Autoimmune hepatitis medical therapy

Jump to navigation Jump to search

Autoimmune hepatitis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating autoimmune hepatitis differential diagnosis

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Diagnostic of choice

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Autoimmune hepatitis medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Autoimmune hepatitis medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Autoimmune hepatitis medical therapy

CDC on Autoimmune hepatitis medical therapy

Autoimmune hepatitis medical therapy in the news

Blogs on Autoimmune hepatitis medical therapy

Directions to Hospitals Treating Autoimmune hepatitis

Risk calculators and risk factors for Autoimmune hepatitis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Medical Therapy

Mainstay treatment of autoimmune hepatitis is pharmacotherapy. Corticosteroids alone or in combination with immunosuppressants are commonly used.

Acute Pharmacotherapies

  • Pharmacologic medical therapies for Autoimmune hepatitis include Prednisone alone and combination of Azathioprine and Prednisone

According to American Association for the Study of Liver Diseases indications for immunosuppressive treatment:

Indications for Immunosuppressive Treatment
Absolute Indications Relative Indications None
Serum AST >10 fold upper limit of normal range(ULN) Symptoms like fatigue, arthralgia, jaundice Asymptomatic with normal or near normal serum

AST and gamma globulin levels

Serum AST >5 fold ULN Serum AST and/or gamma globulin less than absolute criteria Inactive cirrhosis or mild portal inflammation

(portal hepatitis)

Gamma globulin level>2 fold ULN Interface hepatitis Severe cytopenia (white blood cell counts

<2.5 x109/L or platelet counts <50 x 109/L)

Bridging necrosis or multiacinar

necrosis on histological examination

Osteopenia, emotional instability, hypertension, diabetes,

or cytopenia (white blood cell counts <2.5 x109/L

or platelet counts <50 x109/L)

complete deficiency of TPMT activity

precludes treatment with azathioprine

Incapacitating symptoms such as fatigue

and arthralgia

Vertebral compression, psychosis, brittle diabetes,

uncontrolled hypertension, known intolerances

to prednisone or azathioprine

According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Adults with Autoimmune Hepatitis:

  • Preferred regimen (1): Prednisone 60mg PO q24h for 7 days ( Preference:Cytopenia, Thiopurine methyltransferase deficiency, Pregnancy, Malignancy, Short-course (<6 months)
  • Preferred regimen (2): Prednisone 40mg PO q24h for next 7 days
  • Preferred regimen (3): Prednisone 30mg PO q24h for next 7 days
  • Preferred regimen (4): Prednisone 30mg PO q24h for next 7 days
  • Preferred regimen (5): Prednisone 20mg and below PO q24h for maintenance until endpoint
  • Alternative regimen: Combination Therapy which includes Prednisone and Azathioprine
  • Alternative regimen (1): Prednisone 30mg PO q24h for 7 days and Azathioprine 50mg q24h for 7 days
  • Alternative regimen (2): Prednisone 20mg PO q24h for 7 days and Azathioprine 50mg q24h for next 7 days
  • Alternative regimen (3): Prednisone 15mg PO q24h for 7 days and Azathioprine 50mg q24h for next 7 days
  • Alternative regimen (3): Prednisone 10mg PO q24h for 7 days and Azathioprine 50mg q24h for maintenance until endpoint
Immunosuppressive Treatment Regimens for Adults in Autoimmune Hepatitis
Monotherapy

Prednisone only* (mg/day)

Combination Therapy
Weeks Dosage Prednisone Azathioprine

USA (mg/day) EU (mg/kg/day)

First 60 30 50 12
Second 40 20 50 12
Third 30 15 50 12
Fourth 30 15 50 12
Maintenance until endpoint 20 and below 10 50 12
Reasons for Preference Cytopenia, Thiopurine methyltransferase deficiency,

Pregnancy, Malignancy, Short-course (<6 months)

Postmenopausal state, Brittle diabetes, Obesity, Acne,

Emotional lability, Hypertension

Adjunctive therapies:

  • Adjunctive therapy is based on medication and complication occurs due to medication
  • The regular weight-bearing exercise program, vitamin D, calcium supplementation and bisphosphonates should be taken by patient who is taking corticosteroids for long-term
  • Vaccination against hepatitis B virus (HBV) and hepatitis A virus (HAV) should be done as early as possible even before immunosuppression

According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Children in Autoimmune Hepatitis:

