Among the total of symptomatic PB patients included in case series and case reports, 114 patients were treat endoscopically at first. Only in 34 patients (29.8%) a single endoscopic treatment resolved PB alterations and symptoms; among these, 13 patients had common bile duct (CBD) stones as PB manifestation resolved after endoscopic sphincterotomy (ES) + stone extraction (SE). In most cases, repeated treatment were necessary to have a complete resolution of biliary abnormalities, often combined with surgical intervention for portal hypertension: after the first treatment, 49 patients (43%) underwent multiple plastic stent exchange, 4 (3.5%) metallic stent placement, 35 (30.7%) surgical treatment with PSS or splenectomy (with or without esophageal devascularisation), 7 (6%) surgical biliary anastomosis, 2 (1.7%) transjugular intrahepatic porto-systemic shunt (TIPS) and 1 (0.9%) liver transplantation (LT). The duration of follow-up, when reported, range between 2 d and 18 years. In these cases the endoscopic approach can be considered safe, even if some complications have been reported. The most frequent is haemobilia, occurred in 24 procedures (in one case after intracholedocal biopsy). The risk of haemobilia during endoscopic treatment for PB is related to the presence of numerous pericholedocal compensatory collateral veins and congestion of biliary duct walls vessels. In particular, the transient pressure elevation in the distal portion of biliary varices during balloon sweeping can increase the risk of bleeding[21]. For these reasons, a decompressive shunting procedure performed before endoscopic treatment could reduce the risk of haemobilia[21,22].

Cholangitis were also frequent (reported after 53 procedures), but although they can be seen after ERCP in up to 15.4% of cases[23], they are often not directly related to the endoscopic treatment but rather to recurrence of sludge or stones inside the biliary stent and can be treated with stent exchange. Sepsis was observed as well in 3 cases. Mortality directly related to endoscopic treatment was 0%, but one patient died for secondary biliary cirrhosis and one for cholangitis, both developed despite multiple stent placements during the treatment period.

The choice of the endoscopic treatment of PB depends on the type of biliary alterations and includes ERCP with ES, SE (with previous mechanical lithotripsy if necessary) for patients with choledocholithiasis, stricture dilation ± biliary stent or nasobiliary drain placement.

The largest series of PB patients endoscopically treated is described by Saraswat et al[24], who published data about 130 ERCP performed for biliary strictures in 20 symptomatic patients. ES with SE was performed in 8 patients with choledochal stones and 9 patients were treated with plastic stents placement. Eleven patients (for a total of 101 procedures) were treated on the line of postoperative benign biliary strictures, with balloon dilation and plastic stent insertion, that were exchanged every 3-4 mo until LFTs normalizations; in 8/11 case a cholangiogram normalization was achieved as well. ERCP complications included haemobilia in 9/130 procedures and cholangitis in 40/130 (mainly already present at the moment of ERCP and due to delay in stent exchanged).

Khare et al[25] published a case series including 13 patients with EHPVO and PC complicated by symptomatic PB divided in 3 groups according to radiological biliary findings: group A included 5 patients with biliary strictures without choledocholithiasis; group B included 3 patients with choledocholithiasis alone; group C included 5 patients with both biliary strictures and choledocholithiasis. In group A, 4 patients were treated endoscopically with biliary stenting alone (n. 3) or with previous dilation (n. 1), followed by surgical PSS for portal hypertension. In 3/4 patients ERCP resolved biliary strictures, while 1 patient showed persistent stenosis at 12 mo and underwent multiple endoscopic procedures with dilation and stenting. In group B, 2/3 patients were treated with endoscopic SE that was successful in one patient; the other patient underwent stent placement and then surgical intervention for portal hypertension (splenectomy with esophagogastric devascularisation). During the follow-up, this patient needed multiple ERCP for choledochus clearance. In group C, four patients were first treated with endoscopic approach but SE failed in all of these patients; after surgical approaches (PSS or splenectomy with esophagogastric devascularisation), 2/4 patients were successfully managed with repeated ERCP with dilation and SE. No complications were observed after ERCP.

