Portal Cavernoma Cholangiopathy: Indian Perspective

Abstract

Content available: Audio Recording Portal cavernoma cholangiopathy (PCC) refers to the imaging, endoscopic, and clinically noted changes in the intrahepatic extrahepatic and biliary ducts and gallbladder (GB) abnormalities in patients with extrahepatic portal vein (PV) obstruction (EHPVO) with portal cavernoma formation. The portal cavernoma is formed as a result of recanalization of a thrombosed PV, which results in the formation of multiple collateral channels. PCC is seen in 80% to 100% of patients with EHPVO and is largely asymptomatic. The diagnosis is based on biliary tract imaging based on magnetic resonance (MR) imaging (MRI), such as MR cholangiography (MRC) or endoscopic retrograde cholangiography (ERC). Commonly noted are intrahepatic biliary radicle dilatation (IHBRD), smooth indentations, or impressions on the common bile duct (CBD), duct angulations, ectasias, strictures, stones, filling defects, and GB and pericholedochal varices.1 There are several synonyms for PCC, and multiple differential diagnoses need to be considered as shown in Fig. 1. Changes like PCC can be identified in cirrhosis (0%-33%) and noncirrhotic portal hypertension (9%-40%), which are denoted as “portal biliopathy,” but these changes are limited to the intrahepatic biliary radicles (IHBRs).2 Dhiman et al.2 described portal hypertensive biliopathy as “abnormalities of the entire biliary tract including intra and extrahepatic bile ducts, cystic duct, and gallbladder in patients with portal hypertension.” The triad that needs to be fulfilled to make a diagnosis of PCC is presence of a portal cavernoma, cholangiographic changes on ERC or MRC, and absence of alternate etiologies of biliary duct changes.2 One of the key mechanisms of the development of PCC is the direct extrinsic compression by the cavernoma on the extrahepatic biliary tree causing upstream dilatation, areas of indentation, and narrowing or “pseudosclerosing sign.”3 In addition, dilation of the peribiliary venous vascular plexuses, that is, epicholedochal plexus of Saint and pericholedochal plexus of Petren, causes more collaterals to form around the biliary tree. In addition, intraductal collaterals have been described in PCC. On endoscopic ultrasound (EUS), perforating collaterals from the paracholedochal plexus are shown to reach the subepithelial layer of the bile duct. That is why stone removal or large sphincterotomies during ERC can trigger bleeding from these collaterals called hemobilia.4 The association of EHPVO, NCPF, and PCC or portal biliopathy has been well described in India.5 Because the PCC cannot exist without EHPVO, the epidemiology of these two diseases runs parallel, albeit separated by an interval of 6 to 14 years. India has a reduction in new incidence of EHPVO because of fewer cases of umbilical sepsis, omphalitis, and unsafe catheterization in infants. Even so, EHPVO accounts for 68% to 76% of all cases of childhood portal hypertension in India and may be responsible for 20% to 30% of all portal hypertensive bleeding.6 About 90% of persons with EHPVO have imaging evidence of PCC, but only 5% to 30% of such individuals become symptomatic with biliary obstruction. The dilated biliary tree acts as a focus for development of biliary stones, which results in symptoms such as pain, jaundice, and intermittent episodes of cholangitis, biliary colic, chronic cholestasis, and later formation of biliary strictures. The natural history of EHPVO implies that most persons present with variceal bleeding that occurs in the first two decades of life as children or adolescents, whereas the symptoms of PCC tend to occur much later in the third or fourth decade of life. The interval between the diagnoses is 6 to 14 years.5, 6 Clinical and biochemical evidence of chronic hepatic dysfunction, such as cholestasis and portal hypertension-related complications caused by EHPVO, develops over decades. PCC is a progressive condition, and strictures can form as a result of ischemia, chronic inflammation, and fibrosis and can be infectious in origin because of repeated episodes of cholangitis. Because only the vascular component is reversible, the correction of portal flow by portosystemic shunt (PSS) may lead to incomplete resolution of chronic fibrotic PCC strictures.4 Therefore, surgery should be timely, and successful endoscopic therapy for stones should not preclude interventions such as shunt surgery, because ischemic strictures and additional complications can manifest in another duct. Figure 2 shows the natural history of PCC and progressive development of cholangiographic changes in patients. In patients with EHPVO, timely management will also prevent further complications, such as growth restriction and impaired quality of life. The portal hypertension component of PCC can result in secondary complications, such as ascites, chronic hepatic encephalopathy, spontaneous lienorenal shunts, and recurrent variceal bleeding, sarcopenia, and metabolic bone disease. Secondary thromboses of splenic vein or mesenteric veins because of an acquired or inherited thrombophilia