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MedimailJune 2019

Autoimmune Hepatitis (AIH)

• Characterised by –– Female predominance (female : male ratio 3 : 1)– Interface hepatitis– Interface hepatitis– Hypergammaglobulinaemia– Autoantibodies

• Can affect patients of all age groups• Peak age at first manifestation is between 40 & 50, but

manifestations in young childhood are also common• Children and younger adults often have acute disease onset• Children and younger adults often have acute disease onset• Subclinical and asymptomatic disease is common, AIH

therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes

Clinical Subtypes of AIH

Both types can have an acute, even fulminant, presentation, and prompt recognition and treatment are necessary to control inflammatory activity.

https://www.medscape.com/viewarticle/524097


Extrahepatic Disorders Associated with AIH

• As autoimmune hepatitis has a genetic predisposition, and like predisposition, and like other autoimmune diseases is associated with a variety of autoimmune conditions, both family conditions, both family and personal history should be taken carefully.

Lohse AW. Journal of Hepatology 2011 vol. 55 j 171–182

Diagnostic Criteria

• AIH should be considered in any patient with elevated liver enzymes and in any patient with cirrhosis.

• Diagnosis rests primarily on a high index of suspicion. • Diagnosis rests primarily on a high index of suspicion. • Heterogeneity of clinical presentation can make it difficult to

diagnose autoimmune hepatitis.• In 1993, International AIH Group devised a scoring system to help

standardization of patient populations in scientific publications. • This scoring system, revised in 1999, has also been applied by some

to daily clinical practice, for which it had not been primarily designed nor tested, and found to be very cumbersome. designed nor tested, and found to be very cumbersome.

• In 2008, International AIH Group suggested a simplified scoring system for clinical practice, which is useful in most cases.

Revised Criteria for Diagnosis of AIHInternational Autoimmune Hepatitis Group Report 1999

Alvarez F. J Hepatol 1999;31:929–938

Simplified Scoring for AIHInternational Autoimmune Hepatitis Group 2008

Hennes EM. Hepatology 2008;48:169–176Lohse AW. Journal of Hepatology 2011 vol. 55 j 171–182

Liver Chemistries

• Serum aminotransferases (aspartate aminotransferase [AST] and alanineaminotransferase [ALT]) are elevated in 100% of patients at initial presentation.

• Worsening of aminotransferase levels in a patient undergoing treatment • Worsening of aminotransferase levels in a patient undergoing treatment or in a patient who is in remission may signal a resurgence of disease activity.

• Serum bilirubin and alkaline phosphatase values are mildly to moderately increased in 80%-90% of patients. A sharp increase in the alkaline phosphatase values during the course of autoimmune disease might reflect the development of PSC or the onset of hepatocellular carcinoma as a complication of cirrhosis.as a complication of cirrhosis.

• Hypoalbuminemia and prolongation of the prothrombin time are markers of severe hepatic synthetic dysfunction, which may be observed in active disease or decompensated cirrhosis.

https://emedicine.medscape.com/article/172356


IgG or Gamma Globulins

• Elevated IgG with normal levels of IgA and IgM –characteristic of AIH.

• 5-10% of AIH patients are reported to have normal • 5-10% of AIH patients are reported to have normal IgG levels at diagnosis because although they have significantly increased IgG levels during phases of disease activity, but this increase may remain within the normal range.

• Patients with AIH-2 commonly have partial • Patients with AIH-2 commonly have partial immunoglobulin A (IgA) deficiency.

• Also helpful in monitoring disease activity during treatment.

Autoantibodies

• Autoimmune hepatitis is characterized by positive findings on autoantibody tests, as follows:

– AIH-1 - ASMA and ANA– AIH-2 - Anti–LKM-1 antibody– AIH-2 - Anti–LKM-1 antibody– AIH-3 - Antibodies to soluble liver antigen (anti-SLA)

• SMAs - present in 90%-100% of patients with AIH-1. ANAs are present in 10% of patients with AIH-1 and in association with SMAs in 40%-60% of patients with AIH-1.

