Hindawi Publishing Corporation

Case Reports in Critical Care

Volume 2016, Article ID 7389087, 6 pages
http://dx.doi.org/10.1155/2016/7389087

Case Report
Acute Warfarin Toxicity as Initial Manifestation of
Metastatic Liver Disease
Varalaxmi Bhavani Nannaka,1 Nihar Jani,2 Masooma Niazi,3 and Dmitry Lvovsky1
1

Division of Pulmonary and Critical Care Medicine, Bronx Lebanon Hospital Center, Bronx, NY 10457, USA
Department of Internal Medicine, Bronx Lebanon Hospital Center, Bronx, NY 10457, USA
3
Department of Pathology and Histology, Bronx Lebanon Hospital Center, Bronx, NY 10457, USA
2

Correspondence should be addressed to Varalaxmi Bhavani Nannaka; [email protected]

Received 13 November 2015; Revised 10 February 2016; Accepted 11 February 2016
Academic Editor: Chiara Lazzeri
Copyright 2016 Varalaxmi Bhavani Nannaka et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of
liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case
of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with
epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute
respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy,
worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive
supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses.

1. Introduction

2. Case Presentation

The coumarin derivative warfarin, which was licensed in the

United States in 1954 as the first human anticoagulant [1],
remains the most commonly used oral anticoagulant in North
America and the United Kingdom [2, 3]. Warfarin exerts
its anticoagulant effect by acting as a vitamin K antagonist
and inhibiting the biosynthesis of vitamin K-dependent
procoagulant factors II, VII, IX, and X [24].
On the basis of a study done in 5077 cases with 99,628
emergency hospitalizations, warfarin was implicated in 33.3%
of such Emergency Department (ED) visits [5].
Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death.
In the era of liver transplantation, it is important to reach
a definitive diagnosis and identify the cause because liver
transplantation is not indicated if malignant infiltration of the
liver is present and alternative therapies may be available.
Our case presents a finding of acute warfarin toxicity as
initial manifestation of metastatic liver disease in a patient
with stable dose of warfarin for 1.5 years with documented
stable International Normalized Ratio (INR) over the same
period of time.

A 64-year-old woman was brought to ED by a family

member for generalized weakness for 10 days associated with
epigastric pain and discomfort. Patient also reported having
a fall one week prior to her presentation to ED. She noticed
to have dark stools and red urine within few days of the fall.
Her medical history was significant for atrial fibrillation
on warfarin, COPD, active smoking, and hypertension. Additional history of laryngeal cancer was present, which was
treated with radiotherapy and chemotherapy four years ago.
As a followup after presenting with hoarseness of voice three
years ago, recurrent malignancy was ruled out with vocal
cord biopsy. No personal or family history of liver disease
was identified. There were no changes to her medications,
which included warfarin, amlodipine, metoprolol, aspirin,
and atorvastatin.
In ED, patient was tachycardic with a pulse of 160/min,
afebrile, and normotensive. The patient had no evidence
of acute distress or external injury. She had right subconjunctival hemorrhage, and mucous membranes were dry.
Heart examination was significant for tachycardia with no
murmurs, rubs, or gallops. Lungs had good bilateral air

Case Reports in Critical Care

Table 1: Patients laboratory values during hospitalization until death.

Parameter
PT (seconds)
INR
PTT (seconds)
Serum albumin (g/dL)
Alanine aminotransferase (unit/L)
Aspartate transaminase (unit/L)
Alkaline phosphatase (unit/L)
Total bilirubin (mg/dL)
Lactic acid level (mmoles/L)
LDH (unit/L)
Troponin (ng/mL)
CK (unit/L)
CK-MB (ng/mL)
CK-MB%
Haemoglobin (g/dL)
Bicarbonate (mEq/L)

