Transient acute liver dysfunction in the neonate secondary to hemodynamic failure, or shock liver syndrome (SLS), is a well-recognized complication of reduced hepatic blood flow in low cardiac output states (1,2). The peculiar pattern of liver blood flow in neonates, characterized by a large intrahepatic shunt through the ductus venosus and low arterial blood supply, produces an asymmetric response of the right and left lobes to ischemia (3). This phenomenon has been described in an extreme form in deceased neonates and animal models in which necrosis of the right half of the liver develops in response to shock (4–8). We report a neonate with SLS secondary to acute cardiac failure. Imaging obtained at the acute phase of SLS showed, for the first time in vivo, signs compatible with right liver ischemic injury, supporting previous experimental data in lambs on liver vascularization during perinatal distress.
This neonate was born after 39 weeks gestation. The pregnancy was uneventful until a few days before delivery when the mother reported decreased fetal activity. Emergency cesarean section was performed because fetal distress, with fetal tachycardia (greater than 200 bpm) noted on ultrasonographic study. At birth, the neonate was apneic and hypotonic. APGAR score was 3 at 1 minute and 6 at 5 minutes. Pulse oxymetry showed oxygen saturations below 80%. The neonate was immediately intubated and ventilated under 25% FiO2. Heart rate and pulse oxymetry gradually improved and blood pressure was 58/37 mmHg. The abdomen was enlarged by both hepatomegaly and ascites. The spleen was not palpable. Chest radiography showed cardiomegaly and no parenchyma abnormality. Echocardiography showed normal heart structures but a dilated left ventricle with decreased shortening fraction (21%). There was no significant abnormality of heart rhythm or repolarization on electrocardiogram. Blood hemoglobin was 10 g/dL, the platelet count was 60,000/mm3, and blood glucose was 0.3 g/L. Results of serum liver tests are summarized in Table 1. Liver Doppler ultrasonography was asymmetric, showing hyperechogenicity of the right part of the liver up to the median hepatic vein and clear evidence for patency of the ductus venosus (Fig. 1). Magnetic resonance imaging scan of the abdomen performed on day 1 of admission to confirm ultrasonography findings (Fig. 2) showed an obvious asymmetry of the signal in the right and left lobes. The right lobe signal was increased compared to the left. Infectious, metabolic, toxic, and malignant causes of neonatal liver failure were excluded, as previously reported (9). A defect of mitochondrial fatty acid oxidation was excluded by measuring the acylcarnitine profile in plasma and organic acid profile in urine. There was no evidence for traumatic liver injury. Dopamine, dobutamine, volume expansion, transfusion of packed red blood cells, platelets and fresh frozen plasma, antibiotics, and intravenous 10% dextrose resulted in a rapid improvement of the hemodynamic condition (10). Urine output was absent for the first 12 hours and returned to normal with hemodynamic supportive therapy. Seizures of the lips and upper limbs with bilateral spikes on electroencephalogram required phenytoin and phenobarbital for 10 days. The child was extubated on day 8, and inotropic support therapy was discontinued on day 10. Cholestatic jaundice was noted from day 8 as liver function progressively returned to normal (Table 1). Subsequent Doppler ultrasonographies showed normalization of shortening fraction and progressive closure of the ductus venosus with disappearance of hyperechogenicity of the right liver. The child was discharged from the hospital at age 24 days. The persistent cholestatic jaundice was treated with ursodeoxycholic acid from 12 days to 5 months of age (11). At age 12 months all clinical, biochemical, and liver ultrasound examinations were normal.
The case highlights for the first time in vivo that during the perinatal period the right half of the liver is susceptible to ischemia during cardiocirculatory stress (3,4). This case also confirms the favorable natural history of SLS and shows that it may be complicated by transient neonatal cholestasis (11).
This case presents the typical clinical phases previously described as the natural history of SLS in children (1,2). Liver dysfunction associated with a sudden, transient elevation in serum transaminase levels occurred early in the course of circulatory failure and improved rapidly as the hemodynamic condition was corrected by supportive therapy (1,2,10). The acute phase was followed by persistent cholestatic jaundice that lasted several weeks (11–13). The origin of this patient's cardiac failure is unclear. Congenital and metabolic cardiopathies and liver diseases were excluded. The favorable outcome argues against a metabolic origin. Although several postnatal recordings of cardiac rhythm showed no abnormality, fetal tachycardia or transient and acute rhythm abnormality appear the most likely origins of the initial cardiac dysfunction.
During fetal life, the liver receives blood flow from different sources: the hepatic artery, the portal vein, and the umbilical vein. Hepatic arterial blood flow has been shown to be quite low, representing only about 2% of total liver blood flow (3). The portal branch of the left hepatic lobe directly arises from the umbilical vein, then the ductus venosus arises, and the umbilical vein arches to the right lobe, where it is joined by the portal vein. Using radioactive microspheres in fetal lambs, it has been shown that about 50% of umbilical venous blood flow passes through the ductus venosus, bypassing the hepatic parenchyma (7). This proportion increases to 65% during fetal hypoxemia (7,8), with the ductus venosus blood flow preferentially distributed to the ascending aorta and contributing to higher oxygenation of heart and brain (14). After birth, the ductus venosus gradually closes. In the event of perinatal hypoxemia and circulatory failure, the ductus venosus may remain patent, leading to a significant reduction in blood flow to the right liver, compared with the left liver (3,5,6,8). Both liver lobes have similar oxygen consumption. Since the left lobe is supplied mainly by umbilical venous blood with an oxygen saturation of 85%, and the right lobe mainly by portal venous blood with an oxygen saturation of about 70%, the right lobe is already functioning under low oxygen supply conditions (3,8). These considerations have raised the possibility that the right lobe might be more susceptible to hypoxia and ischemia in the fetus subjected to asphyxia or cardiovascular stress (3). This was considered a possible explanation for the greater tendency for necrosis of the right liver lobe found at autopsy in neonates dying from perinatal asphyxia (4). In the current report, liver imaging performed during the acute phase of liver failure showed asymmetric signals from the right and left parts of the liver. This finding is completely consistent with ischemia and necrosis of the right liver produced by intrahepatic shunting through the ductus venosus secondary to cardiocirculatory failure (15). Although we have no direct proof for such a mechanism, this hypothesis is reinforced by the parallel evolution between liver function test improvement and ductus venosus closure. In the clinical setting of neonatal liver failure (9) and in the presence of perinatal distress, we believe that such a condition associated with liver imaging showing asymmetric liver is strongly indicative of ischemic liver injury.
The authors thank Dr. Dalila Habes (Hépatologie Pédiatrique, Hôpital de Bicêtre, Paris, France) for taking care of the patient and Professor Olivier Bernard (Hépatologie Pe diatrique, Hôpital de Bicêtre, Paris, France) for critically reading the manuscript.
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