Biliary atresia (BA) is considered one of the forms of the “syndrome of vanishing bile ducts” (SVBD) and may be related to a number of other abnormalities and syndromes [1, 2]. Causes of SVBD are believed to be developmental, immunological, infective, vascular (ischemia) or chemical [1]. Ischemia is an important component of SVBD and in fact might be connected to the physiopathology of SVBD. Previous experiences with angiographic studies in patients with BA showed significant hepatic arterial abnormalities [3]. Since BA is one of the most common lesions related to SVBD, we reviewed the data collected from a series of patients examined by angiography in an attempt to identify the angiographic findings in patients with BA.

Material and Methods

Forty-six angiograms of patients with BA were reviewed. There were 25 males and 21 females, with a mean age of 22.5 months (range 1.5–141 months). Hepatic and mesenteric angiography were obtained as part of the liver transplantation work-up or as part of the treatment of clinical events. All patients had a histological diagnosis of BA, 7 patients had an additional diagnosis of cirrhosis, 2 liver cysts, 1 patient cystic fibrosis, and 1 Byler’s disease (congenital abnormality of bile salt metabolism).

Indications for angiography were:

  1. 1.

    Small portal vein (<4 mm @ Doppler US)

  2. 2.

    Portal vein not visualized on ultrasound

  3. 3.

    Suspected vascular anomalies

  4. 4.

    Evaluation of previous surgical shunt

  5. 5.

    GI bleeding (acute or recurrent)

  6. 6.

    Hypersplenism assessment

Visceral angiography was performed through the femoral artery under general anesthesia. Pediatric catheters with diameters ranging from 3- to 5-French were used. Heparin was not systematically used, although some patients were heparinized during the procedure. Pharmacologic enhancement of the portal vein was used in about 80% of the patients.

In all patients, clinical findings, such as associated syndromes, and treatments, such as liver transplants and other surgical procedures, were tabulated.

In one additional patient undergoing liver transplantation, the diseased liver was studied using Microfil ® Silicone Rubber Compound (Flow Tech, Inc. Carver, MA) injections in the arterial and portal system. Slices of the organ were dehydrated and treated by an alcohol-methyl salicylate clearing technique and for microscopic observation, according to the technique described previously [4, 5]. This patient did not have angiographic correlation.

Results

Associated Syndromes

No associated syndromes were observed in 37 patients. Polysplenic syndrome was observed in 4 patients, azygos vein continuation in 4 patients, pre-duodenal portal vein in 4 patients, and situs inversus, dextrocardia, partial occlusion of the inferior vena cava (IVC) and bowel malrotation in 1 patient each.

Previous Treatments

The Kasai procedure was performed in 42 of the 46 patients, at the mean age of 2.2 months (range 1–3.5 months). The Kasai procedure failed in 26 patients and surgical reintervention was performed in 3 patients. Failure of Kasai procedures was related to obstruction of the hepatic porto-enterostomy. Liver transplantation was performed in 19 patients (mean age 23.6 months). Severe complications were observed in 9 patients. Two patients underwent retransplantation. Ischemic catastrophe (defined as abrupt elevation of liver enzymes, jaundice and general physical debilitation) occurred in 4 patients (defined by clinical and histological diagnosis).

Angiographic Findings

The portal vein (mean size 4.1 mm, range 3–10 mm) was patent in 43 patients. Portal hepatopetal flow was observed in 20 patient and hepatofugal flow in 21 patients. The presence of gastroesophageal varices was observed in 41 patients (Fig. 1). Other signs of portal hypertension such as splenomegaly, ascites and other collaterals and shunts (retroperitoneal venous collaterals, enlarged paraumbelical vein, reversed enlarged IMV) were present in 39 patients. Spontaneous portosystemic shunts were identified in 19 patients, and in one patient no evaluation was possible.

