Background: The guaiac faecal occult blood test (G-FOBT) is recommended as a screening test for colorectal cancer but its low sensitivity has prevented its use throughout the world. Methods: We compared the performances of the reference G-FOBT (non-rehydrated Hemoccult II test) and the immunochemical faecal occult blood test (I-FOBT) using different positivity cut-off values in an average risk population sample of 10 673 patients who completed the two tests. Patients with at least one test positive were asked to undergo colonoscopy. Results: Using the usual cut-off point of 20 ng/ml haemoglobin, the gain in sensitivity associated with the use of I-FOBT (50% increase for cancer and 256% increase for high risk adenoma) was balanced by a decrease in specificity. The number of extra false positive results associated with the detection of one extra advanced neoplasia (cancer or high risk adenoma) was 2.17 (95% confidence interval 1.65-2.85). With a threshold of 50 ng/ml, I-FOBT detected more than twice as many advanced neoplasias as the G-FOBT (ratio of sensitivity = 2.33) without any loss in specificity (ratio of false positive rate = 0.99). With a threshold of 75 ng/ ml, associated with a similar positivity rate to G-FOBT (2.4%), the use of I-FOBT allowed a gain in sensitivity of 90% and a decrease in the false positive rate of 33% for advanced neoplasia. Conclusions: Evidence in favour of the substitution of G-FOBT by I-FOBT is increasing, the gain being more important for high risk adenomas than for cancers. The automated reading technology allows choice of the positivity rate associated with an ideal balance between sensitivity and specificity.

AND THE COLLABORATIVE STUDY GROUP 4 drug abuse (21 cases, 14 men all õ 40-years-old), previous The aims of this study were the following: 1) to estitransfusion (22 cases, 18 women), and not having paid mate the prevalence of hepatitis C virus (HCV) antibody employment. Although routes of transmission other (anti-HCV) in a population-based survey of French resithan IV drug abuse and transfusion may not be formally dents not selected for risk factors; 2) to investigate the excluded they were not found to be statistically signifiassociation between anti-HCV seropositivity, viremia, cant. Hepatitis C appears to be a major public health the infecting HCV genotype, and the alanine transamiconcern in France. A more active screening policy may nase ( 1 The most serious conseprevalence of 1.15%. Fifty percent of these positive vol-quences of HCV result from chronic infection. However, the unteers also had an abnormal ALT level and 81% were development of an HCV carrier state without major liver HCV-RNA positive by polymerase chain reaction (PCR). anomalies as assessed by liver function tests is not uncomThe prevalence weighted for age, sex, and place of resi-mon and some patients with histological evidence of chronic dence was 1.05% (95% CI: 0.75-1.34). The weighted preva-active hepatitis or cirrhosis present minimal clinical evidence lence was lower among men ú 40-years-old (0.5%; 95% of liver disease.2,3 HCV infection is most commonly identified CI: 0.1-1.0) and was close to 1% in all other age and sex following diagnosis of chronic liver disease of 10 to 30 years groups. Prevalence was inversely correlated with socio-duration. 4 Surveys of overt clinical infections thus give a poor professional status with the highest rate being found estimate of the overall prevalence of HCV infection in the among those with no paid employment (2.2%; 95% CI: general population. Only seroprevalence studies using large 1.3-3.0). The HCV prevalence (1.7%; 95% CI: 1.0-2.3) was numbers of subjects not selected for risk factors can yield highest in southeastern France. Seventy-eight percent accurate information on the health burden associated with of positive intervenous (IV) drug abusers were infected HCV in the general population. Although long-term mortality with HCV genotypes 1a or 3, whereas 80% of the transfu-associated with chronic hepatitis C remains to be detersion-associated cases were infected by HCV genotypes mined, 5 prevalence data from representative surveys would 1b or 2a. Only three variables were significantly associ-help plan clinical and prevention activities. ated with HCV seropositivity in multivariate analysis: IV Most available information about HCV antibody (anti-HCV) seroprevalence in the French population are from studies of high risk groups, 6-8 blood donors (anti-HCV prevalence from 0.6% to 0.8% in 1991, 9,10 and 0.3% in 1994 11 ), and pregAbbreviations: HCV, hepatitis C virus; anti-HCV, HCV antibody; ELISA, enzyme-linked nant women (prevalence from 1% to 2%).12 immunosorbent assay; SIA, strip immunoblot assa...

