What is autoimmune hepatitis?

‘Autoimmune’ is made of two words- ‘auto’ +’immune’- implying altered immunity to cells of one’s own body. Immune system normally recognises ‘self ‘and ‘non-self’ cells. It kills only the ‘non-self’ cells. When there is an alteration in the immune system, it loses this ability to differentiate ‘self’ from ‘non self’; and kills ‘self’ cells.

When such attack of the immune system involves cells of liver, it causes Autoimmune Hepatitis. It may occur as only hepatitis or may occur as a part of other autoimmune diseases.

 

What causes autoimmune hepatitis?

The cause of ‘autoimmunity ‘is hyper-reactive immune system killing the cells of own body. The reason or trigger for this hyper – reactivity is largely unknown. There are some loosely known associations with infections, drugs etc but nothing can be said certainly.

 

What are the symptoms of the disease?

There are various known presentations of this disease. These include:

• Acute Hepatitis like- symptoms include anorexia i.e. ‘ not wanting to eat’, malaise, nausea, vomiting, followed by jaundice, dark colored urine and pale colored stools. There may be right sided abdominal pain. A doctor may be able to detect an enlarged , tender liver. Some such children may progress to acute liver failure- i.e. symptoms like bleeding, altered sleeping patterns, seizures, deep jaundice, may be even coma.

• Chronic hepatitis like- symptoms include slowly progressive loss of appetite, fatigue, weight loss, relapsing jaundice, headache etc lasting for almost 6-24 months.

• Chronic liver disease with complications like- ascites i.e. fluid in abdomen, portal hypertension causing bleeding from the gut in form bloody vomits or black stools, low blood count because of an enlarged spleen and altered behaviour.

 

When to suspect autoimmune hepatitis?

Autoimmune hepatitis is a relatively rare disease. Doctors usually suspect this disease only after ruling out other causes of acute and/or chronic liver disease as per the presentations. The usual causes which are ruled out before looking for autoimmune hepatitis are infections like hepatitis A, Hepatitis E for acute presentation and hepatitis B and hepatitis C for chronic presentations. Rare causes include drugs causing hepatitis, Wilson’s disease, and other metabolic diseases, which may be genetically inherited.

How to diagnose autoimmune hepatitis?

 

The diagnosis of autoimmune hepatitis is based on the liver function tests and presence/absence of certain markers and liver biopsy.

Liver function tests are ALT and AST, which are increased in the active phase of the disease and other tests like PT/INR, bilirubin, albumin.

 

Important markers whose presence or absence aids the diagnosis include the following:

• Ig G- increased

• Antinuclear Antibodies

• Smooth muscle Antibody

• Anti-Liver kidney Mitochondrial Antibody

In children, often these markers may be negative at the initial setting. However, if the index of suspicion is high, then a repeat test with lesser dilution (1:20) should be performed and diagnosis confirmed. However, a subset of children may have all above markers negative and still be worked up and diagnosed as autoimmune hepatitis on liver biopsy (sero-negative hepatitis)

Liver biopsy is necessary for diagnosis of autoimmune hepatitis. Characteristic biopsy findings in the liver biopsy help clinch the diagnosis. Also, a repeat biopsy after treatment helps your doctors decide about how the child has responded to the treatment and how long to continue treatment if necessary.

 

Tests to rule out infections and metabolic causes may be needed before confirming the diagnosis of autoimmune hepatitis. Your doctor would also do the tests for Wilson’s disease like serum ceruloplasmin level and 24 hour urinary copper excretion to rule out Wilson’s disease prior to definitely diagnose autoimmune hepatitis as there is often overlap between Wilson’s disease and autoimmune hepatitis.

 

 

What are the types of Autoimmune Hepatitis?

 

On the basis above mentioned serum markers, the patients of autoimmune hepatitis are divided into two groups:

• Type I- ANA positive, usually older age of presentation around 10 years or more.

• Type II- LKM I positive, seen in younger children with a lesser age of presentation around 6-7 years. This hepatitis is rarely seen in adults.

 

 

How to treat autoimmune hepatitis?

 

Steroids are the corner stone of treatment for autoimmune hepatitis. Oral corticosteroids like Prednisolone are the drug of choice for treatment of autoimmune hepatitis.

 

Immunomodulators like azathioprine are also used for treatment of autoimmune hepatitis. These are used in patients not responding to steroids or showing signs of steroid toxicity like cataracts, growth disturbances, weight gain etc.

 

Other immunomodulators like cyclosporine and mycophenolate mofetil can be used but their usage is limited by availability and cost to children not responding to azathioprine trial.