Fig. 1.
figure 1

6-weeks-old female with biliary atresia, with no Kasai procedure. Angiogram performed as a work up during GI bleeding. A) and B. Early and later arterial phase of a selective hepatic arteriogram, showing enlarged hepatic artery and dense perivascular arterial tufts. Note diffuse hypervascular aspect of the whole liver. Later phase of the angiogram demonstrated intrahepatic hepatofugal portal branches flow (not shown). C. Magnified view of the right lobe of the liver. Note the blunt peripheral hepatic arteries (long arrows) and the vascular tufts surrounding the arteries (arrow heads). D. Left lobe of the liver showing the irregular and blunt peripheral arteries, with remarkable perivascular arterial tufts (arrow heads), suggesting collateral circulation around the peripheral arterial branches. E. Arterial portogram showing occlusion of the portal vein (large arrow) and signs of portal hypertension with gastroesophageal varices.

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The hepatic artery showed enlargement in all 46 patients. Arteriography showed the intrahepatic peripheral hepatic artery branches to have irregularities in contour (strictures, dilatations, abrupt angles and encasement) and images suggestive of peripheral occlusion (Fig. 1). Vascular tuft-like blush surrounding the irregular or occluded peripheral arterial segments was easily observed in 40 patients (Fig. 1) but was much less prominent in the remaining 6 patients. The intensity of the visualized vascular tuft presented a variable degree of density, tending to be more intense in younger patients and less in older patients (Fig. 2), with more marked cirrhotic changes including presence of nodules. The extrahepatic arteries supplying the common bile duct (the peribiliary plexus, the 3 o’clock and 9 o’clock arteries) as described by Northover et al. [8] were angiographically identified in only one of 4 patients not treated by a Kasai procedure (Fig. 3) and showed some degree of abnormality, including tortuosity and occlusion.

Fig. 2.
figure 2

12-years-old-female patient with biliary atresia. Angiogram performed as a pre liver transplant work up. A. Hepatic arteriogram showing straight hepatic arteries but with some bowing of the vessels due to cirrhotic nodules. There is enhancement of the peripheral vessels suggesting perivascular tufts. B. Magnified view of the right lobe showed irregular arterial branches with blunt ends (large arrows) and some degree of perivascular proliferation (arrow heads) suggesting perivascular tufts.

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Fig. 3.
figure 3

Abnormal 9 and 3 o’clock arteries in the projection of the common bile duct (black arrows) in a patient with biliary atresia, without previous Kasai procedure. The angiogram was performed in the gastroduodenal artery. Note the duodenal wall enhancement, and irregular and occluded 9 and 3 o’clock arteries (black arrows).

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The injection of Microfil ® into the arterial and portal circulation showed a marked vascular proliferation within the portal tract, apparently derived from arterial and portal connections, filling the entire portal space (Fig. 4). In areas where only the artery was filled, the vascular proliferation was totally derived from the arterial perfusion.

Fig. 4.
figure 4

Liver specimen from a 1-year-old female with biliary atresia injected with Microfil. There is marked vascular proliferation within the portal tract (VP), apparently derived from arterial and portal connections, filling the entire portal space. Note that the color of the smaller vessels within the portal space is mixed, some are orange and some are white. The portal vein is white (PV). The artery is orange (A). In other areas the vascular proliferation is predominantly orange (not shown). Note the cirrhotic nodules (CN) similar to a cirrhotic liver. No bile ducts were injected because of the biliary atresia.

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Discussion

This is a retrospective study of a group of 46 children with chronic changes secondary to biliary atresia and biliary cirrhosis. Biliary atresia is the most common cause of cirrhosis in children, leading to intrahepatic portal hypertension [6] and may be associated with a number of congenital abnormalities [2]. More recently, BA has been included under the more comprehensive name of Syndrome of Vanishing Bile Duct which includes a number of other diseases that also cause disappearing bile ducts [1]. It was originally thought that the ducts were not formed, however, the current concept is that at some period during the embryonic development or in the neonatal period, bile ducts are damaged by unknown agents or agent and progressively destroyed. This is called “infantile obstructive cholangiopathy”, also known as biliary atresia or hypoplasia [7]. A differentiation between extrahepatic and intrahepatic bile duct atresia is usually made, but it seems that in both there is increasing paucity of all the ducts as the process progresses [7]. A number of processes have been described as possible causes for the development of SVBD, including developmental, immunological, vascular, infective (viral), chemical, hypercoagulation and neonatal asphyxia [1]. Some of these processes are related to vasculitis and ischemia, with ischemia being a common denominator for some of the problems related to SVBD [1]. Other intrahepatic bile duct “ectasias” are probably related to ductal plate malformation in the fetal period [7].

