DISCUSSION
We report two cases of AIH including one case of type I AIH and a case of seronegative AIH finally classified as type I AIH. Our objective is to show through these different forms of AIH reported and the investigations available to Madagascar, the difficulty in making the diagnosis and taking charge of this disease in low-income countries and encouraging our neighboring colleagues who are in a similar situation. The unavailability of liver biopsy plays a major role in this difficulty, but should never constitute an obstacle in terms of autoimmune liver disease.
Type I AIH is the most frequent form (80% of cases), characterized by the presence of ANA (50-70% of cases) and/or SMA (85% of cases) in the typical forms or the presence of anti-SLA antibodies (6-32%) in the atypical forms. While seronegative AIH (10%) represent the particular forms of AIH.7-9 Acute hepatitis with an ALT level of > 10xULN was the mode of revelation of our two observations. This shape represents 25 to 30%.7
The diagnosis of AIH can be confirmed by simple diagnostic criteria associating the absence of other causes, the presence of autoantibodies at a significant level, γ-globulins ≥ 1.5xULN and interface hepatitis on liver biopsy.2, 7-10 Viral hepatitis (HAV, HVB and HVD, HVC, HVE, CMV, HSV, EBV), drug-induced hepatitis, Wilson’s disease, non-alcoholic steatohepatitis, hemochromatosis, chronic alcoholism, α1-antitripsin deficiency, primary biliary cholangitis and primary sclerosing cholangitis are the main differential diagnoses.4-10 Elimination of the latter remains a very important step in retaining the diagnosis of AIH. Histology showing suggestive lesions (interface hepatitis with lymphoplasmacytic infiltrates) is a mandatory component of the diagnosis.7-10 Lack of histology remains a barrier to diagnosing AIH in low-income countries, where liver biopsy is not always available. Yet the other criteria, when considered collectively, have a very strong positive predictive value for the diagnosis of AIH; taken separately, none are specific, justifying the proposal for an AIH diagnostic score by the International Autoimmune Hepatitis Group (IAHG). The total score gives an assessment of the likelihood of a certain or probable AIH diagnosis. The overall sensitivity for a definite or high probability diagnosis of AIH is approximately 90%.2, 7-10 In Madagascar, the diagnosis of AIH is still a challenge. Liver biopsy is not yet available to everyone. The cost of laboratory tests is luxurious for most patients. Systematic use of diagnostic score and test corticosteroid therapy becomes essential. Therefore, we retained the diagnosis of AIH in our observations on bundles of arguments associating the absence of other differential diagnoses, certain or probable diagnosis after the revised AIH score without histology, a complete response or relapse during a trial corticosteroid therapy.
AIH is the first chronic liver disease to have benefited from a medical treatment with proven efficacy on survival.4-6 All recent guidelines propose first-line corticosteroids (up to 60 mg/day) whether or not associated with azathioprine (1 to 2 mg/kg/day). Early initiation of azathioprine is strongly recommended in order to limit the side effects of corticosteroids.2, 4-6 EASL recommends initiation of azathioprine two weeks after administration of corticosteroids.4 Budesonide ± azathioprine is preferable for non-cirrhotic patients. This association is the source of a significant remission rate after 6 months of treatment.11 Our two patients were put on corticosteroids and azathioprine. The introduction of azathioprine was delayed in our patients due to diagnostic uncertainty requiring initial trial corticosteroid therapy as monotherapy. This makes it possible to objectify a non-response and rule out hepato-toxicity to azathioprine later. All our patients were symptomatic with ALT > 10xULN justifying our decision to start treatment because they had formal therapeutic indications according to the current guidelines (BSG and AASLD).5, 7 The therapeutic efficacy is judged on clinical and biological criteria (disappearance of symptoms, reduction or even normalization of transaminases and γglobulins). Complete remission was defined by absence of symptoms, normal concentrations of bilirubin and γ-globulins, transaminases less than 2xULN and normal or mildly inflammatory liver histology.4-6, 8-10Discontinuation of treatment may be considered in the event of prolonged biological remission ≥ 2 years, if possible ≥ 4 years without corticosteroid dependence, absence of cirrhosis, absence of previous relapse, absence of residual histological inflammation and absence of progression of fibrosis on liver biopsy.4-6, 12Kanzler et al in 2001 suggested that treatment for more than 4 years increased the chances of prolonged remission compared to treatment for 2 years.12 A liver biopsy is essential before stopping treatment because the level of residual inflammation is a factor for relapse.13 At two months of treatment, our two of the patients had complete remission. If treatment is stopped, regular biological monitoring(transaminases) could be carried out every month for 4 to 6 months and then every 3 months. This makes it possible to quickly detect a relapse.7-10