How non-alcoholic fatty liver disease and cirrhosis affect the heart.

Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field.

Do You Have To Evaluate The Heart Of The Cirrhotic Patients?

Objectives: To identify patients with occult cardiac dysfunction and itsrelationship with the severity of liver impairment. Method: This is a Judgment (Purposive) Sampling, cross-sectionalstudy that was conducted at Kafrelsheikh University Hospital, Egypt, from November 2019 to December 2020, and comprised adult patients of either gender with liver cirrhosis. After detailed history, a clinical examination, pathological assessment and cardiac evaluation based on electrocardiogram and echocardiography, the patients were divided into three groups. Patients who had dyspnoea or cyanosis were in group A, those who did not have dyspnoea or cyanosis but had electrocardiogram and echocardiography abnormalities were in group B, and patients who did not have dyspnoea, cyanosis or electrocardiogram and echocardiography abnormalities were in group C. The severity of the liver disease was evaluated using Child-Pugh and Model of End Liver Disease scores. Data was analysed using SPSS 20. RESULTS: Of the 300 patients, 153(51%) were males and 147(49%) were females. The overall mean age was 55.1±5.1 years(range: 20-60 years). There were 58(19.33%) patientsin group A, 108(36%) in group B and 134(44.66%) in group C. Group A patientsshowed higher Child-Pugh and Model of End Liver Disease scoresthan the other groups(p<0.05). Child-Pugh score >6 and Model of End Liver Disease score >37 yielded the best accuracy for detecting cardiac abnormalities in group B (p<0.05). CONCLUSIONS: There were significant cardiac changes in cirrhotic patients.

Beta-adrenergic blockade in cirrhosis - harmful or helpful?

INTRODUCTION: Portal hypertension exacerbates the disease course of cirrhosis and is responsible for major complications, including bleeding from esophageal varices, ascites, and encephalopathy. More than 40 years ago, Lebrec and colleagues introduced beta-blockers to prevent esophageal bleeding. However, evidence now suggests that beta-blockers may cause adverse reactions in patients with advanced cirrhosis. AREAS COVERED: This review addresses current evidence for the pathophysiology of portal hypertension, focusing on the pharmacological effects of treatment with beta-blockers, indications for preventing variceal bleeding, their effects on decompensated cirrhosis, and the risk of treating patients suffering from decompensated ascites and renal dysfunction with beta-blockers. EXPERT OPINION: The diagnosis of portal hypertension should be based on direct measurements of portal pressure. Carvedilol or nonselective beta-blockers are the first-line treatment for patients with medium-to-large varices as primary or secondary prophylaxis, in Child C patients with small varices, and sometimes for patients with clinically significant portal hypertension (HVPG ≥ 10 mm Hg, irrespective of the presence of varices) to prevent decompensation. Caution should be used when treating decompensated patients who are suspected of imminent cardiac and renal dysfunction. Future strategies for managing patients with portal hypertension should aim for more personalized treatment that takes into account the disease stage.

Oxidative stress triggers hyperdynamic circulation via central neural activation in portal hypertensive rats.

BACKGROUND: Hyperdynamic circulation in portal hypertension (PHT) depends on central neural activation. However, the initiating mechanism that signals PHT to the central neural cardiovascular-regulatory centers remains unclear. We aimed to test the hypothesis that oxidative stress in the gut initiates the signal that activates central cardiovascular nuclei in portal hypertensive rats. METHODS: Two groups of rats were used. One had portal hypertension produced by partial portal vein ligation, while controls underwent sham operation. Hemodynamics including portal pressure, cardiac output, mean arterial pressure (MAP) and peripheral vascular resistance were measured. Activation of central cardiovascular nuclei was determined by immunohistochemical Fos expression in the paraventricular nucleus (PVN) of the hypothalamus. Myeloperoxidase activity, an oxidative stress marker, was measured in the jejunum. Hydrogen peroxide, the antioxidant N-acetyl-cysteine (NAC) or saline controls were administered for 12-14 days by gavage or osmotic minipumps placed in the peritoneal cavity. RESULTS: Compared with controls, PHT rats showed increased cardiac output (54.2 ± 9.5 vs 33.6 ± 2.4 ml/min/100 g BW, p < 0.01), decreased MAP (96.2 ± 6.4 mmHg vs 103.2 ± 7.8, p < 0.01) and systemic vascular resistance (1.84 ± 0.28 vs 3.14 ± 0.19 mmHg/min/ml/100 g BW, p < 0.01). PHT rats had increased jejunal myeloperoxidase and PVN Fos expression. NAC treatment eliminated the hyperdynamic circulation, decreased jejunal myeloperoxidase and PVN Fos expression in PHT rats, but had no effect on sham controls. H2O2 significantly increased PVN Fos expression and decreased MAP. CONCLUSION: These results indicate that in PHT, mesenteric oxidative stress is the initial signal that activates chemoreceptors and triggers hyperdynamic circulation by central neural cardiovascular-regulatory centers.

