Cardiac Cirrhosis Research Articles

Abstract 4138238: A Tense Race: Correlation of Liver Stiffness with Ultrasound Elastography and Hemodynamics in Fontan Patients.

Background: Ultrasound elastography (USE) is a non-invasive tool to diagnose and monitor liver fibrosis. Patients with Fontan physiology are predisposed to congestive hepatopathy, progressive liver fibrosis, and end-stage liver disease. We sought to determine whether hemodynamics pre- and post-Fontan are associated with increased liver stiffness on USE. Methods: A single-center retrospective study included Fontan patients who had one or more USE between 06/2008-03/2024. Liver stiffness was reported as shear wave elastography (SWE) in m/s. Hemodynamic data pre- and post-Fontan and recent echocardiographic data were collected. Data was analyzed as continuous (linear regression model) and as a dichotomous variable (t-test). Results: A total of 78 post-Fontan USE results in 56 patients were analyzed. Table 1 describes the demographics of our patient population. The spectrum of fibrosis based on USE was normal (3.8%), mild (10.3%), moderate (55.1%) and severe (30.8%). In patients with more than one USE, the average increase in SWE was 0.04m/s per month. Pre-Fontan median Glenn pressure was 12mmHg [IQR 13, 15] (p=0.83). On post-Fontan catheterization, median Fontan pressure was 18mmHg [16, 21] (p=0.86). We did not find a significant correlation between hemodynamics and severity of liver stiffness on USE (Tables 2&3). No correlation was seen between USE and severity of ventricular function or atrioventricular valve regurgitation. SWE as a function of time from Fontan operation (<5 yr, 5-10 yrs, >10 yrs) did not vary significantly. Conclusions: USE as a marker of liver congestion does not correlate with hemodynamics pre- or post-Fontan. Further studies are necessary to determine the clinical utility of USE in Fontan patients.

Abstract 4138624: Looking Beyond Respirophasic Ventricular Interdependence: A Case Report of Constrictive Pericarditis Masquerading as Cirrhosis

Case Presentation: A 67-year-old man with recurrent pleural effusions and concern for cirrhosis was referred for liver transplant. Pleural fluid was transudative by Light’s criteria with a high total protein level of 3.5 g/dL, which made hepatic hydrothorax unlikely. Liver biopsy confirmed congestive hepatopathy without advanced fibrosis. Transthoracic echocardiogram showed left ventricular (LV) ejection fraction 55%, right ventricular (RV) systolic pressure 35 mmHg, normal mitral annular tissue doppler velocities, and early diastolic septal bounce. Right and left heart catheterization showed prominent X and Y descent, elevated and equalized diastolic pressures, but no respiratory discordance in the LV-RV pressure gradient. As etiology of these findings were unclear, he underwent aggressive diuresis and hemodialysis, but repeat right heart catheterization showed persistently elevated right and left filling pressures. Cardiac MRI had no evidence of myocardial or pericardial inflammation/edema but showed pericardial thickening (7.9 mm) and septal bounce. There was no inspiratory septal shift, but the large pleural effusion appeared to limit diaphragm excursion. Given lack of respirophasic ventricular interdependence and thickened pericardium on MRI, CT was ordered, showing pericardial calcifications. Diagnosis of constrictive pericarditis was made, and patient underwent complete pericardiectomy. Pathology confirmed calcified and thick pericardium without acute inflammation. Post-operatively, patient developed RV failure, but recovered with inotrope support and was discharged with improvement in congestive symptoms. Discussion: Constrictive pericarditis classically exhibits respirophasic ventricular interdependence, but large pleural effusions may decrease respiratory variation in intrathoracic pressures, blunting this response. Normal mitral annulus tissue doppler velocities and lack of infiltrative process on cardiac MRI made restrictive cardiomyopathy unlikely. In the absence of respirophasic changes on multimodality testing, constriction can be diagnosed with other supportive features such as diastolic septal bounce, rapid Y descent, diastolic pressure equalization, and pericardial thickening and calcifications.