In 2009 the group from Birmingham published his experience with 13 patients with symptomatic portal biliopathy[17]: at the cholangiography (PB was diagnosed with MRC in 12 patients and with ERCP in 1), 12 patients showed biliary strictures, 10 bile duct stones/sludge, 11 gallbladder stones/sludge. In one patients symptoms (right hypocondrial pain and dark urine) resolved spontaneously, while 12 patients underwent therapeutic ERCP that was successful in 8: in one patients with associated Crohn’s disease plastic stent insertion did not resolved jaundice and the patient, that was not eligible for surgical portal decompression for PVT extension, was listened for liver and small bowel transplantation; one patient had an excellent response to ES and SE. Among 7 patients with jaundice resolution after plastic stent insertion, 2 patients underwent portal decompression for recurrent cholangitis despite multiple ERCP (one with PSS and one with TIPS), 1 needed repeated plastic stent changes and in 3 patients a metallic biliary stent was placed after several repeat plastic stent changes. Among 4 cases in which ERCP was unsuccessful, 2 had spontaneous resolution. The observed complications during a total of 49 ERCP were haemobilia (4%) and sepsis (6%, two cholangitis and one enterococcal sepsis), and no death directly related to biliary complications was observed during the follow-up.

In particular, the last two articles evidence how complex is to choice the appropriate treatment for PB, and the great variability on patients response to the same therapy, even between patients with the same type of biliary manifestation. This is also due to the difficulty to classify the etiology of PB (varicoid type or fibrotic type) based on cholangiographic findings.

Combined treatment with biliary procedures and percutaneous transhepatic portal vein recanalization (balloon dilation + self-expandable stent placement) have also been reported[26].

The role of UDCA administration associated with endoscopic procedures is still uncertain: even if some authors reported the absence of biliary symptoms recurrence after endoscopic treatment associated with UDCA therapy[1,3], equally good results with the only endoscopic management are reported.

All published PB case series and case reports about endoscopic treatment of PB are summarized in Tables 2 and 3[1,3,15,17,20,22-47], respectively.

Indication to surgery in PB patients is given by the need to decompress the portal system through PSS and to resolve the biliary obstruction. In cases in which PB is due to biliary compression by PC, the detension of collateral vessels obtained with the reduction of portal pressure by PSS can resolve in the same time biliary obstruction[30]. The most common PSS performed are proximal spleno-renal shunt or mesocaval shunt, but other types of surgical shunts include meso-gonadal vein shunt, meso-renal shunt, right-porto ovarian shunt, shunt between a portal varix and cava[41,48-51].

However, in patients without resolution of biliary abnormalities and symptoms after PSS, a second stage procedure can be required: biliary stenosis can be managed endoscopically, as explain above, or with surgical construction of a bilioenteric anastomosis. In patients without a suitable patent vein, splenectomy associated with esophagogastric devascularisation could reduce pressure in pericholedochal collateral veins and improve biliary symptoms[52]. A surgical approach with intrahepatic segment 3 bypass has been described to provide definitive treatment for biliary decompression and stone removal in a single time procedure in appropriately selected patients[47].

The largest PB series[52] retrospectively included 56 PB patients who underwent surgery from 1996 to 2010; 32/56 (57.1%) were asymptomatic for PB. To reduce portal hypertension, PSS was performed in 40 patients and splenectomy with devascularisation in 16. After first-line surgery, 7 patients required endoscopic treatment for cholangitis or CBD stones, that was successful in 2 patients, while 5 of them required multiple procedures; 2 patients previously treated with PSS at least needed biliary surgery for dominant CBD stricture that required frequent stent exchanges. In addition, the authors reported a significant reduction in serum biliary levels after first-line surgery (both shunt and no-shunt surgery) and alkaline phosphatases (shunt surgery), confirming that the resolution or improvement in portal hypertension can be effective in relieving biliary obstruction.

