Alcohol use disorder (AUD) is seen in 7% of the world population. In 2019, nearly 3 in 10 adults in the United States (US) consumed аlсоhοl in an unhealthy manner. This alcohol misuse that further increased during the coronavirus disease 2019 pandemic is now persisting, and is associated with rising rates of alcohol-associated hospitalizations, end-organ disease, death, and need for liver transplantation. The current lifetime risk of AUD in the US is estimated to be >30%, and with the steadily rising alcohol consumption in the US, this risk is expected to continue to increase. The effect of excessive alcohol on human health is associated with its lifetime cumulative use and is further impacted by factors like age, gender, nutritional status, concurrent cigarette smoking or drug use, diabetes, increased body weight, kidney disease, other cardiovascular diseases and socio-economic status. In this review we present the complex interplay between alcoholic liver and heart diseases, describing the natural history of each organ involvement and identifying risk factors that are associated with the progression of various alcohol-related end-organ diseases. Abstaining from alcohol or moderating its consumption has been shown to reduce the progression of heart failure, arrhythmias, and hypertension linked to excessive alcohol intake, as well as help prevent alcoholic liver disease. Focus on the identification of other modifiable risk factors associated with various organ injuries in conjunction with public health policies for the safe use of alcohol is needed to mitigate the risk of an impending epidemic of AUD.

Major advances in managing critically ill patients with liver disease have improved their prognosis and access to intensive care facilities. Acute-on-chronic liver failure (ACLF) is now a well-defined disease and these patients can be fast-tracked for liver transplantation (LT) with good outcomes if there are no contraindications. In acute liver failure, plasma exchange has improved prognosis for patients not eligible for immediate transplant. Further advances in novel therapies and refinement of the criteria for early LT in ACLF and also clinical implementation of artificial intelligence tools will probably constitute the next major breakthroughs in critically ill patients with liver disease.

Acute-on-chronic liver failure (ACLF) is a major clinical event in cirrhosis that is characterized by high mortality rates and a short window for liver transplantation. N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been suggested as a prognostic biomarker in cirrhosis. However, its accuracy in predicting the development of ACLF or mortality in candidates for liver transplantation remains unknown. This observational, retrospective, single-center study included 277 consecutive patients with cirrhosis who were listed for liver transplantation between 2014 and 2020 in Hospital Italiano, Buenos Aires, Argentina. Clinical data, including sarcopenia, serum cystatin C (CysC), and NT-proBNP levels, were collected at listing. The median MELD-Na and NT-proBNP levels at the time of listing were 16 points (13-22) and 123 (58-257) pg/mL, respectively. High NT-proBNP levels (≥125 pg/mL) were associated with the development of ACLF (subhazard ratio: 4.00, 95% CI: 1.76-9.10; p <0.001) and mortality (subhazard ratio: 3.89, 95% CI: 1.28-11.79, p =0.02) after adjusting for MELD-Na and CysC. Patients with NT-proBNP ≥125 pg/mL showed a significantly higher incidence of ACLF at 3 months (28.5% vs. 3.6%; p <0.001) and 12 months (49.2% vs. 6.1%; p <0.001). Mortality in the waiting list at 1 year was also significantly higher in patients with NT-proBNP ≥125 pg/mL (22.3% vs. 4%; p <0.001). Serum NT-proBNP emerges as a promising prognostic biomarker for ACLF development and mortality in patients with cirrhosis on the waiting list. Its integration into clinical practice could facilitate preventive interventions and improve prioritization on the waiting list.

Cirrhotic cardiomyopathy is characterised by myocardial dysfunction in patients with cirrhosis in the absence of other cardiac conditions. We aimed to develop and validate a scoring system to identify patients at high risk for reduced global longitudinal strain, a newly proposed marker of myocardial dysfunction in the updated diagnostic criteria for cirrhotic cardiomyopathy.

Prospectively recruited patients with cirrhosis in the training and validation groups underwent identical hepatological and cardiological evaluations, including strain echocardiography. Risk factors for myocardial dysfunction were identified using logistic regression.

