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Background: Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking., Aims: We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center., Methods: We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation., Results: We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28-0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%)., Conclusion: Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Liver diseases are a significant global cause of morbidity and mortality. Liver cirrhosis can result in severe complications such as bleeding, hepatic encephalopathy (HE), and infections. Implementing a clear strategy for intensive care unit (ICU) admission management improves patient outcomes. Hemodynamically significant esophageal/gastric variceal bleeding (E/GVB) and grade 4 HE, when accompanied by the need for renal replacement therapy (RRT), are definitive indications for ICU admission. E/GVB, spontaneous bacterial peritonitis (SBP), and infections with multidrug-resistant organisms (MDRO) require close and stringent critical assessment. Patients with severe hepatorenal syndrome (HRS) or respiratory failure have increased baseline mortality and most likely benefit from early ICU treatment. Rapid identification of sepsis in patients with liver cirrhosis is a crucial criterion for ICU admission. Prioritizing cases based on mortality risk and clinical urgency enables efficient resource utilization and optimizes patient management. In addition, "Liver Units" provide an intermediate care (IMC) level for patients with liver diseases who require close monitoring but do not need immediate intensive care., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as "Guidelines on the Management of Ascites in Cirrhosis." This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome., (© 2024. Asian Pacific Association for the Study of the Liver.)

Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome-acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.

Background: Better understanding of disease pathophysiology has led to advances in managing ascites and its associated complications including hepatorenal syndrome-acute kidney Injury (HRS-AKI), especially medicinal and interventional advances., Aim: To review the latest changes in the management of ascites and HRS-AKI., Methods: A literature search was conducted in Pubmed, using the keywords cirrhosis, ascites, renal dysfunction, acute kidney injury, hepatorenal syndrome, beta-blockers, albumin, TIPS and vasoconstrictors, including only publications in English., Results: The medicinal advances include earlier treatment of clinically significant portal hypertension to delay the onset of ascites and the use of human albumin solution to attenuate systemic inflammation thus improving the haemodynamic changes associated with cirrhosis. Furthermore, new classes of drugs such as sodium glucose co-transporter 2 are being investigated for use in patients with cirrhosis and ascites. For HRS-AKI management, newer pharmacological agents such as vasopressin partial agonists and relaxin are being studied. Interventional advances include the refinement of TIPS technique and patient selection to improve outcomes in patients with refractory ascites. The development of the alfa pump system and the study of outcomes associated with the use of long-term palliative abdominal drain will also serve to improve the quality of life in patients with refractory ascites., Conclusions: New treatment strategies emerged from better understanding of the pathophysiology of ascites and HRS-AKI have shown improved prognosis in these patients. The future will see many of these approaches confirmed in large multi-centre clinical trials with the aim to benefit the patients with ascites and HRS-AKI., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Hepatorenal syndrome (HRS) is associated with a dismal prognosis in patients with cirrhosis, and therapeutic options are limited. Biomarkers to identify patients with poor response to therapy are urgently needed. This study aimed to evaluate the predictive value of serum levels of uromodulin (sUMOD) in patients with cirrhosis and HRS treated with terlipressin and albumin (T/A). In total, 156 patients [81 patients with HRS treated with T/A, 42 patients with cirrhosis without kidney injury, and 33 patients with cirrhosis with prerenal acute kidney injury (AKI)] were included. sUMOD levels were analyzed by ELISA. Patients with HRS were prospectively followed for the composite endpoint of hemodialysis-/liver transplantation-free survival (HD/LTx-free survival). Of the 81 patients with HRS, 40 had HRS type 1 and 41 type 2. In the cohort of patients with HRS treated with T/A, median sUMOD level was 100 ng/mL (IQR 64; 144). sUMOD differed significantly between patients with HRS compared with patients without AKI ( P = 0.001) but not between patients with HRS and prerenal AKI ( P = 0.9). In multivariable analyses, sUMOD levels in the lowest quartile were independently associated with a lower rate of complete response to T/A (OR 0.042, P = 0.008) and a higher risk for reaching the composite endpoint of HD/LTX-free survival (HR 2.706, P = 0.013) in patients with HRS type 2 treated with T/A. In contrast, sUMOD was not significantly associated with these outcomes in patients with HRS type 1. sUMOD may be a valuable biomarker for identifying patients with HRS type 2 treated with T/A to predict response and prognosis. NEW & NOTEWORTHY Biomarkers identifying patients with hepatorenal syndrome (HRS) and poor response to therapy are urgently needed. In this study, lower serum uromodulin (sUMOD) levels were associated with poorer response to therapy with terlipressin and albumin and consequently with poorer prognosis in patients with HRS type 2. In patients with HRS type 1, there was no association between sUMOD and poorer prognosis.

Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Hepatorenal syndrome (HRS) is a feared complication in patients with advanced cirrhosis and is associated with significant morbidity and mortality. While recognized as a distinct physiologic condition for well over one hundred years, a lack of objective diagnostic tests has made the diagnosis one of exclusion. Since 1979, multiple sets of diagnostic criteria have been proposed. Though varying in detail, the principal intent of these criteria is to identify patients with severe, functional acute kidney injury that is unresponsive to volume resuscitation and exclude those with structural injury. However, accurate differential diagnosis remains challenging. Recently, multiple urinary biomarkers of kidney injury, including neutrophil gelatinase-associated lipocalin, have been studied as a means of objectively phenotyping etiologies of acute kidney injury in patients with cirrhosis. Along with markers reflecting tubular functional integrity, including the fractional excretion of sodium, injury markers will likely be incorporated into future diagnostic criteria. Making an accurate diagnosis is critical, as therapeutic options exist for HRS but must be given in a timely manner and only to those patients likely to benefit. Terlipressin, an analog of vasopressin, is the first line of therapy for HRS in much of the world and has recently been approved for use in the United States. Significant questions remain regarding the optimal dosing strategy, metrics for titration, and the potential role of point-of-care ultrasound to help guide concurrent albumin administration., (Published by Elsevier Inc.)

Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion. A state of increased intrahepatic vascular resistance characteristic of advanced cirrhosis and portal hypertension is accompanied by maladaptive peripheral arterial vasodilation and reduction in systemic vascular resistance and mean arterial pressure. As a result of a fall in effective arterial blood volume, there is a compensatory activation of the sympathetic nervous system and the renin-angiotensin system, local renal vasoconstriction, loss of renal autoregulation, decrease in renal blood flow, and ultimately a fall in glomerular filtration rate. Systemic release of nitric oxide stimulated by the fibrotic liver, bacterial translocation, and inflammation constitute key components of the pathogenesis. While angiotensin II and noradrenaline remain the critical mediators of renal arterial and arteriolar vasoconstriction, other novel molecules have been recently implicated. Although the above-described mechanistic pathway remains the backbone of the pathogenesis of HRS-1, other noxious elements may be present in advanced cirrhosis and likely contribute to the renal impairment. Direct liver-kidney crosstalk via the hepatorenal sympathetic reflex can further reduce renal blood flow independently of the systemic derangements. Tense ascites may lead to intraabdominal hypertension and abdominal compartment syndrome. Cardio-hemodynamic processes have also been increasingly recognized. Porto-pulmonary hypertension, cirrhotic cardiomyopathy, and abdominal compartment syndrome may lead to renal congestion and complicate the course of HRS-1. In addition, a degree of ischemic or toxic (cholemic) tubular injury may overlap with the underlying circulatory dysfunction and further exacerbate the course of acute kidney injury. Improving our understanding of the pathogenesis of HRS-1 may lead to improvements in therapeutic options for this seriously ill population., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Individuals with liver disease are susceptible to pathophysiological derangements that lead to kidney dysfunction. Patients with advanced cirrhosis and acute liver failure (ALF) are at risk of developing acute kidney injury (AKI). Hepatorenal syndrome type 1 (HRS-1, also called HRS-AKI) constitutes a form of AKI unique to the state of cirrhosis and portal hypertension. Although HRS-1 is a condition primarily characterized by marked renal vasoconstriction and kidney hypoperfusion, other pathogenic processes, such as acute tubular injury and renal vein congestion, can overlap and further complicate the course of HRS-1. ALF can lead to AKI through mechanisms that involve systemic inflammation, direct drug toxicity, or bile acid-induced tubulopathy. In addition, the growing prevalence of nonalcoholic steatohepatitis is changing the spectrum of chronic kidney disease in cirrhosis. In this installment of AJKD's Core Curriculum in Nephrology, we explore the underpinnings of how cirrhosis, ALF, acute cholestasis, and post-liver transplantation can be associated with various forms of acute, subacute, or chronic kidney diseases. We navigate through the recommended therapies for each condition, including supportive care, pharmacological interventions, kidney replacement therapy, and organ transplantation. Finally, key acid-base and electrolyte disorders associated with hepatobiliary disease are also summarized., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Hepatorenal syndrome has conventionally been regarded as a multisystem syndrome in which pathophysiologic pathways that link cirrhosis with impairment in kidney function are followed by dysfunction of several organs such as the heart. The advances in cardiac studies have helped diagnose more subtle cardiac abnormalities that would have otherwise remained unnoticed in a significant subset of patients with advanced liver disease and cirrhosis. Accumulating data suggests that in many instances, the cardiac dysfunction precedes and predicts development of kidney disease in such patients. These observations point to the heart as a key player in hepatorenal syndrome and challenge the notion that the cardiac abnormalities are either the consequence of aberrancies in hepatorenal interactions or have only minor effects. As such, the disturbances traditionally bundled within hepatorenal syndrome may indeed represent a hepatic form of cardiorenal syndrome whereby the liver affects the kidney in part through cardiorenal pathways (that is, hepato-cardio-renal syndrome)., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hepatorenal syndrome (HRS) frequently complicates alcoholic hepatitis (AH) and portends poor survival in this population. Published literature indicates mixed benefits from renal replacement therapy (RRT) for HRS refractory to medical management. Therefore, we sought to assess the utilization of RRT in AH and clinical outcomes at a national level., Methods: Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified adult patients with AH with a coexisting diagnosis of HRS from the National Readmission Database 2016 through 2019. Mortality, morbidity, and resource utilization were compared. We compared proportions using the Fisher exact test and computed adjusted P-values based on multivariate regression analysis. Analyses were performed using Stata, version 14.2, considering a two-sided P < 0.05 as statistically significant., Results: A total of 73 203 patients with AH were included in the analysis (mean age 46.2 years). A total of 3620 individuals had HRS diagnosis (5%), of which 14.7% (n: 532) underwent RRT. HRS patients receiving RRT had a higher mortality rate than those who did not (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI]: 1.3-2.6, P: 0.01), along with higher resource utilization. Only those patients with HRS who underwent liver transplantation (LT) experienced a mortality reduction (24.4% for those not receiving RRTs and 36.5% for those receiving RRT)., Conclusions: RRT is associated with higher mortality and morbidity when offered to patients with AH and HRS, who do not undergo LT. Therefore, our results suggest careful selection of AH patients when deciding to initiate RRT for HRS., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Acute kidney injury is a common complication of decompensated cirrhosis, frequently requires hospitalization, and carries a high short-term mortality. This population experiences several characteristic types of acute kidney injury: hypovolemic-mediated (prerenal), ischemic/nephrotoxic-mediated (acute-tubular necrosis), and hepatorenal syndrome. Prerenal acute kidney injury is treated with volume resuscitation. Acute-tubular necrosis is treated by optimizing perfusion pressure and discontinuing the offending agent. Hepatorenal syndrome, a unique physiology of decreased effective arterial circulation leading to renal vasoconstriction and ultimately acute kidney injury, is treated with plasma expansion with albumin and splanchnic vasoconstrictors such as terlipressin or norepinephrine. Common acute stressors such as bleeding, infection, and volume depletion often contribute to multifactorial acute kidney injury. Even with optimal medical management, many clinicians are faced with the challenge of initiating renal replacement therapy in these patients. This article reviews the epidemiology, indications, and complex considerations of renal replacement therapy for acute kidney injury in decompensated cirrhosis., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.

