Hellenic Association for the Study of the Liver Clinical Practice Guidelines: Autoimmune hepatitis

Abstract

Autoimmune hepatitis (AIH) is a relatively rare acute or chronic liver disease of unknown etiology characterized by large heterogeneity. Its distribution is global, covering all ages, both sexes and all ethnic groups. The aim of the present Clinical Practice Guidelines (CPG) of the Hellenic Association for the Study of the Liver was to provide updated guidance and help to gastroenterologists, hepatologists, internists and general practitioners for AIH diagnosis and management. AIH diagnosis is based on clinicopathological characteristics: namely, polyclonal hypergammaglobulinemia, particularly of immunoglobulin G (IgG), circulating autoantibodies, interface hepatitis on liver histology, absence of viral hepatitis, and a favorable response to immunosuppression. Clinical manifestations at disease onset are variable, ranging from asymptomatic to the acute/severe form. Aminotransferase and bilirubin levels vary, while the presence of hepatitis at the histological level is a prerequisite for diagnosis. Autoantibodies are the hallmark for AIH diagnosis; therefore, the CPG describe the appropriate serological algorithm for their detection. AIH therapy should aim to achieve complete biochemical (normalization of IgG and aminotransferases) and histological remission. All patients who have active disease, even those with cirrhosis, should be treated with individualized and response-guided induction therapy using prednisolone in combination with azathioprine or mycophenolate mofetil as first-line therapy. Immunosuppression should be given for at least 3 years and for at least 2 years after the achievement of complete biochemical response, while a liver biopsy should be recommended before treatment discontinuation. Current CPG are also provided for several specific conditions and difficult-to-treat patients.

Keywords: Autoimmune hepatitis; autoantibodies; azathioprine; clinical practice guidelines; corticosteroids.

Figure 1

Proposed algorithm for the differential diagnosis between autoimmune hepatitis (AIH) and drug-induced liver injury (DILI) in an index case with biochemical hepatitis, positive liver autoimmune serology and hepatitis on liver histology, irrespective of the presence or absence of high IgG levels AST, aspartate aminotransferase; ALT, alanine aminotransferase; IgG, immunoglobulin G.

Figure 2

Proposed algorithm for routine autoantibody testing in cases with a suspicion of autoimmune hepatitis Anti-SLA/LP, antibodies against soluble liver antigens/liver pancreas; ELISA, enzyme linked immunosorbent assay; Abs, autoantibodies; ANA, antinuclear antibodies; SMA, smooth muscle antibodies; anti-LKM1, anti-liver/kidney microsomal antibody type 1; anti-LC1, antibodies against liver cytosol type-1 antigen; pANCA/ANNA, perinuclear anti-neutrophil cytoplasmic antibodies/anti-nuclear neutrophil antibodies; anti-LKM3, anti-liver/kidney microsomal antibody type 3; AIH, autoimmune hepatitis.

Figure 3

Indications for treatment initiation in defined cases of autoimmune hepatitis (AIH) ULN, upper limit of normal; Abs, autoantibodies; HAI, histological activity index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; IgG, immunoglobulin G.

Figure 4

Suggested therapeutic algorithm for prednisolone in combination with mycophenolate mofetil (MMF) in treatment-naïve AIH patients. *In patients with risk factors (e.g., anti-LKM, anti-LC1, anti-α-actinin, anti-SLA/LP, cirrhosis at diagnosis) the tapering schedule could be applied every 3 weeks. **In relapses (↑AST, ALT ± IgG) prednisolone should be increased to the dose of initial complete response and then tapered, either by increasing the time interval twofold or by decreasing the dose of prednisolone tapering by half at the same time. ***In relapses after corticosteroid withdrawal restart prednisolone at the dose of initial complete response and taper according to **. MMF is given in two divided doses AIH, autoimmune hepatitis; anti-LKM, anti-liver/kidney microsomal antibody; anti-LC1, antibodies against liver cytosol type-1 antigen; anti-SLA/LP, antibodies against soluble liver antigens/liver pancreas; AST, aspartate aminotransferase; ALT, alanine aminotransferase; IgG, immunoglobulin G.