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Cardio-renal syndrome followed by acute hepatitis C in a patient with acute

myeloid leukemia
Abstract
Cardio-renal syndrome involves altering cardiac and renal function. These patients
frequently develop resistance to diuretic therapy, ultrafiltration should emergency be
applied for saving them. Concomitant presence of an active hematologic malignancy
represents an important complicating factor. We present the case of an elderly
patient who during marrow aplasia occurred after the first course of induction
performed for acute myeloid leukemia, appeared on the background of
myelodysplastic syndrome, developed a cardio-renal syndrome, which required
repeated sessions of hemodialysis. Complete hematologic remission obtention and
efficiency of fluid depletion therapy allowed the second course of polychemotherapy,
after which the patient has developed an acute hepatitis C. After months of
complete hematologic remission that persists, the patient will start the standard
antivirusologic treatment.
Key words! acute myeloid leukemia, acute hepatitis, cardio-renal syndrome,
cholesterol, hemodialysis
Introduction
"atients with acute leukemia often have underlying conditions which may
decompensate or cause complications that may endanger life. The situation is even
worse if these decompensations or complications arise when acute leukemia is not in
complete remission. #n addition, acute leukemia predispose to the occurrence of
complications and iatrogenic disorders. #f the ma$ority of the complications creates
difficulties in acute leukemia therapy, the relationship between acute leukemia and
some infections - such as hepatitis C virus %&C'( infection - is questionable. There
were observed %sometime long( remissions of acute leukemia, in patients who had
been infected with &C'. #n addition to nonspecific stimulation of the immune system
of the patient, there may be another e)planation, too! leukemia cells use cholesterol
for their own proliferation and during &C' infection cholesterol synthesis decreases,
including the cholesterol available for them.
Case presentation
The patient, aged *, known with gastro-oesophageal reflu) disease and chronic
asthma, was admitted to the hematology service for bone pain, skin pallor and
petechiae on the legs+ in addition, he presented fatigue, epigastric pain, heartburn,
nausea, loss of appetite, occipital headache and vertigo - clinical manifestations that
occurred a month ago. &e had normal weight, he was afebrile, with no pathological
changes detected on physical e)amination of the respiratory and cardiovascular
sistems+ he was discrete sensitive to palpation in the epigastric and the liver was
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slightly increased in volume %,- cm on the medioclavicular line( and had slightly
higher consistency.
.iological samples showed pancytopenia, positive inflammation tests, slight
decrease in serum cholinesterase and albumin+ there were normal! creatinine,
transaminases, immunoelectrophoresis and &.s antigen and anti-&C' antibodies
were absent. /yelogram showed a trilinear dysplasia and a blasts percentage of
012, of which 12 were pero)ida3o-positive. 4lowcytometry from peripheral blood
isolated a blasts population of -52 with the following phenotype! C6-78, C6--8,
&9A-6:8, C67,-, C6*,-. C6*7-, C6-i.c.-, C61-, C6,5-, C6,7-, C6,;-, C605-,
C600-, C60-1-, TdT-, /"<i.c.8 %*2(. /olecular biology e)amination did not detect
mutations with poor prognosis. =ltrasonographically, the liver was diffusely
hyperechogenic, with no signs of portal hypertension+ the long a)is of the spleen
measure ,5 cm. #magistically, he had a widened peribronhovascular interstitium para-
and infrahilar and radiological signs of left co)arthrosis. 6ental consultation
discovered a periodontal abscess %7.( and echocardiography measured an e$ection
fraction of 1-2.
This acute myeloid leukemia that occurred on the background of a myelodysplastic
syndrome was treated with cytarabine 015 mg > day, ? days 8 idarubicin ,1 mg > day,
- days. @imultaneously, there were treated! the periodontal abscess %with
vancomycin, imipenem and metronida3ole(, and the gastroesophageal reflu) disease
and was performed the prophyla)is of asthma e)acerbations. #ntestinal
decontamination was performed during aplasia and he was transfused with red cell
and platelet concentrates. 6uring aplasia, clinical condition began to worsen
progressively, and low grade fever %-?. A C( appeared+ he had cough with purulent
sputum in small quantities, whee3ing, heartburn and decreased urine output to
,555ml>07h. Bn physical e)amination he presented decreased vesicular murmur and
diffuse whee3ing and crepitation who ascended to bilateral subclavian region+ blood
pressure reached ,*5>;5 mm&g and heart rate ;*>minut+ he developed leg edema,
which then e)panded and have progressed to the stage of anasarca, while creatinine
increased, but not more than -.-; mg > d9, and blood urea increased to ,7? mg > d9.
:adiologically, he had signs of acute pulmonary preedema %imprecisely demarcated
opacities with trend confluence, located mostly in perihilar region( and small bilateral
pleural fluid collections. Cchocardiography showed a left ventricular e$ection fraction
of 12, and the presence of significant pulmonary hypertension. @ince being treated
with furosemide diuresis decreased to 755 m9 > day, it was decided to perform
hemodialysis in intensive care monitoring service. #t was showed that urine culture
was positive with Cnterobacter, sensitive to meropenem, which he have been treated
with. After ,5 hemodialysis sessions and diuretic treatment edema decreased much
and diuresis reached ,55 ml > day+ respiratory and cardiac symptoms have
improved. /yelogram control made at the output of aplasia noted that acute
leukemia was in complete remission. &e was released and returned after a month,
with pallor and swelling that had also a hypoproteinemic component. Cdema
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disappeared, and serum creatinine decreased from 0.;- mg > d9 to ,.1? mg > d9 after
diuretic treatment, albumin, plasma and 0 more hemodialysis sessions,. &e received
a second course of polychemotherapy %cytarabine 055 mg > day, ? days 8 idarubicin
,5 mg > day, - days(. 6uring aplasia he had an episode of fever without
bacteriological documentation, submitted under antibiotherapy, and was transfused
with red cell and platelet concentrates.
