What is the treatment for Indian childhood cirrhosis?

Treatment of Indian Childhood Cirrhosis

D-penicillamine is the primary treatment for Indian childhood cirrhosis (ICC) and should be initiated as early as possible at a dose of 20 mg/kg/day to reduce mortality and reverse liver damage.

Disease Overview

Indian childhood cirrhosis is a rare but severe form of liver disease characterized by:

• Excessive copper deposition in the liver
• Progressive liver damage leading to cirrhosis
• High mortality rate if untreated
• Typical presentation between 10-29 months of age
• Clinical features including abdominal distension, hepatosplenomegaly, and fever

Pathophysiology and Etiology

• ICC is associated with excessive copper ingestion in infancy 1, 2
• Environmental sources of copper include:
  • High copper content in domestic water used for infant formula preparation
  • Use of brass or copper vessels for storing or preparing infant feeds
• There may be a genetic predisposition to copper-associated liver damage 3
• The condition is distinct from Wilson's disease (ceruloplasmin levels remain normal in ICC) 3

Diagnostic Features

• Micronodular cirrhosis with severe hepatocellular necrosis
• Mallory bodies and orcein-positive material on liver histology
• Elevated liver copper concentrations (typically >1000 μg/g dry weight)
• Normal ceruloplasmin levels (distinguishing it from Wilson's disease)
• Elevated urinary and serum copper levels

Treatment Protocol

First-Line Treatment

1. D-penicillamine therapy:
   • Dosage: 20 mg/kg/day 4
   • Duration: Continue for at least 1-7 years (mean 3.5 years) 5
   • Monitor for side effects, particularly proteinuria 5

Monitoring During Treatment

• Regular liver function tests
• Clinical assessment of hepatosplenomegaly
• Duplex Doppler ultrasound examination
• Serial liver biopsies to monitor histological improvement
• Measurement of liver copper concentrations

Expected Treatment Response

• Reduction in hepatosplenomegaly
• Normalization of liver function tests
• Sequential histological improvement:
  • Initial stage: Persistence of inflammation with increased nodularity
  • Intermediate stage: Inactive micronodular cirrhosis with reduced inflammation
  • Late stage: Incomplete fibrous septae or near-normal histology 4
• Decrease in liver copper concentrations from ~1,400 μg/g to ~127 μg/g after 18+ months of treatment 4

Treatment Outcomes

• Early treatment with D-penicillamine reduces mortality from 92% to 53% 2
• Long-term survivors show either inactive micronodular cirrhosis or virtually normal liver histology 5
• Patients treated successfully can discontinue D-penicillamine after 1-7 years without relapse 5

Special Considerations

• Consider liver transplantation for patients who present in advanced stages or fail to respond to D-penicillamine
• Patients with persistent micronodular cirrhosis beyond 4 years should continue D-penicillamine treatment 5
• Prevention strategies include avoiding use of unregulated water supplies for infant feed preparation 2

Follow-up Care

• Regular clinical assessment for symptoms of liver disease
• Periodic liver function tests
• Ultrasound examination to assess liver and spleen size
• Duplex Doppler assessment of hepatic vein flow pattern
• Growth and development monitoring

Prognosis

With early D-penicillamine treatment, long-term survival is possible with good quality of life. Studies show that treated children followed for 5-12 years after diagnosis were well with normal liver function tests 2, 5.