Congenital extrahepatic portosystemic shunt (CEPS) is an anomaly in which the mesenteric venous drainage bypasses the liver and drains directly into the systemic circulation. This anomaly was first reported by Abernethy (1) and has been gradually recognized with the advances in imaging technology and neonatal screening for galactosemia. The symptoms related to CEPS range from incidental findings during radiologic studies to severe conditions, such as the development of hepatic neoplasms, hepatic encephalopathy (HE), pulmonary hypertension (PH), and hepatopulmonary syndrome (HPS). Furthermore, CEPS is often associated with other congenital anomalies, such as cardiac defects, biliary atresia (BA), polysplenia, and situs inversus. Morgan and Superina (2) proposed the classification of CEPS based on the hepatic portal perfusion. Complete portosystemic shunts, not perfusing the liver through the portal vein, are defined as type I, whereas partial shunts with a remaining degree of portal perfusion to the liver are defined as type II. Many previous studies have referred to their classification for understanding of the pathophysiologic implications and further management of their cases. Patients with partial shunts (type II) can be treated by surgical or radiologic intervention with shunt closure; however, liver transplantation (LT) might be considered as a curative operation for symptomatic cases defined as type I. Although some previous studies separately presented the patients undergoing LT for CEPS, the indications and the surgical procedures of LT varied among each patient (2–35).
This study compiled the transplantation cases with CEPS and discussed the role of LT for CEPS.
Preoperative Clinical Features
The age at diagnosis ranged from the neonatal period to 33 years (median, 3.7 years) (Table 1). Most of the cases were diagnosed in childhood, except for 2 adult cases, and 13 cases (38.2%) were diagnosed in patients younger than 1 year. The gender included 15 males and 19 females. The most common initial clues for the diagnosis of CEPS were the symptoms related to HPS or PH in nine cases (26.5%) and galactosemia at neonatal screening in nine cases (26.5%). Six cases (17.6%) were related to BA, including a case, diagnosed by the surgical findings of Kasai operation. HE including mild symptoms was seen in three cases (8.8%). Twenty-three cases (67.6%) presented one or more associated major anomalies. The common associated major anomalies included cardiac defects in 13 cases (38.2%), polysplenia in 9 cases (26.5%), BA in 6 cases (17.6%), situs inversus in 4 cases (11.8%), and intestinal malrotation in 3 cases (8.8%).
Anatomic Features of the Portosystemic Vasculature
The classification of CEPS by Morgan and Superina (2) categorized most of the cases as type I, except for five type II cases. At least eight cases radiologically or macroscopically presented a hypoplastic portal vein in the hilum of the liver. Six cases did not have the inferior vena cava (IVC), and the shunt vessels drained into an azygous system. The new classification proposed by Kobayashi et al. (36) categorizes the anomaly as type A (Fig. 1A) when the superior mesenteric vein (SMV) and the splenic vein (SV) drain directly into the IVC, type B (Fig. 1B) when the SMV and the SV drain into the renal vein, and type C (Fig. 1C) when the SMV and the SV drain into the iliac vein through a dilated inferior mesenteric vein. Therefore, 20 cases were categorized into type A; 6 cases, into type B; and 3 cases, into type C.
The age at LT ranged from 4 months to 45 years (median, 6.8 years) (Table 2). The median interval between the diagnosis and LT was 1.5 years. Some patients underwent LT shortly after the diagnosis because of the severity of their disease, such as progressive HE or an enlarging tumor, whereas the others underwent LT after a follow-up period. The indications of LT were HE in 13 cases (38.2%), which mostly consisted of persistent hyperammonemia (hyperNH3) in 9 cases; pulmonary complications in 11 cases (32.4%), including HPS in 8 cases and PH in 3 cases; tumor in 5 cases (14.7%), including hepatoblastoma in 2 cases and hepatocellular carcinoma in 1 case; liver dysfunction caused by BA in 4 cases (11.8%); and persistent rectal bleeding in 1 case (2.9%). There were 19 living donors and 15 deceased donors. Three patients underwent auxiliary partial orthotopic LT. Portal vein reconstruction required the direct anastomosis between the shunt vessel and the graft portal vein in 18 cases, most of which were categorized as type A portosystemic vasculatures, whereas 7 cases needed some modification for the anastomosis by using an interposition vein graft in 5 cases, a patch vein graft in 1 case, and a patent round ligament in 1 case. Cavoportal transposition was used because there was no feasible portomesenteric drainage vein on the recipient side in 1 case. Matsuura et al. (34) proposed a unique portal vein reconstruction for type C portosystemic vasculatures by using a dilated inferior mesenteric vein, whereas the other two cases used the interposition vein graft.
Thirty patients were alive with a median follow-up period of 18 months. Two patients died because of sepsis related to mesenteric congestion and respiratory failure related to HPS. One patient underwent retransplantation because of biliary stricture 1 month after the first transplantation and died because of chronic rejection afterward.