Association between CMR derived hepatic T1 times, tricuspid regurgitation severity, and outcomes

Abstract Background Hepatic T1 times have been shown to predict adverse clinical outcomes. However, up to date, the various causes contributing to changes in hepatic T1 times are not fully understood. So far, strong correlations with liver congestion and hepatic fibrosis have been demonstrated. Valvular heart disease, especially tricuspid regurgitation (TR), can lead to congestive hepatopathy (CH) and might significantly increase liver T1 values. In contrast, hepatic steatosis – commonly present in patients with cardiovascular disease - would result in lower T1 values. Currently, no studies are investigating the relationship between hepatic T1 times and TR. Methods We retrospectively measured hepatic T1-times, displayed on standard cardiac T1-maps, in an all-comer CMR cohort. Only patients, who underwent a comprehensive transthoracic echocardiogram within three weeks of CMR were included. Results 1029 participants (67±17 y/o, 44% female) had mean hepatic T1-times of 605±79ms. Overall, 41% (417) presented with non/trace, 38% (391) mild, 13% (135) moderate, 8% (85) severe, massive, and torrential tricuspid regurgitation. Liver T1 times were significantly correlated with TR severity (no/trace: 586±72ms; mild: 601±74ms; moderate: 634±84ms; severe/massive/torrential: 665±83ms; r= 0.25, p<0.001). Additionally, when adjusted for higher NT-proBNP levels, and right ventricular function in a linear regression model, TR severity was associated with hepatic T1 times (p<0.001). During follow-up (mean 53±36months), a total of 326 (32%) events occurred. Patients with higher T1 times and more severe tricuspid regurgitation were more likely to suffer events (adj.HR 1.44 [95%CI:1.23-1.69] per 100ms increase, p<0.001). Conclusion Tricuspid regurgitation exerts a notable influence on hepatic T1 times which is likely attributable to hepatic congestion. Importantly, hepatic T1 times were associated with outcomes even after adjustment for NTproBNP, LVEF, and RVEF. This underscores the importance of hepatic T1 times as both a marker of tricuspid regurgitation and an independent predictor of clinical outcomes.

Correlation between portal hypertension and somatic constitution: rationale behind the concept

This review summarizes recent data on the correlation of somatic constitution and portal hypertension.Somatotype reflects the constitutional composition of the human body. Excess endomorphic component (i.e. obesity) increases the risk of portal hypertension (PH - elevated pressure in the portal system above 12 mmHg) development. Among the prehepatic and posthepatic PH causes only congestive hepatopathy, a consequence of heart failure, is connected with obesity. A number of pathways connect the hepatic PH causes with obesity. Firstly, the action of proinflammatory cytokines produced by adipose tissue in greater amount in obesity promotes fatty acid uptake and storage by hepatocytes, leading to elevated oxidative stress and metabolic dysfunctions, activation of stellate cells, that differentiate into myofibroblasts and produce components of the intercellular matrix such as collagen into the perisinusoidal space resulting in fibrosis. Secondly, insulin resistance associated with obesity promotes dysfunction of the hepatic microcirculatory blood vessels, hyperlipidemia and liver steatosis. Thirdly, AMISS (Absence of Meal-induced Insulin Sensitization Syndrome), caused by regular high-carbohydrate and low-protein food consumption, manifested in decreased postprandial secretion of hepatic hormone hepatalin, which increases glucose uptake by skeletal and cardiac muscle, results in prolonged postprandial hyperglycemia, compensatory hyperinsulinemia and hyperlipidemia, leading to increased insulin resistance and a prediabetic state, associated with steatohepatosis. Thus, excess endomorphic component is to be regarded as a prognostic factor for portal hypertension.

S1817 Clinical Outcomes for Patients With Congestive Hepatopathy in Patients With Hyperlipidemia: An Analysis of the National Inpatient Sample

S1817 Clinical Outcomes for Patients With Congestive Hepatopathy in Patients With Hyperlipidemia: An Analysis of the National Inpatient Sample

Real-World Use and Outcomes of Apixaban for Early Post-Surgical Fontan Thromboprophylaxis.

