Pathology of nonalcoholic steatohepatitis.

To date, histologic evaluation, most commonly in the form of liver biopsy, remains the gold standard in evaluation of nonalcoholic fatty liver disease (NAFLD). Histologic evaluation was fundamental to the initial studies that introduced and defined the concept of fatty liver as a liver disease. Currently, liver biopsy in NAFLD serves multiple roles: confirmation (or exclusion) of the diagnosis; distinction of steatohepatitis from "simple steatosis"; assessment of extent of necroinflammatory activity, fibrosis, and architectural alterations. Histopathologic studies have underscored the fact that not all obese and/or diabetic individuals with elevated liver tests have fatty liver disease; for example, hepatic glycogenosis and hepatosclerosis have been described in diabetics, and other significant liver diseases have been documented. Likewise biopsy studies have documented lesions of steatosis or steatohepatitis in unusual patient groups or clinical settings, such as lean individuals, individuals with normal liver tests, patients taking certain medications, patients with co-existent serologically-diagnosed liver disease, and pediatric patients. Biopsy studies have shown that the lesions of NASH may or may not persist in cirrhosis; prior evidence of NASH on liver biopsy serves as a benchmark for the concept that many cases of otherwise cryptogenic cirrhosis developed from NAFLD/NASH. Liver biopsy remains a significant feature of studies delineating long-term outcome of NAFLD, some of which have shown that "simple steatosis" is not always non-progressive and benign. Finally, investigators have noted correlations of proposed pathophysiologic processes in NASH with particular histologic features. Therapeutic trials for NASH rely on histologic evaluation as the most sensitive analysis to document effects of treatment. Treatment trials afford an opportunity to evaluate histologic features of resolution, and these trials have also provided an opportunity for correlations of particular histologic lesions with clinical and laboratory features in well-characterized patient populations. These kinds of studies are currently relatively few, but results of a recent study have reinforced the concept of necessary criteria for diagnosis. Current discussions in pathology include identification of lesions of concern for progression, reproducible methods of diagnosis and semiquantification of lesions, and appropriate nomenclature. Matteoni et al. proposed NAFLD types 1-4 based on long-term outcome studies; Brunt et al. proposed a system of grading and staging for NASH that follows methods of separate assessment for necroinflammatory lesions (grade) and fibrosis (stage) accepted in other forms of non-biliary chronic liver disease. Recently, the Pathology Committee of the NIDDK NASH Clinical Research Network has proposed a system of evaluation that encompasses the entire spectrum of NAFLD from steatosis to steatohepatitis with fibrosis for use in upcoming treatment trials. And, just as the clinician cannot distinguish steatosis and steatohepatitis, the pathologist cannot discern if alcohol abuse may be an underlying cause of the lesions. Proposed nomenclature to align with either extant terminology in other forms of chronic liver disease, or to align with our knowledge of underlying cause(s) (such as metabolic syndrome) will be discussed.     

软肝贴穴位贴敷神灯照射与消鼓软肝方联合西药治疗肝硬化腹水64例临床观察

[目的]观察软肝贴穴位贴敷神灯照射与消鼓软肝方联合西药治疗肝硬化腹水疗效。[方法]使用前瞻性设计方法,对64例住院患者使用软肝贴(水蛭、虻虫各5g,三棱、莪术、元胡、泽兰、马鞭草、大腹皮、姜黄、路路通各15g,共研成细末,醋调匀),穴位贴敷于肝区章门穴、期门穴、日月穴,并用神灯照射30min,1次/d;消鼓软肝方(柴胡、枳壳、陈皮、大腹皮、丹参、赤芍、鸡内金、益母草、泽兰、茯苓、泽泻、葫芦瓢各15g),150mL,1次/d,口服;0.9%氯化钠100mL+还原性谷胱甘肽1.2g,静点,1次/d;呋塞米20mg/次,3次/d,口服;螺内酯20mg/次,3次/d,口服;肌苷0.2/次,3次/d,口服;当白蛋白25g/L时,补充人血白蛋白10g/次,1次/d静点,连续3d。连续治疗30d为1疗程。观测临床症状、肝功能指标、脾脏状况、腹水、不良反应。连续治疗2疗程,判定疗效。[结果]显效39例,有效21例,无效4例,总有效率93.75%(60/64)。[结论]软肝贴穴位贴敷神灯照射与消鼓软肝方联合西药治疗肝硬化腹水,疗效满意,无副作用,值得推广。     

儿童后尿道瓣膜造影诊断及球囊治疗

目的 采用逆行性膀胱造影和排泄尿道造影,显示后尿道瓣膜及并发的尿路梗阻征象。从而做出影像学诊断。将球囊导管插入后尿道扩张、疏通后尿道膜性梗阻。方法 应用以上方法诊断后尿道瓣膜１６例,患儿年龄３个月～４岁,平均年龄２岁６个月。本组病例中３例经造影诊断后行外科手术治疗,１３例采用后尿道球囊治疗。１６例患儿均有出生后排尿困难、尿线不连贯、滴沥状临床特点。结果 １２例造影中直接显示后尿道瓣膜负影,全部病例     

β-Klotho gene variation is associated with liver damage in children with NAFLD

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Sodium localization in the adult brain

Summary Localization of sodium ion was studied by use of s-collidin buffered pyroantimonate technique in the brain tissue involved by triethyltin intoxication and epidural ballooning. Most striking evidence in triethyltin poisoning was occurrence of large amounts of sodium precipitates in a clear space formed by splitting of myelin lamellae. They were variable in size, some of them being round in form, large in size, and situated without any association with the myelin structure, and others being usually connected with the intraperiod dense line which formed a border of the clear space. No significant increase of sodium precipitates was evident in other cellular compartments.In cerebral edema produced by epidural compression, a significant increase of sodium precipitates was seen on the plasma membrane of the endothelial cell and on the internal surface of the astrocytic plasma membrane apposing the capillary. In addition, fine, dense precipitates were found in a small clear space occurred by disarrangement of myelin lamellation.There was evidence of few, dense precipitates in the extracellular space.