The management for CEPS is controversial. The therapeutic approach for CEPS included surgical or radiologic intervention of shunt closure and LT. The occlusion test with a balloon inflated at the site of the shunt should be performed before selecting therapeutic treatment, to evaluate the portal venous branches perfusing the liver and to measure portal vein pressure. Shunt closure should be considered if there are portal venous branches, classified into type II, and the portal vein pressure is lower than 35 mm Hg. Lautz et al. (37) showed an excellent outcome with surgical or radiologic shunt closure from their review of cases with type II CEPS previously reported in the English medical literature. They suggested that symptoms caused by type II CEPS were generally reversible after shunt closure. However, the intrahepatic portal veins may fail to expand after shunt closure with a risk of acute portal hypertension (33). Moreover, it should be kept in mind that there are some cases with multiple portosystemic shunt channels, which may not be able to be closed sufficiently at intervention. If the intrahepatic portal veins fail to expand after the closure of the main shunt channel, then other portosystemic shunt channels could consequently develop. LT might be the best therapeutic option if no portal venous branches can be visualized or the portal vein pressure is constantly high during the occlusion test. Franchi-Abella et al. (33) proposed a well-organized algorism for the investigation and management of CEPS, and they showed the successful outcome of those children with CEPS. They suggested that LT is no longer required because most of their patients could be managed by shunt closure. However, four of their cases showed cavernous transformation after shunt closure, thus possibly indicating nonphysiologic and anatomic portal venous branches. The sufficiency of cavernous transformation for the long-term resolution of CEPS is still questionable.
This review of 34 transplantation cases with CEPS revealed a couple of issues related to the role of LT. The first issue is the indication of LT for CEPS. The present study shows that HPS and PH were the most common indications. HPS is a poor prognostic factor in liver diseases, and the development of HPS should be considered an indication for LT. Egawa et al. (38) also noted that morbidity and mortality after LT became higher and, moreover, the length of period for resolution became longer depending on the severity of HPS. On the other hand, PH is also recognized as a poor prognostic factor in liver diseases. However, there is no consensus on whether PH, especially the severe type, should be indicated for LT because of the reversibility of PH after LT (39). Patients with both of these pulmonary complications should be considered for LT as soon as possible. Soejima et al. (20) noted that prophylactic LT was justified in the cases with CEPS before the development of fetal pulmonary complications. HE was also a common indication of LT for CEPS, and most of the patients, 9 (69.2 %) of 13 patients, were indicated for LT because of persistent hyperNH3 without the patient in a clinically comatose state. Patients with CEPS often have no apparent signs or symptoms of disease until adulthood, at which time HE is the leading presenting symptom (40). The patients with persistent hyperNH3 were diagnosed as having CEPS in the wake of galactosemia at neonatal screening and followed just by medical treatment of hyperNH3, which was slightly increased (serum NH3, ∼100–150 μg/dL). Although they seemed to develop appropriately for their age, neurocognitive testing revealed findings consistent with developmental delay. In addition, brain magnetic resonance imaging showed hyperintensity in bilateral lentiform nuclei on T1-weighted images. Eroglu et al. (41) reported two children with improved neurocognitive function after the treatment of CEPS. These patients also continued to develop intellectually and mentally after LT, whereas the abnormal findings of brain magnetic resonance imaging totally disappeared with normal NH3 level. Therefore, LT for CEPS should be considered, although the patients present persistent hyperNH3 without being in a clinically comatose state, which indicates a poor prognosis for intellectual and mental development.
The next issue is the technical points of the portal vein reconstruction. This review found that several cases needed some modification of the portal vein reconstruction. The type of the anatomy of the portosystemic shunt can be a crucial factor in the selection of the procedure of portal vein reconstruction. The direct drainage into the IVC, categorized into type A, tends to enable the direct anastomosis between the shunt vessel and the graft portal vein, whereas the other types require the interposition vein graft for portal vein reconstruction. It is sometimes difficult to obtain a vein graft for living-donor LT, and various creative procedures are performed. For example, Sanada et al. (26, 27) used a patent round ligament, and Matsuura et al. (34) used a dilated inferior mesenteric vein as the interposition vein grafts. It is important to understand the anatomy of the portosystemic shunt by using various imaging modalities and to conduct meticulous planning before LT, especially living-donor LT.
In conclusion, LT for CEPS showed an excellent outcome. The current study raises two suggestions for LT for CEPS. The development of HPS and PH could be indications for an early LT. Precise planning of portal vein reconstruction is required before LT.
MATERIALS AND METHODS
There were 30 cases of LT for CEPS reported in the English medical literature published or being in press by the end of 2011, including our own previously reported cases (19, 28, 29, 31, 32). Congenital absence of the portal vein and Abernethy malformation were also used to retrieve the cases as a suitable synonym for CEPS. Cases with secondary portal vein obstruction resulting from obvious causes (liver disease, and tumor) and cases where the patient’s profile was not described in detail were excluded. The cases from our department, including the previously reported cases, included three patients who underwent LT at the National Center for Child Health and Development (Tokyo, Japan) and five patients who underwent LT at Kyoto University Hospital (Kyoto, Japan).
This study reviewed these 34 cases and collected data including the patients’ age at diagnosis, gender, clinical symptoms and laboratory data, imaging data, associated anomalies (hepatic involvements and other), age at LT, indication for LT, donor (deceased or living), type of portal vein reconstruction, and survival outcomes.
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