Alanine Aminotransferase Screening Research Articles

Dengue Virus Ribonucleic Acid Detection Rates in Blood Donors Correlate With Local Infection Incidences During a Dengue Outbreak in Taiwan.

Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan. Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors. A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15-4.73), 3.36 (95% CI, 1.31-8.60), and 6.19 (95% CI, 3.14-12.17) per 1000 donors in districts where the weekly dengue incidence was 5-50, 50-200, and 200 or more per 100000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10000 dengue infections. Approximately 0.5%-1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures.

From the Editor’s desk....: July 2018

From the Editor’s desk....: July 2018

The correlation of ALT, HbsAg and HCV-Ab and the effect of different detection modes on the results in blood donors

Objective To investigate the effects of different detection methods on the results for alanine aminotransferase (ALT), HBsAg and hepatitis C virus antibody (HCV-Ab) through testing the blood of 273 316 person time blood donors from 2009 to June2015, and to investigate the distribution of HBsAg, HCV-Ab and ALT and their correlation in blood donors, detection mode of nucleic acid detection in negative samples used enzyme-linked immunosorbent assay (ELISA), the results of blood donors, who were single reagent HBsAg, HCV-Ab positive, were detected again after for 24 weeks (maximum window period), and necessity of ALT screening before collecting blood sample, which provided a basis for the optimization of blood detection methods. Methods The rate method was used to detect ALT, detection of HCV-Ab and HBsAg was used ELISA, nucleic acid detection was performed on HBsAg and HCV-Ab negative blood by enzyme immunoassay, and dry chemistry complete automatic biochemistry analyzer were used for ALT screening before blood sampling in street. The enumeration data were analyzed by the χ2 test with P<0.05 for statistically significant. Results The total ALT positive rate of 273 316 people was 4.09% in Baoji city, the single ALT positive was main (98.17%, 11 185/273 316). The ALT positive rate (5.20%) of male was higher than that of women (1.79%) (χ2=1780.94, P<0.05), and the ALT positive rate of 18~44 years old group (4.48%) was higher than that of 45~55 years old groups (3.26%) (χ2=223.87, P<0.05). The positive rate of ALT before carring out ALT screening (4.90%, 8 448/172 472) was higher than that of after carrying ALT screening (2.71%, 2 737/100 844) (χ2=773.43, P<0.05). Through nucleic acid detection for serums of 143 815 ELISA negative blood donors, there were no HCV-Ab positive and 75 HbsAg positive. The Kappa value was 0.049 between ELISA and nucleic acid examination in single reagent HBsAg positive blood donors after 24 weeks. Conclusions The ALT positive and HBV, HCV had no correlation, and the ALT single positive were main in blood donors. Carrying out ATL blood screening, two times of ELISA detection and one times the nucleic acid detection may improve the blood safety level. HBsAg and HCV-Ab positive blood donors in 24 weeks (maximum window period) after ELISA and nucleic acid detection can be negative. Return blood donation team. The HbsAg and HCV-Ab positive blood donors, who were negative by the ELISA and nucleic acid detection after the 24 week (maximum window period), can return to the blood donation team. Key words: Blood donors; Blood transfusion; Alanine transaminase/BL; Hepatitis B surface antigens/BL; Hepatitis C antibodies/BL

Targeted Hepatic Sonography During Clinic Visits for Detection of Fatty Liver in Overweight Children

