Overview
Definition:
Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease characterized by the presence of autoantibodies, elevated serum immunoglobulins, and characteristic histological findings of interface hepatitis, plasma cell infiltration, and lobular inflammation.
Epidemiology:
AIH affects children and adults, with a bimodal age distribution peaking in adolescence and early adulthood
In pediatrics, it accounts for approximately 10-20% of chronic hepatitis cases
It is more common in females, with a female-to-male ratio of 3:1 to 4:1.
Clinical Significance:
Early diagnosis and prompt treatment are crucial in pediatric AIH to prevent irreversible liver damage, fibrosis, cirrhosis, and potential complications like portal hypertension and liver failure
Effective management with immunosuppressants can lead to sustained remission and improve long-term outcomes, impacting patient morbidity and mortality significantly.
Clinical Presentation
Symptoms:
Asymptomatic presentation is common, often discovered incidentally during routine investigations
Symptomatic children may present with fatigue
Jaundice, often icterus or scleral icterus
Abdominal pain, typically in the right upper quadrant
Nausea and vomiting
Arthralgias or arthritis
Amenorrhea or irregular menstruation in adolescents
Other extrahepatic autoimmune manifestations may be present.
Signs:
Hepatomegaly, which may be firm and tender
Splenomegaly can develop due to portal hypertension
Ascites and peripheral edema indicate decompensated liver disease
Spider angiomata and palmar erythema may be seen in chronic disease
Signs of portal hypertension such as caput medusae and esophageal varices
Jaundice or pale stools.
Diagnostic Criteria:
International Autoimmune Hepatitis Group (IAIHG) criteria are widely used, though modified versions exist
Key components include elevated ALT/AST, presence of autoantibodies (ANA, SMA, anti-LKM1), elevated IgG, histology showing interface hepatitis, and exclusion of other causes like viral hepatitis and drug-induced liver injury
Scoring systems aid in diagnosis and distinguishing AIH types.
Diagnostic Approach
History Taking:
Detailed history of onset of symptoms, duration, and progression
Inquire about family history of autoimmune diseases or liver conditions
Review medications, recent infections, and travel history
Assess for extrahepatic autoimmune symptoms such as thyroid disease, vitiligo, inflammatory bowel disease, or type 1 diabetes
Screening for associated conditions like celiac disease is important.
Physical Examination:
Comprehensive assessment of general condition
Palpation of abdomen for hepatomegaly and splenomegaly
Auscultation for ascites
Examination of skin for jaundice, spider angiomata, palmar erythema, and vitiligo
Assessment for signs of chronic liver disease and portal hypertension.
Investigations:
Liver function tests (LFTs): Elevated ALT and AST are typical, often disproportionate to bilirubin levels
Elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) may be seen
Serum bilirubin may be normal or elevated
Serum immunoglobulin G (IgG) levels are characteristically elevated, often >1.5 times the upper limit of normal
Autoantibodies: Antinuclear antibody (ANA) and smooth muscle antibody (SMA) are common in Type 1 AIH
Anti-liver kidney microsome type 1 (anti-LKM1) antibody is characteristic of Type 2 AIH
Anti-soluble liver antigen (anti-SLA) antibody is seen in Type 3 AIH
Viral serologies: Hepatitis A, B, and C virus serologies must be negative
Autoimmune markers: Thyroid autoantibodies (anti-TPO, anti-thyroglobulin), anti-smooth muscle actin antibodies, and others may be positive
Liver biopsy: Essential for diagnosis, showing interface hepatitis, lobular inflammation, plasma cell infiltration, and fibrosis
Viral hepatitis markers, Wilson's disease evaluation (serum ceruloplasmin, copper), and alpha-1-antitrypsin levels should be checked to exclude other causes of chronic hepatitis.
Differential Diagnosis:
Viral hepatitis (HAV, HBV, HCV, HEV)
Drug-induced liver injury
Wilson's disease
Alpha-1-antitrypsin deficiency
Non-alcoholic steatohepatitis (NASH)
Autoimmune/cholangiopathy overlap syndromes
Primary biliary cholangitis (PBC)
Primary sclerosing cholangitis (PSC)
Genetic conditions affecting liver
Biliary atresia in infants.
Management
Initial Management:
Once diagnosis is confirmed, initiation of immunosuppressive therapy is paramount
The goal is to suppress the autoimmune attack on the liver and achieve biochemical and histological remission
Close monitoring of LFTs and clinical status is essential.
