Author Affiliations: Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital: King’s Healthcare Partners, King’s College Hospital FT NHS Trust Institute of Liver Studies Denmark Hill, London SE5 9RS, UK (Papamichail M, Ali A, Quaglia A, Karani J and Heaton N)

Corresponding Author: Nigel Heaton, MB, BS, FRCS, Professor of Transplant Surgery King’s Healthcare Partners, King’s College Hospital FT NHS Trust Institute of Liver Studies Denmark Hill, London SE5 9RS, UK (Tel: +44-203-2993762; Fax: +44-203-2993575; Email: nigel.heaton@nhs.net)

 

© 2016, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(16)60067-X

Published online January 19, 2016.

 

 

Contributors: PM performed the research and wrote the manuscript. AA collected the data. QA performed histological analysis. KJ performed radiological review. HN wrote and corrected manuscript. All authors contributed to the design and interpretation of the study and to further drafts. HN is the guarantor.

Funding: None.

Ethical approval: Written consent obtained from the patient whom case report is presented.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

ABSTRACT: Intrahepatic portosystemic shunts (IPSS) are rare congenital anomalies arising from disordered portal vein embryogenesis. It has been described in both children and adults and may be asymptomatic or be associated with a variety of neurophysiological and pulmonary complications. When recognized, early intervention to occlude the shunt will reverse the associated complications. Literature review reports of surgical and radiological occlusion of the shunt, but due to its rarity, a standard therapeutic protocol has not been established. A case of a 38-year-old woman with abdominal pain and low grade encephalopathy, diagnosed with an IPSS and treated by right hepatectomy was reported.

 

(Hepatobiliary Pancreat Dis Int 2016;15:329-333)

 

KEY WORDS: intrahepatic portosystemic shunt; liver resection

 

Congenital intrahepatic portosystemic shunt (IPSS) is a rare abnormal communication between the intrahepatic portal and hepatic veins.^[1] Four types have been identified by Park et al based on the morphology of the shunts, which, by definition, have to be at least 1 mm in diameter.^[2] Those include a single vessel communication, which can be either between a main branch of the portal vein and inferior vena cava (IVC) (type 1), peripheral location in one segment (type 2), or through an aneurysm (type 3), and multiple small communications distributed diffusely in both lobes (type 4).^{[2, 3]}

 

IPSS may occur as a result of liver pathology, trauma, intervention, or rarely as a congenital anomaly as described in this report. The latter develops as a result of abnormal portal vein embryogenesis.^{[4, 5]} Patients diagnosed in early life with congenital IPSS commonly present with secondary complications including neurocognitive dysfunction, developmental delay, hypoxia and focal liver lesions (e.g. adenoma, focal nodular hyperplasia). Of note, it has been reported incidentally on imaging in adults presenting with low grade encephalopathy, pulmonary hypertension, hypoglycemia, chronic abdominal pain, and complex neurological disorders, which develop as a consequence of porto-systemic shunting and elevated ammonia levels.^[4-9]

 

CT, MRI and ultrasound can be used to confirm the diagnosis plus measurement of arterial ammonia levels in asymptomatic patients. Conservative management has been proposed previously for those who are able to tolerate their elevated ammonia levels with a stable shunt; however, intellectual and psychosocial function may be improved by early intervention. For patients who do not respond to medical treatment (dietary control, non-absorbable antibiotics), and develop complications, such as encephalopathy or who have an increasing shunt size, definitive treatment should be considered.^{[8, 10]} Reported interventions include image guided endovascular occlusion of the shunt by interventional radiologists, surgical ligation and excision either by formal liver resection or even transplantation. Various endovascular methods have been reported using a wide range of embolization materials.^{[8, 10]}

 

A patient with low grade intermittent encephalopathy and chronic abdominal pain, with a large congenital IPSS, was treated with right hepatectomy. The case of this patient and review of the literature are presented.

 

 

A 38-year-old woman presented to her local hospital with a history of right upper quadrant pain of short duration and a visible superficial vein along the midline axillary line of the abdominal wall. There was no history of abdominal trauma. Subsequent CT imaging revealed a large IPSS in segment 8 of the liver with a communication between the right anterior branch of the portal and the middle hepatic veins, measuring 24 mm in diameter (Fig. 1). The liver parenchyma was unremarkable.

 

There was no medical history other than iron deficiency anemia. Liver biochemistry and arterial ammonia level were within normal limits. No treatment was given and the patient was reviewed one year later for continuing abdominal pain and persistence of the dilated vein of the abdominal wall. It was suspected that an aberrant vessel related to her shunt was communicating with this superficial vein. She underwent laparoscopy, which failed to identify any abnormal venous communication with the abdominal wall. No dilated veins were seen within the abdominal cavity or on the parietal peritoneum. The possibility of embolization of the shunt was discounted by the radiologists due to the large size and the high risk of inadvertent migration of embolic agents (coils, glue etc.) to the pulmonary artery. Of note, the dilated vein on the abdominal wall disappeared after laparoscopy, but her symptoms were unchanged.

