Age Is Not a Criterion in Patient Selection for Kasai Portoenterostomy.

AIMS: The aim of our study was to compare the outcome of Kasai portoenterostomy (KPE) in children with biliary atresia (BA) older than 90 days to children less than 90 days and to study its safety and efficacy in children older than 90 days. SUBJECTS AND METHODS: Relevant data were collected from our prospectively maintained database of all children with BA who underwent KPE over a 5-year period. Children were divided into two groups: Group 1 ≤90 days and Group 2 >90 days. Data analyzed and compared included total and direct bilirubin, aspartate aminotransferase-to-platelet ratio index (APRI), and the outcome of procedure which was defined as a serum direct bilirubin <2 mg/dl within 6 months after surgery. Standard statistical tests were used for analysis.
RESULTS: Out of 62 children, 45 children were in Group 1 and 17 children were in Group 2. Children in Group 2 had similar total and direct bilirubin compared to children in Group 1. APRI, an indicator of fibrosis, was significantly increased in Group 2 (P = 0.08). About 47% of children in Group 2 had Stage III fibrosis on liver histology compared to 22% of children in Group 1. None of the children in Group 2 had synthetic liver failure (refractory ascites, hypoalbuminemia, or coagulopathy unresponsive to Vitamin K) or portal hypertension. KPE was successful in 29.4% of children in Group 2 and 44% in children in Group 1. There was no perioperative mortality in our group.
CONCLUSIONS: KPE was successful in a third of children over 90 days of age and can be safely performed in this group. In the absence of synthetic liver failure, age should not be a disqualification for performing KPE. Copyright:

INTRODUCTION

Biliary atresia (BA) is a cholangiodestructive disorder affecting the intra- and extrahepatic biliary ductular continuum. If left untreated, all children will eventually die of progressive biliary cirrhosis. Kasai portoenterostomy (KPE) is the first line of treatment, and if it fails to control the disease, liver transplantation (LT) is the only curative option. Infants with BA are usually in good health and present with features of obstructive jaundice. In some children, the diagnosis is delayed, and they are referred for surgery well beyond the neonatal period. Children are also referred directly for primary LT because of the perception that they are “too old” for KPE. In our centers, we perform KPE on all children with BA who do not have synthetic liver failure or evidence of portal hypertension. We do not use age at presentation as a cutoff criterion. We evaluated this practice and compared the outcome of KPE in “older” and “younger” children with BA.

SUBJECTS AND METHODS

Since 2013, we have maintained a prospective database of all children who undergo KPE in our institutions. The care of children with BA is standardized. All KPEs are performed by a single surgeon, and the histology is reported by a single pathologist. Contraindications for surgery are evidence of synthetic liver failure and portal hypertension. These include a persistent coagulopathy (international normalized ratio [INR] >1.5) not responding to three doses of Vitamin K injections and low serum albumin (<3.2 mg/dl). The surgical technique used is an extended KPE which involves liver mobilization, dissection of the vessels at the liver hilum to expose the portal plate, excision of the fibrotic portal plate, creation of a 60-cm Roux-en-Y loop, and hepaticojejunostomy extending from the bifurcation of the right hepatic artery into its anterior and posterior branches to the Rex recess on the left. All children receive a tapering regimen of steroids (prednisolone) for 6 weeks and cyclical prophylactic antibiotics for 6 months along with fat-soluble vitamins, ursodeoxycholic acid, and formulas rich in medium-chain triglycerides. Bilirubin levels are monitored 1, 3, and 6 months after surgery. Jaundice clearance is defined as a serum direct bilirubin of <2 mg/dl in 6 months. A routine upper gastrointestinal endoscopy is performed after 1 year with or without variceal banding.

Histological examination

The department of pathology receives wedge liver tissue. The wedge liver is fixed in buffered formalin for 12–24 h. About 4–5-μ thick sections are made from the paraffin-embedded material and stained with hematoxylin and eosin, periodic acid–Schiff (PAS), PAS after diastase, Masson's trichrome, orcein, iron, and rhodanine.

Fibrosis is staged as mild (Stage I): fibrous portal expansion with no bridging septum formation, moderate (Stage II): bridging fibrosis with <50% of portal tracts involved, and severe (Stage III): bridging fibrosis with >50% of portal tracts involved and nodular architecture.

Statistical analysis

Relevant data were collected from our prospectively maintained database of all children with BA who underwent KPE over a 5-year period, and they were divided into two groups: Group 1 (<90 days) and Group 2 (>90 days). Data analyzed included total and direct bilirubin, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and stage of fibrosis. APRI was calculated using the formula AST/upper limit of normal/platelet count expressed as platelets ×10(9)/L×100. Standard statistical tests were used for the analysis. This study was performed after approval from our Institutional Review Board.

