Hepatic Disease with Portal Hypertension and Acute Juvenile Paracoccidioidomycosis: A Report of Two Cases and Literature Review

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole–trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.     

多层螺旋CT门静脉成像在评估肝硬化门脉侧枝血管中的价值

目的：评价多层螺旋CT门静脉成像显示门静脉高压的价值。材料与方法：30例门脉高压患者进行了螺旋CT门脉成像检查,其中10例患者又进行了门静脉造影检查(间接法)。30例患者中全部存在侧枝循环,多数病例有2个或2个以上部位侧枝循环。结果：多层螺旋CT门静脉成像不仅显示了肝内门静脉2-3级分支,还显示了整套门脉侧枝血管系统。在三维门脉像上,脾门静脉曲张29例(占96．7％),其中1例脾静脉因栓子部分闭塞而狭窄,另有1例则完全栓塞血管未显示。胃左静脉曲张28例(占93％),食管或食管旁静脉曲张27例(占90％),胃短静脉(胃后静脉)曲张19例(占63％),胃肾分流血管10例(占33％),腹膜后静脉曲张9例(占30％),脐周静脉曲张伴腹壁静脉曲张6例(占20％)。10例患者CT三维门脉像与间接门静脉造影作比较,前者对门静脉及其侧枝循环的显示好于后者。结论：多层螺旋CT门脉成像是门静脉无创性检查的可靠方法,有较高的临床运用价值。     

门静脉高压治疗现状与展望

门静脉高压症是一种主要因肝脏病变而引起门静脉系统循环异常为主要特点的病症,经过100多年的研究与探索,门静脉高压症的诊断和治疗手段均得到了不断的发展和完善.如非选择性β受体阻断剂和内镜下曲张静脉套扎术对预防有中、重度静脉曲张的患者首次静脉曲张出血均具有各自的优势,气囊阻断经静脉逆行栓塞术对曲张的食管胃底静脉的具有良好疗效,部分性脾栓塞术已成为肝硬化门脉高压脾亢血液病的最主要非手术治疗措施,外科治疗方面联合手术的优势已经逐步体现出来,但门静脉高压症最根本的治疗措施仍是肝移植.但选择何种方式治疗,仍要根据患者肝功能状况及病情变化而定,本文将就门静脉高压治疗现状与展望做一综述.     

Severe Portal Hypertension in Cirrhosis: Evaluation of Perfusion Parameters with Contrast-Enhanced Ultrasonography

Objective

To investigate the role of contrast-enhanced ultrasonography (CEUS) and Doppler ultrasonography (DUS) in the diagnosis of severe portal hypertension (PH) in patients with liver cirrhosis (LC).

Methods

Patients with PH scheduled to receive hepatic venous pressure gradient (HVPG) measurement were recruited for this study. Hepatic DUS and CEUS were performed successively. Several Doppler and CEUS parameters were explored for correlation with HVPG values and their association with severe PH (≥ 12 mmHg of HVPG). Comparison of the parameters between the severe and non-severe PH groups and their correlation with HVPG values was evaluated. A receiver operating characteristic (ROC) curve analysis was also performed to investigate the performance in order to diagnose severe PH.

Results

Fifty-three consecutive patients were enrolled in this study. Among them, 43 patients did not have significant ascites. Compared with the non-severe PH group, portal venous velocity and intrahepatic transit time (ITT) were significantly reduced in the severe PH group (all p<0.05). Difference between inspiratory and expiratory hepatic venous damping indices (ΔHVDI), hepatic venous arrival time (HVAT) and ITT moderately correlated with HVPG (r = -0.358, -0.338, and -0.613, respectively). Areas under the curves for severe PH were 0.94 of ITT and 0.72 of HVAT, respectively (all p<0.05). ITT under 6 seconds indicated severe PH with a sensitivity of 92% and a specificity of 89%.

Conclusions

Hepatic CEUS may be more useful in estimating the HVPG value and determining the presence of severe PH compared to DUS, and ITT was the most accurate parameter to diagnose severe PH.     

