Respiratory dysfunction and pulmonary disease in cirrhosis and other hepatic disorders

End-stage liver disease and its complications are a leading cause of death among adults in the United States, and thousands of patients await liver transplantation. The liver plays a central role in health and homeostasis and thus the diseased liver leads to many deleterious effects on multiple organ systems, including the pulmonary system. We review the general effects of cirrhosis on the respiratory system, including mild hypoxemia, atelectasis, and hepatic hydrothorax. Cirrhosis is associated with 2 unique entities that affect the pulmonary vasculature: hepatopulmonary syndrome and portopulmonary hypertension. Hepatopulmonary syndrome, which is found in approximately 20% of patients awaiting liver transplantation, refers to the triad of hepatic dysfunction, hypoxemia, and intrapulmonary vascular dilations, and responds well to liver transplantation. In portopulmonary hypertension, cirrhosis and portal hypertension lead to pulmonary arterial hypertension, and portopulmonary hypertension has been considered a contraindication for transplantation. Currently, patients must have mild to moderate pulmonary hypertension to be considered for transplantation, and may still require long-term therapy with vasodilators to prevent right-ventricular failure and, consequently, failure of the newly transplanted liver allograft.     

Managing the complications of cirrhosis

The 3 major and potentially fatal complications of cirrhosis of the liver result from portal hypertension and include variceal bleeding, ascites, and encephalopathy. The cause of other complications, eg, thyroid dysfunction and hepatopulmonary syndrome, is uncertain. Several recent advances have occurred in the treatment of varices. However, treatment of ascites is still primarily confined to achieving a negative sodium balance, and therapy for encephalopathy centers on the use of lactulose. Although effective therapy may be available for most complications of cirrhosis, a major complication indicates a poor long-term prognosis. Liver transplantation is the only effective long-term treatment of complications due to cirrhosis.     

Critical care of the liver transplant patient: an update

The unique pathophysiology of patients with end-stage liver disease has important implications for their critical care treatment, particularly in the postoperative state. To gauge hemodynamic parameters and responses, each patient must be carefully evaluated for their place in the clinical spectrum of cirrhosis and portal hypertension. Although the data are limited, the biology of the consequences of liver disease is emphasized by novel treatments of hepatorenal syndrome, portopulmonary hypertension, and hepatopulmonary syndrome. These issues become more relevant with increased adult-to-adult living donor liver transplantation, in which technical considerations may further complicate the general treatment of the postoperative transplant patient.     

Whole-course management of interventional treatment in liver cancer patients with portal hypertension

Primary liver cancer often occurs in patients with hepatitis and cirrhosis. Some patients have portal hypertension due to cirrhosis, and present with varying degrees of collateral circulation, splenomegaly and hypersplenism, ascites, and liver dysfunction. It often interferes with the treatment of tumors and affects the disease prognosis. There are internationally recognized guidelines for interventional treatment of liver cancer and portal hypertension which will not be repeated in this paper. This paper focuses on how to treat portal hypertension and intervene with tumors in the treatment of liver cancer to optimize the management of patients with liver cancer and portal hypertension. We propose that the Interventional Management Mode of Liver Cancer with Portal Hypertension can improve the treatment of liver cancer patients with portal hypertension.     

Current management approaches to portopulmonary hypertension

Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of portal hypertension that is characterised by proliferative changes in the pulmonary microvasculature indistinguishable from other forms of pulmonary arterial hypertension (PAH). Although PoPH is most commonly observed in the setting of cirrhosis, patients with non-cirrhotic portal hypertension are also at risk of developing the disorder. A definitive diagnosis requires invasive haemodynamic confirmation by right heart catheterisation and screening for PoPH should be routinely performed in all patients being considered for liver transplantation. Although severe PoPH is considered a contraindication to liver transplantation, there is now compelling data supporting the use of PAH-specific therapies with the aim of improving pulmonary haemodynamics to allow transplantation to be successfully performed. This review explores possible relevant aetiological factors and summarises current diagnostic and therapeutic approaches for PoPH patients.     