 

Over the next 2 years, the patient had further episodes of right upper quadrant pain, weight loss, alteration in bowel habit, and persistent low iron levels despite supplementation. She was extensively investigated for her abdominal pain in 3 other hospitals and no other cause was identified. Subsequently, she represented to our unit with intermittent low grade hepatic encephalopathy, and a raised arterial ammonia level (61 µmol/L). MRI of the brain was unremarkable. Electroencephalogram confirmed the metabolic nature of the encephalopathy and a decision was made to undertake right hepatectomy.

 

She underwent formal right hepatectomy and during surgery a persistent ductus venosus was also identified and ligated. The liver otherwise appeared normal and there was no portal hypertension. The portal vein pressure rose from 7 to 9 mmHg post ductus venosus ligation and right hepatectomy. The patient made an uncomplicated recovery and was discharged from hospital 6 days after operation.

 

Macroscopic examination of the resection specimen revealed a cluster of dilated parahilar vascular structures close to and seemingly in communication with a hepatic vein tributary. Microscopy of the sections taken from this area showed that the cluster of dilated vascular structure was made predominantly of ectatic portal vein branches, with a nodal point of sclera-hyaline tissue rich in elastic fibres connected to a vascular structure devoid of other component of a portal triad in keeping with a hepatic vein (Fig. 2). There was no significant histological abnormality in the background liver. On follow-up, the patient showed noticeable improvement in her neurological symptoms, and normalization of the ammonia level and ultrasonography of the remnant liver was normal, but she continues to complain of intermittent abdominal pain.

 

 

Congenital portosystemic venous shunts are divided into intra- and extrahepatic and although they may have similar patho-physiological mechanisms they represent two different entities.^[4] Park et al^[2] identified four types of IPSS in addition to a further variant of a patent ductus venosus between the left portal vein and the IVC (Abernethy syndrome). Extrahepatic shunts present a range of malformations in which the portal vein appears to be absent and the superior mesenteric and splenic veins drain to the IVC either separately or by a common trunk (type 1a/1b), and with the portal system preserved.^[11-13] Further classification of extrahepatic shunts based on anatomical, clinical and surgical criteria has been proposed by others.^[13-15] The overall incidence of congenital portosystemic shunts is close to 1:30 000 births and 1:50 000 for those that persist.^{[16, 17]} The prevalence of intrahepatic shunts is estimated to be 0.0235% as reported in a random population sample of asymptomatic adults who participated in an ultrasonography screening program.^[18]

 

There are two reviews identifying congenital portosystemic shunts up to 2012 and 2013 respectively.^[16,19] Bernard et al^[16] reviewed 265 cases in children (<16 years) and classified them according to the site of shunt origin (portal vein, afferent and efferent branches), the communicating systemic vein involved, and the pattern of communication. Of the 265 cases, 59 included patent ductus venosus (male/female ratio 2.6:1) with 46 other intrahepatic shunts. The rest of cases were referring to extrahepatic shunts, as origin of shunt was defined as the main portal vein or its afferent branches (e.g. mesenteric, splenic branches). Sokollik et al^[19] described 131 cases of IPSS in all age groups with a male predominance (2.45:1). Of these, 5 cases were diagnosed prenatally. A number of genetic syndromes and anatomical anomalies have been described in association with congenital intrahepatic shunts and the pathogenesis examined.^{[4, 11, 16, 17, 19-21]}

 

During the fifth week of embryogenesis, the two main vitelline veins, which emerge from the yolk sac and drain to the sinus venosus, cross communicate around the developing duodenum to start forming the vitelline venous system. In the primitive liver, cords surround the intrahepatic component of the vitelline plexus in order to develop the hepatic sinusoidal system. At 8 weeks, involution of the sinusoidal system forms the intrahepatic branches of the portal and hepatic veins.^[12,22] At the same period, the right umbilical vein regresses with the left umbilical vein taking over the entire blood supply and anastomoses with the ductus venosus. The latter obliterates within the first 2 weeks after birth, but delayed closure due to elevated venous pressure (e.g. congenital heart disease) may occur. In this situation, a patent ductus venosus acts as an intrahepatic shunt and may result in hypoplasia of the portal vein.^{[12, 22-24]} By the end of the third month of fetal life, the left vitelline vein completely disappears. The cranial part of the right vitelline vein and the segment that lies inferior to the liver give rise to the terminal branch of the IVC and portal and superior mesenteric veins respectively. Depending on the anatomical level at which the right vitelline vein fails to differentiate, it gives rise either a type 1 IPSS or variants of the type 2 extrahepatic shunt.^{[5, 12, 21, 22]}

 

Abernethy malformation is thought to be a result of excessive involution of the periduodenal vitelline plexus. Similarly, persistent communication of the vitelline venules within the newly formed hepatic sinusoids results in types 2-4 of the intrahepatic shunt as in our case where the right intrahepatic vitelline system persisted as a fistulation between the right portal vein and the middle hepatic veins.^{[5, 12, 21, 22]}