Recreational Shooting of Prairie Dogs: A Portal for Lead Entering Wildlife Food Chains

Abstract: Although lead shot has been banned for waterfowl hunting in North America, some predators continue to exhibit elevated lead burdens, which has been attributed to ingesting metallic lead from other projectiles. Few studies have investigated residual lead fragments in hunted upland animals. Therefore, specific portals for lead entering wildlife food chains remain largely unknown. Prairie dogs (Cynomys spp.) are shot for recreation with minimal regulation in western North America. Because recreational shooters mostly use expanding bullets and rarely remove or bury carcasses, shot prairie dogs could make lead accessible to predators and scavengers. To determine whether and to what degree shot prairie dogs carry lead fragments, we analyzed carcasses shot by recreational shooters with 2 bullet types. Bullet type influenced the probability of bullet fragments being retained in carcasses; 87% of prairie dogs shot with expanding bullets contained bullet fragments, whereas 7% of carcasses shot with non-expanding bullets did. The amount of bullet fragments per carcass also differed between bullet types; carcasses shot with expanding bullets contained a mean of 228.4 mg of the lead-containing bullet core and 74.4 mg of the copper-alloy jacket, whereas carcasses shot with non-expanding bullets averaged only 19.8 mg of the core and 23.2 mg of the jacket. Lead fragments in carcasses shot with expanding bullets were small in size; 73% of all lead mass in each carcass was from fragments that weighed <25 mg each, small enough to be easily ingested and absorbed by secondary consumers. The amount of lead in a single prairie dog carcass shot with an expanding bullet is potentially sufficient to acutely poison scavengers or predators. Therefore, shot prairie dogs may provide an important portal for lead entering wildlife food chains and may pose risks to raptors and carnivores. Managers should consider measures, such as using non-expanding or lead-free ammunition, to reduce the likelihood of lead consumption and poisoning in upland wildlife.     

选择性入肝血流阻断应用于肝癌合并门脉高压手术中的疗效观察

目的：探究选择性入肝血流阻断（SPVE 法）在肝癌合并门脉高压手术中的临床应用效果。方法：选择我院2009 年10 月 ~2014 年10 月期间确诊为肝癌合并门脉高压的患者80 例,按照随机数字数表法分为观察组和对照组各40 例,观察组行SPVE 法进行血流阻断,对照组行全入肝血流阻断法（Pringle 法）进行血流阻断。对比两组手术时间、阻断血流时间、手术中出血量、输血 量、手术前后患者肝功能相关指标及术后并发症发生率。结果：两组手术时间和血流阻断时间对比差异无统计学意义（P>0.05）,而 观察组术中出血量及输血量均小于对照组,差异具有统计学意义（P<0.05）;术后观察组血液中谷丙转氨酶（ALT）、谷草转氨酶 （AST）和总胆红素（TB）水平均低于对照组,而血清蛋白（ALB）和血红蛋白（Hb）水平高于对照组,差异均有统计学意义（均P<0. 05）;观察组并发症发生率为22.5%,明显低于对照组的37.5%,差异有统计学意义（P<0.05）。结论：SPVE法应用在肝癌合并门脉 高压手术中,可以显著减少术中的出血量和输血量,有利于术后肝功能的恢复,有效地降低术后并发症的发生。     

盐敏感性高血压大鼠模型的研究进展

高血压是多基因遗传和多个环境因素相互作用的结果,盐的摄入在高血压的形成中起着关键的作用。本文就感觉神经损伤、Dah 1种、醋酸脱氧皮质酮和部分肾切除等方法建立的盐敏感性高血压大鼠模型的特点及其病理生理学变化作一综述,为进一步研究盐敏感性高血压发病的机制提供依据。     

门静脉高压症大鼠肠系膜组织内皮素B受体表达的变化

目的:探讨胆汁性肝纤维化引起的门静脉高压症(PHT)大鼠肠系膜组织内皮素B受体表达(ETBR)的变化.方法:取体重250±10 g左右的清洁级SD雄性大鼠30只,根据体重随机分为假手术组、模型组,模型制作采用胆总管结扎的方法造成大鼠胆汁性肝纤维化.术后2周和4周分别测定各组的门静脉压力,应用免疫组化和免疫印迹的方法观察肠系膜组织ETBR的表达.结果:术后2周和4周模型组门静脉压力显著升高,分别为11.89±1.38 mmHg和16.34±1.63 mmHg.免疫组化显示假手术组肠系膜组织ETBR主要见于细动脉内皮细胞,而模型组大鼠ETBR的表达不仅见于细动脉内皮细胞,细动脉平滑肌细胞和微动脉表达也很显著.免疫印迹发现假手术组肠系膜组织ETBR含量很少,模型组大鼠ETBR表达明显增多.结论:正常大鼠肠系膜血管组织ETBR表达较少,随着肝组织损伤加剧和PHT形成,肠系膜组织ETBR表达明显增加,可能参与胆汁性肝硬化PHT形成过程.     

