Internal biliary diversion using appendix during liver transplantation for progressive familial intrahepatic cholestasis type 1: A case report

Abstract

BACKGROUND

Progressive familial intrahepatic cholestasis type 1 (PFIC-1) is a genetic cholestatic disease causing end-stage liver disease, which needs liver transplantation (LT). Simultaneous biliary diversion (BD) was recommended to prevent allograft steatosis after transplantation, while increasing the risk of infection. Here, an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.

CASE SUMMARY

An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus. His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%. Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon. Biliary leakage was suspected on the 5^th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver. The liver function returned to normal on the 9^th day post-operation and maintained normal during the 15-month follow-up. Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon. Computerized tomography scan (4 months and 10 months) and liver biopsy (10 months) indicated no steatosis in the allograft. No complaint of recurrent diarrhea, infection or growth retardation was reported during follow-up.

CONCLUSION

Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.

Key Words: Liver transplantation; Progressive familial intrahepatic cholestasis type 1; Biliary diversion; Appendix; Case report

Core Tip: Liver transplantation indicated in end-stage liver disease caused by progressive familial intrahepatic cholestasis type 1 is often performed with biliary diversion (BD). Although effectively preventing allograft steatosis, traditional BD increases post-operative infection risk. Here, we present a case of an 11-month-old progressive familial intrahepatic cholestasis type 1 patient receiving liver transplantation and BD using appendix to prevent post-operative infection. The proximal end and distal end of appendix were connected with intrahepatic biliary duct and colon respectively. Post-operative exams confirmed successful BD and absence of allograft steatosis. Thus, using appendix for BD might be a new surgical approach preventing allograft steatosis and post-transplant infection.

INTRODUCTION

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic liver disorders characterized by progressive cholestasis in childhood, eventually leading to liver fibrosis and end-stage liver disease[1]. Among the 6 subtypes of PFIC, PFIC type 1 (PFIC-1) is caused by mutation in ATP8B1, a gene encoding a P-type aminophospholipid flippase (ATPase) called FIC1[2,3]. Mutation of ATP8B1 impairs the transportation of phospholipid and results in cholestasis[4]. Liver transplantation (LT) is indicated in patients with end-stage liver disease. However, PFIC-1 patients are susceptible to persistent chronic diarrhea and allograft steatosis after transplantation, which may lead to graft dysfunction[5-7]. Therefore, internal biliary diversion (BD) is recommended to skip the absorption of biliary acid in distal ileum and alleviate chronic diarrhea and hepatic steatosis[8-11]. However, direct connection between biliary duct and the colon may expose the hepatobiliary system to gut microbiome which may lead to bacterial translocation and infection[11]. Here, we report a novel surgical method using the appendix for biliary reconstruction. The appendix possesses Gerlach’s valve, which can act as a check valve to prevent intestinal contents regurgitation and gut microbiome translocation, which might reduce the infection risk of BD after LT.

CASE PRESENTATION

Chief complaints

An 11-month-old boy developed progressively worsening jaundice and sclera for over 11 months.

History of present illness

The patient was male, 11 months old, full term with normal delivery. After birth, he developed jaundice and the whole-exon test revealed a mutation in the ATP8B1 gene (c.1798C>T), supporting the diagnosis of PFIC-1.

History of past illness

The baby was born by uneventful spontaneous delivery. The results of the prenatal examination showed no abnormalities.

Personal and family history

The patient had no family genetic history of related liver diseases.

Physical examination

The vital signs of the patients were within normal range, including respiratory rate, heart rate, blood pressure, body temperature and oxygen saturation. The patient had jaundice and sclera.

Laboratory examinations

Laboratory tests showed severe cholestasis with total bilirubin: 313.3 μmol/L and direct bilirubin: 224.4 μmol/L.

Imaging examinations

Preoperative ultrasonography indicated elevated liver elasticity (mean value: 10.0 kPa, median value: 10.1 kPa).

FINAL DIAGNOSIS

According to the provided medical history, the final diagnosis was PFIC-1.

