Autoimmune hepatitis medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Autoimmune hepatitis}}
{{Autoimmune hepatitis}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{MKK}}
 
==Overview==
==Overview==
 
Mainstay treatment of [[autoimmune hepatitis]] is pharmacotherapy. [[Corticosteroids]] alone or in combination with [[immunosuppressants]] are commonly used. Immunosuppressive treatment should be based on serum [[Aspartate transaminase|aspartate aminotransferase]] (AST), serum [[Alanine transaminase|alanine aminotransferase]] (ALT), serum gamma-globulin levels, and histological features. Regimens are different for adults and children. According to course of [[immunosupressants]], further management is planned.
==Medical Therapy==
==Medical Therapy==
Mainstay treatment of autoimmune hepatitis is pharmacotherapy. Corticosteroids alone or in combination with immunosuppressants are commonly used.
Mainstay treatment of [[autoimmune hepatitis]] is pharmacotherapy. [[Corticosteroids]] alone or in combination with [[immunosuppressants]] are commonly used.
=== Acute Pharmacotherapies  ===
=== Acute Pharmacotherapies  ===
*Pharmacologic medical therapies for Autoimmune hepatitis include Prednisone alone and combination of Azathioprine and Prednisone
*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:<ref name="urlwww.aasld.org">{{cite web |url=https://www.aasld.org/sites/default/files/guideline_documents/autoimmunehepatitis2010.pdf |title=www.aasld.org |format= |work= |accessdate=}}</ref> ====
==== According to American Association for the Study of Liver Diseases indications for immunosuppressive treatment: ====
{| class="wikitable"
{| class="wikitable"
! colspan="3" |Indications for Immunosuppressive Treatment
! colspan="3" |Indications for Immunosuppressive Treatment
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|-
|-
|Serum AST >10 fold upper limit of normal range(ULN)
|Serum AST >10 fold upper limit of normal range(ULN)
|Symptoms like fatigue, arthralgia, jaundice
|Symptoms like [[fatigue]], [[arthralgia]], [[jaundice]]
|Asymptomatic with normal or near normal serum
|Asymptomatic with normal or near normal serum


Line 26: Line 24:
|Serum AST >5 fold ULN  
|Serum AST >5 fold ULN  
|Serum AST and/or gamma globulin less than absolute criteria
|Serum AST and/or gamma globulin less than absolute criteria
|Inactive cirrhosis or mild portal inflammation
|Inactive [[cirrhosis]] or mild portal [[inflammation]]


(portal hepatitis)
(portal hepatitis)
|-
|-
|Gamma globulin level>2 fold ULN
|Gamma globulin level>2 fold ULN
|Interface hepatitis
|Interface [[hepatitis]]
|Severe cytopenia (white blood cell counts
|Severe [[Cytopenias|cytopenia]] (white blood cell counts


<2.5 x10<sup>9</sup>/L or platelet counts <50 x 10<sup>9</sup>/L)
<2.5 x10<sup>9</sup>/L or platelet counts <50 x 10<sup>9</sup>/L)
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|Bridging necrosis or multiacinar
|Bridging necrosis or multiacinar
necrosis on histological examination
necrosis on histological examination
|Osteopenia, emotional instability, hypertension, diabetes,
|[[Osteopenia]], emotional instability, [[hypertension]], [[diabetes]],


or cytopenia (white blood cell counts <2.5 x10<sup>9</sup>/L
or [[cytopenia]] (white blood cell counts <2.5 x10<sup>9</sup>/L


or platelet counts <50 x10<sup>9</sup>/L)
or platelet counts <50 x10<sup>9</sup>/L)
|complete deficiency of TPMT activity
|Complete deficiency of TPMT activity


precludes treatment with azathioprine
precludes treatment with [[azathioprine]]
|-
|-
|Incapacitating symptoms such as fatigue
|Incapacitating symptoms such as [[fatigue]]


and arthralgia
and [[arthralgia]]
|
|
|Vertebral compression, psychosis, brittle diabetes,
|[[Vertebral compression]], [[psychosis]], brittle [[diabetes]],


