Cutaneous signs of liver disease: value for prognosis of severe fibrosis and cirrhosis

Background/Aims: Although physicians have looked for cutaneous signs of liver disease for more than a century, their prognostic value has never been evaluated systematically. Methods: Therefore, cutaneous changes were prospectively recorded in all patients referred for liver biopsy from June 2000 to May 2004. Fibrosis was staged from F0 to F4 according to Desmet and Scheuer. The analysis included 744 patients, 520 of whom had chronic hepatitis C while the remaining had other diseases. Results: By univariate analysis, the frequency of several skin changes was associated with the degree of fibrosis. In general, at fibrosis F0–1 skin changes were infrequent; they became more frequent at F2 and were frequent at F3–4. To analyse the predictive value of skin changes, patients with fibrosis F0–2 were compared with those with F3–4. Final logistic regression included spider naevi, palmar erythema, teleangiectasia, bleeding signs and dry skin as well as age and gender. When routine laboratory values were included in the analysis, prothrombine time, γ‐glutamyltransferase and albumin proved to be significant. Receiver operating characteristic (ROC) showed a good discrimination of fibrosis F0–2 from F3–4 by the modelled score on combining skin changes and laboratory tests: at the cost of 2% of non‐diagnosed patients with F3–4, one might have saved 60% of biopsies. ROC was less useful in discriminating fibrosis F0–1 from F2–4. The discriminative power of skin changes was better than the laboratory values and the aspartate aminotransferase/platelet ratio. Conclusions: The results prove that it is quite useful to look for skin changes in patients with liver disease.     

瞬时弹性成像在肝纤维化无创性诊断中的应用

肝组织活检是目前肝纤维化疾病诊断的金指标,但具有局限性。近年来,无创性诊断方法的确立已成为国内外学者关注的热点。目前临床常用多种血清纤维化指标进行肝纤维化的评价,但其敏感性和特异性尚无法令人满意。国外研制出瞬时弹性测定的方法用于肝纤维化评估,此文对FibroScan在肝纤维化无创性诊断的研究进展进行综述。     

肝纤维化无创诊断研究进展

慢性肝脏疾病是一个全球性的重大公共健康问题,肝纤维化是疾病发展中关键病理阶段之一,其分期及程度对肝病的治疗和预后起决定性作用。近年来,随着新型无创诊断方法的不断涌现,其在很大程度上取代了肝穿刺活检来评估慢性肝病的严重程度。这些方法大致可分为以下两类:基于血清生物标志物的"生物学"方法和基于弹性成像技术的"物理学"方法。本文将对常见肝病中肝纤维化的无创诊断方法的相关研究进展进行简要综述。     

彩色超声与慢性肝炎肝纤维化分期的相关性分析

目的探讨超声诊断慢性乙型肝炎(CHB)患者代偿期肝硬化的价值。方法 2010年1月至2015年1月行肝活组织检查的CHB患者226例,收集患者B型超声资料,利用Logistic回归分析与代偿期肝硬化程度相关的指标,采用受试者工作特征曲线下面积(AUROC)评价B型超声诊断代偿期肝硬化的价值。结果超声指标中SWV、门静脉主干内径、胆囊壁厚度、脾脏长径、脾脏厚度、脾脏面积、脾静脉内径、门静脉最大流速共8项指标与肝脏炎症分级和纤维化分期均相关。其中,SWV、门静脉主干内径、脾脏长径、门静脉最大流速、脾静脉内径与组织学代偿期肝硬化独立相关,AUC均0.7。结论超声的部分影像学指标对预测组织学代偿期肝硬化有潜在的价值。     

非创伤性诊断肝纤维化临床研究进展

正确评估肝纤维化程度有利于临床治疗和随访慢性肝病。笔者就非创伤性诊断肝纤维化的不同方法、适应证和步骤的最新进展进行讨论。瞬间弹性超声检查与多项血清标志物组合的诊断模型,符合非创伤性肝纤维化诊断技术的多项要求,能有效诊断严重肝纤维化（S≥3期）,但区分轻、中度肝纤维化（S≤2期）欠佳。目前,非创伤性诊断肝纤维化方法仍不成熟,还不能完全取代肝脏活体组织检查。     

Non-invasive diagnosis of liver fibrosis and cirrhosis

The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.     

