Overall Bottom Line
- AIH is characterized by immune-mediated destruction of hepatocytes leading to either acute liver failure or chronic liver disease.
- AIH is most often confused with drug-induced liver disease.
- The disease preferentially affects women under age 60 and typically responds well to treatment with immunosuppressive agents.
- Overlap syndromes exist in which features of both autoimmune hepatitis and cholestatic liver disease are present.
Section 1: Background
Definition of disease
- AIH is a chronic (>6 months) progressive immune-mediated inflammation of the liver, histologically most commonly characterized by an interface hepatitis, biochemically by a marked hypergammaglobulinemia, high titers of autoantibodies, elevated aminotransferases, and clinically by fatigue.
- AIH-overlap syndromes are characterized by the concomitant occurrence of AIH with PBC or PSC.
Disease classification
- Over time the classification of AIH has been changed multiple times. The current classifications are:
Type 1 AIH
- The most common form of AIH. It is distinguished by serum ANA or ASMA, elevated IgG levels and elevated aminotransferase levels.
Type 2 AIH
- Distinguished by anti-LKM autoantibodies in the presence of elevated aminotransferase levels. This form of AIH more often occurs in children and is more common in Europe than the USA.
- Of patients with the autoimmune polyglandular syndrome 1 10–15% also have type 2 AIH.
Type 3 AIH
- Characterized by antibodies against soluble antigen from liver and pancreas (anti-SLA/LP) in the presence of elevated aminotransferase levels.
AIH–PBC overlap syndrome
- Infrequently individuals meet criteria for both AIH and PBC with both ANA and AMA present. Histology and significantly elevated aminotransferases consistent with AIH are usually required for this diagnosis beyond just the presence of ANA and AMA together.
AIH–PSC overlap syndrome
- In addition to meeting criteria for AIH, evidence of extra- or intra-hepatic bile duct stenosis/dilatation is observed. This uncommon overlap is more frequent in children and may be a triad of disease that includes IBD.
Prevalence
- The overall disease prevalence is approximately 10 in 10 000 and peak onset is typically in young or middle-aged individuals.
- The prevalence is threefold higher in women than men.
Economic impact
- Due to the limited number of affected individuals the overall economic impact of AIH is not very high; however, the costs for individual treatment can be high since lifelong treatment with immunosuppressive drugs and possibly liver transplantation may be necessary.
- According to UNOS a single liver transplant costs $314 600 on average with annual follow up care costs averaging $21 900.
Etiology
- Drug or environmental toxin exposures may trigger an autoimmune response directed against hepatocytes. A classic example is halothane exposure triggering AIH.
Pathophysiology
- The mechanism by which a drug or environmental toxin induces AIH is uncertain. There may be cross-reactivity with a self-antigen or exposure may lead to modification of a self-antigen making it immunogenic.
- Activation of autoreactive lymphocytes leads to primarily T-cell mediated destruction of hepatocytes, chiefly in zone 1 of the hepatic lobule bordering the portal tract (i.e. interface hepatitis).
- The disease activity may flare periodically with long quiescent periods or more rarely progress slowly to cirrhosis without any flares. In the latter group, aminotransferase levels may be relatively normal.
Risk factors
- Age (less than 60) and gender (female) are the primary risk factors.
- Those with other autoimmune diseases are more likely to develop AIH.
- Pregnancy is also a risk factor for disease onset and flares.
- Medications including minocycline and nitrofurantoin may cause a drug-induced AIH.
Section 2: Prevention
- Prevention of AIH is not generally considered feasible beyond avoidance of drugs and toxins known to induce AIH.
Screening
- Screening for AIH is not cost effective in any at risk group.
Primary prevention
- Avoid drugs or toxins known to induce AIH.
Secondary prevention
- Maintenance immunosuppressive therapy reduces the number of disease flares in individuals diagnosed with recurrent AIH.
Section 3: Diagnosis (Algorithm 12.1)
Clinical Pearls
- AIH should be suspected in any person who presents with unexplained fatigue or jaundice and elevated aminotransferase levels, particularly younger women.
- ANA, ASMA, and anti-LKM levels should be checked.
- If these autoantibodies are absent in the presence of cryptogenic chronic hepatitis, anti-SLA/LP should be checked.
- A liver biopsy should be performed if AIH is suspected.
- The elevation in serum AST and ALT levels usually occurs at a 1:1 ratio.
- If AP or GGT levels are also significantly elevated, additional evaluation should be done to rule out alcoholic hepatitis or cholestatic liver disease (e.g. PBC, PSC).
- A validated scoring system has been developed by the IAIHG to aid in diagnosis since many features of autoimmune hepatitis are non-specific.
- Patients with type 3 AIH (anti-SLA/LP positive) do not differ from those with classic type 1 AIH with respect to age, gender and the response to immunosuppressive therapy. Antibodies against SLA/LP do not define a clinically discrete form of AIH, but they may be regarded as a specific diagnostic marker of AIH. The search for anti-SLA/LP attains special importance in patients with cryptogenic chronic hepatitis. Approximately 25% of these patients have anti-SLA/LP in serum, allowing for a change in diagnosis from cryptogenic hepatitis to AIH in which conventional autoantibodies are absent.
Simplified diagnostic criteria for AIH (Source: Hennes et al, 2008. Reproduced with permission of John Wiley & Sons Ltd.)
Differential diagnosis
| Differential diagnosis | Features |
|---|---|
| PBC | AMA and elevated AP levels are detectable along with intra-hepatic portal tract inflammation |
| PSC | Extra- and/or intra-hepatic abnormalities of the biliary tree are detectable on imaging. Atypical p-ANCA more likely present and associated with IBD |
| Viral hepatitis | Serological evidence of viral infection |
| Drug-induced liver injury | History of drug or toxin exposure. If LFT elevations persist after discontinuation of exposure, AIH may be present |
| Wilson disease | Kayser–Fleischer rings may be present. Low serum ceruloplasmin and high urinary copper level. Neurological or behavioral changes may be present |
Related posts:
24: Portopulmonary Hypertension
25: Pregnancy-Related Liver Disease
38: Liver Transplantation: A Pediatric Perspective
36: Approach to Jaundice in Infancy
53: Recurrent Disease Post-Liver Transplantation: Autoimmune Diseases, Hepatitis B and NASH
34: Diagnosis and Management of Acute Liver Failure: A Pediatric Perspective
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