Hepatitis Profile Interpretation by Microcomputer

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1 Hepatitis Profile Interpretation by Microcomputer CHRISTOPHER M. FRAUENHOFFER, M.D. AND CLIFFORD H. URBAN, M.D. A simple BASIC computer program for interpreting two serologic markers of hepatitis A virus infection and five serologic markers of hepatitis B virus infection is described. The program is based on a two-dimensional matrix (table) containing all possible combinations of positive and negative test results with their associated interpretations. Clinically relevant reports are consistent, reliable, and legible. Sample reports are included. (Key words: Hepatitis A; Hepatitis B; Interpretive reporting; Microcomputer). Am J Clin Pathol 985; 84: APPROXIMATELY 6,000 cases of hepatitis B, 30,000 cases of hepatitis A, and 8,000 cases of unclassified hepatitis are reported each year in the United States. Nearly 0% of those infected with hepatitis B virus (HBV) become chronic carriers of surface antigen, and the overall mortality rate is estimated to be %. 5 The diagnosis of hepatitis rests on a combination of clinical suspicion and appropriate positive laboratory tests. Currently available serologic tests for hepatitis A virus (HAV) infection include those for IgM antibody to HAV, and for the combined IgG-IgM antibody to HAV. Tests for HBV infection are for the surface antigen (HB s Ag), the "e" antigen (HB e Ag), the antibody to HB e Ag (anti-hbe), the antibody to the core antigen (anti-hbc), and the antibody to HB s Ag (anti-hbs). Using these serologic markers, it has been possible to demonstrate the rise and fall of antigens and antibodies in persons infected with HAV or HBV, and to relate these to the clinical course and outcome. 6 Conversely, one can infer the current stage of disease in an individual patient by observing the pattern of positive and negative serologic markers. The presence or absence of these markers in a single specimen can be related to a clinically relevant statement bearing such information as the degree of infectivity, the presence or absence of immunity, or even the likelihood of chronicity. Several authors have constructed algorithms -6 ' 7 or tables,4,8 to make interpretation of markers easier, in part because some physicians are unsure of their meaning. 3 Algorithms or tables for interpreting test data are helpful in many cases, but the amount of information contained in them is usually limited to a few short Received March 3, 984; received revised manuscript and accepted for publication March 5, 985. Address reprint requests to Dr. Frauenhoffer: Department of Pathology, Albert Einstein Medical Center, Fifth and Reed Streets, Philadelphia, Pennsylvania 947. Department of Pathology, Albert Einstein Medical Center, Mt. Sinai-Darotf Division, Philadelphia, Pennsylvania, and Department of Pathology, Phoenixville Hospital, Phoenixville, Pennsylvania phrases, and they may not be readily available when needed. We wanted our reports to include comments on the clinical significance of the results and to recommend further testing when appropriate. A small microcomputer suitable for producing these reports in a reproducible (and legible) manner was used. The intent of this brief report is not to detail the clinical significance of HAV and HBV markers, but rather to describe our simple computer program. Materials and Methods The computer program was written in BASIC for a TRS-80 Model III Microcomputer with 48K RAM, two disk drives, and printer. The program occupies 8K memory and can produce a printed report within 30 seconds of the last test entry. We used the algorithms and tables listed in the references to construct a single table that included all possible combinations of positive and negative hepatitis A and hepatitis B markers. An interpretive comment was assigned to each unique combination. The program has been used for more than a year and has produced more than 300 patient reports at one author's (CHU) hospital. Design of the Computer Program The program is based on the familiar binary system, since each marker is either positive or negative. In this system, the number of possible combinations is n, where n is the number of variables (serologic markers). Using a tabular format, one can show the four possible patterns for HAV markers (Table ). Further, if a positive in the first column is assigned a value of, and a positive in the second column is assigned a value twice that of the first column (i.e., positive = ), we can obtain a number 0 through 3 for the sum of each row. Negative results always have a value 0. Each numerical value is the sum of the values in that row, and no number occurs more than once. 366

