Alpha-2-macroglobulin (A2M) is a proteinase inhibitor. Cells synthesizing A2M are in first-order hepatocytes and in second-order activated Ito cells (in culture starting at day 4-5 after seeding). This study was undertaken in 525 alcoholic patients with different histological stages of alcoholic liver disease to assess if the A2M could improve the diagnostic value of PGA index for detection of cirrhosis or fibrosis among drinkers, particularly in patients without clinical symptoms of liver failure and portal hypertension, and to assess the specific correlation of serum A2M with the score of liver fibrosis adjusted for steatosis and alcoholic hepatitis and thereafter adjusted for GGT, PT, and ApoA1, the three components of the PGA index. In 525 alcoholic patients, we have demonstrated the independent diagnostic value of A2M. The predictive values of the weighted score, using linear discriminant function combining PT, GGT, ApoA1 and A2M of the PGAA score and of the PGA score were assessed in a training step and validated in a second step. Then, 316 alcoholic clinically asymptomatic patients were studied. In these patients, the discriminant function permitted correct classification of 72% of patients. The PGAA index had comparable diagnostic value with 70% of patients correctly classified. On the other hand, the PGA index including only PT, GGT, and ApoA1 had classified correctly less patients (65%) than the discriminant function and the PGAA index (P < 0.01). For a value of 7, PGAA had 79% specificity and 89% sensitivity for the diagnosis of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the performance of screening for preeclampsia and intrauterine growth restriction by combining second trimester maternal serum screening and uterine Doppler ultrasound. Methods: A cohort of 2,615 women underwent both maternal serum screening (using human chorionic gonadotropin (hCG) and α-fetoprotein (AFP)), and second trimester uterine artery Doppler. The sensitivity, specificity and predictive value of different combinations of both tests were compared. Results: The mean values for hCG and AFP were significantly higher in women with subsequent preeclampsia (p < 0.0003 and p < 0.03, respectively). Taking into account obstetrical history, hCG and AFP levels, notching on uterine artery Doppler and parity, the adjusted odds ratios were significantly higher for a high level of hCG for preeclampsia, intrauterine growth restriction (IUGR) and pregnancy-induced hypertension. AFP level >1.5 MoM (multiples of the median) was significantly correlated with subsequent IUGR. The presence of a uterine notch was associated with a significantly higher risk of both preeclampsia and IUGR. The combination of an elevated serum level and the presence of a uterine notch had a positive predictive value (PPV) for preeclampsia of 25 and 21% for hCG and AFP, respectively. The combination of a bilateral notch with a low level of hCG or a high level of AFP had a PPV for IUGR of 50 and 43%, respectively. The sensitivity of the different tests ranged from 2 to 40%. Conclusion: The combination of serum markers and abnormal uterine Doppler ultrasound improves the identification of women at risk for subsequent pregnancy complications. These results should encourage care providers to perform a uterine Doppler ultrasound when serum markers are abnormal. However, the sensitivity of these tests is too low to provide an efficient generalized screening.

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