Patients with Fontan physiology are at heightened risk of thrombosis related to passive venous return leading to increased stasis, as well as acquired thrombophilia from congestive hepatopathy. Variability exists for post-Fontan thromboprophylaxis, with no consensus on best practices. Direct oral anticoagulants offer advantages over conventional anticoagulants including fewer drug-drug interactions, no dietary restrictions, and less frequent monitoring. Herein, we report our single center experience utilizing apixaban thromboprophylaxis in children post-Fontan procedure. Single center, retrospective, cohort study evaluating apixaban thromboprophylaxis dosing strategies, efficacy, and safety in children admitted post-Fontan procedure at Boston Children's Hospital. Between September 2019 and December 2023, 62 children, median age 3.2years (2.1-10.5years), weight 13.9kg (9.5-56.3kg) received apixaban at a median of 93days post-Fontan (7-1421days). Over a total of 93days of apixaban exposure, there was 1 treatment-related thrombosis event (0.07 per 1000 person-days on apixaban) and 3 combined treatment-related clinically relevant non-major (CRNM) and major bleeding events (0.22 per 1000 person-days on apixaban). Apixaban for post-Fontan thromboprophylaxis was feasible with low rates of bleeding and thrombosis.

Abstract Tu037: Unraveling the Cellular Mechanisms of Cardiogenic Liver Disease

Background: Right heart failure (RHF) is associated with chronically elevated central venous pressures which can lead to hepatic dysfunction, fibrosis, and ultimately cirrhosis. Despite the prognostic importance of liver disease in RHF little is understood about the cellular and molecular changes that define cardiogenic liver disease. Filling this knowledge gap has the potential to lead to better diagnostic and therapeutic approaches for patients with heart failure and liver dysfunction. Aims: 1) To evaluate the key clinical and pathologic features of cardiogenic liver disease in humans 2) To explore shifts in the cellular landscape in the congested liver using human samples and a mouse model congestive hepatopathy. Methods: We identified 34 patients with heart failure who underwent liver biopsy due to concern for cardiogenic liver disease. These biopsy samples were stained for numerous cellular markers (macrophage subsets, activated stellate cells, endothelial cells, biliary cells) and compared to normal controls. Clinical data was also collected for the included patients. To model cardiogenic liver disease in a mouse we performed partial IVC ligation (pIVCL) to induce liver congestion and then assessed the liver response using flow cytometry, tissue imaging and mRNA analysis. Results: Liver biopsies from patients with cardiogenic liver disease demonstrated increased liver fibrosis, macrophage aggregates, and biliary metaplasia. The severity of biliary metaplasia was closely associated with the extent of liver congestion. Using multi-marker staining the metaplastic cells were found to be of hepatocyte origin. Interestingly, the liver niche containing metaplastic biliary cells was also enriched for recruited macrophages and activated stellate cells. Similar pathologic features were observed in the mouse model of liver congestion. Conclusions: In this study we identified biliary metaplasia and macrophage recruitment as key pathologic features of cardiogenic liver disease. Ongoing investigation of the interplay between macrophages and metaplastic biliary in humans and animal models of congestive hepatopathy may lead to the discovery of novel disease mechanisms and biomarkers for liver dysfunction in heart failure.

Prognostic Indicators of Morbidity and Mortality in Children with Congestive Hepatopathy Presenting with Ascites.

Objectives: Congestive hepatopathy is a significant complication for children suffering from right-sided heart disease (RHD). We hypothesize that hospitalized pediatric patients with ascites will have congestive hepatopathy leading to advanced liver disease if their cardiac condition is RHD versus non-right-sided heart disease (NRHD). Methods: This is a retrospective cohort study of pediatric patients who presented with an ascites diagnosis (ICD-10 R18) and at least one cardiac diagnosis. Patient demographics, past medical history, laboratory values, imaging results, calculated clinical scores (e.g., APRI, FIB-4), treatment, length of stay (LOS), and death at hospital discharge were analyzed. Results: Of the 136 patients with ascites, 21 patients presented with a primary cardiac disease (12 in RHD and 9 in NRHD). Of these patients, eight (38%) were female, and nine (43%) were White, seven (33%) were Black, and five (24%) were unknown. The RHD group had a mean age of 5.1 Y (vs. 9.5 Y in NRHD). The mean APRI score in RHD patients was 2.87, and it was 0.85 in NRDH. Treatments were similar, with most patients requiring diuretics (11 RHD (92%) vs. 8 NRDH (89%)); 5 RHD (42%) vs. 4 NRDH (44%) required inotropic support. RHD patients had a longer LOS, with an average of 92 days vs. 52 days for NRDH patients. Overall, each group had one death at discharge (8% RHD vs. 11% NRDH). Conclusions: In the realm of children with ascites, the subset grappling with congestive heart disease paints a unique picture. In this context, ascites stands as an elusive predictor of liver decompensation, defying conventional diagnostic pathways.

