Indian Childhood Cirrhosis - Causes, Diagnosis, and Treatment

What Is Indian Childhood Cirrhosis?

Indian childhood cirrhosis is a severe type of chronic liver disorder affecting children in the Indian subcontinent. The word cirrhosis is derived from the Greek word 'kirrhos' in which the surface of the liver appears orange or tawny at autopsy. The malfunctioning of the liver leads to yellowing of the skin and sclera (whites of the eye) in the affected children. With increasing age, the condition worsens leading to progressive liver damage, and finally causes irreversible liver disease (liver cirrhosis) in young children or young adults. If the disease is left untreated, it may even lead to liver failure. The disease was first reported in Kolkata in the year 1880 and was referred to as infantile cirrhosis or infantile biliary cirrhosis. But it was first documented in the year 1930. The possible etiologic agent of the disease is unknown. The disease has got a genetic predisposition.

What Is the Epidemiology of Indian Childhood Cirrhosis?

The disease is found to be endemic in some parts of the Indian subcontinent. This juvenile disease is very rarely reported in other countries. The disease is most frequently present in children who fall between one to three years of age group. Indian childhood cirrhosis is considered to be one of the major causes of morbidity and mortality in children below the age of five years.

What Is the Difference Between Indian Childhood Cirrhosis and North American Indian Childhood Cirrhosis?

North American Indian childhood cirrhosis is exclusively found in the young children of Ojibway-Cree descent in the Abitibi region of the northwestern region of Quebec, Canada (North America), hence the name. Approximately, thirty affected children from this population have been documented. Whereas, Indian childhood cirrhosis is found only in the Indian subcontinent. But otherwise, both diseases are similar in clinical presentation. Indian childhood cirrhosis should not be confused with North American Indian cirrhosis which occurs due to genetic mutations in the CIRH1A gene, which codes for cirhin.

What Is the Cause of Indian Childhood Cirrhosis?

Three possible etiological theories have been suggested:

• Firstly, it is suggested that the condition simply occurs due to ingestion of copper in high amounts or in siblings who share the same food and environment and are quite likely to be affected by the disease equally.

• Secondly, it may be reported that there can be another hereditary condition related to a defective mechanism in the copper metabolism. However, there is no distinct pattern of inheritance that is identifiable. It may be a result of poor penetrance of the genotypes either in causing increased copper storage or in causing liver damage due to copper deposition. This is just a hypothesis that is restricted to the geographical location of India and absent in other continents. So this is a debatable topic.

• The third hypothesis suggests the possible role of both genetics and excessive copper deposition in the etiopathogenesis of Indian childhood cirrhosis.

What Are the Predisposing Factors for Indian Childhood Cirrhosis?

1. Environmental factors may be partially responsible for two conditions:

• If children suffering from Indian childhood cirrhosis are normal genetically in correlation with the copper metabolism, then it is suggested that other trace elements such as zinc or molybdenum may be responsible for causing the condition since they impair the absorption of copper.
• Another possibility can be the ingestion of another element. This ingested agent can interfere with the excretion of the copper element from the liver. For example, pyrrolizidine alkaloids of the plant Heliotropium europaeum can have toxic effects on the liver.

2. Copper (instead of zinc) can be actively extracted from brass. This copper that is avidly taken up is then bound to casein from which it can be easily and fully removed by the process of picolinate chelation.

3. Milk serves as an effective carrier of copper that is served in a brass utensil to the enterocytes of infants.

What Are the Clinical Features of Indian Childhood Cirrhosis?

The clinical manifestations of the condition include:

1. Age - The usual age of occurrence varies from six months up to five years. However, the incidence peaks at approximately two years of age.

2. Clinical Features- Three clinical stages of Indian childhood cirrhosis have been identified:

• Early Stage - An early stage with a sudden onset is characterized by loss of appetite and disturbed bowel movements, liver enlargement, and presentation of jaundice occasionally.
• Intermediate Stage - An intermediate stage is characterized by mood swings, jaundice present minimally, hepatomegaly present remarkably, spleen enlargement and occasional edema in the subcutaneous tissues, ascites (fluid accumulation in the abdomen), and increased susceptibility to various infections.
• Late Stage - A late stage is characterized by an increasing degree of jaundice, remarkable hepatosplenomegaly, and subsequent progression to liver failure and even death.

What Are the Diagnostic Investigations for Indian Childhood Cirrhosis?

The diagnosis of the disease includes:

1. Testing for the ceruloplasmin levels which can be either normal or low.

2. Liver biopsy to demonstrate copper deposits histochemically either by

• Orcein dye to stain copper-binding protein.
• Rhodanine dye to stain copper.

3. Quantitative techniques such as atomic absorption spectrophotometer to measure the quantity of copper deposited in the liver.

How Indian Childhood Cirrhosis Is Managed?

• Copper vessels should be avoided when used for infants and young adults.

• The cytopathic effect of copper is reversed or modified directly by penicillamine therapy if given at an early stage.

What Is the Differential Diagnosis of Indian Childhood Cirrhosis?

• Alcoholic Liver Disease - It occurs due to excessive use of alcohol which severely damages the liver.

• Wilson’s Disease - It is a rare hereditary disorder that causes excess copper accumulation in the liver, brain, and other organs of the body. Most cases of Wilson’s disease are diagnosed between the ages of five and thirty-five. There is the presence of neurological symptoms along with liver symptoms.

Conclusion:

Indian childhood cirrhosis is a chronic liver disorder primarily occurring in the pediatric age group and is exclusively present in the Indian subcontinent. The primary cause is the toxic copper deposited in the liver which leads to jaundice-like symptoms in children. It is one of the main causes of morbidity among children below the age of five years. The disease usually worsens with age causing liver cirrhosis and finally liver failure causing life-threatening complications in the affected child. It is crucial to identify the disease at an early stage and immediately start the treatment.