The purpose of this study was to assess the feasibility and utility of targeted hepatic sonography to evaluate for hepatic steatosis during a subspecialty clinic visit. In this pilot study, we performed targeted hepatic sonography on 25 overweight children aged 7 to 17 years consecutively seen in a pediatric obesity clinic. Long-axis images of the right lobe of the liver and a split-screen image of liver and spleen were taken. Images were interpreted in real time by the radiologist and shown to the family. Demographics, clinical measurements, and laboratory parameters were also collected from the specialty clinic visit on the same day. Sonography required a median of 4 minutes during the visit (interquartile range, 3-5 minutes). All consented patients completed the study. The median alanine aminotransferase (ALT) level was 23 U/L in those with no steatosis (n = 14), 26 U/L with mild steatosis (n = 6), and 41 U/L with moderate/marked steatosis (n = 5). Children with ALT levels of 25 to 50 U/L had very variable sonographic measures of hepatic steatosis. When the participants were categorized by the overall degree of fatty liver, hepatic steatosis was significantly associated with the aspartate aminotransferase level (P = .028), ALT level (P = .003), and diastolic blood pressure (P = .05) but did not correlate with age, sex, Latino race, or insulin resistance. Targeted hepatic sonography added information not apparent from routine ALT screening and provided immediate feedback to clinicians and families about the effect of obesity on end organs. This examination could be a feasible, informative addition to screening for children at high risk for nonalcoholic fatty liver disease who are seen in clinics that specialize in obesity.

Serum alanine aminotransferase levels in relation to hepatitis B and C virus infections among drug abusers in an area hyperendemic for hepatitis B.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major agents responsible for hepatitis in Taiwan. The purpose of this study was to assess the serum alanine aminotransferase (ALT) activity in relation to HBV and HCV infection among drug abusers. This survey included 769 male drug abusers aged 14-59 years, from the Kaohsiung Narcotic Abstention Institute and Kaohsiung Prision. The prevalence of HBsAg seropositivity was 21.5%, and anti-HCV seropositivity was 27.2%, respectively. Drug abusers with HBsAg or anti-HCV had higher serum AST and ALT levels than those without HBsAg and anti-HCV. The prevalence of raised ALT and AST (> or =45 IU/liter) in the HCV-positive group was more significant than in the negative group, while that of the HBsAg-positive group did not reach statistical significance. Among the HCV-positive group, ALT levels are more closely associated with HCV infection than AST levels. Our results indicated that HCV infection plays an important role in the etiology of raised ALT activity among drug abusers, while HBV infection plays a minor role. ALT screening still remains a simple and valuable method in the early recognition of HCV infection.

Non-specific and specific anti-HCV results correlated to age, sex, transaminase, rhesus blood group and follow-up in blood donors.

Second generation enzyme immunoassays (EIA-2) for antibodies to hepatitis C virus (anti-HCV) have a higher specificity and sensitivity than first generation enzyme immunoassays (EIA-1). We studied how many anti-HCV-positive blood donors were missed by the EIA-1, how many were false positive, how false-positive donors should be dealt with and how the results of the EIA-2 correlate to demographic data and serum alanine aminotransferase (ALT) level. A total of 208, 544 northern German blood donors, not preselected for anti-HCV negativity, were tested for anti-HCV with EIA-2 and, if repeatability reactive (rr), were retested with a licensed supplementary test (RIBA-2). 0.43% of the donors were EIA-2 rr, but only 0.12% of women and 0.09% of men were RIBA-2 positive. RIBA-2 positivity rates were very low in donors 18 to 27 years old (0.03% and 0.05%) and rose with age in women but not in men. Infected women were significantly more often Rhesus-negative than men. The rate of unspecifically positive EIA-2 results (entirely negative in RIBA-2) increased with age in both sexes and did not correlate with ALT. The ALT distribution was age-dependent with a different pattern for men and women. Confirmation of EIA-2 results with RIBA was rare when ALT was low and frequent when ALT was high. ALT screening before introduction of Anti-HCV detected one out of six infected donors. To exclude this one infectious donation, 46 uninfected donations had to be excluded in addition. Only 8% of the then RIBA-2-positive donors were not detected by EIA-1. Apparent seroconversions in EIA-2 are usually not specific; only 1 out of 66 apparent seroconversions could be confirmed by RIBA-2 suggesting recent HCV infection. 0.15% of the donor population showed an inconsistent EIA-2 pattern during follow-up. We conclude that donors should not be excluded from further donations, even on the basis of multiple EIA-1 positive results or on the basis of only one EIA-2 positive donation. Anti-D-immunoglobulin prophylaxis may have been a source of infection in some Rhesus-negative women. ALT screening should not be discontinued because recent HCV infection can be detected earlier by ALT than by anti-HCV, but exclusion limits should be elevated to increase specificity and limit unnecessary exclusion of donations.