2 Vol. 84 No. 3 BRIEF SCIENTIFIC REPORTS 367 For HBV, there are five markers and 5 or 3 possible combinations. If a positive marker is assigned a value of in the first column, and double the value for a positive in each succeeding column (column =, column 3 = 4, column 4 = 8, column 5 = 6), one can obtain a value for the sum of each row. Each unique row will yield a unique number from 0 to 3 (3 possible combinations). Thus, if all HBV markers are negative, then the sum of the row is zero. Taking a hypothetical case where all markers are positive, the sum of the row would be 3 (i.e., ). In a more realistic situation, a positive HB s Ag (value ) arid positive HB e Ag (value ) with all other markers being negative, will yield a sum of 3. The only way to obtain this sum is through this combination. Table is a partial list of the 3 possible combinations. For the sake of simplicity in the computer program, the HAV markers are treated separately from the HBV markers. In each case when the test results have been entered, the computer adds the values of the markers and searches for the interpretive comment associated with that code number. The code numbers for HAV markers and for HBV markers are printed near the right margin on the report for easy reference. Appropriate comments are also generated when applicable. A sample computer report for a complete profile is in Figure. Not every patient needs the complete battery of HAV and HBV markers. A comprehensive profile is available, but fewer tests are more appropriate in some cases, such as in the evaluation of existing immunity prior to Table. Two Serologic Markers for HAV. Four Possible Combinations and Abbreviated Interpretations Anti-HAV IgG-IgM Anti-HAV IgM Sum Interpretation 0 3 No HAV exposure Remote HAV infection Acute HAV exposure Acute HAV exposure administration of hepatitis B vaccine. The five most commonly requested groups of tests at the hospital of one author (CMF) are the following: () All HAV and HBV markers (complete profile) () HAV markers only (3) HAV markers and HB s Ag (4) HB s Ag, HB e Ag, and anti-hbe (5) Anti-HBs, anti-hbc, and anti-hbe Other partial profiles can be developed as needed. The limited profiles use the same coding system for allocating the appropriate diagnosis, although it is a little more complex to evaluate studies in which some markers have not been requested. A sample report for profile 5 is in Figure. Discussion Information consists of pertinent data appropriately organized for easy interpretation, and part of the post- Table. Five Serologic Markers for HBV. The Complete Table Lists 3 Possible Combinations. Interpretations are Abbreviated HB 5 Ag HB e Ag Anti-HBe 4 Anti-HBc 8 Anti-HBs 6 Sum Interpretation (") (") No HBV exposure Early acute HBV Unusual; infectious Acute HBV; infectious Remote HBV; noninfectious Acute HBV; infectious Remote HBV; recovery 5 6 Chronic HBV After immunization 4 Remote HBV; recovery

3 368 FRAUENHOFFER AND URBAN A.J.C.P. September 985 ALBERT EINSTEIN MEDICAL CENTER MT. SINAI-DAROFF DIVISION FIFTH AND REED STREETS PHILADELPHIA, PA 947 DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE C. M. FRAUENHOFFER, M.D. CHAIRMAN PATIENT NAME : SEX : FEMALE ROOM : 34 A SAMPLE, PATIENT DATE DRAWN :03/04/85 DATE REPORTED : 03/05/85 DOCTOR : JONES MER*=*TITIS RROF- I l_e INTERPRETATI ON TEST NAME ANT I-HEPATITIS A IMMUNOGLOBULIN (IgG and ANTI-HEPATITIS A IMMUNOGLOBULIN (IgM) HEPATITIS B SURFACE ANTIGEN HEPATITIS 'e' ANTIGEN ANTIBODY TO HEPATITIS 'e' ANTIGEN ANTIBODY TO HEPATITIS B CORE ANTIGEN ANTIBODY TO HEPATITIS B SURFACE ANTIGEN IgM) RESULT negat i ve POSITIVE #** INTERPRETATION CODE The pattern of HAV serologic markers indicates that this patient has evidence o-f prior remote exposure to Hepatitis A and is now immune to HAV, The pattern o-f HBV serologic markers indicates that this patient has early acute infection with HBV and is highly infectious ( + HBeAg). Persistence of HBsAg longer than 6 months indicates the chronic carrier state. RECOMMENDATIONS : If the chronic carrier state is a clinical consideration then repeat profiles at monthly or bi-monthly intervals may be indicated. The HbsAg will persist longer than 6 months in the carrier state. PATHOLOGIST M.D, NAME : SAMPLE, PATIENT DOCTOR JONES DATE 0 3/04/85 FlG.. Sample report showing pattern of prior exposure to HAV with recovery, and acute infection with HBV. The code, 3 at the right margin is the sum of HAV markers, HBV markers (see text). Code for HAV carries the comment of remote exposure and immunity to HAV. Code 3 for HBV carries the comment of acute infectious phase of HBV infection.