Emergency Endoscopy after Gastrointestinal Haemorrhage in 50 Patients with Portal Hypertension

Endoscopy was carried out in 50 patients with oesophageal varices within 24 hours of a major haematemesis or melaena. Sources of bleeding were identified in 42 of the cases and in only 19 patients was bleeding due to oesophageal varices. Bleeding from gastric varices was present in 11 patients, and a variety of acute and chronic lesions made up the remainder. In contrast with previous series haemorrhage from erosive gastric lesions was seen in only five patients and was no more common in 23 patients with alcoholic cirrhosis than in the group as a whole.     

门静脉高压脾功能亢进对大鼠肝癌发生率的影响

目的:通过对门静脉高压脾功能亢进大鼠药物诱导肝癌过程中进行脾脏切除,探讨门静脉高压脾功能亢进对大鼠肝癌发生率的影响。方法:将雌雄SD大鼠性别内分别分为对照组、脾亢组、脾亢切脾组,脾功能亢进大鼠模型采用门静脉缩窄术联合脾静脉结扎术进行制备,各组均予以DEN(二乙基亚硝胺)腹腔注射,按体重20mg/kg给药,每周3次,12周停药,14周处死。其中,脾亢脾切除组于给药第四周进行脾切除术,手术恢复期间持续给药。观察各组实验动物的肝脏大体变化及病理改变,计算成瘤率。结果:实际成瘤率显示脾亢组较对照组明显升高,而雄性脾亢切脾组的成瘤率较脾亢组有所降低。雌性脾亢切脾组成瘤率同脾亢组差异不明显。结论:门静脉高压脾功能亢进状态下进行脾切除,对于雄性能减低肝癌发生的风险,对于雌性的意义不大,给临床实际工作提供了新的思路。     

S-甲基异硫脲对大鼠门脉高压症食管静脉曲张的影响

目的观察诱导型一氧化氮合酶抑制剂SMT对大鼠门脉高压症食管静脉曲张的影响。方法健康雄性SD大鼠60只随机分为5组,假手术组、模型组、低剂量组、中剂量组和高剂量组。假手术组仅分离门静脉、左肾上腺静脉关腹,其余组门脉缩窄两步法加左肾上腺静脉结扎,建立门脉高压症食管静脉曲张模型。假手术组与模型组手术后给予腹腔注射生理盐水,其余3组手术后给予腹腔注射不同浓度SMT。手术后21 d,检测大鼠门脉血中TNOS、iNOS的活性及NO的浓度,免疫组化CD34标记食管血管内皮,测量每组大鼠食管横切面黏膜下血管的数目、面积。结果模型组大鼠门脉血中TNOS活性与iNOS活性以及NO浓度和食管黏膜下血管数目,血管平均截面积,血管总面积均较假手术组显著升高（P〈0.01）。中、高剂量组大鼠门脉血中TNOS活性与iNOS活性以及NO浓度和食管黏膜下血管的数目、血管平均面积、血管总面积较模型组均显著下调（P≤0.01）。结论大鼠门脉高压食管静脉曲张的发病机制中有NO参与,门脉缩窄型门脉高压食管静脉曲张病中NO主要由iNOS生成,SMT对大鼠门脉高压食管静脉曲张可能具有一定保护作用。     

左侧门脉高压症并上消化道出血的诊断与治疗（附14 例临床分析）

目的:探讨左侧门脉高压症合并上消化道出血的诊断和治疗方法。方法:回顾分析我院近10年来收治的14例左侧门脉高压症合并上消化道出血患者的诊治措施和随访结果。结果:14例患者均有呕血或(和)黑便史,无肝硬化、腹水及肝功能异常等表现。14例患者中胰体尾占位6例,胰腺假性囊肿4例,慢性胰腺炎4例。14例患者均采用手术治疗。9例患者获得随访,定期内镜复查,曲张静脉明显改善或消失,随访5月～8年均无再出血。结论:胰腺疾病病史、无肝硬化和肝功能正常、孤立性胃底静脉曲张和脾肿大及脾亢是诊断左侧门脉高压症的基本要点。该疾病可通过脾切除术或联合胃底周围血管离断术结合原发胰腺疾病的治疗来获得治愈。     

Effect of Meal Ingestion on Liver Stiffness in Patients with Cirrhosis and Portal Hypertension

Background and Aims

Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population.

Methods

In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured.

Results

Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes.

Conclusions

Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.     

Soluble TNF-Alpha-Receptors I Are Prognostic Markers in TIPS-Treated Patients with Cirrhosis and Portal Hypertension

Background

TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS.

Methods

Forty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics.

Results

Before TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not.

Conclusion

Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension.