Autoantibodies related to interferon therapy in chronic hepatitis B may affect the therapeutic response to interferon]

We have evaluated the problem of autoantibodies such as antinuclear antibodies (ANA), smooth muscle antibody (SMA) and antibodies to thyroid microsomal (TMA) and to thyroglobulin (TGA) related to interferon therapy in 27 patients with chronic hepatitis B. Anti-interferon antibody was also studied by Western blot method. Eight patients had ANA and 2 had SMA during interferon therapy. However, 6 of the 8 patients were ANA positive and one of the 2 was SMA positive prior to interferon treatment. No patients developed TMA, TGA or anti-interferon antibody. Eight (29.6%) of the 27 patients had clearance of both DNA polymerase and HBeAg and persistent normalization in alanine aminotransferase levels with interferon therapy. Seven of the 8 responders developed none of the autoantibodies related to interferon therapy. These results suggest that the presence of ANA or SMA during treatment may affect the therapeutic response to interferon.     

Clinical significance of serum auto-antibodies in Chinese patients with chronic hepatitis C: Negative role of serum viral titre and genotype

Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) have been reported in 10–66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto-antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and HCV genotype) were compared between patients with and without serum auto-antibodies. Fifty-eight (48%) patients were associated with positive serum autoantibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto-antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not correlated to the presence of serum auto-antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.     

Antinuclear antibodies in patients with systemic lupus erythematosus: a comparison of counterimmunoelectrophoresis and immunoblotting

Summary Traditionally, the method used mostly to identify antinuclear antibody (ANA) specificities is the counterimmunoelectrophoresis technique (CIE), in which a salt extract of rabbit thymus powder (so-called extractable nuclear antigen or ENA) serves as the source of antigen. Recently, the immunoblotting technique (IBT) has been introduced in the serology of antinuclear antibodies. A nuclear extract of HeLa cells is generally used as antigen in this method. In this paper, we compared both methods using sera of patients with active systemic lupus erythematosus (SLE). Only anti-Sm, anti-RNP, and Anti-SSB were taken into consideration, as the former technique only allowed the identification of these specificities. Within these restrictions, we found that, of 77 patients with SLE, 21 had CIE-detectable antibodies in their circulation and 29 IBT-detectable antibodies. Anti-RNP and anti-SSB were detected more frequently with the CIE than with the IBT; anti-Sm, on the other hand, was detected more frequently with the IBT than with the CIE. Several significant correlations were found between incidences of measured antibody specificities and disease features. The presence of anti-RNP (both if measured with the IBT or with the CIE) was found to be negatively correlated with nephritis. If measured with the IBT, the presence of anti-Sm correlated negatively with hematological disorders, and the presence of anti-SSB correlated positively with renal involvement. Only if measured with the CIE did the presence of anti-SSB correlate negatively with central nervous system disorders.     

Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome

Autoantibodies in hepatitis C virus–infected patients may indicate autoimmune hepatitis or other immune‐mediated diseases. This may impact safety and efficacy of interferon‐based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched‐pair analysis was performed matching one autoantibody‐positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.     

Induction of autoantibodies during prolonged treatment with infliximab

OBJECTIVE: To determine the frequency and correlates of autoantibody formation in patients with rheumatic diseases treated with infliximab in a routine clinical setting. METHODS: All patients receiving at least 5 infusions of infliximab, and with anticipated continuation, were prospectively evaluated for the development of the following antibodies: antinuclear antibody (ANA), anti-DNA, anti-Sm, anti-RNP, anti-SSA and anti-SSB. Correlates with pharmacologic treatments, response to infliximab, and adverse events were assessed. RESULTS: Seventy-six percent of 42 patients receiving prolonged treatment with infliximab developed new autoantibodies, and these persisted in 57%. The most common new autoantibody was ANA in 45%, followed by anti-DNA in 33%, anti-Sm in 31%, and anti-RNP in 29%. New autoantibody formation was associated with both a greater number of infusions (p = 0.015) and a higher total dose of infliximab infused (p = 0.047). No other treatment, disease characteristic, or loss of efficacy to infliximab discriminated between those developing antibodies compared to those without new antibody formation. No patient developed clinical signs of a new connective tissue disease. CONCLUSION: Autoantibody formation is seen commonly in patients receiving prolonged treatment with infliximab. Concomitant immunosuppressive treatments did not preclude the formation of antibodies. The clinical significance of antibody formation remains to be determined.     

