Hepatitis C virus and kidney: a strong association with different clinical aspects
Evangelos Cholongitas, Fourth Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 49, Konstantinopoleos Street, 54642 Thessaloniki, Greece
Tel: +30 2310 892110
Fax: +30 2310 999942
The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis in patients with type II mixed cryoglobulinaemia. The principal clinical manifestations of glomerular disease in HCV-infected patients are the presence of proteinuria and haematuria with or without impaired kidney function. Pharmaceutical regimens vary because the main pathogenesis of renal dysfunction often mediated by cryoglobulins has not been fully elucidated. HCV infection remains common in patients on renal replacement therapy and has an adverse impact on their survival. Safe and effective pharmaceutical regimens have not been yet established and nosocomial spread within dialysis units continues to occur. Monotherapy with interferon for HCV infection is probably more effective in dialysis than in non-uraemic patients, while experience with ribavirin is limited because of its adverse haemolytic effect. Based on shortage of cadaver kidneys and the fact that HCV renal transplant recipients have better survival than stay on maintenance haemodialysis or at list for transplantation, health organization proposed the use of cadaver kidneys from anti-HCV-positive donors, bringing up concerns and conflicting views. This present review describes the main renal manifestations of HCV infection, the epidemiological and clinical characteristics of chronic kidney disease population and comments on the limitations and shortcomings of current therapeutical regiments.
Chronic infection with hepatitis C virus (CHC) is the second most common chronic viral liver disease with more than 170 million cases documented worldwide (1). It is estimated that 5–20% of patients with CHC will develop cirrhosis and 1–4% hepatocellular carcinoma. At risk for hepatitis C virus (HCV) transmission are drug users, patients who received blood products before 1992 and patients undergoing chronic haemodialysis (HD). More rarely, HCV is transmitted by unprotected sexual contact and vertical transmission (to the fetus from the infected mother) (2, 3). Of particular interest is the fact that CHC is often accompanied by other organ manifestations except the liver. The involvement of the kidneys is one of the most significant extrahepatic disorders of CHC and varies in frequency from 10 to 20% in the USA up 60% in Japan (4, 5).
Chronic infection with hepatitis C virus could be both the main cause and the complication of chronic kidney disease (CKD). For instance, on one hand, CHC is associated with essential mixed cryoglobulinaemia (MC) leading to membranoproliferative glomerulonephritis (MPGN) (6), and on the other, patients with CKD have an increased risk of infection because of prolonged use of vascular access and the frequent exposure to contaminated medical equipment. As a result, CHC reflects the most common chronic liver disease in patients with end-stage renal disease (ESRD) (7, 8) and consists a significant cause of mortality among HD and kidney transplant patients (9). This review aims to present key data on the association of CHC and CKD. The most common renal manifestations of CHC, the epidemiological and the clinical characteristics of HCV-infected patients requiring renal replacement therapy (HD and kidney transplantation) are described, while the limitations and the inadequacies of the current antiviral therapeutic regimens are discussed in this patient population.
Hepatitis C virus and extrahepatic renal manifestations
The most common renal disease associated with CHC is the MPGN in patients with type II MC (10). Over 80% of patients with MC are suffering from CHC, while cryoglobulins are present in all patients with MPGN associated with CHC. Although the mechanisms that cause renal damage are not fully elucidated (11), it seems that the formation of immune complexes [HCV antigens, anti-HCV IgG antibody and rheumatoid factor (RF) IgM κ] contribute to the in situ tissue destruction owing to the deposition of virus nuclear protein and immunoglobulins in the glomerular capillary wall, renal interstitium and tubules (12).