condition like JAK2V617F, MTHFR, or Factor V Leiden mutations or protein C and protein S deficiencies have been identified in India.7 Delaying interventions can also worsen the prognosis because of difficulty of finding a suitable vein in a portosplenic system with extensive thromboses. The late presentation of such patients in India makes intervention difficult because definitive surgery cannot be offered because of comorbid illness, and they are dependent on periodic ERC stenting to manage chronic biliary strictures.5, 7 Secondary biliary cirrhosis can develop in patients with chronic biliary obstruction. In such cases, liver transplantation (LT) is also difficult because a neoportal inflow will be difficult to reconstruct. Screening of patients with EHPVO requires a Duplex Doppler ultrasonography (USG) with color Doppler of the PV, which shows the cavernoma, extent of thrombosis, presence of varices, and portal hypertension–related changes. Biliary changes of PCC in the form of IHBRD, biliary stones, and cholecystitis are also seen. Contrast-enhanced computed tomography can be useful in early diagnosis and planning of surgery of patients, but MRI with cholangiopancreatography (MRCP) is now the diagnostic modality of choice in PCC. MRI can demonstrate the vascular anatomy of the liver using gradient-recalled-echo and spin-echo sequences, and MR angiography can diagnose the direction and flow dynamics of PV blood flow.8 The accepted MRC classification of PCC is given by Llop et al.9 Grade 0 has no abnormality, grade I has angulations or irregularities of the bile ducts, grade II has indentations or strictures without dilatation, and grade III has strictures with dilatation. Dilatation is defined as extrahepatic duct and/or intrahepatic ductal diameter of >7 and 4 mm, respectively.9 Figure 3 shows the classical findings described on MRC. Table 1 compares different imaging modalities for diagnosis and management of PCC. Endoscopic therapy is the primary therapy for PCC with ductal stones, acute cholangitis, or symptomatic or fibrotic strictures that did not resolve after surgery or in patients who are not candidates for PSS. ERC allows us to dilate strictures, remove stones, and manage cholangitis, and is a long-term management alternative for persons in whom surgery cannot be done. ERC is the procedure of choice in acute cholangitis. Knowledge of the collateral supply around the biliary ducts is useful to prevent hemobilia during sphincterotomy or removal of large stones. The modality of EUS is now complementary to ERC to detect the perforators and subepithelial biliary vessels and guide biliary drainage.10 The use of self-expanding fully covered metallic stents for the management of hemobilia is also widely used in India.11 Figure 4 shows the correspondence of strictures seen on MR and ERC and the likelihood of resolution of strictures after interventions. Table 2 shows the important series from India on endoscopic management of PCC.5, 6, 10, 12, 13 5, symptomatic intraductal ultrasonography done in all The most common surgical intervention in PCC is the creation of PSSs. They are the treatment of choice for symptomatic PCC, especially to avoid the additional problems associated with EHPVO, such as growth failure and hepatic encephalopathy and cytopenias. Only 15% to 20% of patients have residual disease and require a subsequent bilioenteric drainage to resolve residual strictures. The surgery of choice is the Meso Rex bypass so that the physiological flow of nutrient-rich blood from the gut can reach the liver. In India, the most performed surgery is the proximal splenorenal shunt. Table 3 summarizes the important studies on PSS from India.6, 10, 14-18 Failure of endoscopic treatment is managed by percutaneous transhepatic biliary drainage (PTBD) as a rescue therapy that gives time for definitive procedures in patients. In instances where patients present with cholangitis, altered mentation, or unstable hemodynamic states, PTBD can be offered at the bedside as an immediate mechanism for draining infected bile. Another intervention that has come into the fore is the use of transjugular intrahepatic portosystemic shunt (TIPS) in which an attenuated PV can be recanalized by first cannulating the splenic vein, entering the PV remnant, dilating the track, and placing the TIPS stent. The procedure has been used with good tolerance and long-term outcomes.19 A simplified algorithm for PCC management is presented in Fig. 5. PCC and EHPVO remain diseases associated with childhood portal hypertension in India, and the management protocols are still difficult to extrapolate because patients present at different clinical stages. The difficulty in understanding the vascular anatomy, lack of timely endoscopic and surgical interventions, poor knowledge of the disease, and late presentation are still barriers to managing this condition in India. With improved access to advanced endoscopic interventions and readily available expert radiology and surgical care, the outcomes are excellent in patients with PCC with symptomatic disease.

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