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Journal of Hepatology Jul 2021Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and... (Review)
Review
Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes.
Topics: Acute-On-Chronic Liver Failure; Humans; Inflammation; Liver Circulation; Liver Cirrhosis; Oxidative Stress; Prognosis
PubMed: 34039492
DOI: 10.1016/j.jhep.2021.01.002 -
Nature Reviews. Gastroenterology &... Apr 2019The liver microcirculatory milieu, mainly composed of liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs) and hepatic macrophages, has an essential... (Review)
Review
The liver microcirculatory milieu, mainly composed of liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs) and hepatic macrophages, has an essential role in liver homeostasis, including in preserving hepatocyte function, regulating the vascular tone and controlling inflammation. Liver microcirculatory dysfunction is one of the key mechanisms that promotes the progression of chronic liver disease (also termed cirrhosis) and the development of its major clinical complication, portal hypertension. In the present Review, we describe the current knowledge of liver microcirculatory dysfunction in cirrhotic portal hypertension and appraise the preclinical models used to study the liver circulation. We also provide a comprehensive summary of the promising therapeutic options to target the liver microvasculature in cirrhosis.
Topics: Combined Modality Therapy; Humans; Hypertension, Portal; Liver Circulation; Microcirculation; Vascular Resistance
PubMed: 30568278
DOI: 10.1038/s41575-018-0097-3 -
International Journal of Molecular... Dec 2020Liver disease resulting from heart failure (HF) has generally been referred as "cardiac hepatopathy". One of its main forms is congestive hepatopathy (CH), which results... (Review)
Review
Liver disease resulting from heart failure (HF) has generally been referred as "cardiac hepatopathy". One of its main forms is congestive hepatopathy (CH), which results from passive venous congestion in the setting of chronic right-sided HF. The current spectrum of CH differs from earlier reports with HF, due to ischemic cardiomyopathy and congenital heart disease having surpassed rheumatic valvular disease. The chronic passive congestion leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis ("cardiac cirrhosis") and hepatocellular carcinoma after several decades of ongoing injury. Contrary to primary liver diseases, in CH, inflammation seems to play no role in the progression of liver fibrosis, bridging fibrosis occurs between central veins to produce a "reversed lobulation" pattern and the performance of non-invasive diagnostic tests of liver fibrosis is poor. Although the clinical picture and prognosis is usually dominated by the underlying heart condition, the improved long-term survival of cardiac patients due to advances in medical and surgical treatments are responsible for the increased number of liver complications in this setting. Eventually, liver disease could become as clinically relevant as cardiac disease and further complicate its management.
Topics: Heart Failure; Humans; Liver; Liver Circulation; Liver Diseases
PubMed: 33321947
DOI: 10.3390/ijms21249420 -
The American Journal of Gastroenterology Jan 2020Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure,... (Review)
Review
Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.
Topics: Gastroenterology; Humans; Liver; Liver Circulation; Liver Diseases; Mesentery; Practice Guidelines as Topic; Societies, Medical; Splanchnic Circulation; United States; Vascular Diseases
PubMed: 31895720
DOI: 10.14309/ajg.0000000000000486 -
Clinical Journal of Gastroenterology Oct 2019Liver cirrhosis is associated with multiple vascular syndromes affecting almost all body systems. Many of these syndromes are directly related to impaired liver function... (Review)
Review
Liver cirrhosis is associated with multiple vascular syndromes affecting almost all body systems. Many of these syndromes are directly related to impaired liver function and sometimes reversible after liver transplantation while others arise secondary to portal hypertension and ascites. Altered expression of angiogenic and vasoactive compounds (most importantly nitric oxide), endothelial dysfunction, dysregulated neurohormonal control, and systemic inflammatory state play differential roles in mediating homeostatic instability and abnormal vasogenic response. Important vascular features encountered in liver disease include portal hypertension, splanchnic overflow, abnormal angiogenesis and shunts, portopulmonary syndrome, hepatopulmonary syndrome, and systemic hyperdynamic circulation. Redistribution of effective circulatory volume deviating from vital organs and pooling in splanchnic circulation is also encountered in liver patients which may lead to devastating outcomes as hepatorenal syndrome. Etiologically, vascular syndromes are not isolated phenomena and vascular dysfunction in one system may lead to the development of another in a different system. This review focuses on understanding the pathophysiological factors underlying vascular syndromes related to chronic liver disease and the potential links among them. Many of these syndromes are associated with high mortality, thus it is crucial to look for early biomarkers for these syndromes and develop novel preventive and therapeutic strategies.