The MC in the context of CHC consists of a lymphoproliferative disorder (13) and the best-studied extrahepatic syndrome of CHC. Its incidence increases with the duration of CHC and is associated with the severity of liver fibrosis (14). Although the predisposing factors for the expression of cryoglobulinaemic vasculitis in patients with CHC remain unclear, there are links with older age, longer duration of CHC and increased number of B lymphocytes in patients' blood and liver (15). Glomerulonephritis is developed several years, often decades, after initial infection with HCV (16) and suggests a worse prognostic factor for the outcome of chronic liver disease (17). The typical renal manifestations in HCV-infected patients include nephrotic range proteinuria and microscopic haematuria, while 80% of patients may develop hypertension, 50% mild renal failure (18) and 20 and 25% acute nephritis and nephrotic syndrome, respectively, with rapid deterioration of renal function. However, the renal disease may be asymptomatic, and thus HCV-infected patients are recommended to be screened for proteinuria, haematuria, hypertension, RF and cryoglobulins (19, 20). Usually, blood laboratories reveal cryoglobulins type II, IgM RF and low values of C3, C4 and C1q (18). On renal biopsy, the most common findings are focal proliferation of capillary wall and mesangial hyperplasia with crescents and subendothelial eosinophilic deposits on some glomeruli. On immunofluorescence microscopy, the most characteristic finding is the fixation of C3, IgM and IgG on the capilliary wall and mesangium, showing a fibrinary or dotted-line pattern on electronic microscopy (cryoglobulin deposition) (12).
Other renal manifestations in CHC patients are MPGN without cryoglobulinaemia, membranous nephropathy, proliferative glomerulonephritis (21), focal segmental glomerular sclerosis (22) and IgA nephropathy (23). Furthermore, cases of fibrillary and immunotactoid glomerulopathy (24, 25) and renal thrombotic microangiopathy associated with anticardiolipin antibodies have been reported (11, 25).
Therapy of hepatitis C virus-related glomerulonephritis
The mainstay management for HCV-related glomerulonephritis is immunosuppressive therapy (corticosteroids and cytotoxic agents), plasmapheresis and antiviral therapy. The proven beneficial measures for nephroprotection (blood pressure lowering, antiproteinuric and lipid-lowering agents) are applicable in the majority of cases, given that the predominant clinical manifestations of the disease are proteinuria, hypertension and progressive reduction of renal function.
Owing to the relationship between HCV infection and the immune response targeting the glomeruli, there are two modern approaches for the therapy of HCV-related glomerulonephritis: (i) antiviral treatment with a combination of standard or pegylated interferon (IFN) with ribavirin (RBV) without significant side effects in order to achieve sustained viral response (SVR) (16) and (ii) immunosuppressive therapy (including rituximab administration) followed by antiviral treatment, particularly in patients with acute nephritic or nephrotic syndrome (26). Generally, the combined therapy with IFN [either in its standard or pegylated (PEG-IFN) form] and RBV aims to reduce the viral load and rituximab aims to reduce B lymphocytes (through its adherence to the CD20 cell surface antigen). Rituximab seems to have better results than classic immunosuppressants, corticosteroids and cyclophosphamide, achieving complete or partial clinical remission in 80–90% of the cases, with skin and renal disease responding better compared with nerve or joint disease. Rituximab affects mainly monoclonal IgM production, cryoglobulin composition and renal immune complex deposition by improving the vasculitic symptoms (27, 28). Patients with severe manifestations should be treated more aggressively, not only by immunosuppressive agents but also with plasma exchange therapy for the first 6 months and then after having achieved remission, should start antiviral treatment (29). Plasmapheresis has a more direct and effective impact on rapidly progressive glomerunephritis involving the central nervous, gastro-intestinal and respiratory system, provided it is combined with immunosuppressive therapy to prevent cryoglobulin redeposition after the session (30).
Depending on the degree of proteinuria and renal failure, the Kidney Disease: Improving Global Outcomes (KDIGO) (31) and the American Association for the Study of Liver Diseases (AASLD) (32) guidelines are follows: all patients should be treated with angiotensin-converting enzyme inhibitor and angiotensin receptor (AT2) blockers. In patients with cryoglobulinaemia, mild proteinuria and slow progression of renal disease treatment is suggested with IFN (standard or PEG-IFN form) in low doses combined with RBV (31–38) (Tables 1 and 2). In patients with a significant degree of proteinuria and an acute flare of cryoglobulinaemia, rituximab (although its exact dose has not been elucidated yet) or cyclophosphamide with methylprednisolone or plasmapheresis followed by the appropriate antiviral therapy after remission should be prescribed.