Hepatorenal syndrome (HRS) is a diagnosis of exclusion defined as acute kidney injury (AKI) with cirrhosis and ascites, with serum creatinine unresponsive to standardized volume administration and diuretic withdrawal. Persistent intravascular hypovolemia or hypervolemia may contribute to AKI and be revealed by inferior vena cava ultrasound (IVC US), which may guide additional volume management. Twenty hospitalized adult patients meeting HRS-AKI criteria had IVC US to assess intravascular volume after receiving standardized albumin administration and diuretic withdrawal. Six had IVC collapsibility index (IVC-CI) ≥50% and IVCmax ≤0.7 cm suggesting intravascular hypovolemia, 9 had IVC-CI <20% and IVCmax >0.7 cm suggesting intravascular hypervolemia, and 5 had IVC-CI ≥20% to <50% and IVCmax >0.7 cm. Additional volume management was prescribed in the 15 patients with either hypovolemia or hypervolemia. After 4-5 days, serum creatinine levels decreased ≥ 20% without hemodialysis in 6 of 20 patients - 3 with hypovolemia received additional volume, and 2 with hypervolemia plus one with 'euvolemia' and dyspnea were volume restricted and received diuretics. In the other 14 patients, serum creatinine failed to persistently decrease ≥20% or hemodialysis was required indicating that AKI did not improve. In summary, fifteen of 20 patients (75%) were presumed to have intravascular hypovolemia or hypervolemia by IVC ultrasound. Six of the 20 patients (40%) improved AKI by 4-5 days of follow-up with additional IVC US-guided volume management, and thus had been misdiagnosed as HRS-AKI. IVC US may more accurately define HRS-AKI as being neither hypovolemic nor hypervolemic, and guide volume management, decreasing the frequency of HRS-AKI misdiagnosis.

Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology. The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances. Understanding these mechanisms is crucial for the timely identification and management of HRS. The diagnosis of HRS is primarily clinical and relies on specific criteria that consider the exclusion of other causes of renal dysfunction. The management of HRS comprises two main approaches: vasoconstrictor therapy and albumin infusion, which aim to improve renal perfusion and mitigate the hyperdynamic circulation often seen in advanced liver disease. Additionally, strategies such as liver transplantation and renal replacement therapy are essential considerations based on individual patient characteristics and disease severity. This review article provides a comprehensive overview of hepatorenal syndrome, focusing on its pathophysiology, diagnostic criteria, and current management strategies.

Acute renal failure (ARF) development is likely the most relevant event in the natural history of severely decompensated cirrhosis. It is a common complication affecting 20-49% of inpatients with decompensated cirrhosis. Also, its presence is associated with a notable increase in morbidity and mortality, and hampers management of classical cirrhosis decompensations such as ascites or hepatic encephalopathy.

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Finding the ideal balance between efficacy and safety of immunosuppression is challenging, particularly in cases of severe TAFRO syndrome. We herein report a 60-year-old man diagnosed with grade 5 TAFRO syndrome mimicking hepatorenal syndrome that was successfully treated by glucocorticoid, tocilizumab, and cyclosporin despite virus infection. Furthermore, by examining 14 peer-reviewed remission cases, we revealed that the recovery periods among inflammation, renal dysfunction, and thrombocytopenia were quite different, with recovery from thrombocytopenia notably slow. All patients requiring dialysis were successfully withdrawn from dialysis, and the reversibility from kidney injury was good. This clinical information will help clinicians plan treatments and tailor the intensity of immunosuppression.

