Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.

Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome. In advanced cirrhosis, the quality of albumin is decreased due to high oxidative stress and a proinflammatory state. Therefore, the administration of i.v. albumin would seem to be of pathophysiological relevance and benefit. Yet, the questions that remain are who, when, how much, and how often. While albumin infusion is recommended after large-volume paracentesis, at diagnosis of spontaneous bacterial peritonitis, in acute kidney injury, and in hepatorenal syndrome, the amount and schedule of albumin to be administered require refinement, particularly given complications related to volume overload that have become increasingly apparent. Other indications for albumin such as infections other than spontaneous bacterial peritonitis, hyponatremia, HE, prevention of poor outcomes in hospitalized, and in outpatients with cirrhosis are still debated. The results of studies in these settings are either negative, controversial, or inconclusive. This sheds some doubts regarding the use of albumin as a "one size fits all" strategy. The indication and patient selection are crucial and not always intuitive. The amount and frequency also seem to play a role in the success or failure of albumin. This review will critically discuss the evidence and underline areas where there are indications for albumin use and others where evidence is still insufficient and will have to await the development/results of randomized controlled trials.

Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality.

Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients.

This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding.

Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included.

The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21-46, I2 = 61.4%], early rebleeding rate was 16% [95% CI 11-20, I2 = 37.4%], late rebleeding rate was 39% [95% CI 36-42, I2 = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24-31, I2 = 91.6%], 3% [95% CI - 2 to 8, I2 = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2-10, I2 = 0%], all-cause mortality rate was 17% [95% CI 12-22, I2 = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor.

Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications.

Acute kidney injury (AKI) is a common complication among patients with decompensated cirrhosis and its development is associated with worse prognosis in terms of survival. Patients with decompensated cirrhosis may develop a unique type of AKI, known as hepatorenal syndrome (HRS-AKI), characterized by marked impairment of kidney function due to haemodynamic changes that occur in late stages of liver cirrhosis. Besides, patients with cirrhosis also may develop chronic alterations of kidney function (chronic kidney disease, CKD), the incidence of which is increasing markedly and may be associated with clinical complications. The aim of this review is to provide the reader with an update of the most relevant aspects of alterations of kidney function in patients with cirrhossi that may be useful for theri clinical practice.

Hepatorenal syndrome (HRS) is a serious complication of decompensated liver cirrhosis that results in acute kidney injury (AKI). The mortality rate is high. Endothelial dysfunction secondary to liver cirrhosis is a key driver of the development of portal hypertension, which is eventually complicated by ascites and HRS. Ultimately, splanchnic vasodilation and excess gut lymph production result in ascites, low effective arterial blood volume, and maladaptive compensatory mechanisms that contribute to renal hypoperfusion and injury. While the only curative treatment is liver transplantation, vasoconstrictors and albumin have been the mainstay of treatment for candidates who are ineligible or waiting for transplantation. On September 14, 2022, terlipressin, a V1 vasopressin receptor agonist, was approved by the Food and Drug Administration for the treatment of HRS-AKI. In clinical trials, terlipressin plus albumin have been superior to albumin alone and equivocal to noradrenaline plus albumin in renal function improvement. Terlipressin, however, does not improve survival, is costly, and is associated with severe adverse events-including severe cardiac and vascular complications. The aim of this review is to provide an overview of terlipressin pharmacology, adverse events-with a focus on cardiovascular complications-and comparative randomized controlled trials that resulted in the Food and Drug Administration's approval of terlipressin. New literature since its approval and ongoing clinical trials will also be highlighted.