uncontrolled hypertension, known intolerances
uncontrolled [[hypertension]], known intolerances


to prednisone or azathioprine
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
==Recommendations for the Treatment of Autoimmune Hepatitis==
* Alternative regimen (3): Prednisone 10mg PO q24h for 7 days and Azathioprine 50mg q24h  for maintenance until endpoint
*Immunosuppressive treatment should be based on serum [[Aspartate transaminase|aspartate aminotransferase]] (AST), serum [[Alanine transaminase|alanine aminotransferase]] (ALT), serum gamma-globulin levels, and histological features.Various treatment used for adults and children:<ref name="pmid23808490">{{cite journal |vauthors=Czaja AJ |title=Review article: the management of autoimmune hepatitis beyond consensus guidelines |journal=Aliment. Pharmacol. Ther. |volume=38 |issue=4 |pages=343–64 |year=2013 |pmid=23808490 |doi=10.1111/apt.12381 |url=}}</ref>
**[[Prednisone]] or [[prednisolone]] with [[azathioprine]] (adults)
**[[Prednisone]] with [[azathioprine]] or 6-[[mercaptopurine]] (children)
**[[Prednisone]] or [[prednisolone]] alone
*Monitoring for bone disease.
*Adjunctive therapies for [[bone disease]] (weight-bearing exercise program, [[vitamin D]] and [[calcium]] supplementation, [[bisphosphonates]]).
*Pretreatment vaccination against [[hepatitis A virus]] (HAV) and [[hepatitis B virus]] (HBV).
*Management of treatment side effects and risks, including during [[pregnancy]].
*Alternative drug therapies for suboptimal response ([[cyclosporine]], [[tacrolimus]], or [[Mycophenolate sodium|mycophenolate mofetil]]).
*[[Hepatic]] [[ultrasonography]] to detect [[hepatocellular carcinoma]] (HCC).
*[[Liver transplantation]], management of recurrent disease after transplant with drug therapy and/or retransplantation in certain patients.
 
== '''According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Adults with Autoimmune Hepatitis''' ==
* Preferred regimen (1):<ref name="urlwww.aasld.org">{{cite web |url=https://www.aasld.org/sites/default/files/guideline_documents/autoimmunehepatitis2010.pdf |title=www.aasld.org |format= |work= |accessdate=}}</ref>
** [[Prednisone]] 60mg PO q24h for 7 days ( '''Preference:Cytopenia, Thiopurine methyltransferase deficiency,''' '''Pregnancy, Malignancy, Short-course (<6 months)'''
** Tapering of [[prednisone]] should be done as follow:
*** [[Prednisone]] 40mg PO q24h for  next 7 days
*** [[Prednisone]] 30mg PO q24h for  next 7 days
*** [[Prednisone]] 30mg PO q24h for  next 7 days
*** [[Prednisone]] 20mg and below PO q 24h for maintenance until endpoint
* Preferred regimen (2): Combination Therapy which includes [[Prednisone]] and [[Azathioprine]]:
** Tapering of prednisone should be done as follow:
*** [[Prednisone]] 30mg PO q24h for 7 days and [[Azathioprine]] 50mg q24h  for 7 days
*** [[Prednisone]] 20mg PO q24h for 7 days and [[Azathioprine]] 50mg q24h  for next 7 days
*** [[Prednisone]] 15mg PO q24h for 7 days and [[Azathioprine]] 50mg q24h  for next 7 days
*** [[Prednisone]] 10mg PO q24h for 7 days and [[Azathioprine]] 50mg q24h  for maintenance until endpoint
{| class="wikitable"
{| class="wikitable"
| colspan="5" |                                        '''Immunosuppressive Treatment Regimens for Adults in Autoimmune Hepatitis'''
| colspan="5" |                                        '''Immunosuppressive Treatment Regimens for Adults in Autoimmune Hepatitis'''
|-
|-
| colspan="2" |Monotherapy
| colspan="2" |'''Monotherapy'''


