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