Hepatorenal syndrome (HRS) is a serious complication of cirrhosis. HRS nomenclature has recently changed to HRS-AKI (acute kidney injury). HRS is a complex response to chronic vasodilatory changes brought about by portal hypertension and exacerbated by inflammatory responses that portends poor prognosis to patients with cirrhosis. This syndrome is commonly seen in the setting of infections, particularly spontaneous bacterial peritonitis. Because of the frequency of renal injury in the patient with cirrhosis, HRS-AKI has to be considered high in the differential diagnosis of AKI. Discontinuation of potential triggering agents and elimination of pre-renal AKI, intrinsic renal disease, and structural uropathy as causes of injury are imperative on presentation. Volume expansion with albumin and vasoconstrictive drugs to counteract the underlying splanchnic vasodilation constitutes the most effective medical modality to manage this process. Although the most effective therapy is generally considered to be liver transplantation (LT), the logistic barriers of offering this life-saving therapy on time to all needing it is a major limitation. Terlipressin has been shown to reverse HRS-AKI in a significant proportion of those treated and consequently can lead to increased LT patient survival and freedom from renal replacement therapy. We will review the impact of HRS on the management of patients awaiting LT, present strategies to prevent this significant complication, and discuss major implications of recent therapeutic advances in the setting of LT., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In 2015 the International Club of Ascites gave an accurate, exact and new definition of acute renal injury in cirrhotic patient, identifying objective criteria of severity and recoding hepatorenal syndrome as a particular form of renal dysfunction for which excessive renal vasoconstriction is one of the main, but not the only, pathophysiological mechanisms. In this review we tried to outline new pathophysiological and therapeutic insights, and to summarize the most recent recommendations. Vasopressor such as terlipressin and norepinephrine, in combination with albumin, still represent the first line therapy. However, the new discoveries in the pathophysiology of the disease have led the search for new pharmacological approaches, although, to date, the only definitive remedy is represented by liver (or simultaneous liver-kidney) transplantation.

Chinese Society of Hepatology of Chinese Medical Association organized relevant experts to update the Guidelines on the management of ascites and complications in cirrhosis in 2017 and renamed it as Guidelines on the management of ascites in cirrhosis. It provides guiding recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS).

Introduction: Mortality caused by cirrhosis is now the 14th most common cause of death worldwide and 12th most common in the United States. We studied trends in inpatient mortality and hospitalization charges associated with cirrhotic decompensation from esophageal variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome from 2007 to 2017., Materials and Methods: Using the National Inpatient Sample databases, we first isolated patients 18 years or older with the diagnosis of cirrhosis using International Classification of Diseases, Ninth Revision (ICD-9) or International Classification of Diseases, Tenth Revision (ICD-10) codes. We then identified patients with the admission diagnosis of esophageal variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. Time-series regression was used to determine whether a trend occurred over the study period. We also evaluated for patient-related demographic changes over the study period., Results: A total of 259,897 cirrhotic patients with the studied decompensations were captured. During the study period, time-series regression confirmed downtrends in mortality rates and length of stay for all types of decompensations. Conversely, we found increases in hospitalization charges for all types of decompensations. Patient age increased over the study period. Patients were also more likely to be White and pay with., Conclusion: From 2007 to 2017, inpatient mortality rates and lengths of stay decreased for cirrhotic decompensations for all causes of decompensation. Total charges, conversely, increased for all causes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Acute kidney injury (AKI) is a common complication of cirrhosis, burdened by high morbidity and mortality rates and progression to chronic kidney disease. Hepatorenal syndrome (HRS) is a peculiar type of functional AKI observed in cirrhotic patients with ascites. HRS diagnosis is still clinical, once pre-renal azotemia and intrinsic kidney damage have been excluded by applying well-established and internationally adopted criteria. HRS is considered reversible because of the absence of intrinsic renal damage. However, HRS reversibility has been questioned, due to the lack of response to treatment with vasoconstrictors plus albumin in a relevant percentage of patients and to the persistence of renal dysfunction in HRS patients who underwent liver transplantation (LT). Indeed, LT is the only ultimate treatment, as it solves both liver failure and portal hypertension. Thus, the presence of renal damage in HRS can be hypothesized. In this scenario, neutrophil gelatinase-associated lipocalin (NGAL), one of the most promising biomarkers, may help in characterizing the type of renal injury, distinguishing between HRS and acute tubular necrosis. This review gathers the available evidence in favor and against the presence of structural lesions in HRS in terms of either renal histology and urinary biomarkers with a particular focus on NGAL. The ability to properly characterize which component of renal dysfunction prevails - functional rather than structural - entails a relevant clinical impact for the treatment of these patients, both in terms of medical therapy and liver vs. combined liver-kidney transplantation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Hepatorenal syndrome (HRS) is a primarily functional form of acute kidney injury (AKI) that develops in patients with decompensated cirrhosis. The pathophysiologic cascade that leads to HRS begins with pooling of blood in the splanchnic system, resulting in a decrease in effective circulating arterial volume. The definitive treatment of HRS is liver transplantation. When this is not possible, HRS is treated with a combination of vasoconstrictor agents and intravenous albumin. Although the combination of midodrine and octreotide is used in the United States, the recently approved terlipressin, an analog of vasopressin, is likely to become the first-line standard of care., (Published by Elsevier Inc.)