Hour (hr) 0

hr 6

>169
Unrecordable
92
2.8
420
973
435
1
13.3

275.3
23.8
66.8

0.21
872
40.42
4.6
12
10

entry with no wheezing, crackles, or crepitations. Abdominal

examination revealed soft but mildly tender epigastrium with
normal bowel sounds, whereas rectal examination showed
stool mixed with dark blood. She was alert and oriented to
time/place/person but appeared slightly lethargic, no focal
neurological deficits on neuro examination were found.
Laboratory studies revealed anemia with hemoglobin
concentration of 7.2 mg/dL with baseline values around
12 mg/dL less than 3 months ago, leukocytosis with white
blood cell count of 15 k/uL, normal platelet count of 232 k/uL,
prothrombin time (PT) of 169 seconds, partial thromboplastin time (PTT) of 92 seconds, and unrecordable INR.
Chemistry showed prerenal azotemia with blood urea nitrogen levels of 54 mg/dL, creatinine of 1.3 mg/dL, bicarbonate
of 10 mEq/L, and normal serum electrolytes. Liver function
tests (LFTs) showed hypoalbuminemia with albumin of
2.8 g/dL, transaminitis with alanine aminotransferase (ALT)
of 420 U/L, aspartate transaminase (AST) of 973 unit/L, and
alkaline phosphatase (ALP) of 435 unit/L. Other significant
laboratory values were elevated lactic acid to 13.3 mmoles/L,
lactate dehydrogenase (LDH) level of 8003 unit/L, elevated
troponin of 0.206 ng/mL, creatine kinase (CK) of 872 unit/L,
and creatine kinase MB (CKMB) of 40 ng/mL with MB% of
<5. Please refer to Table 1 for laboratory values during the
hospitalization. Hepatitis A, B, and C serologies were negative
and serum acetaminophen level was <15 ng/dL.
Her INR two weeks prior to her presentation was 2.8 with
normal LFTs four weeks prior to admission. She had been on
stable dose of warfarin for the past 1.5 years. Please refer to
Table 2 for warfarin dosage and INR levels in the past one
year.
Initial chest X-ray (Figure 1) did not show any evidence
of an acute pulmonary edema or pneumonia. Computed
Tomography (CT) scan of the abdomen (Figure 2) showed

13

hr 15
57.7
5.1
44.3
2.4
1234
2475
393
1.4
6.6
8003
0.32
1059
44.01
4.2
7.2

hr 18

hr 22

hr 30

61.1
5.4
46.7
2.6
1201
2344
369
1.5
17

72
6.4
54.1
2.1
1312
2548
403
1.3
18

130.3
11.4
98.9
1.8
2179
3681
379
1.3
15

0.48
1220
53.75
4.2
9.7
5

0.88
1179
66.06
5.6
8.7
6

1.58
1283
72.28
5.6
7.8
3

Table 2: Warfarin dosing and INR prior to hospitalization.

Time frame
2 weeks ago
2 months ago
6 months ago
1 year ago
1.5 year ago

INR
2.8
2.4
2.2
2.9
3.7

Warfarin dose (mg)

4
4
4
4
5

Figure 1: Chest X-ray.

markedly enlarged abnormal heterogeneous liver suggestive

of an infiltrative process with no obvious free fluid or
evidence of significant bleeding. CT scan of the head was
negative for acute intracranial hemorrhage, infarction, or
masses.

Case Reports in Critical Care

Figure 4: Cut section of liver with diffuse showed involvement by

numerous tumor masses and nodules replacing most of the liver
parenchyma.
Figure 2: CT of the abdomen without contrast showed markedly
enlarged abnormal heterogeneous liver.

Figure 5: Liver diffusely involved by poorly differentiated squamous

cell carcinoma (low power magnification).
Figure 3: Liver weighed 4950 grams and that is enlarged with intact
smooth capsule with soft tan brown parenchyma which was nearly
completely replaced by multiple discrete tumor masses.

