Two Cases of Progressive Familial Intrahepatic Cholestasis Type 2: Role of Surgery with Brief Review of Literature.

Progressive familial intrahepatic cholestasis (PFIC) is a rare bile acid transporter defect and autosomal recessive disorder with type 2 being the most common type. Partial internal or external biliary diversion delays its progression to end-stage liver disease. Here, we discuss two cases of type 2 PFIC.

INTRODUCTION

Progressive familial intrahepatic cholestasis (PFIC) is a very rare disorder. The defect is in the bile acid transport and secretion that results in intrahepatic cholestasis progressing to end-stage liver disease (ESLD).[1] The incidence is 1 in 50,000–100,000 live births.[12345] The role of surgery in deciding its fate has been unique as a palliative procedure. Till date, largest series of only 24 children has been reported in the Indian population.[2]

The aim was to highlight the role of partial internal biliary diversion procedure as its key primary therapy to delay the progression to ESLD. We discuss here the successful surgery and follow-up of two siblings of type 2 PFIC.

CASE REPORTS

Case 1

A 7-year-old male with body weight 15 kg, height 3 feet 2 inch, presented with complaints of jaundice, pruritus, and clay-colored stool with scratch marks over abdomen and extremities and 4 cm palpable liver below the costal margins. His birth weight was 2.25 kg, delivered by cesarean section without significant perinatal and postnatal events. He was diagnosed with a case of type 2 PFIC at 9 months of age based on liver histology and serum gamma-glutamyltransferase (GGT) level. Liver biopsy revealed intrahepatic cholestasis, and serum GGT level was 27 IU/L (15–85 IU/L). Ultrasonography abdomen revealed enlarged liver with heterogeneous parenchyma. Magnetic resonance cholangiopancreatography and upper gastrointestinal endoscopy findings were normal. He was admitted several times before reporting to us, for chronic diarrhea and bleeding from gums for which he received medical management. He had mild osteopenia in hand X-ray but no clinical signs of rickets. He was on ursodeoxycholic acid (UDCA) and Vitamin A, D, E, and K supplementation. Preoperative blood investigations showed normal hemogram, liver function test (LFT) showed total bilirubin 21.8 mg/dl, conjugated bilirubin 13.5 mg/dl, unconjugated bilirubin 8.3 mg/dl, alkaline phosphatase (ALP) 2183 (90–280 U/L), alanine aminotransferase (ALT) 190 (10–40 IU/L), aspartate aminotransferase (AST) 260 (8–37 mg/dl), serum bile acids 155 (0.5–10 μmol/l), and Vitamin D3 4.51 ng/ml. Liver biopsy was repeated which showed intrahepatic cholestasis with moderate fibrosis and inflammatory cells [Figure 1].

Figure 1

(a and b) Photographs of the siblings with type 2 progressive familial intrahepatic cholestasis, (c) low-power field liver biopsy, (d) high-power field liver biopsy

Case 2

A 5-year-old sibling of case 1 with body weight 10 kg, height 2 feet, presented with similar complaints. His birth weight was 3.25 kg diagnosed at 3 months of age. However, he did not present with any extrahepatic manifestations such as malabsorption, bleeding, or rickets. Liver biopsy revealed intrahepatic cholestasis with mild fibrosis between the portal triads [Figure 1]. Preoperative blood reports revealed normal hemogram, LFT revealed total bilirubin 13.3 mg/dl, conjugated bilirubin 11.4 mg/dl, unconjugated bilirubin 1.9 mg/dl, ALP 2263U/L, ALT 174 IU/L, AST 199 IU/L, serum bile acids 170 μmol/l, and Vitamin D3 6.91 ng/ml.

Operation and postoperative follow-up

The procedure was performed under general anesthesia. The abdomen was opened through an extended right upper transverse skin incision. Gallbladder was identified, and the proposed site approximately 15–20 cm from the duodenojejunal flexure was marked. A segment of jejunum approximately 10 cm was taken over mesenteric pedicle, and end-to-end anastomosis of the jejunum was done. The jejunal segment was transferred retrocolic and anastomosed with the gallbladder at one end and the other end with the mid-transverse colon on the antimesenteric side (cholecystojejunocolonic anastomosis) [Figure 2]. We slightly modified our technique in case 2 by incorporating intussuscepted nipple valve to prevent migration of bacteria and stool.

Figure 2

(a) Cholecystojejunocolonic anastomosis, (b) jejunocolonic anastomosis, (c) intussuscepted nipple valve, (d) schematic diagram of three anastomosis (1) cholecystojejunal, (2) jejunocolonic, (3) jejunojejunal

Postoperative period was uneventful and discharged on day 10 on oral medications. Jaundice and pruritus were assessed by 5-D itch score in the postoperative period and follow-up visit.[2] Postoperative after 2-month blood reports in Case 1, LFT showed total bilirubin 4.6 mg/dl, conjugated bilirubin 3.2 mg/dl, unconjugated bilirubin 1.4 mg/dl, ALP 234 U/L, ALT 221 IU/L, AST 309 IU/L, and serum bile acids 54 μmol/L. In Case 2, LFT showed total bilirubin 3.9 mg/dl, conjugated bilirubin 2.7 mg/dl, unconjugated bilirubin 1.2 mg/dl, ALP 269 U/L, ALT 67 IU/L, AST 43 IU/L, and serum bile acids 60 μmol/l. Apart from the dramatic response in the biochemical findings, there was also picking up weight in the children by 2 kg at 2 months, and they were itch free and without any episode of cholangitis.

DISCUSSION

PFIC is an autosomal recessive bile acid transport disorder which is detected by its genetic defect, liver histology, immunostaining, and serum GGT levels and characteristics clinical features of jaundice and pruritus with or without extrahepatic manifestations such as malabsorption and bleeding from gums.[12345]

Medical management with UDCA and Vitamin A, D, E, and K is given from the time at initial diagnosis. The first case was diagnosed at 9 months and the second case at 3 months and finally intervened at 7 years of age and 5 years, respectively, which was much delayed. In our cases, there was not much decline in the symptoms with medication. Thus, we support earlier retrospective series where medical management failed to control the symptoms of pruritus and ongoing liver function deterioration in the majority.[5]

Partial biliary diversion procedure has been described earlier in several case reports and series. Yang et al. reported on 14 children of which partial external biliary drainage (PEBD) has been performed in 11, and there was 85% resolution in pruritus in follow-up patient although three patients developed stomal prolapse.[3] In another study in 24 children, 7 of 24 children underwent conversion from PEBD to PIBD (ileocolonic anastomosis) mainly due to patient preference or electrolyte abnormality.[4] Agarwal et al. found in Indian population on 24 children, 7 refractory to medical management, 3 required PIBD, 1 underwent PEBD, and 3 liver transplantation but none of the PIBD required further surgery.[2] In our cases of type 2 PFIC, we found positive outcome in the postoperative period without any mortality or morbidity.

PFIC is a disease with challenging diagnosis and management. The primary goal of management should be ideally delaying liver damage by a PIBD procedure preferably cholecystojejunocolonic anastomosis to avoid complications such as stomal prolapse and electrolyte imbalance as found in PEBD. Long-term follow-up is required to have a better understanding on the outcome of PIBD.

Declaration of patient consent

These authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.