Overview
Definition:
Autoimmune sclerosing cholangitis (ASC) is a rare, chronic, inflammatory, and fibrosing disease of the intrahepatic and/or extrahepatic bile ducts, characterized by autoimmune features and progressive cholestasis leading to cirrhosis and portal hypertension
It is a distinct entity in pediatric populations, often presenting differently than adult primary sclerosing cholangitis.
Epidemiology:
ASC is considered a pediatric-specific variant of autoimmune liver disease
Its exact incidence and prevalence are not well-established due to its rarity and diagnostic challenges, but it accounts for a significant proportion of pediatric autoimmune liver diseases
It can occur at any age in childhood, with a bimodal peak incidence in early childhood (3-5 years) and adolescence (8-10 years)
There is a female predilection, similar to other autoimmune hepatitides.
Clinical Significance:
ASC is crucial for pediatric residents and DNB/NEET SS aspirants to recognize due to its progressive nature and potential for severe complications, including liver failure and the need for transplantation
Early diagnosis and appropriate management are vital to improve long-term outcomes and prevent irreversible liver damage
Understanding its unique pediatric presentation and diagnostic criteria is essential for accurate management.
Clinical Presentation
Symptoms:
Jaundice, particularly conjugated hyperbilirubinemia
Pruritus, often severe
Abdominal pain, typically in the right upper quadrant
Fatigue and malaise
Poor growth and failure to thrive in younger children
Steatorrhea due to malabsorption
Recurrent cholangitis episodes, presenting with fever, chills, and abdominal pain
Bone disease (rickets, osteoporosis) due to vitamin D malabsorption
Symptoms suggestive of portal hypertension in later stages, such as splenomegaly and ascites.
Signs:
Icteric sclerae and skin
Hepatomegaly, often firm
Splenomegaly, especially with portal hypertension
Signs of chronic liver disease: palmar erythema, spider angiomata
Xanthomas due to hyperlipidemia
Signs of malnutrition
Cachexia in advanced disease
Signs of cholangitis: fever, RUQ tenderness.
Diagnostic Criteria:
No single universally accepted diagnostic criteria exist for pediatric ASC, but consensus guidelines often require the presence of: 1
Autoimmune hepatitis features (elevated ALT/AST, presence of autoantibodies like ANA, ASMA, anti-LKM-1, elevated IgG)
2
Cholestatic pattern on liver biochemistry (elevated ALP, GGT, bilirubin)
3
Imaging findings suggestive of biliary strictures and dilatations (MRI/MRCP, ERCP)
4
Exclusion of other causes of secondary sclerosing cholangitis (e.g., biliary atresia, choledochal cyst, genetic disorders, viral infections).
Diagnostic Approach
History Taking:
Detailed birth history to exclude neonatal cholestasis
History of recurrent infections, fever, or unexplained abdominal pain
Growth parameters and nutritional status
Family history of autoimmune diseases or liver disorders
Presence of other autoimmune conditions (e.g., inflammatory bowel disease, thyroiditis, type 1 diabetes)
Medications and recent infections
Detailed inquiry about pruritus and its severity.
Physical Examination:
Assess for jaundice and pruritic excoriations
Evaluate growth and nutritional status
Palpate the abdomen for hepatomegaly and splenomegaly, noting liver consistency
Auscultate for ascites
Assess for signs of portal hypertension
Examine skin for xanthomas and spider angiomata
Assess for signs of rickets or skeletal abnormalities.
Investigations:
Liver function tests: ALT, AST, ALP, GGT, total and direct bilirubin
Albumin, prothrombin time (INR) to assess synthetic function
Complete blood count to assess for anemia and leukocytosis/leukopenia
Autoantibody profile: ANA, ASMA, anti-LKM-1, anti-SLA/LP
Immunoglobulin levels (especially IgG)
Serology for viral hepatitis (HAV, HBV, HCV, HEV)
Magnetic Resonance Cholangiopancreatography (MRCP): preferred initial imaging to assess intra- and extrahepatic bile ducts for strictures, dilatations, and irregularities
Endoscopic Retrograde Cholangiopancreatography (ERCP): may be necessary for more detailed visualization and potential biopsy, but carries higher risks in children
Liver biopsy: crucial for histological assessment to confirm inflammation and fibrosis, and to rule out other conditions
characteristic findings include chronic portal and periportal inflammation, bile duct damage, and fibrosis.
