Wong Hoi She, WingChiu Dai, JamesYY Fung, TanTo Cheung, AlbertCY Chan ,Chung Mau Lo

Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China

TotheEditor:

Recurrent pyogenic cholangitis (RPC), also known as Hong Kong disease [1], is an unique disease entity with a decreasing incidence.It is characterized by the formation of intrahepatic biliary pigmented stones, which results in stricturing of the biliary tree followed by obstruction and repeated attacks of cholangitis.Inadequate treatment eventually leads to liver abscess, parenchymal atrophy, complications of cirrhosis including end-stage liver disease,and risk of cholangiocarcinoma.Treatment for RPC in the initial phase of presentation include sepsis control with antibiotics and drainage of the biliary system, either endoscopically or radiologically.Definitive management requires surgery such as partial hepatectomy and/or hepaticocutaneous jejunostomy.The formation of the cutaneous limb would allowsubsequent clearance of intrahepatic ductal stones by endoscopic means.Whether to perform hepatectomy or not would depend on the severity of cirrhosis and the presence of stones, liver abscess, and liver atrophy.Liver transplantation (LT) has been reported as a potential treatment option for patients with diffuse bilateral RPC [2]or secondary biliary cirrhosis.However, the evidence is scarce.We shall report a series of our patients who received LT as the definitive treatment for RPC.

We included patients who received LT for RPC from January 2006 to December 2019.Patients’ characteristics, indications, operative details and postoperative outcomes were analyzed.The patients were prioritized for deceased donor liver transplantation(DDLT) according to their model for end-stage liver disease (MELD)scores while they were also encouraged to consider living donor liver transplantation (LDLT) since the organ donation rate was low.The indications for LT were: (i) decompensated liver cirrhosis, (ii)failure to remove all stones in the intrahepatic ducts ( Fig.1 ), and(iii) failed conservative management with repeated cholangitis and emergence of resistant microbes.

Fig.1.Computed tomography scan showing extensive intrahepatic duct stones in a patient with recurrent pyogenic cholangitis (thin arrow: intrahepatic duct stones;thick arrow: dilated intrahepatic ducts).

For LDLT, the operative procedure has been described elsewhere [3].For DDLT, the procurement and implantation procedures were performed in a standardized fashion.Most of the patients received hepaticocutaneous jejunostomy before and therefore hepaticojejunostomy was the choice of biliary reconstruction for all patients included here.Basiliximab (20 mg) was given within 6 h of graft reperfusion and on postoperative day 4.Hydrocortisone was injected intraoperatively (1 g) and on postoperative day 1 (500 mg).Tacrolimus was given postoperatively and titrated to achieve a trough level of 5–10 ng/mL with renal dosage adjustment.Mycophenolate mofetil was also given and gradually tapered.Maintenance steroid was not given routinely.All patients also took 200 mg of fluconazole, 480 mg of cotrimoxazole daily and 400 mg of acyclovir thrice a day orally for the initial 3 months postoperatively.For patients with renal impairment or glucose-6-phosphate dehydrogenase deficiency, precluding oral administration of cotrimoxazole, pentamidine inhalation (300 mg) was given monthly for 3 months instead.

Continuous variables were described as median with range.Hospital mortality was defined as postoperative mortality during hospital stay.Overall survival was calculated from the day of operation to the last follow-up visit or death.

The study reviewed 9 patients.One of the patients failed to receive intended operation and died.This patient was, therefore, excluded from analysis.The remaining 8 patients’ demographics and indications were shown in the Table 1.Most of them had previous cholecystectomy and bile duct exploration, and some had received hepatectomy for intrahepatic ductal stones or liver atrophy.They had recurrent biliary sepsis requiring external percutaneous transhepatic biliary drainage, and bile culture yielded multiple organisms including multi-drug-resistant organisms.The 8 patients’median age was 51.5 years.The median MELD score was 24.The median waiting time was 67 days.Half of the patients received DDLT and the other half received LDLT.The median operative time was 699 min.The median hospital stay was 30 days.All patients recovered well.Pathology showed RPC with or without cirrhosis.No recurrent disease was found in these patients after LT.

