linked to extrahepatic complications, including chronic glomerulonephritis, sepsis, chronic allograft nephropathy, post-transplantation diabetes mellitus, and abnormal metabolism of calcineurin-inhibitors. Transmission of HCV infection by grafts from HCV-infected donors has been unequivocally demonstrated. Registry analyses suggest that recipients of kidneys from anti-HCV antibody positive donors are at increased risk of mortality. Renal grafts from HCV-infected donors should be restricted to viremic anti-HCV positive recipients. Several drugs have been recently licensed for therapy of HBV infection but availabledata in patients with CKD is mostly limited to experience with lamivudine. The standard of care for hepatitis C infection in patients on regular dialysis is monotherapy with conventional interferon, according to recent guidelines. Only dire circumstances justify interferon use after renal transplantation.     

The association between hepatitis C infection and survival after orthotopic liver transplantation

BACKGROUND & AIMS: The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV. METHODS: Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics. RESULTS: Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70). CONCLUSIONS: HCV infection significantly impairs patient and allograft survival after liver transplantation.     

To transplant or not to transplant recurrent hepatitis C and liver failure

In summary, re-OLT accounts for 10% of all OLTs performed and is associated with significantly increased resource use, and decreased survival compared with primary OLT. After transplantation into an HCV-infected recipient, infection of the allograft by HCV is invariable. As patients survive longer after liver transplantation, it is likely that allograft failure related to HCV recurrence will occur. Results of re-OLT for HCV are inferior to those of primary grafting, paralleling the results for retransplantation for other indications. Many studies have demonstrated that HCV infection significantly impairs patient and allograft survival after liver retransplantation, regardless of etiology of allograft failure. Patient survival rates with HCV infection are 57% to 65% at 1 year, as compared with 65% to 82% among patients without HCV infection. Experience with retransplantation is limited, however, and studies are difficult to interpret because of small sample sizes and lack of uniform definitions of survival, HCV recurrence, and allograft failure. Similar to outcomes after retransplantation for non-HCV related indications, the most common causes of death are sepsis and multi-organ failure. The high mortality associated with retransplantation has not universally been caused by recurrent disease, however recent studies have demonstrated that re-recurrent HCV occurs and the natural history is similar, if not more accelerated, after the second transplant. HCV infection may, in fact, increase mortality in a group of patients already predisposed to an inferior outcome. Preoperative serum creatinine and bilirubin have been consistently associated with survival after retransplantation and favorable results are attainable with strict selection criteria. The increasing use of expanded donor criteria, in particular, LRLT, raises important practical and ethical issues with regards to the HCV-positive transplant recipient and will become a challenge to the transplant community as a whole. With the donor morbidity and mortality associated with LRLT currently estimated at 32% and 0.3%, respectively, one must determine how much risk is acceptable to the donor in relation to the outcome in the recipient. This is especially true in HCV-infected recipients, in whom HCV re-recurrence may occur in the second allograft and lead to accelerated failure. LRLT, however, would not deplete the organ pool and would lead to the use of scarce cadaveric organs to patients who are awaiting primary liver transplantation. Despite inferior outcomes, a better tactic may be to consider retransplantation for recurrent HCV in those whose primary transplant was a LDLT, as the initial allograft did not deplete the donor pool. Given the shortage of donor organs and the increasing number of patients with HCV-induced allograft cirrhosis, identifying ways to improve allograft survival in HCV-infected patients represents an important focus for further research. Additional studies are needed to further explore the mechanisms underlying the reduction in survival and to identify which HCV-positive individuals are at greatest risk for poor survival. Studies are beginning to emerge that demonstrate that HCV recurrence can be modified with combination antiviral therapy and that the HCV virus can be eliminated. Additional longitudinal prospective studies are needed to assess the exact impact of HCV on survival after retransplantation, the effects of the newer immunosuppressive agents such as sirolimus and mycophenolate mofetil on HCV, the use of preemptive antiviral therapy on HCV eradication and fibrosis modification, and the appropriateness of expanded donor criteria. Until we have longer follow-up and greater experience with the HCV-positive recipient with allograft failure, retransplantation should be considered a viable option for highly selected patients, particularly in patients in whom renal failure and severe hyperbilirubinemia have not occurred.     

Treatment of recurrent hepatitis C after liver transplantation

Chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Europe, and more than 20,000 patients worldwide have undergone transplantation for complications of chronic hepatitis C. In North America, HCV accounts for 15% to 50% of the liver transplants performed in United States transplant programs. To maximize the long-term survival of liver transplant recipients who have HCV infection, eradication of infection is the ultimate goal. Pretransplant antiviral therapy with the goal of achieving viral eradication before transplantation is a consideration in some patients, especially those who have mildly decompensated liver disease. This article focuses on the management of liver transplant recipients who have HCV infection at the time of transplantation. Prophylactic and preemptive therapies, as well as treatment of established recurrent disease, are the strategies reviewed.     

Transmission of infection with human allografts: essential considerations in donor screening

Transmission of infection via transplantation of allografts including solid organs, eyes, and tissues are uncommon but potentially life-threatening events. Donor-derived infections have been documented following organ, tissue, and ocular transplants. Each year, more than 70?000 organs, 100?000 corneas, and 2 million human tissue allografts are implanted worldwide. Single donors may provide allografts for >100 organ and tissue recipients; each allograft carries some, largely unquantifiable, risk of disease transmission. Protocols for screening of organ or tissue donors for infectious risk are nonuniform, varying with the type of allograft, national standards, and availability of screening assays. In the absence of routine, active surveillance, coupled with the common failure to recognize or report transmission events, few data are available on the incidence of allograft-associated disease transmission. Research is needed to define the optimal screening assays and the transmissibility of infection with allografts. Approaches are reviewed that may contribute to safety in allograft transplantation.     

Hepatitis C virus infection in patients on renal replacement therapy

Hepatitis C virus infection is a frequent clinical problem in patients on dialysis and renal transplant recipients. The local prevalence rates of hepatitis C virus infection in patients on peritoneal dialysis, hemodialysis, or after kidney transplantation are 2%, 9%, and 6%, respectively. Conventional diagnosis of hepatitis C virus infection is by anti-hepatitis C virus immunoassays. However, up to 10% of immunosuppressed patients may be negative for anti-hepatitis C virus but positive for hepatitis C virus RNA. Repeated blood transfusions and a long duration of dialysis are major risk factors for hepatitis C virus infection among patients with renal failure. Although the risk of acquiring hepatitis C virus infection through transfusions has decreased considerably with the advent of screening tests for anti-hepatitis C virus, precautionary measures should be instituted rigorously at renal units to prevent nosocomial transmission. Hepatitis C virus infection in dialysis patients often assumes a relatively mild course. In contrast, renal allograft recipients can develop potentially life-threatening exacerbations, as exemplified by fibrosing cholestatic hepatitis. Liver disease of variable severity can be observed in about two thirds of hepatitis C virus-positive renal allograft recipients. In the majority of patients, however, the adverse effect of hepatitis C virus infection on survival may not be evident in the first decade after renal transplantation. Hepatitis C virus-positive patients with renal failure should not be excluded from kidney transplantation, but should be assessed individually with regard to the severity of liver disease before transplantation. Dialysis patients with hepatitis C virus infection, especially those with a potential for kidney transplantation, should be considered for treatment with interferon, because the risk of interferon in inducing renal allograft dysfunction is too high to justify its routine use in renal allograft recipients.