**3. Diagnosis**

Detection of HCV infection is based primarily on the type of laboratory test used and its sensitivity and specificity. Any false positive tests will lead to unnecessary waste of precious

potential organs for transplant (Natov & Periera, 2012). A large collaborative study was performed in United States that looked at the positive and negative predictive values of antibody screening tests. Eight organ procurement organizations representing different geographical regions studied 3078 cadaver organ donors. Using first generation enzyme linked immunosorbent assay ELISA1 anti-HCV test, the prevalence was found to be 5.1% (1.5-16.7%). Using the second generation ELISA2, the prevalence was 4.2%, with positive predictive value of 55% and negative predictive value of 100%. Some investigators have suggested the use of third generation ELISA3 tests to screen cadavers for HCV that be‐ cause of its improved specificity showed only 3.7% prevalence. On the other hand, the prevalence of HCV RNA (ribonuclease acid) detection by Polymerase chain reaction (PCR) was only 2.4%. Although discarding all ELISA2 positive organs would eliminate transmis‐ sion of HCV, there will be waste of 1.8% that will be discarded based on ELISA2 positivity while they are HCV RNA negative. However, it is currently not practical to test cadavers for HCV RNA status prior to organ procurement (Challine et al., 2004). The current practice in major centers is still to screen organ donors for antibodies against HCV. The serum amino‐ transferase levels are usually normal in uremic patients, and therefore are not considered reliable in determining disease activity and severity of fibrosis in this group. For clinically suspicious patients with elevated serum aminotransferase levels but negative antibody test, an HCV RNA assay with a detection limit of less than 50 IU/mL is recommended to rule out infection (Pawlotsky, 2002).

that HCV infection might be associated with increased insulin resistance contributing to

HCV has been associated with renal disease in both native and transplanted kidneys. It is in fact reported to be more associated with glomerular disease in renal transplants than native kidneys. This association is suggested to be secondary to immunosuppressive therapy leading to increased HCV RNA titres (Periera et al., 1995; Burstein & Rodby, 1993). In renal transplant recipients, HCV infection has been implicated in pathogenesis of acute glomerulopathy, de novo immune complex glomerulonephritis in allograft, and chronic allograft nephropathy (CAN) (Cosio et al., 1996; Roth et al., 1995; Ozdemir et al., 2006; Morales et al., 1997; Mahmoud et al., 2005). De novo membranoproliferative glomerulonephritis (MPGN), and de novo membranous glomerulonephritis (MGN), with or without mixed cryoglobulinemia are the most frequent glomerular patterns of injury seen in association with HCV infection in renal allografts. In 2001, one study reported the prevalence of de novo MPGN and MGN to be 45.4% and 18.2% in HCV positive transplant recipients as compared to 5.7% and 7.7% in HCV negative recipients (Cruzado et al., 2001). Subsequently, another study in 2006 reported the prevalence of de novo GN to be 34% in HCV infected recipients and only 6.6% in HCV negative recipients (Ozdemir et al., 2005). In general higher prevalence of autoimmune GN was associated with poor graft outcome, and even worse than de novo GN in HCV negative patients

Proteinuria is a common manifestation of kidney disease in HCV infected patients and renal biopsy is used to establish the diagnosis of glomerular injury, however currently it is impos‐ sible to determine HCV as the cause of glomerular damage based solely on morphologic

In 2005, Mahmoud et al reported a higher rate of CAN in HCV infected patients who did not receive interferon (IFN) therapy prior to renal transplant. Recent data also shows increased rate of graft failure due to CAN in HCV positive recipients than HCV negative (Scott et al., 2010). The Spanish Chronic Allograft Nephropathy Group analyzed 4304 renal transplant recipients with 587 of them being HCV positive over a period of 1990 to 2002. The study reported HCV infection to be associated with early proteinuria, lower renal function, de novo GN, chronic rejection, graft loss, and lower survival than HCV negative recipients (Morales et al., 2010). Another implication of HCV infection is its association with development of early graft dysfunction due to acute glomerular lesion. Examples of such lesions include acute transplant glomerulopathy, and de novo renal thrombotic microangiopathy (Cosio et al., 1996, Baid et al., 1995). Acute transplant glomerulopathy is mostly considered to be an atypical variant of acute cellular rejection and is also present more commonly in HCV positive

Detection of HCV infection is based primarily on the type of laboratory test used and its sensitivity and specificity. Any false positive tests will lead to unnecessary waste of precious

development of NODAT.

236 Current Issues and Future Direction in Kidney Transplantation

(Carbone et al., 2011).

assessment of renal biopsy. (Natov & Periera, 2012).

recipients (Cosio et al., 1996a, 1996b).

**3. Diagnosis**

There is limited data on the impact of different HCV genotypes on survival after transplanta‐ tion. Data reported by New England Organ Bank had relatively small number of patients and HCV genotype distribution to reach a conclusion (Natov et al., 1999).

Liver biopsy remains the gold standard for assessment of liver damage and fibrosis. Several scoring systems are used for assessment of hepatic fibrosis that use various criteria such as activity index and special stains for collagen deposition. Examples of these scoring systems include hepatic activity index (HAI), Knodell score and the Matavir system. Patients with HCV infection can have evidence of histologic liver disease in the absence of elevated transaminases and abnormal liver function tests. Therefore there may be merit in performing liver biopsy on all anti-HCV positive patients on transplant wait list. In patients with histologic evidence of liver disease, the decision to proceed or not with transplantation should be made with extreme caution as post-transplant immunosuppression may exacerbate liver disease (Zylerberg et al., 2002).
