Elastographical and Ultrasonic Properties of the Liver and Hepatic Circulation during severe preeclampsia/HELLP Syndrome

Severe preeclampsia/HELLP-syndrome is a severe complication of pregnancy, which
occurs during the second and third trimester. The syndrome has significant
morbidity and mortality of mother and child. It is characterized by arterial
hypertension, hemolysis and elevated liver enzymes and can be complicated by
hematoma and rupture of the liver in rare cases.
During a normal pregnancy, physiological and functional changes of the liver
occur, but
little is known about hepatic blood flow. In 1947 Munnell and Taylor1 published
the first study on hepatic vessels during pregnancy in which hepatic vein
catheterization was performed in pregnant women. In 15 patients with normal
pregnancies the hepatic blood flow was not different from nonpregnant women. In
a much later period, 2002, a second study with Doppler ultrasound of the
hepatic vessels was performed. In 67 healthy pregnant women and 22 nonpregnant
women the total liver blood flow was increased during the third trimester, in
which the major determinant seemed to be the portal venous return2.
In the study of Roobottom et al.3 and Pekindel et al.4 loss of pulsatility in
venous Doppler waveforms was demonstrated, also implicating changes in the
hepatic perfusion.
A few conducted studies specifically investigating alterations in the hepatic
artery and portal vein in severe preeclampsia/HELLP-syndrome demonstrated
varying and contradictive results. Oosterhof et al.5 demonstrated excessive and
abnormal constriction of the hepatic artery, whereas Kurzel et al.6 could not
demonstrate a significant difference. The latter study only was conducted in
the postpartum period.
Kawabata et al.7 studied the predictive value of dual hepatic flow in patients
with severe preeclapmsia/HELLP syndrome. In patients with severe
preeclampsia/HELLP the dual hepatic blood supply was lowered significantly.
In women with severe preeclampsia/HELLP syndrome in which liver pathology has
been examined focal necrosis in the liver parenchyma, edema and also focal
thrombosis occurs. The etiology is not known.
In order to test our hypothesis that the elastographical properties change
during severe preeclampsia/HELLP syndrome due to thrombosis, inflammation and
edema we performed a pilot study in 17 patients with severe preeclampsia and
the HELLP syndrome in which there appeared to be a significant difference in
elastographical properties, which resolve very quickly after delivery. To this
date there are no investigations on elastographical properties in pregnant
women.
In order to test our second hypothesis that alterations in blood flow cause
damage to the liver parenchyma through ischemia and constriction of the hepatic
artery we want to investigate the hepatic perfusion by abdominal ultrasound
combined with Doppler measurements.
During this examination the following investigations will be performed:
- aspect liver parenchyma (steatosis, signs of bleedings/edema)
- aspect of the biliary tract (dilation, stones and sludge)
- hepatic veins (diameter, flow pattern and flow velocity)
- portal vein (diameter, flow pattern and flow velocity)
- hepatic artery (flow pattern, flow velocity, resistance index)
- the presence or absence of ascites
- length and width of the spleen
- Inferior vena cava (diameter, flowpattern, flow velocity)

Also, when an arterial or deep venous line is present blood will be drawn
during the investigation. This to determine the severity of the syndrome during
the examination which might change.
Laboratory testing includes:
- Bloodcount
- Liverenzymes with bilirubin
- Albumine, uric acid and haptoglobin
- Renal function tests (kreatinin and urea)
- Glucose
- Prothtombine time

The aim of this study is to test the hypothesis that severe pre-eclampsia/HELLP
syndrome in comparison to patients without severe preeclampsia/HELLP are
accompanied by changes in hepatic circulation and themselves cause changes in
elastographic properties of hepatic tissue due to edema, thrombosis and
inflammation.

All patients admitted to the high care and obstetrical ward in the Sophia
Children*s Hospital and the ICU in the Erasmus Medical Centre in Rotterdam with
severe pre-eclampsia and the HELLP-syndrome are asked to participate.
After written informed consent abdominal Doppler ultrasound in combination with
elastography (by FibroScan) will be performed by two physicians. Before this
investigation the patients will be asked to answer questions concerning
previous liver diseases, other diseases, use of medication, smoking and/or
alcohol and family history (see CRF-form).
Abdominal ultrasound investigation takes approximately 20 minutes, whereas
transient elastography takes approximately 10 minutes.
Total examination time including abdominal ultrasound, measuring elasticity and
answering of the questions takes 45 minutes.
When an arterial or deep venous line is present blood will be drawn, otherwise
blood is taken during regular testing moments while admitted.
During admission additional elastographical measurements with the FibroScan
will be taken on day 3 and 5, and when necessary at day 7. This will take
approximately 10 minutes. There are no requirements necessary before taking the
measurements, also there will be no additional testing via blood or questions.
Next to these patients, women with a healthy pregnancy visiting the outpatient
clinic with a matching gestational age will be asked to participate as a
healthy control. In addition, a CRF-form will be requested to answer and
abdominal Doppler ultrasound and elastography will be performed.

All patients admitted to the high care and obstetrical ward in the Sophia
Children*s Hospital and the ICU in the Erasmus Medical Centre in Rotterdam with
severe pre-eclampsia and the HELLP-syndrome are asked to participate.
After written informed consent abdominal Doppler ultrasound in combination with
elastography (by FibroScan) will be performed by two physicians. Before this
investigation the patients will be asked to answer questions concerning
previous liver diseases, other diseases, use of medication, smoking and/or
alcohol and family history (see CRF-form).
Abdominal ultrasound investigation takes approximately 20 minutes, whereas
transient elastography takes approximately 10 minutes.
Total examination time including abdominal ultrasound, measuring elasticity and
answering of the questions takes 45 minutes.
When an arterial or deep venous line is present blood will be drawn, otherwise
blood is taken during regular testing moments while admitted.
During admission additional elastographical measurements with the FibroScan
will be taken on day 3 and 5, and when necessary at day 7. This will take
approximately 10 minutes. There are no requirements necessary before taking the
measurements, also there will be no additional testing via blood or questions.
Next to these patients, women with a healthy pregnancy visiting the outpatient
clinic with a matching gestational age will be asked to participate as a
healthy control. In addition, a CRF-form will be requested to answer and
abdominal Doppler ultrasound and elastography will be performed.