肝纤维化无创诊断的研究进展

肝纤维化是一种由不同肝病发展而来的威胁生命的疾病,是最常见的死因之一,以细胞外基质增加,组织重列并改建为特点。判断肝纤维化程度及炎症活动度的最可靠指标为肝脏活检,但活检是一项有创检查,应用有一定的限制,因而寻找准确、可靠地无创检查方法为肝纤维化的病情判断和疗效考核提供依据是非常有必要的。近年来,随着血清学和影像学的发展,血清标志物模型、瞬态弹性成像等可以比较准确的诊断肝纤维化,减少了对肝活检的需要,但是由于其各自的缺点至今没有一种无创方法可以替代肝活检的金标准地位,寻找一种理想的标志物仍需继续努力。     

Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis

BACKGROUND/AIMS: Evaluation of the degree of hepatic fibrosis is especially important in patients with chronic liver disease. Our aim was to study the diagnostic accuracy of abdominal ultrasonography for cirrhosis or fibrosis. METHODS: Twenty-three clinical (n=12) and Doppler ultrasonic (n=11) variables were recorded in 243 patients with chronic (alcoholic and viral) liver disease under conditions close to those of clinical practice. Fibrosis was classified into six grades by two pathologists. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables, then by stepwise analysis. RESULTS: A) Diagnosis of cirrhosis: 1) whole group (n=243): diagnostic accuracy was globally 84%, and 84% with two variables: spleen length, portal velocity; 2) compensated chronic liver disease (n=191): diagnostic accuracy was globally 85%, and 82% with two variables: liver surface, liver length (right kidney); 3) alcoholic compensated chronic liver disease (n=109): diagnostic accuracy was globally 86%, and 88% with two variables: spleen length, liver length (middle clavicle); 4) viral compensated chronic liver disease (n= 83): diagnostic accuracy was globally 86% and 86% with one variable: liver surface. By subtracting the proportion of patients who could not be investigated due to anatomical limitations, the highest calculated univariate diagnostic accuracy decreased by 7%. B) Diagnosis of fibrosis: diagnostic accuracy was globally 84% for extensive fibrosis. CONCLUSIONS: Cirrhosis can be correctly diagnosed in 82-88% of patients with chronic liver disease using a few ultrasonographic signs. However, the diagnostic accuracy of ultrasound is decreased by the anatomical limitations of this technique.     

肝纤维化非创伤性诊断的新近认识

对肝纤维化做出早期诊断,并动态监测其变化,对于慢性肝病的治疗及改善预后有着重要的意义。目前肝纤维化的诊断和分期的"金标准"仍是肝穿刺活组织病理检查,但因其局限性,近年来人们一直致力于寻找更准确的非创伤性的诊断方法。这些方法包括:血清纤维化标志物和数学模型、超声、超声定量、超声弹性成像技术、CT、磁共振成像(MRI)、核医学,总结了各种方法的优缺点,对其临床使用的合理选用及如何相互对照验证进行了分析。认为未来的方向可能是将上述检测方法进行联合检测和综合评估,以提高肝纤维化非创伤性诊断的临床使用价值。     

纤维化扫描仪用于肝纤维化无创诊断研究进展

肝纤维化是各种慢性肝病共同的病理表现,肝穿刺活检是目前诊断肝纤维化的金标准,其有创性限制了在临床上的广泛应用,因此无创性诊断方法成为研究热点.目前临床常用的各种无创诊断方法的特异性和敏感性不能令人满意.法国学者研究出瞬时弹性测定方法用于肝纤维化的诊断,具有无创、无痛、客观、定量等优点.此文就纤维化扫描仪的原理、临床应用...     