Transcriptome analysis of mesenteric arterioles changes and its mechanisms in cirrhotic rats with portal hypertension.

Portal hypertension (PHT) is a major cause of liver cirrhosis. The formation of portosystemic collateral vessels and splanchnic vasodilation contribute to the development of hyperdynamic circulation, which in turn aggravates PHT and increases the risk of complications. To investigate the changes in mesenteric arterioles in PHT, cirrhotic rat models were established by ligating the common bile ducts. After 4 weeks, the cirrhotic rats suffered from severe PHT and splanchnic hyperdynamic circulation, characterized by increased portal pressure (PP), cardiac output (CO), cardiac index (CI), and superior mesenteric artery (SMA) flow. Mesenteric arterioles in cirrhotic rats displayed remarkable vasodilation, vascular remodeling, and hypocontractility. RNA sequencing was performed based on these findings. A total of 1,637 differentially expressed genes (DEGs) were detected, with 889 up-regulated and 748 down-regulated genes. Signaling pathways related to vascular changes were enriched, including the vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase-AKT (PI3K-AKT), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling pathway, among others. Moreover, the top ten hub genes were screened according to the degree nodes in the protein-protein interaction (PPI) network. Functional enrichment analyses indicated that the hub genes were involved in cell cycle regulation, mitosis, and cellular response to oxidative stress and nitric oxide (NO). In addition, promising candidate drugs for ameliorating PHT, such as resveratrol, were predicted based on hub genes. Taken together, our study highlighted remarkable changes in the mesenteric arterioles of cirrhotic rats with PHT. Transcriptome analyses revealed the potential molecular mechanisms of vascular changes in splanchnic hyperdynamic circulation.

Association of low mechano-energetic efficiency and prognosis in liver cirrhosis.

BACKGROUND: In cirrhosis, cardiac systolic dysfunction as part of cirrhotic cardiomyopathy affects prognosis. Myocardial mechano-energetic efficiency (MEE) is an estimate of left ventricular performance. In this study we investigated the relation of MEE to patient characteristics and its impact on survival in patients with cirrhosis. PATIENTS AND METHODS: We included 283 patients with cirrhosis of different severity according to the Child-Pugh classifications (A/B/C: 106/87/90). All patients had a liver vein catheterization and a hemodynamic investigation performed including determination of cardiac output (CO), stroke volume and heart rate (HR). These data were used to assess MEE, which was defined as (stroke volume/HR) × 1.666. RESULTS: Eighty-nine percent of patients had portal hypertension (hepatic venous pressure gradient >5 mmHg) and 80% indications of hyperdynamic circulatory state (increased CO and HR). There was no difference in MEE in Child-Pugh class C patients (2.03) versus Child-Pugh class A (1.98) and B (2.05) patients. In Child-Pugh class C patients, low MEE was associated with a poorer prognosis. CONCLUSION: In our study, MEE does not seem to be associated with severity of the liver disease, but in patients with advanced disease low MEE is associated with a poorer prognosis. The prognostic impact of MEE should be further investigated.

Radio frequency ablation for the intrauterine treatment of giant placental chorioangioma associated with fetal compromise: A case report.

