Pulmonary arteritis with pulmonary arterial thrombosis and recurrent endopulmonary embolization

Summary A 41-year-old woman underwent medical examination for superficial thrombophlebitis of both lower legs. Incidentally a chronic myelogenous leukemia was diagnosed and chemotherapeutically treated. Three weeks after the first attendance the patient again suffered superficial thrombophlebitides of all extremities. Clinically she exhibited symptoms of recurrent mild pulmonary embolization. Contrast venography revealed no signs of deep venous thrombosis of legs, pelvis, or cava inferior. Despite continuous full-dose intravenous heparin administration the patient died, with signs of fulminant pulmonary embolization. Surprisingly, necropsy revealed a complete thrombotic occlusion of the pulmonary arterial system caused by pulmonary arteritis with signs of recurrent pulmonary embolization from a parietal truncus pulmonalis thrombosis. In addition, an appositional growth of parietal thrombi central from peripheral arterial ramifications had occurred. Simultaneously, superficial thrombophlebitis of all extremities was observed without any additional signs of general vasculitis. There was no strong evidence for a causal relationship between the chronic myelogenous leukemia and pulmonary arteritis nor for any other underlying systemic disorder. Therefore we consider the pulmonary arteritis a possibly primary one. This very rare disease is discussed with respect to the literature.Abbreviation CML chronic myelogenous leukemia     

Novel insights into autoimmune liver diseases provided by genome-wide association studies

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are complex disorders, resulting from the interaction of genetic and environmental factors. For many years, investigators have attempted to delineate the genetic architecture of these conditions, aiming to elucidate disease pathogenesis and identify molecular targets for pharmacotherapy. Early genetic studies consisted of HLA association studies and non-HLA candidate gene association studies, designed to identify association with selected HLA or non-HLA loci. HLA association studies identified HLA risk loci that are now well-established. Non-HLA candidate gene studies were less fruitful because they were mostly underpowered to detect modest effects and were frequently designed to investigate one or two functional polymorphisms, meaning that gene coverage was poor. Furthermore, weak associations detected in one small cohort were often never validated. If replication studies were undertaken, the results were often conflicting. More recently, a series of genome-wide association studies (GWAS) and related study designs have evaluated the impact of common genetic variants (frequency >5% in the general population) across the entire genome. These studies have identified several non-HLA risk loci for autoimmune liver disease. The majority of risk loci detected are similar to those of non-hepatic immune-mediated diseases, suggesting that outcomes from GWAS and related genetic studies reflect broad phenotypic themes rather than traditional clinical conditions. The specific genetic basis of these PBC and PSC associated inflammatory themes as determined by GWAS is described and discussed in the context of interacting genetic and non-genetic (including environmental) factors.     

The role of natural killer cells in autoimmune liver disease: A comprehensive review

Natural Killer (NK) cells are important players of the innate arm of the immune system and provide an early defense against pathogens and tumor-transformed cells. Peripheral blood NK (PB-NK) cells were first identified because of their ability to spontaneously kill tumor-cell targets in vitro without the need for specific antigen priming, which is the reason that they were named ‘natural killer’ cells. The characterization of NK cells in human tissues and body organs represented another important step forward to better understand their physiology and physiopathology. In this regard, many reports revealed over the past decade a differential anatomic distribution of NK cell subsets in several sites such as the intestine, lung, cervix, placenta and liver as well as in secondary lymphoid organs such as spleen, lymph nodes and tonsils. Among all these tissues, the liver is certainly unique as its parenchyma contains an unusually high number of infiltrating immune cells with 30–50% of total lymphocytes being NK cells. Given the constant liver intake of non-self antigens from the gastrointestinal tract via the portal vein, hepatic NK (H-NK) cells must retain a certain degree of tolerance in the context of their immune-surveillance against dangers to the host. Indeed, the breakdown of the tolerogenic state of the liver-associated immune system has been shown to induce autoimmunity. However, the role of NK cells during the course of autoimmune liver diseases is still being debated mainly because a complete characterization of H-NK cells normally resident in healthy human liver has not yet been fully disclosed. Furthermore, the differences in phenotype and functions between human and mouse H-NK cells often preclude translation of results obtained from murine models into experimental approaches to be performed in humans. Here, we provide an extensive characterization of the phenotype of H-NK cells physiologically resident in the human liver by both mentioning data available in literature and including a set of original results recently developed in our laboratory. We then review our current knowledge in regard to the contribution of H-NK cells in regulating local immune homeostasis and tolerance as well as in inducing the development of liver autoimmunity.     