Topics: Collateral Circulation; Hepatopulmonary Syndrome; Hepatorenal Syndrome; Humans; Hypertension, Portal; Hypertension, Pulmonary; Liver Circulation; Liver Cirrhosis; Pulmonary Circulation; Splanchnic Circulation; Syndrome; Vascular Diseases; Vasodilation
PubMed: 30980261
DOI: 10.1007/s12328-019-00956-0 -
Expert Review of Gastroenterology &... May 2019Cirrhosis with portal hypertension and related complications are associated with a high mortality. Excess of circulating vasodilators and cardiodepressive substances... (Review)
Review
Cirrhosis with portal hypertension and related complications are associated with a high mortality. Excess of circulating vasodilators and cardiodepressive substances lead to a hyperdynamic circulation with changed myocardial structure and function. The entity cirrhotic cardiomyopathy seems to be involved in different aspects of hepatic decompensation, which focuses on new targets of treatment. Areas covered: This review deals with contemporary aspects of cirrhotic cardiomyopathy, and the literature search was undertaken by PubMed with 'cirrhotic' and 'cardiomyopathies' as MeSH Terms. Cirrhotic cardiomyopathy is defined as the presence of systolic and diastolic dysfunction and electrophysiological abnormalities. The diagnosis is based on contemporary Doppler/Echocardiography measurements or quantitative magnetic resonance imaging. Cirrhotic cardiomyopathy is independent of the etiology of the liver disease but related to severity and survival. Expert commentary: The outcome of invasive procedures and liver transplantation is influenced by the presence of cardiac dysfunction. Therefore, a cautious cardiac evaluation should be included in the patient evaluation prior to liver transplantation. Liver transplantation ameliorates most of the abnormalities seen in cirrhotic cardiomyopathy, but no specific treatment can yet be recommended.
Topics: Animals; Cardiomyopathies; Hemodynamics; Humans; Liver Circulation; Liver Cirrhosis; Liver Transplantation; Risk Factors; Treatment Outcome
PubMed: 30802157
DOI: 10.1080/17474124.2019.1587293 -
Journal of Gastrointestinal Surgery :... Jun 2020The "Small-for-Size" syndrome is defined as a liver failure after a liver transplant with a reduced graft or after a major hepatectomy. The later coined "Small-for-Flow"... (Review)
Review
BACKGROUND
The "Small-for-Size" syndrome is defined as a liver failure after a liver transplant with a reduced graft or after a major hepatectomy. The later coined "Small-for-Flow" syndrome describes the same situation in liver resections but based on hemodynamic intraoperative parameters (portal pressure > 20 mmHg and/or portal flow > 250 ml/min/100 g). This focuses on the damage caused by the portal hyperafflux related to the volume of the remnant.
METHODS
Relevant studies were reviewed using Medline, PubMed, and Springer databases.
RESULTS
Portal hypertension after partial hepatectomies also leads to a higher morbidity and mortality. There are plenty of experimental studies focusing on flow rather than size. Some of them also perform different techniques to modulate the portal inflow. The deleterious effect of high posthepatectomy portal venous pressure is known, and that is why the idea of portal flow modulation during major hepatectomies in humans is increasing in everyday clinical practice.
CONCLUSIONS
Considering the extensive knowledge obtained with the experimental models and good results in clinical studies that analyze the "Small-for-Flow" syndrome, we believe that measuring portal flow and portal pressure during major liver resections should be performed routinely in extended liver resections. Applying these techniques, the knowledge of hepatic hemodynamics would be improved in order to advance against posthepatectomy liver failure.