Giant placental chorioangiomas associated with fetal hyperdynamic circulation complications are rare to see. Here, we summarized a case of giant placental chorioangioma associated with fetal anemia and heart failure treated by radiofrequency ablation (RFA) combined with cordocentesis and intrauterine transfusion. The sonographic appearance of the placental chorioangioma was atypical which was isoechoic with unclear boundary. RFA was performed successfully at 27 weeks of gestation, when the chorioangioma has increased to 17.0 × 10.6 × 12.3 cm3 . Unfortunately, intrauterine fetal demise was found on the first day after operation. After induction of labor, it was pathologically confirmed as placental chorioangioma.

Femoral Pulse Pressure Variation Is Not Interchangeable with Radial Pulse Pressure Variation during Living Donor Liver Transplantation.

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has not rather than never studied in patients undergoing liver transplantation whether PPV measured at peripheral sites, such as the radial artery, do represent central PPV for evaluating blood volume. In this retrospective study, 51 liver transplant recipients were enrolled. The two PPVs had been automatically recorded every minute in electrical medical records. A total 1878 pairs of the two PPVs were collected. The interchangeability of PPV measured at the radial and the femoral artery was analyzed by using the Bland−Altman plot, four-quadrant plot, Cohen's kappa (k), and receiver operating curve. The bias and limits of agreement of the two PPVs were −1.3% and −8.8% to 6.2%, respectively. The percentage error was 75%. The concordance rate was 65%. The Kappa of PPV-radial determining whether PPV-femoral was >13% or ≤13% was 0.64. We found that PPV-radial is not interchangeable with PPV-femoral during liver transplantation. Additionally, PPV-radial failed to reliably track changes of PPV-femoral. Lastly, the clinical decision regarding blood volume status (depletion or not) is significantly different between the two PPVs. Therefore, PPV-femoral may help maintain blood volume circulating to major organs including the newly transplanted liver graft for liver transplant recipients.

Gut-liver axis in cirrhosis: Are hemodynamic changes a missing link?

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease, especially cirrhosis. This introduces the concept of the gut-liver axis, which can be imagined as a chain connected by several links. Gut dysbiosis, small intestinal bacterial overgrowth, and intestinal barrier alteration lead to bacterial translocation, resulting in systemic inflammation. Systemic inflammation further causes vasodilation, arterial hypotension, and hyperdynamic circulation, leading to the aggravation of portal hypertension, which contributes to the development of complications of cirrhosis, resulting in a poorer prognosis. The majority of the data underlying this model were obtained initially from animal experiments, and most of these correlations were further reproduced in studies including patients with cirrhosis. However, despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development, the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied. They remain a missing link in the gut-liver axis and a challenge for future research.

What's New in Cirrhotic Cardiomyopathy?-Review Article.

Cirrhotic cardiomyopathy (CCM) is a relatively new medical term. The constant development of novel diagnostic and clinical tools continuously delivers new data and findings about this broad disorder. The purpose of this review is to summarize current facts about CCM, identify gaps of knowledge, and indicate the direction in which to prepare an updated definition of CCM. We performed a review of the literature using scientific data sources with an emphasis on the latest findings. CCM is a clinical manifestation of disorders in the circulatory system in the course of portal hypertension. It is characterized by impaired left ventricular systolic and diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. However, signs and symptoms reported by patients are non-specific and include reduced exercise tolerance, fatigue, peripheral oedema, and ascites. The disease usually remains asymptomatic with almost normal heart function, unless patients are exposed to stress or exertion. Unfortunately, due to the subclinical course, CCM is rarely recognized. Orthotopic liver transplantation (OLTx) seems to improve circulatory function although there is no consensus about its positive effect, with reported cases of heart failure onset after transplantation. Researchers indicate a careful pre-, peri-, and post-transplant cardiac assessment as a crucial point in detecting CCM and improving patients' prognosis. There is also an urgent need to update the CCM definition and establish a diagnostic algorithm for early diagnosis of CCM as well as a specific treatment of this condition.

The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes.