HBV前C区突变及干扰素抗体对干扰素疗效的影响

目的：探讨干扰素治疗与乙型肝炎病毒前C区突变（1896位点C→A点突变）及干扰素抗体的关系。方法：分别以PCR法及酶联免疫吸附试验法（ELISA）检测86例慢性HBV感染患者血清中HBV前C区突变株及干扰素抗体。结果：CHB重度组检出率明显高于慢性携带者及CHB轻度组,P＜0．005;38例CHB接受干扰素治疗,突变株组和野生株组对干扰素素近期应答率相似,但突变株组复发率为70．0％,显著高于野生株组的23．1％;干扰素抗体阳性组的近期应答率38．5％,显著低于阴性组的72．0％。结论：突变感染与肝病严重程度有关,HBV前C区突变和干扰素抗体可影响干扰素的抗病毒疗效。     

Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate...     

A case of chronic hepatitis C developing insulin-dependent diabetes mellitus associated with various autoantibodies during interferon therapy

We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.     

乙型肝炎患者乙型肝炎病毒前C区变异 及干扰素抗体对干扰素治疗的影响

目的　探讨干扰素治疗与乙型肝炎病毒(HBV)前C区变异(1896位点G→A点变异)及干扰素抗体的关系。方法　分别以PCR及ELISA方法检测86例慢性HBV感染患者血清中HBV前C区变异株及干扰素抗体。结果　ALT>100IU/L组变异株检出率(40.4%)显著高于ALT≤100IU/L组(8.8%),两组比较差异有显著性(P<0.005);CHB重度组检出率明显高于慢性携带者及CHB轻度组(P<0.005);38例CHB接受干扰素治疗,变异株组和野生株组对干扰素近期应答率相似,但变异株组复发率(70.0%)显著高于野生株组(23.1%);干扰素抗体阳性组的近期应答率(38.5%)显著低于阴性组(72.0%)。结论　变异株感染与肝病严重程度有关,HBV前C区变异和干扰素抗体可影响干扰素的抗病毒疗效。     

Effect of lactoferrin in patients with chronic hepatitis C: combination therapy with interferon and ribavirin

OBJECTIVES: Lactoferrin has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of combined triple therapy of lactoferrin, interferon and ribavirin in patients with CHC. METHODS: A total of 111 Japanese patients with CHC were randomly assigned to a lactoferrin group (n = 50) and a control group (n = 61). The lactoferrin group was treated with lactoferrin for 8 weeks and then with lactoferrin, interferon and ribavirin for 24 weeks; the control group was treated with interferon and ribavirin for 24 weeks. Serum anti-lactoferrin antibody, clinical and laboratory measurement were determined. RESULTS: The mean HCV RNA titer significantly decreased at the end of lactoferrin monotherapy. Sustained virological response to therapy was significantly higher (P < 0.05) in the lactoferrin responder group (55%) than in the control group (18%). CONCLUSIONS: The results show that the decrease in HCV RNA titer by lactoferrin monotherapy contributes to the effectiveness of the combined therapy of interferon and ribavirin in patients with CHC. Lactoferrin is a potential useful adjunct treatment for patients with CHC.     

