Cardiac dysfunction in patients with cirrhosis and acute decompensation.

The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.

Single-cell RNA sequencing of cystic fibrosis liver disease explants reveals endothelial complement activation.

BACKGROUND & AIMS: Cystic fibrosis (CF) is considered a multisystemic disorder in which CF-associated liver disease (CFLD) is the third most common cause of mortality. Currently, no effective treatment is available for CFLD because its pathophysiology is still unclear. Interestingly, CFLD exhibits identical vascular characteristics as non-cirrhotic portal hypertension, recently classified as porto-sinusoidal vascular disorders (PSVD). METHODS: Since endothelial cells (ECs) are an important component in PSVD, we performed single-cell RNA sequencing (scRNA-seq) on four explant livers from CFLD patients to identify differential endothelial characteristics which could contribute to the disease. We comprehensively characterized the endothelial compartment and compared it with publicly available scRNA-seq datasets from cirrhotic and healthy livers. Key gene signatures were validated ex vivo on patient tissues. RESULTS: We found that ECs from CF liver explants are more closely related to healthy than cirrhotic patients. In CF patients we also discovered a distinct population of liver sinusoidal ECs-coined CF LSECs-upregulating genes involved in the complement cascade and coagulation. Finally, our immunostainings further validated the predominant periportal location of CF LSECs. CONCLUSIONS: Our work showed novel aspects of human liver ECs at the single-cell level thereby supporting endothelial involvement in CFLD, and reinforcing the hypothesis that ECs could be a driver of PSVD. Therefore, considering the vascular compartment in CF and CFLD may help developing new therapeutic approaches for these diseases.

Towards a Standardized Classification of the Hepatobiliary Manifestations in Cystic Fibrosis (CFHBI): A Joint ESPGHAN/NASPGHAN Position Paper.

The broad spectrum of hepatobiliary involvement in cystic fibrosis (CF) has been commonly referred to as cystic fibrosis liver disease (CFLD). However, differences in the definitions of CFLD have led to variations in reported prevalence, incidence rates, and standardized recommendations for diagnosis and therapies. Harmonizing the description of the spectrum of hepatobiliary involvement in all people with CF (pwCF) is deemed essential for providing a reliable account of the natural history, which in turn supports the development of meaningful clinical outcomes in patient care and research. Recognizing this necessity, The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) commissioned and tasked a committee to develop and propose a systematic classification of the CF hepatobiliary manifestations to increase uniformity, accuracy, and comparability for clinical, registry, and research purposes. This report describes the committee's combined expert position statement on hepatobiliary involvement in CF, which has been endorsed by NASPGHAN and ESPGHAN. We recommend using CFHBI (Cystic Fibrosis Hepato-Biliary Involvement) as the updated term to describe and classify all hepatobiliary manifestations in all pwCF. CFHBI encompasses the current extensive spectrum of phenotypical, clinical, or diagnostic expressions of liver involvement observed in pwCF. We present a schematic categorization of CFHBI, which may also be used to track and classify the changes and development of CFHBI in pwCF over time. The proposed classification for CFHBI is based on expert consensus and has not been validated for clinical practice and research purposes. Achieving validation should be an important aim for future research.

Pre-hospital symptom clusters and symptom network analysis in decompensated cirrhotic patients: A cross-sectional study.

AIMS: To generate pre-hospital symptom networks, explore core, bridge and sentinel symptoms, identify pre-hospital symptom clusters and analyse relationship between influencing factors and symptom clusters in decompensated cirrhosis patients. DESIGN: A cross-sectional study design using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. METHODS: Demographical, physiological, psychological and sociological characteristics and the pre-hospital symptoms of 292 decompensated cirrhotic patients were collected from October 2021 to March 2023 in China. Frequencies, percentages, means, standard deviations, independent samples t-tests, one-way analysis of variance, exploratory factor analysis, multiple stepwise regression analysis and network analysis were used for data analysis. RESULTS: 'I don't look like myself' and itching were core and bridge symptoms, while bloating and lack of energy were sentinel symptoms in decompensated cirrhotic patients. Monthly family income, anxiety, depression, social support and disease duration influenced the neuropsychological symptom cluster, with worrying as the strongest predictor symptom. Influential factors for cirrhosis-specific symptom cluster included Child-Pugh class, monthly family income, disease duration, anxiety and depression, with itching being the strongest predictor symptom. Monthly family income, disease duration and depression were influential factors for gastrointestinal symptom cluster, with loss of appetite as the strongest predictor symptom. CONCLUSIONS: Neuropsychological, cirrhosis-specific and gastrointestinal symptom clusters were formed in decompensated cirrhotic patients. Through network analysis, direct connections between symptoms, symptom clusters and their influencing factors were revealed, thereby offering clinicians a foundation for effectively managing patients' pre-hospital symptoms. IMPACT: Decompensated cirrhosis patients commonly have multiple symptoms, while the management of pre-hospital symptoms is often suboptimal. This study identified neuropsychological, cirrhosis-specific, gastrointestinal symptom clusters and recognized core, bridge and sentinel symptoms in these patients. It also revealed the most prominent symptoms within each cluster. This provides insight into the hierarchy of symptoms, improving symptom management in decompensated cirrhosis. PATIENT AND PUBLIC INVOLVEMENT: There was no patient or public involvement.

Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension.

BACKGROUND: Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis. Although primary prevention drugs, including non-selective ß-blockers, have effectively reduced the incidence of bleeding, their efficacy is limited due to side effects and related contraindications. With recent advances in precision medicine, precise drug treatment provides better treatment efficacy. DATA SOURCES: Literature search was conducted in PubMed, MEDLINE and Web of Science for relevant articles published up to May 2022. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/. RESULTS: The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs. According to the site of action, these drugs could be classified into four classes: intrahepatic, extrahepatic, both intrahepatic and extrahepatic targets and others. All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension. CONCLUSIONS: This review classified and summarized the promising drugs, which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension, demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis.

BACKGROUND: Porto-sinusoidal vascular disease (PSVD) and portal vein thrombosis (PVT) are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system. As PVT may be a consequence of PSVD, in PVT patients at presentation, a pre-existing PSVD should be suspected. In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management, but it could be challenging. In this setting ultrasonography may be valuable in differential diagnosis. The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and "pure" PVT and then to suspect PVT secondary to a pre-existing PSVD. METHODS: Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse (ARFI). RESULTS: ARFI was higher and superior mesenteric vein (SMV) diameter was wider in PSVD patients than in PVT patients. Thus, a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT (the area under the curve = 0.780; 95% confidence interval: 0.690-0.869). CONCLUSIONS: A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities.

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium.

BACKGROUND: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV-GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV-GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). METHODS: One hundred and thirty-five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D-STE) were performed, and dual X-ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. RESULTS: LV-GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV-GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV-GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3 , p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. CONCLUSION: In our study, absolute LV-GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end-stage liver disease.

Partial splenic embolization as a rescue and emergency treatment for portal hypertension and gastroesophageal variceal hemorrhage.

BACKGROUND: Partial splenic embolization (PSE) is a non-surgical procedure which was initially used to treat hypersplenism. Furthermore, partial splenic embolization can be used for the treatment of different conditions, including gastroesophageal variceal hemorrhage. Here, we evaluated the safety and efficacy of emergency and non-emergency PSE in patients with gastroesophageal variceal hemorrhage and recurrent portal hypertensive gastropathy bleeding due to cirrhotic (CPH) and non-cirrhotic portal hypertension (NCPH). METHODS: From December 2014 to July 2022, twenty-five patients with persistent esophageal variceal hemorrhage (EVH) and gastric variceal hemorrhage (GVH), recurrent EVH and GVH, controlled EVH with a high risk of recurrent bleeding, controlled GVH with a high risk of rebleeding, and portal hypertensive gastropathy due to CPH and NCPH underwent emergency and non-emergency PSE. PSE for treatment of persistent EVH and GVH was defined as emergency PSE. In all patients pharmacological and endoscopic treatment alone had not been sufficient to control variceal bleeding, and the placement of a transjugular intrahepatic portosystemic shunt (TIPS) was contraindicated, not reasonable due to portal hemodynamics, or TIPS failure with recurrent esophageal bleeding had occurred. The patients were followed-up for six months. RESULTS: All twenty-five patients, 12 with CPH and 13 with NCPH were successfully treated with PSE. In 13 out of 25 (52%) patients, PSE was performed under emergency conditions due to persistent EVH and GVH, clearly stopping the bleeding. Follow-up gastroscopy showed a significant regression of esophageal and gastric varices, classified as grade II or lower according to Paquet's classification after PSE in comparison to grade III to IV before PSE. During the follow-up period, no variceal re-bleeding occurred, neither in patients who were treated under emergency conditions nor in patients with non-emergency PSE. Furthermore, platelet count increased starting from day one after PSE, and after one week, thrombocyte levels had improved significantly. After six months, there was a sustained increase in the thrombocyte count at significantly higher levels. Fever, abdominal pain, and an increase in leucocyte count were transient side effects of the procedure. Severe complications were not observed. CONCLUSION: This is the first study analyzing the efficacy of emergency and non-emergency PSE for the treatment of gastroesophageal hemorrhage and recurrent portal hypertensive gastropathy bleeding in patients with CPH and NCPH. We show that PSE is a successful rescue therapy for patients in whom pharmacological and endoscopic treatment options fail and the placement of a TIPS is contraindicated. In critically ill CPH and NCPH patients with fulminant gastroesophageal variceal bleeding, PSE showed good results and is therefore an effective tool for the rescue and emergency management of gastroesophageal hemorrhage.