In a cohort of 452 consecutive patients, 278 were excluded due to non-cirrhotic cardiomyopathy or conditions potentially affecting strain measurements. The prevalence of reduced global longitudinal strain was 9.8% (13/133) in the training group and 19.5% (8/41) in the validation group. Multivariate logistic regression revealed BMI ≥ 28 kg/m2 (OR 7.02), CAP > 260 dB/m (OR 8.53), and age > 57 years (OR 4.68) as independent predictors of reduced myocardial contractility. These variables were combined and weighted based on their beta coefficients to develop the Liver-heart score (CAP > 260 dB/m [2 pts], BMI ≥ 28 kg/m2 [2 pts], age > 57 years [1 pt]). The AUC-ROC was 0.84 in the training and 0.83 in the validation cohort. A Liver-heart score of 5 points was associated with increased mortality, observed at 2 years (44.4% vs. 17.3%) and the end of the follow-up period (66.7% vs. 37.7%, HR 1.3, p < 0.01).

The Liver-heart score can accurately rule out reduced myocardial contractility and may be useful for risk stratification in cirrhotic patients.

Background: Chronic liver disease (CLD) and cirrhosis contribute to approximately 2 million deaths annually, with primary causes including alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and chronic hepatitis B and C infections. Among these, MASLD has emerged as a significant global health concern, closely linked to metabolic disorders and a leading cause of liver failure and transplantation. Objective: This review aims to highlight the interplay between cirrhosis and cardiac dysfunction, emphasizing the pathophysiology, diagnostic criteria, and management of cirrhotic cardiomyopathy (CCM). Methods: A comprehensive literature review was conducted to evaluate the hemodynamic and structural cardiac alterations in cirrhosis. Results: Cirrhosis leads to portal hypertension and systemic inflammation, contributing to CCM, which manifests as subclinical cardiac dysfunction, impaired contractility, and electrophysiological abnormalities. Structural changes, such as increased left ventricular mass, myocardial fibrosis, and ion channel dysfunction, further impair cardiac function. Vasodilation in the splanchnic circulation reduces peripheral resistance, triggering compensatory tachycardia, while the activation of the renin-angiotensin-aldosterone system (RAAS) promotes fluid retention and increases cardiac preload. Chronic inflammation and endotoxemia exacerbate myocardial dysfunction. The 2005 World Congress of Gastroenterology (WCG) and the 2019 Cirrhotic Cardiomyopathy Consortium (CCC) criteria provide updated diagnostic frameworks that incorporate global longitudinal strain (GLS) and tissue Doppler imaging (TDI). Prolonged QT intervals and arrhythmias are frequently observed. Managing heart failure in cirrhotic patients remains complex due to intolerance to afterload-reducing agents, and beta-blockers require careful use due to potential systemic hypotension. The interaction between CCM and major interventions, such as transjugular intrahepatic portosystemic shunt (TIPS) and orthotopic liver transplantation (OLT), highlights the critical need for thorough preoperative cardiac evaluation and vigilant postoperative monitoring. Conclusions: CCM is a frequently underdiagnosed yet significant complication of cirrhosis, impacting prognosis, particularly post-liver transplantation. Early identification using echocardiography and thorough evaluations of arrhythmia risk in cirrhotic patients are critical for optimizing management strategies. Future research should focus on targeted therapeutic approaches to mitigate the cardiac burden in cirrhotic patients and improve clinical outcomes.

Diuretics are commonly discontinued in patients with cirrhosis with acute kidney injury (AKI) because they are presumed to trigger hepatorenal syndrome type 1 (HRS-1). We hypothesized that if HRS-1 is adequately treated with a vasoconstrictor (mean arterial pressure [MAP] effectively increased), diuretics are safe and effective.

Records of hospitalized patients with cirrhosis who received i.v. furosemide while receiving i.v. norepinephrine as a vasoconstrictor to treat HRS-1 were examined. We assessed change in urine output (UOP), trajectory of serum creatinine (sCr), and impact of portopulmonary hypertension (PoPHTN) on the therapeutic response.

Twenty-six patients with HRS-1 received i.v. furosemide (median: 2 days, 160 mg boluses every 6-24 hours) added to i.v. norepinephrine. Median age was 51 years; 91% were of White race, 36% were women, and median model for end-stage liver disease score was 32. The median initial sCr was 4.0 mg/dl. Before treatment, median UOP was 358 ml/d. Norepinephrine alone led to a median increase in UOP to 850 ml/d. Addition of furosemide to norepinephrine induced a subsequent increase in median UOP to 2072 ml/d (P < 0.0001), which was not observed in a control group (n = 22) who did not receive furosemide. Nineteen patients (73%) treated with norepinephrine plus furosemide (median MAP increase, 16 mm Hg) either maintained or improved their sCr trajectory. The magnitude of norepinephrine-induced increase in MAP correlated with the norepinephrine plus furosemide-induced UOP (r = 0.67, P = 0.0002), and the correlation coefficient was numerically stronger among those with PoPHTN.