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database., Methods: Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups' baseline patient characteristics and treatments were compared., Results: The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child-Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis., Conclusions: HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice., (© 2023. The Author(s).)

Purpose: Albumin, the most abundant and arguably most important protein in the human body, plays a unique role in decompensated cirrhosis because its structure and function are quantitatively and qualitatively affected. A literature review was performed to provide insights into albumin use. The manuscript was developed using a multidisciplinary approach; 2 hepatologists, a nephrologist, a hospitalist, and a pharmacist, who are all members of or work closely with the Chronic Liver Disease Foundation, collaborated to write this expert perspective review., Summary: Cirrhosis represents the potential end in the spectrum of all chronic liver diseases. Decompensated cirrhosis, defined by the overt manifestation of liver failure (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased mortality. Human serum albumin (HSA) infusion serves an important role in the treatment of advanced liver disease. The benefits of HSA administration in patients with cirrhosis are widely accepted, and its use has been advocated by several professional societies. However, inappropriate HSA use can lead to significant adverse patient events. This paper discusses the rationale for the administration of HSA in the treatment of complications of cirrhosis, analyzes the data on the use of HSA in cirrhosis, and streamlines practical recommendations set forth in published guidance., Conclusion: Use of HSA in clinical practice needs to be improved. The objective of this paper is to empower pharmacists to facilitate and improve the use of HSA in patients with cirrhosis at their practice sites., (© American Society of Health-System Pharmacists 2023.)

Ascites is the most common decompensation-associated complication of cirrhosis leading to reduced survival. Following significant development of antimicrobial resistance and studies comparing therapeutic options, the American Association for the Study of Liver Diseases released a new guidance providing an in-depth review of those studies and updated guidelines based on expert opinions and emerging data. We review salient 2021 guidance recommendations to provide brief pearls for diagnosis and management of ascites and relevant conditions associated with decompensated cirrhosis, such as hyponatremia, hepatic hydrothorax, spontaneous bacterial peritonitis, and hepatorenal syndrome, and use of transjugular intrahepatic shunt., (Copyright © 2023 The Cleveland Clinic Foundation. All Rights Reserved.)

Background and Aims: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data., Methods: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens., Results: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay., Conclusions: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Renal failure is one of the most prevalent complications in patients with cirrhosis and is of the utmost prognostic relevance. Acute kidney injury (AKI) in cirrhosis results from a spectrum of etiologies, of which hepatorenal syndrome (HRS) carries the worst prognosis. Correct differentiation of the etiology of AKI in cirrhosis is imperative, as treatment defers substantially. This review summarizes the current diagnostic criteria, pathophysiology, diagnosis, and therapeutic concepts for AKI and HRS-AKI in cirrhosis., Competing Interests: Disclosure The authors have no conflict of interest or funding sources to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Hepatorenal syndrome is a major complication in patients with cirrhosis and associated with high mortality. Predictive biomarkers for therapy response are largely missing. Cytokeratin18-based cell death markers are significantly elevated in patients with complications of chronic liver disease, but the role of these markers in patients with HRS treated with vasoconstrictors and albumin is unknown., Methods: We prospectively analyzed a total of 138 patients with HRS, liver cirrhosis without HRS and acute kidney injury treated at the University Medical Center Mainz between April 2013 and July 2018. Serum levels of M30 and M65 were analyzed by ELISA and clinical data were collected. Predictive ability was assessed by Kaplan-Meier curves, logistic regression and c-statistic. Primary endpoint was response to therapy., Results: M30 and M65 were significantly increased in patients with HRS compared to non-HRS controls (M30: p < 0.0001; M65: p < 0.0001). Both serum markers showed predictive ability for dialysis- and LTX-free survival but not overall survival. Logistic regression confirmed M30 and M65 as independent prognostic factors for response to therapy. A novel predictive score comprising bilirubin and M65 showed highest predictive ability to predict therapy response., Conclusions: Serum levels of M30 and M65 can robustly discriminate patients into responders and non-responders to terlipressin therapy with a good predictive ability for dialysis- and LTX-free survival in cirrhotic patients. Cell death parameters might possess clinical relevance in patients with liver cirrhosis and HRS., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