Topics: Hemodynamics; Hepatectomy; Humans; Liver; Liver Circulation; Liver Failure; Liver Regeneration; Portal Pressure; Portal Vein
PubMed: 32314232
DOI: 10.1007/s11605-020-04576-9 -
Annals of Hepatology Mar 2018Fontan-associated liver disease is a hepatic disorder arising from hemodynamic changes and systemic venous congestion following Fontan surgery. The histological changes... (Review)
Review
Fontan-associated liver disease is a hepatic disorder arising from hemodynamic changes and systemic venous congestion following Fontan surgery. The histological changes produced in the liver are similar but not equivalent to those seen in other forms of cardiac liver disease. While the natural history of this form of liver disease is not well established, over time many Fontan patients develop portal hypertension-related complications such as ascites, variceal hemorrhage or encephalopathy. Fontan survivors also show an increased risk of hepatocellular carcinoma. Early diagnosis of advanced liver disease is mandatory for the prevention and treatment of complications such as hepatocellular carcinoma, esophageal varices and malnutrition. This review updates current knowledge of the pathophysiology and management of Fontan-associated liver disease including new diagnostic methods and treatments.
Topics: Fontan Procedure; Heart Defects, Congenital; Hemodynamics; Humans; Liver; Liver Circulation; Liver Diseases; Risk Factors; Treatment Outcome
PubMed: 29469053
DOI: 10.5604/01.3001.0010.8634 -
International Journal of Surgery... Oct 2020Small-for-Size Syndrome (SFSS) is one of the most feared complication of adult split liver and living donor liver transplantation. SFSS stems from a... (Review)
Review
Small-for-Size Syndrome (SFSS) is one of the most feared complication of adult split liver and living donor liver transplantation. SFSS stems from a disproportionate/excessive portal vein flow relative to the volume of the implanted liver graft, and is currently one of the major practical limits to partial liver grafts' transplantation. In the last few decades many graft inflow modulation (GIM) techniques have been proposed to curtail the portal vein flow, allowing for successful transplantation of small partial liver grafts. Graft inflow modulation techniques span from Splenic Artery Ligation (SAL), to Splenectomy, Porto-Systemic Shunts and the lately proposed Splenic Devascularization. A patient tailored approach balancing the risk of SFSS with GIM specific morbidity, is more important than identifying the ideal GIM technique. Here we summarize the most recently published data to provide general indications in the challenging preoperative choice of a GIM techniques.
Topics: Adult; Female; Humans; Ligation; Liver; Liver Circulation; Liver Diseases; Liver Transplantation; Living Donors; Male; Middle Aged; Organ Size; Portal Vein; Splenectomy; Splenic Artery; Transplants
PubMed: 32738547
DOI: 10.1016/j.ijsu.2020.07.003 -
Radiographics : a Review Publication of... 2016Congestive hepatopathy (CH) refers to hepatic abnormalities that result from passive hepatic venous congestion. Prolonged exposure to elevated hepatic venous pressure... (Review)
Review
Congestive hepatopathy (CH) refers to hepatic abnormalities that result from passive hepatic venous congestion. Prolonged exposure to elevated hepatic venous pressure may lead to liver fibrosis and cirrhosis. Liver dysfunction and corresponding clinical signs and symptoms typically manifest late in the disease process. Recognition of CH at imaging is critical because advanced liver fibrosis may develop before the condition is suspected clinically. Characteristic findings of CH on conventional images include dilatation of the inferior vena cava and hepatic veins; retrograde hepatic venous opacification during the early bolus phase of intravenous contrast material injection; and a predominantly peripheral heterogeneous pattern of hepatic enhancement due to stagnant blood flow. Extensive fibrosis can be seen in chronic or severe cases. Hyperenhancing regenerative nodules that may retain hepatobiliary contrast agents are often present. Magnetic resonance (MR) elastography can show elevated liver stiffness and may be useful in evaluation of fibrosis in CH because it can be incorporated easily into routine cardiac MR imaging. Preliminary experience with MR elastography suggests its future use in initial evaluation of patients suspected of having CH, for monitoring of disease, and for assessment after therapy. To facilitate appropriate workup and treatment, radiologists should be familiar with findings suggestive of CH at radiography, ultrasonography, computed tomography, MR imaging, and MR elastography. In addition, knowledge of underlying pathophysiology, comparative histologic abnormalities, and extrahepatic manifestations is useful to avoid diagnostic pitfalls and suggest appropriate additional diagnostic testing. (©)RSNA, 2016.
Topics: Heart Diseases; Humans; Liver Circulation; Liver Diseases; Vascular Diseases
PubMed: 27284758
DOI: 10.1148/rg.2016150207