After a month, he returned asthenic, with loss of appetite, and chemotherapy could
not be performed because of hepatic cytolysis %A@T -?0 #= > 9, A9T *7 #= > 9(. &.s
antigen and anti-&C' antibodies were negative again. After a month, he had! A@T
7- #= > 9, A9T ,;7 #= > 9, total bilirubin 0.0* mg > dl, and direct bilirubin ,.1* mg >
dl. 'irological determinations were performed this time! #g/ antibodies anti-hepatitis
A virus %negative(, #g/ antibodies anti-cytomegalovirus %absent(, hepatitis . virus
6DA %undetectable(, hepatitis C virus :DA - positive %,,-?,,7-5.55 #= > m9(. After
another month he had! normal A@T, A9T 15 #= > 9, creatinine ,.0* mg > d9,
cholesterol 05; mg > d9, and anti-hepatitis C virus antibodies were positive.
/yelogram established that acute leukemia is still in complete remission. 4ibroTest
had a value of 5.*0 %score 4- - portal and periportal fibrosis with numerous septa(
and ActiTest - 5.;? %score A- E severe necro-inflammatory activity E portal
inflammatory in$uries and hepatocyte necrosis(. After another two months, acute
leukemia was still in complete remission, and hepatic cytolysis - minimal. The patient
will begin treatment with pegylated interferon 8 ribavirin.
Discussion
The elderly patient had acute leukemia on the background of a myelodysplastic
syndrome %trilinear dysplasia(. &is performance status was good at first, but it
deteriorated during the first post-chemotherapy aplasia after the emergence of acute
bronchitis, on the background of chronic asthma. This inflammatory process
contributed at increasing the resistance in pulmonary arterial circulation and the
pulmonary hypertension with right heart decompensation. Although left ventricular
e$ection fraction was normal, increased retrograde venous pressure, including at the
renal veins, with a diminishing of transrenal perfusion pressure, contributed to
decreasing the glomerular filtration rate %,(, hydro-saline retention emergence,
refractory to diuretic therapy , which required hemodialysis. A cardio-renal syndrome
can also appear in patients with normal left ventricular e$ection fraction. This can be
e)plain by the involvment of neurohormonal factors, the disruption of intrarenal
hemodynamics, and the decreasing of transrenal perfusion pressure. %,(
#n our opinion, this cardio-renal syndrome fits best in type #, although we can not
e)clude type ## and '. #t is known that in addition to the five known types there are
also combined forms, combined forms in which our patient can be included because
he had chronic asthma and chronic pulmonary heart, initially compensated, that have
progressed to decompensation in the conte)t of acute respiratory infection. The daily
,*5 mg of furosemide have proven to be ineffective.
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We have not increased the dose because a high dose of diuretics could contribute to
neurohormonal activation and vasoconstriction which are involved in worsening renal
function %,, *(. C)tracorporeal ultrafiltration, realised during hemodialysis, is an
efficient way to remove e)cess body fluid in patients with chronic heart failure
refractory to medical treatment %-(. &emodialysis and ultrafiltration are also indicated
for the treatment of acute cardiorenal syndrome %7(, as those of our patient. The
patients with severe heart failure have the best chance of benefiting from this method
of fluid removal %1(. =nfortunately, the optimal rate to fluid removal was not
established. %-(
The access for acute dialysis increases the infection risk %0(, that adds those related
to transfusions made. @o our patients developed an acute hepatits C on the
background of pre-e)isting liver fibrosis favored by previous right heart
decompensation.
#nfection with hepatitis viruses is relatively common among patients with hematologic
malignancies. Thus, in :ussia, in a group of 01? patients, of whom 051 had acute
leukemia, only 0;.72 had no specific markers of infection with hepatitis viruses, and
,.72 of those with hepatitis C had markers of coinfection with hepatitis ., too %?(.
The presence of hepatitis C virus infection to the presented patient can cause
difficulties regarding further chemotherapy in case of acute leukemia relapse.
Therefore, we opted for therapy with pegylated interferon 8 ribavirin, although he has
not yet chronic hepatitis. Bn the other hand, the period of complete remission of
acute leukemia %over months( after only two courses of induction chemotherapy
%without high-dose cytarabine, due to impaired performance status after the first
treatment( is surprisingly long. The e)planation may be low cholesterol synthesis
during infection with hepatitis C %( and high cholesterol needs of the leukemia cells,
which they use for their own proliferation %;(.
We e)pect that during the antiviral therapy the pacient will be predisposed to the
occurrence of malignant hemopathy relapse by increasing cholesterol available for
leukemic cells. Therefore, the patient has indication for therapy with some statins,
which lower cholesterol synthesis and have other useful pleiotropic effects in both
acute leukemia and in antiviral therapy - reduce &C' replication, especially in
combination with pegylated interferon 8 ribavirin, and significantly increase the
likelihood of sustained complete virological response, as observed in clinical studies
with fluvastatin %,5(.
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