Place of Steroid Therapy in Severe and Fulminant Form of Autoimmune Hepatitis AIH

1
Place of Steroid Therapy in Severe and Fulminant
Form of Autoimmune Hepatitis (AIH)

• P Ichai, JC Duclos-Vallée, M Gonzalez, D Azoulay,
  D Castaing and D Samuel

Centre Hépato-Biliaire, Liver Intensive Care
Unit, Hôpital Paul Brousse, Faculté de Médecine
Paris Sud Villejuif - France
2
Introduction

• Steroids represent the current management of
  therapy in AIH with a remission rate of 30 .
• However the interest, the time of introduction
  and the potential secondary effects of this kind
  of the therapy in severe form and particularly in
  fulminant AIH are not certain.
• Moreover, the fact that steroid therapy could
  avoid liver transplantation must be confirmed.

3
Methods (1)

• Diagnostic Criteria for suspected Autoimmune
  Hepatitis were
• No active viral infection
• Increased ALT
• Immunoglobulin G gt 1,5 times normal
• Antinuclear antibodies (ANA), Smooth Muscle
  antibodies (SMA), or Anti LKM-1 gt 1/80
• No antimitochondrial antibodies

4
Methods (1)

• Histologic findings if a liver biopsy was made at
  admission
• Interface hepatitis
• No biliary lesions, granulomas or changes
• suggestive of another disease
• Plasma cell infiltrate
• Prednisolone Therapy (1 mg/kg) was indicated in
  patients with these criteria at admission
• Neither patients didnt present histological
  cirrhosis on specimens liver biopsy and/or
  native liver.

5
Patients at Admission (1986 - 2005)

• 15 patients (13 F, 2 M)
• Mean age 36 13 yrs (16 - 67)
• Hepatic encephalopathy 9/15 pts
• Stage 1 2 pts Stage 2 2 pts
• Stage 3 4 pts Stage 4 1 pt
• Bilirubin 438 142 ?m/l
• Prothrombin time 22 10 , Factor V 27 10
  
• ALT 887 900 IU/l
• Creatinine 83 23 ?m/l

6
Patients (2) Auto-immun characteristics

• AIH Type 1 12 pts
• Type 2 3 pts
• Mean values IgG 24.5 g/l
• ANA 2 pts (1/100)
• SMA 7 pts ( 1/80 to 1/640)
• ANA SMA 2 pts ( 1/50 to 1/160)
• No antibodies 4 pts

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Patients (3)

• Liver histology was available before LT in 9 pts
• AIH was suspected on liver histological findings
  in 4 pts (marked plasma cell infiltrate)
• In the others patients, diagnosis of AIH was
  performed before LT on Clinical Findings and
  Increased IgG level

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Patients with Corticosteroid Therapy (3)

• 12/15 pts treated
• Treatment started in the referring center since
  24 43 days 4 pts
• Corticosteroid therapy started at the time of
  admission in our ICU in 8 pts
• Before treatment, 5/12 pts had hepatic
  encephalopathy
• 3/15 pts not treated
• Due to a rapid deterioration of clinical
• condition or because of a late diagnosis

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• Results
• (15 pts with AIH)

• 12/15 pts underwent Liver Transplantation (78.5
  )
• Clinical Biological characteristics at time of
  LT
• Hepatic Encephalopathy 12 pts
• Bilirubin 339 136 ?m/l
• PT 15 5
• Factor V 19 8
• ALT 558 564 IU/l
• Creatinine 78 17 ?m/l
• 3/15 pts were not transplanted
• 1/3 pt improved with corticosteroid therapy
• 2/3 pts had contraindication to LT

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ResultsPatients treated by Corticosteroids

• Mean duration of steroid treatment 24.7 32.6
  d
• Delay between therapy and LT 17 20.3 d
• Hepatic Encephalopathy occurred under therapy
  4 pts

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ResultsPatients treated by Corticosteroid (2)

• Delay between admission LT 14.7 23.1 d
• Hepatic Encephalopathy at time of LT 8 / 9 pts
  
• Liver test at time of LT
• Bilirubin 356 ?m/l
• ALT 653 IU/l
• PT 15

12

• Outcome

• 12/15 pts alive with a range follow-up from 4.5
  months to 17 years
• AIH Recurrence 4/15 pts
• 3 pts died
• Cause of death
• Septic complication in 2 pts
• Gram negative septicemia 1 pt (after LT)
• Disseminated aspergillus 1 pt
• Acute pancreatitis with probable of recurrence
  of autoimmune disease after LT 1 pt

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• Conclusion

• Corticosteroid therapy is poorly effective in
  severe and fulminant form of Autoimmune hepatitis
  
• Only 1/12 pt improved during steroid treatment
• Corticosteroid therapy at this stage of disease
  should not be used because of a high risk of
  septic complication
• Liver transplantation remains the treatment of
  reference in these severe forms of autoimmune
  hepatitis.