Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: A pilot study

AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients.METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustainedresponders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three timepoints (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs.RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy.CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- α may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.

Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma

AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs.

Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (ANA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). CONCLUSION:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.

用于纳米网络的软件定义超材料设计与开发

介绍了一类可通过软件来控制电磁特性的可编程超材料。这种软件定义超材料(SDM)源于超材料与纳米网络的结合。超材料是一种人工结构,具有特殊的材料特性,在自然界中无法找到这类材料。自超材料出现以来,近几年许多研究领域都取得了突破性进展,例如电磁隐身(隐身衣)、辐射吸收、声波光波过滤,以及可应用于传感器和植入式通信设备的高效能天线等。然而,现有的超材料结构是"僵化"的,即,它们不具备可重构功能。这一缺陷使超材料只有少数具有精密设备的实验室才能制造,这阻碍了该领域的发展与创新,尤其是限制了超材料的应用范围,使得它只能在静态结构中应用。文章所提出的软件定义超材料类似于"可塑的"(可重构)超材料,其特性可以通过计算机接口来编程控制。这种控制是通过在超材料结构并入纳米机器网络来实现的。纳米机器可以接收来自用户的指令并对超材料外轮廓做出简单的几何调整,以达到调整超材料电磁特性的目的。文章讨论了软件定义超材料的结构、预期特性和实现方面的问题,并通过对预期性能的仿真讨论了合适的纳米组网模型,概括总结了在软件定义超材料的分析、设计、样机研究、制造和初始应用场景等方面所存在的研究难点。