原位辅助性部分肝移植治疗门静脉高压症的实验研究

目的 在原位辅助性部分肝移植(APOLT)动物模型基础上，观察其对猪肝硬化门静脉高压症的初步治疗效果。方法 采用结扎胆总管的方法复制猪胆汁性肝硬化动物模型，6只健康良种幼猪作为供体组，6只肝硬化模型猪为受体组，肝移植采用APOLT术。术中观察血流动力学和生化指标；术前、术后当天及7d观察门静脉压力、血胆红素及肝功能，同时用彩色多普勒超声检查门静脉最大流速及流量。结果 胆总管结扎8周后见肝脏假小叶形成，小叶周围结缔组织增生明显，有胆栓及胆泥沉积，证实胆汁性肝硬化模型成功。6只猪APOLT术后5只存活。术后7d动物活杀病理检查见移植肝形态、色泽正常，各吻合口无扭曲、漏血和血栓形成；移植肝部分肝小叶结构紊乱，肝细胞萎缩或消失，肝小叶内大量淋巴细胞和浆细胞浸润，中央静脉周围肝小叶细胞浊肿，可见淋巴细胞浸润；受体肝无明显变性及坏死。术后7d存活猪经彩色多普勒超声检察发现，移植肝门静脉血流比宿主肝门静脉血流增多，回流通畅，移植肝功能良好。血总胆红素、丙氨酸转氨酶及天冬氨酸转氨酶等肝功能指标明显好转，术后7d门静脉压力与术前相比显著降低。结论 APOLT术对门静脉高压症有一定的治疗作用，是一种较有希望的治疗肝硬化门静脉高压的新方法。     

安全施行门奇断流术治疗107例门脉高压合并脾亢的初步体会

目的探讨安全施行门奇断流术合理的围术期管理方法以及术中的技术要点。方法回顾性分析我中心2010年7月至2011年6月收治的107例肝硬化门静脉高压患者围术期管理及其效果。结果术中失血量平均为(251.40±179.95)ml,其中肝功Child B级者失血量为(209.89±109.6)ml,Child C级者失血量为(487.50±294.68)ml,两组分布比较差异有统计学意义(P<0.05);平均输血量为(545.45±311.01)ml,其中Child B级组3例,输血率为3.30%,Child C级组8例,输血率为50%,两组输血率差异有统计学意义(P<0.05);术后6例发生肝性脑病;术后2例继发肝肾综合征。结论术前积极改善肝功能,术中有效控制出血,保护性利尿,以及术后早期营养支持等综合措施是提高手术成功率和降低并发症发生率的有效方法。     

Pulmonary hypertension associated with liver cirrhosis and hepatitis-B antigenemia

An autopsy case of pulmonary hypertension in a 29-year-old Japanese female with macronodular, posthepatic liver cirrhosis and hepatitis-B antigenemia was presented. No recognizable known cardio-pulmonary disease or portal thrombosis was obtained. Hepatitis-B antigen was demonstrated in the cirrhotic hepatocytes by a specific peroxidase antiperoxidase method. Characteristic pulmonary arterial changes including plexiform lesions with varying developmental stages were widely observed throughout the lungs. Complication of these two distinct disease processes seems to be rarely encountered in the literature. Discussion was focused on the possible interrelationship between the liver cirrhosis with hepatitis-B antigenemia and pulmonary hypertension. Proposed were presumptive underlying humoral, particularly immunological, abnormalities common to these diseases rather than mere incidental complications.     

肝肺综合征研究进展

肝肺综合征(hepato-pulmonary syndrome,HPS)是在慢性肝病和(或)门脉高压的基础上出现肺内血管异常扩张、气体交换障碍、动脉血氧合作用异常,导致低氧血症及一系列的病理生理变化和临床表现,是终末期肝脏病的严重肺部并发症。动物实验表明肺微血管扩张、血管新生和血管内单核巨噬细胞聚集是导致气体交换异常的主要原因,但具体机制仍不明确。目前HPS尚缺乏有效的治疗药物,肝移植仍是最有效的治疗方法。本研究将重点讨论HPS的发病机制和临床诊治相关的新进展。     

