Cost-Effectiveness of Noninvasive Screening for Alcohol-Related Liver Fibrosis.

BACKGROUND AND AIMS: Alcohol-related liver disease is often undetected until irreversible late-stage decompensated disease manifests. Consequently, there is an unmet need for effective and economically reasonable pathways to screen for advanced alcohol-related fibrosis. APPROACH AND RESULTS: We used real-world data from a large biopsy-controlled study of excessive drinkers recruited from primary and secondary care, to evaluate the cost-effectiveness of four primary care initiated strategies: (1) routine liver function tests with follow-up ultrasonography for test-positives, (2) the enhanced liver fibrosis (ELF) test with hospital liver stiffness measurement (LSM) for positives, (3) a three-tier strategy using the Forns Index to control before strategy 2, and (4) direct referral of all to LSM. We used linked decision trees and Markov models to evaluate outcomes short term (cost-per-accurate diagnosis) and long term (quality-adjusted life-years [QALYs]). For low-prevalence populations, ELF with LSM follow-up was most cost-effective, both short term (accuracy 96%, $196 per patient) and long term (incremental cost-effectiveness ratio [ICER] $5,387-$8,430/QALY), depending on whether diagnostic testing had lasting or temporary effects on abstinence rates. Adding Forns Index decreased costs to $72 per patient and accuracy to 95%. The strategy resulted in fewer QALYs due to more false negatives but an ICER of $3,012, making this strategy suited for areas with restricted access to ELF and transient elastography or lower willingness-to-pay. For high-prevalence populations, direct referral to LSM was highly cost-effective (accuracy 93%, $297 per patient), with ICERs between $490 and $1,037/QALY. CONCLUSIONS: Noninvasive screening for advanced alcohol-related fibrosis is a cost-effective intervention when different referral pathways are used according to the prevalence of advanced fibrosis. Patients in the primary health care sector should be tested with the ELF test followed by LSM if the test was positive, whereas direct referral to LSM is highly cost-effective in high-prevalence cohorts.

The value of routine laboratory screening in the neonatal intensive care unit.

BACKGROUND: Healthcare spending is expected to grow faster than the economy over the next decade, and the cost of prematurity increases annually. The aim of this study was to investigate the frequency of intervention after routine laboratory testing in preterm infants. METHODS: This was a retrospective study of preterm infants (≤34 weeks) admitted to the NYU Langone Health NICU from June 2013 to December 2014. Data collected included demographics, results of laboratory tests, and resulting interventions. Intervention after a hemogram was defined as a blood transfusion. Intervention after a hepatic panel was defined as initiation or termination of ursodiol or change in dose of vitamin D. Subjects were stratified into 3 groups based on gestation (<28 weeks, 28-31 6/7 weeks, 32-34 weeks). Chi-square analysis was used to compare the frequency of intervention between the groups. RESULTS: A total of 135 subjects were included in the study. The frequency of intervention after a hemogram was 8.4% in infants <28 weeks, 4.6% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks; this difference was found to be statistically significant (p = 0.02). The frequency of intervention after a hepatic panel was 4.2% in infants <28 weeks, 5.7% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks, which was not found to be a statistically significant different. CONCLUSION: No interventions were undertaken post-routine laboratory testing in any infant 32-34 weeks and routine testing in this population may be unnecessary. Further studies are needed to elucidate if routine testing affects neonatal outcomes.

Cost-comparison analysis of FIB-4, ELF and fibroscan in community pathways for non-alcoholic fatty liver disease.

BACKGROUND: The identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies. METHODS: A probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected. RESULTS: Introduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively. The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline. CONCLUSION: Our analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.

Referral pathways for patients with NAFLD based on non-invasive fibrosis tests: Diagnostic accuracy and cost analysis.

