丙肝患者HCV-RNA阳性与自免肝抗体相关性研究

目的探讨丙肝患者HCV-RNA阳性感染与自免肝抗体产生的相关性。方法对330例丙肝抗体Ig G(+)患者进行HCV-RNA检测及相关的自免肝抗体检测。结果 330例肝炎患者中,有182例HCV-RNA阳性,阳性率为(55.1%),148例患者HCV-RNA阴性,阴性率为(44.8%)。将其分为两组,第一组:丙肝抗体Ig G(+),HCV-RNA均为阳性,测得AMA-M2阳性13例(7.1%),SLA阳性23例(12.6%),LKM-1阳性40例(22%),LC-1阳性11例(6%);第二组:丙肝抗体Ig G(+),HCV-RNA阴性,测得AMA-M2阳性4例(2.7%),SLA阳性6例(4.1%),LKM-1阳性19例(12.8%),LC-1阳性4例(2.7%)。两组自免肝抗体阳性率差异有统计学意义(χ2=93.4,P<0.05)。结论丙肝患者自免肝抗体检测阳性率与丙肝患者HCV-RNA阳性呈正相关。

Inhibition of p38 mitogen-activated protein kinase attenuates experimental autoimmune hepatitis: Involvement of nuclear factor kappa B

To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） in murine experimental autoimmune hepatitis （EAH）.METHODS： To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud＇s adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B （NF-KB） were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines （interferon-y, IL-12, IL-1β and TNF-α） were observed.RESULTS： The activity of p38 MAPK and NF-~：B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~：B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.

Historical reflections on autoimmune hepatitis

Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier(and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody(ANA),smooth muscle antibody(SMA) and liver-kidney microsomal(LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being(relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients

AIM: To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1. METHODS: Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies. RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.

Study on Antibodies to Liver Antigens in Chinese Patients with Different Liver Diseases

In order to observe several antibodies to liver antigens in Chinese patients with different liver diseases and to discuss the characteristics of the autoantibodies in autoimmune liver diseases, from 1412 patients, detected by indirect immunofluorescence (IIF) initially, 230 patients with abnormal ALT were chosen and divided into 5 groups: ① autoimmune diseases group, 42 cases: 18 with autoimmune hepatitis (AIH), 21 with primary biliary cirrhosis (PBC), 3 with primary sclerosing cholangitis(PSC). ② HAV group, 23 cases; ③ HBV group, 70 cases; ④ HCV group, 35 cases and ⑤ Non A-E group, 60 cases. First, ANA, AMA, SMA, liver-kidney microsomal antibody (LKM) and so on were tested by IIF.Then, LKM-1, liver cytosolic-1 (LC-1), soluble liver antigen/liver pancreas (SLA/LP) and subtype of AMA (M2) as well as ANA profile such as SS-A, SS-B and dsDNA were tested by Western blot and immunoblot strips assay, respectively. The results were that among 1412 cases, those diagnosed as AIH, PBC and PSC accounted for 12.7‰, 14.9‰ and 2.1‰, respectively, of the samples being tested. 2/230 with LKM-1 and 2/230 with SLA/LP were seen in individuals infected with AIH and HCV, respectively. All patients with PBC showed AMA and M2 antibodies. No specific ANA pattern was seen in AIH by IIF but anti-actin was only found in patients with AIH. In Non A-E group, four cases were positive of AMA and M2; three had high titer of SMA and other 4 had SS-A, SS-B or dsDNA antibodies, etc. It was concluded that the detection of anti-liver antigens, ANA profile and AMA subtypes were helpful for the diagnosis of autoimmune liver diseases and overlap syndromes. In patients with Non A-E hepatitis, the diagnosis of PBC or AIH should be taken into consideration.