Ultrasound examination in jaundiced patients. Is computer-assisted preclassification helpful?

In this study we attempted to determine the diagnostic accuracy and reproducibility of ultrasonography (US) for jaundice and to see how US can best be combined with preliminary clinical-biochemical diagnoses to plan the invasive work-up. US proved reproducible in two diagnostic departments (127 agreements in 135 cases). But, since obstruction was underdiagnosed (15 double-false negatives), the predictive value of a negative result was only 0.83. By adding a term which represents the US conclusion, obstruction or not, to the Copenhagen pocket diagnostic chart score (based on the logistic model) we found that an obstructive conclusion increases the odds of obstruction by a factor of 25, and a non-obstructive conclusion decreases the odds by a factor of only 1.9. We conclude that the preliminary diagnosis is frequently sufficiently certain to be unalterable by US. This leaves only 40% of the jaundice cases in which US is necessary to plan invasive work-up. The US workload can even, it appears, be reduced to about 22% without appreciable penalty in terms of unrewarding invasive procedures. Using these strict indications, four US examinations seem to suffice to avoid one such error. Relying on either US or clinical-biochemical data alone is inferior to the combined strategy.

Determination of T1- and T2-relaxation times in the spleen of patients with splenomegaly.

Twenty-nine patients with known splenomegaly and seven healthy volunteers were examined. The T1 and T2 relaxation times were read out from a region of interest centrally in the spleen. Even though different mean T1 and T2 relaxation times were found between the groups, the great scatter and the considerable overlap between the groups makes the contribution of relaxation time measurements to the differential diagnosis of splenomegaly of limited value.

Prolonged T1 in patients with liver cirrhosis: an in vivo MRI study.

Fifteen patients with liver cirrhosis and two control groups were examined. The first control group consisted of 7 healthy volunteers, and the second group of 17 patients with nonfocal liver diseases. The T1 and T2 relaxation times were calculated from signal intensities read out from a region of interest centrally located in the liver. T1 relaxation time was longer in the patients with liver cirrhosis than in the two reference groups. Ten patients had a liver biopsy taken prior to the MRI study. No correlation was found between histopathology and the measured relaxation times.

Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis. Survival and prognostic factors.

Hepatic encephalopathy and gastrointestinal (GI) bleeding are the most serious complications in cirrhosis. The purpose of this study was to examine survival after the first episode of GI bleeding or coma, or both, and to identify variables associated with the subsequent survival in 284 consecutive patients with cirrhosis admitted to one division of hepatology over a period of 81 months. Patients who only bled had markedly longer survival than those who only had coma, whereas those who had both bleeding and coma had by far the poorest survival, only 15% being alive 1 year later. Several other variables showed a significant association with survival. In a Cox multiple regression analysis the following four variables showed significant association with a short survival: coma and bleeding at the episode, ascites, low prothrombin index, and high serum creatinine. The prognostic index derived from the Cox model, which was validated by a split-sample testing technique, may be used to refine prognostic estimation in this subgroup of severely ill cirrhotic patients.

A decision tree for early differentiation between obstructive and non-obstructive jaundice.

We present a method for early differentiation between obstructive and non-obstructive jaundice. On the basis of 14 variables (clinical data and clinical chemical tests, all available within 48 h) a simple decision tree or flow chart has been constructed. The diagnostic yield was as follows: 857 of 982 consecutive jaundiced patients (87%) in a data base and 98 of 108 patients in an independent test sample (91%) were correctly classified. Decision trees for the differentiation between benign or malignant causes within the obstructive group and between acute or chronic causes within the non-obstructive group are also presented. The resulting four-way classification was correct for 77% of the patients in the data base and for 72% of the patients in the test sample. The decision trees are compared with previous methods founded on Bayes' rule and logistic discrimination. The decision trees enable a quick and reliable classification of jaundiced patients, thus providing a valid basis for rational planning of the further diagnostic study.

Intolerance to tartrazine in aspirin-induced asthma: results of a multicenter study.

One hundred and fifty-six German, Italian and Polish patients with confirmed aspirin-induced asthma underwent open oral challenges with increasing doses of tartrazine up to 25 mg. All positive challenges were repeated under double-blind conditions. Only 4 of 156 patients (all Polish) had positive reactions in a double-blind test, as evidenced by a fall in FEV1 greater than 25% from baseline and corresponding clinical symptoms. Sixty-five patients who tolerated 25 mg tartrazine well received 50-3,000 mg tartrazine and none showed adverse reactions. Thus, intolerance to tartrazine appears to be rare among Central-European and South-European patients with aspirin-induced asthma, its frequency amounting to about 2.6%.

Serum aminoterminal procollagen type III peptide in acute viral hepatitis. A long-term follow-up study.

The development of chronic viral liver disease is associated with increased deposition of connective tissue in the liver. The aminoterminal propeptide of procollagen type III (P-III-NP) is considered to reflect the metabolism of collagen type III, one of the major collagen types in liver fibrosis. The purpose of the present study was to elucidate, whether S-P-III-NP in patients with viral hepatitis was related to injury and repair processes in the liver. S-P-III-NP was determined in a prospective longitudinal study of 63 patients with acute viral hepatitis followed to healing or development of chronic liver disease. Two assays were applied. The P-III-NP Ria-gnost assay, which measures mainly the intact propeptide, and the P-III-NP Fab-assay, in which the antibody exhibits equal affinity to the intact propeptide as well as the degradation product col 1. At the onset of viral hepatitis, S-P-III-NP determined in either assay was equally elevated in the two groups. From the second month of follow-up, significantly higher levels in both assays were observed in patients developing chronic disease. During follow-up, the highest P-III-NP RIA-gnost values were seen in patients with chronic active hepatitis, and active cirrhosis. S-P-III-NP decreased towards normal levels during development of inactive cirrhosis. In the individual patient, S-P-III-NP Ria-gnost was positively related to transaminases. During follow-up of uncomplicated hepatitis a normalization of transaminases occurred before normalization of S-P-III-NP RIA-gnost. Considering, that S-P-III-NP, in contrast to the conventional laboratory variables, reflects the metabolism of type III collagen, it is assumed that determination of S-P-III-NP may provide new information on fibrogenesis in viral liver disease.