Prednisone only* (mg/day)
'''Prednisone only* (mg/day)'''
| colspan="3" |Combination Therapy
| colspan="3" |'''Combination Therapy'''
|-
|-
|Weeks
|Weeks
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|-
|-
|Reasons for Preference
|Reasons for Preference
| colspan="2" |Cytopenia, Thiopurine methyltransferase deficiency,
| colspan="2" |[[Cytopenia]], Thiopurine methyltransferase deficiency,


Pregnancy, Malignancy, Short-course (<6 months)
[[Pregnancy]], [[Malignancy]], Short-course (<6 months)
| colspan="2" |Postmenopausal state, Brittle diabetes, Obesity, Acne,
| colspan="2" |[[Postmenopausal]] state, Brittle [[diabetes]], [[Obesity]], [[Acne]],


Emotional lability, Hypertension
[[Emotional lability]], [[Hypertension]]
|}
|}
'''Adjunctive therapies''':  
'''Adjunctive therapies''':  
* Adjunctive therapy is based on medication and complication occurs due to medication
*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   
*The regular weight-bearing exercise program, [[vitamin D]], [[calcium]] supplementation and [[Bisphosphonate|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
*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'''  
== '''According to American Association for the Study of Liver Diseases, Immunosuppressive Treatment Regimens for Children in Autoimmune Hepatitis''' ==
'''Pediatric:'''  
*Preferred regimens:  
*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   
**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
**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  
***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
***Continue daily [[prednisone]] dose with or without [[azathioprine]] or switch to alternate day  [[prednisone]] dose adjusted in response with or without [[azathioprine]].
{| class="wikitable"
{| class="wikitable"
! colspan="3" |Immunosuppressive Treatment Regimens for Children with Autoimmune Hepatitis
! colspan="3" |Immunosuppressive Treatment Regimens for Children with Autoimmune Hepatitis
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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
|
* [[Prednisone]] taper over 6 -8 weeks to 0.1 -0.2 mg/kg daily or 5 mg daily


with azathioprine, 1- 2 mg/kg daily
* [[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]]
* 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
* 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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|-
|-
|
|
*Cosmetic (usually mild)
*[[Cosmetic]] (usually mild)
**Facial rounding Cytopenia
**[[Facial rounding]]
**Weight gain
**[[Weight gain]]
**Dorsal hump striae
**[[Dorsal hump striae]]
**Hirsutism
**[[Hirsutism]]
**Alopecia
**[[Alopecia]]
|80% (after 2 years)
|80% (after 2 years)
|
|
*Hematologic (mild)
*[[Hematologic]] (mild)
** Cytopenia
**[[Cytopenia]]
|46% (especially with cirrhosis)
|46% (especially with [[cirrhosis]])
|-
|-
|
|
*Somatic (usually mild)
*Somatic (usually mild)
**Emotional instability
**[[Emotional instability]]
**Glucose intolerance
**[[Glucose intolerance]]
**Cataracts
**[[Cataracts]]
|13% (treatment ending)
|13% (treatment ending)
|
|
*Hematologic (severe)
*[[Hematologic]] (severe)
**Leucopenia
**[[Leucopenia]]
**Thrombocytopenia
**[[Thrombocytopenia]]
|6% (treatment ending)
|6% (treatment ending)
|-
|-
|
|
*Somatic (severe)
*Somatic (severe)
**Osteopenia
**[[Osteopenia]]
**Vertebral compression
**[[Vertebral compression]]
**Diabetes (brittle)
**[[Diabetes]] (brittle)
** Psychosis
**[[Psychosis]]
** Hypertension (labile
**[[Hypertension]] (labile)
|13% (treatment ending)
|13% (treatment ending)
|
|
* Somatic (usually mild)
* Somatic (usually mild)
** Nausea
**[[Nausea]]
** Emesis
**[[Rash]]
** Rash
**[[Fever]]
** Fever
**[[Arthralgias]]
** Arthralgias
|5%
|5%
|-
|-
|
|
*Inflammatory/neoplastic
*Inflammatory/neoplastic
**Pancreatitis
**[[Pancreatitis]]
**Opportunistic infection
**Opportunistic [[infection]]
**Malignancy
**[[Malignancy]]
|Rare
|Rare
|
|
* Neoplastic
*[[Neoplastic]]
** Nonhepatic cell types
**Non-hepatic cell types
|3% (after 10 years)
|3% (after 10 years)
|-
|-
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|
|
|
|
* Hematologic/enteric Rare (treatment ending)
*[[Hematologic]]/enteric Rare (treatment ending)
** Bone marrow failure
**[[Bone marrow failure]]
**Villous Atrophy
**[[Villous Atrophy]]
**Malabsorption
**[[Malabsorption]]
Teratogenic during pregnancy
Teratogenic during pregnancy
|Rare
|Rare
|}
|}