The patient had been given vitamin K and multiple

transfusions of Fresh Frozen Plasma (FFP) to reverse coagulopathy.
After admission to intensive care unit (ICU), there was
a rapidly progressive decline in the patients clinical status.
She developed acute respiratory failure requiring mechanical
ventilation, hypotension necessitating vasoactive agents, and
liver failure with worsening LFTs. In addition, she progressed
to worsening of coagulopathy, elevated cardiac markers, and
lactic acidosis. Her multiorgan failure did not improve with
aggressive resuscitative measures, culminating in cardiac
arrest and death.
Autopsy revealed that patients liver weighed 4950 grams
(Figures 3 and 4), and it was enlarged with intact smooth
capsule with soft tan brown parenchyma which was nearly
completely replaced by multiple discrete and near-confluent
sheets of white masses, some with central punctate hemorrhage, ranging in size from approximately 0.3 to 3 cm in
the greatest dimension. These tumor masses replaced nearly
90% of the total liver volume. Histopathology (Figures 5 and
6) showed poorly differentiated squamous cell carcinoma
secondary to metastasis. Review of prior pathology from
the time of LC surgery (Figures 7 and 8) showed moderately differentiated squamous cell carcinoma, which was
histopathologically consistent with the observed metastasis in
the liver.

Figure 6: Autopsy of the liver on high magnification showing areas

of poorly differentiated squamous cell carcinoma (high power
magnification).

3. Discussion
Warfarin therapy has a narrow risk-to-benefit profile. Its
pharmacokinetics is complex. The effective half-life of warfarin ranges from 20 to 60 hours, with a mean of about
40 hours. The maximum dose effect occurs up to 48 hr
after administration of a single dose and persists for the
next 5 days. The drug is completely absorbed after oral
administration, and peak concentrations occur within 4
hours. The warfarin metabolism occurs mainly in the liver. It
involves the cytochrome P450, and in particular, the CYP2C9
isoenzyme. Very little is excreted unchanged in the urine and
the bile [6].

Figure 7: Biopsy of the vocal cord showed invasive well differentiated squamous cell carcinoma showing cohesive nests and intracytoplasmic keratinization.

Figure 8: Left vocal cord mass showing deeply invasive, moderately

differentiated squamous cell carcinoma.

Supratherapeutic levels of anticoagulation with warfarin

result from the administration of inappropriately high doses,
altered protein binding, decreased vitamin K intake, reduced
synthesis, or increased clearance of vitamin K-dependent
clotting factors and the simultaneous use of other compounds
that interfere with warfarin metabolism. Elderly patients can
also exhibit an exaggerated response to warfarin, in part
because they tend to store less vitamin K than younger people
[7]. Therefore, it is not surprising that the most common
complication of warfarin use is adverse bleeding [8].
Before concluding that warfarin toxicity is the responsible
cause for coagulopathy, many other conditions need to
be considered. Differential diagnosis of prolonged PT and
PTT is numerous and can be divided into inherited and
acquired. Inherited causes include prothrombin, fibrinogen,
factor V, X, and combined factor deficiency. Acquired causes
are mostly due to impaired synthesis, loss, or increased
consumption or inhibition of coagulation factors. Impaired
synthesis stems from vitamin K deficiency or hepatic disease.
Massive bleeding may be responsible for the loss of coagulation factors, when the intravascular volume is replaced by
crystalloids, colloids, and red blood cells without replacing
coagulation factors. Disseminated Intravascular Coagulation
(DIC) pathophysiology is explained by increased consumption of coagulation factors. Inhibition of coagulation factors
is seen with presence of inhibitor antibodies to prothrombin,
fibrinogen, factor V, X, or direct thrombin inhibitor or
iatrogenic with use of vitamin K antagonists (warfarin) or

