Indian childhood cirrhosis of liver is almost exclusively confined to children in the Indian subcontinent. The clinical picture is characteristic, with onset around the first year of life. There is progressive distension of the abdomen, marked irritability, unexplained irregular low grade pyrexia, a firm hepatomegaly with sharp leafy margin, splenomegaly and progressive liver cell failure, ascites and jaundice with fatal termination in a large majority of the cases.
Epidemiology

Indian Childhood Cirrhosis is seldom reported from countries outside India. Most cases occur between the ages of 6 months and 4 years. Among twins, the member of the pair on mixed or artificial feeding in predisposed families was reported to have developed cirrhosis of liver. If the other twin was purely breast-fed for first six months, he or she escaped the illness. Siblings of index cases had 10 percent higher risk of developing cirrhosis. No recognized pattern of inheritance was observed. High familial incidence appeared to be related to environmental factors. Recently, a significant decline in the incidence of Indian Childhood Cirrhosis has been observed in all parts of India.
Etiopathogenesis

Following factors are considered in etiopathogenesis: Toxic. Tanner et al. (1979) and Marwaha et al. (1981) reported evidence of excess of copper binding proteins in the livers of patients with Indian Childhood Cirrhosis by orcein staining. Liver copper was high. In an earlier epidemiologic study Chawla et al. (1973) reported that unlike general pattern of dietary practices in the community, the babies with Indian Childhood Cirrhosis had been weaned earlier and milk supplements were added to breast feeding, often before the age of 3 months in 77 per cent of patients. A large proportion of families of index cases used copper or copper alloy pots for boiling milk and cooking food. During boiling of milk, copper is released from the copper pots and this is probably absorbed in excess from the gut by infant.

Immunologic. A variety of immunological disturbances were reported in patients with Indian Childhood Cirrhosis. High levels of circulating immune complexes may indicate that an environmental insult might alter the hepatocyte or tissue proteins and initiate an immune mediated injury to the liver.
Nutritional. Patients with marasmus and kwashiorkor do not progress to Indian Childhood Cirrhosis. Good nutrition does not protect these children from the disease. Fatty change was minimal or absent.
Pathology

Gross general shape of the liver is maintained. The size is variable, and its color ranges from grey tan to frank green. The capsule shows patchy thickening, and the surface is finely nodular. The cut edge shows exaggerated lobular markings with small or no parenchymal nodules. The portal vein and the biliary passages are patent, the lymphatics appear normal.
Microscopic

The essential feature is marked hepatocyte damage, manifesting as degenerative changes in the cytoplasm. Fatty change is minimal. Clumps of eosinophilic hyaline are seen in the hepatocytes usually in the perinuclear area. This is called Mallory’s hyaline and is observed in about 15 percent of the hepatocytes. The nuclei appear more prominent in contrast to the pale cytoplasm. Mononuclear infiltration interspersed with a few polymorphonuclear leucocytes is seen in the mesenchyme. The fibrous septa are fairly cellular. Kupffer’s cells show mild degree of proliferation. The regenerative process is slow and this explains the absence of nodularity on gross examination of the liver. Cholestasis is seen intracellularly as well as in the form of canalicular and ductal plugs. The vascular channels are patent.

Clinical features

The onset is generally vague and ill defined, ranging from no symptoms to an icteric onset. Some infants get what is known as the pre-cirrhotic symptom complex characterized by irritability, disturbed appetite, chalky, pasty stools and distension of abdomen. There is variable constipation or diarrhea and often slight irregular fever. The failure to thrive is progressive despite an adequate diet. The patients with an icteric onset constitute 10 to 70 per cent of patients according to different workers. The jaundice either merges imperceptibly with cirrhosis or there is a symptom-free gap of a few months to a year followed by a florid type of cirrhosis.
There is diffuse hepatomegaly and the enlargement may be differential. The surface is smooth or finely nodular; coarse nodules are seldom palpable. The edge is typically sharp, leafy and well defined. The spleen is enlarged and ascites is usually present. Evidences of hepatocellular failure in the form of palmar erythema and spider nevi appear terminally. A peculiar garlic odor is present in patients with impending liver cell failure. Gastrointestinal bleeds though present are not very common, possibly because of the quick progression as the portovenous channels have not opened up. Terminally, there is jaundice and hepatic coma is often associated with       gastrointestinal bleeding.

Tuberculosis

In disseminated tuberculosis the hepatosplenomegaly is associated with low grade fever, weight loss, generalized lymphadenopathy. Ascites when present is exudative and not transudate, as in cirrhosis. The presence of pulmonary pathology and family history of tuberculosis may give a clue to the diagnosis.
Chronic hemolytic anemia.

Moderately severe progressive anemia non responsive to antianemic therapy, and hepatosplenomegaly which may or may not be associated with the typical thalassemia like facies suggest the clinical diagnosis of chronic hemolytic anemia. Spleen may regress in some cases of sickle anemia with history of repeated crises.
Persistent hepatitis. This may follow the usual viral hepatitis and should be diagnosed if the clinical course exceeds three months. A variable soft hepatomegaly with or without splenomegaly is observed. The transaminases are persistently elevated. Mild hyperbilirubinemia may be associated. The clinical course is slow and benign. Histopathological confirmation is essential for the diagnosis.
Chronic aggressive hepatitis

It is not a common sequel of hepatitis in infancy. Clinically the diagnosis is made on the basis of a multi-system involvement associated with moderate firm hepatosplenomegaly and variable ascites. The course is rapidly progressive and downhill.
Metabolic cirrhosis

These are rare causes. The clinical profile in all these shows involvement of other systems and features include rickets in cystinosis and tyrosinosis; hypoglycemia, cataracts, mental retardation in galactosemia; Kayser Fleischer rings, extrapyramidal involvement in Wilson disease, and diabetes and hyperpigmentation associated with hepatosplenomegaly in hemochromatosis.
Genetic causes of large liver in childhood. Wilson disease, galactosemia, fructosemia, glycogen storage disease type, tyrosinosis, alpha-1-antitrypsin deficiency, cystic fibrosis, Niemann-pick disease, cystinosis, cholesterol ester storage disease, Gaucher disease, Hurler syndrome, Byler disease, sickle cell disease and thalassemia.
Chronic malaria and kala-azar

History of malaria or kala-azar should be obtained in patients from endemic zones for these diseases. These diseases must be excluded before a diagnosis of Indian Childhood Cirrhosis is made specially because clinical distinction is often difficult.
Veno-occlusive disease

The clinical picture is similar. History of ingestion of heliotropes or toxic weeds is useful. Histopathological examination is necessary for confirmation of the diagnosis. It has been described recently from Afghanistan and some parts of Central India besides the previously reported cases from West Indies.
Non-genetic causes of cirrhosis of liver in childhood. Neonatal hepatitis, lesions of biliary tract as in biliary atresia, choledochal cyst, ascending cholangitis and cystic fibrosis, post hepatic causes e.g. acute viral hepatitis, chronic active hepatitis, drug toxins or poisons and radiation.