Combined heart-liver transplantation for congestive hepatopathy with bridging fibrosis: Is it warranted?
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ABSTRACT:
SUBMITTER: Izzy M
PROVIDER: S-EPMC8319371 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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Combined heart-liver transplantation for congestive hepatopathy with bridging fibrosis: Is it warranted?
Izzy Manhal M Alexopoulos Sophoclis S Shingina Alexandra A
JHEP reports : innovation in hepatology 20210422 4
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Project description: Not available
| S-EPMC8326421 | biostudies-literature
Project description: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.
| S-EPMC7764741 | biostudies-literature
Project description:Congestive hepatopathy (CH) with chronic passive congestion is characterized by the progression of liver fibrosis without prominent inflammation and hepatocellular damage. Currently, the lack of reliable biomarkers for liver fibrosis in CH often precludes the clinical management of patients with CH. To explore fibrosis biomarkers, we performed proteome analysis on serum exosomes isolated from patients with CH after the Fontan procedure. Exosomal cluster of differentiation (CD)44 levels were increased in patients with CH compared to healthy volunteers and was accompanied by increases in serum levels of soluble CD44 and CD44 expression in the liver. To address the roles of CD44 in CH, we established a mouse model of chronic liver congestion by partial inferior vena cava ligation (pIVCL) that mimics CH by fibrosis progression with less inflammation and cellular damage. In the pIVCL mice, enhanced CD44 expression in hepatic stellate cells (HSCs) and deposition of its ligand hyaluronan were observed in the liver. Blood levels of soluble CD44 were correlated with liver fibrosis. The blockade of CD44 with specific antibody inhibited liver fibrosis in pIVCL mice and was accompanied by a reduction in S100 calcium-binding protein A4 expression following activation of HSCs. Conclusion: Chronic liver congestion promotes fibrosis through CD44. This identifies CD44 as a novel biomarker and therapeutic target of liver fibrosis in patients with CH.
| S-EPMC8369942 | biostudies-literature
Project description:Background: We aimed to review the indications and outcomes of adults undergoing combined heart-liver transplantation (CHLT) in the US using national registry data. Methods: Adult (≥18 years) CHLT recipients in the United Network for Organ Sharing database were included (09/1987-09/2020; era 1 = 1989-2000, era 2 = 2001-2010, era 3 = 2011-2020). Survival analysis was conducted by means of Kaplan-Meier method, log-rank test, and Cox regression. Results: We identified 369 adults receiving CHLT between 12/1989-08/2020. The number of adult CHLT recipients (R2 = 0.75, p < 0.001) and centers performing CHLT (R2 = 0.80, p < 0.001) have increased over the study period. The most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common in era 3 was congenital heart disease (p = 0.03). The 1-, 3-, and 5-years patient survival was 86.8, 80.1, and 77.9%, respectively. In multivariable analysis, recipient diabetes [adjusted hazard ratio (aHR) = 2.35, 95% CI: 1.23-4.48], CHLT between 1989-2000 compared with 2011-2020 (aHR = 5.00, 95% CI: 1.13-22.26), and sequential-liver first CHLT compared with sequential-heart first CHLT (aHR = 2.44, 95% CI: 1.15-5.18) were associated with increased risk of mortality. Higher left ventricular ejection fraction was associated with decreased risk of mortality (aHR = 0.96, 95% CI: 0.92-0.99). Conclusion: CHLT is being increasingly performed with evolving indications. Excellent outcomes can be achieved with multidisciplinary patient and donor selection and surgical planning.
| S-EPMC8842230 | biostudies-literature
Project description:BackgroundCombined heart-liver transplantation (CHLT) is a promising technique to address end stage organ failure in patients with concomitant heart failure and chronic liver disease. While most experience with CHLT has involved adult patients, the expanding population of children born with univentricular congenital heart disease who underwent the Fontan procedure and develop Fontan-associated liver disease (FALD) has emerged as a growing indication for pediatric CHLT.MethodsCurrently, CHLT is performed at a select subset of experienced transplant centers, especially in the pediatric population.ResultsWhile technically demanding, CHLT may offer survival benefit when compared to heart transplant alone with decreased rejection of both synchronous allografts and equivalent outcomes with respect to waitlist time and post-operative complications. Limitations in the technique can be attributed to need for an appropriate multidisciplinary care center, challenges with donor organ availability and allocation, and the complexity associated with patient selection and peri-operative management.ConclusionIn this review, we summarize the history of CHLT, discuss patient selection, and highlight key facets of peri-operative care in the pediatric population.
