Liver Failure Complicating a Febrile Illness in a



Liver Failure Complicating a Febrile Illness in a
Liver Failure Complicating a Febrile Illness in a
Middle-Aged Man
Abhinav Vasudevan, Zaid Ardalan, and Peter Angus
Department of Gastroenterology and Liver Transplantation, Austin Hospital, Heidelberg, Victoria, Australia
A 53-year-old safety
inspector from rural
Australia was transferred to a major
liver center with liver
failure, one week after presentation to
another hospital with
10 days of fevers,
headache, lethargy
and myalgias and a
chest x-ray showing
consolidative changes.
He was treated initially for community- acquired pneumonia with ceftriaxone. Despite an improvement in his respiratory
status, his clinic state deteriorated with ongoing fevers and worsening hyperbilirubinemia, coagulopathy and renal
impairment requiring hospital transfer and admission to the high dependency unit where his antibiotics were changed to
tazobactam and piperacillin.
His past history included type 2 diabetes mellitus, hypertension and a chronic alcohol intake of over 400 grams per
week. He had no history of recent travel and no close contacts were unwell. His medications were atenolol, amlodipine and
valsartan. He was an ex-smoker. He had recently worked in an abattoir (a slaughterhouse) inspecting conditions for the
processing of cattle.
Blood tests at the time showed a normocytic anaemia with haemoglobin of 98g/L (reference range 130-180g/L), white cell
count 12.3x109/L (4.0-11.0x109), neutrophils 10.1x109/L (2-7.5x109), lymphocytes 0.5x109/L (1.0-4.0x109), international
normalized ratio 2.2, urea 12.2 mmol/L (3.0-9.2mmol/L), creatinine 114 micromol/L (62 micromol/L to 106 micromol/L),
bilirubin 337 micromol/L (<18 micromol/L), alanine aminotransferase 51 units/L (<41 units/L), aspartate aminotransferase
83units/L (<40units/L), gamma GT 65 units/L (N<60units/L), alkaline phosphatase 52 units/L (40-130units/L), albumin 24
g/L (35-52g/L) and C reactive protein of 305mg/L (normal <5mg/L). Serial blood and urine cultures, serology for hepatitis A,
B, C, E, cytomegalovirus (CMV), Ebstein Barr virus (EBV), herpes simplex virus (HSV), influenza, brucellosis, antinuclear
antibody (ANA), anti-mitochondrial antibody (AMA) and anti-liver kidney microsomal (anti-LKM) antibody were negative. Antismooth muscle antibody (ASMA) was positive with a titre of 1:320. Coxiella Burnetti phase II IgM and phase I serologies were
negative but phase II IgG was strongly positive (>3200 units). CT of the abdomen showed features consistent with underlying
cirrhosis with portal hypertension and small volume ascites, but no lymphadenopathy or mass lesions were seen.
He was treated for presumed alcoholic hepatitis with pentoxyfilline for 1 week with no improvement in his clinical state
and persistent liver function derangement, with bilrubin rising to 324 micromol/L, ALT 113 units/L and AST 133units/L.
A liver biopsy was performed which showed background cirrhosis with a steatohepatitis pattern as well as extensive small
granulomas (Figure A) with the appearance of poorly formed rings surrounding a central lipid vacuole (Figure B).
What is the cause of the patients liver deterioration?
A. Alcoholic hepatitis
D. Sarcoidosis
B. Hodgkin’s lymphoma
E. Autoimmune hepatitis
C. Q fever hepatitis
Gastroenterology 2016;150:1542–1544
Look on page 1544 for the answer and see the Gastroenterology web site ( for more
information on submitting your favorite image(s) to Practical Teaching Cases.
We thank Dr Khashayar Asadi for providing the photos of the histology specimens.
Conflicts of interest
The authors disclose no conflicts.
© 2016 by the AGA Institute
Answer (Page 1542): Q fever hepatitis
The correct answer is C: This patient had underlying alcoholic cirrhosis with acute decompensation of liver function and
evidence of a very active granulomatous hepatitis on histology. His long-term alcohol consumption is a major risk for
alcoholic hepatitis and the histological finding of an active steatohepatitis is compatible with this diagnosis. However the
rapid deterioration in his condition raised concerns that another illness was present and alcoholic hepatitis would not
explain the prodrome of a prolonged flu-like febrile illness or positive ASMA results. Hepatic sarcoidosis is accompanied by
lung involvement in the majority of cases, the granulomas are often at an identical stage of maturation and there may be
evidence of an intrahepatic cholestasis on histology. All of these features were absent in this case. Despite the positive
ASMA, features of autoimmune hepatitis were not found on biopsy. Although Hodgkin’s disease can be associated with liver
granulomas, there was no lymphadenopathy or mass lesions identified on imaging to suggest lymphoma.
Q fever is a zoonotic infection caused by the pleomorphic gram-negative coccobacilli Coxiella Burnetti. The bacterium is
highly infective and transmitted by inhalation of aerosol particles from the excrement of infected animals. Domesticated
livestock and small rodents are major reservoirs of the bacterium. Acute Q fever is usually a mild or asymptomatic infection,
with only 2-5% of cases requiring hospitalization.1 Cases requiring hospitalisation most commonly present as fever of
unknown origin, but pneumonia and hepatitis are also common manifestations. It often begins as a “flu-like” illness with
non-specific fevers, headaches and myalgias and varying severity of pneumonia and/or hepatitis. The frequency of pneumonia and hepatitis show geographical variation for unclear reasons. The duration of fevers varies from 5 to 56 days.2
Elevated liver enzymes occur in up to 85% of cases.3 Jaundice and frank hepatitis are uncommon with acute Q fever,
although in our patient the disease may have precipitated acute liver decompensation in the setting of alcoholic cirrhosis. Q
fever hepatitis may cause a prolonged febrile illness with liver biopsy classically showing so-called fibrin ring granulomaswith central lipid droplets. A minority of cases will develop chronic infection, with the most commonly involved organs
being the heart, blood vessels, bone or the liver. Autoantibodies are common in Q fever infections, including a positive
ASMA, AMA and antibodies to phospholipids, although their significance is unknown.
During the course of a Q fever infection, Coxiella Burnetti undergoes phase variation with changes to the antigen
structure on the outer cell membrane surface of the organism, resulting in different antibody responses by the host immune
system. The antibody response during an acute infection is predominantly to phase II antigens while antibodies to phase I
antigens are higher during chronic infection. It can take 3 to 4 weeks for antibodies to become positive and almost 40% of
cases have negative serology when first tested. IgG class titres to phase II antigens can develop very early on in Q fever sera,
however one would also expect IgM antibodies to be positive during an acute infection, which were not evident on initial
serology in our patient. The clinical history with known exposure to cattle and evidence of granulomas on liver histology
prompted repeat Q fever antibody testing. On repeat testing, phase II antibodies for IgM and IgG were both strongly positive
(>3200) suggesting acute Q fever. He was treated with 4 weeks of doxycycline 200mg. He was discharged from hospital
after 4 weeks with normal liver biochemistry.
Raoult D, Marrie T, Mege J. Natural history and pathophysiology of Q fever. Lancet Infect Dis 2005;5:219–226.
Parker NR, Barralet JH, Bell AM. Q fever. Lancet 2006;367:679–688.
Fournier PE, Marrie TJ, Raoult D. Diagnosis of Q fever. J Clin Microbiol 1998;36:1823–1834.

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