Frequent overlap of active hepatitis in recurrent primary sclerosing cholangitis after living-donor liver transplantation relates to its rapidly progressive course

Recurrence of primary sclerosing cholangitis after liver transplantation is a challenging issue. Liver pathologies of recurrent primary sclerosing cholangitis after living-donor liver transplantation have not been reported. Here, liver pathologies of explanted grafts and biopsies of 9 patients who underwent retransplantation for recurrent primary sclerosing cholangitis were compared with those of native livers. Recurrence was diagnosed in 13 of 36 patients for primary sclerosing cholangitis post-living-donor liver transplantation, and 9 of them underwent retransplantation. All explanted grafts revealed biliary cirrhosis with sclerosing cholangitis, and 6 patients had additional features of active hepatitis. Liver biopsies showed that 3 had active hepatitis in addition to fibrous cholangitis at recurrence of primary sclerosing cholangitis. Two developed active hepatitis later after the diagnosis of recurrence. In explanted grafts, in addition to extensive hilar lymphoplasmacytic cholangitis, 4 cases showed hilar xanthogranulomatous cholangitis. The latter was not evident in 7 native livers. Ductopenia was extensive in all native livers, although such changes were relatively mild in explanted grafts at retransplantation. Patients with recurrent primary sclerosing cholangitis developed progressive graft failure, and the interval between diagnosis of recurrence and retransplantation (mean, 3.2 years) was shorter than that between diagnosis of primary sclerosing cholangitis and first transplantation (mean, 7.7 years). The rather rapid deterioration of recurrent primary sclerosing cholangitis after liver transplantation may be related to the frequent overlap of active hepatitis.     

Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics,treatments, and outcomes

Background/Aims

Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone.

Methods

This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes.

Results

The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups.

Conclusions

The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.     

肝病患者自身抗体特征性的研究

目的：观察抗肝抗原自身抗体在我国不同类型肝病患者中的存在状况；探讨自身免疫性肝脏疾病的自身抗体特征。方法：间接免疫荧光法初筛1412例肝功能异常血清，从中选择28例：①自身免疫性肝病组42例：初步诊断为AIH18例、PBC21例、PSC3例。②HAV组23例；③DBV组70例；④HCV组33例；⑤非甲—非戊型肝炎组60例。结合Western blot、酶免疫条带技术等分别检测ANA、AMA、SMA、LKM—1、LC—1、SLA/LP和AMA-M2亚型、dsDNA及ENA类多种抗体。结果：1412例中诊断AIH、PBC和PSC者分别为送检标本的12．7‰，14．9‰和2．1‰。28例血清中2例LKM—1阳性和2例SLA／LP阳性；按AIH的分型标准，自身免疫性肝病组属于I型AIH者14例(78％)，Ⅱ型2例(11％)，Ⅲ型2例(11％)；AIH患者ANA抗体未见特定的荧光类型。PBC患者AMA和M2全部阳性；其ANA以核膜型为主(7／14)。NonA—E组4例AMA和M2阳性，3例SMA高滴度阳性，4例出现SS-A、SS-B或dsDNA等抗体。结论：三型自身免疫性肝炎在中国都存在，肝抗原自身抗体和ANA及AMA的分型检测有助于自身免疫性肝病的诊断与治疗；少数非甲—非戊型肝炎应考虑自身免疫性肝病诊断。     

Granulomatous cholangitis in chronic hepatitis C: A new diagnostic problem in liver pathology

