Hepatitis: Kalantar-Zadeh K

Kalantar-Zadeh K, Daar ES, Eysselein VE, Miller LG. · Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910, USA. · Int Urol Nephrol. · Pubmed #17009087 No free full text.

Abstract: Among the 350,000 maintenance dialysis patients in the USA, the mortality rate is high (20-23% per year) as is the prevalence of hepatitis C virus (HCV) infection (5-15%). An additional same number of dialysis patients in the USA may be infected with HCV but have undetectable HCV antibodies. Almost half of all deaths in dialysis patients, including HCV-infected patients, are due to cardiovascular disease. Since over two-thirds of dialysis patients die within 5 years of initiating dialysis and because markers of malnutrition-inflammation complex syndrome (MICS), rather than traditional cardiovascular risk factors, are among the strongest predictors of early death in these patients, the impact of HCV infection on nutritional status and inflammation may be a main cause of poor survival in this population. Based on data from our cross-sectional and limited longitudinal studies, we hypothesize that HCV infection confounds the association between MICS and clinical outcomes in dialysis patients and, by doing so, leads to higher short-term cardiovascular events and death. Understanding the natural history of HCV and its association with inflammation, nutrition and outcomes in dialysis patients may lead to testing more effective anti-HCV management strategies in this and other similar patient populations, providing benefits not only for HCV infection but the detrimental consequences associated with this infection. In this article, we review the link between the HCV infection and mortality in dialysis patients and compare HCV antibody to molecular methods to detect HCV infection in these individuals.

Regidor DL, Kovesdy CP, Mehrotra R, Rambod M, Jing J, McAllister CJ, Van Wyck D, Kopple JD, Kalantar-Zadeh K. · Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90509-2910, USA. · J Am Soc Nephrol. · Pubmed #18667733 No free full text.

Abstract: Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos > or =120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P < 0.001). This association remained among diverse subgroups of hemodialysis patients, including those positive for hepatitis C antibody. A rise in AlkPhos by 10 U/L during the first 6 mo was incrementally associated with increased risk for death during the subsequent 2.5 yr. In summary, high levels of serum AlkPhos, especially >120 U/L, are associated with mortality among hemodialysis patients. Prospective controlled trials will be necessary to test whether serum AlkPhos measurements could be used to improve the management of renal osteodystrophy.

Kalantar-Zadeh K, Kilpatrick RD, McAllister CJ, Miller LG, Daar ES, Gjertson DW, Kopple JD, Greenland S. · Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, CA 90509-2910, USA. · J Am Soc Nephrol. · Pubmed #17429053 links to  free full text

Abstract: In maintenance hemodialysis (MHD) patients, hepatitis C virus (HCV) infection is common and may be associated with poor clinical outcomes. It was hypothesized that HCV infection would be associated with high all-cause and cardiovascular mortality in these patients after controlling for demographic and clinical characteristics, including surrogates of malnutrition-inflammation complex syndrome. A national database of 13,664 MHD patients who underwent HCV antibody serology testing at least once during a 3-yr interval (July 2001 through June 2004) was analyzed. Measurements included third-generation HCV enzyme immunoassay and routine laboratory measurements. The HCV enzyme immunoassay was reported positive in 1590 (12%) patients. In logistic regression models that included case mix and available surrogates of malnutrition-inflammation complex syndrome, HCV infection was associated with younger age, male gender, black race, Hispanic ethnicity, Medicaid insurance, longer dialysis vintage (duration), unmarried status, HIV infection, and smoking history. In proportional-hazards regressions, the mortality hazard ratio that was associated with HCV infection was 1.25 (95% confidence interval 1.12 to 1.39; P < 0.001). Mortality hazards were higher among incident (dialysis duration <6 mo) than prevalent HD patients. Subgroup analyses indicated that HCV was associated with higher all-cause and cardiovascular mortality across almost all clinical, demographic, and laboratory groups of patients. Hence, in MHD patients, HCV infection exhibits distinct demographic, clinical, and laboratory patterns, including associations with higher dialysis treatment vintage, and is associated with higher mortality. More diligent efforts to prevent and treat HCV infection may improve outcomes in MHD patients.

Kalantar-Zadeh K, Miller LG, Daar ES. · Division of Nephrology and Hypertension, Los Angeles Biomedical Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. · Am J Kidney Dis. · Pubmed #16112048 No free full text.

Abstract: BACKGROUND: Hepatitis C virus (HCV) infection is associated with an increase in proinflammatory cytokine levels. Similar changes are seen in maintenance hemodialysis patients with malnutrition-inflammation-cachexia syndrome (MICS), which is associated with poor clinical outcomes in this population. We hypothesized that HCV transcription-mediated amplification (TMA), a sensitive qualitative molecular test for HCV RNA, may identify maintenance hemodialysis patients with HCV infection not detected by means of antibody enzyme immunoassay (EIA), particularly in those with MICS. METHODS: We evaluated HCV status in 314 maintenance hemodialysis patients by using HCV antibody EIA (version 2.0; Abbott Laboratories, Abbott Park, IL) and HCV TMA (Bayer Diagnostics Laboratories, Berkeley, CA). Results: Twenty-five patients (8%) were EIA positive (EIA+)/TMA+; 4 patients (1%), EIA+/TMA negative (TMA-), and 22 patients (7%), EIA-/TMA+. In the 47 TMA+ patients, the sensitivity of EIA for HCV infection was only 53%. TMA+ patients had lower albumin levels and higher tumor necrosis factor alpha and serum glutamic oxaloacetic transaminase levels than TMA- patients. EIA+/TMA+ patients were more likely than EIA-/TMA+ or EIA-/TMA- patients to have hypoalbuminemia and higher iron and transaminase levels. Of all TMA+ patients, EIA- patients were more likely to have diabetes, be on dialysis therapy longer, and have lower liver enzyme levels and higher proinflammatory cytokine levels, including tumor necrosis factor alpha and interleukin 6. CONCLUSION: Maintenance hemodialysis patients infected with HCV according to TMA have clinical features suggestive of MICS. In this population, HCV EIA appears to have a low sensitivity for the identification of HCV infection, which may be caused by the confounding effect of MICS or other demographic or clinical factors. These apparently false-negative HCV antibody test results are seen in persons with a longer time on hemodialysis therapy, mirroring observations in other populations with serious progressive conditions, such as human immunodeficiency virus infection.

Kalantar-Zadeh K, McAllister CJ, Miller LG. · Division of Nephrology and Hypertension, Harbor-UCLA Medical Center 1000 West Carson Street, Torrance, CA 90509-2910, USA. · Nephrol Dial Transplant. · Pubmed #15905194 links to  free full text

Abstract: BACKGROUND: The association between hepatitis C virus (HCV) infection and clinical and laboratory measures in maintenance haemodialysis (MHD) patients are poorly understood. METHODS: We analyzed data from over 37,000 MHD patients who underwent MHD for at least 3 months in DaVita dialysis clinics across USA in July 2001. RESULTS: The presence of HCV infection was determined using enzyme immunoassay (EIA), which was performed in 2778 MHD patients and was positive in 363 (13%) individuals. In a multivariate logistic regression model that adjusts for case-mix and available surrogates of malnutrition-inflammation complex syndrome (MICS), the following were independent predictors of HCV infection: younger age, male gender, Black race, Hispanic ethnicity, higher haemoglobin, lower serum albumin, higher total iron binding capacity, higher creatinine, and higher serum glutamic oxaloacetic transaminase (SGOT). Among receiver operating characteristics of commonly measured laboratory values in this population, the SGOT had the highest area. An SGOT > or =25 u/l had an adjusted odds ratio of 4.96 (95% confidence interval: 3.75-6.57) for HCV antibody positivity (sensitivity 50%, specificity 87%). HCV EIA positivity among MHD patients younger than 65 years was associated with 40-80% higher hazard ratio of all-cause and cardiovascular death during the 2 year follow-up (July 2001 to June 2003) after adjustment for case-mix and measures of MICS. CONCLUSION: HCV infection, as diagnosed by EIA, has distinct racial, age and laboratory predilections in MHD patients. HCV positivity among MHD patients younger than 65 years is associated with significantly higher cardiovascular mortality. More diligent HCV detection and treatment may improve cardiovascular survival in MHD patients.