====Contraindicated medications====
{{MedCondContrAbs
|MedCond = Autoimmune hepatitis|Pegylated interferon alfa-2b}}
==Sample==
==Immunosuppressive treatment with course of action in AIH==
==Immunosuppressive treatment with course of action in AIH==
{{familytree/start |summary= Immunosuppressive treatment with course of action in Autoimmune Hepatitis }}
{{familytree/start |summary= Immunosuppressive treatment with course of action in [[autoimmune Hepatitis]] }}
{{familytree | | | | | | | | | | | | | C02 | | | | | |C02=Drug treatment includes:<br>•Corticosteroids<br>•Azathioprine|C03=C03}}
{{familytree | | | | | | | | | | | | | C02 | | | | | |C02=Drug treatment includes:<br>•[[Corticosteroids]]<br>•[[Azathioprine]]|C03=C03}}
{{familytree | | | | | |,|-|-|-|v|-|-|-|^|-|-|-|v|-|-|-|-|-|-|-|.| }}
{{familytree | | | | | |,|-|-|-|v|-|-|-|^|-|-|-|v|-|-|-|-|-|-|-|.| }}
{{familytree | | | | | |!| | | |!| | | | | | | |!| | | | | | | |!| | }}
{{familytree | | | | | |!| | | |!| | | | | | | |!| | | | | | | |!| | }}
{{familytree | | | | | D01 | | D02 | | | | | | D03 | | | | | | D04 | |D01=Remission:<br>•Absence of symptoms<br>•Normal Serum Transaminase<br>•Normal bilirubin<br>•Normal gamma globulin level<br> •Normal histology or<br> inactive cirrhosis|D02=Incomplete response:<br>•Some or no improvement<br> in clinical,<br> laboratory,and histological<br>features despite<br>compliance with therapy<br> after 2-3 year<br>|D03=Treatment failure:<br>•Worsening clinical<br>laboratory<br>and histological features<br>despite compliance<br>with therapy<br>Development of jaundice<br>,ascites or<br> hepatic encephalopathy<br>|D04=Drug toxicity:<br>•Development of intolerable<br>cosmetic changes,<br> symptomatic
{{familytree | | | | | D01 | | D02 | | | | | | D03 | | | | | | D04 | |D01=Remission:<br>•Absence of symptoms<br>•Normal Serum [[Transaminase]]<br>•Normal [[bilirubin]]<br>•Normal gamma globulin level<br> •Normal histology or<br> inactive cirrhosis|D02=Incomplete response:<br>•Some or no improvement<br> in clinical,<br> laboratory,and histological<br>features despite<br>compliance with therapy<br> after 2-3 year<br>|D03=Treatment failure:<br>•Worsening clinical<br>laboratory<br>and histological features<br>despite compliance<br>with therapy<br>Development of [[jaundice]]<br>,[[ascites]] or<br> [[hepatic encephalopathy]]<br>|D04=Drug toxicity:<br>•Development of intolerable<br>[[cosmetic changes]],<br> symptomatic [[osteopenia]],<br>[[emotional instability]],<br> poorly controlled [[hypertension]],<br>brittle [[diabetes]]<br> or progressive [[cytopenia]]}}
osteopenia,<br> emotional instability,<br> poorly controlled hypertension,<br>brittle diabetes<br> or progressive cytopenia}}
{{familytree | | | | | |!| | | |!| | | | | | | |!| | | | | | | |!| | }}
{{familytree | | | | | |!| | | |!| | | | | | | |!| | | | | | | |!| | }}
{{familytree | | | | | |!| | | |!| | | | | | | |!| | | | | | | |!| | }}