BACKGROUND/AIMS: Non-invasive fibrosis tests (NITs) can be used to triage non-alcoholic fatty liver disease (NAFLD) patients at risk of advanced fibrosis (AF). We modelled and investigated the diagnostic accuracy and costs of a two-tier NIT approach in primary care (PC) to inform secondary care referrals (SCRs). METHODS: A hypothetical cohort of 1,000 NAFLD patients with a 5% prevalence of AF was examined. Three referral strategies were modelled: refer all patients (Scenario 1), refer only patients with AF on NITs performed in PC (Scenario 2) and refer those with AF after biopsy (Scenario 3). Patients in Scenarios 1 and 2 would undergo sequential NITs if their initial NIT was indeterminate (FIB-4 followed by Fibroscan®, enhanced liver fibrosis (ELF)® or FibroTest®). The outcomes considered were true/false positives and true/false negatives with associated mortality, complications, treatment and follow-up depending on the care setting. Decision curve analysis was performed, which expressed the net benefit of different scenarios over a range of threshold probabilities (Pt). RESULTS: Sequential use of NITs provided lower SCR rates and greater cost savings compared to other scenarios over 5 years, with 90% of patients managed in PC and cost savings of over 40%. On decision curve analysis, FIB-4 plus ELF was marginally superior to FIB-4 plus Fibroscan at Pt ≥8% (1/12.5 referrals). Below this Pt, FIB-4 plus Fibroscan had greater net benefit. The net reduction in SCRs was similar for both sequential combinations. CONCLUSIONS: The sequential use of NITs in PC is an effective way to rationalize SCRs and is associated with significant cost savings.

Routine monitoring of liver function tests in lung cancer resections - a necessary burden?

BACKGROUND: Increased availability of routine investigations results in significant over-investigation, burdening patients with unnecessary tests as well as increasing cost. We aimed to identify the extent of monitoring of liver function tests in lung resections, and to ascertain whether any impact on clinical decision-making occurred. METHODS: Cases were identified using theatre records coded as "lobectomy/bilobectomy" in the three-month period 20 June 2017 to 20 September 2017. Electronic records were used to collect patient data. RESULTS: A total of 91 cases were included; 77 (85%) patients had 1 set of pre-operative LFTs, 12 (13%) patients had 2 sets, and 2 (2%) patients had 0 sets; 69 (76%) had normal LFTs pre-operatively; 298 sets of LFTs were measured post-operatively, with a median of 3 sets per patient; 61 (67%) patients had either normal or static LFTs post-operatively, 13 (14%) had isolated rise in GGT, 16 (17%) had derangement of ALT and AST, and 1 patient (1%) had deranged ALP. Altered clinical decision-making due to LFTs derangement was recorded in two cases (2%). CONCLUSION: Clinicians have an obligation to justify expense, and practise in a cost-effective manner. Our data suggest that the routine perioperative monitoring of LFTs in thoracic surgery does not give any clear benefit to patient care.

Predictive Variables for Abnormal Comprehensive Metabolic Panel Testing and Potential Cost Savings in Children Receiving Pediatric Emergency Department Care.

OBJECTIVE: The aim of this study was to determine variables predictive of abnormal comprehensive metabolic panel (CMP) results in pediatric emergency department (PED) patients and the potential cost savings of a basic metabolic panel (BMP) versus a CMP. METHODS: This is a retrospective cross-sectional descriptive study of children (<18 y) at an urban academic PED (annual census, 22,000). Clinical data included 12 clinical variables: right upper quadrant pain, overdose, emesis, liver disorder, malignancy, heart disease, bleeding disorder, jaundice, right upper quadrant tenderness, hepatomegaly, ascites/peripheral edema and shock, and the liver function test (LFT) results not in a BMP (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, and albumin). RESULTS: There were 207 children in the study population. The mean age was 8 years. There were 106 boys (51%).Variables significantly associated with abnormal LFT result were history of liver disease (P = 0.007), history of heart disease (P = 0.040), jaundice (P = 0.045), and hepatomegaly (P = 0.048). The false-negative rate was 16%. However, of the 10 patients for whom this false-negative rate remained true, the LFT values were marginally abnormal, and performance of further investigation of these results was minimal to none. There were 66 patients with no clinical variables and normal CMP results. With a cost difference of $21 between BMP and CMP, this gives a potential savings of $7125 if extrapolated for 1 year in our PED. CONCLUSIONS: Limiting testing to a BMP for patients with none of the 12 clinical variables has the potential annual cost savings of $7125.