Brain-Derived Neurotrophic Factor as a Potential Diagnostic Marker in Minimal Hepatic Encephalopathy

Abstract Background Based on the etiology, liver cirrhosis is sub-classified into viral hepatitis (hepatitis B, C, and D), due to toxins (alcohol and drugs), autoimmune hepatitis, Cholestatic (primary biliary cholangitis, and primary sclerosing cholangitis), vascular (Budd-Chiari syndrome, sinusoidal obstruction syndrome, and cardiac cirrhosis), and metabolic causes (hemochromatosis, NASH, Wilson disease, alpha-1 antitrypsin deficiency, cryptogenic cirrhosis). Aim of the Work The aim of the current study is to detect Minimal Hepatic Encephalopathy (MHE) among cirrhotic patients of Child C with no or clinically manifest encephalopathy using Brain-Derived Neurotrophic Factor (BDNF) and study the diagnostic value of BDNF serum marker versus Psychometric Hepatic Encephalopathy Score (PHES) in detecting MHE. Patients and Methods 90 patients were enrolled into a clinical cross-sectional study. All patients gave informed written consent. Patients are divided equally into 3 groups, 30 patients each. Patients are either in-patient or out-patients in Ain shams University Hospitals. Group 1 The Examined Group (EG): includes 30 patients diagnosed as hepatitis C, cirrhotic, Child class C with no overt or clinically manifest encephalopathy. Group 2 The Hepatic Encephalopathy Group (HEG): includes 30 patients diagnosed as hepatitis C, cirrhotic, Child class C with overt or clinically manifest encephalopathy. Group 3 The Control Group (CG): includes 30 healthy individuals (volunteers). Results In the present study among the whole sample (n = 90), there was a significant positive correlation between PHES score & BDNF serum level with Hb, platelet count and albumin. While, there was a significant negative correlation between PHES score and BDNF serum level with AST, ALT, total bilirubin, direct bilirubin, INR and Child’s Score. On the other hand, Stawicka et al. 2021, reported that BDNF had a negative correlation with bilirubin (R = –0.35, p = 0.005) and international normalized ratio (INR) (R = –0.37, p = 0.003), and positive with platelets (R = 0.36, p = 0.004), while no associations with age, sex, body mass index (BMI), waist-hip ratio (WHR), creatinine and ammonia. Conclusion MHE constitutes a significant medical problem in a common patient population. Unfortunately, it is often underdiagnosed, likely related to the notion that testing is time consuming requiring highly specialized personnel. Additionally, the term ‘MHE’ may create the impression that this condition has limited impact on patient’s wellbeing; however, it has been shown that MHE has clinical implications on the patient as well as public safety concerns. Diagnosing and treating MHE is difficult owing to the subclinical nature of the disease. The use of Psychometric Hepatic Encephalopathy Score (PHES) and Brain-Derived Neurotrophic Factor could be of great help in early detection of the condition and to give suitable preventive treatment.

Congestive Hepatopathy: Pathophysiology, Workup, and Imaging Findings with Pathologic Correlation.

