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EASL releases guidelines for autoimmune hepatitis

The European Association for the Study of the Liver has released a clinical practice guideline for the diagnosis, treatment and management of autoimmune hepatitis.

“The aim of the present clinical practice guideline is to provide guidance to hepatologists and general physicians in the diagnosis and treatment of [autoimmune hepatitis] in order to improve care for affected patients,” the authors wrote in the Journal of Hepatology. “In view of the limited data from large controlled studies and trials, many recommendations are based on expert consensus … The guidelines are a resource of information and recommendations based on the largest experience available thus far.”

According to the guidelines, the prevalence of autoimmune hepatitis (AIH) varies, ranging from 15 to 25 cases per 100,000 people in Europe. It can affect all age groups and is currently increasing among men and women.

“AIH prevalence and clinical expression seem to vary according to ethnicity. … The disease is more common and more severe in North American Aboriginal/First Nations populations compared with predominantly Caucasian, non-First Nations populations,” the authors wrote.

Key recommendations were outlined for diagnosing and treating AIH among various populations.

Diagnosis

Detecting auto-antibodies is critical in diagnosing AIH. Laboratory clinicians and personnel should “increase their expertise” on disease expression and interpreting liver autoimmune serology to benefit their patients, according to the guidelines.

“[Auto-antibody] tests must be ordered specially on the basis of reliable clinical data and rest results must not be interpreted outside the specific clinical context. Only then can sensible evidence-based decisions be made, and the potential of serological work-up exploited to the benefit of the patient,” the authors wrote.

Indirect immunofluorescence is the recommended test of choice for detecting certain auto-antibodies such as antinuclear, smooth muscle, liver and kidney microsomal antigens and liver cytosol type 1 antigen. Immunoassays should be used for soluble liver antigens or liver-pancreas auto-antibodies.

Since there is not a diagnostic “gold standard,” clinicians should regard any diagnostic score tool as only an aid to diagnosing AIH and should be used with personal clinician judgement. The simplified scoring system of the International Autoimmune Hepatitis Group (IAIHG) is useful for everyday clinical practice, whereas the revised clinical system of the IAIHG can be helpful for diagnosing difficult to treat patients.

Liver biopsy is considered a prerequisite for diagnosing AIH, according to the guidelines. It is also used to guide treatment decisions and should be performed before treatment. In addition, biopsy under visual control via mini-laparoscopy has also been shown to be safe even in cases of advanced coagulopathy. See the list of guidelines for other diagnosis recommendations.

Treatment

“The aim of treatment in AIH is to obtain complete remission of the disease and to prevent further progression of liver disease,” the authors wrote. “This requires mostly permanent maintenance therapy or induction of a sustained remission following treatment withdrawal.”

The authors recommend that all patients with active AIH be treated and dosage of treatment should be “adapted to the activity of the disease,” according to the guidelines.

Patients in spontaneous remission may not require therapy. However, they should be closely monitored for the future.

For the first line of treatment for AIH, the authors recommend predniso(lo)ne (initial dose of 0.5-1 mg/kg per day) as initial therapy followed by azathioprine (initial dose of 50 mg per day) after 2 weeks. In patients with acute severe AIH, high doses of intravenous corticosteroids (at least 1 mg/kg) are recommended as early as possible. If there is no improvement within 1 week, emergency liver transplantation should be the next option, according to the guidelines.

Clinicians should re-evaluate if the patient fails therapy or does not provide an adequate response to it.

“The majority of AIH patients respond well to steroid-based immunosuppressive treatment and serum transaminases improve to levels within the normal range,” the authors wrote.

The guidelines state that treatment should be continued for a minimum of 3 years and for at least 2 years after complete normalization of serum transaminases and IgG levels.

Patients who experience biochemical remission for more than 2 years should undergo liver biopsy prior to treatment withdrawal. Treatment should not be discontinued in these patients nor in those with continued histological disease activity.

Patients should be closely monitored after treatment withdrawal and undergo lifelong surveillance. Patients who relapsed during drug withdrawal following sufficient immunosuppression therapy or those who experienced a flare during maintenance therapy should be kept on immune suppression therapy permanently.

For maintenance therapy, the authors recommend that patients with mild disease who are unable to tolerate azathioprine begin prednisolone monotherapy. For all other patients, steroid-free monotherapy with azathioprine or mycophenolate mofetil (MMF) should be used for maintenance therapy.

In children, higher doses of steroid may be needed at the start of therapy. Managing AIH in children is similar to adults, according to the authors. Controlled AIH is not a contraindication to pregnancy or breastfeeding and maintenance therapy can be continued. Mild flares can occur in the first trimester and after delivery. MMF is contraindicated in pregnancy.  

“In elderly patients or in those with co-morbidity, the choice of steroid therapy should be considered carefully,” the authors wrote.

Measuring bone density is recommended at baseline of steroid therapy. All patients who receive steroid therapy should also be provided a supplement of vitamin D and proper calcium intake is recommended.

According to the authors, in patients with suboptimal response to treatment regardless of reconfirmation of diagnosis and adherence, dosages of prednisolone and azathioprine should be increased or other medications should be considered.

In patients with primary sclerosing cholangitis, ursodeoxycholic acid (UDCA) and immunosuppressants are recommended. In patients with dominant AIH features, the authors recommend immunosuppressants alone and then add UDCA if it does not work.

Patients who begin treatment for AIH post-liver transplantation should follow the standard procedures for management. The authors also recommend that hepatitis A and B vaccinations and annual influenza vaccination be given to all patients with AIH.

“Diagnosis and treatment of AIH have seen enormous progress over the past 50 years, and the majority of affected patients can be treated very successfully with a normal or near normal life expectancy and good quality of life,” the authors wrote. “Nonetheless, many patients still experience considerable morbidity and mortality.”

See the list of guidelines for other treatment recommendations.

Conclusion

The authors concluded: “In addition to clinical research, basic research focusing on the etiology of AIH and aiming to understand the underlying pathophysiology will be the key to improved treatment of the disease. At present, the majority of patients need drug treatment every day of their life, leading to both physical as well as psychosocial impairment in the quality of life in many of them.

“Patients want cure, not suppression of disease activity, and for most patients, if not all, we are at present unable to provide a cure for their disease. In order to reach curative treatment, we have to closely collaborate with basic scientists and follow development in immunology and related disciplines.” – by Melinda Stevens

Disclosures: Please see the full study for a list of all authors’ relevant financial disclosures.