Vibert et al[30] published a case series including 19 symptomatic PB patients and propose an interesting 3 steps approach: (1) biliary drainage and antibiotic therapy if cholangitis is present; (2) surgical PSS; and (3) biliodigestive anastomosis with hepatico-jejunal anastomosis with Roux-en-Y. Patients were divided in two groups according to feasibility of PSS: 10 patients were included in the PSS group, 9 patients in the no PSS (NPSS) group. In the first group, one patient with severe sepsis from cholangitis underwent percutaneous transhepatic biliary drainage (PTBD) with extraction of intrahepatic stones. Then, a splenorenal shunt was performed in all 10 patients. Mortality was nil, and complications rate was 27%, including one chylus fistula and 2 early thrombosis, successfully treated with anticoagulant therapy or angiographic-guided pneumatic dilation. Initially, PSS was successful in biliary symptoms resolution in 70% of cases, but within 30 mo after PSS 5/10 patients required a bilioenteric anastomosis because of persistent jaundice or recurrent cholangitis. In the NPSS group, 3 patients were initially treated with endoscopic approach (1 ES and 2 plastic stent placement); PTBD was positioned in 6 patients (in 3 cases because of recurrence of biliary symptoms after endoscopic treatment); biliodigestive anastomosis was performed in 4 patients. Among these, one patient initially treated with endoscopic stent placement, 2 patients initially treated with PTBD and 4 patients treated with biliodigestive anastomosis needed repeated transhepatic cholangioscopies to remove intrahepatic stones and to improve biliary drainage; except for 2 patients lost in follow-up, at long-term follow-up one patient died for severe cholangitis and haemobilia while other patients were asymptomatic.

Overall, 173 patients underwent surgery intervention as first or second step for PB treatment: PSS was performed in 131 patients, PSS with splenectomy in 7, splenectomy with devascularisation in 18, devascularisation in 1 and 16 patients underwent biliary surgery (biliodigestive anastomosis, cholecystectomy, choledochotomy). The reported follow-up after surgical intervention ranged between 4 mo and 15 years. Considering patients underwent PSS alone as first treatment for PB, biliary symptoms relieve in 64.1% of cases, while in patients firstly treated with surgical biliary anastomosis, only in 30% of cases no other treatment was required.

A total of 6 death was reported: 1 patients died after 10 years from splenectomy for recurrence of gastrointestinal bleeding, 1 patient died for decompensated alcoholic cirrhosis, one for perforated duodenal ulcer and one for cholangitis and haemobilia after 8.6 years from biliodigestive anastomosis, 2 patients died for intraoperative bleeding during surgery on bile duct (choledocholithotomy and hepaticojejunostomy), suggesting a higher risk of bleeding from biliary tree due to the presence of numerous compensatory collateral veins and the congestion of biliary and splanchnic venous system. Table 4[2,3,19,25,30,51-58] summarized papers about surgical intervention in PB patients.

In addition to surgical PSS, a TIPS placement can be a valid alternative to improve portal hypertension. Since 1996, Görgül et al[59] observed the resolution of “pseudocholangiocarcinoma” sign after TIPS in 3 patients. In a case report, a 45-years-old woman affected by cholestatic jaundice due to compression on CBD by extrahepatic portal and splenic vein thrombosis with collateral, was treated with TIPS: in order to decompress the biliary tree before the procedure, a biliary stent was placed and the day after TIPS was successfully performed. The biliary stent was removed after 1 wk and, at 14 mo follow-up, the patient was asymptomatic and MR/MRCP showed a significant improvement of biliary alterations and of cavernoma size[60]. Another case report described resolution of cholangiographic CBD abnormalities and normalization of LFTs after TIPS performed in a patient with PB and portal hypertension secondary to PVT[61]. In the case series published by Cellich et al[23] including 13 PB patients, one of these was initially treated with TIPS that was unsuccessful; patient underwent PSS and multiple endoscopic treatment and, at least, bilioenteric anastomosis. Oo et al[17] reported 2 patients successfully treated with TIPS: one after repeated ERCP with plastic stent exchanges obtaining resolution of biliary symptoms and reduction in portal pressure; the second was successfully treated with temporary PTBD placement followed by TIPS. Even if the use of TIPS in PB patients is anecdotal, this technique seems effective and safe in treatment of portal hypertension and PB secondary to PC. However, due to the vascular alterations secondary to PC, TIPS is not always technically feasible.

There are few data about LT for PB patients. In literature only 4 cases are reported (1 regarding a paediatric patient), 2 living donor LT and 2 deceased donor LT[62-65]. Indication for LT was secondary biliary cirrhosis, recurrent cholangitis (even with suspicion of cholangiocarcinoma) despite multiple endoscopic treatments, often associated with gastrointestinal bleeding[62-64]; Zhang et al[65] reported 3 successful living donor LT in 3 paediatric patients with PC, one of these with jaundice and evidence of dilated biliary duct due to PC compression, consistent with PB; however, in all 3 cases the major indication for LT was deteriorating liver function ad recurrent gastrointestinal bleeding. In all the 4 cases of LT for PB the outcome was favourable after a follow up of 12-26 mo.