Idiopathic non-cirrhotic portal hypertension in a patient with Talaromyces marneffei infection: a case report.

BACKGROUND: The etiopathogenesis of idiopathic non-cirrhotic portal hypertension (INCPH) is so far poorly understood. Altered immunity, blood diseases, infections, congenital defects and drug exposure have been documented in a part of patients with INCPH owing to increased recognition of the disorder in patients with HIV, or various haematological disorders or autoimmune diseases. We aim to discuss the possible etiopathogenesis of INCPH. CASE PRESENTATION: We reported that a patient with intestinal infection of T. Marneffei and hyper-IgE syndrome, a group of rare primary immunodeficiency disorders, was finally diagnosed with INCPH for gastroesophageal variceal bleeding. The diagnosis was mainly based on histopathological features. Transjugular intrahepatic portosystemic shunt was performed and there was no recurrence of melena during the six-month follow-up. CONCLUSION: In the context of immunodeficiency, INCPH may associated with intestinal infections. Thus, screening for enterogenic infection and immunological disorders in patients with unexplained portal hypertension is necessary.

Comparison of long-term outcomes of splenectomy with periesophagogastric devascularization and transjugular intrahepatic portosystemic shunt in treating cirrhotic portal hypertension patients with recurrent variceal bleeding.

PURPOSE: Transjugular intrahepatic portosystemic shunt (TIPS) and splenectomy with periesophagogastric devascularization (SPD) are widely used to treat cirrhotic portal hypertension (PH) and prevent variceal rebleeding. However, direct comparisons between these two approaches are rare. This study was designed to compare the long-term outcomes of TIPS and SPD in patients with cirrhotic PH and variceal rebleeding. METHODS: The study included cirrhotic PH patients with a history of gastroesophageal variceal bleeding between 18 and 80 years of age who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2012 to January 2022. Patients were enrolled into two groups according to TIPS or SPD was performed. Baseline characteristics were matched using propensity score matching (PSM). RESULTS: A total of 230 patients underwent TIPS, while 184 underwent SPD. PSM was carried out to balance available covariates, resulting in a total of 83 patients in the TIPS group and 83 patients in the SPD group. Patients in SPD group had better liver function during 60 months follow-up. Five-year overall survival rates in SPD group and TIPS group were 72 and 27%, respectively, at 2 years were 88 and 86%, respectively. The 2- and 5-year freedom from variceal rebleeding rates were 95 and 80% in SPD group and 80 and 54% in TIPS group. CONCLUSIONS: SPD is clearly superior to TIPS in terms of OS and freedom from variceal rebleeding in patients with cirrhotic PH. In addition, SPD improved liver function in patients with cirrhotic PH.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Cirrhotic Cardiomyopathy Following Bile Duct Ligation in Rats-A Matter of Time?

Cirrhotic patients often suffer from cirrhotic cardiomyopathy (CCM). Previous animal models of CCM were inconsistent concerning the time and mechanism of injury; thus, the temporal dynamics and cardiac vulnerability were studied in more detail. Rats underwent bile duct ligation (BDL) and a second surgery 28 days later. Cardiac function was assessed by conductance catheter and echocardiography. Histology, gene expression, and serum parameters were analyzed. A chronotropic incompetence (Pd31 < 0.001) and impaired contractility at rest and a reduced contractile reserve (Pd31 = 0.03, Pdob-d31 < 0.001) were seen 31 days after BDL with increased creatine (Pd35, Pd42, and Pd56 < 0.05) and transaminases (Pd31 < 0.001). A total of 56 days after BDL, myocardial fibrosis was seen (Pd56 < 0.001) accompanied by macrophage infiltration (CD68: Pgroup < 0.001) and systemic inflammation (TNFα: Pgroup < 0.001, white blood cell count: Pgroup < 0.001). Myocardial expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was increased after 31 (Pd31 < 0.001) and decreased after 42 (Pd42 < 0.001) and 56 days (Pd56 < 0.001). Caspase-3 expression was increased 31 and 56 days after BDL (Pd31 = 0.005; Pd56 = 0.005). Structural changes in the myocardium were seen after 8 weeks. After the second surgery (second hit), transient myocardial insufficiency with secondary organ dysfunction was seen, characterized by reduced contractility and contractile reserve.

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.

Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension.

