Steven K. Herrine, MD
Associate Professor of Medicine
Thomas Jefferson University
Estimates of the prevalence of HCV antibodies in patients on hemodialysis (HD) range from 15-48% in North America (1). Prevalence rates are somewhat higher in other parts of the world, particularly in Egypt and Saudi Arabia. The incidence of HCV in HD patients is on the decline, probably due to blood product screening and tighter infection control measures in HD units. Similar to the case of HCV patients with normal renal function, the incidence of active viremia, as assessed by HCV RNA, is around 85% (2). Histologic activity is demonstrable in around 60% of patients on renal replacement therapy with anti-HCV (3). Unlike the non-HD population, in part because baseline ALT levels are depressed in patients on HD (4), 50-65% of patients with anti-HCV have normal aminotransferases (5). In fact, abnormal transaminases are seen in only 1/3 of those HD patients with biopsy proven hepatitis. Although the natural history of HCV infection in the HD population is largely unknown, liver failure is the cause of death in 8 to 28% of long-term renal transplant survivors (2).
Presence of anti-HCV in patients with end stage renal disease (ESRD) correlates well with multiple transfusions, time on hemodialysis, history of IVDU and previous transplant (2). Prevalence of HCV is much more frequent in patients with ESRD on hemodialysis (30%) than on peritoneal dialysis (<5%). Based on the high prevalence of anti-HCV in dialysis units, nosocomial infection is coming under scrutiny. Homogeneity of HCV serotypes has been demonstrated in patients from the same HD center (6). Physical proximity of HD patients to an infected patient is a risk factor for seroconversion. Steps to reduce nosocomial infection in HD units, including single-use heparin vials, glove changes between patients, cleaning and disinfection of all instruments and environmental surfaces that are routinely touched and dedicated dialysis machines have been suggested to reduce the incidence of HCV. No particular type of dialysis membrane has been implicated in the spread of HCV. The CDC does not currently recommend dedicated machines, patient isolation or a ban on reprocessing of dialyzers.
Diagnosis of HCV in HD Patients
Some patients have a fluctuating pattern of viremia, with virus free intervals of up to 4 weeks (7). Third generation EIA assays appear to be able to reduce false positive and false negatives. Viral load, as measured by branched-chain DNA or quantitative PCR, is in the same range as non-HD patients. Genotype frequency also matches that of the non-HD population. Liver biopsy has been suggested in patients with ESRD and HCV, especially those undergoing evaluation for renal transplantation, since liver histology has been shown to correlate with outcome after transplant (8). Liver histology can be abnormal despite normal aminotransferases with high frequency in this group, so normal liver tests need not dissuade the clinician from recommending biopsy. There does not appear to be increased risk associated with percutaneous biopsy in the ESRD population. The routine use of vasopressin (DDAVP) prior to percutaneous liver biopsy has not been established as the standard of care.
Interferon Therapy in Hosts with End-Stage Renal Disease
Very few data exist on interferon therapy of HCV in the end-stage renal disease population. To date only a handful of small trials are available for review in the published literature. Initial response rates (ETR) are comparable to those of non-HD patients when the data are analyzed assuming intention-to-treat. Sustained virologic response (SVR) rates have also been in the range of the series in non-ESRD patients. Data has emerged showing severe anemia in those ESRD patents receiving ribavirin, hence this indication is relatively contraindicated.
HCV After Renal Transplantation
Most HCV infection is transmitted before or during the time of transplantation, but the estimated risk of new infection following transplant is 0.45% per year (9). HCV can be transmitted in a renal graft but the rate of transmission is not well defined (10). Of those with HCV RNA, about 50% of patients develop abnormal transaminases after transplantation. Transplantation of an HCV(+) graft has not been shown to affect 5 year survival (2). Transplantation of an HCV(+) graft into an HCV(-) recipient remains controversial, since anti-HCV does not imply immunity, especially in a virus with the heterogeneity of HCV. Recent analyses have shown no difference in five-year survival between those HCV(+) recipients receiving HCV(+) grafts vs those receiving HCV(-) grafts. Pretransplantation HCV is associated with an increased risk of post-transplant liver disease, but data on survival is mixed. Based on data that immunosuppression dramatically increases viral load (11), there is theoretical reason to believe that a significant rise in the incidence of hepatic morbidity and mortality will result in this population.
IFN in Renal Transplant Patients
Experience with the use of interferon alpha as an anti-CMV agent following renal transplantation was complicated by a high incidence of steroid-resistant rejection and graft loss. An early attempt by Chan et al. to treat chronic hepatitis C in a transplant recipient with stable renal function met with virologic success, but the graft was lost 9 months after therapy (12). Another single case report of interferon use in a patient with combined HBV and HCV disease did not precipitate graft rejection, cleared HBV and led to a non-sustained virologic response for HCV (13). The largest series to date involves 16 patients, 37% of whom developed acute or subacute renal failure with IFN. Of these six patients (37%), 3 developed irreversible renal failure with diffuse interstitial edema leading to interstitial fibrosis (14). Based on these limited data, routine use of interferon for the therapy of HCV after renal transplantation should not be recommended.
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- Pol S. Thiers V. Carnot F, et al. Efficacy and tolerance of alpha-2b interferon therapy on HCV infection of hemodialyzed patients. Kidney Int. 47(5):1412-8, 1995.
- Chan TM. Hepatitis C virus infection in patients on renal replacement therapy. Nephrology. 2(Suppl 1):S 85-S 87, 1996.
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- Rostaing L. Izopet J. Cisterne JM, et al. Prevalence of antibodies to hepatitis C virus and correlation with liver disease in renal transplant patients. American Journal of Nephrology. 17(1):46-52, 1997.
- Sampietro M, Baladamenti S, Salvadori S, et al. High prevalence of rare hepatitis C virus in patients treated in the same hemodialysis unit: evidence for nosocomial transmission of HCV. Kidney Int. 1995;47:911-7.
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- Rao KV, Anderson RW, Kasiske BL, et al. Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients. Am J Med. 1993;94:241-50.
- Chan TM. Lok AS. Cheng IK. Chan RT. Prevalence of hepatitis C virus infection in hemodialysis patients: a longitudinal study comparing the results of RNA and antibody assays. Hepatology. 17(1):5-8, 1993.
- Pirson Y. Goffin E. Hepatitis C infection in renal transplant patients-new insights and unanswered questions. Nephrology, Dialysis, Transplantation. 11(Suppl 4):42-45, 1996.
- Fong TL, Valinluck B, Govindarajan S, et al. Short-term prednisone therapy affects aminotransferase activity and hepatitis C viral RNA levels in chronic hepatitis C. Gastroenterology. 1994;107:196-9.
- Chan TM. Lok AS. Cheng IK. Ng IO. Chronic hepatitis C after renal transplantation. Treatment with alpha-interferon. Transplantation. 56(5):1095-8, 1993.
- Rostaing L. Izopet J. Cisterne JM, et al. Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient. Scandinavian Journal of Urology & Nephrology. 30(6):485-487, 1996.
- Rostaing L. Modesto A. Baron E, et al. Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C. Nephron. 74(3):512-516, 1996.
Copyright August 2003 – Hepatitis C Support Project - All Rights Reserved. Permission to reprint is granted and encouraged with credit to the Hepatitis C Support Project.
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