Table 1. Antiviral therapy in hepatitis C virus(+) glomerulonephritis depending upon patient's glomerular filtration rate (31, 32)
|GFR>50 ml/min/1.73 m2||As on HCV(+) patients without kidney disease||PEG-IFN|
a-2a180 μg/weekly or a-2b1.5 μg/kg/weekly
|GFR=15–50 ml/min/1.73 m2||Monotherapy with PEG-IFN on adjusted doses. In case of RBV administration; meticulous attention to side effects, mainly haemolytic anaemia||PEG-IFN|
a-2a135 μg/weekly or a-2b1 μg/kg/weekly
|GFR<15 ml/min/1.73 m2 (including and haemodialysis patients)||Monotherapy only with standard IFN⇒PEG-IFN on adjusted doses||IFN|
3 MU t.i.d. weekly or
a-2a135 μg/weekly or
Table 2. Results of interferon therapy in hepatitis C virus(+) glomerulonephritis (data from the most recent six studies)
|2004||Alric et al. (33)||18||1, 4:14/18|
2, 3: 4
|IFN: 3 MU t.i.d. weekly|
|66.7||Significant decrease of proteinuria in SVR responders|
|PEG-IFN: 1.5 mcg/kg/weekly (n=4)|
+RBV: 600–1000 mg/daily for 6–24 months
|2006||Cua et al. (34)||1||4||PEG-IFN a-2b|
1.5 mcg/kg/weekly for 44 months (after unsuccessful therapy with IFN)
|NA||Disappearance of proteinuria|
|2007||Garini et al. (35)||4||1, 1b/1a, 1b||IFNa: 3 MU t.i.d. weekly|
+RBV: 15 mg/kg/daily(n=2) or
|75||Decrease of proteinuria in SVR responders|
Relapse of proteinuria in one patient with no HCV RNA eradication
|PEG-IFN a-2b: 100 μg/kg/weekly|
+RBV800 mg/daily (n=1) or
|PEG-IFN a-2b80 mcg/weekly|
+RBV: 15 mg/kg/daily (n=1) for 28–48 weeks
|2008||Abbas et al. (36)||40||3a||IFNa: 3 MU t.i.d. weekly|
+RBV: 200–1000 mg/daily for 6–12 months
|26.6||Significant decrease of proteinuria and normalization of C3 and C4 concentration in SVR responders|
|2009||Lo et al. (37)||1||NA||IFNa: 3 MU daily for 6 months|
Then IFNa:3 MU every other day for 9 months
|NA||Disappearance of serum cryoglobulins, proteinuria and signs of cutaneous vasculitis|
|2010||Namba et al. (38)||1||1b||IFNa: 6 MU t.i.d. weekly for 2 weeks|
Then PEG-IFN a-2b:40 μg/weekly
mg/daily for 6–12 months
|NA||Significant decrease of proteinuria|
However, a number of issues need further clarification regarding the exact duration of the treatment, its efficacy and safety (30). The antiviral treatment is usually prescribed for 6–12 months (in patients who respond to IFN within the first 3 months of treatment) (39, 40). Patient's response to antiviral therapy depends on the viral genotype. SVR is achieved in 65–90% of patients with genotypes 2 and 3, compared with only 30–50% of those with genotype 1 (16).
Hepatitis C virus and haemodialysis
Hepatitis C virus-infected HD patients have lower survival rates compared with HCV(+) patients without renal failure, because they also present comorbid diseases, including co-infections [for instance with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)] (16). The prevalence of CHC among patients with ESRD on maintenance HD is higher than the general population, ranging from 1.9 to 84.6% (41), with the highest records in Brazil (42), Perou (43) and Bosnia-Herzegovina (42). In Greece, the disease prevalence ranges from 9.9% in 1945 to 24% in 2005 (44). The high seropositivity rate reflects intensive viral exposion and hospital transmission in HD environment because of frequent subcutaneous vascular punctures, frequent transfusions (although they have been dramatically reduced since erythropoietin use and blood product control in recent years) and inadequate screening for CHC (45). Predisposal factors for infection considered are time on HD (46–50), diabetes mellitus, young age, receiving HD treatment from multiple different centres and co-infection with HBV and HIV (51–55).