{{familytree | | | | | |!| | | |!| | | | | | | |!| | | | | | | |!| | }}
{{familytree | | | | | E01 | | E02 | | | | | | E03 | | | | | | E04 | |E01=•Gradual taper<br> of prednisone over<br>6 week period<br>•Serum AST or ALT<br>, total bilirubin ,<br> and gamma globulin levels<br>every 3 weeks<br> during tapering then<br> every 3-6 months after stopping|E03=Reduction in doses of prednisone<br> by 2.5 mg/month until<br> lowest level possible<br> (<10 mg daily) to prevent worsening<br> of serum AST or ALT abnormalities<br>Indefinite azathioprine therapy (2 mg/kg daily)<br> as an alternative treatment<br> if corticosteroid intolerance||E02=•Prednisone, 60 mg daily<br>, or prednisone,<br> 30 mg daily,and azathioprine<br>, 150 mg daily, for<br> at least 1 month<br>Dose reduction of<br> prednisone by 10mg<br> and azathioprine by<br> 50 mg for each month of improvement<br> until standard treatment doses <br>are achieved|E04=Reduction in dose<br>or discontinuation of offending drug<br>Maintenance on tolerated<br>drug in adjusted dose}}
{{familytree | | | | | E01 | | E02 | | | | | | E03 | | | | | | E04 | |E01=•Gradual taper<br> of [[prednisone]] over<br>6 week period<br>•Serum [[AST]] or[[ALT]]<br>, total [[bilirubin]] ,<br> and [[gamma globulin]] levels<br>every 3 weeks<br> during tapering then<br> every 3-6 months after stopping|E02=•Reduction in doses of [[prednisone]]<br> by 2.5 mg/month until<br> lowest level possible<br> (<10 mg daily) to prevent worsening<br> of serum [[AST]]or [[ALT]] abnormalities<br>•Indefinite [[azathioprine]] therapy (2 mg/kg daily)<br> as an alternative treatment<br> if [[corticosteroid]] intolerance||E03=•[[Prednisone]], 60 mg daily<br>, or [[prednisone]],<br> 30 mg daily<br>• [[Azathioprine]]<br>, 150 mg daily, for<br> at least 1 month<br>Dose reduction of<br> [[prednisone]] by 10mg<br>•[[Azathioprine]] by<br> 50 mg for each month of improvement<br> until standard treatment doses <br>are achieved|E04=•Reduction in dose<br>or discontinuation of offending drug<br>Maintenance on tolerated<br>drug in adjusted dose}}
{{familytree | | | | | |!| | | | | | | | | | | |!| | | | | | | |!}}
{{familytree | | | | | |!| | | | | | | | | | | |!| | | | | | | |!}}
{{familytree | | |,|-|-|^|-|-|.| | | | | |,|-|-|^|-|-|.|,|-|-|-|^|-|-|-|.|}}
{{familytree | | |,|-|-|^|-|-|.| | | | | |,|-|-|^|-|-|.|,|-|-|-|^|-|-|-|.|}}
{{familytree | | F01 | | | | F02 | | | | F03 | | | | F04 | | | | | | | F05 |F01=Relapse:<br>•Restart corticosteroid<br>and Azathioprine|F02=Inactive disease:<br> Monitor lab test|F03=Liver transplant|F04=Empiric cyclosporin/Tarcolimus|F05= }}
{{familytree | | F01 | | | | F02 | | | | F03 | | | | F04 | | | | | | | F05 |F01=Relapse:<br>Restart [[corticosteroid]]<br>and [[Azathioprine]]|F02=Inactive disease:<br> Monitor lab test|F03=[[Liver transplant]]|F04=Empiric [[Cyclosporine]]3 mg BD/[[Tacrolimus]]|F05= Empiric [[Mycophenolate mofetil]]}}
{{familytree/end}}
{{familytree/end}}