A case of chronic hepatitis C at the pre-clrrhotic stage complicated with hepatocellular carcinoma is reported. The patient, a 64 year old female, showed elevated levels of serum alkaline phosphatase and immunoglobulin M. Anti-mitochondrial antibodies were negative by indirect immuno-fluorescence. Western blotting using beef heart mitochondria and recombinant polypeptides coding for mitochondrial antigens revealed that the patient's serum was positive only for the E2-subunit of the branched chain ketoacid dehydro-genase complex. In the non-neoplastic liver, chronic non-suppurative cholangitis surrounded by epitheliold granuloma, resembling the granulomatous destructive cholangltis of primary biliary cirrhosis, was found. The damaged bile ducts were immunohistochemically minimally positive or ambiguous for HLA-DR, and their expression of the E2-subunit of the pyruvate dehydrogenase complex E2 (PDC-E2) was diffuse or granular, and not typical of primary biliary cirrhosis. There was no bile duct loss, and orcein-positive copper binding granules reflecting chronic cholestasis were negative in periportal hepatocytes. The overall features in this case were consistent with primary biliary cirrhosis presenting an infrequent profile of antimitochondrial antibodies and atypical expression of HLA-DR and PDC-E2 on biliary epithelial cells, with late superimposition on chronic hepatitis C. However, It is also possible that this is a case of chronic hepatitis C with hepatitis-associated bile duct damage accompanied by granulomatous reaction. Either way, this case raises new diagnostic issues in the differential diagnosis of chronic liver diseases presented with granulomatous cholangitis.     

不同肝病患者抗肝抗原自身抗体的研究

目的：观察我国不同类型肝病患者中几种抗肝抗原自身抗体的存在状况；探讨自身免疫性肝脏疾病的自身抗体特征。方法：由1412例标本中选择230例肝功能异常患者分为5组：①自身免疫性肝病组42例：自身免疫性肝炎（AIH）18例、原发性胆汁性肝硬化（PBC）21例、原发性硬化性胆管炎（PSC）3例。②HAV组23例；③HBV组70例；④HCV组35例；⑤非甲-戊型肝炎组60例。用间接免疫荧光、Western blot、酶免疫条带技术等分别检测抗核抗体（ANA）、抗线粒体抗体（AMA）、平滑肌抗体（SMA）、肝肾微粒抗体I型（LKM-1）、肝细胞胞溶质抗原I型（LC-1）、可溶性肝抗原（SLA）/肝胰抗原（LP）和AMA-M2亚型，以及SS-A、SS-B、dsDNA等多种抗体。结果：1412例中诊断AIH、PBC和PSC者分别为送检标本的1.27%，1.49%和0.21%。230例血清中2例LKM-1阳性和2例SLA/LP阳性，分别见于AIH和HCV感染者。PBC患者AMA和M2全部阳性；其ANA以核膜型为主（7/14）；AIH患者ANA抗体未见特定的荧光类型，而抗-Actin仅见于AIH者。非甲-戊组4例AMA和M2阳性，3例SMA高滴度阳性，4例出现SS-A、SS-B或dsDNA等抗体。结论：肝抗原抗体和ANA及AMA分型的检测有助于自身免疫性肝端正和重叠多种免疫性肝病的诊断；非甲-戊型肝炎诊断时应考虑自身免疫性疾病。     

HLA-DR Allele Frequencies in Mexican Mestizos with Autoimmune Liver Diseases Including Overlap Syndromes

Autoimmune liver diseases are sometimes difficult to differentiate from hepatic overlap syndromes (OS). The objective of this study was to use polymorphic genetic markers to better distinguish clinical heterogeneity in autoimmune liver disease. Since autoimmunity is the result of autoantibody production we studied HLA-DR alleles in 20 patients with autoimmune hepatitis (AIH), 16 with primary biliary cirrhosis (PBC), 10 with OS, and in 99 ethnically matched healthy individuals. Patients with OS had significantly higher alkaline phosphatase and total bilirubin levels than patients with AIH. OS patients had a higher prevalence of positive antinuclear antibodies and a higher AIH score than patients with PBC. Patients with OS also had higher total immunoglobulin levels (IgG isotype) as compared to patients with PBC. We found in PBC patients a higher gene frequency of HLA-DR4 and DR1 as compared to healthy controls (p = 0.03, OR = 2.2 and p = 0.004, OR = 4.3, respectively) and to OS patients (p = 0.01, OR = 6.8, and p = 0.004, OR = 10.0, respectively). On the other hand, the gene frequency of HLADR5 was significantly decreased in the total group of patients as compared to healthy controls suggesting a protective role of this allele for developing autoimmune liver disease.     

