Autoimmune Hepatitis Clinical Practice Guidelines (2019)

Hellenic Association for the Study of the Liver

Reviewed and summarized by Medscape editors

February 04, 2019

The guidelines on the diagnosis, treatment, and follow-up of autoimmune hepatitis were released on January 1, 2019, by the Hellenic Association for the Study of the Liver.[1]

Clinical Characteristics

Autoimmune hepatitis (AIH) should be considered a possibility in any individual with acute or chronic hepatitis, particularly in those with high immunoglobulin G (IgG) levels.

Untreated AIH carries high morbidity and mortality rates, so early and accurate diagnosis is mandatory.

Screening for concomitant autoimmune diseases can be considered in patients with AIH (particularly autoimmune thyroiditis), as AIH is associated with various other autoimmune-mediated conditions.

Cirrhosis should be suspected upon AIH diagnosis, since nearly one-third of adults and half of children with AIH are at the stage of cirrhosis at AIH diagnosis.

The presentation of acute AIH can take one of two clinical forms, as follows:

  • Acute worsening of previously undiagnosed or misdiagnosed AIH

  • Original acute-onset AIH without chronic lesions on liver histology

AIH can be classified as either (1) AIH-1, antinuclear (ANA), smooth muscle (SMA), and/or soluble liver antigens/liver pancreas antibody (anti-SLA/LP)–positive or (2) AIH-2, anti-liver/kidney microsomal antibody type-1 (anti-LKM1), anti-liver/kidney microsomal antibody type-3 (anti-LKM3), and/or liver cytosol type-1 antigen (anti-LC1)–positive.

Complications

Patients with AIH-related cirrhosis should undergo ultrasonography every 6 months to monitor for hepatocellular carcinoma (HCC).

Workup

All children with AIH should undergo magnetic resonance cholangiopancreatography (MRCP) at minimum to rule out autoimmune sclerosing cholangitis.

Patients who have AIH with cholestatic features should undergo testing for primary biliary cholangitis (PBC).

Interface hepatitis, hepatocyte rosetting, and emperipolesis strongly support but do not confirm AIH.

In daily clinical practice, the 2008 simplified score should be used for AIH diagnosis.

The 1999 revised score can help diagnose difficult AIH cases, since it incorporates treatment response as an important parameter.

Diagnosis of AIH-PBC and AIH–primary sclerosing cholangitis (PSC) variants should not be based on diagnostic scores, but they may be used cautiously in the diagnosis of childhood AIH and acute or fulminant disease.

Treatment

The goal of AIH therapy is to achieve complete biochemical and histological remission to prevent disease progression.

All patients with active disease, including those with advanced fibrosis or cirrhosis, should undergo treatment.

Induction treatment

Induction treatment for AIH should be tailored to the patient and be guided by treatment response.

First-line therapy for AIH should be prednisolone 0.5-1 mg/kg/day PO given in one dose in the morning plus azathioprine at an initial morning dose of 50 mg/dL, usually after 2 weeks, if bilirubin levels are <6 mg/dL.

Afterward, azathioprine should be increased up to 1-2 mg/kg/day (maintenance dose).

In patients with noncirrhotic AIH who are not candidates for conventional corticosteroid therapy (eg, serious comorbidities), budesonide 9 mg/day plus azathioprine may be used as induction treatment.

Maintenance treatment

Corticosteroid-free azathioprine monotherapy (mycophenolate mofetil [MMF] is an alternative) is the optimal maintenance treatment.

In patients with mild AIH and azathioprine intolerance who have a complete response after induction therapy, low-dose long-term prednisolone monotherapy may be used to maintain remission.

Maintenance dosing should be adjusted so that persistent biochemical response (normalization of aspartate aminotransferase [AST], alanine aminotransferase [ALT], and IgG) is maintained.

Immunosuppression should be administered for at least 3 years and for at least 2 years after a complete biochemical response is achieved.

Maintenance therapy should not be discontinued without a complete biochemical or histological response (hepatitis activity index [HAI] score >3).

Monitoring

Close long-term monitoring should be maintained after treatment is discontinued, since relapses are most common during the first 6-12 months posttreatment but may occur many years afterward.

Transaminase levels usually increase after IgG levels increase in patients with AIH relapse, but liver biopsy is not suggested.

Relapses should be treated in a manner similar to that of the initial treatment schedule; this schedule is also effective in re-inducing full remission.

Long-term (probably life-long) maintenance treatment is suggested in patients whose AIH relapses during drug-withdrawal or maintenance treatment despite adequate treatment (≥4 years of immunosuppression).

Liver biopsy is recommended before treatment discontinuation in patents with AIH who have been in complete biochemical remission for at least the last 2 years of immunosuppression.

The decision to withdraw treatment should depend on direct collaboration between the patient and doctors.

Bone density should be measured upon treatment initiation and vitamin D supplementation and adequate calcium intake recommended in all patients receiving corticosteroid treatment.

If primary complete biochemical remission does not occur despite adequate treatment, misdiagnosis or therapy noncompliance should be suspected.

Patients with non-intense disease who do not respond to therapy may receive prednisolone and azathioprine at maximum doses (1 mg/kg/day and 2 mg/kg/day, respectively) as a trial; management at an expert center is recommended if there is no response.

Thioguanine nucleotides (TGN) testing could help guide redesign of the treatment strategy, since undetectable TGN may indicate altered azathioprine metabolism or noncompliance, while high TGN levels may suggest toxicity.

Treatment adherence is vital for optimal outcomes, especially in children, adolescents, and young adults.

In patients with azathioprine intolerance, MMF be considered an alternative.

Treatment in pregnancy

Pregnancy and breastfeeding are not contraindicated in females with AIH in remission.

Maintenance treatment with prednisolone, with or without azathioprine, should be continued in previously diagnosed females under therapy.

Mild flares can be observed during the first trimester and more frequently, especially in the postpartum period, requiring increased immunosuppression.

MMF should be discontinued at least 3 months prior to conception (in females or males undergoing treatment), since MMF is absolutely contraindicated in pregnancy.

For more information, please go to Autoimmune Hepatitis.

For more Clinical Practice Guidelines, please go to Guidelines.

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