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HAROLD W. HOROWITZ,1 BRAD DWORKIN,2 GILDA FORSETER,1 ROBERT B. NADELMAN,1 CHRIS CONNOLLY,1
BARBARA B. LUCIANO,3 JOHN NOWAKOWSKI,1 THOMAS A. OBRIEN,4 MARK CALMANN,4 AND GARY P. WORMSER1
1412
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WBS: Hepatology
HOROWITZ ET AL.
A retrospective convenience sample population was obtained to determine the frequency of abnormal liver function
studies in a population without Lyme disease. The charts
of 100 randomly selected employee health applicants at our
hospital from 1993 who had serum biochemistry profiles performed at preemployment evaluation were reviewed. Individuals who had exposure to blood products were excluded, as
were people with a history of active hepatitis, alcohol abuse,
or illicit intravenous drug use. None of these individuals had
a known history of Lyme disease. All controls had negative
serum studies for hepatitis B surface antigen and antibodies
to hepatitis C. Information regarding gastrointestinal symptoms were not generally available for controls.
Early localized Lyme disease was defined as a single EM
lesion without objective neurological involvement, carditis,
or arthritis. Early disseminated Lyme disease was defined
by the presence of multiple EM lesions or at least one EM
lesion with objective neurological or cardiac abnormalities or
arthritis.
Serum from visits at 3 months or 6 months after presentation was tested for the presence of total antibody to hepatitis
A by enzyme immunoassay by HAVAB EIA (Abbott Laboratories, Abbott Park, IL). All patients with evidence of HAV
antibodies had serum from the initial visit tested for hepatitis
A virus immunoglobulin M by HAVAB-M (Abbott Laboratories). Serum from 3 or 6 months after presentation was
tested for hepatitis B virus core antibody by enzyme-linked
immunosorbent assay (ELISA) (Ortho Diagnostic Systems,
Inc., Raritan, NJ). For patients who tested positive for hepatitis B core antibody, serum from the initial visit was tested for
hepatitis B virus surface antigen by ELISA (Ortho Diagnostic
Systems, Inc.). Serum from 3 or 6 months after presentation
was tested for hepatitis C virus antibody by ORTHO HCV
3.0 ELISA (Ortho, Diagnostic Systems, Inc.).
Antibodies to B. burgdorferi in serum were detected by a
polyvalent ELISA using Whittaker Stat ELISA kits (Whittaker Bioproducts, Inc., Walkersville, MD) according to the
manufacturers instructions. Culture of B. burgdorferi was
performed in modified Barbour-Stoenner-Kelly media using
techniques previously described.12,13
Statistical analysis was performed using x2, Fishers exact
test, or Students t test (all two-tailed) as indicated. For those
with abnormal liver function tests, a paired t test was used
to compare the mean value at baseline with the mean value
20 days later. All values are expressed as mean { SD.
RESULTS
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Patients
(n 115)
Controls
(n 100)
Age (yr)
Sex (male)
Any LFT elevation
ALT
AST
ALP
GGT
Total bilirubin
1 Liver test elevation
Liver test 2 times normal
44.0 { 14.3
75 (65%)
46 (40%)
31 (27%)
18 (16%)
22 (19%)
32 (28%)
3 (3%)
31 (27%)
16 (14%)
31.8 { 12.3
45 (45%)
19 (19%)
7 (7%)
4 (4%)
8 (8%)
4 (4%)
1 (1%)
4 (4%)
2 (2%)
.001
.005
.001
.001
.006
.028
.001
.625
.001
.002
Abbreviations: LFT, liver function test; ALP, alkaline phosphatase; GGT, g-glutamyl transpeptidase.
WBS: Hepatology
Characteristic
Age (yr)
Sex (male)
Duration EM (days)
Size largest EM (cm)
Number EM lesions
Disseminated disease
Temperature
37.77C
GI symptoms
ELISA positive
Culture positive
ELISA or culture
positive
Normal LFT
(n 69)
Abnormal
LFT
(n 46)
43.6 { 13.8*
40 (58%)
7.5 { 6.6
15.6 { 6.9
3.3 { 12
13 (19%)
44.6 { 15
35 (76%)
8.5 { 7.6
18.6 { 12.8
7.3 { 15.7
22 (48%)
.632
.072
.504
.092
.124
.002
7 (10%)
18 (26%)
47 (68%)
32/56 (57%)
10 (22%)
17 (37%)
38 (83%)
17/43 (40%)
.148
.301
.129
.103
53 (77%)
41 (89%)
.153
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HOROWITZ ET AL.
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FIG. 1. Prospective evaluation of liver function tests in Lyme disease patients with EM at presentation and at 20 days after initiation
of treatment. j, mean values with 95% confidence bars. Dark horizontal bar represents the upper limit of normal for the liver function
test.
Patients
(n 108)
Controls
(n 100)
26 (24%)
9 (8%)
2 (2%)
19 (19%)
4 (4%)
2 (2%)
.472
.256
1.0
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WBS: Hepatology
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WBS: Hepatology
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
HOROWITZ ET AL.
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WBS: Hepatology