抗核抗体阳性肝硬化患者的临床特点

为了探讨抗核抗体 (ANA)阳性肝硬化患者的临床特点及环磷酰胺的治疗效果 ,检测 82例肝硬化患者血清ANA ,比较ANA阴性和阳性肝硬化患者的临床特点 ,观察环磷酰胺治疗ANA阳性肝硬化患者的疗效。结果与ANA阴性肝硬化患者比较 ,ANA阳性肝硬化患者女性多见 ,发病年龄较大 ,乙型肝炎病毒感染率低 ,Child -Pugh分级C级比例高 ;腹水、下肢浮肿症状较重 ;血清白蛋白水平低、球蛋白水平高 (P <0 0 5 )。ANA阳性肝硬化患者经环磷酰胺治疗后症状均好转 ,其中与对照组比较 ,腹水、下肢浮肿症状改善明显 (P <0 0 5 ) ;血清总蛋白、白蛋白水平增加 ,球蛋白水平下降 (P <0 0 5 ) ;部分患者ANA转阴 (P <0 0 5 )。说明ANA阳性肝硬化患者有其自身的临床特点 ,环磷酰胺治疗有效。     

Long-term follow-up of patients with chronic hepatitis C treated with alpha-interferon.

We reanalyzed the results of a pilot study of recombinant alpha-interferon therapy for chronic non-A, non-B hepatitis in light of the recent discovery of the hepatitis C virus and the development of diagnostic assays for this agent. Stored serum samples from 10 patients treated between 1984 and 1986 were tested for antibody to hepatitis C virus and hepatitis C virus RNA before, during and after therapy. In addition, the current clinical, serum biochemical and virological statuses of these patients were evaluated to determine the long-term effects of interferon therapy. All patients had evidence of hepatitis C virus infection, with hepatitis C viral RNA, antibody to hepatitis C virus or both markers detectable in serum. Serum hepatitis C virus RNA was found to disappear in seven of eight patients whose aminotransferase levels became normal with interferon therapy but remained present in two patients who did not respond to therapy. Levels of hepatitis C virus RNA decreased and disappeared when serum aminotransferases fell to normal levels but rose with subsequent elevation of aminotransferase levels in two patients who had relapses in disease when interferon was stopped. During a follow-up of 3 to 6 yr, hepatitis C virus RNA remained undetectable in the six patients whose serum aminotransferase levels remained normal after interferon therapy. However, neither initial titers of hepatitis C virus RNA nor disappearance of viral RNA from serum during treatment predicted a sustained response. Thus long-term beneficial responses to alpha-interferon can occur in patients with chronic hepatitis C and are associated with sustained loss of hepatitis C virus RNA from serum.     

Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.     

Antinuclear antibody titer and treatment response to peginterferon plus ribavirin for chronic hepatitis C patients

Positive serum antinuclear antibody (ANA) is not infrequent in chronic hepatitis C virus (HCV)-infected patients. This prospective study evaluated the impact of ANA on the response to and safety of peginterferon/ribavirin combination therapy for chronic hepatitis C patients in clinical practice. We enrolled 243 consecutive patients who were treated with a 24-week regimen of peginterferon-α plus ribavirin, with a 24-week follow-up period. ANA titer was determined before antiviral treatment. The primary end-point was sustained virological response (SVR), defined as HCV RNA <50 IU/mL throughout the follow-up period. Overall, 187 (77.0%) patients experienced a SVR. In the 105-patient HCV genotype non-1 group, patients with ANA titer ≥1:80 had a significantly lower SVR rate than those with ANA titer <1:80 (67.7% vs. 95.8%, respectively, p = 0.013). In contrast, in the 138-patient HCV genotype 1 group, the SVR rate did not differ between patients with and without ANA titer ≥1:80. Multivariate regressive analyses showed that ANA ≥1:80, age and HCV RNA levels were independent factors associated with SVR in HCV genotype non-1 patients; whereas HCV RNA levels and hepatic fibrosis were prognostic predictors of SVR in HCV genotype 1 patients. The frequencies of adverse events were similar between patients with and without ANA seropositivity. Peginterferon/ribavirin combination therapy is effective and safe in ANA-positive chronic hepatitis C patients. A high ANA titer was a negative prognostic factor for treatment response in HCV genotype non-1 patients.     