Differential Diagnosis:
Primary Sclerosing Cholangitis (PSC) in adults: ASC in children shares features with PSC but often has stronger autoimmune markers and may respond better to immunosuppression
Biliary Atresia: should be excluded in infants with conjugated hyperbilirubinemia
Choledochal Cysts: structural abnormalities of the bile ducts
Genetic disorders: Cystic Fibrosis, Alpha-1 Antitrypsin Deficiency, Wilson's Disease, Familial Intrahepatic Cholestasis
Infections: Viral cholangitis, parasitic infections
Drug-induced cholestasis.
Management
Initial Management:
Symptomatic relief of pruritus with bile acid sequestrants (e.g., cholestyramine)
Vitamin supplementation (fat-soluble vitamins A, D, E, K)
Nutritional support to address malabsorption and growth failure
Management of complications like portal hypertension
Initiation of immunosuppressive therapy if autoimmune features are prominent and other causes are excluded.
Medical Management:
Immunosuppressive therapy is the cornerstone of medical management
Corticosteroids (prednisolone) are often used as initial induction therapy, gradually tapered
Other immunosuppressants may include azathioprine, mycophenolate mofetil, or tacrolimus for maintenance therapy
Ursodeoxycholic acid (UDCA) may be used, although its efficacy in pediatric ASC is less established than in adult PSC
Specific dosages and protocols vary and should be individualized based on disease severity and response.
Surgical Management:
Surgical intervention is generally reserved for complications or when medical management fails
Procedures may include biliary diversion (e.g., choledochojejunostomy) for severe extrahepatic duct involvement or refractory symptoms
Liver transplantation is indicated for end-stage liver disease, irreversible portal hypertension, or hepatocellular carcinoma
Medical management aims to delay or prevent the need for transplantation.
Supportive Care:
Regular monitoring of liver function tests, nutritional status, and growth
Management of pruritus, steatorrhea, and complications of cholestasis and portal hypertension
Bone health monitoring and management of vitamin D deficiency
Psychological support for the child and family
Multidisciplinary team approach involving pediatric hepatologists, gastroenterologists, surgeons, dietitians, and psychologists.
Complications
Early Complications:
Recurrent cholangitis with sepsis
Worsening jaundice and pruritus
Malabsorption and malnutrition
Acute liver failure.
Late Complications:
Cirrhosis and advanced fibrosis
Portal hypertension with its sequelae: ascites, variceal bleeding, hepatic encephalopathy
Hepatopulmonary syndrome
Cholangiocarcinoma (rare in pediatrics but a risk in adults)
Bone disease (osteopenia, osteoporosis).
Prevention Strategies:
Early diagnosis and prompt initiation of immunosuppressive therapy to halt disease progression
Regular monitoring for early signs of complications
Optimizing nutritional status and vitamin absorption
Prophylaxis against cholangitis with appropriate antibiotics in susceptible individuals
Close follow-up to manage disease flares and potential adverse effects of medications.
Prognosis
Factors Affecting Prognosis:
Age at diagnosis (younger onset may have more aggressive disease)
Extent of bile duct involvement (intrahepatic vs
combined vs
extrahepatic)
Response to immunosuppressive therapy
Presence and severity of autoimmune features
Development of complications like cirrhosis and portal hypertension
Degree of fibrosis at diagnosis.
Outcomes:
Prognosis varies widely
With effective immunosuppression and supportive care, some children may achieve remission or stable disease with a good quality of life
However, a significant proportion may progress to cirrhosis and liver failure, necessitating liver transplantation
Early diagnosis and treatment are critical for a better outcome.
Follow Up:
Lifelong follow-up is generally recommended, even in patients who achieve remission
Monitoring includes regular liver function tests, autoantibody levels, imaging of the biliary tree, nutritional assessment, bone mineral density scans, and screening for portal hypertension and complications
DNB and NEET SS candidates should understand the long-term implications and management requirements.
Key Points
Exam Focus:
ASC is a pediatric-specific autoimmune liver disease affecting bile ducts
It presents with cholestasis, pruritus, and often features of autoimmune hepatitis
MRCP is the key imaging modality
Treatment involves immunosuppression (corticosteroids, azathioprine) and supportive care
Liver transplantation is a treatment option for end-stage disease.
Clinical Pearls:
Think of ASC in a child with unexplained cholestatic jaundice, pruritus, and elevated liver enzymes, especially if other autoimmune markers are positive
Always exclude biliary atresia in infants
MRCP is invaluable for diagnosing biliary strictures and dilatations
Remember to supplement fat-soluble vitamins and manage pruritus aggressively.
Common Mistakes:
Delaying diagnosis by not considering autoimmune etiology in pediatric cholestatic liver disease
Misdiagnosing ASC as other forms of pediatric liver disease without thorough investigation
Inadequate immunosuppression or premature withdrawal of therapy
Failing to adequately monitor for and manage complications like portal hypertension and nutritional deficiencies.