We read with great interest the practice guidelines for the diagnosis and management of autoimmune hepatitis recently issued by the American Association for the Study of Liver Diseases (AASLD). 1 In particular, we appreciate the new definition of biochemical remission, which now requires not only normal bilirubin and gamma-globulin levels but also normal serum aminotransferases; this is at variance with the 2002 definition, 2 which considers aminotransferase levels lower than twice the upper limits of normal to be sufficient. According to the 2002 criteria, nearly 80% of patients with autoimmune hepatitis enter remission within 3 years. The recently coined new definition will result in a tremendous change in the rate of response to immunosuppressive treatment for autoimmune hepatitis.
Here we present our own experience, which has already been published in part, 3 and compare the different response rates according to the 2002 and 2010 definitions of remission.
Among 163 consecutive Italian patients with autoimmune hepatitis diagnosed at a single center, 119 (73%) entered remission according to the 2002 AASLD criteria, whereas only 42 patients (26%) of the same cohort fulfilled the 2010 AASLD criteria. Among 89 patients with a follow-up longer than 60 months, 65 (73%) had aminotransferase levels lower than twice the upper limit of normal (2002 criteria), but only 23 (25.8%) consistently maintained normal aminotransferase levels (2010 criteria) with low steroid doses (2-4 mg of methylprednisolone daily or every other day). Interestingly, from a clinical standpoint, after a mean follow-up longer than 100 months, only 1 of the 23 patients (4%) fulfilling the 2010 criteria of remission experienced histological worsening of the disease (mild to severe liver histology), whereas 36 of the 66 patients (54.5%) whose aminotransferase levels did not normalize had histological (14 with severe histology and 9 with cirrhosis) or clinical evidence (11 with endstage liver disease, 1 with decompensated cirrhosis, and 1 with hepatocellular carcinoma) of uncontrolled and evolving liver disease.
In summary, in our experience, the application of the 2010 criteria flips the previously codified remission rate from 73% to 26%. Complete-response patients have a very good long-term prognosis virtually free of significant clinical events, whereas patients whose serum aminotransferases are unable to be stably normalized are those with the highest probability of developing long-term complications, which not rarely may prove to be lethal. These are the patients most likely to benefit from new pharmacological, cellular, and molecular therapies. 4,5