BACKGROUND AND AIMS: The cardiovascular hormones renin/angiotensin/aldosterone (RAA), brain-type natriuretic peptide (BNP)and arginine-vasopressin (AVP) are key regulators of systemic circulatory homeostasis in portal hypertension (PH). We assessed (i) the activation of renin, BNP and AVP across distinct stages of PH and (ii) whether activation of these hormones correlates with clinical outcomes. METHODS: Plasma levels of renin, proBNP and copeptin (AVP biomarker) were determined in 663 patients with advanced chronic liver disease (ACLD) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 11/2011 and 02/2019. We stratified for Child stage (A-C), HVPG (6-9 mmHg, 10-15 mmHg, ≥ 16 mmHg) and compensated vs. decompensated ACLD. RESULTS: With increasing PH, hyperdynamic state was indicated by higher heart rates (6-9 mmHg: median 71.0 [IQR 18.0] bpm, 10-15 mmHg: 76.0 [19.0] bpm, ≥ 16 mmHg: 80.0 [22.0] bpm; p < 0.001), lower mean arterial pressure (6-9 mmHg: 103.0 [13.5] mmHg, 10-15 mmHg: 101.0 [19.5] mmHg, ≥ 16 mmHg: 99.0 [21.0] mmHg; p = 0.032) and lower serum sodium (6-9 mmHg: 139.0 [3.0] mmol/L, 10-15 mmHg: 138.0 [4.0] mmol/L, ≥ 16 mmHg: 138.0 [5.0] mmol/L; p < 0.001). Across HVPG strata (6-9 mmHg vs. 10-15 mmHg vs ≥ 16 mmHg), median plasma levels of renin (21.0 [50.5] vs. 25.1 [70.9] vs. 65.4 [219.6] µIU/mL; p < 0.001), proBNP (86.1 [134.0] vs. 63.6 [118.0], vs. 132.2 [208.9] pg/mL; p = 0.002) and copeptin (7.8 [7.7] vs. 5.6 [8.0] vs. 10.7 [18.6] pmol/L; p = 0.024) increased with severity of PH. Elevated renin levels independently predicted first hepatic decompensation (adjusted hazard ratio [aHR]: 1.69; 95% confidence interval [95% CI] 1.07-2.68; p = 0.025) and mortality in compensated patients (aHR: 3.15; 95% CI 1.70-5.84; p < 0.001) and the overall cohort aHR: 1.42; 95% CI 1.01-2.01; p = 0.046). Elevated copeptin levels predicted mortality in decompensated patients (aHR: 5.77; 95% CI 1.27-26.33; p = 0.024) and in the overall cohort (aHR: 3.29; 95% CI 1.36-7.95; p = 0.008). ProBNP levels did not predict clinical outcomes. CONCLUSIONS: The cardiovascular hormones renin, proBNP and AVP are activated with progression of ACLD and PH. Renin activation is a risk factor for hepatic decompensation and mortality, especially in compensated patients. Increased plasma copeptin is a risk factor for mortality, in particular in decompensated patients.

Bacterial infections adversely influence the risk of decompensation and survival in compensated cirrhosis.