肾素血管紧张素系统与肝纤维化、肝硬化

循环肾素-血管紧张素系统(renin angiotensin system，RAS)为一内分泌系统，能分泌血管紧张素Ⅱ(angiotensin Ⅱ，AngⅡ)，AngⅡ具有广泛的生物学效应，作用于全身多个器官，主要通过AngⅡ和特异性的膜受体作用来调控。在许多组织或器官，如肾脏、心脏和血管中存在着独立的局部RAS^[1]，亦可合成AngⅡ，AngⅡ以旁分泌、自分泌、细胞内分泌等形式作用于组织和细胞，与组织细胞特异性受体结合，发挥一。系列功能调控作用。新近研究表明，肝脏亦存在着局部RAS^[2,3]，肝脏局部RAS、循环RAS与肝纤维化、肝硬化有着密切的关系。     

Contrast-enhanced ultrasound in the diagnosis of nodules in liver cirrhosis

Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography(CT)or magnetic resonance imaging(MRI)or as an initial diagnostic test for small newly detected liver nodules.CEUS has unique advantages over CT and MRI including no renal excretion of contrast,real-time imaging capability,and purely intravascular contrast.Hepatocellular carcinoma(HCC)is characterized by arterial-phase hypervascularity and later washout(negative enhancement).Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase.However,there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout.Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rimlike or diffuse hypervascularity followed by rapid washout.Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS.CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance.CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.     

彩色多普勒超声半定量评分对早期乙型肝炎肝硬化的诊断价值

目的 研究彩色多普勒超声半定量评分诊断早期乙型肝炎肝硬化的临床价值。方法 选择2014年8月~2015年12月在我院诊治的肝硬化患者136例和慢性乙型肝炎患者364例,使用GE Logiq E8彩色多普勒超声诊断仪检测肝脏超声并进行半定量评分,常规进行肝活检。结果 肝硬化组门静脉流量、流速和内径分别为（86.3±7.5） ml/min、（3.8±0.1） cm/s、（11.5±1.4） mm,均明显高于慢性乙型肝炎组[分别为（62.3±6.4） ml/min、（3.1±0.1） cm/s、（8.7±1.6） mm,P<0.05];慢性乙型肝炎组肝静脉清晰度、肝表面被膜、胆囊壁、肝脏边缘形态、肝脏实质回声、肝内韧带、脾脏面积评分和总分分别为（1.1±0.3）分、（1.2±0.3）分、（1.1±0.2）分、（1.0±0.4）分、（1.1±0.5）分、（1.0±0.2）分、（1.4±0.4）分、（8.12±0.39）分,均明显低于肝硬化组[分别为（2.6±0.3）分、（4.1±1.2）分、（1.9±0.3）分、（1.9±1.0）分、（2.7±0.4）分、（1.4±0.5）分、（4.1±1.6）分、（15.1±1.1）分,P<0.05];彩色多普勒超声半定量评分对早期乙型肝炎肝硬化的诊断灵敏度为96.3%,特异度为92.31%,阳性预测值为82.4%,阴性预测值为98.5%。结论 彩色多普勒超声半定量评分对早期乙型肝炎肝硬化的诊断具有较高的灵敏度和特异度,可作为临床筛检早期乙型肝炎肝硬化的有效方法。     

超声造影在肝硬化诊断中的作用

随着新的超声造影剂及声学技术的发展，对肝脏病变的超声诊断进入了一个全新的阶段，超声造影已经提高了早期诊断肝硬化及肝硬化结节背景下小肝癌的准确性，本文就超声造影在肝硬化诊断中的作用作一综述。     

Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

AIMS/BACKGROUND: Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis. METHODS: Interventions encompassed peroral colchicine at any dose versus placebo or no intervention. The trials could be double-blind, single-blind or unblinded. The trials could be unpublished or published as an article, an abstract, or a letter, and no language limitations were applied. All analyses were performed according to the intention-to-treat METHOD: MEDLINE, The Cochrane Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register and full text searches were combined. RESULTS: Combining the results of 14 randomized clinical trials including 1138 patients demonstrated no significant effects of colchicine on mortality (odds ratio (OR): 0.91; 95% confidence interval (CI) 0.64, 1.31), liver related mortality (OR: 0.98; CI 0.56, 1.74), complications (OR: 1.06; CI 0.65, 1.73), and the other outcomes. Colchicine was associated with a significantly increased risk of adverse events (OR: 4.41; CI 2.24, 8.70; p< 0.001). CONCLUSIONS: Colchicine should not be used for liver fibrosis or liver cirrhosis irrespective of etiology. Future trials on colchicine for liver diseases ought to be large.     

Assessment of portal hemodynamics by ultrasound color Doppler and laser Doppler velocimetry in liver cirrhosis.

