DSG-I型电脑肝病治疗仪治疗酒精性肝病

目的观察肝病治疗仪治疗酒精性肝病的疗效。方法53例酒精性肝病患者随机分为两组,对照组给予常规的保肝治疗,治疗组在常规治疗基础上加用肝病治疗仪照射肝区。观察治疗前后患者临床症状,肝功能及肝纤维化指标的变化。结果治疗组患者治疗后ALT、TBIL和肝纤维化指标显著降低。临床症状明显改善。结论DSG-I型肝病治疗仪能明显改善酒精性肝病患者的临床症状,恢复肝功能,降低肝纤维化的指标。     

Spontaneous IgA Synthesis by Blood Mononuclear Cells in Alcoholic Liver Disease

Changes in the concentration and composition of serum immunoglobulin A (IgA) and deposits of IgA in tissues are well-known characteristics of alcoholic liver disease. We investigated whether these changes also accompany IgA synthesis by peripheral blood mononuclear cells (MNC), by counting immunoglobulin-producing cells using a solid-phase enzymatic 'spot' test, and by analysis of immunoglobulin content in lysed cells with culture supernatant using conventional enzymatic methods. Patients with alcoholic liver disease exhibited a significantly higher number of spontaneously IgA-producing cells than did normal healthy controls (1.7 X 10(6) cells/blood and 0.5 X 10(6) cells/blood, respectively, P less than 0.01). The IgA content of MNC directly after isolation was also higher (38 and 13 ng/10(6) MNC, respectively, P less than 0.01), as was the IgA production during an unstimulated 6-day culture period (520 and 95 ng/10(6) MNC put into culture, respectively, P less than 0.001). The spontaneously IgA-producing cells assessed directly after isolation of mononuclear cells correlated with the IgA production during an unstimulated culture (P less than 0.01). We conclude that in alcoholic liver disease, B lymphocytes circulate which may have been activated in vivo.     

Observations on the Ultrastructure of Hepatocyte Cytoplasmic Inclusions in Alcoholic Liver Disease

Abstract

Hepatocyte cytoplasmic inclusions in six biopsy and eight autopsy liver specimens from patients with chronic alcoholism showing unequivocal alcoholic hyalin (Mallory bodies) at the light microscopic level were defined by electron microscopy. Additionally, these structures were found to be generally identifiable in the same and other paraffin embedded liver tissue reprocessed for electron microscopy. The inclusions were ultrastructurally grouped as five nonmembrane limited and two complete or partially membrane bound admixtures of fibrillar, granular and amorphous components of variable distribution and electron density. Membrane free types included characteristic (A) interdigitating filaments, (B) closely packed filamentous and amorphous material, (C) whorl-like fibrils in parallel array, (D) loosely arranged discrete or intertwined long wavy fibrils or membranous fragments, (E) large serpiginous masses of highly electron dense amorphous material. Membrane limited forms showed (F) scattered vesicular and fibrillar or (G) uniformly particulate and fibrillar content, completely or partially surrounded by a single or double membrane respectively.

The demonstrated ultrastructural diversity of hepatocyte cytoplasmic inclusions and their stability even after postmortem autolysis of paraffin processing, or both, is of significance in diagnosis as well as in potential analysis of isolated liver cell fractions.     

酒精性肝病肝细胞ICAM-1表达的实验研究

目的 研究细胞间黏附分子-1（ICAM-1）在酒精性肝病发病过程中的表达及意义。方法 选择雄性Wistar大鼠40只，分为正常对照组（简称对照组）和酒精性肝病模型组（简称模型组），每组各20只。采用FACScan型流式细胞仪，检测两组动物复制模型后的4、8、12、16周末肝细胞ICAM-1的表达。结果 与对照组比较，模型组在复制模型后8周、12周及16周末的ICAM-1表达有显著性增加（P〈0．05）；模型组自身比较，在复制模型8周末之后，肝细胞ICAM-1的表达逐步加重（P〈0．05）。结论 酒精性肝病病情严重程度与肝细胞ICAM-1的表达呈正相关，提示ICAM-1参与酒精性肝病的发生和发展。     

Clinical Characteristics and Prognostic Impact of Bacterial Infection in Hospitalized Patients with Alcoholic Liver Disease

Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na <135 mM/L, albumin <2.5 g/dL, C-reactive protein ≥20 mg/L, systemic inflammatory response syndrome (SIRS) positivity were independently associated with bacterial infection in patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P < 0.001) higher than those without infection (22.3% vs. 5.1% and 32.3% vs. 8.2%, respectively). Furthermore, bacterial infection (HR, 2.2; 95% CI, 1.049-4.579, P = 0.037), SIRS positivity (HR, 2.5; 95% CI, 1.240-4.861, P = 0.010), Maddrey''s discriminant function score ≥32 (HR, 2.3; 95% CI, 1.036-5.222, P = 0.041), and hemoglobin <12 g/dL (HR, 2.4; 95% CI, 1.081-5.450, P = 0.032) were independent predictors of short-term mortality. In conclusion, bacterial infection and SIRS positivity predicted short-term prognosis in hospitalized patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.

Graphical Abstract

相似文献   

Effect of Lipopolysaccharide on the Progression of Non‐Alcoholic Fatty Liver Disease in High Caloric Diet‐Fed Mice

The incidence of non‐alcoholic steatohepatitis (NASH) is increasing. Because gut microbiota have been highlighted as one of the key factors in the pathogenesis of metabolic syndrome, we investigated the involvement of the bacterial component in the progression of non‐alcoholic fatty liver (NAFL) to NASH. C57BL/6 mice were fed with maintenance food (MF, groups A and B) or a high caloric diet (HCD, groups C and D) for 1 month. Mice were then divided into four groups: Groups A and C were inoculated with PBS, while groups B and D were inoculated with lipopolysaccharide (LPS) plus complete Freund's adjuvant (CFA). The inoculations were performed a total of 3 times over 3 months. At 6 months, while hepatic steatosis was observed in groups C and D, cellular infiltration and fibrosis were less evident in group C than in group D. Inflammatory cytokines were upregulated in groups B and D. 16S rRNA pyrosequencing of whole colon homogenates containing faeces showed that certain bacterial groups, such as Bacteroidaceae, Peptostreptococcaceae and Erysipelotrichaceae, were increased in groups C and D. Although loading of bacterial components (LPS) resulted in hepatic inflammation in both MF‐ and HCD‐fed mice, HCD feeding was more crucial in the progression of NAFL during the triggering phase.     

Deletion of Mir155 Prevents Fas-Induced Liver Injury through Up-Regulation of Mcl-1

Fas-induced apoptosis is involved in diverse liver diseases. Herein, we investigated the effect of Mir155 deletion on Fas-induced liver injury. Wild-type (WT) mice and Mir155 knockout (KO) mice were i.p. administered with the anti-Fas antibody (Jo2) to determine animal survival and the extent of liver injury. After Jo2 injection, the Mir155 KO mice exhibited prolonged survival versus the WT mice (P < 0.01). The Mir155 KO mice showed lower alanine aminotransferase and aspartate aminotransferase levels, less liver tissue damage, fewer apoptotic hepatocytes, and lower liver tissue caspase 3/7, 8, and 9 activities compared with the WT mice, indicating that Mir155 deletion prevents Fas-induced hepatocyte apoptosis and liver injury. Hepatocytes isolated from Mir155 KO mice also showed resistance to Fas-induced apoptosis, in vitro. Higher protein level of myeloid cell leukemia-1 (Mcl-1) was also observed in Mir155 KO hepatocytes compared to WT hepatocytes. A miR-155 binding site was identified in the 3′-untranslated region of Mcl-1 mRNA; Mcl1 was identified as a direct target of miR-155 in hepatocytes. Consistently, pretreatment with a siRNA specific for Mcl1 reversed Mir155 deletion–mediated protection against Jo2-induced liver tissue damage. Finally, restoration of Mir155 expression in Mir155 KO mice abolished the protection against Fas-induced hepatocyte apoptosis. Taken together, these findings demonstrate that deletion of Mir155 prevents Fas-induced hepatocyte apoptosis and liver injury through the up-regulation of Mcl1.miRNAs are a class of small noncoding RNAs that regulate gene expression through binding to specific sequences of their targeted mRNAs.¹ miR-155 was initially identified as a specific miRNA for hematopoietic and immune cells and is among the first miRNAs linked to immunity and inflammation.^2–4 Indeed, miR-155 has been shown to modulate the production of cytokines in various immune cells; the expression of Mir155 is up-regulated in multiple immune cell lineages on stimulation with Toll-like receptor ligands, inflammatory cytokines, and specific antigens.^5–9 Subsequent studies have shown that miR-155 also mediates functions outside the hematopoietic and immune systems.^10,11 In the liver, miR-155 has been shown to play a role in hepatocarcinogenesis,^12–15 although its mechanism of action remains to be further defined. miR-155 has also been shown to contribute to alcohol-induced liver injury through induction of tumor necrosis factor α production in macrophages.¹⁶ Interestingly, the level of miR-155 is increased in serum and plasma in patients with alcoholic and inflammatory liver injuries.^17,18 These observations suggest a potential role of miR-155 in liver injury and liver diseases. However, at present, the biological functions and mechanisms of miR-155 in liver cells have not been delineated.The current study aimed to determine the effect and mechanism of miR-155 in Fas and lipopolysaccharide (LPS)/d-galactosamine (D-GalN)–mediated liver injury in mice. Our data show that deletion of Mir155 protects against Fas-induced hepatocyte apoptosis and liver injury but not LPS/D-GalN–induced liver injury. The role of miR-155 in hepatocytes was demonstrated by in vitro studies using hepatocytes isolated from Mir155 knockout (KO) mice. Myeloid cell leukemia-1 (Mcl-1) was identified as a direct target of miR-155 in hepatocytes. Our results reveal a novel role of miR-155 in hepatocytes for regulation of Mcl1 and protection against Fas-induced apoptosis.     