4 Vol. 84. No. 3 BRIEF SCIENTIFIC REPORTS 369 ALBERT EINSTEIN MEDICAL CENTER MT. SINAI-DAROFF DIVISION FIFTH AND REED STREETS PHILADELPHIA, PA 947 DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE CM. FRAUENHOFFER, M.D. CHAIRMAN PATIENT SEX : ROOM : NAME MALE 345 SAMPLE, PATIENT DATE DRAWN :03/05/85 DATE REPORTED : 03/06/85 DOCTOR : JONES :R«^-T I T i s RROR I l_e I NTERPRI I OM TEST NAME ANTI-HEPATITIS A IMMUNOGLOBULIN <IgG and ANTI-HEPATITIS A IMMUNOGLOBULIN (IgM) HEPATITIS B SURFACE ANTIGEN HEPATITIS 'e' ANTIGEN ANTIBODY TO HEPATITIS 'e' ANTIGEN ANTIBODY TO HEPATITIS B CORE ANTIGEN ANTIBODY TO HEPATITIS B SURFACE ANTIGEN IgM) RESULT INTERPRETATION CODE 8 No serologic markers -for HAV were ordered on this study. Hepatitis B Viral antibodies were requested on this sample. Studies -for HBV antigens were not ordered. All antibodies to HBV are present. The patient has had prior exposure and is now immune. These statements presume that the HBsAg is negative since some Hepatitis B carriers have antigens and antibodies circulating at the same time. The presence o-f" both HBsAg and anti-hbs may indicate circulating immune complexes sometimes associated with glomerulonephritis, cryoglobulinemia, polyarteritis, etc. RECOMMENDATIONS : None PATHOLOGIST., M.D. NAME : SAMPLE, PATIENT DOCTOR : JONES DATE FIG.. Sample report of profile selection #5 which includes only antibodies to hepatitis B. 0 3/0 5/85

5 370 FRAUENHOFFER AND URBAN A.J.C.P. -September 985 analytical responsibility of the laboratory is to provide information, not just data. Correct interpretation of organ profiles or other multi-parameter tests is frequently a challenge in which we as pathologists can provide assistance. We have described a simple computer program for interpreting any one of several hepatitis profiles, thereby assuring at least some internal consistency. Our clinicians recognize that the reports do not claim to be clinical diagnoses and that decisions to hospitalize, isolate, immunize, or treat patients can be made properly only with a combination of clinical and laboratory information. References. Chang YW: Serologic markers of viral hepatitis. Diagn Med 983; 6(5):8-39. Dienstag JL: Serologic testing for hepatitis. Lab Management 98; 0(8):-8 3. Hoofnagle JH: Serologic markers of hepatitis B virus infection. Ann Rev Med 98; 3:- 4. Hoffnagle JH: Type A and type B hepatitis. Lab Med 983; 4: Immunization Practices Advisory Committee Centers for Disease Control: Immune globulin for protection against viral hepatitis. Morbidity Mortality Weekly Report. 98; 30(34): Polesky HF: Serologic tests in viral hepatitis, Clinical Laboratory Annual. Edited by HA Homburger, JG Batsakis. New York, Appleton Century Crofts, 98, pp Soloway HB: Interpreting hepatitis profiles. Diagn Med 980; 3(): 6-34

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