Case Reports in Critical Care

with use of heparin or combined warfarin and heparin use.
Warfarin is highly bound (approximately 97%) to plasma protein, mainly albumin. The high degree of protein binding is
one of several mechanisms whereby other drugs interact with
warfarin. Liver failure may be differentiated from vitamin K
deficiency by measuring factor V, which is not vitamin Kdependent [9]. The presence of inhibiting antibodies can be
confirmed by mixing studies. A diagnosis of DIC may be
made using a simple scoring system based on platelet count,
PT, D-dimer levels, and fibrinogen levels [10]. In the case
described above, there was no evidence to suggest intentional
overdose of warfarin, no use of compound that could have
potentially increased the warfarin levels, and no prior history
of inherited bleeding disorder. In our clinical practice, just
as reported in Budnitz et al. [5], majority of coagulation
abnormalities detected upon admission to our hospital are
related to warfarin.
Our patient presented with severe warfarin induced
coagulopathy. Results of autopsy revealed near complete
infiltration of the liver with laryngeal cancer metastasis. The
liver is the most common site for metastatic tumor deposits
with evidence of hepatic metastasis in 36% of all patients
who die from cancer [11]. Diffuse parenchymal metastasis
is a rare pattern of liver metastasis. Watson reviewed the
literature from the period 1868 to 1954 and reported 18 such
cases [12]; Rowbotham and colleagues recognized 18 (0.44%)
patients with fulminant hepatic failure (FHF) attributable to
cancerous hepatic infiltration among 4020 hospital admissions [11]. The incidence of distant metastases in squamous
cell carcinoma of head and neck approaches 20%25%. The
most common sites of metastases are lung (70%75%), liver
(17%38%), and bone (23%44%) [13]. Acute liver failure
(ALF) secondary to diffuse metastatic infiltration of the liver
is rare and has an extremely poor prognosis.
The mechanism of ALF in the setting of neoplastic
infiltration is multifactorial. Massive cytokine release has
been implicated as a cause of liver failure. Cytokine release
can cause liver failure by damaging bile ducts both directly
and via recruitment of effector cells, and by activation of
leucocytes and hepatic sinusoidal cells, thus impeding hepatic
sinusoidal microcirculation. Liver failure may also occur
due to ischemia produced by tumor emboli compromising
the portal venous circulation, or nonocclusive infarction
of liver due to shock from other causes such as sepsis or
cardiac dysfunction. The direct effect of tumor infiltration
with replacement of hepatocytes is probably more important
as a mechanism in nonhaematological malignancies. Indeed,
FHF rarely develops in metastatic carcinomatosis in the
absence of hypotension [14]. Our patient had normal LFTs
four weeks prior to the development of ALF and then
rapidly progressed. She has had infiltration of the liver over
a period of time with no evidence of clinical or laboratory
abnormalities, which then rapidly progressed to ALF as a
result of further insult from hypotension and cytokine release
likely secondary to sepsis or cardiac event.
Clinical presentation and laboratory findings of neoplastic infiltration of liver are vague and far from being
pathognomonic. Hyperbilirubinemia may be the result of
either hepatic parenchymal infiltration or extrahepatic biliary

Case Reports in Critical Care

obstruction. It is well known that the increase in serum
aminotransferases represents liver cell destruction and may
be the only laboratory test indicating liver dysfunction prior
to its clinical manifestation. But in our patient her LFTs were
normal four weeks prior to admission. However, elevated
serum LDH levels appear to correlate better with metastasisrelated hepatic failure, since it is believed that elevated levels
represent rapid tumor growth, by reflecting either the liver
cell destruction process or an elevated production of LDH
enzyme by neoplastic cells themselves. There are reports that
correlate LDH serum levels with hepatic metastases from
malignant melanoma, small cell lung cancer (SCLC) patients
[1518]. Extremely high serum LDH levels represent diffuse
replacement of the liver parenchyma and are associated with
a higher risk of development of FHF and a poor prognosis
[19, 20]. Several authors suggest that an increase in serum
LDH levels in cancer patients may prelude ALF [16, 21, 22].
These findings are well supported by the results of LFTs in
our patient, who had extremely elevated serum LDH levels.
Death is usually a direct consequence of the FHF, rather than
the underlying malignancy. Acute warfarin toxicity on the
stable dose of warfarin without any alternative cause was not a
presentation in any of the reported case series. Because of the
rapid progression of FHF, appropriate imaging procedures
are usually difficult to perform. However, CT scan of the
abdomen in our patient showed markedly enlarged liver with
heterogeneity suggesting infiltrative process (Figure 2).
There have been case reports of liver metastasis-induced
FHF from haematologic malignancies [2325], breast cancer
[26, 27], small cell carcinoma of lung [16, 2830], colon
cancer, urothelial cancer [31], and malignant melanoma [20,
22, 3234]. Coagulopathy, on stable dose of warfarin, was
not a presenting feature in any of these cases, but in our
indexed case the main presentation was severe coagulopathy
associated with ALF secondary to near complete infiltration
of liver with metastatic disease. Unfortunately, the prognosis
of patients with FHF resulting from malignant infiltration is
dismal. The majority of patients do not survive shortly after
the onset of liver failure [11, 26, 35]. According to a review
by Allison et al., concerning 21 reported cases of ALF due to
metastatic breast carcinoma, 18 cases died within 3 days to 7
months. Regrettably our patient died in less than 24 hours of
admission to ICU.