全身炎症反应综合征对肝硬化患者的肝肾功能以及临床结局的影响

目的 研究肝硬化患者合并全身炎症反应综合征(SIRS)的发生率以及SIRS对肝肾功能和临床结局的影响.方法 选择我院收治的肝硬化患者203例作为研究对象,对其在住院期间的临床表现、实验室指标以及临床评分进行随访记录,并以患者死亡和出现门静脉高压并发症作为随访终点.结果 81例患者合并SIRS.合并SIRS组黄疸发病率、细菌感染率、白细胞计数升高、血红蛋白降低、血清肌酐升高、丙氨酸转氨酶升高、血清胆红素升高、国际标准化比值(INR)、心率、血清白蛋白降低和Child-Pugh评分升高密切相关,差异均具有统计学意义(均P＜0.05).合并SIRS组病死率、门静脉高压出血发生率、肝性脑病发生率以及1型肝肾综合征(HRS-1)均显著高于未合并SIRS组患者(均P ＜0.01).死亡患者SIRS发病率显著高于存活患者(P＜0.01).门静脉高压并发症患者SIRS发病率显著高于无门静脉高压并发症的患者(P＜0.01).SIRS和Child-Pugh分级评分是患者死亡(SIRS:OR=0.505,P＜0.01;Child-Pugh分级:OR =0.412;P＜0.01)和门静脉高压并发症(SIRS:OR=0.494,P＜0.01;Child-Pugh分级:OR =0.309;P＜0.01)的独立影响因素.结论 SIRS好发于中晚期肝硬化患者,且与门静脉高压并发症密切相关,合并SIRS的患者其病死率显著增高.     

Pathogenesis, diagnosis, and treatment of alcoholic liver disease

Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.     

Does interferon improve portal hypertension?

Chronic hepatitis C is the leading cause of advanced liver disease in the Western world. Most patients with liver cirrhosis develop portal hypertension (PHT) (i.e. an abnormal gradient between portal and inferior vena cava pressures), responsible for the most frequent and severe complications of liver disease and, as a consequence, the main cause of death and liver transplantation in those patients. The existence of a potential beneficial effect of antiviral therapy (AVT) on liver inflammation and fibrosis, partially independent of the degree of virological response, has been recently reported. However, the possible influence of these histological changes on PHT has not been evaluated. In this article, we summarize the available findings regarding the effect of AVT on PHT in patients with advanced chronic hepatitis C, as well as its possible implications for clinical practice and future avenues of investigation.     

Pulmonary hypertension complicating portal hypertension: portopulmonary hypertension]

Portopulmonary hypertension is a condition with a poor prognosis, which is defined as precapillary pulmonary hypertension complicating portal hypertension mainly due to cirrhosis of various etiologies. A mean pulmonary arterial pressure greater than 25 mmHg at rest with a pulmonary capillary wedge pressure less than 15 mmHg and a pulmonary vascular resistance greater than 120 dynes.sec.cm-5, in the setting of the presence of portosystemic shunting has been proposed as hemodynamic criteria for portopulmonary hypertension. Prevalence of pulmonary hypertension ascertained by right cardiac catheterization was 2% among patients with cirrhosis, and reached to 4% particularly among candidates for liver transplantation. Hyperdynamic systemic circulation seen commonly in patients with cirrhosis appeared to be normalized by complication of pulmonary hypertension with a contraction of circulating plasma volume. Long term treatment by epoprostenol administration or nitric oxide inhalation could induce a gradual decline in pulmonary arterial pressure in patients with poor response to acute vasodilator administration.     

Role of Nurse Practitioners in the Management of Cirrhotic Patients

Patients with end-stage liver disease (ESLD) often suffer from complications that require ongoing management with outpatient providers. Complications include ascites, hepatic encephalopathy, hyponatremia, pulmonary vascular complications, and esophageal varices. Patients with cirrhosis need to be referred to a hepatologist to establish care and potential evaluation for liver transplantation. Nurse practitioners (NPs) involved in the care of cirrhotic patients are well positioned to provide supportive care, improve symptom management, and prevent complications associated with further decompensation. This article discusses the role of NPs in the management of patients with cirrhosis.     

Place de la réanimation chez le cirrhotique

In cirrhotic patients, liver insufficiency and portal hypertension represent a source of potentially life threatening complications, which may justify intensive care. In addition to specific complications (variceal bleeding, hepatic encephalopathy and hepatorenal syndrome), cirrhosis is a condition which favors non-specific complications including severe bacterial infections and acute renal failure. Apart from these complications, cirrhosis is constantly associated with dysfunctions of several organs and systems (cardiocirculatory system, respiratory system, central nervous system, immune system and coagulation). When severe complications occur, dysfunctions of these organs and system can progress and lead to multi-organ failure. As a result, the prognosis of cirrhotics in intensive care units is poor. A major issue is to determine which patients should be admitted to intensive care. Different prognostic scores have been proposed but none is perfect. Practically, admission in an intensive care unit is justified in the absence of significant hepatic insufficiency or when hepatic insufficiency is reversible, when liver transplantation is possible, and in case of iatrogenic complications. In other conditions, mortality is close to 100% and intensive care may not be justified. Theoretically, the correction of hepatic insufficiency could help to improve the results of intensive care in cirrhotic patients. The tolerance and efficacy of artificial liver support systems (albumin dialysis and bioartificial liver) remain unclear. However, these systems offer attractive perspectives.     

