HCV response in patients with end stage renal disease treated with combination pegylated interferon alpha-2a and ribavirin.
ABSTRACT To determine the efficacy and safety of combination therapy in patients with hepatitis C virus (HCV) and end-stage renal disease (ESRD).
There is little data on the treatment of ESRD patients with pegylated interferon and ribavirin. We designed a pilot study to determine the initial and 12-week posttreatment viral response.
A nonrandomized, prospective observational study of adjusted-dose combination therapy. Twenty patients were enrolled and began pegylated interferon at 135 microg/wk SC, and 4 weeks later ribavirin was started at 200 mg PO weekly, increasing gradually to 3 times a week for a total of 48 weeks.
Twenty patients: M:F 18:2; mean age 52.4 years; genotype 1: 18, non-genotype 1: 2. Of the 20 patients, 5 withdrew before starting treatment. Of the 11 patients who reached 3 months, 6 had early virologic response, defined as at least a 2-log drop in their HCV count (54.5%). Of the 5 patients who were treated for 1-year, only 1 patient had a response 12 weeks after treatment. Side effects included 4 cases of anemia and 1 patient with headache.
The initial response rate in individuals taking 3 months of treatment in our study is comparable with studies in non-ESRD patients with no serious adverse side effects. However, the sustained posttreatment rate was low. This demonstrates that combination therapy is a safe therapeutic option in the ESRD population with HCV infection which needs further testing to determine if increasing the length of treatment and/or the dose of ribavirin will affect posttreatment rates.
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ABSTRACT: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most common and serious causes of liver damage in patients with chronic kidney disease (CKD). The natural histories of HBV and HCV infections in patients with CKD are not fully understood; however, recent evidence has emphasized the adverse effect of HBV and/or HCV infection on survival in this population. Chronic liver disease is the fourth most important cause of death after renal transplantation. The negative effect of HCV infection on survival among renal transplant recipients has been linked to liver dysfunction and extrahepatic complications, such as chronic glomerulonephritis, post-transplantation diabetes mellitus, chronic allograft nephropathy, and sepsis. The transmission of HCV by solid organ transplantation has been unequivocally demonstrated. Renal transplant recipients who receive kidneys from HCV-positive donors are at increased risk of death. Although several studies have shown that in patients with HCV infection and chronic renal failure renal transplantation is associated with better survival than is dialysis, recent clinical guidelines recommend that kidneys from HCV-infected donors should not be used in HCV-seropositive recipients without detectable HCV viremia. Monotherapy with conventional interferon has been suggested to be a useful treatment for hepatitis C infection in patients on dialysis. Although no evidence suggests that patients with CKD are more prone to suffer from hepatic toxic effects than individuals with normal kidney function, patients with CKD usually receive multiple medications; and drug interactions may, therefore, have a role in the pathogenesis of drug-induced liver disease in this population.Nature Reviews Nephrology 04/2010; 6(7):395-403. DOI:10.1038/nrneph.2010.37 · 8.37 Impact Factor
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ABSTRACT: Liver disease related to chronic viral hepatitis is a major cause of morbidity and mortality in renal transplant patients. There is no agreement upon the influence of chronic hepatitis B (HBV) and hepatitis C (HCV) infection in patient and graft survival. The aim of the study was to evaluate the influence of HBV and HCV on patient and graft short and long term survival, in the patients transplanted at our institution. We evaluated the influence of antiHCV and HBsAg status (positive vs. negative); sex; age (> 49 years vs. < 49 years at transplantation); time on dialysis (> 3 vs. < 3 years); acute rejection; kind of graft (deceased vs. living donor, and kidney versus kidney and pancreas); number of transplantations; use of induction immunosuppression; and maintenance immunosuppression treatment (comparing the traditional triple therapy containing azathioprine, cyclosporine and prednisone vs. newer regimens which include tacrolimus, mycophenolate mofetil, sirolimus, etc) on the survival, long term and within the first month of transplantation, of the graft and the patients transplanted in our Institution between January 1991 and August 2009. We included 542 patients, 60% males. median age of 42.03 years (SD 13.06 years). 180 patients (33%) were antiHCV positive and 23 (4%) were HBsAg positive. AntiHCV positive, traditional triple therapy and acute rejection were associated with diminished graft survival. Older age, antiHCV positive, HBsAg positive, deceased donor, kidney-pancreas transplantation and traditional triple therapy were associated with diminished patient survival. Traditional triple therapy was associated with diminished one month graft survival; and older age and antiHCV positive were associated with diminished one month patient survival. In our experience, antiHCV positive status was associated with diminished long term patient and graft survival, and diminished six month graft survival; and HBsAg positive was associated with diminished patient survival.Annals of hepatology: official journal of the Mexican Association of Hepatology 04/2010; 9(3):271-7. DOI:10.1016/S0168-8278(10)61072-0 · 2.19 Impact Factor
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ABSTRACT: 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.Journal of Medical Virology 05/2010; 82(5):768-75. DOI:10.1002/jmv.21542 · 2.22 Impact Factor