Utilization of Reflex Testing for Direct Bilirubin in the Early Recognition of Biliary Atresia.

BACKGROUND: Delayed diagnosis of biliary atresia is an important cause of pediatric end-stage liver failure and liver transplantation. We sought to determine whether direct bilirubin is underutilized by retrospectively reviewing patients with biliary atresia. Further, we aimed to determine the role of reflex testing for direct bilirubin in patients suspected for jaundice. METHODS: The time intervals between total bilirubin and direct bilirubin measurements were retrospectively reviewed in patients with biliary atresia. We also audited the results of two major laboratories that had implemented reflex testing for direct bilirubin. We evaluated the clinical impact and cost of reflex testing in infants with increased direct bilirubin (>1.5 mg/dL; >25 µmol/L). RESULTS: In patients with known biliary atresia, an isolated total bilirubin measurement preceded direct bilirubin measurement in 46% (40/87) of patients; with a median delay of 19 days (interquartile range 3-44 days). In the community setting, direct bilirubin had a higher clinical specificity for biliary atresia than in the hospital setting. Reporting direct bilirubin results in 1591 infants younger than 2 weeks of age in the community was associated with three admissions to the hospital, one of whom was diagnosed with biliary atresia. The cost for the two laboratories for direct-bilirubin testing was estimated at US$3200 (NZ$4600) for each newly diagnosed case of biliary atresia. CONCLUSIONS: We identified underutilization of direct bilirubin as a cause of delay in the recognition of biliary atresia and show that reflex testing for direct bilirubin in jaundiced infants is a cost-effective solution.

Reducing liver function tests for statin monitoring: an observational comparison of two clinical commissioning groups.

BACKGROUND: Current liver function testing for statin monitoring is largely unnecessary and costly. Statins do not cause liver disease. Both reduction in test frequency and use of a single alanine transaminase (ALT) rather than a full seven analyte liver function test (LFT) array would reduce cost and may benefit patients. AIM: To assess LFT testing in relation to statin use and evaluate an intervention to reduce full-array LFTs ordered by GPs for statin monitoring. DESIGN AND SETTING: Two-year cross-sectional time series in two east London clinical commissioning groups (CCGs) with 650 000 patients. One CCG received the intervention; the other did not. METHOD: The intervention comprised local guidance on LFTs for statin monitoring and access to a single ALT rather than full LFT array. RESULTS: Of the total population, 17.6% were on statins, accounting for 43.2% of total LFTs. In the population without liver disease, liver function tests were 3.6 times higher for those on statins compared with those who were not. Following intervention there was a significant reduction in the full LFT array per 1000 people on statins, from 70.3 (95% confidence interval [CI] = 66.3 to 74.6) in the pre-intervention year, to 58.1 (95% CI = 55.5 to 60.7) in the post-intervention year (P<0.001). In the final month, March 2016, the rate was 53.2, a 24.3% reduction on the pre-intervention rate. CONCLUSION: This simple and generalisable intervention, enabling ordering of a single ALT combined with information recommending prudent rather than periodic testing, reduced full LFT testing by 24.3% in people on statins. This is likely to have patient benefit at reduced cost.

Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005­December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

From the bench to the field in low-cost diagnostics: two case studies.

Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field--the processes intended to evaluate operation and performance under realistic conditions--are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments.

The effect of hepatitis C treatment response on medical costs: a longitudinal analysis in an integrated care setting.