术前内镜下胆道内外引流的临床意义

目的：探讨术前内镜下胆道内外引流（ENBD）和／或ERBD）对梗阻性黄疸患者进行治疗和术前准备的临床意义。方法：根据病因将胆道梗阻病例33例分为良性组（21例）,恶性组（12例）。33例患者实施急诊或择期引流的同时行胆道造影以明确诊断。结果;所有患者胆道均得到充分引流,急性胆管炎者胆道感染得以迅速控制,免于急诊手术;恶性组除2例晚期胰头癌患者仅行ERBD姑息治疗外,其余经ERBD或ENBD引流后,TB均降至40μmol/L以下,为手术创造了条件。全部行根治性手术,除1例出现肝残而胆瘘外,余无并发症发生,无手术死亡率。结论：术前ENBD和ERBD确有进一步的影像学诊断价值和微创及良好的胆道引流减压减黄效果,急诊床旁ENBD尤其对急性重症胆管炎及老年急性胆管炎的治疗具有特别重要的意义。     

Portopulmonary hypertension

Portopulmonary hypertension (PPHT) is a respiratory complication of portal hypertension, defined as an increase in mean pulmonary artery pressure (PAP) of > 25 mmHg with an increase in pulmonary vascular resistance of > 240 dyn.s/cm(-5) and a normal pulmonary capillary wedge pressure ( < 15 mmHg), which often occurs in subjects with liver cirrhosis. Histopathological features of PPHT are endothelial and smooth-muscle cell proliferation and fibrosis leading to luminal obstruction in the resistance arteries. The pathogenesis of PPHT may result from an imbalance between vasoconstrictor and vasodilating factors. The most common pulmonary symptom is exertional dyspnea; fatigue, chest pain and syncope occur more often at an advanced stage. Edema, ascites and prominent jugular veins are signs of both decompensated hepatic cirrhosis and right ventricular failure. Right heart catheterisation is the gold standard for the diagnosis and defines PPHT in mild disease with PAP less than 35 mmHg, moderate disease with PAP between 35 and 45 mmHg, and severe disease with PAP of 45 mmHg or higher. The medical treatment of portopulmonary hypertension is based on the treatment of other forms of pulmonary arterial hypertension, including vasomodulating pharmacologic agents. Liver transplantation is accompanied by high risk of mortality, generally due to acute right ventricular failure and cardiovascular collapse. The prognosis of PPHT is poor with mean survival of 15 months.     

Surgical management of super-super obesity with grade III esophageal varices and liver cirrhosis: The ultimate challenge

The risk of complications after bariatric surgery is high in morbidly obese patients suffering from liver cirrhosis along with moderate to severe portal hypertension. Esophageal varices are even considered as a contraindication for bariatric surgery by many surgeons. We report the case of a 40-year-old gentleman with a body mass index of 65.3 kg/m², with multiple comorbidities including type 2 diabetes mellitus, severe obstructive sleep apnea. On evaluation, he had Child-Pugh A liver cirrhosis with portal hypertension along with grade III esophageal varices and splenomegaly. After adequate optimization, laparoscopic sleeve gastrectomy was performed. The patient is doing well at a follow up of 12 months with an adequate weight loss and resolution of comorbidities. Sleeve gastrectomy can be performed in a morbidly obese Child-Pugh A cirrhotic patient with portal hypertension and esophageal varices with proper counseling regarding more than usual risk for morbidity and mortality.     

Screen for portopulmonary hypertension, especially in liver transplant candidates

Pulmonary artery hypertension may develop in some patients with liver disease and portal hypertension. Although pulmonary artery hypertension may be asymptomatic in its early stages, it should be looked for especially if a patient is a candidate for liver transplantation, as it may make transplantation riskier.