BACKGROUND & AIMS: Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. METHODS: Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. RESULTS: 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). CONCLUSION: Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.

Cardiovascular events after liver transplantation: MACE hurts.

The curative therapy for patients with end-stage liver disease is liver transplantation. However, liver transplantation challenges the cardiovascular system, and is associated with major adverse cardiovascular events (MACE). Immediately after implantation of the liver graft, changes in cardiac preload and afterload increase the cardiac workload. Longer-term postoperatively, a more sedentary lifestyle and enhanced appetite increase obesity and body mass index. Immunosuppressants may also affect the cardiovascular system. All these factors that liver recipients encounter impact the function of the cardiovascular system. Cardiac events are the third-leading cause of death in liver recipients. This review describes the pertinent factors that predispose to development of MACE after liver transplantation, and how to predict these cardiovascular events in the post-transplant period. We review the roles of metabolic syndrome, renal dysfunction, non-alcoholic fatty liver disease, diagnostic tests such as imaging and biomarkers, and parameters such as systolic and diastolic dysfunction, and QT interval prolongation in cardiovascular events. We summarize the current literature on scoring systems to predict cardiovascular events.

Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. METHODS: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. RESULTS: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1-306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. CONCLUSIONS: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.

Rotational thromboelastometry-guided blood component use in cirrhotic children undergoing invasive procedures: Randomized controlled trial.

BACKGROUND & AIMS: This randomized controlled trial (RCT) was conducted with the aim to evaluate the efficacy and safety of using ROTEM-based transfusion strategy in cirrhotic children undergoing invasive procedures. METHODS: This was an open-label, RCT which included (i) children under 18 years of age with liver cirrhosis; (ii) INR between 1.5 and 2.5; and/or (iii) platelet count between 20 × 109 /L and 50 × 109 /L (for procedures other than liver biopsy) and between 40 × 109 /L and 60 × 109 /L (for liver biopsy); and (iv) listed for invasive procedures. Stratified randomization was done for children undergoing liver biopsies. Patients randomized to the ROTEM and conventional groups received blood component transfusion using predefined criteria. RESULTS: A total of 423 invasive procedures were screened for inclusion of which 60 were randomized (30 in each group with comparable baseline parameters). The volume of total blood components, fresh frozen plasma (FFP) and platelets transfused was significantly lower in ROTEM as compared to conventional group. Only 46.7% of children in ROTEM group received a blood component compared to 100% in conventional group (p < .001). The requirement of FFP (ROTEM: 43.3%, Conventional: 83.3%, p = .001) was significantly lower in the patients receiving ROTEM-guided transfusions. There was no difference in procedure-related bleed and transfusion-related complications between the two groups. ROTEM was cost-effective (p = .002) despite the additional cost of the test. CONCLUSION: ROTEM-based transfusion strategies result in lower blood component transfusion in cirrhotic children undergoing invasive procedures without an increase in risk of procedure-related bleed. ROTEM-guided transfusion strategy is cost-effective.

Impact of cardiac dysfunction on morbidity and mortality in liver transplant candidates.

The prognostic role of cardiac dysfunction in cirrhotic patients is increasingly recognized. We studied its impact on morbidity and mortality before and after liver transplantation (LT) including development of post-transplant cardiovascular disease (CVD). In this retrospective study, cirrhotic patients who underwent LT assessment from January 2010 to December 2020 were reviewed. Demographics, cardiac investigations and clinical courses were analyzed to identify the prevalence of cardiac dysfunction and its role in LT outcomes. Survival analysis was performed using Cox proportional hazard regression modelling, with LT as a time-varying covariate and as an interaction variable with cardiac dysfunction. Three hundred and eight patients (70% male) were studied. The median (interquartile range) age at LT assessment was 56 (12) years. Cardiac dysfunction was found in 178 (58%) patients (diastolic, 169; systolic, 26; both, 17) and was significantly associated with hepatorenal syndrome/acute kidney injury and peri- and post-transplant morbidity (adjusted odds ratio [aOR] 1.94, 95% CI 1.06-3.52, P < .001; aOR 2.01, 95% CI 1.06-3.82, P = .033; aOR 1.9, 95% CI 1.01-3.65, P = .023, respectively). Cardiac dysfunction was not associated with mortality before (adjusted hazard ratio [aHR] 1.01, 95% CI .99-1.01) or after LT (aHR .74, 95% CI .4-1.05. Post-transplant CVD (61% cardiac failure) occurred in 36 patients, and there was no significant association with cardiac dysfunction (P = .11). Cardiac dysfunction was common in LT candidates and was significantly associated with morbidity before and after LT. Studies on the role of advanced echocardiographic parameters to improve diagnosis of cardiac dysfunction and optimize LT outcomes are needed.