A recent report of angiographic examination of several young patients diagnosed with BA described changes in the periphery of the hepatic arterial circulation of the liver, suggesting the possibility of vascular abnormalities that could be related to bile ducts ischemia or vasculitis [3], which led us to review cases of BA with available angiographic studies.

In a review of 46 cases of BA, we confirmed the presence of significant changes in the portal circulation and peripheral arterial circulation in the liver. Despite the identification of some abnormalities, such as portal occlusion, the main angiographic findings were reduced portal size, with reversal of the portal flow in about half the patients. The hepatic artery showed enlargement in all patients. In all 46 patients studied by arteriography, the intrahepatic peripheral hepatic artery branches presented with irregularities in contour (strictures, dilatation, abrupt angles and encasement) and images suggestive of peripheral arterial occlusion (Fig. 1). Vascular tuft-like-blush surrounding the peripheral arterial segments was easily observed in 40 patients (Fig. 1) but was much less prominent in the remaining 6 patients, possibly due to inadequate angiographic technique. In some of the patients with prominent vascular tufts the intrahepatic hepatofugal portal vein flow in peripheral branches seems to have been initiated in those tufts. The intensity of the visualized vascular tuft presented a variable degree of density, tending to be more intense in younger patients and less in older patients (Fig. 2) with more marked cirrhotic changes including presence of nodules. In older patients with more advanced liver cirrhosis the prominence of nodules may lead to a reduction in the arterial circulation, therefore reducing the prominence of the vascular tuft findings of younger patients.

The angiographic changes observed in this group of patients suggested that the vascular tufts represented collateral circulation, circumventing vascular occlusion in the peripheral arterial circulation. However, the microcirculation injection with Microfil ® showed a slightly different picture. There was marked vascular proliferation within the portal tract, apparently derived from both arterial and/or portal connections, filling the entire portal space (Fig. 4). In areas where only the artery was filled, the vascular proliferation was totally derived from the arterial perfusion. In other areas the vascular proliferation showed filling with the same color of the portal filling by Microfil. We could not prove the presence of occluded peripheral arterial branches on the Microfil ® injection. Nevertheless, the bidirectional filling of the vascular tufts by Microfil showed close correlation with the vascular tufts as the possible source of the reversed flow in the peripheral portal branches. It was impossible to differentiate the vascular peribiliary plexus from the vascular tuft, due to the exuberance of the proliferation (Figure 4).

It is generally accepted that biliary atresia starts by paucity of the extrahepatic bile ducts, and gradually progresses to the intrahepatic bile ducts. At this time the presentation of the peribiliary plexus in the extrahepatic segment of the bile ducts is unknown. In addition, it was rare to perform hepatic arteriograms in patients before the Kasai procedure and therefore unusual to identify the arteries supplying the extrahepatic common bile duct, as described by Northover et al. [8]. It is interesting, however, to speculate on the possible role of the occlusion of the peribiliary plexus in the common bile duct, including the presence of the abnormal 9 and 3 o’clock arteries as related to ischemia of the duct (Fig. 3), especially when compared with the anatomical findings in the literature [8, 9]. Nevertheless, in only 4 cases was it possible to observe these changes, and no consistent conclusion can be drawn from that observation.

In conclusion, the presence of angiographically demonstrable perivascular arterial tufts in the periphery of the hepatic arterial circulation is common in cases of BA, and may be a characteristic angiographic finding for the diagnosis of BA. Although the vascular findings described here may suggest that they could be related to the arterial/biliary process encountered in BA, our data do not necessarily support that theory. In addition, the angiograms suggested distorted and occluded peripheral arterial branches, and this finding was not corroborated by the liver specimen injected with Microfil—only the tufts within the portal spaces were demonstrated. Further studies of the liver microcirculation architecture in liver specimens from patients with BA undergoing transplantation are warranted.