Introduction:
Intrahepatic bile duct paucity is a cause rather than a disease. A condition with reduced interlobular bile ducts (PIBD) is defined as the paucity of interlobular bile ducts (PIBD). Paucity means the decrease or absence of something, and cholestasis is a liver disease caused by reduced amounts of bile from the liver. Therefore the decrease of interlobular bile ducts results in reduced bile flow from the liver resulting in cholestasis.
What Is Neonatal Cholestasis?
Neonatal cholestasis is a liver disease that results in reduced bile flow and excretion. This causes conjugated hyperbilirubinemia (due to high bilirubin levels due to systemic illness, like hepatic diseases) in neonates. PIBD is one of many causes which can cause this condition. Causes of cholestasis include bacterial, viral, or protozoal infections. Most cholestasis leads to end-stage liver disease despite medical treatments. And these patients will require liver transplantation. However, some prognostic factors determine if the transplantation will be successful, such as cardiac involvement and the severity of the liver disease. The presence of heart disorders increases the mortality rate.
What Causes Paucity of Intrahepatic Bile Ducts?
The lack of intrahepatic bile ducts is often associated with other syndromes and rarely occurs in isolation. The exact cause of it is unknown. If it is associated with AGS (Alagille syndrome), it is considered an autosomal dominant disease. The genetic condition occurs due to the mutation of the JAG-1 gene in 90 % of the cases.
What Are the Clinical Features of Paucity of Intrahepatic Bile Ducts?
The name itself is the most remarkable feature of the condition, lack of bile ducts can be seen. It can occur either due to a syndrome or without other associated features. If it is due to a syndrome, congenital disabilities are seen.
The scarcity of the intrahepatic bile duct in neonates can have the following effects:
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Jaundice.
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Conjugated hyperbilirubinemia.
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Pruritus (itching sensation).
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Xanthoma (build-up of fats under the skin's surface)
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Abnormal liver function tests.
Alagille Syndrome:
In most cases, PIBD is associated with different congenital anomalies in the form of Alagille syndrome (AGS). The features of this syndrome include the following:
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Chronic Cholestasis: Seen in about 90 % of patients.
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Cardiac Anomalies: 85 % to 91 % of cases.
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Musculoskeletal Abnormalities: Seen in 39 % to 87 % of cases.
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Dysmorphic Face: In 77 % to 95 % of cases.
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Ocular Anomalies: In 61 % to 88 % of cases.
It is considered AGS if a patient has three of the five features. In addition, the patient also tends to have a mutation of the Jagged-1 gene. AGS's main features are cholestasis, cardiac involvement, and, in some cases, musculoskeletal abnormality. The most common musculoskeletal abnormality is asymptomatic butterfly vertebrae. In this case, the vertebras get split sagittally, and this is diagnosed radiographically.
In neonates where PIBD is associated with AGS, there may be features such as cardiovascular symptoms or failure to thrive. In addition, due to the resultant cholestasis, the intestine's bile acids decrease, leading to the malabsorption of lipids and fat-soluble vitamins. This, in turn, leads to severe growth retardation and malnutrition.
How to Diagnose Paucity of Intrahepatic Bile Ducts?
For a condition to qualify as PIBD, there should be a loss of more than 50 % of portal tracts containing at least ten. For this to be identified, a liver biopsy is necessary. The causes of PIBD in syndromic cases and nonsyndromic cases are diagnostic differentiation. A lack of interlobular biliary ducts characterizes Alagille syndrome. The patients show symptoms before six months, such as failure to thrive, cardiovascular symptoms, or jaundice. Liver biopsy is used to diagnose a lack of bile ducts, but to determine whether it is AGS is based on other clinical features. As there are currently no tests available specific to AGS, be it biochemical, radiological, histopathological, or clinical; it is based on clinical features that AGS is identified, such as the following:
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Congenital Heart Disease: The most common abnormalities involve the pulmonary valve, pulmonary artery, and branches. Pulmonary stenosis is also another common finding.
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Ocular Findings: Defects of the anterior chamber and retinal pigmentary changes.
Diagnostic procedures include:
- MRCP: Or magnetic resonance cholangiopancreatography, and ERCP or endoscopic retrograde cholangiopancreatography. This helps to evaluate the biliary anatomy. ERCP helps to display the narrowing of extrahepatic biliary ducts and uniform narrowing of the intrahepatic ducts.
- Ultrasonography: This can determine portal hypertension and help to identify if transplantation is required.
The primary importance of these tests is that it helps to eliminate other causes of neonatal cholestasis. The tests may not be specific to AGS but help rule out other causes and to determine associated malformations.
How to Treat Alagille Syndrome?
The severity of morbidity and mortality are associated with liver and cardiac involvement. Treatment for IBD includes treating intractable pruritus caused by cholestasis. Surgery may be required to bypass the blockage. The doctor may prescribe antibiotics in cases where the infection is suspected.
There is no specific treatment for Alagille syndrome, and the existing management modalities depend on treating the affected organ. Symptomatic medications may relieve itching sensations, along with moisturizers for skin care. The patients may be required to take vitamin supplements and high-calorie food. In case of liver failure, liver transplantation may be recommended. Genetic testing and discussion with family members can prevent the risk in future generations.
Conclusion:
The lack of intrahepatic bile ducts is the reduction or absence of bile ducts. This is one of the causes of neonatal cholestasis. In most cases, PIBD is associated with a syndromic condition called Alagille syndrome, associated with cardiovascular and ophthalmic findings and duct paucity. In patients with cholestasis, liver transplantation is often the treatment option.