Detection and identification of antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing

OBJECTIVE: To provide data on (a) the probability of detecting antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing and (b) the probability of detecting more specific antinuclear reactivities (anti-DNA and anti-extractable nuclear antigens (anti-ENA)) in serum samples with a positive screening test (indirect immunofluorescence on HEp-2 cells). METHODS: Serum samples from 10 550 consecutive patients sent to the laboratory for ANA detection were analysed. In ANA positive serum samples (23.5% of referred serum samples), ANA were identified by indirect immunofluorescence on Crithidia, by immunodiffusion, and by line immunoassay. Because anti-SSA antibodies were the most frequently identified ANA, sensitively detected by line immunoassay, additional immunoassays were developed to confirm the specificity of the line immunoassay result. RESULTS: At least one fine reactivity could be identified in 21.1% of ANA positive serum samples: anti-dsDNA in 3.2%; anti-ENA (anti-SSA 10.5%, anti-SSB 6.7%, anti-RNP 2.7%, anti-Sm 1.8%, anti-Scl70 1.2%, anti-Jo-1 0.2%) in 15.8%, rRNP and anti-Cenp-B in respectively 0.5% and 4.0%. Multiple reactivities were found in 7.9%. For anti-ENA antibodies, line immunoassay was more sensitive than immunodiffusion (15.4% v 7.7%; p<0.0001). The sensitive detection of anti-SSA antibodies by line immunoassay was confirmed by additional assays. CONCLUSIONS: The data from this analysis are useful in estimating the probabilities of detecting specific ANA. Line immunoassay was shown to be a sensitive test for the detection of anti-ENA antibodies.     

Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-α therapy

BACKGROUND AND AIMS Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy. PATIENTS AND METHODS We studied prospectively 207 patients positive for anti-HCV and viral RNA. One hundred and forty-four of them received a therapeutic trial of one year with interferon-α. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients. RESULTS Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti-DNA and anti-Sjögren’s antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjögren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued. CONCLUSIONS No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre-existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.     

Hepatitis C Virus and Cardiomyopathy

The importance of hepatitis C virus infection has been recently noted in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. In a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with hypertrophic cardiomyopathy and in 42 of 663 patients (6.3%) with dilated cardiomyopathy; these prevalences were significantly higher than that found in volunteer blood donors in Japan. Hepatitis C virus antibody was detected in 650 of 11,967 patients (5.4%) seeking care in 5 academic hospitals. Various cardiac abnormalities were found, and arrhythmias were the most frequent. These observations suggest that hepatitis C virus infection is an important cause of a variety of otherwise unexplained heart diseases. As a collaborative research with National Cardiovascular Center and Juntendo University, we tried to detect hepatitis C virus genomes using paraffin sections of autopsied hearts. Among 106 hearts examined, beta-actin gene was amplified in 61 hearts (52.6%). Among these, hepatitis C virus RNA was detected in 13 hearts (21.3%), and negative strands in 4 hearts (6.6%). Hepatitis C virus RNA was found in 6 hearts (26.0%) with hypertrophic cardiomyopathy, 3 hearts (11.5%) with dilated cardiomyopathy, 4 hearts (33.3%) with myocarditis. These hepatitis C virus RNA positive samples were obtained between 1979 and 1990, indicating that hepatitis C virus RNA can be amplified from paraffin-embedded hearts preserved for many years. More recently, we examined the effect of interferon on myocardial injury associated with active hepatitis C. As TL-201-SPECT was a more sensitive method to detect myocardial injury induced by hepatitis C virus than electrocardiography or echocardiography, we used TI-SPECT scores to evaluate the effect of interferon on myocardial injury. SPECT scores improved in 8 patients (53%) out of 15 patients in whom interferon therapy was completed. Circulating hepatitis C virus disappeared after interferon therapy in all 11 patients with improvement or no change, but hepatitis C virus genomes persisted in the blood in 2 aggravated patients. Although this study is preliminary, interferon therapy is a promising treatment for myocardial diseases caused by hepatitis C virus infection.     