Limited utility of alanine aminotransferase screening of hepatitis C antibody-screened blood donors.

The introduction of hepatitis C virus (HCV) screening has significantly reduced the frequency of posttransfusion hepatitis C. To examine the current added value of alanine aminotransferase (ALT) screening, all donor screening at two large blood centers was reviewed. From July 1991 through March 1994, 1,258,000 allogeneic blood donors were screened by enzyme immunoassay for anti-HCV: 343,000 donations by the first-generation test (HCV 1.0) and 915,000 donations by the second-generation test (HCV 2.0). Donations with positive EIA results were confirmed with a recombinant immunoblot assay. Of these donors, 1,637 (0.13%) were confirmed as HCV-positive and 21,666 (1.72%) had elevated ALT. To estimate the additional margin of safety due to ALT screening, all donors who seroconverted were reviewed, and those donors who had elevated ALT but were HCV negative on a previous donation were identified. One hundred eleven HCV seroconversions were observed: 19 seroconversions from HCV 1.0-negative to HCV 1.0-confirmed-positive, 82 apparent seroconversions from HCV 1.0-negative to HCV 2.0-confirmed-positive, and 10 seroconversions from HCV 2.0-negative to HCV 2.0-confirmed-positive. The number of apparent HCV 1.0-negative to HCV 2.0-positive seroconversions was much greater than expected, which reflected the increased sensitivity of HCV 2.0. Only 15 donors were identified who had an elevated ALT on a previous HCV-negative blood donation, and all of these were among those who apparently seroconverted from HCV 1.0-negative to HCV 2.0-confirmed-positive. Out of the 10 HCV 2.0-seroconverting donors, no donor was found who was initially HCV 2.0 negative with elevated ALT and later was HCV 2.0 positive; nor were such donors found among 4 additional HCV 2.0-seroconverting donors. With the introduction of HCV 2.0 screening. ALT appears to have little value as a surrogate test for hepatitis C, and ALT testing was unable to detect any donors who later seroconverted, as detected by HCV 2.0.

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

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. 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. 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. 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.

Age, Sex and Transaminase Dependency of Specific and Nonspecific Results from Enzyme Immunoassays for Antibodies to Hepatitis C Virus and Follow-Up of Blood Donors

Second-generation enzyme immunoassays (EIA-2) for antibodies to hepatitis C virus (anti-HCV) have an improved specificity and sensitivity compared to first-generation enzyme immunoassays (EIA-1). Therefore the question arises how many anti-HCV-positive blood donors were missed by the EIA-1, how many were false positive, how false-positive donors should be dealt with and how the results of the EIA-2 correlate with demographic data and surrogate testing for serum alanine aminotransferase (ALT). A total of 208,544 individual North German blood donors not preselected for anti-HCV negativity were tested for anti-HCV with EIA-2 and, if repeatedly reactive (rr), with a licensed supplementary test (RIBA-2). Overall, 0.43% of the donors were EIA-2 rr, but only 0.12% of women and 0.09% of men were RIBA-2 positive. RIBA-2 positivity rates were very low in donors 18 to 27 years old (0.03% and 0.05%) and clearly rose with age in women but not in men. The rate of unspecifically positive EIA-2 results (entirely negative in RIBA-2) rose with age in both sexes and did not correlate with ALT. The ALT distribution was age dependent with a completely different pattern for men and women. Anti-HCV positivity was strongly correlated with ALT albeit on a very low level: more than 97% of donors with strongly elevated ALT were anti-HCV negative. Follow-up and comparison of EIA-1, EIA-2 and RIBA-2 results for the subsequent donations showed that only 8% of now RIBA-2-positive donors were not detected by EIA-1. Apparent seroconversions in EIA-2 are usually not specific: only one out of 66 apparent seroconversions could be confirmed by RIBA-2. 0.15% of the donor population showed an inconsistent EIA-2 pattern during follow-up. We therefore suggest that donors should not be excluded from further donations on the basis even of multiple EIA-1 positive results or on the basis of only one EIA-2-positive donation. The value of ALT screening for transfusion safety should be reconsidered.