Updating prognosis and therapeutic effect evaluation in cirrhosis with Cox's multiple regression model for time-dependent variables.

A multivariate Cox regression analysis with time-dependent variables has been performed on the data of 415 patients with cirrhosis included in a controlled clinical trial of 10-15 mg prednisone daily versus placebo. The analysis showed that a poor prognosis was associated with a low prothrombin index, marked ascites, GI bleeding, high age, high daily alcohol consumption, high bilirubin and alkaline phosphatase and low albumin values, little liver connective tissue inflammation, and poor nutritional status. Prothrombin index and ascites showed significant interaction with the treatment in such a manner that high prothrombin index and absence of ascites were associated with a beneficial effect of prednisone, whereas low prothrombin index and presence of ascites were associated with a harmful effect of prednisone treatment. The final model was validated in independent patients by comparing their actual survival with that predicted from the model, using a split-sample testing technique. The prognostic factors were combined with an index that can be used to update prognosis whenever changes occur in the clinical status of a patient during the course of the disease. The probability of surviving the next 3 or 6 months can be estimated from the prognostic index at any time during the course. The index may be of value for the correct timing of special therapeutic procedures such as liver transplantation.

Computer diagnosis in jaundice. Bayes' rule founded on 1002 consecutive cases.

Extensive clinical and clinical chemical information was collected from 1002 consecutive jaundiced patients. Initial selection of variables based on Chi 2-tests or Mann-Whitney U-test allowed the removal of 64 of the 107 variables originally collected. A further selection of variables was carried out using a modified version of Bayes' rule thus reducing the number of variables from 43 to 22. Of the 982 patients with a final diagnosis 743 patients (76%) could be classified correctly into one of 13 diagnostic categories. The Bayes' rule was also applied to a test group of a further 110 jaundiced patients and found to perform equally well: of 108 patients with a final diagnosis 81 (75%) were correctly classified. A comparison between the clinician's diagnosis and the computer-aided diagnosis according to Bayes' rule demonstrated agreement with regard to one of the 13 diagnostic alternatives in 734 patients (75%), of whom 81 patients were wrongly diagnosed. In the test group agreement upon diagnosis was found in 80 patients (74%). By plausibly combining the computer-aided and the clinician's preliminary diagnoses, more correct classifications were obtained than with either method alone. Many diagnostic modalities such as ultrasound examination, CT-scan, and direct cholangiography are at hand today for the differential diagnosis of jaundice. Computer-aided diagnosis using Bayes' rule has proved a reliable tool for the clinician and can be used in the planning of a diagnostic strategy for the individual jaundiced patient.

Changes of laboratory variables with time in cirrhosis: prognostic and therapeutic significance.

The time change of laboratory variables in cirrhosis was studied by analysis of data from 488 patients with cirrhosis included in a controlled clinical trial of long-term prednisone vs. placebo. In the placebo group, a marked regression towards normal was seen within 3 months of entry into the trial (increase in serum albumin, acetylcholinesterase, cholesterol, hemoglobin and decrease in erythrocyte sedimentation rate). The subsequent course did not show a clear pattern, except for a slight increase in serum bilirubin and decrease in albumin. When studied in relation to the time of death in patients dying from a "hepatic" cause, marked increase in bilirubin and decrease in prothrombin index, albumin and cholesterol were seen in the year prior to death with little change before that time. In the prednisone group, a more marked decrease in bilirubin, SGOT, alkaline phosphatase, gamma-globulin, sulfobromophthalein retention, erythrocyte sedimentation rate and increase in leukocytes, prothrombin index and cholesterol were seen during the first 3 months. In relation to time of death from a "hepatic" cause, similar changes were seen as in the placebo group except that alkaline phosphatase increased and cholesterol did not decrease. A beneficial effect of prednisone on survival, as expressed by a previously developed therapeutic index, was associated with decrease in SGOT, alkaline phosphatase and gamma-globulin within the first 3 months. An increase in SGOT during prednisone seemed to be associated with harmful effects of therapy.

Survival after jaundice: a prospective study of 1000 consecutive cases.

A consecutive series of 1002 jaundiced adult patients covering 23 different causes of jaundice is presented. Patients were followed up for 2 to 7 years. The survival for the 784 patients included during their first episode of jaundice was calculated for each diagnostic category. Examples of decreased survival as compared with the general population were (figures indicate 3 months' and 5 years' survival, respectively): alcoholic cirrhosis 0.81, 0.35; cryptogenic cirrhosis 0.78, 0.32; pancreatic carcinoma 0.54, 0.04; cholangiocarcinoma 0.26, 0.00; and heart failure with liver congestion 0.47, 0.07. Ten of 172 patients with acute viral hepatitis died, 1 of fulminant hepatitis and 9 because of suicide or accidents. Of 105 patients with gallstones 37 died during the study period, but in only 9 of these could death be attributed to the gallstone disease. New diagnostic methods and types of treatment for jaundiced patients have been developed during recent years. To justify fully these diagnostic and therapeutic modalities, knowledge of the prognosis for the various causes of jaundice is essential.