BACKGROUND: Studies suggest that chronic hepatitis C patients who achieve sustained virologic response (SVR) have lower risks of liver-related morbidity and mortality. Given the substantial costs and complexity of hepatitis C virus (HCV) antiviral treatment, post-treatment benefits are important to understand.   OBJECTIVE: To determine whether health care costs and utilization for up to 5 years after treatment differed between patients who achieved SVR and those who did not.  METHODS: Kaiser Permanente Medical Care Program patients receiving HCV treatment with pegylated interferon and ribavirin (Peg-IFN/RBV) from 2002 to 2007 were retrospectively analyzed, excluding those with human immunodeficiency virus (HIV) or chronic hepatitis B. Health care utilization and costs for up to 5 years after treatment completion were derived from electronic records. We compared mean annual cost and overall post-treatment costs (standardized to year-2007 dollars), and yearly utilization counts between the SVR and non-SVR groups, adjusting for pretreatment costs, age, sex, baseline cirrhosis, and race using gamma and Poisson regression models.  RESULTS: The 1,924 patients eligible for inclusion were a mean age of 50 years; 63% male; 58% white, non-Hispanic; 62% with genotype 1; and 48% who had achieved SVR. The mean duration of post-treatment time was 3 years, and patients without SVR incurred significantly higher health care costs than patients with SVR. For each post-treatment year, total adjusted costs were significantly higher in the non-SVR group than in the SVR group, with rate ratios (RRs) and 95% CIs ranging from 1.26 (95% CI, 1.13-1.40) to 1.64 (95% CI, 1.38-1.96), driven mostly by hospital and outpatient pharmacy costs. When all post-treatment years were considered collectively, the non-SVR group had significantly higher costs overall (RR=1.41; 95% CI, 1.17-1.69) and in each category of costs. The adjusted difference in yearly total mean costs was $2,648 (95% CI, 737-4,560). In post-treatment years 2-5, adjusted liver-specific laboratory test rates were 1.8 to 2.3 times higher in the non-SVR group than in the SVR group (each year, P less than 0.001). During post-treatment years 1-5, adjusted yearly liver-related hospitalization rates were up to 2.45 times higher (95% CI, 1.56-3.85), and medicine/GI clinic visit rates were up to 1.39 times higher (95% CI, 1.23-1.54) in the non-SVR group compared with the SVR group.  CONCLUSION: Health care utilization and costs after HCV antiviral therapy with Peg-IFN/RBV, particularly for liver-related tests, outpatient drugs, and hospitalizations, were significantly lower for patients who achieved SVR than for those without SVR. Our observations are consistent with the potentially lower risk of severe liver disease among patients with SVR. 

A paper-based multiplexed transaminase test for low-cost, point-of-care liver function testing.

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout "bins" [<3× upper limit of normal (ULN), 3 to 5× ULN, and >5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.

Liver function testing is not helpful for early diagnosis of metastatic uveal melanoma.

OBJECTIVE: To study the relevance of liver function test (LFT) results for early detection of liver metastasis of uveal melanoma. DESIGN: Evaluation of diagnostic test. PARTICIPANTS: Eighty-eight patients were included in whom metastasis developed while undergoing semiannual follow-up with LFTs, including aspartate-aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), and phosphatase alkaline (PA). As controls, 174 patients with uveal melanoma without metastasis were included. METHODS: The diagnostic attributes of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each test were estimated from cross-tabulation tables of test results according to the diagnosis of metastasis. The proportions of false-positive results between groups of patients with and without metastasis were compared in log-binomial regression models. MAIN OUTCOME MEASURES: Sensitivity, specificity, PPV, NPV, and cost evaluation. RESULTS: Metastases were detected after LFT abnormality (at least 1 abnormal test result) in 40 (45%) patients. The overall sensitivity of LFTs ranged from 12.5% to 58.0%, and the PPV ranged from 9.4% to 38.6%. The overall specificity and NPV were 90% or greater. The proportions of false-positive results between groups of patients with and without metastasis did not differ significantly (all P≥0.38). Using a cost evaluation, semi-annual screening by LFTs was calculated to cost $35.5/year per patient, including liver imaging induced by true and false-positive results. CONCLUSIONS: Isolated or combined LFTs for AST, ALT, γGT, LDH, and PA are not helpful for detection of early metastasis. However, the high NPVs suggest that LFT screening can allow clinicians to reassure the patient when the LFT results are negative.