Liver congestion is increasingly encountered in clinical practice and presents diagnostic pitfalls of which radiologists must be aware. The complex altered hemodynamics associated with liver congestion leads to diffuse parenchymal changes and the development of benign and malignant nodules. Distinguishing commonly encountered benign hypervascular lesions, such as focal nodular hyperplasia (FNH)-like nodules, from hepatocellular carcinoma (HCC) can be challenging due to overlapping imaging features. FNH-like lesions enhance during the hepatic arterial phase and remain isoenhancing relative to the background liver parenchyma but infrequently appear to wash out at delayed phase imaging, similar to what might be seen with HCC. Heterogeneity, presence of an enhancing capsule, washout during the portal venous phase, intermediate signal intensity at T2-weighted imaging, restricted diffusion, and lack of uptake at hepatobiliary phase imaging point toward the diagnosis of HCC, although these features are not sensitive individually. It is important to emphasize that the Liver Imaging Reporting and Data System (LI-RADS) algorithm cannot be applied in congested livers since major LI-RADS features lack specificity in distinguishing HCC from benign hypervascular lesions in this population. Also, the morphologic changes and increased liver stiffness caused by congestion make the imaging diagnosis of cirrhosis difficult. The authors discuss the complex liver macro- and microhemodynamics underlying liver congestion; propose a more inclusive approach to and conceptualization of liver congestion; describe the pathophysiology of liver congestion, hepatocellular injury, and the development of benign and malignant nodules; review the imaging findings and mimics of liver congestion and hypervascular lesions; and present a diagnostic algorithm for approaching hypervascular liver lesions. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Morphometric Indicators of Liver Acini of Deceased Newborns Depending on the Time of Death.

We studied morphometric changes in the liver acini of dead newborns depending on the duration of the postmortem period. Autopsy samples of the liver tissue from 49 dead newborns were divided into 7 groups depending on the time of death. Liver tissue samples were taken from the upper and lower areas of the liver in the supine position of newborns; paraffin sections were prepared and stained with hematoxylin and eosin. The morphometric analysis of histological preparations revealed a progressive decrease in the mean size of the liver plates (trabeculae) and, conversely, an increase in the area of sinusoids with increasing the duration of the postmortem period; these changes were due to the postmortem redistribution of the blood and autolysis processes. More significant changes were noted in acinar zone 3 of the lower part of the liver. The revealed intra-acinar features of postmortem changes should be taken into account for their differential diagnosis with pathological processes that developed during life, in particular, the signs of congestion and peliosis of the liver.

Ketamine induced acute systolic heart failure

Background: Studies have shown major cardiovascular effects associated with ketamine use disorder including dose-dependent negative inotropic effects. Preoperative ketamine use has been linked to ketamine-induced stress cardiomyopathy. Case presentation: A 28-year-old female with a history of recurrent cystitis and ketamine use disorder (twice weekly for 14 years) presented with bilateral lower extremity oedema and shortness of breath for 3 months. She was tachycardic with a troponin level of 0.07 ng/ml and a B-type natriuretic peptide (BNP) level of 2511 pg/ml. Electrocardiogram showed normal sinus rhythm and transthoracic echocardiography (TTE) showed left ventricular ejection fraction (EF) of 15%, dilated left ventricle, and severe tricuspid and mitral regurgitation. Computed tomography (CT) scan of the chest and abdomen showed bilateral pleural effusions with congestive hepatopathy and ascites. The patient was started on intravenous furosemide, metoprolol, and sacubitril/valsartan. Rheumatological workup including complement levels, and antinuclear anti-double-stranded DNA was negative. A repeat TTE 2 weeks later revealed an EF of 25% and moderate tricuspid regurgitation. Four months later, the EF was 54% with normal left ventricular cavity size. Conclusion: Although ketamine use disorder is increasing, data on long-term side effects is minimal. Screening for ketamine use disorders should be considered in patients presenting with acute systolic heart failure. Long-term studies are needed to evaluate the benefits of adding ketamine screening to standard urine toxicology.

Congestive Hepatopathy: A Review of the Literature.

Congestive hepatopathy (CH), stemming from compromised hepatic venous flow or heightened intrahepatic pressure, represents a significant consequence of cardiovascular conditions like congestive heart failure (CHF). This review of literature encapsulates the core aspects of this condition, characterized by hepatic congestion, cellular injury, and impaired liver function. Diagnostic challenges arise due to symptoms mirroring primary liver diseases. Management revolves around addressing the underlying cause and mitigating fluid retention. This review of literature provides a snapshot of CH's complexity, emphasizing its clinical implications and the need for comprehensive understanding in clinical practice.