Table 1Clinical details of patients having liver transplant for recurrent pyogenic cholangitis.

Regarding the excluded patient, he received a cholecystectomy and his peptic ulcer disease necessitated distal gastrectomy with Billroth II reconstruction.The patient suffered from repeated episodes of bleeding esophageal varices and hepatic encephalopathy.With a MELD score of 18, the patient was listed for DDLT.Total hepatectomy was planned.Despite prolonged fine dissection and adhesiolysis, the liver hilum could not be safely approached due to the presence of dense adhesions from previous operations and repeated episodes of cholangitis.Attempted dissection lasted for more than 6 h.In view of the prolonged cold ischemic time of the deceased donor graft, the operation was aborted and the graft was given to another patient.The patient deteriorated and developed liver failure.The patient passed away four days after the laparotomy.

In this case series, indications for LT were extended to include RPC.In particular, these patients had developed complications of cirrhosis and resistant organisms with the risk of postoperative sepsis in an immunocompromised state.They had recurrent biliary stones with repeating cholangitis, and the stones were too numerous to clear.Further endoscopic or surgical treatments might not be appropriate as they had undergone previous drainage or hepatectomy.Operating on such patients would be difficult and risky due to the distorted anatomy and the presence of cirrhosis.Repeating cholangitis would result in prolonged use of antibiotics, which affects patient’s quality of life.A recent history (<6 months) ofantimicrobial usage significantly increases the risk of emergence of resistant organisms [4].There have been reports on multiple drug resistance isolated from intra-abdominal infections and, in particular, biliary infections [5].The presence of resistant organism results in high morbidity and mortality due to inadequate coverage by antibiotics and drainage of the biliary system [6].The extended use of antimicrobial therapy also increases medical costs and prolongs hospitalization.In addition, cirrhotic patients have an increased risk of acute-on-chronic liver failure.They are more susceptible to bacterial infection [7], with a higher mortality.Unless there is overt manifestation of active systemic infection, LT accompanied by adequate antibiotic or antifungal therapy may be acceptable for patients with existing bacterial or fungal infection [8].In view of the risk of liver failure with increasing use of antibiotics and the risk of development of resistant organisms, LT is the definitive treatment to clear the stones, strictures, and infections.LT relieves symptoms,lowers the re-admission rate, and improves quality of life.Furthermore, LDLT allows earlier transplant, thereby reducing the chance of severe biliary sepsis.

RPC is a risk factor for cholangiocarcinoma.Early detection of cholangiocarcinoma makes resection or LT feasible.Selection criteria and neoadjuvant chemoradiotherapy have been developed as part of the treatment protocol, and the 5-year survival can be as high as 65% in perihilar cholangiocarcinoma [9].Currently, we do not offer LT for cholangiocarcinoma.

We suggest LT as the definitive treatment for recalcitrant RPC.Only patients who have failed conventional interventions and patients with complications would be considered LT.The risk and difficulty of the recipient operation are increased due to inflammation and fibrosis from repeating sepsis, adhesions from previous operations, and cirrhosis.However, given the potential benefits of LT,early LT should be considered.

The number of patients in this single-center, retrospective study is small.Moreover, the study covers a long period, during which treatment strategies evolved.However, this is the first case series on LT for RPC.Hopefully it can provide some insight into the management of severe RPC.

In summary, LT should be offered to patients with RPC uncontrolled by prolonged use of antibiotics and when complications of cirrhosis appear.

Acknowledgments

None.

CRediT authorship contribution statement

Wong Hoi She :Data curation, Formal analysis, Methodology,Writing ? original draft.Wing Chiu Dai :Supervision, Writing ?review & editing.James YY Fung :Supervision, Writing ?review &editing.Tan To Cheung :Supervision, Writing ?review & editing.Albert CY Chan :Conceptualization, Supervision, Writing review &editing.Chung Mau Lo :Supervision, Writing ?review & editing.

Funding

None.

Ethical approval

This study was approved by the Ethics Committee of the University of Hong Kong.Written informed consent was obtained from all participants.

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.