Cost-effective screening for acute hepatitis C virus infection in HIV-infected men who have sex with men.

BACKGROUND: We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex with men. METHODS: One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100000 per quality-adjusted life-year (QALY) gained. RESULTS: All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor-based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ≤1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. CONCLUSIONS: Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence, regular screening with LFTs, with or without an HCV Ab test, is the optimal strategy.

[Cost of screening for hepatocarcinoma in patients with cirrhosis: a prospective study]. / Coste del cribado del hepatocarcinoma en pacientes cirróticos: un estudio prospectivo.

INTRODUCTION: Current clinical guidelines recommend biannual screening for hepatocarcinoma in cirrhotic patients; however, the cost of this preventive activity is unknown. OBJECTIVE: To determine the cost of ultrasound screening for hepatocarcinoma in patients with cirrhosis. PATIENTS AND METHOD: Data on patients diagnosed with liver cirrhosis in a population of 245,042 inhabitants were prospectively gathered. The screening tests performed and cases of hepatocarcinoma diagnosed during the annual follow-up were included in the analysis. The cost of these tests was calculated based on the tariffs paid by insurance companies for health coverage of civil servants. RESULTS: In 2009, there were 374 patients with cirrhosis; of these, 99 were aged > 80 years, with a performance status of >2 or associated comorbidities. During the annual follow-up, the remaining patients underwent a total of 602 visits (abdominal ultrasound, blood test), four contrast-enhanced computed tomography scans, nine magnetic resonance scans, two scintigraphies, four aspiration biopsies, four radiographs and six contrast ultrasound scans. In our environment, the total estimated cost of these procedures was 37,946 €, indicating that the cost of a screening program for hepatocellular carcinoma according to the above-mentioned selection criteria is 0.155 € per inhabitant/year. If only cirrhotic patients suitable for screening are included, the annual cost of screening is 138 € per patient. CONCLUSION: The cost of an ultrasound screening program for hepatocarcinoma is 0.155 € per inhabitant/year. These data should be taken into account when considering population-based screening programs.

A million-dollar work-up for abdominal pain: is it worth it?

BACKGROUND AND AIM: Pain-predominant-functional gastrointestinal disorders (PP-FGIDs) are common. The diagnosis is clinical and there are no biological markers to characterize these conditions. Despite limited evidence, investigations are commonly performed. The aim of the study was to investigate diagnostic practices, yield, and costs in children with PP-FGIDs. PATIENTS AND METHODS: Charts of all of the children older than 4 years diagnosed as having abdominal pain were reviewed. Results and costs of diagnostic investigations were analyzed. RESULTS: Of 243 children with abdominal pain, 122 (50.2%) had PP-FGIDs (79 girls, mean age 12.7 years). All of the children underwent diagnostic work-up. Complete blood cell count was done in 91.8% of patients. None had elevated white blood cells, platelets, and low albumin. Six had either elevated erythrocyte sedimentation rate or C-reactive protein, but none had elevation of both; 4 of these 6 cases underwent endoscopies with normal results in 3 cases; Helicobacter pylori was found in 1 case. One child had elevated tissue transglutaminase 1 only antibodies with normal endoscopy. Amylase, lipase, direct bilirubin, stool cultures, and ova or parasites were always normal. One child had intermittent elevation of aspartate aminotransferase and alanine transaminase. There were no significant abnormalities in urinalysis or electrolytes. Abdominal x-rays were done in 38.5%, showing only retained stools in 13% of these patients. Abdominal ultrasound and computed tomography scan were done in 23.7% and 9% of cases, respectively, but were of no clinical value; 33.6% patients had esophagogastroduodenoscopy (9.7% abnormal: Helicobacter pylori, chemical gastritis, esophagitis) and 17.2% had colonoscopy (9.5% abnormal: rare fork crypts, lymphoid hyperplasia). Total costs: $744,726. Average cost per patient: $6104.30. CONCLUSIONS: In children with PP-FGIDs, investigations are common, costs are substantial, and yield is minimal.