"Fontan Conduit Stent-Angioplasty and Progression of Fontan-Associated Liver Disease".

Patients with Fontan circulation insidiously develop congestive hepatopathy related to chronically reduced cardiac output and central venous hypertension, also known as Fontan-associated liver disease (FALD). Fontan pathway obstruction is increasingly detected and may accelerate FALD. The impact of conduit stent angioplasty on FALD is unknown. Retrospective, single-center review of patients with Fontan circulation who underwent conduit stent angioplasty at cardiac catheterization over 5-year period. Demographics and cardiac histories were reviewed. Labs, liver ultrasound elastography, echocardiogram, hemodynamic and angiographic data at catheterization were recorded pre- and post-stent angioplasty. Primary outcome was change in hepatic function via MELD-XI scores and liver stiffness (kPa), with secondary outcomes of ventricular function, BNP, and repeat catheterization hemodynamics. 33 patients underwent Fontan conduit stent angioplasty, 19.3 ± 7.0years from Fontan operation. Original conduit diameter was 19.1 ± 1.9mm. Prior to angioplasty, conduit size was reduced to a cross-sectional area 132 (91, 173)mm2 and increased to 314 (255, 363)mm2 post-stent. Subjects' baseline median MELD-XI of 11 (9, 12) increased to 12 (9, 13) at 19 ± 15.5months post-angioplasty (n = 22, p = 0.053). There was no significant change in liver stiffness at 12.1 ± 8.9months post-angioplasty (n = 15, p = 0.13). Median total bilirubin significantly increased (1.4 [0.9, 1.8]), from baseline 1.1 [0.7, 1.5], p = 0.04), as did median BNP (41 [0, 148] from baseline 34 [15, 79]; p = 0.02). There were no significant changes in ventricular function or repeat invasive hemodynamics (n = 8 subjects). Mid-term follow-up of Fontan subjects post-conduit stent angioplasty did not show improvements in non-invasive markers of FALD.

Rejection in the setting of combined Heart and Liver Transplantation

IntroductionEach year the number of combined heart-liver transplants (HLT) increases, with two distinct patient populations proceeding down this pathway. The first are patients with congenital heart disease (CHD), most commonly single ventricle patients palliated with Fontan. The second group are those with long standing congestive hepatopathy, amyloidosis, hemochromatosis, or alcohol induced myopathies and liver disease.One argument for HLT has been the low rate of rejection even among sensitized patients, with reported rejection rates ranging from 0% to 31%. Historically, those with CHD have been highly sensitized which in some cases may prevent or at least delay transplantation. As such, a recent consensus statement by Emamaulee et al. suggest that “there may be an immunological benefit to proceed with HLT with significantly fewer acute cellular and humoral rejection episodes”. The aim of this study is to demonstrate that HLT patients remain at risk for rejection and have required treatment for it. ResultsThere were 15 patients who underwent HLT from January 2017 to February 2022. Of the four patients who did not have CHD, none were considered sensitized, and all underwent induction with basiliximab per our institutional protocol. One of these had rejection. Rejection episodes were identified in four of the 11 CHD patients (36%) patients. ConclusionsIn our study of 15 HLT, including 11 CHD patients (73% denied transplant at ≥ 1 center) demonstrated a higher rate of rejection than previously reported. While theoretically, HLT may mitigate the likelihood of rejection, the risk still exists, and patients benefit from close monitoring commensurate with single organ transplant.

Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice.