IgM Turnover in Chronic Liver Disease

The turnover of radioiodine-labelled homologous IgM was studied on 16 occasions in 15 patients with chronic liver disease (e.g. cryptogenetic cirrhosis, chronic hepatitis, alcoholic cirrhosis). Nine were untreated, 5 received prednisone, and 2 azathioprine at the time of investigation. Serum IgM varied from 0.55 to 4.02 g per 1. Four patients had normal IgM turnover. In 6 studies the serum IgM concentration was elevated owing to an increased synthesis rate; however, in 5 of them the fractional catabolic rate, too, was accelerated. In 3 studies a normal serum concentration was combined with a high normal synthesis rate and increased degradation rate. One patient who was reinvestigated after 11 months of azathioprine treatment showed a decrease in serum IgM due to lowered synthesis. The IgM turnover pattern was not correlatable0 to the type of cirrhosis or to the treatment.     

非酒精性脂肪性肝病的治疗研究

非酒精性脂肪性肝病（NAFLD）是一种由胰岛素抵抗、肝脏炎症、高脂血症等多种原因导致的慢性肝脏疾病。NAFLD现已成为欧美等发达国家以及我国最常见的慢性肝病之一。根据流行病学调查显示,NAFLD在我国发病率约为15%,而在欧美等发达国家发病率已超过20%。NAFLD死亡率高于普通人群,因此针对NAFLD的有效治疗十分重要。目前在临床上针对其治疗主要包括生活方式干预、药物治疗以及外科手术治疗。本文结合国内外文献对NAFLD的治疗研究进行综述。     

Liver Mitochondria in Health and Disease

Abstract

Samples of formaldehyde fixative solutions were taken from a random selection of 100 tissues submitted to a large tissue repository. The solutions were tested for formaldehyde concentration, pH, osmolality, content of organic solvents and buffering capacity. There were considerable variations in the fixative samples with respect to all variables tested. While all tissue repository specimens examined were adequate for histopathology, this adequacy was presumably due to extended formaldehyde immersion, a luxury not often enjoyed in a clinical setting. Simple analytical procedures within the reach of many clinical laboratories are described for testing fixative solutions.     

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases

Background: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs.

Methods: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies.

Results: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies.

Conclusions: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.     

Isolation of Induced Pluripotent Cells from Stromal Liver Cells of Patients with Alcoholic Cirrhosis

Bulletin of Experimental Biology and Medicine - Stromal liver cells obtained from liver biopsy specimens of a patient with alcoholic cirrhosis can proliferate for a long time in culture passing...