Autoimmune Hepatitis (AIH)

 

  • Disease of unknown cause characterized by-
  •          – Interface hepatitis
  •          – Lymphoplasmacytic infiltration of the portal tract on histologic examination
  •          – Hypergammaglobulinemia
  •         – Autoantibodies
  • Diagnosed by above features and exclusion of other chronic liver diseases

 

Epidemiology:

  • – Highest prevalence in north America and northern European white people
  • – F:M= 3:1
  • – Men are affected at an earlier age (peak in late teen)
  • – Peak incidence in women after menopause

 

                                          Classification

 

                   Type I AIH:

  • – Accounts for 90% AIH cases
  • – Characterized by SMA, ANA or both
  • – Concurrent extrahepatric immunologic diseases are common
  •                     Autoimmune thyroiditis
  •                     Grave’s disease
  •                     Pernicious anemia
  •                     Systemic sclerosis
  •                     Coombs positive hemolytic anemia
  •                     Celiac disease
  •                     ITP
  •                     Cryoglobulinemia
  •                     Leucocytic vasculitis
  •                     Nephritis
  •                     Erythema nodosum
  •                     SLE
  • – Acute onset is common presentation
  • – Variable clinical and histologic severity
  • – Rarely failure to treatment
  • – Variable relapse after drug withdrawal
  • – Variable need for long term maintenance therapy

 

                              Type II AIH:

  • – Accounts for 10% AIH cases
  • – Signature antibody: LKM1
  • – Associated antibody: Anti liver cytosol-1 (Anti LC-1)
  • – Age distribution: most are children (2-14 years)
  • Extra-hepatic autoimmune diseases:
  •                   Autoimmune thyroiditis
  •                   Vitiligo
  •                   Type I DM
  • – Frequent failure of treatment
  • – Frequent relapse after drug withdrawal

 

  •                                    Type III AIH:
  • – Type III AIH is characterized by the presence of ASLA (anti soluble liver antigen antibody)
  • – This classification type has been abandoned as ASLA present in 10-30% Type I and type II AIH patients
  • – ASLA is regarded as a possible prognostic marker for identifying patients who may relapse after cessation of corticosteroid therapy
  •                            Drug induced autoimmune-like hepatitis
  • – Circulating autoantibodies, elevated GGT and biopsy shows features similar to that seen in classic AIH
  • – Resolution occur after drug discontinuation but may require treatment with prednisolone
  • – Culprit drugs
  •                     Minocycline
  •                     Nitrofurantoin
  •                     Methyldopa
  •                    • Hydralazine

 

 

                              Clinical presentation of AIH:

 

  • Variable at the onset of disease
  • – Asymptomatic
  • – Acute AIH
  • – Fulminant liver failure
  • – End-stage liver disease
  • – Cholestatic feature may be present but they do not dominate the clinical picture
  • – Pruritus, hyperpigmentation, wt. loss virtually exclude the disease
  • Acute onset of AIH includes (25% AIH patients acutely)
  •         – Acute exacerbation of chronic AIH
  •        – True AIH without histologic findings of CLD
  •        – Centrilobular (zone3) necrosis usually present in acute presentation
  •        – Autoantibodies/other classical features may be absent

                     Physical findings

  • – Depends on clinical status of the patient
  • – Completely normal to features of CLD and or portal HTN

 

                      Complications of AIH:

  • – HCC is less common than other liver disease, but its occurrence is strictly associated with cirrhosis
  • – Drug related complications occur in 25% patients

 

                   Laboratory findings:

  • – Variable
  • Severe AIH: transaminase may elevate > 10 times ULN

               

          Histologic findings:

  • – Interface hepatitis
  • – Lymphocytic infiltration of portal area

 

                      

                  Figure: Patterns of Liver Damage

 

                                                  Simplified scoring system for the diagnosis of AIH

                           

 

 

       

  •                          Treatment of autoimmune hepatitis            
  •                                              (EASL-2015)

                                   

                               Aim of treatment

  • – Treatment of disease specific and treatment associated complications
  • – Complete biochemical and histological resolution of the disease
  • – Early recognition of extrahepatic manifestation of AIH associated other autoimmune diseases
  •                   Surveillance : All active AIH should be treated
  •                   Definition of biochemical response:
  • – Normalisation of IgG and transaminase
  • Definition of histological response:
  •           – Normal histology or minimal hepatitis(HAI<4 or equivalent)
  • ** Only patients in spontaneous remission may not require therapy but must be followed up 3-6 monthly

 

 

 

                       Remission induction

  • – Prednisolone followed by addition of azathioprine after 2 weeks
  • – Initial dose of prednisolone : 1 mg/kg/day
  • – Start azathioprine when bilirubin <6 mg/dl and ideally 2 weeks after initiation of steroid
  •                     Initial dose of AZA 50 mg/day
  •                     Maintenance dose: 1-2 mg/kg

 

  • In severe AIH
  •             – I.V corticosteroid ( ≥ 1mg/kg)
  •             – Lack of response within 7 days: liver transplantation
  • Treatment of sub-optimal response
  •             – Confirm diagnosis and adherence
  •            – Increase the dose of prednisolone and azathioprine or
  •            – Use alternative medication (Mycophenolate mofetil, tacrolimus)

 

                                       

 

                                                    Treatment withdrawal

  • – Immunosuppressive treatment should be continued for at least 3 years and for 2 years following complete normalization of transaminase and IgG
  • Treatment should not be discontinued if
  •            • There is no biochemical remission
  •             Continued histological disease activity (HAI >3)
  • – If biochemical response persists for 2 years, a liver biopsy should be considered before treatment withdrawal
  • – A relapse occurs most commonly within 12 months after treatment withdrawal
  • – An increase in IgG can precede the rise of transaminase
  • – If patient relapse during withdrawal or a flare occur during maintenance therapy, maintenance with immunosuppressant should be continued permanently

 

                                                              Maintenance of Remission

  • – In mild disease and if patient is intolerant to AZA, prednisolone can be considered for maintenance
  • – All other patients, Azathioprine (or MMF) should be the goal of maintenance therapy

                            


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