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Subject: Autoimmune Hepatitis
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Autoimmune hepatitis (AIH) is a chronic inflammatory disease of unknown cause, which leads to the progressive destruction of the liver parenchyma.
Characterized by: Interface hepatitis by histological exam, and/or hypergammaglobulinemia, and/or circulating auto-antibodies
Type I + antinuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)
Type II + antiliver/kidney/microsomal antibodies (LKM/LC-1)
Anti-neutrophilic circulating antibody (pANCA) and soluble liver antibodies (SLA) can be used as surrogate markers in absence of conventional auto antibodies profile.
AIH has features in common (10%) with primary sclerosis cholangitis (PSC), primary biliary cirrhosis (PBC), and autoimmune cholangitis.
AIH affects predominantly women of all ages, all ethnic origins.
1/2 of the patients with type I classic AIH are women under age of 40.
Gender ratio: 3.6:1
Clinical course is more aggressive in children.
Elderly may have milder disease.
AIH accounts for 5.6% of all liver transplants in the US.
AIH Type I DRB1*0301: Younger patients, aggressive disease, less response to therapy
AIH Type I DRB1*0401: Older patients, better response to therapy
AHI Type II DRB1*0701: More common in Southern Europe
External factors interacting with host genetic susceptibility trigger immunoreactions targeted to hepatic cells.
Antibody-dependent and cellular-mediated hepatocyte cytotoxicity
Targeted antigens in the liver are not known.
Serum autoantibodies are not involved in the direct damage; useful in diagnosis and monitoring.
Inflammation causes necrosis and fibrosis deposition in the liver parenchyma.
Methyldopa, minocycline, isoniazid, nitrofurantoin, hydralazine
Drug-induced AIH responds to drug withdrawal.
Diabetes mellitus type1
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED syndrome)
Easy to make diagnosis in typical cases
No pathognomonic features
Diagnostic criteria have been codified and updated by an international panel (IAHG) and require the presence of characteristic features and exclusion of other known causes of liver disease.
A scoring system that attributes negative and positive points to clinical and laboratory features is useful in difficult diagnoses (1)[A].
Personal or family history of autoimmune diseases
History of medications known to cause chronic hepatitis
Personal history of other liver diseases
Inquire about alcohol use
Signs and symptoms:
Right upper quadrant discomfort
Acute hepatitis: 30–40% of all cases, usually symptomatic
Chronic hepatitis: Usually asymptomatic, discovered during routine work-up for abnormal liver function tests (LFTs)
Cirrhosis: 25% of patients have cirrhosis at time of initial presentation
1/2 of children with AIH will present with cirrhosis
Jaundice, muscular wasting, spider angioma
AST and ALT >5 × normal
Polyclonal hyperglobulinemia globulin ≥1.5 × normal
ANA, SMA, SLA, pANCA, LKM1 ≥1:80
Absent marker of viral infection (EBV, Hep A, B, C)
Normal alpha-1 antitrypsin phenotype, ceruloplasmin
Periportal hepatitis (interface hepatitis)
Predominant lymphocytes, plasma cells often present
Variable degree of fibrosis
Absence of biliary changes and granulomas
PBC: Autoimmune chronic hepatitis with destruction of biliary epithelia leading to cirrhosis may present with AIH feature
AMA often present (rarely in AIH)
Biliary epithelia infiltration, granulomas in liver biopsy
Abnormal endoscopic retrograde cholangiopancreatography
Predominantly cholestatic picture
Overlapping syndromes and atypical presentations pose a diagnostic challenge in these cases.
Order additional antibodies (pANCA, anti-LC-1, anti-SLA, anti-ASGPR)
Use IAHG score system
AIH may occur de novo in pregnancy.
Liver biopsy must be performed if suspected and therapy started.
AIH might improve during pregnancy (2)[C].
Pregnant women with AIH have higher frequency of prematurity, low birth weight infants, and fetal losses. Acute fulminant hepatitis has been reported (2)[B].
Exacerbation of the disease commonly follows delivery.
Corticosteroids and azathioprine are likely safe in pregnancy but prednisolone alone is the preferred treatment.
In the first 3 years of therapy, 80% of the patients will achieve biochemical and histological remission (3)[B].
Long-term remission: 15% after drug withdrawal
Approximately 85% will relapse after discontinuation of the therapy and require long-term treatment.
Prompts reevaluation of diagnosis
Consider an increased dose or change in regimen
Acute severe hepatitis not responding to therapy should be referred for liver transplant.
Absolute indication for therapy: AST >10 × normal; AST >5 × upper limit of normal and gamma globulin level >2 × normal; bridging or multilobular necrosis in biopsy (4)[A]
The benefit of therapy in mild, asymptomatic disease has not been established and should be balanced with the risks of therapy (5)[B].
Prednisone alone 60 mg/day or prednisone 30 mg/day + azathioprine 1–2 mg/kg/day (4)[A]
Use a prednisone tapering schedule to reach the maintenance dose of 10–20 mg/day in 4–6 weeks.
Clinical and biochemical normalization occurs in first 3–6 months. Histology lags behind.
The duration of therapy has not been established; however, after initial tapering, maintenance doses should be continued at least for 1 year.
Repeat liver biopsy 3 months after normalization of laboratories indices is the only confident method to confirm the treatment endpoint (4)[B].
Relapse: Reinstitute original treatment schedule. Long-term treatment with azathioprine 2 mg/kg/day after complete steroid tapering is preferred treatment after the first exacerbation (4)[B].
Mycophenolate mofetil, cyclosporine A, tacrolimus
Budesonide can be used as first line in non-cirrhotic patients to minimize corticosteroid side effects (6)[B].
Refer to a hepatologist for liver biopsy and initial diagnosis and treatment.
Refer to transplantation center for decompensated liver disease.
None have been demonstrated effective
Consider possible hepatotoxicity of herbal preparations
Acute liver failure and decompensated cirrhosis benefit from liver transplant.
Disease will recur, but is generally mild and does not affect graft survival.
Outpatient treatment is the norm.
Acute hepatitis may require hospitalization if severe.
Acute liver failure has been described (rare)
Monitor coagulopathy and mental status
A liver transplant is indicated for acute liver failure.
Follow aminotransferases and gamma globulin to normalization
Long-term therapy with immunosuppressants may be required if remission is not achieved.
Liver biopsy at 1 year of therapy is required for the diagnosis of sustained remission and the discontinuation of therapy.
Decompensated liver disease requires dietary modification (salt, water, and animal protein restriction).
Survival at 10 years: 10%
Improves to 80–93% with corticosteroid treatment (4)[A]
Hepatocellular carcinoma is rare
Presents as acute or chronic hepatitis
More frequent in women
It is associated with other autoimmune diseases.
Active disease progresses to end-stage liver disease without treatment.
Prognosis with treatment is generally good.