In patients with HRS-1 who are adequately treated with norepinephrine and achieved an optimal MAP increment, addition of i.v. furosemide enhances diuresis without negatively affecting renal recovery.

Cirrhotic portal hypertension, the most prevalent and clinically significant complication of liver cirrhosis, manifests as elevated portal venous pressure and is associated with severe complications. Although much research on the mechanisms of portal hypertension has focused on liver fibrosis, less attention has been given to the role of intrahepatic and extrahepatic vascular dysfunction, particularly with respect to extrahepatic vasculature. While the role of hepatic fibrosis in cirrhotic portal hypertension is undeniable, the underlying mechanisms involving intrahepatic and extrahepatic vasculature are highly complex. Sinusoidal capillarization and endothelial dysfunction contribute to increased intrahepatic vascular resistance. Hemodynamic changes in the extrahepatic circulation, including splanchnic vasodilation and hyperdynamic circulation, play a significant role in the development of portal hypertension. Additionally, therapeutic strategies targeting these vascular mechanisms are diverse, including improvement of sinusoidal microcirculation, therapies targeting hepatic stellate cells activation, and pharmacological modulation of systemic vascular tone. Therefore, in this review, we will discuss the vascular-related mechanisms and treatment progress of portal hypertension in cirrhosis to provide a new theoretical basis and practical guidance for clinical treatment.

Cirrhotic cardiomyopathy (CCM) is a diagnostic entity defined as cardiac dysfunction (diastolic and/or systolic) in patients with liver cirrhosis, in the absence of overt cardiac disorder. Pathogenically, CCM stems from a combination of systemic and local hepatic factors that, through hemodynamic and neurohormonal changes, affect the balance of cardiac function and lead to its remodeling. Vascular changes in cirrhosis, mostly driven by portal hypertension, splanchnic vasodilatation, and increased cardiac output alongside maladaptively upregulated feedback systems, lead to fluid accumulation, venostasis, and cardiac dysfunction. Autocrine and endocrine proinflammatory cytokines (TNF-alpha, IL-6), as well as systemic endotoxemia stemming from impaired intestinal permeability, contribute to myocardial remodeling and fibrosis, which further compromise the contractility and relaxation of the heart. Additionally, relative adrenal insufficiency is often present in cirrhosis, further potentiating cardiac dysfunction, ultimately leading to the development of CCM. Considering its subclinical course, CCM diagnosis remains challenging. It relies mostly on stress echocardiography or advanced imaging techniques such as speckle-tracking echocardiography. Currently, there is no specific treatment for CCM, as it vastly overlaps with the treatment of heart failure. Diuretics play a central role. The role of non-selective beta-blockers in treating portal hypertension is established; however, their role in CCM remains somewhat controversial as their effect on prognosis is unclear. However, our group still advocates them as essential tools in optimizing the neurohumoral pathologic axis that perpetuates CCM. Other targeted therapies with direct anti-inflammatory and antioxidative effects still lack sufficient evidence for wide approval. This is not only a review but also a comprehensive distillation of the insights from practicing clinical hepatologists and other specialties engaged in advanced approaches to treating liver disease and its sequelae.

Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunction in patients with cirrhosis, in the absence of any primary heart disease. These changes are mainly due to the malfunction or abnormalities of cardiomyocytes. Similar to non-cirrhotic heart failure, cardiomyocytes in cirrhotic cardiomyopathy demonstrate a variety of abnormalities: from the cell membrane to the cytosol and nucleus. At the cell membrane level, biophysical plasma membrane fluidity, and membrane-bound receptors such as the beta-adrenergic, muscarinic and cannabinoid receptors are abnormal either functionally or structurally. Other changes include ion channels such as L-type calcium channels, potassium channels, and sodium transporters. In the cytosol, calcium release and uptake processes are dysfunctional and the myofilaments such as myosin heavy chain and titin, are either functionally abnormal or have structural alterations. Like the fibrotic liver, the heart in cirrhosis also shows fibrotic changes such as a collagen isoform switch from more compliant collagen III to stiffer collagen I which also impacts diastolic function. Other abnormalities include the secondary messenger cyclic adenosine monophosphate, cyclic guanosine monophosphate, and their downstream effectors such as protein kinase A and G-proteins. Finally, other changes such as excessive apoptosis of cardiomyocytes also play a critical role in the pathogenesis of cirrhotic cardiomyopathy. The present review aims to summarize these changes and review their critical role in the pathogenesis of cirrhotic cardiomyopathy.