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Zusammenfassung Die Lokalisation von Natrium-Ionen im Hirngewebe nach Triäthylzinn-Vergiftung und epiduraler Ballonkompression wurde mittels des S-Collidin-gepufferten Pyroantimonat-Technik untersucht. Bei der TET-Vergiftung fiel das Auftreten großer Mengen von Natrium-Niederschlägen in einem hellen, durch Aufsplitterung der Myelinlamellen gebildeten Spalt auf. Sie wechselten in ihrer Größe. Einige runde, größere Präcipitate fanden sich ohne Beziehung zu Myelinstrukturen, während andere mit der intraperiodischen dichten Linie in Verbindung standen, welche den hellen Spalt begrenzte. In anderen Zellkompartimenten war keine eindeutige Zunahme von Natrium-Niederschlägen nachweisbar.Bei Hirnödem nach Ballonkompression fand sich eine deutliche Zunahme von Natrium-Niederschlägen an den Plasmamembranen der Endothelzelle und an der inneren Oberfläche der Astrocytenmembran, welche der Capillare anliegt. Daneben fanden sich zarte, dichte Präcipitate in einem durch Desorganisation der Myelin-Lamellierung gebildeten schmalen hellen Spalt. Wenige, dichte Niederschläge fanden sich im extracellulären Raum.

     

Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation

IntroductionDiagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation.AimTo assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH).Patients and methodsRetrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated.ResultsSeventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50–64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1–5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p = 0.047) and 20.58 (p = 0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k = 0.033).DiscussionAnalytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH.     

Does obesity affect the outcomes in takotsubo cardiomyopathy? Analysis of the Nationwide Inpatient Sample database, 2010‐2014

Background

Obesity can lead to increased oxidative stress which is one of the proposed mechanisms in the etiopathogenesis of takotsubo cardiomyopathy (TCM).

Hypothesis

The presence of obesity adversely impacts clinical outcomes in TCM patients.

Methods

We queried the Nationwide Inpatient Sample database (2010‐2014) to identify adult patients admitted with a principal diagnosis of TCM with and without obesity. We compared the categorical and continuous variables by Pearson χ² and Student t test, respectively, in propensity‐score matched cohorts.

Results

The study cohort comprised 612 obese TCM (weighted n = 3034) and 5696 nonobese TCM (weighted n = 28 186) patients. Obese TCM patients were more often younger and private‐insurance enrollees. Cardiac complications including acute myocardial infarction (9.0% vs 7.4%; P = 0.04), cardiac arrest (2.3% vs. 0.4%; P < 0.001), cardiogenic shock (4.3% vs. 3.2%; P = 0.03), congestive heart failure (5.0% vs. 3.8%; P = 0.02), respiratory failure (12.9% vs. 11.0%; P = 0.021) and use of mechanical hemodynamic support (Impella; 0.2% vs. 0.0%, P = 0.02) were significantly higher among obese TCM patients. There were no significant differences between the 2 groups in all‐cause mortality (1.0% vs. 0.8%; P = 0.35), arrhythmia (24.5% vs. 22.7%, P = 0.123), length of stay (3.7 ±3.5 vs. 3.7 ±3.6 days; P = 0.68), and total hospital charges ($40 780.16 vs. $42 575.14; P = 0.08).

Conclusions

Obese TCM patients were more susceptible to developing TCM‐related cardiac complications than were nonobese TCM patients, without any impact on all‐cause in‐hospital mortality, LOS, and hospital charges.     

Angiographic long-term follow-up of primary apical ballooning of the left ventricle

Acute and reversible left ventricular apical wall motion abnormalities presenting with chest pain, electrocardiographic (EKG) changes and cardiac markers release, in the absence of coronary artery stenosis, have already been identified as a possible distinct clinical entity: the so-called Tako-Tsubo syndrome. A 65-year-old man with history of hypertension, hypercholesterolemia and smoking, was admitted at the emergency room of a secondary referral institution with a severe and prolonged (45 min) chest pain, irradiated to the left arm, associated with neurovegetative syndrome. The clinical presentation suggested an acute myocardial infarction (AMI). Interestingly no coronary artery stenoses or vasospasm reaction to administration of acetylcholine could be detected. A slow flow phenomenon was present. The left ventricle angiography confirmed a mild depression of left ventricle systolic function (EF 45%), with akinesia of antero-lateral wall and the typical apical ballooning-like profile. At 3-month follow-up, the patient continued to be asymptomatic and the echocardiogram showed a progressive normalization of left ventricle segmental motion and ejection fraction with a complete restoration only after 6 months. At 1 year the coronary angiography confirmed the absence of coronary stenosis, with complete regression of the ventricular apical ballooning at left ventricle catheterization. At two-year follow-up the patient is still asymptomatic. A slow resolution of the syndrome should be included in the diagnostic criteria for apical ballooning.     

Current status,problems, and perspectives of non-alcoholic fatty liver disease research

Non-alcoholic fatty liver disease(NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver(NAFL) or non-alcoholic steatohepatitis(NASH) based on the existence of ballooned hepatocytes,although the states have been known to transform into each other. Moreover,since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus,identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.