4. Conclusion
Delayed distant metastasis is rare in head and neck cancer.
ALF secondary to malignant infiltration of the liver due to
delayed distant metastasis from laryngeal cancer was never
reported in the literature to our best knowledge. Acute
warfarin toxicity on stable dose of warfarin without any alternative cause is rare. Neoplastic infiltration of liver should be
considered in the differential diagnosis when patients present
with severe coagulopathy with ALF, and laboratory evidence
of cellular destruction. Efforts must be made to determine the
etiology of the disease, as it influences prognosis and prompt
institution of specific therapies that might lead to recovery. Supportive care with close communication concerning
end-of-life issues should be considered the standard of care

5
in patients presenting with ALF secondary to solid tumor
malignancies since the prognosis is invariably poor.

Conflict of Interests
None of the authors has a financial relationship with a
commercial entity that has an interest in the subject of the
paper. No financial support was used for this case report.

References
[1] C. M. Kessler, Urgent reversal of warfarin with prothrombin
complex concentrate: where are the evidence-based data?
Journal of Thrombosis and Haemostasis, vol. 4, no. 5, pp. 963
966, 2006.
[2] J. P. Hanley, Warfarin reversal, Journal of Clinical Pathology,
vol. 57, no. 11, pp. 11321139, 2004.
[3] A. C. Butler and R. C. Tait, Management of oral anticoagulantinduced intracranial haemorrhage, Blood Reviews, vol. 12, no.
1, pp. 3544, 1998.
[4] G. Pindur and S. Morsdorf, The use of prothrombin complex
concentrates in the treatment of hemorrhages induced by oral
anticoagulation, Thrombosis Research, vol. 95, no. 4, pp. S57
S61, 1999.
[5] D. S. Budnitz, M. C. Lovegrove, N. Shehab, and C. L. Richards,
Emergency hospitalizations for adverse drug events in older
Americans, The New England Journal of Medicine, vol. 365, no.
21, pp. 20022012, 2011.
[6] J. Hirsh, J. E. Dalen, D. R. Anderson et al., Oral anticoagulants:
mechanism of action, clinical effectiveness, and optimal therapeutic range, Chest, vol. 119, supplement 1, pp. 8S21S, 2001.
[7] J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin, American Heart
Association/American College of Cardiology foundation guide
to warfarin therapy, Circulation, vol. 107, no. 12, pp. 16921711,
2003.
[8] V. Olmos and C. M. Lopez, Brodifacoum poisoning with
toxicokinetic data, Clinical Toxicology, vol. 45, no. 5, pp. 487
489, 2007.
[9] B. Bailey, D. K. Amre, and P. Gaudreault, Fulminant hepatic
failure secondary to acetaminophen poisoning: a systematic
review and meta-analysis of prognostic criteria determining the
need for liver transplantation, Critical Care Medicine, vol. 31,
no. 1, pp. 299305, 2003.
[10] K. Bakhtiari, J. C. M. Meijers, E. De Jonge, and M. Levi,
Prospective validation of the International Society of
Thrombosis and Haemostasis scoring system for disseminated
intravascular coagulation, Critical Care Medicine, vol. 32, no.
12, pp. 24162421, 2004.
[11] D. Rowbotham, J. Wendon, and R. Williams, Acute liver failure
secondary to hepatic infiltration: a single centre experience of 18
cases, Gut, vol. 42, no. 4, pp. 576580, 1998.
[12] A. J. Watson, Diffuse intra-sinusoidal metastatic carcinoma of
the liver, The Journal of Pathology and Bacteriology, vol. 69, no.
1-2, pp. 207217, 1955.
[13] J. G. Spector, D. G. Sessions, B. H. Haughey et al., Delayed
regional metastases, distant metastases, and second primary
malignancies in squamous cell carcinomas of the larynx and
hypopharynx, Laryngoscope, vol. 111, no. 6, pp. 10791087, 2001.
[14] P. Rajvanshi, K. V. Kowdley, W. K. Hirota, J. B. Meyers, and E.
B. Keeffe, Fulminant hepatic failure secondary to neoplastic