Severe alcoholic hepatitis is the most lethal complication in alcohol dependent patients. The concurrence of infections in these patients is very frequent. Both produce a systemic inflammatory response syndrome (SIRS), secondary to intense release of inflammatory cytokines, which can complicate the diagnosis. In our study, Interleukin (IL)-6 and IL-10 levels are higher in patients with SIRS (p<0.001 and p = 0.033, respectively). IL-4, IL-6, Interferon-gamma (IFNγ), Tumor necrosis factor alpha (TNFα) and IL-17 levels correlate with liver function, as estimated by MELD-Na (p = 0.018, p = 0.008, p = 0.009, p = 0.016 and p = 0.006, respectively). Malondialdehyde (MDA), a product of lipid peroxidation and marker of cell damage, also correlates with liver function (p = 0.002), but not with SIRS or infections. Only elevated IL-6 correlates independently with the presence of infections (RR=1.023 IC 95% 1.000-1.047), so it may be useful for the correct diagnosis in these patients. Values greater than 30 pg/mL have a sensitivity: 86.7% and specificity: 94.7% for the diagnosis of infections.

Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage. Intravenous (IV) albumin increases effective arterial blood volume and is used in the prevention of acute kidney injury (AKI) and death after large-volume paracentesis and in patients with spontaneous bacterial peritonitis (SBP). The combination of vasoconstrictors and albumin is used in the reversal of hepatorenal syndrome (HRS-AKI), the most lethal complication of cirrhosis. Because a potent vasoconstrictor, terlipressin, was recently approved by the US Food and Drug Administration, and because recent trials have explored use of IV albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and IV albumin in the following 3 specific scenarios: variceal hemorrhage, ascites and SBP, and HRS.

This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. It underwent internal peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Some of the statements are unchanged from published guidelines because of lack of new evidence in the literature. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality and evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Vasoactive drugs should be initiated as soon as the diagnosis of variceal hemorrhage is suspected or confirmed, preferably before diagnostic and/or therapeutic endoscopy. BEST PRACTICE ADVICE 2: After initial endoscopic hemostasis, vasoactive drugs should be continued for 2-5 days to prevent early rebleeding. BEST PRACTICE ADVICE 3: Octreotide is the vasoactive drug of choice in the management of variceal hemorrhage based on its safety profile. BEST PRACTICE ADVICE 4: IV albumin should be administered at the time of large-volume (>5 L) paracentesis. BEST PRACTICE ADVICE 5: IV albumin may be considered in patients with SBP. BEST PRACTICE ADVICE 6: Albumin should not be used in patients (hospitalized or not) with cirrhosis and uncomplicated ascites. BEST PRACTICE ADVICE 7: Vasoconstrictors should not be used in the management of uncomplicated ascites, after large-volume paracentesis or in patients with SBP. BEST PRACTICE ADVICE 8: IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI. BEST PRACTICE ADVICE 9: Vasoactive drugs (eg, terlipressin, norepinephrine, and combination of octreotide and midodrine) should be used in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis. BEST PRACTICE ADVICE 10: Terlipressin is the vasoactive drug of choice in the treatment of HRS-AKI and use of concurrent albumin can be considered when accounting for patient's volume status. BEST PRACTICE ADVICE 11: Terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line. BEST PRACTICE ADVICE 12: Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3. The benefits may not outweigh the risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with a Model for End-stage Liver Disease ≥35.

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 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.

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with advanced cirrhosis. Prophylactic Norfloxacin used to be considered effective in SBP prevention, but in recent years its efficacy has been partially compromised by increasing quinolone-resistant bacteria. However, whether the effects of alternative prophylactic regimens are superior to norfloxacin remains controversial. The goal of this study is to compare the effects of norfloxacin with other antibiotics in SBP prophylaxis for cirrhotic patients.

We systematically searched Pubmed, Embase, and Cochrane Library Databases. Two reviewers independently identified relevant random control trials (RCTs) comparing the role of norfloxacin and other antibiotics in SBP prevention.

Eight studies comprising 1043 cirrhotic patients were included in this study. Norfloxacin and alternative antibiotics displayed comparable effects in SBP prophylaxis, survival benefit, overall infection prevention, and safety. Subgroup analyses revealed that rifaximin prophylaxis could reduce the recurrence of SBP with fewer adverse events but failed to improve overall survival compared with norfloxacin.

