Congenital Hepatic Fibrosis

We present four pediatric patients with histologically proven congenital hepatic fibrosis. The patients had diverse manifestations. The first two patients were seven-year old identical twins who presented with hepatosplenomegaly and were found to have portal hypertension with esophageal varices. The third patient was a newborn who had intractable ascites, secondary to portal hypertension. The fourth patient was a seven-year old with adult type polycystic disease of the kidney but no evidence of portal hypertension. Contrary to what has been reported in the literature of the appearance of portal hypertension in the late childhood period, congenital hepatic fibrosis may present in any age group with portal hypertension.     

Imaging of Hepatic Fibrosis

Purpose of Review

The purpose of this review is to discuss the current imaging techniques for non-invasive assessment of liver fibrosis (LF).

Recent Findings

Elastography-based techniques are the most widely used imaging methods for the evaluation of LF. Currently, MR elastography (MRE) is the most accurate non-invasive method for detection and staging of LF. Ultrasound-based vibration-controlled transient elastography (VCTE) is the most widely used as it can be easily performed at the point of care but has technical limitations especially in the obese. Innovations and technical improvements continue to evolve in elastography for improving accuracy and avoiding misinterpretation from confounding factors. Other imaging methods including diffusion-weighted imaging (DWI), hepatocellular contrast-enhanced (HCE) MRI, T1 relaxometry, T1ρ imaging, textural analysis, liver surface nodularity, susceptibility-weighted imaging, and perfusion imaging are promising but need further evaluation and clinical validation.

Summary

MRE is the most accurate imaging technique for assessment of LF.

     

二尖瓣反流经导管介入微创治疗新进展

随着微创及介入治疗技术在心脏瓣膜病的治疗中不断发展,心脏瓣膜病治疗的适应证逐渐扩大,尤其在二尖瓣反流的介入治疗领域,各项实验技术成果在动物及临床实验当中取得显著效果。现介绍二尖瓣反流经导管介入治疗的新进展,并针对当前研究热点,重点对有关技术的临床研究进展做一综述。     

肝性脑病的药物治疗

肝性脑病常可发生于失代偿肝硬化或各种重型肝炎,指导患者合理饮食、避免诱发因素固然重要,但对已发生的肝性脑病,在去除诱因的基础上采取包括药物治疗在内的综合治疗更为迫切,其中,药物治疗是最重要的治疗方法之一。本文主要介绍一些常用的药物。降血氨治疗动物实验和临床患者监测表明,血氨与肝性脑病的症状和脑电图异常程度相关,所以,氨中毒仍然被认为是肝性脑病的重要机制。而且,降血氨治疗对于缓解肝性脑病的症状有效,所以,降血氨是肝性脑病药物治疗的主要部分。减少氨的产生与吸收1. 乳果糖　乳果糖是人工合成的双糖(6 半乳糖5葡萄…     

肝纤维化的临床研究进展

肝纤维化是所有慢性肝病的共同特征，多种因素参与其发生和发展。各种因素所致的肝纤维化的进程不同，但目前对其自然史的认识尚不全面。肝纤维化的非创伤性诊断临床实际应用尚有一定距离。对临床、生化和影像等指标进行综合评估应是今后努力的方向。肝纤维化和肝硬化可出现逆转和消失完全改变了对其治疗的认识。目前尚无有效的肝纤维化治疗药物，最有效的治疗方法仍是病因治疗。肝纤维化药物治疗开发存在不少困难，但前景广阔。     

酒精性肝纤维化的病理研究

本文观察了66例酒精性肝病(ALD)的肝纤维化特点。酒精性肝纤维化(AHF)主要有三种形成方式:①窦周纤维化,最具特征;②静脉周围纤维化;③汇管区及汇管区周围纤维化,后者包括汇管区胶原增多,扩大,汇管区周围星芒状纤维化及界板侵蚀。重度AHF时以Ⅰ型胶原沉积为主。AHF的形成与Ito细胞增殖密切相关。图像定量分析表明,酒精性肝病肝纤维化程度重于慢性病毒性肝炎者。     

Recent Developments in Gene Therapy for Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a life-threatening Mendelian disorder with a mean life expectancy of 33 years despite maximally tolerated standard lipid-lowering therapies. This disease is an ideal candidate for gene therapy, and in the last few years, a number of exciting developments have brought this approach closer to the clinic than ever before. In this review, we discuss in detail the most advanced of these developments, a recombinant adeno-associated virus (AAV) vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing. We also review ongoing development of approaches to enhance transgene expression, improve the efficiency of hepatocyte transduction, and minimize the AAV capsid-specific adaptive immune response. We include a summary of key gene therapy approaches for HoFH in pre-clinical development, including RNA silencing of t?he gene encoding HMG-CoA reductase (HMGCR) and induced pluripotent stem cell transplant therapy.     

