Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. The Retrovirus Epidemiology Donor Study

BACKGROUND: Since the mid-1980s, blood banks in the United States have screened donors for elevated alanine aminotransferase (ALT) in an effort to prevent posttransfusion hepatitis. The present study was designed to quantitate the residual value of ALT screening following the implementation of hepatitis C virus (HCV) assays. STUDY DESIGN AND METHODS: Two approaches were used. First, a database of 2.3 million donations made by 586,507 volunteer blood donors between 1991 and 1993 was used to compare the incidence of seroconversion to hepatitis B virus (HBV) and HCV marker positivity in donors with elevated ALT values and with normal ALT values. Second, the duration of ALT elevation prior to HBV and HCV seroconversion was determined from 34 well-documented cases of posttransfusion HBV and HCV; elevated-ALT window periods were multiplied by rates of HBV and HCV incidence in donors to project the yield of ALT screening. Predictive value and cost- effectiveness analyses were also performed to compare the value of ALT screening before and after HCV screening was implemented. RESULTS: Both approaches indicate that ALT testing does not detect HBV in the window phase but does currently identify approximately 3 HCV window-phase donations per 1 million donations; this contrasts with ALT detection of approximately 1800 HCV-infectious units per 1 million donations prior to anti-HCV screening. Currently, only 8 in 10,000 donated units with elevated ALT (negative anti-HCV) are infected with HCV. The cost of continued ALT screening was estimated at $7,931,000 per quality- adjusted year of life saved. CONCLUSION: The yield, predictive value, and cost-effectiveness of ALT screening of blood donors have declined dramatically with the implementation of progressively improved anti-HCV assays. ALT screening of volunteer blood donors should be discontinued.     

Increased detection of hepatitis C virus infection in commercial plasma donors by a third-generation screening assay

BACKGROUND: Routine screening of blood donations with second-generation hepatitis hepatitis C virus (HCV) assays has substantially reduced the occurrence of posttransfusion hepatitis. However, following the development of third-generation assays, several studies indicated that these assays may identify HCV-infected individuals who are not identified by second-generation assays. STUDY DESIGN AND METHODS: The sensitivity of a third-generation HCV enzyme-linked immunosorbent assay (ELISA-3) was compared with a second-generation ELISA (ELISA-2) in a side-by-side study of 9936 commercial blood donors. ELISA-reactive specimens were subjected to supplemental analysis by third-generation recombinant immunoblot assay and polymerase chain reaction. RESULTS: ELISA-3 demonstrated greater sensitivity than ELISA-2, detecting 1 additional recombinant immunoblot assay-positive specimen per 2000 tested. ELISA-3 also detected 1 additional HCV-infectious polymerase chain reaction-positive unit among approximately 10,000 units screened. CONCLUSION: The incremental sensitivity achieved with ELISA-3 can be expected to eliminate approximately 20 infectious donations per week among those made by commercial donors in the United States. In accordance with previous studies, most of the improved sensitivity of ELISA-3 derives from its increased detection of anti-c33c (NS3), rather than from the inclusion of HCV antigen NS5.     

Orthotopic liver transplantation in a patient with carbamyl phosphate synthetase deficiency and cystic fibrosis

A 15-year-old female with carbamyl phosphate synthetase deficiency, cystic fibrosis, and cystic fibrosis-related diabetes underwent orthotopic cadaveric liver transplantation. Metabolic control was maintained during the procedure with nutritional support and the use of intravenous sodium phenylacetate and benzoate. Her postoperative course was complicated by seizures and a transient decline in her pulmonary function tests, which returned to preoperative levels within one year of the transplant. Now, four years post-transplant, her quality of life has dramatically improved. There are only four Canadian centres with paediatric liver transplantation programs. However, expert medical care for adults with inborn error of metabolism is even more limited, suggesting that access to adult medical care is one of the many factors to be considered when liver transplantation is contemplated for patients with metabolically unstable conditions.     

Detection of human sperm acrosome reaction: comparison between methods using double staining, Pisum sativum agglutinin, concanavalin A and transmission electron microscopy

The acrosome reaction is an important marker for human sperm function. Since different laboratory techniques may be used for the detection of this exocytotic process, the purpose of the present study was to compare three common markers [Pisum sativum agglutinin (PSA), concanavalin A (ConA), double staining] and transmission electron microscopy for identification of acrosomal changes. Preliminary findings had demonstrated that similar results were achieved with Trypan Blue and Hoechst 33258 staining. Therefore, supravital stainings were omitted. In various experiments, human spermatozoa were treated with two concentrations (10 and 3.3 microM) of calcium ionophore A23187 for 15, 30 and 60 min after capacitation for 3 and 6 h at 37 degrees C. The percentages of spermatozoa with acrosomal loss detected by fluorescein isothiocyanate (FITC)-ConA were consistently lower than those obtained by double staining or FITC-PSA, which showed comparable results. Following 6 h of capacitation and incubation with 10 microM ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all spermatozoa showed almost complete loss of the acrosomal content. Binding of FITC- ConA to the acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa obtained from the same sample. FITC-ConA and double staining or FITC-PSA detect different stages of the acrosome reaction and may be helpful for a differentiated evaluation of this sperm function.