Persistent alanine aminotransferase elevation in healthy Swedish blood donors--mainly caused by obesity.

Five hundred consecutive healthy blood donors were tested for serum alanine aminotransferase (ALT) and 44 (8.8%) had increased levels. Donors with and without raised ALT were compared in several aspects but only weight (expressed as percentage of ideal body weight) and sex differed significantly (119.1 +/- 14.5 and 106.3 +/- 12.8%, respectively; p less than 0.001 and males 97.7 and 77.1%, respectively; p less than 0.01). The 44 donors with raised ALT were followed up and in 13 out of 15 donors with persistently raised ALT without obvious reason, a liver biopsy was performed. Ten donors had various degrees of liver steatosis, 2 had normal liver morphology and in 1 donor chronic hepatitis could not be ruled out. If ALT screening is introduced as a surrogate test for non-A, non-B hepatitis in Swedish blood donors, we suggest that a correction for overweight must be considered in order to minimize donor loss.

Surrogate testing for non-A, non-B hepatitis in Queensland, Australia: An ALT microtitre tray method for screening blood donors

The estimation of plasma alanine aminotransferase (ALT) has been proposed as a surrogate test to identify potential non-A, non-B hepatitis carriers in blood donor populations. This report describes an ALT screening procedure which uses wells of microtitration trays as reactant vessels. The method utilizes a rate reading photometer, is economical and conveniently fits into the routine workflow. Within-batch and between-batch precision was 4.1% and 6.3% at enzyme concentrations of 49 IU/I. Results of testing 29,675 healthy blood donors gave values which ranged between 1.0 IU/I and 214 IU/I. A study of 762 donations showed a significant difference in mean ALT values between males and females (p less than 0.01). When a cut-off value of 46 IU/I was used, 2.5 percent of donations were considered unsuitable for transfusion. The medico-legal implications that may arise from the introduction of this screening test into the routine work flow are discussed.

Should Donor Blood Be Screened for Elevated Alanine Aminotransferase Levels?

We examined the cost-effectiveness of alanine aminotransferase (ALT) screening of donor blood to prevent non-A, non-B posttransfusion hepatitis. Based on estimated costs of ALT screening, blood replacement, and medical evaluation of donors with high ALT levels, we concluded that screening at an ALT level of 45 IU would cost $3.82 per unit. In a population requiring an average of 3.7 units per transfusion, one case of hepatitis would be prevented for every 115 units screened, resulting in a cost of $439 per case prevented. With an estimated direct medical cost of $1,181 per case of non-A, non-B hepatitis, expected net savings for each case prevented would be $742. Screening at other ALT thresholds would be less cost-saving. Sensitivity analyses indicate that screening would be cost-saving for a wide range of cost estimates and number of units per transfusion. Alanine aminotransferase screening is warranted until more sensitive and specific screening tests for transmissibility of non-A, non-B hepatitis become available.

Inactivation of Hepatitis B and Non-A, Non-B Viruses by Combined Use of Tween 80®, β-Propiolactone, and Ultraviolet Irradiation

To assess the sterilization efficacy of a combined Tween 80, beta-propiolactone and ultraviolet irradiation procedure applied to a F VIII preparation to which an estimated 10(5.9) chimpanzee infectious doses (CID50) of hepatitis B virus had been added per ml, two chimpanzees were inoculated with 10 ml each of treated and untreated preparations. The untreated preparation, which was obtained from donors with normal alanine aminotransferase (ALT) levels, induced non-A, non-B hepatitis in both recipient animals, and delayed hepatitis B infection in one of these. Neither animal receiving the treated preparation developed either type of hepatitis. When subsequently challenged with the untreated material, both of the latter animals developed non-A, non-B and hepatitis B infection, proving their susceptibility to both types of infection. It was concluded that the combined procedure inactivated an estimated 10(6.9) CID50 of hepatitis B virus and an unknown quantity of a non-A, non-B virus. The finding of non-A, non-B virus infectivity in a pooled F VIII preparation despite careful ALT screening of plasma donors emphasizes the necessity of subjecting such preparations to sterilization procedures.