| S-EPMC10842164 | biostudies-literature
Project description:Heart failure and liver disease often coexist because of systemic disorders and diseases that affect both organs as well as complex cardio-hepatic interactions. Heart failure can cause acute or chronic liver injury due to ischaemia and passive venous congestion, respectively. Congestive hepatopathy is frequently observed in patients with congenital heart disease and after the Fontan procedure, but also in older patients with chronic heart failure. As congestive hepatopathy can evolve into cirrhosis and hepatocellular carcinoma, screening for liver injury should be performed in patients with chronic cardiac diseases and after Fontan surgery. Fibrosis starts in the centro-lobular zone and will extend progressively to the portal area. Chronic liver injury can be reversible if heart function improves. However, in the case of terminal heart failure, uncontrolled by medical resources or by assistive device support, the combination of heart and liver transplants must be discussed in patients with chronic advanced liver fibrosis. In this review of the literature, we will focus on congestive hepatopathy and its complications, such as liver fibrosis and hepatocellular carcinoma, with the aim of improving the management and surveillance of patients experiencing these complications.
| S-EPMC7902554 | biostudies-literature
Project description:BackgroundWe evaluated whether combined heart and liver transplant (H+LTx) can protect the heart graft from the development of cardiac allograft vasculopathy using coronary three-dimensional (3D) volumetric intravascular ultrasound (IVUS).MethodsFrom 2004 to 2009, we identified 24 isolated heart transplant (HTx) and 10 H+LTx recipients in whom two coronary 3D IVUS studies were performed 1 year apart. Baseline 3D IVUS was performed at 0.22 (0.17-1.16) years after transplantation, with follow-up 3D IVUS exams performed after baseline exam (0.96 [0.83-1.08]).ResultsRate of plaque volume and plaque index (plaque volume/vessel volume) progression was attenuated in the H+LTx group (0.3±1.1 vs. 1.5±2.9 mm/mm; P=0.08 and 0.01±0.03 vs. 0.1±0.1; P=0.004, respectively). Rejection burden was much lower in the H+LTx patients. Outcome analysis in 66 consecutive patients (56 HTx and 10 H+LTx) was performed irrespective of performance of second coronary IVUS. H+LTx was associated with reduced rate of cardiac events (P=0.04), which remained significant when adjusted for the difference in the primary etiology for heart disease (P=0.05).ConclusionsOur preliminary serial 3D coronary IVUS data show that H+LTx attenuates cardiac allograft vasculopathy by decreasing the rate of plaque volume and plaque index progression and improves coronary-related outcomes. Because of the small numbers and the differences in etiology of heart disease, our data should be interpreted cautiously, and larger clinical trials would be required to recommend H+LTx for improved coronary remodeling.
| S-EPMC3733541 | biostudies-literature
Project description:Congestive hepatopathy is becoming increasingly recognized among Fontan-palliated patients. Elevated central venous pressure is thought to drive the pathologic progression, characterized by sinusoidal dilatation, congestion, and fibrosis. A clinically relevant large animal model for congestive hepatopathy would provide a valuable platform for researching novel biomarkers, treatment, and prevention. Here, we report on a titratable, sheep pulmonary artery banding model for this disease application. Pulmonary artery banding was achieved by progressively inflating the implanted pulmonary artery cuff. Right ventricular catheter was implanted to draw venous blood samples and measure pressure. The pulmonary artery cuff pressure served as a surrogate for the intensity of pulmonary artery banding and was measured weekly. After about 9 wk, animals were euthanized, and the liver was harvested for histopathological assessment. Nine animal subjects received pulmonary artery banding for 64 ± 8 days. Four of the nine subjects exhibited moderate to severe liver injury, and three of those four exhibited bridging fibrosis. Increasing pulmonary artery cuff pressure significantly correlated with declining mixed venous oxygen saturation (P = 3.29 × 10-5), and higher congestive hepatic fibrosis score (P = 0.0238), suggesting that pulmonary artery banding strategy can be titrated to achieve right-sided congestion and liver fibrosis. Blood analyses demonstrated an increase in plasma bile acids, aspartate aminotransferase, and γ-glutamyltransferase among subjects with moderate to severe injury, further corroborating liver tissue findings. Our large animal pulmonary artery banding model recapitulates congestive hepatopathy and provides a basis to bridge the current gaps in scientific and clinical understanding about the disease.NEW & NOTEWORTHY We present here a large animal platform for congestive hepatopathy, a disease growing in clinical prevalence due to the increasing number of Fontan-palliated patients. Further data are needed to develop a better clinical management strategy for this poorly characterized patient population. Previous reports of animal models to study this disease have mostly been in small animals with limited fidelity. We show that congestive hepatopathy can be replicated in a chronic, progressive pulmonary artery banding model in sheep. We also show that the banding strategy can be controlled to titrate the level of liver injury. To date, we do not know of any other large animal model that can achieve this level of control over disease phenotype and clinical relevance.