RESULTS

Of the 62 children who underwent KPE in our institution over 5 years, there were 45 children in Group 1 (median age: 67 days, range: 23–90 days) and 17 children in Group 2 (average age: 119 days, range: 91–139 days). The total and direct bilirubin was 10.9 ± 3.4 and 7.2 ± 2.1 mg/dl in Group 1 compared to 10.9 ± 3.2 and 7.4 ± 2.9 mg/dl in Group 2. The average APRI was 1.06 (range: 0.30–5.8) in Group 1 and 1.67 (range: 0.63–8.72) in Group 2. The children in Group 1 had a similar total and direct bilirubin compared to Group 2 (P = 0.97 and P = 0.76, respectively). APRI, an indicator of fibrosis, was significantly higher in Group 2 compared to Group 1 (P = 0.008). About 47% (n = 8) of children in Group 2 had Stage III fibrosis on liver histology compared to 22% (n = 10) of children in Group 1 (P = 0.07). In Group 1, 44% (n = 20) of children had ductules in the hilar plate <200 microns in size. In Group 2, 47% (n = 8) had ductules in the hilar plate <200 microns in size. This difference was not statistically significant (P = 0.85). Ductular size did not impact the outcome of KPE in both groups. None of the children over 90 days had synthetic liver failure (ascites, low albumin, and uncorrectable INR) or portal hypertension. KPE was successful in 29.4% (n = 5) of children in Group 2 and 44% (n = 20) in children in Group 1. There was no perioperative mortality or decompensation of liver disease after KPE.

In Group 1, follow-up periods ranged from 6 to 54 months (mean: 30 months). Twelve out of forty-five (27%) children in this group are alive with native liver. In Group 2, follow-up periods ranged from 6 months to 63 months (mean: 35 months). Three out of seventeen (18%) children in this group are alive with native liver with a follow up ranging from 3 to 5 years [Table 1].

Table 1

Follow-up period of children >90 days

Number of patients	Follow-up
10	<6 months
2	6-12 months
3	3-5 years
2	Lost to follow-up

DISCUSSION

The consensus report on neonatal cholestasis syndrome was released by the Pediatric Gastroenterology Subspecialty Chapter of the Indian Academy of Pediatrics. They observed that there was a long delay in parents seeking medical attention and that the average age of presentation to specialized centers was 3.5 months.[1] Eighteen years after the report was published, this scenario still holds true. There is a delay in the diagnosis of BA because parents and primary medical caregivers fail to recognize this problem. This is evident in our study as the average age of children presenting to us was 80 days. The consensus report also recommended that referring doctors need to be educated that there is no cutoff for late referral. We have observed that even today, children older than 90 days are not referred for KPE because of a perception that they are “too old.” We performed this study to dispel the myth that the age of “90 days” was not an absolute number in patient selection for KPE.

Since one of the centers in our study performs about 50 pediatric LTs every year, we also noticed that older children are referred directly to us for primary LT. Mieli-Vergani and Tizzard from King's College Hospital reported that primary LT should be offered only to infants with decompensated liver disease.[2] In 2001, Chardot et al. reported that success at KPE could be achieved until the age of 141 days. They stated that since a late KPE may cause decompensation of advanced liver disease, it was important to rule out synthetic liver dysfunction before KPE.[3] Hence, the only clearly established contraindication for KPE is decompensated liver disease, and we have followed this in our practice.

Several studies have attempted to predict the outcome of KPE.[45678] They analyzed histopathological findings such as stage of liver fibrosis, APRI, and most frequently age at surgery. Although no single factor has been categorically identified to date, it is logical to assume that with increasing age, the liver damage increases, thus decreasing the chance of success of KPE. However, Davenport et al. reported a 40% 5-year native liver survival (NLS) for infants who were operated on after 100 days of age.[9] They also noted that the restoration of bile flow leads to the resolution of liver disease. In 2017, the Japanese Biliary Atresia Registry reported a 20-year NLS of 20% in children who were older than 151 days at the time of operation.[10]

Our centers perform an average of 12–13 KPEs every year. In our experience, there was a significant advantage in performing this operation in older children because nearly a third of them cleared jaundice. We were encouraged when the oldest child in our series at 138 days cleared jaundice. Although APRI which is an indicator of liver fibrosis was higher in older children and half of them had Stage III fibrosis, jaundice clearance was 29.4% in this group compared to 44% in children <90 days.

We experienced difficulties in following up our patients. Most of them do not return to clinic if they do not clear jaundice. This imposed difficulties in computing NLS. Since the follow-up period is <6 months in most patients, we are unable to comment on long-term NLS of these patients. However, three children who were older than 90 days at the time of KPE are among our longest survivors with follow-up periods of >3 years.

CONCLUSIONS

KPE must be offered to all children with BA who do not have decompensated liver disease. Children should not be discriminated because of age and the operation must be performed in all children, even those older than 90 days, giving them a chance to survive into adulthood with their native livers, thereby avoiding LT with the consequent need for prolonged immunosuppression. Although LT in infants has only a small mortality and morbidity, a sizeable number of our patients do not have access to LT because of cost constraints. Age is not a criterion in patient selection for KPE, especially in such situations where this operation offers infants with BA their only shot at life.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.