The hepatorenal syndrome develops in a small percentage of patients with advanced liver disease. The pathogenesis involves intravascular volume contraction secondary to pooling of blood in the splanchnic vessels, stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone pathway, and increased intra-abdominal pressure secondary to the formation of large volumes of ascitic fluid. The treatment options are limited, and liver transplant is the only definitive form of management. Here we suggest an alternative approach to treating hepatorenal syndrome based on the unexpected continuous peritoneal drainage in a 36-year-old man hospitalized with hepatic encephalopathy and hepatorenal syndrome. A total of 11.2 L ascitic fluid drained over 5 days from a paracentesis puncture site with marked improvement in renal function; the creatinine decreased from 3.3 mg/dL to 0.7 mg/dL and the BUN decreased from 42 mg/dL to 10 mg/dL. The discussion with this case report summarizes the pathogenesis, including the effect of intra-abdominal pressure, of the hepatorenal syndrome, outlines medical management, and makes a proposal for clinical study based on this case., Competing Interests: Declaration of competing interest None, (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Hepatorenal syndrome (HRS) contributes to significant morbidity and mortality in hospitalised patients with cirrhosis., Aims: To examine recent trends, magnitude and outcomes of HRS in the National Inpatient Sample (NIS) database METHODS: Among the NIS database on cirrhosis hospitalisations (2016-2019) due to alcohol (ALD), chronic viral hepatitis (CVH), or NASH and complicated by acute kidney injury (AKI) were analyzed., Results: Of 113,454 hospitalisations, 18,735 (16.5%) had HRS (mean age 56 years, 36% females, 68% whites, 80% ALD, 7% NASH) with a stable trend over time. Among 1:1 propensity-matched 36,090 hospitalisations, the odds of HRS were 12% higher in NASH versus CVH. Based on weighted national estimates, there were 27,180 (8.3 per 100,000 US population) HRS hospitalisations in 2019, with economic burden of $4.2 billion USD. Mean hospitalisation and total charges (ALD vs. CVH vs. NASH) were 11 versus 10.8 versus 9.2 days and 151,000 versus 157,000 versus 120,000 USD, respectively; p < 0.001. In-hospital mortality was 18.9%, higher in HRS (25.8 vs. 12%, p < 0.001), and decreased by 15% annually. Survivors were more likely to be discharged to short- or long-term care facilities (HRS vs. non-HRS [42 vs. 27%, p < 0.001]); only 28.7% received palliative care., Conclusion: HRS was the cause of AKI in 16.5% of patients hospitalised with cirrhosis and conferred significant healthcare burden with 27,180 HRS hospitalisations in 2019 and requiring an estimated 4.2 billion USD for hospital care. While there has been a decrease in in-hospital mortality over time, it remained high at 23.7% in 2019 in those with HRS., (© 2022 John Wiley & Sons Ltd.)

AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions., (Copyright © 2022 by the American Society of Nephrology.)