Pediatric

  • Preferred regimens:
    • Initial regimen (1): Prednisone 1- 2 mg/kg (upto60mg/day) PO q24h for 14 days either alone or in combination with azathioprine, 1- 2 mg/kg q24h
    • Maintenance regimen (2): Prednisone taper to 0.1 -0.2 mg/kg q24h or 5 mg q24h for 6 -8 weeks
      • if added initially, azathioprine at constant dose
      • Continue daily prednisone dose with or without azathioprine or switch to alternate day prednisone dose adjusted in response with or without azathioprine
Immunosuppressive Treatment Regimens for Children with Autoimmune Hepatitis
Initial Regimen Maintenance Regimen Endpoint
  • Prednisone, 1- 2 mg/kg daily (up to 60 mg/day),

for two weeks either alone or in combination

with azathioprine, 1- 2 mg/kg daily

  • Prednisone taper over 6 -8 weeks to

0.1 -0.2 mg/kg daily or 5 mg daily

  • Azathioprine at constant dose if added initially
  • Continue daily prednisone dose with or without azathioprine or switch to alternate day prednisone dose adjusted to response with or without azathioprine
  • Normal liver tests for 1- 2 years during treatment
  • No flare during entire interval
  • Liver biopsy examination discloses no inflammation
Frequency and Nature of Side Effects Associated with Treatment in Adults with Autoimmune Hepatitis
Prednisone-Related Side Effects Azathioprine-Related Side Effects
Type Frequency Type Frequency
  • Cosmetic (usually mild)
    • Facial rounding Cytopenia
    • Weight gain
    • Dorsal hump striae
    • Hirsutism
    • Alopecia
80% (after 2 years)
  • Hematologic (mild)
    • Cytopenia
46% (especially with cirrhosis)
  • Somatic (usually mild)
    • Emotional instability
    • Glucose intolerance
    • Cataracts
13% (treatment ending)
  • Hematologic (severe)
    • Leucopenia
    • Thrombocytopenia
6% (treatment ending)
  • Somatic (severe)
    • Osteopenia
    • Vertebral compression
    • Diabetes (brittle)
    • Psychosis
    • Hypertension (labile
13% (treatment ending)
  • Somatic (usually mild)
    • Nausea
    • Emesis
    • Rash
    • Fever
    • Arthralgias
5%
  • Inflammatory/neoplastic
    • Pancreatitis
    • Opportunistic infection
    • Malignancy
Rare
  • Neoplastic
    • Nonhepatic cell types
3% (after 10 years)
  • Hematologic/enteric Rare (treatment ending)
    • Bone marrow failure
    • Villous Atrophy
    • Malabsorption

Teratogenic during pregnancy

Rare

Contraindicated medications

Autoimmune hepatitis is considered an absolute contraindication to the use of the following medications:

Sample

Immunosuppressive treatment with course of action in AIH

 
 
 
 
 
 
 
 
 
 
 
 
Drug treatment includes:
•Corticosteroids
•Azathioprine
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Remission:
•Absence of symptoms
•Normal Serum Transaminase
•Normal bilirubin
•Normal gamma globulin level
•Normal histology or
inactive cirrhosis
 
Treatment failure:
•Worsening clinical
laboratory
and histological features
despite compliance
with therapy
Development of jaundice
,ascites or
hepatic encephalopathy
 
 
 
 
 
Incomplete response:
•Some or no improvement
in clinical,
laboratory,and histological
features despite
compliance with therapy
after 2-3 year
 
 
 
 
 
Drug toxicity:
•Development of intolerable
cosmetic changes,
symptomatic osteopenia,
emotional instability,
poorly controlled hypertension,
brittle diabetes
or progressive cytopenia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•Gradual taper
of prednisone over
6 week period
•Serum AST or ALT
, total bilirubin ,
and gamma globulin levels
every 3 weeks
during tapering then
every 3-6 months after stopping
 
•Prednisone, 60 mg daily
, or prednisone,
30 mg daily,and azathioprine
, 150 mg daily, for
at least 1 month
Dose reduction of
prednisone by 10mg
and azathioprine by
50 mg for each month of improvement
until standard treatment doses
are achieved
 
 
 
 
 
Reduction in doses of prednisone
by 2.5 mg/month until
lowest level possible
(<10 mg daily) to prevent worsening
of serum AST or ALT abnormalities
Indefinite azathioprine therapy (2 mg/kg daily)
as an alternative treatment
if corticosteroid intolerance
 
 
 
 
 
Reduction in dose
or discontinuation of offending drug
Maintenance on tolerated
drug in adjusted dose
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F01
 
 
 
F02
 
 
 
F03
 
 
 
 
 
 
 
 
 

Recommendations for the Treatment of Autoimmune Hepatitis (DO NOT EDIT)

  1. Immunosuppressive treatment based on serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma-globulin levels, and histological features
    1. Prednisone or prednisolone with azathioprine (adults)
    2. Prednisone with azathioprine or 6-mercaptopurine (children)
    3. Prednisone or prednisolone alone
  2. Monitoring for bone disease
  3. Adjunctive therapies for bone disease (weight-bearing exercise program, vitamin D and calcium supplementation, bisphosphonates)
  4. Pretreatment vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV)
  5. Management of treatment side effects and risks, including during pregnancy
  6. Alternative drug therapies for suboptimal response (cyclosporine, tacrolimus, or mycophenolate mofetil)
  7. Hepatic ultrasonography to detect hepatocellular carcinoma (HCC)
  8. Liver transplantation, management of recurrent disease after transplant with drug therapy and/or retransplantation in certain patients}}

References

Template:WS Template:WH