It is noteworthy that the lack of a reliable method for early diagnosis of HCV seropositivity is partly responsible for the increased prevalence of CHC in this patient group. In particular, the diagnosis of CHC is based on the detection of antibodies against the virus by enzyme-linked immunoassay (ELISA) and determination of HCV RNA by polymerase chain reaction (PCR). It is known that ELISA, first- and second-generation tests, detects false negative results in 2.6% of immunocompromised patients (56) (group to which HD patients belong); therefore, the ELISA third-generation test is suggested for anti-HCV evaluation in HD patients. Moreover, samples for HCV RNA testing should be obtained at the initiation of HD session, before heparin administration and blood contact with the haemofilter, because part of the HCV RNA binds to the dialyser membrane, affecting the accurate determination of viral load and changing the reliability of the method (57). More contemporary and sensitive methods for the qualitative detection of the virus, such as the HCV RNA qualitative assay based on transcription-mediated amplification (TMA), are considered a better option. The largest study evaluating TMA has been conducted in Greece, where in 366 HD patients the percent virus detection increased to 33.3% (44). Of particular interest is the capability to find the virus nuclear antigen even before the detection of its antibodies by ELISA. Therefore, HCV infection can be determined 1.5 months earlier than the virus antibodies by ELISA and only 2 days later by the detection of viral RNA (58, 59).
Furthermore, significant difficulties for early diagnosis of HCV infection are pointed out when the course of infection is indolent and liver biochemistry increase is mild (60, 61). Generally, HD patients without chronic liver disease have lower aminotransferase values compared with the non-numeric population. This feature complicates the diagnosis of HCV infection in HD patients, because liver enzyme values do not increase significantly above or they may be within the normal range. By using a lower cut-off value of serum alanine aminotransferase (ALT), e.g. reduced by half (62) or ALT ≥27 IU/l (63), HD patients with HCV infection could be identified. Consequently, it is recommended monitoring ALT monthly, screening for HCV antibodies every 6 months (64, 65) and hepatitis A and B vaccination, as co-infection with other hepatotropic viruses aggravates the prognosis (66–68).
Basically, the exact extent of liver damage can only be established by liver biopsy (69–72). Transjugular liver biopsy is preferable over the percutaneous owing to the abnormalities of platelet function that characterize these patients (73, 74). Regarding the non-invasive tests (75), although at first Fibrotest was considered a reliable marker of liver fibrosis on HD patients (thus great portion of liver biopsies could have been avoided) (76), recent data queried its diagnostic value (77); thus, more research is necessary in this field. It has been suggested that the degree of liver damage was milder in HCV(+) HD patients compared with HCV(+) patients without renal failure or chronic renal disease without been on HD (61, 78). This fact could be attributed to different immunological status, lower viral load (79), prolonged hepatocellular growth factor secretion (80) and increase in endogenous IFN after each HD session (81). Similar findings have been found in patients with recurrent CHC after liver transplantation, where the progression rate of liver fibrosis was lower in HCV(+) patients with renal insufficiency compared with HCV(+) patients with normal renal function (82). Nevertheless, HCV(+) HD patients have poorer prognosis compared with HD patients without HCV infection. In a recent meta-analysis, which included seven trials with 11 589 patients, it was found that HCV(+) HD patients presented 1.3 times greater risk of death (mainly because of the development of cirrhosis and hepatocellular carcinoma) with regard to HCV(−) HD patients (83).
Treatment of hepatitis C virus (+) haemodialysis patient
Treatment of HCV(+) HD patients is complex and difficult. Joint action of nephrologists and hepatologists for close monitoring of these patients is necessary, as still an optimal antiviral treatment regimen has not been determined (84–96) (Table 3). The value of HCV genotype as a predictor of response to IFN therapy is debatable. Patients with CHC on HD may receive standard IFN (2a or 2b) in a dose of 3 mU three times weekly or a reduced dose of PEG-IFN, 2a or 2b, 135 μg and 1 μg/kg/week, respectively, with or without the addition of low-dose RBV (32). PEG-IFN alone does not seem to overweigh standard IFN in achieving SVR, because around one-third of CHC patients on HD were successfully treated by standard or PEG-IFN monotherapy. Moreover, the combination of IFN with RBV in a markedly reduced dose might be tested, providing that the levels of haemoglobin are under close monitoring (32, 97–99). Finally, in terms of acute HCV infection, the early introduction of PEG-IFN in patients who did not have spontaneous clearance of HCV by 16 weeks has been associated with high SVR rates (100, 101). In addition, taking into account the possible mild course of HCV infection, it seems reasonable that antiviral therapy is not an optimal option for patients with a diminished likelihood of survival or with complications such as diabetes mellitus or congestive heart failure (68, 102, 103).
