Preliminary Study On Diagnostic Criteria And Susceptibility In Autoimmune Hepatitis

PartⅠPreliminary study on diagnostic criteria and clinical features in autoimmune hepatitisAims:Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is critical for the outcomes, since timely immunosuppression treatment is really life-saving. In 1993, the International Autoimmune Hepatitis Group (IAIHG) proposed diagnostic criteria, which were revised in 1999. Another simplified scoring system was published in 2008. All above three scoring systems had been evaluated through different clinical and laboratory findings of AIH patients. The sensitivity and specificity of revised diagnostic scoring system (1999) and simplified scoring criteria (2008) were compared. The clinical features, laboratory data and therapeutic results of patients with AIH,primary biliary cirrhosis (PBC) and AIH-PBC overlap syndrome (OS) were investigated in order to find out simple and reliable parameters for the diagnosis and prognosis of autoimmune liver diseases (AILD).Methods:1. The descriptive, revised (1999) and simplified scoring criteria (2008) were applied to the 85 AILD patients received liver biopsy. The medical data were recorded for calculating these three criteria scores for comparing with the differences among them.2. About 85 patients were diagnosed as or as not AIH following the descriptive diagnostic criteria regarded as the "golden standard" in this artical. The sensitivity, specificity and the Youden's index of revised diagnostic scoring system (1999) and simplified scoring criteria (2008) were calculated respectively. 3. The clinical features, laboratory data and therapeutic effects of patients (60 AIH,39 OS and 78 PBC) were recorded so as to analysis the characters of these three kinds of diseases.4. The positive rate of celiac lymphadenophathy were compared byχ2-test among the patients with AIH, OS, PBC and the controls after CT scanning or B-us checking.Results:1. The quantity of patients diagnosed by revised diagnostic scoring system (1999) is statistically higher than those diagnosed by the other two diagnostic criteria. The concentration of serum GLO is the lowest in the patients diagnosed by revised diagnosic scoring system comparaed with others.2. The sensitivity for definite AIH (>15 points) was 85.71%, the specificity was 95.83% and the Youden's index was 0.82 in revised diagnostic scoring system (1999). For those classified as probable AIH (≥10 points), the sensitivity was 83.78%, the specificity was 56.25% and the Youden's index was 0.40. In simplified diagnostic scoring criteria, the sensitivity for definite AIH (≥7 points) was 100%, the specificity was 95.83% and the Youden's index was 0.96. For those classified as probable,AIH (≥6 points), the sensitivity was 89.19%, the specificity was 83.33% and the Youden's index was 0.73.3. Female preponderance was in common among the patients with AIH, PBC and OS. The patients with PBC had a higher female/male ratio (8.75:1), however, no statistical differences were observed. In the age of 50-70, the percentage of patients with AIH, PBC and OS was 55%,71.80% and 58.98% respectively. The concentration of serum GLO was significantly higher in the AIH and OS groups. Otherwise, the levels of ALP, GGT and TBIL were significantly higher in OS and PBC groups. The concentration of IgG and the positive rate of SMA in patients with AIH were significantly higher than those with OS and PBC. The positive rate of AMA was significantly higher in OS group than others. In the therapeutic study, obviously decreased concentration of ALT, AST, ALP and TBIL were observed prior and posterior to the therapy in AIH group. While the level of ALT, AST, ALP and GGT were found significantly lower before and after treatment in PBC and OS groups. After the treatment for 6-12 months, the biochemistry value in the three groups of patients are all getting approach to the normal controls.4. The lymphadenophathy were observed in the patients with AIH, OS, PBC and the controls (61.22%,93.33%,66.67% and 14%, respectively) after CT scanning or B-us testing. The amount of patients with lymphadenophathy in OS group was significantly higher than other groups.Conclusions:1. For diagnosing AIH, the descriptive, revised (1999) and simplified diagnostic scoring system is different. In clinical work, we should evaluate them as a whole and give correct diagnosis for AIH.2. The Youden's index in simplified scoring criteria (2008) is higher for scores of≥6 (probable AIH) and≥7 (definite AIH) than revised diagnostic scoring system (1999).3. The majority patients with AIH, PBC and OS are female. The peak range of age of AILD is 50-70. The characteristic features in patients with AIH were high concentration of GLO and IgG and high positive rate of SMA. The concentration of ALP, GGT and TBIL were higher in patients with OS and PBC. The positive rate of AMA in OS patients was significantly higher than that in other groups. Following our study, most of the biochemistry parameters could decrease following timely treatment.4. The lymphadenophathy is the remarkable clinical manifestation in AILD patients and it can be regarded as an important auxiliary diagnosis target for AILD, especially for AIH-PBC patients. Meanwhile, the lymphadenophathy may be a probable prognosis target for these patients, a follow-up visit should be useful for these kinds of patients.PartⅡAssociation of CD24 and Fas gene polymorphism with susceptibility to autoimmune hepatitisAims:Genome scanning studies suggest an important role of genes outside the major histocompatibility complex (MHC) in autoimmune diseases (AID). Key candidate genes are those involved in immune regulation and immune homeostasis preservation, including the genes involved in apoptosis. Our aim was to determine the association between the susceptibility in autoimmune liver diseases (AILD), especially in autoimmune hepatitis (AIH), and Fas gene polymorphism at position 670,ⅣS2nt176 andⅣS5nt82 and CD24 gene polymorphism at position 170.Methods:The genotypes of CD24 P170, Fas-670, Fas IVS2nt176 and FasⅣS5nt82 in the patients (48 AIH,19 PBC) and 68 normal controls were determined by polymerase chain reaction (PCR) following restrictive fragment length polymorphism (RFLP) or site specific PCR. The frequency of genotype and alleles were analyzed for revealing the relationship between gene polymorphisms and susceptibility of AIH and PBC. Results:1. No overall differences were observed in CD24 P170 genotype distribution and allele frequency between the AIH patients and the controls. The same results were found in PBC group.2. Significant differences were displayed in Fas-670 genotype distribution and the allele frequency between AIH patients and the controls. The frequency of AA genotype (39.58% vs 26.47%) and allele (64.58% vs 48.53%) in AIH group was higher than those in the control group. No overall differences were observed in Fas-670 genotype distribution and allele frequency between the PBC patients and the controls.3. No overall differences were observed in Fas IVS2nt176 and FasⅣS5nt82 genotype distribution and allele frequency between the AIH patients and the controls. The same results were displayed in PBC group. Meanwhile, the two genes have certain relevance.Conclusions:The Fas-670 gene polymorphism is obviously associated with the AIH susceptibility. The Fas-670 A is the susceptive allele for AIH. No significant relevance was observed between the polymorphisms of Fas IVS2nt176, IVS5nt82 and CD24 P170 and the susceptibility for AIH. Fas-670, Fas IVS2nt176, Fas IVS5nt82 and CD24 P170 gene polymorphisms have also no relations to the PBC susceptibility.