Other antibiotics are a reasonable alternative to norfloxacin in the prophylaxis of SBP. Rifaximin prophylaxis could be an alternative choose of antibiotic for SBP prevention because of its better protective effect and safety.

Twenty per cent albumin (1.5 g/kg at diagnosis and 1 g/kg on day three, infused over six-hour duration) is recommended particularly in high-risk spontaneous bacterial peritonitis (SBP). Whether reduced dose albumin infusion is as effective as the standard dose albumin infusion is not clear. The aim of this study was to compare standard dose albumin infusion with reduced dose albumin infusion in acute kidney injury (AKI) development or progression in patients with cirrhosis and high-risk SBP.

Sixty-three patients were randomized to the standard dose albumin arm (n = 31) and reduced dose albumin arm (n = 32, 0.75 g/kg at diagnosis and 0.5 g/kg 48 h later). The albumin was infused over six-hour duration in both groups. When the patient developed respiratory distress, the albumin infusion was stopped and that dose (i.e. of day one or day three) was not restarted and no attempt was made to finish the whole dose of that day. However, the next dose was started at the pre-calculated infusion rate if there was no evidence of respiratory distress at the start of next infusion.

All 31 patients in standard dose and two (6.25%) in the reduced dose group developed symptomatic circulatory overload (p < 0.001), with infusions being stopped prematurely. The actual albumin dose received on day one was similar in both groups and only slightly higher in the standard dose group on day three. Resolution of SBP, progression of AKI to higher stage, in-hospital mortality and 28 days' mortality were similar in both groups.

For treatment of SBP, standard dose albumin infusion (1.5 g/kg at diagnosis and 1 g/kg 48 hours later) infused over six hours is not tolerated by Indian patients. The effectiveness of standard dose albumin infused over more prolonged periods, as compared to reduced dose albumin, should be evaluated in further studies.

Clinical Trials.gov Identifier: NCT04273373 .

Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.

Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI.

A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation.

172 patients (age 57 ± 13, model of end-stage liver disease [MELD]-sodium 22 ± 8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P = 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality.

HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.

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.

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.

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.

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit.

Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX.

Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this condition.

This paper evaluates key evidence-based updates concerning SBP for the emergency clinician.

SBP is commonly due to Gram-negative bacteria, but infections due to Gram-positive bacteria and multidrug resistant bacteria are increasing. The typical presentation of SBP includes abdominal pain, worsening ascites, fever, or altered mental status in a patient with known liver disease; however, some patients may be asymptomatic or present with only mild symptoms. Paracentesis is the diagnostic modality of choice and should be performed in any patient with ascites and concern for SBP or upper gastrointestinal bleeding, or in those being admitted for a complication of cirrhosis. Ultrasound should be used to optimize the procedure. An ascites absolute neutrophil count (ANC) ≥ 250 cells/mm³ is diagnostic of SBP. Ascitic fluid should be placed in blood culture bottles to improve the culture yield. Leukocyte esterase reagent strips can be used for rapid diagnosis if available. While many patients will demonstrate coagulation panel abnormalities, routine transfusion is not recommended. Management traditionally includes a third-generation cephalosporin, but specific patient populations may require more broad-spectrum coverage with a carbapenem or piperacillin-tazobactam. Albumin infusion is associated with reduced risk of renal impairment and mortality.

An understanding of literature updates can improve the care of patients with suspected SBP.

The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications.

A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes.

Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100 g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate.

Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections.

Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites. Currently, the accuracy of the model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) as prognostic scores in this cohort is unclear. This study aimed to evaluate and compare the accuracy of MELD and MELD-Na for predicting 90-day mortality and determine whether the mortality risk estimates they provide accurately reflect the poor prognosis of patients with SBP Methods: Patients with cirrhosis and SBP were retrospectively identified from ascitic fluid samples sent for microscopy, culture and sensitivity analysis (1/1/18-31/12/20) and a previous audit. MELD and MELD-Na scores at diagnosis were calculated and associations with 90-day mortality were assessed using univariate analysis. Receiver operator characteristic curves were compared, and standardised mortality ratios (SMRs) were calculated by comparing the number of deaths observed to the number predicted by MELD and MELD-Na.