血清腺苷脱氨酶和淀粉样蛋白A辅助诊断自身免疫性肝炎患者临床价值分析*

目的 分析应用血清腺苷脱氨酶(ADA)和淀粉样蛋白A(SAA)辅助诊断自身免疫性肝炎(AIH)患者的临床价值。方法 2017年1月～2018年12月我院收治的AIH患者60例,乙型肝炎、丙型肝炎和酒精性肝炎患者98例和同期健康人100例,采用胶乳比浊法检测血清SAA,采用谷氨酸脱氢酶偶联速率法检测血清ADA,采用间接免疫荧光法检测血清抗核抗体(ANA),采用免疫印迹法检测血清抗肝肾微粒体Ⅰ型(LKM-1)、抗肝细胞浆抗体Ⅰ型(LC-1)、抗可溶性肝抗原/肝胰抗原(SLA/LP)。 结果 AIH组血清SAA水平为(58.7±6.2)mg/L,显著高于非AIH组【(12.3±2.5)mg/L,P<0.05】或健康人【(6.3±1.2)mg/L,P<0.05】,血清ADA水平为(88.4±10.1)U/L,显著高于非AIH组【(17.7±3.0)U/L,P<0.05】或健康人【(10.3±2.1)mg/L,P<0.05】;AIH组血清ANA、抗LKM-1和抗SLA/LP阳性率分别为68.3%、16.7%和11.7%,而仅非AIH组血清ANA阳性率为42.9%(P<0.05); 在本组AIH患者,血清ANA诊断的灵敏度、特异度和准确性分别为68.3%、57.1%和60.0%,而以血清SAA＞52.1 mg/L或ADA＞77.9 U/L为截断点,对血清ALT升高者在排除常见病因引起的肝功能损伤后,其辅助诊断AIH的灵敏度、特异度和准确性分别被提高到76.7%、89.8%和70.4%。结论 对血清自身抗体阴性者,在排除常见的引起肝损伤的病因后,血清ADA或/和SAA异常升高,有助于对AIH的诊断,值得进一步探讨。     

原发性胆汁性肝硬化患者60例自身抗体检测分析

目的研究原发性胆汁性肝硬化(PBC)患者自身抗体的类型。方法分析北京大学人民医院1995-01~2004-12收治的60例原发性胆汁性肝硬化患者的自身抗体检测结果和临床资料。结果60例患者中抗线粒体抗体(AMA)阳性者45例(75%),抗核抗体(ANA)阳性者36例(60%),其中斑型ANA14例(23%),多核点ANA12例(20%),核膜型ANA10例(16%),着丝点型ANA6例(10%),均质型ANA1例(1·6%),抗SSA阳性者12例(20%),抗SSB阳性者6例(10%),抗RNP阳性者1例。对比AMA阴性者中多核点型ANA阳性者3例,核膜型ANA阳性者4例。7例PBC患者存在一种以上的ANA荧光模式。AMA阳性和阴性患者临床资料,两组患者的年龄、生化及免疫学指标差异无显著性意义。结论AMA阳性和阴性患者有相似的临床表现、生化和免疫学指标。除AMA外,PBC患者可出现多种自身抗体。多核点型和核膜型ANA的检测有助于AMA阴性PBC的诊断。     

Clinical Characteristics of Patients with Hepatitis C Virus-Related Chronic Liver Disease Seropositive for Anticentromere Antibody

The association between anticentromere antibody (ACA) and hepatitis C virus (HCV) infection remains unclear. We subjected eight patients with HCV-related chronic liver disease (CLD) seropositive for ACA to a battery of clinical and laboratory tests. The patient cohort was dominated by females, and four of the eight (50%) patients had a concomitant autoimmune disease. All of the patients had high titers of ACA (≥1:320). The histological activity index scores in chronic hepatitis C (CH-C) patients with ACA were significantly higher than those in CH-C patients without antinuclear antibody (ANA) (12.8 ± 1.8 vs. 8.3 ± 4.5, P = 0.0372). The frequency of human leukocyte antigen (HLA) DR-8 in patients with HCV-related CLD seropositive for ACA was significantly higher than that in patients with CH-C seronegative for ANA (71 vs. 18%, P = 0.0108). These findings suggest that ACA is induced by chronic HCV infection in association with HLA DR-8, and that CH-C patients with ACA exhibit more severe hepatic fibrosis and inflammation than CH-C patients without ANA.