子宫动脉插管栓塞在妇产科良性疾病应用进展

子宫动脉插管栓塞是治疗妇科及产科各种出血的有效方法之一。生殖道及盆腔出血传统的治疗方法是局部保守治疗失败后行双侧的髂内动脉或子宫动脉结扎术 ,对于子宫动脉结扎后仍有顽固性出血的病人 ,为了挽救病人的生命 ,则行子宫全切术 ,病人失去了再生育的机会。手术治疗的缺点包括髂内动脉结扎的失败率高 ,需全身麻醉 ,术后易有并发症如感染、出血及输尿管损伤。六十年代 ,诊断性血管造影术是用于胃肠道手术探查止血失败 ,以明确动脉出血病灶的部位 ,随后有了多种经皮穿刺治疗胃肠道出血的方法 ,包括动脉内注入血管收缩剂 ,Ｗｈｏｌｅｙ气囊…     

Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression

The interferon (IFN) signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity. We have generated a unique murine model named ARE-Del, with chronic overexpression of IFNγ, by altering IFNγ metabolism. Importantly, these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis, including high titers of autoantibodies and portal inflammation. We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis. To study this hypothesis, ARE-Del^+/− mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied. JAK inhibition resulted in a significant reduction in portal inflammation and bile duct damage, associated with a significant reduction in splenic and hepatic CD4⁺ T cells and CD8⁺ T cells. Functionally, ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγ and TNF from splenic CD4⁺ T cells. Additionally, ruxolitinib treatment also decreased the frequencies of germinal center B (GC B) cells and T follicular helper (Tfh) cells and led to lower serological AMA levels. Of note, liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib treatment. Mechanistically, ruxolitinib inhibited the secretion of IL-6, TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro, indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway. Our data highlight the significance, both immunologically and clinically, of the JAK/STAT signaling pathway in autoimmune cholangitis.     

Strongyloides stercoralis hyperinfection in patient with autoimmune hepatitis and purpura fulminans

Strongyloidiosis is usually an asymptomatic chronic nematodal disease. The term hyperinfection is used to denote autoinfection, a phenomenon in which the number of worms increases enormously. Development or exacerbation of gastrointestinal and pulmonary symptoms is seen, (A) and the detection of increased numbers of larvae in stool and or sputum is the hallmark. It is known to occur with a change in immune status of the host; this can occur due to immunosuppressants. Cytomegalovirus (CMV) is also known to suppress host immunity. Due to the nonspecific presentation, the diagnosis is frequently missed, and the outcome remains poor with 15–87% mortality despite therapy. We report here a case of Strongyloides stercoralis hyperinfection following immunosuppressive therapy for autoimmune hepatitis and concomitant CMV infection with purpura fulminance and frank sepsis, with fatal outcome.     

Autoimmune hepatitis type 1 and primary biliary cirrhosis have distinct bone marrow cytokine production

We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation.     

Minimal hepatic encephalopathy may be present despite the absence of non-invasive and elastography evidence of cirrhosis in patients with primary biliary cholangitis

PurposeMinimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis.Patients and methodsFifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score.ResultsMHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC ​= ​0.753, CI_95% ​= ​0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE.ConclusionsMHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC.     

Increased proliferation activities of vascular endothelial cells and tumour cells in residual hepatocellular carcinoma following transcatheter arterial embolization

AIMS: Transcatheter arterial embolization induces extensive ischaemic necrosis or hypoxia via the obstruction of the hepatic artery in hepatocellular carcinoma (HCC). Ischaemia is strongly correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cell proliferation. The aim of this study was to evaluate whether ischaemic necrosis induced by transcatheter arterial embolization could increase the proliferative activities of intratumoral endothelial cells or tumour cells in the residual HCC. METHODS AND RESULTS: Using a double immunohistochemical technique (Ki67 antibody to determine the proliferative activity and CD34 antibody to highlight the intratumoral endothelial cells), we performed immunohistochemical staining for 24 HCCs treated by transcatheter arterial embolization. Seven HCCs without any preoperative transcatheter arterial embolization and nine cirrhosis cases were also studied as the control cases. The residual tumour was then divided into five areas at 0.5 mm intervals, according to the distance from the necrotic margin induced by embolization. The Ki67 labelling indices of the intratumoral endothelial cells and tumour cells were counted in each area. The correlation between the indices and the corresponding distance from the ischaemic necrosis was analysed. The Ki67 labelling index of intratumoral vascular endothelial cells in the area less than 0.5 mm from the necrotic margin (area 1) was 10.60 +/- 3.64% (mean +/- SD), which was twofold greater than those of the other areas more than 0.5 mm from the margin (areas 2--5) and those of the control HCCs without preoperative transcatheter arterial embolization. In addition, the proliferation labelling index of the tumour cells was 35.77 +/- 11.45% (mean +/- SD) in area 1. This was higher than those of areas 2--5 and control HCCs without preoperative transcatheter arterial embolization. There was a positive correlation between the proliferation of both endothelial and tumour cells and ischaemic necrosis (P < 0.05). CONCLUSIONS: Our study suggests that the proliferative activity of intratumoral endothelial cells and tumour cells is increased by ischaemic necrosis induced by transcatheter arterial embolization, and its effect is maximal in the area adjacent to the necrosis (less than 0.5 mm from the necrotic margin).     