Table 3. Results of interferon therapy in hepatitis C virus(+) haemodialysis patients (from studies published between 2006 and 2010)
|2006||Russo et al. (84)||16||15||NA||PEG-IFN a-2b||0.5–1 mcg/kg/week for 24 weeks||12.5|
|2007||Rocha et al. (85)||23||10||5||IFN a||3 MU t.i.d./weekly for 48 weeks or 5 MU t.i.d./weekly for 24 weeks||43|
|2007||Casanovas-Taltavul et al. (86)||12||7||4||PEG-IFN a-2a||135 mcg/week for 48 weeks||25|
|2007||Amarapurkar et al. (87)||6||1||3||PEG-IFN a-2b||1 mcg/kg/week for 24 weeks||50|
|2007||Chan et al. (88)||6||2||4||PEG-IFN a-2a||135 mcg/week for 48 weeks||33|
|2007||Espinosa et al. (89)||16||NA||NA||PEG-IFN a-2a (n=7)|
PEG-IFN a-2b (n=9)
|135 mcg/week for 48 weeks (n=7)|
1.5 mcg/week for 48 weeks (n=9)
|2009||Liu et al. (90)||25||20||5||PEG-IFN a-2a||135 mcg/week for 24 weeks||48|
|2008||Akhan et al. (91)||12||12||0||PEG-IFN a-2a||135 mcg/week for 24 weeks||50|
|2008||Ayaz et al. (92)||22||22||0||PEG-IFN a-2a||135 mcg/week for 24 weeks||50|
|2008||Ucmak et al. (93)||12||12||0||PEG-IFN a-2a||135 mcg/week for 24 weeks||50|
|2008||Arrais et al. (94)||15||9||6||IFN a||3 MU t.i.d./weekly for 48 weeks||NA|
|2007||Sikole et al. (95)||14||13||1||PEG-IFN a-2a||135 mcg/week for 48 weeks||41.6|
|2010||Alsaran et al. (96)||13||13||0||PEG-IFN a-2a||135 mcg/week for 48 weeks||69|
Based on KDIGO recommendations, candidates for antiviral treatment are patients who meet the criteria for inclusion in the list for kidney transplantation because they are considered to have higher survival advantage (3, 45) (Table 4). Successful pretransplant treatment reduces post-transplant virological relapse, incidence of diabetes mellitus and de novo glomerulonephritis in HCV(+) recipients (102, 103).
Table 4. Antiviral therapy for hepatitis C virus(+) haemodialysis patients candidating for renal transplantation (KDIGO) (31)
|IFN: 3 MU t.i.d./weekly or|
|PEG-IFN: α-2a 135 μg/weekly or α-2b 1 μg/kg/weekly|
| ± RBV induction dose 200 mg/daily, subsequently adjusted to plasma concentration of RBV|
Hepatitis C virus and renal transplantation
The CHC is a point of great concern in the renal transplantation (RT), as 5–40% of kidney transplant recipients suffer from CHC (104). The HCV(+) recipients present increased morbidity not only because of liver pathology but also because of other comorbidities. They are at a high risk developing post-transplant diabetes mellitus, sepsis (16), glomerulonephritis (105, 106), renal graft nephropathy (acute and chronic) and renal thrombotic microangiopathy (107).
Prospective hepatitis C virus (+) renal transplant donors
Several studies have shown that the use of kidney grafts from anti-HCV-positive donors in HCV(+) recipients is associated with superior patient survival compared with those remaining on dialysis (108). Hence, as the list of candidate recipients is constantly increasing without the concomitant augment of available donor organs, the KDIGO statements have allowed RT from HCV(+) donor to HCV(+) recipient since 2008 (31). This cannot be stated for HCV(−) recipients, because the published evidence for documenting this point is not enough to reach a final conclusion.
Prospective hepatitis C virus (+) renal transplant recipients
Hepatitis C virus (+) kidney graft recipients showed a higher risk of rapidly progressive liver disease because of the immunosuppressive therapy after RT. It was found that there was a 1.8–30.3-fold increment on viral load after RT (109). Nevertheless, the highest viral load did not appear to correlate strictly with rapidly histological deterioration of liver lesions after RT (110, 111). These patients typically exhibit chronic hepatitis with its complications and very rarely fibrosing cholestatic hepatitis, a special type that includes severe cholestasis and rapidly progressive liver failure (111).