Medical Management:
Steroids: Prednisolone is the first-line treatment, typically initiated at 1-2 mg/kg/day orally (maximum 60 mg/day) until biochemical remission (normal LFTs) is achieved, usually within 2-4 weeks
Once remission is attained, the dose is gradually tapered to a maintenance dose, often 0.1-0.2 mg/kg/day
Azathioprine: Used as a steroid-sparing agent, usually added after achieving remission with steroids
It is initiated at 1-1.5 mg/kg/day orally (maximum 100-150 mg/day)
Azathioprine helps to reduce steroid-related side effects and maintain remission
Combination therapy with low-dose steroids and azathioprine is the standard maintenance regimen
Mycophenolate mofetil (MMF) can be an alternative in steroid-refractory or intolerant patients, dosed at 600-1200 mg/m2/day
Tacrolimus is also an option for refractory cases.
Surgical Management:
Liver transplantation is reserved for patients with end-stage liver disease, decompensated cirrhosis, intractable disease, or hepatocellular carcinoma that is not amenable to other treatments
It is a life-saving option for those with severe, unresponsive AIH.
Supportive Care:
Nutritional support: Ensuring adequate caloric and protein intake is vital
Vitamin supplementation (fat-soluble vitamins) may be necessary in cases of malabsorption
Monitoring for side effects of immunosuppressive therapy, including bone marrow suppression (leukopenia, thrombocytopenia), gastrointestinal upset, and increased infection risk
Regular monitoring of blood counts and liver enzymes is crucial.
Complications
Early Complications:
Steroid-induced side effects: Cushingoid features, weight gain, osteoporosis, hypertension, hyperglycemia, mood changes, and increased susceptibility to infections
Azathioprine-induced side effects: Bone marrow suppression (leukopenia, anemia, thrombocytopenia), pancreatitis, and gastrointestinal intolerance.
Late Complications:
Fibrosis progression leading to cirrhosis
Portal hypertension with complications like ascites, variceal bleeding, and hepatic encephalopathy
Hepatocellular carcinoma (HCC) risk is increased, though lower than in viral hepatitis-related cirrhosis
Liver failure requiring transplantation.
Prevention Strategies:
Careful steroid dose tapering to minimize side effects
Use of azathioprine or MMF as steroid-sparing agents
Regular monitoring of blood counts and LFTs
Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) may be considered in patients on high-dose immunosuppression
Screening for osteoporosis
Close follow-up with a hepatologist.
Prognosis
Factors Affecting Prognosis:
Response to immunosuppressive therapy, presence of cirrhosis at diagnosis, genotype, and adherence to treatment regimen are key prognostic factors
Early diagnosis and prompt, consistent treatment lead to better outcomes.
Outcomes:
With appropriate treatment, a significant proportion of pediatric patients achieve long-term remission, with normal or near-normal LFTs and histology
Sustained remission allows for dose reduction or even discontinuation of therapy in some cases
However, some patients may require lifelong immunosuppression.
Follow Up:
Lifelong monitoring is recommended
Regular clinical assessments and biochemical monitoring (LFTs, IgG) are required
Bone density screening and monitoring for steroid side effects are essential
Screening for HCC may be indicated in patients with cirrhosis.
Key Points
Exam Focus:
Distinguish AIH from other causes of chronic hepatitis in children
Recognize typical autoantibody profiles (Type 1 vs
Type 2)
Understand the stepwise approach to immunosuppressive therapy: induction with steroids followed by maintenance with azathioprine
Be aware of steroid and azathioprine side effects and monitoring requirements
Know indications for liver transplantation.
Clinical Pearls:
Always consider autoimmune etiology in unexplained chronic hepatitis, especially in young females
A liver biopsy is crucial for definitive diagnosis and assessment of fibrosis
Early introduction of azathioprine can significantly reduce steroid-related morbidity
Maintain a high index of suspicion for associated autoimmune disorders.
Common Mistakes:
Delaying diagnosis due to atypical presentation or not performing comprehensive autoantibody screening
Inadequate immunosuppression leading to treatment failure
Over-reliance on steroids without timely introduction of azathioprine
Failure to monitor for and manage drug-induced side effects
Not excluding other causes of chronic liver disease before commencing immunosuppression.