Chronic heart failure (CHF) is often linked to liver malfunction and systemic endothelial dysfunction. However, whether cardio-hepatic interactions in heart failure involve dysfunction of liver sinusoidal endothelial cells (LSECs) is not known. Here we characterize LSECs phenotype in early and end stages of chronic heart failure in a murine model. Right ventricle (RV) function, features of congestive hepatopathy, and the phenotype of primary LSECs were characterized in Tgαq*44 mice, with cardiomyocyte-specific overexpression of the Gαq protein, at the age of 4- and 12-month representative for early and end-stage phases of CHF, respectively. 4- and 12-month-old Tgαq*44 mice displayed progressive impairment of RV function and alterations in hepatic blood flow velocity resulting in hepatic congestion with elevated GGT and bilirubin plasma levels and decreased albumin concentration without gross liver pathology. LSECs isolated from 4- and 12-month-old Tgαq*44 mice displayed significant loss of fenestrae with impaired functional response to cytochalasin B, significant changes in proteome related to cytoskeleton remodeling, and altered vasoprotective function. However, LSECs barrier function and bioenergetics were largely preserved. In 4- and 12-month-old Tgαq*44 mice, LSECs defenestration was associated with prolonged postprandial hypertriglyceridemia and in 12-month-old Tgαq*44 mice with proteomic changes of hepatocytes indicative of altered lipid metabolism. Tgαq*44 mice displayed right-sided HF and altered hepatic blood flow leading to LSECs dysfunction involving defenestration, shift in eicosanoid profile, and proteomic changes. LSECs dysfunction appears as an early and persistent event in CHF, preceding congestive hepatopathy and contributing to alterations in lipoprotein transport and CHF pathophysiology.

Liver stiffness is associated with right heart dysfunction, cardiohepatic syndrome, and prognosis in pulmonary hypertension

BackgroundPulmonary hypertension (PH) can lead to congestive hepatopathy, known as cardiohepatic syndrome (CHS). Hepatic congestion is associated with increased liver stiffness, which can be quantified using shear wave elastography. We aimed to investigate whether hepatic shear wave elastography detects patients at risk in the early stages of PH. MethodsSixty-three prospectively enrolled patients undergoing right heart catheterization (52 diagnosed with PH and 11 with invasive exclusion of PH) and 52 healthy volunteers underwent assessments including echocardiography and hepatic shear wave elastography. CHS was defined as increased levels of ≥ 2 of the following: gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. Liver stiffness was defined as normal (≤ 5.0 kPa) or high (> 5.0 kPa). ResultsCompared with normal liver stiffness, high liver stiffness was associated with impaired right ventricular (RV) and right atrial (RA) function (median [interquartile range] RV ejection fraction: 54 [49; 57]% vs. 45 [34; 51]%, p < 0.001; RA reservoir strain: 49 [41; 54]% vs. 33 [22; 41]%, p < 0.001), more severe tricuspid insufficiency (p < 0.001), and higher prevalence of hepatovenous backflow (2% vs 29%, p < 0.001) and CHS (2% vs. 10%, p = 0.038). In the patient subgroup with precapillary PH (n = 48), CHS and high liver stiffness were associated with increased European Society of Cardiology/European Respiratory Society 2022 risk scores (p = 0.003). ConclusionsShear wave liver elastography yields important information regarding right heart function and may complement risk assessment in patients with (suspected) PH.

Fibrosis Progression in Patients with Budd–Chiari Syndrome and Transjugular Intrahepatic Portosystemic Shunt (TIPS): A Long-Term Study Using Transient Elastography

Hepatic vein outflow obstruction causes congestion of the liver, leading to necrosis, fibrosis, and portal hypertension (PH). A transjugular intrahepatic portosystemic shunt (TIPS) reduces congestion and PH by providing artificial outflow. The aim of the study was to investigate fibrosis progression in patients with Budd–Chiari syndrome (BCS) and TIPS using transient elastography (TE). From 2010 to 2022, 25 patients received 80 TEs using FibroScan®, Echosens, Paris, France (3.2 ± 2.1 per patient). TIPS function was assessed via Doppler ultrasound or radiological intervention. At the time of TE examination, 21 patients had patent shunts. Four patients had occluded shunts but normal pressure gradients during the intervention. The first TE measurement performed 9.8 ± 6.8 years after the BCS diagnosis showed stiffness values of 24.6 ± 11.5 kPa. A second or last measurement performed 7.0 ± 2.9 years after the first measurement showed similar stiffness values of 24.1 ± 15.7 kPa (p = 0.943). Except for three patients, the liver stiffness was always &gt;12 kPa, indicating advanced fibrosis. Stiffness values obtained &lt;5 years (n = 8, 23.8 ± 9.2 kPa) or &gt;5 years after the BCS diagnosis (24.9 ± 12.7 kPa) did not differ (p = 0.907). In addition, stiffness was not related to the interval between BCS and TIPS implantation (p = 0.999). One patient received liver transplantation, and two patients died from non-hepatic causes. Most patients developed mild to moderate cirrhosis, possibly during the early phase of the disease. Timing of TIPS did not influence fibrosis progression. This and the release of portal hypertension may argue in favor of a generous TIPS implantation practice in patients with BCS.