AIH type Conventional Autoantibodies Nonconventional AutoantibodiesAIH type 1* ANA, ASMA pANCA, anti-SLA/LP

AIH type 2** Anti-LKM1 Anti-LC1, anti-LKM3, anti-SLA/LP

patients with AIH-1.• LKM-1 antibodies are present in 40%-45% of patients with AIH-2 and are

associated with anti-LC1 antibodies in 50% of patients. Anti-LC1 antibodies occur alone in 30% of patients with AIH-2.

• Other autoantibodies may be evident. Atypical perinuclear antineutrophilcytoplasmic antibodies (pANCA) are frequently present.



Histology

• Necessary prerequisite for diagnosis of AIH.• However, histology is not diagnostic in itself.• Revised scoring system distinguishes histology ‘‘compatible with AIH’’,

scoring as 1 point, from histology ‘‘typical for AIH’’, scoring as 2 points. scoring as 1 point, from histology ‘‘typical for AIH’’, scoring as 2 points. • Compatible with AIH is almost any hepatitic picture not suggestive of non-

alcoholic steatohepatitis (NASH) or drug-induced inflammation. • Characteristic features suggesting typical AIH include interface hepatitis,

portal and periportal inflammation, presence of plasma cells, rosetting of hepatocytes, and emperipolesis.


Diagnostic Algorithm for AIH



Management Algorithm for Patients with Definite AIH

Complete remission is defined as both AST and ALT as well as IgGbelow the upper limit of normal. Incomplete remission is defined as improvement of AST/ALT within 2 the upper limit of normal, or normalization of AST and ALT without complete normalization of IgG.


Management Algorithm for Patients with Possible AIH


Characteristics of Variant Syndromes

Ben-Ari, Czaja. Gut 2001;49:589–594

Points to Consider in AIH

• Despite several studies having confirmed the value of the diagnostic score in clinical practice, two subgroups of patients may be missed by standard diagnostic criteria and require special attention: 1. Acute and fulminant AIH1. Acute and fulminant AIH2. Pediatric AIH

• Absence of viral hepatitis was generally thought to be a prerequisite for making a diagnosis of AIH, but in a few patients viral and AIH may co-exist.

• Cirrhosis in AIH is often irregular and macronodular, and may easily be overlooked by percutaneous liver biopsy.

– Laparoscopy is helpful in making a diagnosis of cirrhosis in AIH, as cirrhosis may be overlooked in up to 40% of cases without macroscopic assessment of the liver. overlooked in up to 40% of cases without macroscopic assessment of the liver.

– Diagnosis of cirrhosis may influence the choice and dose of the immunosuppressive agents prescribed, has prognostic implications, and forms the basis for regular screening for complications of cirrhosis, such as esophageal varices or hepatocellular carcinoma.

• Response to immunosuppression is characteristic and supports the diagnosis.

• Liver biopsy is recommended prior to trial of treatment withdrawal.

Tests Done in SRLTEST METHOD CODE

Biopsy (Small Tissue Biopsy/ Specimen) Histopathology 1500

Liver Biopsy with special stains Histopathology 1663Liver Biopsy with special stains Histopathology 1663

Histopath Reflex to Custom IHC Panel - Liver Biopsy Immunohistochemistry 9243RFX

IgA, IgM & IgG Immunoglobulin,Quantitative Nephelometry 1045

Autoimmune Hepatitis Panel-1 (ANA, SMA, AMA, LKM-1)

Immunofloroscence Assay/ Enzyme Immunoassay 1019A

Autoimmune Hepatitis Panel-2 (ANCA, SLA) Immunofloroscence Assay/ Enzyme Immunoassay 1019B

17

Enzyme Immunoassay

Hepatitis Screening Panel (CBC, SGPT, SGOT, Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, HBsAg, HAV IgM, Hepatitis E IgM)

Automated Cell Counter/ Automated (Micro -

Agglutination) and ModifiedWestergren Method/

Spectrophotometry/ ELISA/ Enzyme Immunoassay

5011

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