The most common congenital abnormalities associated with IPSS are cardiac defects (e.g. ASD, VSD) which alter the hemodynamic conditions in the liver and potentially play a role in the creation and persistence of the shunt (e.g. patent ductus venosus).^{[12, 21, 23, 24]} Abnormalities such as splenic artery aneurysm, coronary artery fistula, primitive hypoglossal artery and cutaneous heamangiomas have also been found in association with these shunts suggesting that there may be a general mis-signaling in embryogenesis of vascular structures.^[4,11] Renal agenesis, biliary atresia and genetic syndromes include Trisomia 21, Leopard, and Rendu-Osler-Weber have also been seen in association with IPSS.^{[13, 16, 17, 20, 21]}

 

IPSS may be an incidental finding on imaging or give a variety of complications, due to the portosystemic shunt.^{[8, 19]} Hepato-pulmonary syndrome, pulmonary hypertension encephalopathy, failure to thrive, neonatal cholestasis, developmental delay, neurophysiological dysfunction and liver tumor have all been reported in infants, children and adults with IPSS.^{[8, 25]} Regenerating liver nodules are thought to be due to alteration in local hemodynamics and compensatory increase in arterial flow. Of these, focal nodular hyperplasia (FNH), adenoma and nodular regenerative hyperplasia (NRH) are most commonly seen, but hemangioma and HCC have also been reported.^[21] Newborn children may be diagnosed with a IPSS on routine screening for galactosemia without enzyme deficiency.^{[16, 23, 26]} Intrauterine growth restriction due to a high flow shunt resulting in poor liver perfusion has also been reported.^[27]

 

In adults, the likelihood of symptoms increase with age over 50 years.^{[9, 18]} Low grade encephalopathy, neurological impairment, abdominal pain, and hypoglycemia are common problems due to high flow shunts and raised arterial ammonia levels. A shunt ratio >60% is a prognostic guide for symptom occurrence, but asymptomatic patients with low shunt function may develop symptoms when precipitating factors such as gastrointestinal bleeding or constipation affect ammonia levels.^[7,9,28] Unusual findings such as Parkinsonism and spastic paraparesis have also been described in association with high ammonia levels (192 µg/dL, range 30-86).^{[9, 29]}

 

Due to the rarity of this congenital abnormality, large series with a standard therapeutic approach are not available. Management is influenced by patient age, shunt size and severity of symptoms and complications. Shunts which are diagnosed prenatally or during infancy do not necessarily require definitive treatment, as many will spontaneously close by the age of 1-2 years with resolution of symptoms.^{[18, 27, 30]} For those that persist, early intervention prevents or reverses pulmonary complications and neuro-developmental delay.^{[5, 6, 25]}

 

Observation and monitoring of arterial ammonia levels seems to be sufficient in asymptomatic adult patients with low flow shunts.^{[7, 28]} Medical management of elevated ammonia levels with protein restriction and non-absorbable antibiotics, along with monitoring of the shunt size has been advocated in cases of mild symptomatology.^{[4, 8, 9]} Intervention is indicated for patients with an increased shunt ratio >60% and complications and those with worsening symptoms.^[31] The choice of surgical or radiological approach depends on local expertise, shunt anatomy and size, and the patient’s medical status. Surgical ligation of the portal vein or hepatectomy is replaced by less invasive interventional radiology, endovascular techniques.^[25] Rapid improvement in symptoms, correction of ammonia levels and regression of focal lesions after radiological occlusion of the shunt has been reported.^{[6, 8, 10]} Catheter insertion is most commonly attempted via a trans-hepatic or trans-caval route using either common femoral or internal jugular vein access and selection of embolic material is dependent on shunt size.^[22] Coils are preferred for small communications as opposed to large diameter shunts, which carry the risk of coil migration.^{[5, 32]} Recently, a multi-layered device has been introduced (Amplatzer vascular plug, AVP II; AGA Medical Plymouth, MN, USA) for the occlusion of larger shunts and can be used either alone or in combination with coils.^{[6, 8, 10]} In cases where significant post-embolization portal hypertension is anticipated (>30 mmHg), a temporary balloon occlusion of the shunt and the estimation of portal pressure rise are recommended.^{[19,24,25,33]} Alternatively, a two-stage approach with a reduction stent followed by surgical or radiological occlusion at a later phase allows the liver to adapt to hemodynamic changes.^{[19, 24, 25, 33]} Other adverse side effects include elevation of serum liver enzymes, shunt recurrence and procedure related complications (bleeding, thrombosis).^{[6, 22]}

 

Surgical resection or transplantation may be required for very large multifocal shunts, or previous failed radiological or laparoscopic intervention. In addition, if there is associated liver pathology such as regenerating focal lesions of uncertain nature, those that do not reverse after occlusion of the shunt or those that malignancy is suspected (e.g. hepatocellular carcinoma), resection/transplantation is indicated.^{[17, 25, 33-35]} In our case, the large size (24 mm) excluded a safe radiological approach and hepatectomy provided resolution with only a transient rise in portal pressure.

 

Congenital IPSS is a rare abnormality, which presents throughout life. Classifications, which delineate pathophysiology rather than purely anatomy, are needed to help guide management.^{[22, 36]}

 

 

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