Hepatic composite tumor in a patient with primary sclerosing cholangitis

A focal intrahepatic enhancing lesion with associated bile duct stricture was identified in a 25-year-old woman with a history of primary sclerosing cholangitis (PSC) who was being evaluated for increasing liver enzymes. Partial hepatectomy was performed, revealing a composite tumor with neuroendocrine and cholangiocarcinomatous differentiation. Only one composite tumor of the liver has been previously reported in the literature [H. Hidaka, S. Kuwao, S. Kokubu, K. Yanagimoto, A. Satomichi, M. Takada, T. Nakazawa, K. Saigenji, Mixed carcinoid-adenocarcinoma of the liver, Intern. Med. 39 (2000) 910–913], and to our knowledge, this is the first report of such a tumor in association with PSC. We report this very unusual case and discuss the potential association of neuroendocrine carcinoma with primary sclerosing cholangitis.     

Decreased serum DNase1-activity in patients with autoimmune liver diseases

Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC). Sera from 146 patients with chronic hepatitis B or C, 140 with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and 114 healthy individuals served as disease and healthy controls. Available serum samples during remission from 50 AIH and 39 PBC patients were also investigated by paired analyzes. DNase1-activity was significantly lower in AIH, PBC and PSC compared to viral hepatitis (p?p?p?=?0.03), NAFLD/NASH (p?p?p?p?1400?mg/dl; p?p?p?p?=?0.008). In PSC, DNase1-activity was inversely associated with alkaline phosphatase (ALP) (p?p?p?相似文献   

部分脾栓塞在肝癌伴脾亢介入治疗中的应用

目的:对原发性肝癌(肝癌)伴脾功能亢进(脾亢)患者行部分脾栓塞,使其血细胞恢复正常,以便能进一步行肝动脉化疗。方法:对46例不能行手术切除、且血细胞明显低于正常的肝癌伴脾亢的患者行部分脾栓塞术,栓塞面积控制在50%-70%,栓塞前后测定血细胞数量,并作方差分析和t检验。结果:脾栓术后24小时、48小时、72小时、1周、2周、4周的血WBC和PLT均较栓塞前明显升高(P<0.05和P<0.01)。结论:部分脾栓塞能治疗脾功能亢进,提高血细胞数量,使肝癌伴脾亢患者的肝动脉化疗能正常进行。     

Using GWAS to identify genetic predisposition in hepatic autoimmunity

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major hepatic autoimmune conditions. Patient morbidity and mortality remain high across these three diseases, and an unmet need for rational therapy exists. Disease understanding has focused on combining clinical and laboratory based science to provide better insights into the joint host and environmental factors necessary for the initiation, and perpetuation, of hepato-biliary inflammation. Twin studies, family studies, population studies and an inter-relationship with other autoimmune phenomena suggest a genetic component to risk for each disease. Until recently, understanding of this genetic risk has been limited to HLA haplotypes. Associations with risk-conferring and protective HLA haplotypes are present in all three diseases. Over the last few years, genome-wide association studies (GWAS), and related genetic association studies, have greatly increased understanding of the genetic risk signature of these three diseases and autoimmunity in general. Here we consider the rationale for GWAS in general and with specific reference to hepatic autoimmunity. We consider the process of GWAS, and highlight major findings to date. Potential functional implications of key findings are discussed including the IL-12/STAT4 pathway in PBC and the CD28/IL-2 pathway in PSC. We describe the marked pleiotropy demonstrated by PBC and PSC, which is consistent with other autoimmune diseases. Further, we focus on specific gene associations including SH2B3, which is common to all three diseases, and FUT2 in PSC, which represents a link between environment and genetics. We review attempts to translate GWAS findings into basic laboratory models including in vivo systems and highlight where clinical observations relate to genetics. Finally we describe deficiencies in GWAS to date and consider future study of genetics in hepatic autoimmunity.