Case Reports in Critical Care

infiltration of the liver, Journal of Clinical Gastroenterology, vol.
39, no. 4, pp. 339343, 2005.

[15] H. B. Harrison, H. M. Middleton III, J. H. Crosby, and M. N.

Dasher Jr., Fulminant hepatic failure: an unusual presentation
of metastatic liver disease, Gastroenterology, vol. 80, no. 4, pp.
820825, 1981.
[16] B. M. McGuire, D. L. Cherwitz, K. M. Rabe, and S. B. Ho, Smallcell carcinoma of the lung manifesting as acute hepatic failure,
Mayo Clinic Proceedings, vol. 72, no. 2, pp. 133139, 1997.
[17] Y. Fujiwara, K. Takenaka, K. Kajiyama et al., The characteristics
of hepatocellular carcinoma with a high level of serum lactic
dehydrogenase: a case report, Hepato-Gastroenterology, vol. 44,
no. 15, pp. 820823, 1997.
[18] S. J. Finck, A. E. Giuliano, B. D. Mann, and D. L. Morton,
Results of ilioinguinal dissection for stage II melanoma,
Annals of Surgery, vol. 196, no. 2, pp. 180186, 1982.
[19] F. Tas, A. Aydiner, E. Topuz, H. Camlica, P. Saip, and Y. Eralp,
Factors influencing the distribution of metastases and survival
in extensive disease small cell lung cancer, Acta Oncologica, vol.
38, no. 8, pp. 10111015, 1999.
[20] H. S. Te, T. D. Schiano, M. Kahaleh et al., Fulminant hepatic
failure secondary to malignant melanoma: case report and
review of the literature, The American Journal of Gastroenterology, vol. 94, no. 1, pp. 262266, 1999.
[21] R. H. Schreve, O. T. Terpstra, L. Ausema, J. S. Lameris, A.
J. van Seijen, and J. Jeekel, Detection of liver metastases.
A prospective study comparing liver enzymes, scintigraphy,
ultrasonography and computed tomography, British Journal of
Surgery, vol. 71, no. 12, pp. 947949, 1984.
[22] P. M. G. Bouloux, R. J. Scott, J. E. Goligher, and C. Kindell,
Fulminant hepatic failure secondary to diffuse liver infiltration
by melanoma, Journal of the Royal Society of Medicine, vol. 79,
no. 5, pp. 302303, 1986.
[23] G. A. Morali, E. Rozenmann, J. Ashkenazi, G. Munter, and
D. Z. Braverman, Acute liver failure as the sole manifestation
of relapsing non-Hodgkins lymphoma, European Journal of
Gastroenterology and Hepatology, vol. 13, no. 10, pp. 12411243,
2001.
[24] K. Esfahani, P. Gold, S. Wakil, R. P. Michel, and S. Solymoss,
Acute liver failure because of chronic lymphocytic leukemia:
case report and review of the literature, Current Oncology, vol.
18, no. 1, pp. 3942, 2011.
[25] T. M. Shehab, M. S. Kaminski, and A. S. F. Lok, Acute liver
failure due to hepatic involvement by hematologic malignancy,
Digestive Diseases and Sciences, vol. 42, no. 7, pp. 14001405,
1997.
[26] H. E. Nazario, R. Lepe, and J. F. Trotter, Metastatic breast
cancer presenting as acute liver failure, Gastroenterology and
Hepatology, vol. 7, no. 1, pp. 6566, 2011.
[27] K. H. Allison, C. L. Fligner, and W. T. Parks, Radiographically
occult, diffuse intrasinusoidal hepatic metastases from primary
breast carcinomas: a clinicopathologic study of 3 autopsy cases,
Archives of Pathology and Laboratory Medicine, vol. 128, no. 12,
pp. 14181423, 2004.
[28] K. Sato, Y. Takeyama, T. Tanaka, Y. Fukui, H. Gonda, and R.
Suzuki, Fulminant hepatic failure and hepatomegaly caused
by diffuse liver metastases from small cell lung carcinoma: 2
autopsy cases, Respiratory Investigation, vol. 51, no. 2, pp. 98
102, 2013.