 

Children in whom corticosteroids may not help are those who present with acute liver failure. These children usually require urgent liver transplant as a life saving procedure.

Liver transplant is also indicated in children with chronic liver disease with complications like massive bleeding varices or other complications due to chronic liver failure and cirrhosis, where the disease is far advanced.

 

 

How long the treatment should be continued?

 

Since autoimmune hepatitis is a slowly progressive ongoing disease, steroids are to be used for a prolonged period usually for 2-3 years. To start with, doses of steroids are high and they are gradually reduced over a period of time depending upon the laboratory results- ALT/AST. Hence these blood tests will have to be done on a regular basis.

 

Definitive remission i.e. reduction of disease is confirmed on a biopsy in a child who is responding well to treatment decided on the basis of laboratory results.

 

It has been observed that type 1 autoimmune hepatitis have a better response to drug therapy and earlier disease reduction as compared to type 2, although it is not a thumb rule.

 

Is the treatment definitive?

 

In children, relapses after treatment are known in about 50% of children especially those who are LKM1 positive. In such children lifelong immunosupression may be needed.

Treatment failure and disease progression is known in another 20% of children. For such children, liver transplant could be considered; though recurrence of the disease is also known post transplant in about 20% of patients.

 

 

If one of my children is affected, will other children be affected?

 

There is a genetic predisposition in children with autoimmune hepatitis. However, exact probability of inheritance is not known.

 

Important articles about autoimmune hepatitis:

 

Autoimmune liver disease in children

Yachha SK1, Srivastava A, Chetri K, Saraswat VA, Krishnani N. J Gastroenterol Hepatol. 2001 Jun;16(6):674-7.

http://www.ncbi.nlm.nih.gov/pubmed/11422621

 

Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics.

Nikolaos K Gatselis, Kalliopi Zachou, George K Koukoulis, George N Dalekos. World J Gastroenterol 2015 January 7; 21(1): 60-83.

http://www.ncbi.nlm.nih.gov/pubmed/25574080

 

Autoimmune hepatitis in children: an overview of the disease focusing on current therapies.

Della Corte C1, Sartorelli MR, Sindoni CD, Girolami E, Giovannelli L, Comparcola D, Nobili V.

Eur J Gastroenterol Hepatol. 2012 Jul;24(7):739-46.

http://www.ncbi.nlm.nih.gov/pubmed/22495399

 

Fulminant hepatic failure of autoimmune aetiology in children.

Di Giorgio A1, Bravi M, Bonanomi E, Alessio G, Sonzogni A, Zen Y, Colledan M, D'Antiga L. J Pediatr Gastroenterol Nutr. 2015 Feb;60(2):159-6

http://www.ncbi.nlm.nih.gov/pubmed/25304891

 

Significance of histopathological features in differentiating autoimmune liver disease from nonautoimmune chronic liver disease in children.

Kumari N1, Kathuria R, Srivastav A, Krishnani N, Poddar U, Yachha SK. Eur J Gastroenterol Hepatol. 2013 Mar;25(3):333-7

http://www.ncbi.nlm.nih.gov/pubmed?term=Eur+J+Gastroenterol+Hepatol.+%5B...

 

Diagnostic criteria for autoimmune hepatitis in children: A challenge for pediatric hepatologists

Priscila Menezes Ferri, Alexandre Rodrigues Ferreira, Débora Marques Miranda, Ana Cristina Simões e Silva. World J Gastroenterol 2012 September 7; 18(33): 4470-4473.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435769/

 

Autoimmune hepatitis in childhood: The role of genetic and immune factors

Priscila Menezes Ferri Liu, Débora Marques de Miranda, Eleonora Druve Tavares Fagundes,

Alexandre Rodrigues Ferreira, Ana Cristina Simões e Silva. World J Gastroenterol 2013 July 28; 19(28): 4455-4463.

http://www.ncbi.nlm.nih.gov/pubmed/23901220

 

Clinicopathological profile and management of severe autoimmune hepatitis.

Ramachandran J, Sajith KG, Pal S, Rasak JV, Prakash JA, Ramakrishna B. Trop Gastroenterol. 2014 Jan-Mar;35(1):25-3.

http://www.ncbi.nlm.nih.gov/pubmed/25276903

 

Autoimmune hepatitis in a teenage boy: 'overlap' or 'outlier' syndrome--dilemma for internists.

Talukdar A1, Khanra D, Mukherjee K, Saha M. BMJ Case Rep. 2013 Feb 8;2013.

http://www.ncbi.nlm.nih.gov/pubmed/23396934