Correlation of hepatitis C RNA and serum alanine aminotransferase in hepatitis B and C seronegative healthy blood donors.

INTRODUCTION: Historically, serum alanine transaminase (ALT) has been used as a surrogate marker in the detection of hepatitis viruses in blood donors. With the availability of newer sensitive technologies for the detection of seroconversion, the value of ALT becomes questionable but continues to be used for this purpose with subsequent discarding of ALT elevated blood units. OBJECTIVE: The present study aims to evaluate the significance and cost effectiveness of ALT as a surrogate marker for hepatitis C virus infection in healthy asymptomatic blood donors who were serologically negative. MATERIALS AND METHODS: The study was conducted at clinical laboratory of a tertiary care hospital for a period of one year from November 2006 to October 2007. All donors were screened serologically for hepatitis B, C and HIV I and II, syphilis and malaria and those tested positive were excluded from further evaluation. Gender-wise reference ranges and minimal and markedly raised results for ALT (described respectively as one and two folds increase above reference range) were defined and, accordingly, donors were grouped into three. Two hundred seronegative blood donors were randomly selected from all three groups of ALT results and tested for hepatitis C nucleic acid through Amplicor HCV RNA test. The cost of discarding an ALT -only elevated blood unit was also assessed. During the study period, 25117 subjects donated blood. EIGHT HUNDRED AND RESULTS: Seventy two donors (3.4%) were positive for one or more serological tests. ALT of all donors ranged from 0-1501 U/L (Mean +/- SD; 33.4 +/- 25.45 U/L). The donors seronegative for all disease markers were 24245 (96.6%). Of these, 21164 (87.2%) donors had their ALT within reference range while 2874 (11.8%) and 207 (0.8%) of donors had minimal and markedly elevated results. Thus, 621 blood bags (red cells, platelets and plasma) costing $ 39200.0 were discarded based on ALT results alone. Of 200 seronegative donors evaluated for hepatitis C nucleic acid, only one within markedly elevated ALT levels was found to be positive. The present work did not support a positive association between hepatitis C virus nucleic acid and elevated ALT in healthy serologically negative blood donors. CONCLUSION: We did not find serum ALT testing in donors as cost effective strategy for detection of hepatitis C virus ribonucleic acid. As the number of samples tested by us was small we suggest further work to evaluate the value of ALT levels in serologically negative donors in association with hepatitis C antigen and NAT testing to elucidate the true burden of disease in geographical regions where hepatitis C is endemic and voluntary blood donation is sparse.

[ALT screening for chronic liver diseases: scrutinizing the evidence]. / ALT als Screeningparameter für Lebererkrankungen: eine kritische Evaluation der Evidenz.

Elevated serum amino-transferase levels may be associated with liver injury. Testing for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is part of many routine screening approaches. The aim of this manuscript was to scrutinize the evidence for using ALT testing as a primary screening parameter for liver diseases. We conclude that (i) elevated serum ALT levels indicate a high specificity and a reasonable sensitivity liver injury, (ii) 10 - 25 % of German adults have elevated ALT levels, (iii) ALT values are increased in the majority but not all patients with acute and chronic liver disease (iv) elevated ALT-values are associated with an increased risk of liver-specific mortality, (v) elevated ALT values are also a risk factor for non-hepatic diseases including diabetes mellitus type 2, metabolic syndrome, cardiovascular diseases and malignancies, (vi) many liver diseases identified by an ALT screening can be treated successfully including prevention of development of clinical endpoints, (vii) an ALT-screening is very likely to be cost-effective although studies are needed for Germany to support this conclusion.