BACKGROUND & AIMS: The prognosis of compensated cirrhosis is good until decompensation. In decompensated cirrhosis, bacterial infections (BIs) are common and increase the risk of death. The incidence and prognostic implications of BIs in compensated cirrhosis are less-well characterized. This study aimed to assess whether BIs influence the risk of decompensation and survival in patients with compensated cirrhosis. METHODS: This is a cohort study nested to the PREDESCI study, a double-blind, multicenter, randomized controlled trial designed to assess whether ß-blockers could prevent decompensation of cirrhosis. Patients with compensated cirrhosis and hepatic venous pressure gradient ≥10 mmHg were included. Development of BIs during follow-up was prospectively registered. Using a competing-risk time-dependent regression analysis, we investigated whether BIs affect the risk of decompensation and survival. Decompensation was defined as development of ascites, bleeding or overt encephalopathy. RESULTS: A total of 201 patients were randomized and followed for a median of 36 months (IQR 24-47 months); 34 patients (17%) developed BIs, which occurred before decompensation in 33 cases, and 29 (14%) developed ascites. Respiratory and urinary tract infections were the most frequent BIs. Decompensation occurred in 26% patients with BIs vs. 16% without BIs. Patients with BIs were at higher risk of decompensation (subdistribution hazard ratio [SHR] 2.93; 95% CI 1.02-8.42; p = 0.047) and of developing ascites (SHR 3.55; 95% CI 1.21-10.47; p = 0.022) than those without BIs. Risk of death was also higher in patients with BIs (subdistribution HR 6.93; 95% CI 2.64-18.18; p <0.001), although decompensation occurred before death in 71% of such cases. CONCLUSIONS: BIs have a marked impact on the natural history of compensated cirrhosis, significantly increasing the risk of decompensation, mainly that of ascites, and increasing the risk of death, which usually occurs after decompensation. Our results suggest that BIs may constitute a target to prevent decompensation. LAY SUMMARY: It is widely known that bacterial infections are common and increase the mortality risk in patients with decompensated cirrhosis. However, the relevance of bacterial infections in compensated cirrhosis has not been well studied. This study shows that in patients with compensated cirrhosis and clinically significant portal hypertension, bacterial infections occur as frequently as the development of ascites, which is the most frequent decompensating event. Bacterial infections increase the risk of progression to decompensation, mainly by increasing the risk of ascites, and also increase the risk of death, which usually occurs after decompensation. CLINICALTRIALS. GOV IDENTIFIER: NCT01059396.

Occurrence and progression of hemodynamic dysfunction in cirrhotic portal hypertension / 中华消化外科杂志

Cirrhotic portal hypertension refers to a series of syndroms characterized by structural abnormality and dysfunction of hepatic sinusoid caused by chronic liver injury and obstructing portal-systemic blood flow, resulting in gradually increased portal venous system pressure as clinical manifestations. Increased intrahepatic resistance and portal venous system blood flow are main causes for cirrhotic portal hypertension. The structural abnormality and dysfunction of hepatic sinusoid cause not only increased intrahepatic resistance, but also substance exchange barriers between hepatic sinusoidal blood and hepatocytes, resulting in splanchnic artery dilation and increased blood flow and pressure of portal venous system. Dysfunction of splanchnic hemodynamic is an important factor for hyperdynamic circulation in cirrhotic portal hypertension. As the disease progresses, cirrhotic portal hypertension can continuously promote the activation of hyperdynamic circulation, which in turn can accelerate the development of cirrhotic portal hyperten-sion. This vicious circle is the main reason for the irreversible and untreatable end-stage liver disease. The authors review the pathophysiological mechanisms of cirrhotic portal hypertension, splanchnic hemodynamic dysfunction and hyperdynamic circulation.

Short-term hemodynamic effects of ß-blockers influence survival of patients with decompensated cirrhosis.

BACKGROUND & AIMS: Whether the effect of ß-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of ß-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. METHODS: Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting ß-blockers and again after 1 to 3 months of treatment (short-term). RESULTS: Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under ß-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with ß-blockers than survivors (21 ± 14% vs. 15 ± 16%; p <0.05) and CO under ß-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004). CONCLUSIONS: In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to ß-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of ß-blockers on CO might adversely influence survival in decompensated cirrhosis. LAY SUMMARY: ß-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of ß-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of ß-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of ß-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.

Pathophysiological-based treatments of complications of cirrhosis.

Detailed knowledge and understanding of the pathophysiological mechanisms and changes in hepatic and splanchnic function leading to the development of haemodynamic changes and portal hypertension in patients with cirrhosis are essential since it guides the search for targets to ameliorate liver-related abnormalities. Recent research has focused on the gut-liver axis, changes in intestinal permeability, translocation of bacterial products, and inflammation as important drivers of haemodynamic alterations and thereby targets for treatment. Additionally, treatment strategies should focus on microbiotic modulation, antiangiogenics, anti-inflammatory strategies, and modulation of bile acid metabolism. This paper aims to review contemporary pathophysiological-based treatment principles of the major complications of cirrhosis and portal hypertension and future targets for treatment.