| S-EPMC10042593 | biostudies-literature
Project description:BackgroundData are limited on outcomes after heart transplantation in patients bridged-to-transplantation (BTT) with a total artificial heart (TAH-t).MethodsThe UNOS database was used to identify 392 adult patients undergoing heart transplantation after TAH-t BTT between 2005 and 2020. They were compared with 11 014 durable left ventricular assist device (LVAD) BTT patients and 22 348 de novo heart transplants (without any durable VAD or TAH-t BTT) during the same period.ResultsTAH-t BTT patients had increased dialysis dependence compared to LVAD BTT and de novo transplants (24.7% vs. 2.7% vs. 3.8%) and higher levels of baseline creatinine and total bilirubin (all p < .001). After transplantation, TAH-t BTT patients were more likely to die from multiorgan failure in the first year (25.0% vs. 16.1% vs. 16.1%, p = .04). Ten-year survival was inferior in TAH-t BTT patients (TAH-t BTT 53.1%, LVAD BTT 61.8%, De Novo 62.6%, p < .001), while 10-year survival conditional on 1-year survival was similar (TAH-t BTT 66.8%, LVAD BTT 68.7%, De Novo 69.0%, all p > .20). Among TAH-t BTT patients, predictors of 1-year mortality included higher baseline creatinine and total bilirubin, mechanical ventilation, and cumulative center volume <20 cases of heart transplantation involving TAH-t BTT (all p < .05).ConclusionSurvival after TAH-t BTT is acceptable, and patients who survive the early postoperative phase experience similar hazards of mortality over time compared to de novo transplant patients and durable LVAD BTT patients.
| S-EPMC9771925 | biostudies-literature
Project description:Right ventricular (RV) function is an important predictor of prognosis in patients with heart failure. However, the relationship of the RV free wall longitudinal strain (RV FWS) and the degree of hepatic dysfunction during the acute worsening of heart failure (AWHF) is unknown. We sought to determine associations of RV FWS with laboratory liver function tests and parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV FAC), maximal tricuspid jet velocity (TR Vmax), RV S' velocity, and estimated RV systolic pressure (RVSP). A total of 42 AWHF patients from the CATSTAT-HF study were stratified in two groups by the RV FWS median (-16.5%). Patients < RV FWS median had significantly prolonged international normalized ratio (INR; p = 0.002), increased total bilirubin (p < 0.001) and alkaline phosphatase (ALP; p = 0.020), and decreased albumin (p = 0.005) and thrombocytes (p = 0.017) compared to patients > RV FWS median. RV FWS independently correlated to total bilirubin (β = 0.457, p = 0.004), ALP (β = 0.556, p = 0.002), INR (β = 0.392, p = 0.022), albumin (β = -0.437, p = 0.013), and thrombocytes (β = -404, p = 0.038). Similarly, TAPSE, RV FAC, and RV S' significantly correlated with RV FWS. In conclusion, RV impairment, reflected in reduced RV FWS, is independently associated with a higher degree of hepatic dysfunction among patients with AWHF (CATSTAT-HF ClinicalTrials gov number, NCT03389386).
| S-EPMC7290588 | biostudies-literature