Autoimmune hepatitis medical therapy: Difference between revisions

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* Prednisone, 1- 2 mg/kg daily (up to 60 mg/day),
* [[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
for two weeks either alone or in combination
 
with azathioprine, 1- 2 mg/kg daily
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* [[Prednisone]] taper over 6 -8 weeks to 0.1 -0.2 mg/kg daily or 5 mg 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
* [[Azathioprine]] at constant dose if added initially
* Continue daily prednisone dose with or without azathioprine or switch to alternate day  prednisone to adjust to response  with or without [[azathioprine]]
* Continue daily [[prednisone]] dose with or without [[azathioprine]] or switch to alternate day  [[prednisone]] to adjust to response  with or without [[azathioprine]]
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* Normal liver tests for 1- 2 years during treatment
* Normal liver tests for 1- 2 years during treatment
* No flare during entire interval
* No flare during entire interval
* Liver biopsy examination discloses no inflammation
* [[Liver biopsy]] examination discloses no [[inflammation]]
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Revision as of 18:33, 31 December 2017

Autoimmune hepatitis Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  :Manpreet Kaur, MD [2]

Overview

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

Medical Therapy

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

Acute Pharmacotherapies

According to American Association for the Study of Liver Diseases indications for immunosuppressive treatment:[1]

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

Recommendations for the Treatment of Autoimmune Hepatitis

According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Adults with Autoimmune Hepatitis:[1]

  • 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

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

Pediatric

  • Preferred regimens:
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
  • 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

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
 
Incomplete response:
•Some or no improvement
in clinical,
laboratory,and histological
features despite
compliance with therapy
after 2-3 year
 
 
 
 
 
Treatment failure:
•Worsening clinical
laboratory
and histological features
despite compliance
with therapy
Development ofjaundice
,ascites or
hepatic encephalopathy
 
 
 
 
 
Drug toxicity:
•Development of intolerable
cosmetic changes,
symptomatic osteopenia,
emotional instability,
poorly controlled hypertension,
brittle diabetes
or progressive cytopenia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•Gradual taper
ofprednisone over
6 week period
•Serum AST orALT
, total bilirubin ,
and gamma globulin levels
every 3 weeks
during tapering then
every 3-6 months after stopping
 
•Reduction in doses of prednisone
by 2.5 mg/month until
lowest level possible
(<10 mg daily) to prevent worsening
of serum ASTor ALT abnormalities
•Indefinite azathioprine therapy (2 mg/kg daily)
as an alternative treatment
if corticosteroid intolerance
 
 
 
 
 
Prednisone, 60 mg daily
, or prednisone,
30 mg daily
Azathioprine
, 150 mg daily, for
at least 1 month
Dose reduction of
prednisone by 10mg
Azathioprine by
50 mg for each month of improvement
until standard treatment doses
are achieved
 
 
 
 
 
•Reduction in dose
or discontinuation of offending drug
Maintenance on tolerated
drug in adjusted dose
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relapse:
Restart corticosteroid
and Azathioprine
 
 
 
Inactive disease:
Monitor lab test
 
 
 
Liver transplant
 
 
 
Empiric cyclosporin/Tarcolimus
 
 
 
 
 
 
Empiric Mycophenolate Mofetil

Long-Term Follow up

  • Perform liver function tests weekly during the first 6-8 weeks of treatment and then every 2-3 months depends upon results
  • Abdominal imaging studies (eg, ultrasound, CT, MRI) every 6 months
  • Alpha-fetoprotein testing is done every 6 months

Treatment of overlap syndrome

Overlap Syndrome is diagnosed when patients who present with the features of primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) along with the features of AIH, PBC-AIH or PSC-AIH.[3][4][5]

Treatment of overlap syndrome
Types Drugs
AIH-PBC Prednisone or prednisolone
  • 30 mg OD × 7days
  • 20 mg OD × 7days
  • 15 mg OD × 15days
  • 10 mg thereafter

Combined with azathioprine

  • 50 mg OD from start, or
  • 1 mg/kg/day to 2 mg/kg/day
AIH-PBC Prednisone or prednisolone in combination with azathioprine as above combined with Ursodeoxycholic acid: 13 mg/kg/day to 15 mg/kg/day
AIH-PSC Prednisone or prednisolone 0.5 mg/kg/day tapered to 10 mg/day to 15 mg/day

Combined with azathioprine 50 mg/day to 75 mg/day

Combined with Ursodeoxycholic acid 13 mg/kg/day to 15 mg/kg/day

AIH-cholestatic syndrome Prednisone or prednisolone in combination with azathioprine as above combined with Ursodeoxycholic acid: 13 mg/kg/day to 15 mg/kg/day

References

  1. 1.0 1.1 "www.aasld.org" (PDF).
  2. Czaja AJ (2013). "Review article: the management of autoimmune hepatitis beyond consensus guidelines". Aliment. Pharmacol. Ther. 38 (4): 343–64. doi:10.1111/apt.12381. PMID 23808490.
  3. Czaja AJ (2013). "Diagnosis and management of the overlap syndromes of autoimmune hepatitis". Can. J. Gastroenterol. 27 (7): 417–23. PMC 3956022. PMID 23862175.
  4. Al-Chalabi T, Portmann BC, Bernal W, McFarlane IG, Heneghan MA (2008). "Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long-term outcome and survival". Aliment. Pharmacol. Ther. 28 (2): 209–20. doi:10.1111/j.1365-2036.2008.03722.x. PMID 18433467.
  5. Chazouillères O, Wendum D, Serfaty L, Rosmorduc O, Poupon R (2006). "Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome". J. Hepatol. 44 (2): 400–6. doi:10.1016/j.jhep.2005.10.017. PMID 16356577.

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