New Developments in the Diagnosis,Therapy, and Monitoring of Eosinophilic Esophagitis

Purpose of review

Eosinophilic esophagitis (EoE) has transformed over the past two decades from a little-known entity to a significant cause of morbidity in the adult and pediatric population. We reviewed the most recent advancements in the diagnosis, therapy, and long-term monitoring of EoE.

Recent findings

Based on clinical, endoscopic, histologic, immunologic, and genetic similarities, there is growing consensus to move away from distinguishing proton pump inhibitor responsive esophageal eosinophilia as an entity distinct from EoE. An increasing number of studies have identified duration of untreated disease as an important determinant of esophageal stricture formation. New approaches to the empiric elimination diet including one, two, four, and step-up protocols were developed to reduce the need for repeated endoscopies during reintroduction of food triggers. Topical steroids remain the mainstay of medical therapy but newer formulations are under development to optimize esophageal delivery. Novel, disease activity monitoring techniques are being evaluated that assess esophageal inflammatory activity without the need for endoscopy.

Summary

Understanding of EoE has increased remarkably from the first identification of the disease. The underlying pathogenesis continues to be explored leading to shifts in diagnostic criteria as well as novel therapeutic targets. Innovative methods to monitor disease are under investigation and more research is needed to understand the natural history of EoE.

     

Noninvasive Markers of Hepatic Fibrosis in Chronic Hepatitis B

A serum biomarker (FibroTest; Biopredictive, Paris, France; FibroSure; LabCorp, Burlington, USA) and liver stiffness measurement (LSM) by Fibroscan (Echosens, Paris, France) have been extensively validated in chronic hepatitis C. This review updates the clinical validation of serum biomarkers and LSM in patients with chronic hepatitis B (CHB). One meta-analysis combined all published studies and another used a database combining FibroTest individual data. Sensitivity analysis assessed the impact of several factors, including authors’ independence, length of biopsy, ethnicity, hepatitis B early antigen status, viral load, and alanine aminotransferase value. Only two biomarkers had several validations: FibroTest (8 studies, 1,842 patients), and Fibroscan (5 studies, 618 patients). For the diagnosis of advanced fibrosis, the standardized area under the receiver operating curve was 0.84 (0.79–0.86) for FibroTest and 0.89 (0.83–0.96) for LSM, without significant difference. No significant factors of variability were identified for FibroTest’s performance. In conclusion, FibroTest and LSM were the most validated biomarkers of fibrosis in CHB. However, the reliability of Fibroscan must be better assessed.     

Cytokine Regulation of Hepatic Stellate Cells in Liver Fibrosis

Cytokines constitute a major class of mediators responsible for “activation” of hepatic stellate cells (HSCs) in vitro and in vivo. They are largely divided into mitogenic (transforming growth factor-α, platelet-derived growth factor, interleukin-1, tumor necrosis factor-α, and insulin-like growth factor) and fibrogenic (transforming growth factor-β and interleukin-6) cytokines. In addition to their mitogenic (stimulation of cell proliferation) and fibrogenic (induction of matrix proteins) properties, they are also shown to confer in vitro unique cellular changes known to be the key features of HSC “activation,” including loss of vitamin A, stimulation of migration, enhanced cellular contractility, and matrix metalloproteinase and tissue inhibitor of metalloproteinase induction. Potential cellular sources of the cytokines consist of hepatic macrophages, endothelial cells, biliary epithelial cells, lymphocytes, platelets, hepatocytes, and activated HSCs. To better understand the mode of actions and the pathogenetic significance of cytokineskhemokines involved in “activation” of HSCs, the following four questions need to be addressed: (1) What other cytokines are expressed by HSCs to establish critical autocrine stimulation? (2) What are endogenous or exogenous priming factors for HSC stimulation? (3) What is the mechanism of activation for transforming growth factor-β, the pivotal fibrogenic cytokine? (4) How important are HSC-derived proinflammatory mediators in liver fibrosis? This review will discuss these questions, along with the current understanding of the role of cytokines in HSC activation.