Biliary atresia (BA) is a fibroinflammatory, obliterative cholangiopathy affecting 1/10,000-20,000 newborns.[1-3] If untreated, it is fatal in the first 2-3 years of life. There are two forms of treatment for BA: the Kasai portoenterostomy (KPE), which is performed during the neonatal period, and liver transplantation (LT), which is curative. The KPE is typically considered a palliative measure, because most patients now undergo LT in childhood even if they have received timely KPE. However, a few patients survive into adulthood with their native liver (NL), warranting careful follow-up. The purpose of this review is to summarize the complications and recommended follow-up in this subset of BA patients.
chronic liver disease
Burden of Disease
Based on the few reports of long-term survival (10-20 years) in BA patients who have their NL, it is estimated that approximately 15%-48% of patients do not require LT in the 20 years or more after KPE.[4, 5] The number of patients reaching adulthood with biliary cirrhosis secondary to BA appears to be steady and is not influenced by the era of the KPE. Only three major prognostic factors determining likelihood of survival with NL at 20 years post-KPE have been shown convincingly: 1) anatomical type of the biliary remnant (type 1 is most favorable), 2) nonsyndromic form, and 3) KPE operation in first month of life. Worldwide, neonatal screening efforts aim to refer newborns for early surgery, because KPE prior to 60 days of age has been shown to improve survival with NL.[7, 8] Only time will tell whether these efforts translate into more BA patients reaching adulthood with their NL.
The Long-Term Survivor of BA and KPE with Native Liver
Patient history reveals that most patients enjoy a reasonable quality of life and are gainfully employed, except for those who have a severe neonatal course leading to developmental delay. On physical examination, body mass index or weight Z-score are variable. Height is usually within the predicted range. Hard hepatomegaly is often palpable below the xyphoid, owing to left medial segment hypertrophy. Splenomegaly is normal, except for a small percentage of patients who may not develop portal hypertension. Rarely, the patient can be jaundiced (see the “Liver Biochemistry” section below). The classic stigmata of chronic liver disease (CLD) are frequently appreciated on detailed clinical examination and may direct work-up and surveillance.
There are conflicting data about liver biochemistry in long-term BA survivors. In short, serum levels of aminotransferases and conjugated bilirubin show a inter- and intra-individual variability.[10-13] Patients with conjugated hyperbilirubinemia also present with abnormal prothrombin time and serum albumin concentration.[12, 13]
The radiological findings are summarized in Table 1.
|Intrahepatic or anastomotic stones|
|Sclerosing cholangitis–like findings|
|Spontaneous spleno-renal shunts|
It is now accepted that the systemic complications of CLD are manifold. The following sections summarize only those systems for which there is clinical or published evidence in patients with BA.
Most BA patients have cirrhosis, which is appreciated clinically as described above. The prevalence of portal hypertension is variable among reports, suggesting the use of different definitions. A small fraction of patients appear to be devoid of clinical or biological signs of CLD; one study reported 6/28 survivors >20 years post-KPE. However, ascending cholangitis and biliary stones are a frequent cause of hospital admission. There is no evidence to support a late repeat of portoenterostomy; therefore, such complications often lead to LT (Table 2). Another complication is late onset acute-on-chronic liver failure warranting emergent LT, usually in response to a second “hit” (e.g., pregnancy, cholangitis, or sepsis). Finally, liver nodules are a common ultrasonographic finding that often pose a diagnostic dilemma and necessitate careful surveillance. Hepatocellular carcinoma has been reported in long-term KPE survivors; however, this is a rare and incidental finding on the explanted liver, and it does not alter posttransplantation prognosis.
|Portal hypertension complications: ascites, variceal bleeding|
|Acute-on-chronic liver failure|
The pulmonary complications of cirrhosis and portal hypertension are hepatopulmonary syndrome (HPS) and portopulmonary hypertension. Possible predictors of HPS are the presence of spider naevi and splenomegaly with thrombocytopenia. Patients presenting with biliary atresia splenic malformation may be at increased risk of developing HPS.
Neurological and Cognitive Complications
There is no published evidence on the incidence of chronic hepatic encephalopathy in children or young adults with BA. However, evidence in younger children with BA suggests that there are characteristic deficits early in life. Scant reports suggest that children with CLD may have findings consistent with hepatic encephalopathy (HE) on spectroscopy and 1H magnetic resonance imaging. In our center, a surprisingly large proportion of long-term survivors report neurological problems, including petit mal and grand mal seizures, attention deficit disorder, psychiatric comorbidities, and moderate to severe learning disabilities. In a significant fraction of these, we have identified the characteristic T1 hyperintensity of the pallidi associated with hepatic encephalopathy.
Although no studies have examined myocardial function in adolescents and young adults with BA, BA has been associated with left ventricular dysfunction in infants warranting LT. Cirrhotic cardiomyopathy is a phenomenon that is well characterized in adults; therefore, it is reasonable to consider that this specific subset of patients may have some degree of myocardial dysfunction warranting follow-up. Furthermore, patients with the syndromic form of BA (e.g., biliary atresia splenic malformation) often present with congenital heart disease; consequently, careful evaluation of right-sided heart pressures is warranted prior to transplantation, because these patients may require specialized intraoperative management.
Endocrine, Obstetric/Gyencologic, and Reproduction Complications
There are no data on endocrine status in long-term BA patients. Growth and sexual development (see below) are grossly normal, suggestive of normal endocrine function. Menstruation has been reported to begin normally in females, and secondary sexual characteristics in males have been shown to develop in a timely fashion.[13, 21] There are several reports of normal, healthy infants born to mothers with BA.[11, 21] However, severe complications have arisen in women during pregnancy. These include gastrointestinal hemorrage, cholangitis, and postpartum liver failure.
Prognostic Factors and Indications for LT
The common indications for LT in adolescents and young adults with BA are summarized in Table 2.
Follow-up and Medical Treatment
|Fat-soluble vitamin levels|
|Complete blood count|
|Liver function tests|
|Liver and Doppler ultrasound|
|Esogastroduodenoscopy and variceal band ligation|
|Screening for HE per institutional protocol|
|Dual energy X-ray absorptiometry scan|
|Fat-soluble vitamin supplementation|
|Consider beta-blockadea for esophageal varices prophylaxis|
|Diuretics as needed|
Adolescents and young adults who are 10-20 years post-KPE may enjoy a relatively normal liver function and quality of life. A majority will present with late complications that may warrant LT (Table 2). Clinical follow-up resembles that in adult patients with CLD, but it is important to consider that the systemic and central nervous system manifestations of portal hypertension occur in a developing brain and may have far-reaching effects, though they are not well understood.