Patients with cirrhosis are known to be prone to infections. Infections can trigger organ failures and decompensations in cirrhosis. Septic shock can increase mortality by fourfold and cause hemodynamic imbalances, adding to the already hyperdynamic circulation. Management of septic shock in cirrhosis can be tricky due to this complex interplay of altered hemodynamics, immune function, and coagulation.

In this review, we explore the pathophysiological basis, screening, monitoring and management of septic shock in cirrhosis. We also explore novel biomarkers, the growing challenge of multidrug-resistant pathogens and novel and adjunctive therapies. Finally, we propose an algorithm for the management of septic shock in cirrhosis. We conducted a comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library using the keywords and MeSH terms like 'septic shock,' 'cirrhosis,' 'liver disease,' 'sepsis' among others. The search was restricted to peer-reviewed articles in English.

The difficulties in managing septic shock in cirrhosis are discussed, emphasizing personalized approaches over protocol-driven care. Fluid and vasopressor management, antibiotic timing and selection, the role of adjunctive therapies, the importance of lactate clearance, gut failure, and the need for further research in this population are highlighted.

Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grades 2 to 3 as a potentially life-saving treatment. When a transplant is not indicated, palliative care should be considered after 3 to 7 days of full organ support in patients with at least four organ failures or a CLIF-C ACLF score of >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.

Liver cirrhosis is a significant global health concern, and cirrhotic cardiomyopathy (CCM) is a notable complication affecting both adults and children. While CCM is well-studied in adults, understanding its manifestation and diagnostic criteria in pediatric patients remains a challenge. This review explores the evidence for structural and functional cardiac alterations in children with liver cirrhosis. Structural abnormalities, including increased left ventricular mass index (LVMI) and altered left ventricular wall thickness ratios, are prevalent in pediatric CCM. These abnormalities persist even after liver transplantation, highlighting the systemic impact of liver disease. Evidence suggests that altered systolic and diastolic function, as well as electrocardiographic abnormalities such as prolonged QT intervals, are common in pediatric CCM. Blood biomarkers, including brain natriuretic peptide (BNP) and troponin levels, offer insights into cardiac function in pediatric cirrhotic patients. Elevated BNP levels correlate with adverse outcomes, indicating its potential as a prognostic marker. However, further research is needed to elucidate the diagnostic utility of these biomarkers in pediatric CCM.

This review provides estimates of the standardized mean difference among selected cardiac parameters in children with and without cirrhosis. Tailored diagnostic criteria and comprehensive assessment methods will be essential for accurate diagnosis and effective management of pediatric CCM.

• CCM adds to the burden of care of patients with cirrhosis. • Diagnostic criteria for adults are evolving, but there are no specific criteria for pediatric CCM.

• Cardiac function in children with cirrhosis indicates some parameters not considered in adults are altered. • Effect size estimations for certain parameters provide a guideline for future research into pediatric CCM.

Hepatic transplantation (HT) is the standard of care of end-stage liver disease with Cirrhotic Cardiomyopathy (CCM), but medical treatment with combination of diuretics and non-selective beta blockers are important before and after that. Owing to its particular pathophysiology unlike another etiologies of heart failure, in CCM angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type I receptor blockers (ARB), and angiotensin receptor neprilysin inhibitor (ARNI) are not recommended. Transjugular intrahepatic porto-systemic shunt (TIPS) has indications in CMM but its potential benefits and risks must be considered and more researh is necessary. HT is a demanding therapy but the most effective one, and showed improvement in QTc, diastolic and systolic dysfunction; in recent decades, in spite of more severe ill patients (more severe MELD score), survival has improved significantly due to better surgical techniques, intensive care, immunosupresive drugs, and images.