Background: Patients with decompensated cirrhosis are well known to experience morbidity and mortality., Aim: We assessed clinical characteristics, health-care utilization, and economic burden according to the type, number, and combination of decompensation-related complications., Methods: We used recent nationally representative sample data from 2016 to 2018, covering approximately 13% of hospitalized patients in South Korea annually. Decompensation-related complications included ascites, hepatic encephalopathy (HE), gastroesophageal variceal (GEV) bleeding, and hepatorenal syndrome (HRS)., Results: Among 14 601 patients with decompensated cirrhosis, 11 201 (76.7%) experienced ≥ 1 decompensation-related complications, and approximately three-quarters underwent hospitalization. The most prevalent decompensation-related complications were ascites (54.8%), GEV bleeding (33.2%), HE (27.4%), and HRS (3.6%). Patients with GEV bleeding exhibited the highest hospitalization rate (95.7%), and patients with HE or HRS underwent hospitalization for 4 weeks/year due to decompensated cirrhosis. Hospitalization costs were 1.9 times higher in patients with HRS than in those with ascites alone ($9022 vs $4673; P < 0.01). Once patients developed decompensation-related complications, 41.3% had ≥ 2 types of decompensation-related complications. As the number of decompensation-related complications increased from 0 to ≥ 3, health-care utilization and economic burden significantly increased in a stepwise manner; patients with ascites, GEV bleeding, and HE visited medical institutions 2.2 times more (11 vs 5/year; P < 0.01) and incurred 6.4 times greater medical expenditure ($11 060 vs $1728/year; P < 0.01) than those with ascites only., Conclusion: A substantial proportion of patients had multiple decompensation-related complications and socioeconomic burdens for decompensated cirrhosis considering admission rate, hospital stay, and costs increased markedly, depending on the number of decompensation-related complications., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest associated with the work presented in this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cirrhosis is a complex disease and has devastating effects on the liver. People living with the condition are at risk for many complications such as hepatorenal syndrome (HRS). If diagnosed with this condition, the prognosis is often poor. Therefore, it is imperative that treating providers are aware of the symptoms and methods to either prevent or adequately treat the syndrome. Timely referral, prevention, early recognition, and initiation of treatment are key components for prevention or improving the prognosis for HRS. Excluding potentially contributing factors and/or conditions is also vitally important for diagnostic purposes. Comorbid conditions may be present and further complicate diagnosis. Fluid volume replacement, administration of albumin, and vasoconstrictors as warranted are important for improving the hemodynamic status and potential reversal of HRS-acute kidney injury (HRS-AKI)., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hepatorenal syndrome (HRS) is defined as a functional renal failure without major histologic changes in individuals with severe liver disease and it is associated with a high mortality rate. Renal hypoperfusion due to marked vasoconstriction as a result of complex circulatory dysfunction has been suggested to be the cornerstone of HRS. Splanchnic and peripheral arterial vasodilation and cirrhotic cardiomyopathy result in effective arterial hypovolemia and compensatory activation of vasoconstrictor mechanisms. The efficacy of current therapeutic strategies targeting this circulatory dysfunction is limited. Increasing evidence suggests a substantial role of systemic inflammation in HRS via either vascular or direct renal effects. Here we summarize the current understanding of HRS pathophysiology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hepatorenal syndrome (HRS) is a hemodynamically driven process mediated by renal dysregulation and inflammatory response. Albumin, antibiotics, and β-blockers are among therapies that have been studied in HRS prevention. There are no Food and Drug Administration-approved treatments for HRS although multiple liver societies have recommended terlipressin as first-line pharmacotherapy. Renal replacement therapy is the primary modality used to bridge to definitive therapy with orthotopic liver transplant or simultaneous liver-kidney transplant. Advances in our understanding of HRS pathophysiology and emerging therapeutic modalities are needed to change outcomes for this vulnerable population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hepatorenal syndrome (HRS) is acute kidney injury (AKI) that occurs without evidence of structural abnormalities in the kidneys in patients with liver disease. It is thought to be due to splanchnic vasculature dilatation that is associated with intense increase of renal arteries' tone, leading to renal cortex ischemia and AKI. Nitric oxide, endotoxins, neurohormonal changes, bacterial infection, high serum bilirubin and bile acids are examples for factors contributing to HRS development. Nevertheless, other unknown factors may have role in HRS pathophysiology. Hence, further discussion and research are needed to clearly understand HRS. Plasma volume restoration and vasoconstrictors are the cornerstone of HRS treatment. Others such as octreotide, noradrenaline, infection control, systemic inflammatory response prevention, shunting, and renal replacement therapy are currently used to manage HRS. Liver or combined liver and kidney transplantation is currently the ultimate cure for HRS. This review was written to help in better understanding the pathogenesis, diagnosis, and treatment options for HRS., (Copyright © 2022 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications., Competing Interests: Disclosure Dr J.F. Gallegos-Orozco was the principal investigator for the University of Utah site of the terlipressin and albumin in type 1 hepatorenal syndrome trial sponsored by Mallinckrodt Pharmaceuticals. Dr S. Chandna and Dr E. Rodriguez Zarate have nothing to disclose., (Published by Elsevier Inc.)