TREATMENT

This patient then received ABO compatible living donor LT, in which his mother donated the left lateral segment, weighted 251 g with graft-to-recipient weight ratio as 2.9%. The operation was uneventful with bleeding of 50 mL. To conduct the internal BD, the free appendix was cut off from the ileocecal junction area with the blood supply vessels connected. Then the appendix was reconstructed at the junction of transverse and ascending colon, with the distal end was anastomosed with the bile duct (Figure 1).

Figure 1 Surgical technique schematic diagram. A: Excision of the diseased liver; B: Biliary reconstruction; C: Excision range of appendix.

OUTCOME AND FOLLOW-UP

The recovery of this patient after transplantation was smooth. His tracheal intubation was removed 3 days after operation with a length of stay in computerized tomography of 8 days. Biliary leakage was suspected on the 5^th day after transplantation and exploratory laparotomy indicated a small amount of bile-like effusion at the cutting surface of the allograft. No abnormality was found at the appendiceal-colonic and biliary-appendiceal anastomotic stomas. The liver function returned to normal on the 9^th day post-operation and this patient was discharged on the 18^th day after transplantation. The maintenance immunosuppressive strategy was tacrolimus and prednisone.

During the 15-month follow up, the patient had no complaint of recurrent diarrhea or growth retardation. Biochemical parameters for liver function were routinely tested during follow-up visits and no obvious abnormality was reported. Upper abdomen computerized tomography was carried out in the 4^th and 10^th months after LT operation and no graft steatosis was found, as presented in Figure 2A and B. Fine needle liver biopsy, performed 10 months after LT, showed no damage of hepatic lobular structure and no steatosis. A radionuclide cholangiography, performed 10 months after LT, showed that bile was excreted into the transverse colon directly with no expansion of intrahepatic biliary tract (Figure 2C). The postoperative blood vitamin E and vitamin K1 levels were below normal. Thus, regular intramuscular vitamin E and vitamin K1 injections were prescribed and the subsequent lipid soluble vitamin concentrations were closely monitored.

Figure 2 Imaging examination. A: Upper abdomen computerized tomography performed 4 months after liver transplantation (LT) operation; B: Upper abdomen computerized tomography performed 10 months after LT operation; C: Radionuclide cholangiography performed 10 months after LT operation (upper left corner: Cholangiography 45 minutes after the injection of radionuclide, nuclide concentrated in intrahepatic bile duct; upper right corner: Cholangiography 1.5 hours after the injection of radionuclide, nuclide concentrated in anastomosed colon; lower left corner: Cholangiography 4 hours after the injection of radionuclide, nuclide concentrated in transverse colon; lower right corner: Cholangiography 5 hours after the injection of radionuclide, nuclide concentrated in the whole colon).

DISCUSSION

PFIC-1 patients who receive LT treatment encounter high risk of allograft steatosis and refractory diarrhea, which makes BD a common and necessary surgical procedure during LT[5,6]. However, traditional internal BD may expose the liver directly to the excessive gut microbiome in the colon, leading to microbiome translocation and post-operation infection such as cholangitis[11]. In this study, we used appendix to construct a novel “appendiceal-colonic anastomosis” in an 11-month-old boy with PFIC-1 during LT to prevent the translocation of colon microbiome. The recipient experienced normal recovery after transplantation and no steatosis or diarrhea was found during the follow-up. Cholangiography also indicated the drainage of bile flow directly into colon. Our report has provided a novel approach for BD in PFIC-1 LT recipients with less post-transplant infection risk.

CONCLUSION

To reduce the risk of infection while preventing allograft steatosis, using the appendix to replace the bile duct for BD has become a new exploration, which is expected to prevent colonic microbiota translocation and reduce the risk of infection through the Gerlach valve. In this study, replacing the bile duct with the appendix for biliary enteric anastomosis can achieve normal BD function. This successful case may provide a new treatment strategy for PFIC-1 Liver transplant recipients.

ACKNOWLEDGEMENTS

Here, we would like to express our sincere gratitude to the patients’ families and patients for their support of our work.