BACKGROUND: Color Doppler is a noninvasive method for assessing portal hemodynamics. Laser Doppler velocimetry is useful in assessment of microcirculatory abnormalities in portal hypertensive gastropathy (PHG). AIMS: To study portal hemodynamics by color Doppler and gastric mucosal blood flow (GMBF) by laser Doppler velocimetry in patients with cirrhosis. METHODS: Twenty-eight patients with cirrhosis of liver (24 men) and 10 healthy subjects (7 men) were studied. Portal venous blood flow (PVBF) and portal flow velocity (PFV) were assessed by color Doppler at the level where the hepatic artery crosses the portal vein, and GMBF was measured by laser Doppler velocimetry. RESULTS: PVBF (379.5 [102.9] mL/min), PFV (5.3 [1.1] cm/sec) and GMBF (3.5 [0.8] volts) were significantly lower in patients with cirrhosis than in controls. PVBF and PFV were significantly lower in patients in Child class B and C than those in class A. Patients with ascites had significantly lower PVBF, PFV and GMBF than those without; values were also lower in patients with PHG than in those without. History of bleeding had no relation with PVBF and PFV. GMBF showed good correlation with PVBF (r=0.58, p<0.001) and with PFV (r=0.48, p<0.01). CONCLUSIONS: In cirrhosis of liver, PVBF, PFV and GMBF are significantly lower, and the changes increase with increasing severity of liver disease.     

Functional asplenia after severe varicella zoster-infection diagnosis by colour Doppler ultrasound

Infiltrative, inflammatory or thromboembolic processes in the parenchyma of the spleen can cause a functional loss of the organ. This phenomenon is called functional asplenia and occurs as a complication especially in sickle cell disease, lupus erythematosus and after bone marrow transplantation. We present the case of a patient with Crohn's disease under immunosuppressive therapy who developed a spontaneous covered spleen rupture in the course of a septic shock with DIG due to a Varizella zoster infection. Later on, sonography showed a diminution of the spleen size. No flow signals could be derived by colour doppler measurements from the spleen. Because of the colour doppler findings we suspected a functional asplenia which was then verified by spleen scintigraphy and Howell-Jolly-Bodies in the blood count. Remarkably, the Crohn's disease remains in complete remission since the development of the functional asplenia (for 4 years now). The underlying pathomechanism remains unclear.     

New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and Doppler.

BACKGROUND: Large discrepancies exist concerning the incidence of myocardial bridging. This has been reported to be 0.5%-2.5% following coronary angiography but 15%-85% following autopsy. The purpose of the study was to use intravascular ultrasound and intracoronary Doppler to study the morphology and flow characteristics of myocardial bridging in order to find feasible parameters of this syndrome. METHODS AND RESULTS: Intravascular ultrasound was performed in 62/69 patients in whom typical angiographic 'milking effects' were present. In 48 patients, intracoronary Doppler was performed. A specific, echolucent 'half moon' phenomenon surrounding the myocardial bridge was found in all the patients. The thickness of the half moon area was 0.47 +/- 0.19 mm in diastole and 0.52 +/- 0.23 mm in systole. There was systolic compression of the myocardial bridge with a lumen reduction during systole of 36.4 +/- 8.8%. Using intracoronary Doppler, a characteristic early diastolic 'finger tip' phenomenon was observed in 42 (87%) of the patients. All patients showed no or reduced antegrade systolic flow. Coronary flow velocity reserve was 2.03 +/- 0. 54. After intracoronary nitroglycerin injection, retrograde systolic flow occurred in 37 (77%) of the 48 patients, with a velocity of -22. 2 +/- 13.2 cm. s(-1). Intravascular ultrasound revealed atherosclerotic involvement of the proximal segment in 61 (88%) of the 69 patients, with an area stenosis of 42 +/- 13%. No plaques were found in the bridge or distal segments in the 62 patients in whom it was possible to introduce the ultrasound catheter throughout the bridging segment. CONCLUSION: Myocardial bridging is characterized by the following morphological and functional signs: a specific, echolucent half moon phenomenon over the bridge segment, which exists throughout the cardiac cycle; systolic compression of the bridge segment of the coronary artery; accelerated flow velocity at early diastole (finger-tip phenomenon); no or reduced systolic antegrade flow; decreased diastolic/systolic velocity ratio; retrograde flow in the proximal segment, which is provoked and enhanced by nitroglycerin injection.