Background/Objectives: Cardiovascular involvement in severe cirrhosis presents diagnostic challenges and carries significant prognostic implications. This study aims to evaluate the relationship between liver disease severity and portal hypertension with the burden of diastolic dysfunction. Methods: We prospectively enrolled patients with hepatic cirrhosis, classified according to the Child-Pugh criteria. Of the 102 patients included, 65 were classified as Group A (non-severe cirrhosis: Child-Pugh Classes A and B) and 37 as Group B (severe cirrhosis: Child-Pugh Class C). Portal vein and spleen diameters were assessed using abdominal ultrasound. All patients underwent echocardiographic evaluation. LV systolic function was assessed by measuring ejection fraction, while diastolic function was evaluated using three parameters: E/Em ratio, E/Vp ratio, and indexed left atrial volume. Results: We observed a significantly greater burden of diastolic dysfunction in Group B compared to Group A. Specifically, the E/Vp ratio was 2.2 ± 0.4 in Group B versus 1.9 ± 0.3 in Group A (p < 0.001); the indexed LA volume was 34.5 ± 3.2 mL/m2 in Group B versus 30.1 ± 2.9 mL/m2 in Group A (p < 0.001); and the E/Em ratio was 17.0 ± 3.0 in Group B versus 11.5 ± 2.8 in Group A (p < 0.001). Additionally, the mean diameters of the portal vein and spleen were larger in Group B, with measurements of 14.3 ± 2.1 mm versus 11.5 ± 1.6 mm for the portal vein and 15.0 ± 1.2 mm versus 11.7 ± 1.5 mm for the spleen (p < 0.001), which correlated with the extent of diastolic dysfunction. Conclusions: Diastolic dysfunction was prevalent in 55% of patients with liver cirrhosis. The burden of diastolic dysfunction was higher in patients with severe hepatic cirrhosis compared to those with milder forms, and it correlated with the severity of portal hypertension, as assessed by measuring portal vein diameter and spleen diameter.

Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear.

In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured.

In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A.

Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.

The clinical syndrome of cirrhotic cardiomyopathy (CCM) occurs quite frequently in decompensated chronic liver disease (DCLD) patients without any prior incidence. The compromised life expectancy under such conditions was the key that prompted us to conduct this study.

This study was planned to study the prevalence of diastolic dysfunction in chronic liver disease patients, to understand the diagnostic criteria of left ventricular diastolic dysfunction (LVDD) in cirrhotic patients, and to evaluate its occurrence as an early indicator of CCM.

A hospital-based, cross-sectional study was conducted on 158 patients, admitted to the Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, India, who conformed to our criteria for inclusion and exclusion. The study period was for 18 months. The subjects were clinically and radiologically diagnosed with chronic liver disease. Regression analysis for variables was performed to score the effects of potential variables with outcomes for diastolic dysfunction (DD) prediction.

Out of 158 patients, 116 belonged to the age group of 31-60 years, pronouncing age to be a significant factor for LVDD. Fifty-three subjects had serum bilirubin levels >2mg/dL and we found serum bilirubin levels to bear a significant correlation with LVDD by exhibiting a p-value <0.0001. Both the Child-Turcotte-Pugh score class (p-value=0.0180) and QTc (p-value <0.0001) bear significant correlation with the development of LVDD, which is also evident from their area under the curve (AUC) values of 0.64 in the receiver operating characteristic (ROC) curve.

Our study concludes that LVDD is an early indicator for assessing the severity of liver cirrhosis in DCLD. The correlation of DCLD with prolonged QTc could predispose patients with DCLD to ventricular arrhythmias. Hence, such patients should undergo serum bilirubin tests, and electrocardiographic checks at regular intervals for early detection, to increase their overall survival rates.

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n  = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E / e ' was strongly correlated with serum LBP ( r  = 0.731; P  < 0.001), PRA ( r  = 0.714; P  < 0.001) and GFR ( r  = -0.609; P  < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P  = 0.01 and 53.3 vs. 28.2%; P  = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.

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.

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome (HRS), outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context. In the absence of established heart disease, cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease. It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities. Despite the clinical description of these potential cardiac-related complications of the liver, the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS. Yet from a physiological sense, temporality (prior onset) of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients. In this review, we discuss current concepts surrounding how the heart may influence the development and progression of HRS, and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting. The temporality of heart and kidney dysfunction in HRS will be discussed. For a subgroup of patients who receive portosystemic shunting, the dynamics of cardiorenal interactions following treatment is reviewed. Continued research to determine the unknowns in this topic is anticipated, hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.