==Recommendations for the Treatment of Autoimmune Hepatitis (DO NOT EDIT)==
==Long-Term Follow up==
*Perform [[Liver function tests|liver function]] tests weekly during the first 6-8 weeks of treatment and then every 2-3 months depends upon results
*Abdominal imaging studies (e.g, [[ultrasound]], [[CT]], [[MRI]]) every 6 months 
*[[Alpha-fetoprotein]] testing is done every 6 months


# Immunosuppressive treatment based on serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma-globulin levels, and histological features
==Treatment of overlap syndrome==
## Prednisone or prednisolone with azathioprine (adults)
Overlap Syndrome is diagnosed when patients who present with the features of [[primary biliary cirrhosis]] ([[Primary biliary cirrhosis|PBC]]) or [[primary sclerosing cholangitis]] ([[Primary sclerosing cholangitis|PSC]]) along with the features of AIH, [[PBC]]-AIH or [[PSC]]-AIH<ref name="pmid23862175">{{cite journal |vauthors=Czaja AJ |title=Diagnosis and management of the overlap syndromes of autoimmune hepatitis |journal=Can. J. Gastroenterol. |volume=27 |issue=7 |pages=417–23 |year=2013 |pmid=23862175 |pmc=3956022 |doi= |url=}}</ref><ref name="pmid18433467">{{cite journal |vauthors=Al-Chalabi T, Portmann BC, Bernal W, McFarlane IG, Heneghan MA |title=Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long-term outcome and survival |journal=Aliment. Pharmacol. Ther. |volume=28 |issue=2 |pages=209–20 |year=2008 |pmid=18433467 |doi=10.1111/j.1365-2036.2008.03722.x |url=}}</ref><ref name="pmid16356577">{{cite journal |vauthors=Chazouillères O, Wendum D, Serfaty L, Rosmorduc O, Poupon R |title=Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome |journal=J. Hepatol. |volume=44 |issue=2 |pages=400–6 |year=2006 |pmid=16356577 |doi=10.1016/j.jhep.2005.10.017 |url=}}</ref>
## Prednisone with azathioprine or 6-mercaptopurine (children)
{| class="wikitable"
## Prednisone or prednisolone alone
! colspan="2" |Treatment of overlap syndrome
# Monitoring for bone disease
|-
# Adjunctive therapies for bone disease (weight-bearing exercise program, vitamin D and calcium supplementation, bisphosphonates)
|Types
# Pretreatment vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV)
|Drugs
# Management of treatment side effects and risks, including during pregnancy
|-
# Alternative drug therapies for suboptimal response (cyclosporine, tacrolimus, or mycophenolate mofetil)
|AIH-PBC
# Hepatic ultrasonography to detect hepatocellular carcinoma (HCC)
|[[Prednisone]] or [[prednisolone]]
# Liver transplantation, management of recurrent disease after transplant with drug therapy and/or retransplantation in certain patients}}
* 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==
==References==

Revision as of 20:34, 9 January 2018

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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. Immunosuppressive treatment should be based on serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma-globulin levels, and histological features. Regimens are different for adults and children. According to course of immunosupressants, further management is planned.

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

  • Preferred regimen (1):[1]
    • Prednisone 60mg PO q24h for 7 days ( Preference:Cytopenia, Thiopurine methyltransferase deficiency, Pregnancy, Malignancy, Short-course (<6 months)
    • Tapering of prednisone should be done as follow:
  • Preferred regimen (2): Combination Therapy which includes Prednisone and Azathioprine:
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:
    • 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
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
80% (after 2 years) 46% (especially with cirrhosis)
13% (treatment ending) 6% (treatment ending)
13% (treatment ending) 5%
Rare 3% (after 10 years)

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 of jaundice
,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
of prednisone 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 Cyclosporine3 mg BD/Tacrolimus
 
 
 
 
 
 
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 (e.g, 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 cirrhosis (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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