Histopathological Spectrum and Molecular Characterization of Liver Tumors in the Setting of Fontan-Associated Liver Disease.

Univentricular heart is corrected with the Fontan procedure (FP). In the long term, so-called Fontan-associated liver diseases (FALDs) can develop. The aim of this study is to analyze the molecular profile of FALDs. FALDs between January 1990 and December 2022 were reviewed for histology and immunohistochemistry, laboratory data, and images. Targeted next generation sequencing (NGS), performed on the DNA and RNA of both neoplastic and non-lesional liver tissue, was applied. A total of 31/208 nodules > 1 cm in diameter were identified on imaging, but a liver biopsy was available for five patient demonstrating the following: one hepatocellular adenoma (HA), two hepatocellular carcinomas (HCCs), one fibrolamellar carcinoma (FLC), and one intrahepatic cholangiocarcinoma (ICC). Molecular analysis showed a copy number alteration involving FGFR3 in three cases (two HCCs and one ICC) as well as one HCC with a hotspot mutation on the CTNNB1 and NRAS genes. Tumor mutational burden ranged from low to intermediate. A variant of uncertain significance in GNAS was present in two HCCs and in one ICC. The same molecular profile was observed in a non-lesional liver. A DNAJB1-PRKACA fusion was detected only in one FLC. Neoplastic FALDs show some unusual molecular profiles compared with non-Fontan ones. The presence of the same alterations in non-lesional cardiac cirrhosis could contribute to the development of FALD.

THE USE OF REFLEXOLOGY ACCORDING TO THE “BALANCING HEXAGRAMS” TECHNIQUE IN THE COMPLEX REHABILITATION OF ARTHROPATHIES

Abstract. Traditional Chinese medicine is half syndromes, not diseases. This is the identification of a wider range of problems than just individual nosologies: usually, this is a comorbidity, with regular involvement of other tissues, other systems. For example, the syndrome of traditional Chinese medicine "Congestion of the liver" includes the facilitated formation of various pain syndromes in a person, often their combination, and not just a liver disease such as hepatitis. Similarly, Bi syndrome includes more than just "pain in the knee" or osteoarthritis of the knee joint. The article describes the concept of Bi syndrome in traditional Chinese medicine, its classification. The article also presents the main theoretical principles of the "balancing hexagrams" method and its practical implementation. Also given is a clinical case: treatment of a patient with subacute postinfectious arthropathy of the right sphenoid and ankle joints. Purpose. To consider the peculiarities of the use of reflexotherapy by the method of "balancing hexagrams" in the complex rehabilitation of arthropathies. Scientific novelty. For the first time in our country, the technique of compiling acupuncture prescriptions and acupuncture using the method of "balancing hexagrams" was used in the complex rehabilitation of arthropathies. Methods. We consider one clinical case of the use of reflexology using the method of "balancing hexagrams" in complex rehabilitation of arthropathies. The methods of clinical objective neurological examination, the method of syndromic diagnosis of traditional Chinese medicine, the pulse diagnosis method, and the tongue diagnosis method were used. We consider one clinical case of the use of reflexotherapy using the method of "balancing hexagrams" in complex rehabilitation of arthropathies. The methods of clinical objective neurological examination, the method of syndromic diagnosis of traditional Chinese medicine, the pulse diagnosis method, and the tongue diagnosis method were used. Results. As a result of treatment using the method of "balancing hexagrams", the patient's condition improved: it was possible to balance him and achieve a pain-free period. Conclusions. 1. Patients with arthropathies are found in the practice of a reflexologist. 2. The use of the acupuncture method "balancing hexagrams" can be effective in the complex of treatment measures for arthropathies.