Pathological abnormalities in splenic vasculature in non-cirrhotic portal hypertension: Its relevance in the management of portal hypertension.

BACKGROUND: Portal hypertension (PH) is associated with changes in vascular structure and function of the portosplenomesenteric system (PSMS). This is referred to as portal hypertensive vasculopathy. Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients. Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy. In view of this, it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH (NCPH). AIM: To investigate pathological abnormalities of splenic vein in patients with NCPH, and suggest its possible implications in the management of PH. METHODS: A prospective observational study was performed on 116 patients with NCPH [Extrahepatic portal vein obstruction (EHPVO): 53 and non-cirrhotic portal fibrosis (NCPF): 63] who underwent proximal splenorenal shunt (PSRS), interposition shunt or splenectomy with devascularization in JIPMER, Pondicherry, India, a tertiary level referral center, between 2011-2016. All patients were evaluated by Doppler study of PSMS, computed tomography porto-venogram and upper gastrointestinal endoscopy. An acoustic resonance forced impulse (ARFI) scan and abdomen ultrasound were done for all cases to exclude cirrhosis. Intraoperative and histopathological assessment of the harvested splenic vein was performed in all. The study group was divided into delayed and early presentation based on the median duration of symptoms (i.e. 108 mo). RESULTS: The study group comprising of 116 patients [77 (66%) females and 39 (34%) males] with NCPH had a median age of 22 years. Median duration of symptoms was 108 mo. The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding (hematemesis and melena). The ARFI scan revealed a median score of 1.2 (1.0-1.8) m/s for EHPVO and 1.5 (0.9-2.8) m/s for NCPF. PSRS was performed in 84 patients (two of whom underwent interposition PSRS using a 10 mm Dacron graft); splenoadrenal shunt in 9; interposition mesocaval shunt in 5; interposition 1st jejunal to caval shunt in 1 patient and devascularization with splenectomy in 17 patients. Median pre-splenectomy portal pressure was 25 (range: 15-51) mm Hg. In 77% cases, the splenic vein was abnormal upon intraoperative assessment. Under macroscopic examination, wall thickening was observed in 108 (93%), venous thrombosis in 32 (28%) and vein wall calcification in 27 (23%) cases. Upon examination under a surgical magnification loupe, 21 (18%) patients had intimal defects in the splenic vein. Histopathological examination of veins was abnormal in all cases. Medial hypertrophy was noted in nearly all patients (107/116), while intimal fibrosis was seen in 30%. Ninety one percent of patients with intimal fibrosis also had venous thrombosis. Vein wall calcification was found in 22%, all of whom had intimal fibrosis and venous thrombosis. The proportion of patients with pathological abnormalities in the splenic vein were significantly greater in the delayed presentation group as compared to the early presentation group. CONCLUSION: Pathological changes in the splenic vein similar to those in cirrhotic patients with PH are noted in NCPH. We recommend that PH in NCPH be treated as systemic and pulmonary hypertension equivalent in the gastrointestinal tract, and that early aggressive therapy be initiated to reduce portal pressure and hemodynamic stress to avoid potential lethal effects.

Mechanisms in fluid retention - towards a mutual concept.

Fluid retention is a common and challenging condition in daily clinical practice. The normal fluid homoeostasis in the human body is based on accurately counter-balanced physiological mechanisms. When compromised fluid retention occurs and is seen in pathophysiologically different conditions such as liver cirrhosis, heart and kidney failure, and in preeclampsia. These conditions may share pathophysiological mechanisms such as functional arterial underfilling, which seems to be a mutual element in cirrhosis, cardiac failure, cardiorenal and hepatorenal syndromes, and in pregnancy. However, there are also distinct differences and it is still unclear whether kidney dysfunction or arterial underfilling is the initiating factor of fluid retention or if they happen simultaneously. This review focuses on similarities and differences in water retaining conditions and points to areas where important knowledge is still needed.

An update on cirrhotic cardiomyopathy.

INTRODUCTION: 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.