Although the complications of chronic liver disease incur the morbidity of HCV-infected recipients, their survival may not differ significantly from HCV(−) recipients (112, 113). Most studies have highlighted a slight difference at 5-year survival, but at 10 years, the survival of HCV(+) renal transplant recipients reduces significantly (114). Although these findings were confirmed in a recent meta-analysis (114), it is brought again to notice that despite the complications, HCV-infected recipients have better survival than when left without RT (115–117). In conclusion, HCV(+) patients with ESRD should not be definitely excluded from the RT list.
Every prospective HCV-infected recipient must necessarily go through a liver biopsy in order to determine the degree of liver fibrosis, because it is considered a crucial predictive factor for liver progression post-RT (118). Generally, HCV(+) kidney transplant candidates presented significant liver fibrosis, although without exceeding the severity level of HCV(+) patients without kidney disease and normal liver biochemistry (119). Cirrhosis is the contra-indication for RT, as it is strongly related with post-transplant patient mortality and renal graft impairment. Furthermore, the advance of liver fibrosis should be monitored before and after RT. The common liver histological findings for this patient group have not been notified yet. The majority of studies underline the negative influence of RT to CHC infection (118). However, Kamar et al. (120) documented stability or regression of CHC on >50% of kidney recipients and emphasized that HCV diversification 3 years after RT could predict the outcome of liver fibrosis. In this direction, the liver biopsy and the non-invasive tests may play a key role for the assessment of liver dysfunction on HCV-infected renal patients (76).
Treatment of hepatitis C virus infection after kidney transplantation
Generally, antiviral therapy after RT is not considered a safe option (121). It is recommended only in terms of fibrosing cholestatic hepatitis or de novo glomerulonephritis (31, 32) (Table 5). Post-transplant use of IFN has limited efficacy, high cost and increases the risk of irreversible renal graft rejection in 15–64% of cases (122, 123) by promoting the cytotoxic action of T lymphocytes and monocytes, cytokine and HLA antigen production (124). Relating to RBV, although its administration does not result in graft rejection, when given as a monotherapy it showed no impact on liver fibrosis (125, 126). Nevertheless, there is a pilot study pointing out that PEG-IFN a alone or with RBV combination, achieved significant SVR with a low risk of renal dysfunction in RT recipients with favourable genotypes (127), while new antiviral drugs are anticipated with great interest (16).
Table 5. Antiviral therapy of hepatitis C virus(+) renal transplant recipients in case of fibrosing cholestatic hepatitis and de novo glomerulonephritis (31, 32)
|Fibrosing cholestatic hepatitis||IFN (3 MU t.i.d. weekly) or|
PEG-IFN (α-2b 1 μg/kg/weekly⇒a-2a 180 μg/weekly)
+RBV on low doses carefully, for avoiding renal graft rejection (better option)
|De novo glomerulonephritis||De novo glomerulonephritis with mild proteinuria, stable renal function and moderate renal histological lesions||Antiviral therapy only, depending on the degree of liver damage|
|Severe de novo glomerulonephritis under risk of chronic graft dysfunction||IFNα or|
24 weeks for genotypes 2 and 3 or 48 weeks for genotypes 1 and 4
Regarding the maintenance of immunosuppressive treatment after RT, cyclosporine and mycophenolic acid appeared to suppress viral replication, contrary to steroids and anti-CD3 antibody (OKT3), which appeared to have a negative effect.
Conclusion and suggestions
Although the correlation of cryoglobulinaemic glomerulonephritis with CHC is apparent, several pathophysiological mechanisms require further investigation. These mechanisms include: (a) the occurrence of manifested cryoglobulinaemia only in a few HCV-infected patients, (b) the process leading to the proliferation of B lymphocytes with the participation of RF and (c) the exact procedure by which immune complexes are causing endothelial damage (6). In addition, there are questions relating to the treatment of HCV-connected glomerulonephritis that need clarification. More intensified studies should be conducted for HCV(+) patients with declined renal function.
Regarding HD patient population, although the post-transfusion transmission of HCV has been eliminated because of serological screening of blood and blood products and the routine use of erythropoietin for dialysis in patients with severe anaemia, the rate of nosocomial HCV transmission is still high, particularly in the non-industrialized world because of inadequate infection control. Third-generation ELISA should be the first diagnostic approach, while screening HCV RNA by PCR is costly and time consuming. Management of these patients is a medical challenge. Achieving SVR may lead to renal function amelioration, reduce the extrahepatic disease manifestations and guard against post-transplant complications.