[29] H. Miyaaki, T. Ichikawa, N. Taura et al., Diffuse liver metastasis

of small cell lung cancer causing marked hepatomegaly and fulminant hepatic failure, Internal Medicine, vol. 49, no. 14, pp.
13831386, 2010.
[30] Y. T. Hwang, J. W. Shin, J. H. Lee et al., A case of fulminant
hepatic failure secondary to hepatic metastasis of small cell lung
carcinoma, The Korean Journal of Hepatology, vol. 13, no. 4, pp.
565570, 2007.
[31] M. Alcalde, M. Garcia-Diaz, J. Pecellin et al., Acute liver
failure due to diffuse intrasinusoidal metastases of urothelial
carcinoma, Acta Gastro-Enterologica Belgica, vol. 59, no. 2, pp.
163165, 1996.
[32] E. Bellolio, F. Schafer, R. Becker, and M. A. Villaseca, Fulminant hepatic failure secondary to diffuse melanoma infiltration
in a patient with a breast cancer history, Journal of Postgraduate
Medicine, vol. 59, no. 2, pp. 164166, 2013.
[33] G. G. Kaplan, S. Medlicott, B. Culleton, and K. B. Laupland,
Acute hepatic failure and multi-system organ failure secondary
to replacement of the liver with metastatic melanoma, BMC
Cancer, vol. 5, article 67, 2005.
[34] T. Fusasaki, R. Narita, M. Hiura et al., Acute hepatic failure
secondary to extensive hepatic replacement by metastatic amelanotic melanoma: an autopsy case report, Clinical Journal of
Gastroenterology, vol. 3, no. 6, pp. 327331, 2010.
[35] E. Athanasakis, E. Mouloudi, G. Prinianakis, M. Kostaki, M.
Tzardi, and D. Georgopoulos, Metastatic liver disease and
fulminant hepatic failure: presentation of a case and review
of the literature, European Journal of Gastroenterology and
Hepatology, vol. 15, no. 11, pp. 12351240, 2003.

MEDIATORS
of

INFLAMMATION

The Scientific
World Journal
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014

Gastroenterology
Research and Practice
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014

Journal of

Hindawi Publishing Corporation

http://www.hindawi.com

Diabetes Research
Volume 2014

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

International Journal of

Journal of

Endocrinology

Immunology Research
Hindawi Publishing Corporation
http://www.hindawi.com

Disease Markers

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Volume 2014

Submit your manuscripts at

http://www.hindawi.com
BioMed
Research International

PPAR Research
Hindawi Publishing Corporation
http://www.hindawi.com

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Volume 2014

Journal of

Obesity

Journal of

Ophthalmology
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014

Evidence-Based
Complementary and
Alternative Medicine

Stem Cells
International
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Journal of

Oncology
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Parkinsons
Disease

Computational and
Mathematical Methods
in Medicine
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014

AIDS

Behavioural
Neurology
Hindawi Publishing Corporation
http://www.hindawi.com

Research and Treatment

Volume 2014

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Hindawi Publishing Corporation

http://www.hindawi.com

Volume 2014

Oxidative Medicine and

Cellular Longevity
Hindawi Publishing Corporation
http://www.hindawi.com

Volume 2014