Except for increased serum alkaline phosphatase (AP) effects on metabolic, synthetic, and excretory hepatic levels, the changes in liver function test (LFT) values functions. 2 The biliary excretion of bromosulfophthaduring normal pregnancy have not been clearly estab-lein decreases during pregnancy. 3,4 Some authors have lished, mainly because most studies do not include stated that there is a subclinical physiological cholestamatched controls. We therefore measured the serum val-sis during pregnancy. 5 The increase in plasma volume ues of routine liver tests including 5 -nucleotidase and that occurs during pregnancy leads to hemodilution 6,7 total bile acids in 103 healthy pregnant women (first tri-and decreases the serum protein concentrations. Semester, n Å 34; second trimester, n Å 36; third trimester, rum alkaline phosphatase levels increase in late pregn Å 33) and in 103 age-matched controls not receiving nancy because of both a production of the placental oral contraception. Fasting blood samples were taken.isoenzyme and an increase in the bone isoenzyme. [8][9][10] Because of hemodilution, serum albumin levels were significantly lower during all trimesters. As expected, AP It is therefore not surprising that changes in liver funcactivity was significantly higher in the third trimester. tion tests (LFTs) occur during pregnancy. NevertheSerum aspartate transaminase (AST) activity and total less, except for increased alkaline phosphatase levels, bile acid (TBA) concentrations did not differ between which have been clearly demonstrated, the changes in pregnant and nonpregnant women. Serum alanine the other LFT values have not been clearly established, transaminase (ALT) activity was slightly higher in the and a recent review in this field has shown that there second-trimester pregnant women than in controls (6.8 are some discordances in the literature. 11 The identifi-{ 4.5 vs. 8.2 { 5.8, P Å .04), although all values remained cation of these physiological changes is important for within normal limits. In pregnant women, total and free the diagnosis of liver diseases during pregnancy.bilirubin concentrations were significantly lower durThus, the aim of this study was to evaluate the ing all three trimesters, as was conjugated bilirubin during the second and third trimesters. Serum g-glutamyl changes in serum levels of routine LFTs, i.e., alkaline transpeptidase (GGT) activity was significantly lower in phosphatase (AP), alanine transaminase (ALT), asparthe second and third trimesters. Serum 5 -nucleotidase tate transaminase (AST), g-glutamyltranspeptidase activity was slightly but significantly higher in the sec-(GGT), total and conjugated bilirubin, 5 -nucleotidase, ond and third trimesters. The knowledge of these results and total bile acids (TBA) during normal pregnancy is useful for the interpretation of LFT values and the compared with a control group of nonpregnant women. hemodilution. The pregnant woman experiences physiological PATIENTS AND METHODSchanges to support fetal growth and development. Dur...

We investigated variations in sensitivity of an immunochemical (I-FOBT) and a guaiac (G-FOBT) faecal occult blood test according to type and location of lesions in an average-risk 50-to 74-year-old population. Screening for colorectal cancer by both non-rehydrated Haemoccult II G-FOBT and Magstream I-FOBT was proposed to a sample of 20 322 subjects. Of the 1615 subjects with at least one positive test, colonoscopy results were available for 1277. A total of 43 invasive cancers and 270 high-risk adenomas were detected. The gain in sensitivity associated with the I-FOBT was calculated using the ratio of sensitivities (RSN) according to type and location of lesions, and amount of bleeding. The gain in sensitivity by using I-FOBT increased from invasive cancers (RSN ¼ 1.48 (1.16 -4.59)) to high-risk adenomas (RSN ¼ 3.32 (2.70 -4.07)), and was inversely related to the amount of bleeding. Among cancers, the gain in sensitivity was confined to rectal cancer (RSN ¼ 2.09 (1.36 -3.20)) and concerned good prognosis cancers, because they involve less bleeding. Among high-risk adenomas, the gain in sensitivity was similar whatever the location. This study suggests that the gain in sensitivity by using an I-FOBT instead of a G-FOBT greatly depends on the location of lesions and the amount of bleeding. Concerning cancer, the gain seems to be confined to rectal cancer.

Immunochemical faecal occult blood tests (I-FOBT) detect more effectively advanced neoplasia than guaiac tests (G-FOBT). The study aim was to compare the performance of an I-FOBT whilst varying the positivity threshold and considering four analysis modalities: one sample was performed (MG 1 ), two samples were performed and at least one sample was positive (MG 21 ), both samples were positive (MG 211 ) or the mean of the two samples' log-transformed haemoglobin contents exceeded the cutoff (MG 2m ). Screening for colorectal cancer using both G-FOBT and two samples' I-FOBT was performed by an average-risk population sample of 20,322 subjects. Among the 1,615 subjects with at least one positive test, 1,277 had a satisfactory colonoscopy result; 43 invasive cancers and 270 high-risk adenomas were detected. The I-FOBT was reinterpreted under each analysis modality (a random selection of one sample led to MG 1 ). For all modalities, increasing the positivity threshold decreased sensitivity and increased specificity. The relative ROC curves (in reference to G-FOBT) demonstrated similar performance for MG 1 and MG 21 , and improved performance for MG 2m . MG 211 sensitivity was limited within the range of positivity thresholds evaluated. For any specificity, MG 2m provided the highest sensitivity. For any sensitivity, MG 2m provided the highest specificity. For any positivity rate, MG 2m provided both the highest sensitivity and specificity. This study suggests the replacement of MG 21 by MG 1 or, for even better performance, by MG 2m provided that two samples are performed with similar participation (which should be explored). The targeted positivity rate could then be achieved by choosing the positivity threshold. ' UICCKey words: colorectal neoplasms; occult blood; mass screening; sensitivity and specificity; colonoscopy A recent systematic review of randomised trials 1 has confirmed that the screening of average-risk populations using the guaiac faecal occult blood test (G-FOBT) reduces specific mortality related to colorectal cancer. However, the low sensitivity of G-FOBT limits the extent of its benefit. Numerous studies have emphasised the relevance of immunochemical faecal occult blood tests (I-FOBT) in improving the sensitivity of screening.2-8 Several authors have concluded that evidence obtained in favour of testing with guaiac can be extended to the immunochemical test without new trials.9-13 However, screening is aimed at large samples of asymptomatic populations and a gain in sensitivity is not to be counterbalanced by reduced specificity. Some I-FOBT are automatically read, and provide a quantitative measure of faecal bleeding. They consequently allow a positivity threshold to be chosen to optimise the balance between test sensitivity and specificity. Furthermore, as for the G-FOBT, I-FOBT can involve one, two or more samples. Previous papers assessing the influence of the positivity threshold on test performance did not report the results of each sample, when available, in screening settings. 3,5,[1...