The validity of laboratory evidence in the diagnosis of the sequelae of acute hepatitis.

Summary Twenty-one patients, who had had acute hepatitis from six months to ten years before were studied by means of a group of laboratory procedures which included serum bilirubin determinations, examination of the urine for urobilinogen, the bromsulf alein test, hippuric acid synthesis, determination of the serum cholesterol, and of the prothrombin level, the cephalin cholesterol flocculationtest, thymol turbidity and thymol flocculation tests, and colloidal gold reaction. Five of these patients had symptoms suggesting chronic active hepatitis, seven had hepatomegaly. The others had no clinical evidence of hepatic disease. Some abnormality in the responses to one or more of these tests was noted in all of the patients. In two patients who were symptom-free, however, the only abnormality was very slight hypercholesterolemia, which may be considered to be of only questionable significance. The hippuric acid synthesis test was not abnormal in any of the eighteen patients in whom it was performed. The amount of urobilinogen in the urine was normal in twenty of the twenty-one patients studied. These two tests seemed relatively insensitive in detecting residual hepatic changes following hepatitis. The various flocculation tests gave normal responses in all but four of the patients. The cephalin cholesterol flocculation was positive in two and the colloidal gold reaction was positive in three. In only two patients were the flocculation tests strikingly abnormal. Although one of these two patients had clinical evidence of active liver disease, such evidence was much less pronounced in the other patient, so that in these two individuals no correlation between positive flocculations and the clinical features of hepatitis could be observed. In general the flocculation tests were of little value in the recognition of residual liver dysfunction. Hyperbilirubinemia was found in fourteen of the twenty-one patients. This consisted of increase in only the direct reacting bilirubin in nine of the fourteen patients. No instance of marked increase in the indirect reacting bilirubin was seen. The degree of hyperbilirubinemia was slight in most instances, but even this slight increase in bilirubin may have diagnostic significance and indicate definite hepatic dysfunction since it was not encountered without other evidence of liver disturbance. Some degree of excessive bromsulf alein retention was also encountered in fourteen of the twenty-one patients studied. This was also usually of slight degree. Although found frequently, bromsulf alein retention was occasionally absent in the face of other evidence of hepatic dysfunction, so that a normal response to the bromsulf alein test may not be considered as excluding the presence of residual hepatic dysfunction following hepatitis. In eight of the twenty-one patients, a low prothrombin level was found. All eight of these patients had abnormal responses to one or more of the other tests used, but in some instances the hypoprothrombinemia was the most striking laboratory evidence of hepatic disorder. Vitamin K was given to five of these eight patients and the prothrombin level responded slowly or not at all to this therapy. The hypothrombinemia seems, therefore, to indicate that a specific liver dysfunction remained following acute hepatitis. Determination of prothrombin is suggested as a valuable addition to the liver function tests usually employed in the search for sequelae of hepatitis. The abnormality may exist even though other liver function tests are relatively normal. Lowering of the cholesterol ester ratio, was seen in only one patient and only one patient had decrease of the total cholesterol. Ten of the twenty-one patients had hypercholesterolemia. Although this finding need not indicate dysfunction of the liver, its demonstration in association with other laboratory evidence of hepatic disturbance following hepatitis calls for further investigation. In this group of patients we could not find any close relation between the clinical features—symptoms and hepatomegaly—and the responses to the liver function tests used. Patients who had had acute hepatitis not infrequently gave abnormal responses to various liver function tests. The degree of abnormality was often slight and not necessarily indicative of disease that was active clinically. The prognostic significance of such findings can be determined only by repeated studies.