Of the 567 patients identified, 15 patients with cirrhosis and SBP were included. The 90-day mortality rate was 66.7% (10/15). Only concurrent hyponatremia (<135mmol/L) was associated with mortality (6/10 non-survivors vs 0/5 survivors, p=0.04). The difference in MELD and MELD-Na's C-statistic was not significant: 0.66 (95% Cl:0.35-0.98) vs 0.74 (95% Cl:0.47-1.0) respectively (p=0.72). Patients with a MELD-Na >18.5 had significantly higher 90-day mortality than patients with MELD-Na ≤18.5 (88.9% (8/9) vs. 33.3% (2/6), p=0.05). The SMR (95% Cl) for each MELD decile evaluated was 33.3 (0-79.5), 11.1 (0.2-22.0) and 3.4 (0-7.0) for scores ≤9,10-19 and 20-29 respectively. For each MELD-Na tertile, these were: 25 (0-59.6), 5.2 (0.1-10.3) and 2.7 (0.1-8.1) for scores <17,17-26, ≥27 respectively.

In a small cohort of patients with cirrhosis and SBP, the MELD's accuracy in predicting 90-day mortality was limited. MELD-Na's accuracy was higher but not significantly. Both scores consistently underestimated participants' mortality, therefore future studies could evaluate the accuracy of alternative prognostic scores in this patient group.

Assess outcomes in patients with an index presentation of spontaneous bacterial peritonitis (SBP) over a 13-year period.

SBP, a bacterial infection of ascites, has a poor prognosis.

Retrospective cohort study assessing mortality (standardised to 32 months) and prognostic factors in patients with SBP during two periods: period 1 (June 2006-November 2012) and period 2 (December 2012-May 2019).

The study included 178 patients who were followed up for 11.6 (29.2) months. Mortality was high, with 12-, 24- and 32-month survival being 32%, 26% and 24%, respectively. Inpatient mortality was 36% with mortality in those surviving hospitalisation being 62%. Serum creatinine at the time of SBP diagnosis was an independent predictor of mortality at 32 months [hazard ratio (HR) 1.002, P = 0.023] and inpatient mortality (HR 1.003, P = 0.035). Positive ascitic fluid culture and ascitic fluid neutrophil count were independent predictors of 32-month (HR 1.679, P = 0.008) and inpatient mortality (HR 1.0001, P = 0.005), respectively. Patients in period 2 had lower ascitic fluid albumin (5.9 ± 3.3 g/L vs. 10.8 ± 5.4 g/L, P < 0.001), higher ascitic fluid neutrophil count (815.0 cells/mm3 vs. 345.0 cells/mm3, P < 0.001) and higher rates of hepatorenal syndrome-acute kidney injury (58 vs. 35%, P = 0.002). Mortality at 32 months and mortality in those surviving hospitalisation were similar at 78 vs. 73%, P = 0.392 and 66 vs. 58%, P = 0.355, for periods 1 and 2, respectively.

Despite more advanced initial presentations, mortality rates have remained similar over the last 13 years. Serum creatinine at the time of SBP diagnosis is an independent predictor of mortality.

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.

(1) Background: Spontaneous bacterial peritonitis (SBP) is a major and severe complication in cirrhosis patients with ascites. Over the years, advance in antibiotic treatment has led to changes in microbial patterns in some regions, including the emergence of extended-spectrum beta-lactamases resistant (ESBL)-producing bacteria and an increase in Gram-positive bacteria (GPC). In addition, three SBP types (classic SBP, culture-negative neutrophilic ascites (CNNA), and monomicrobial non-neutrocytic bacterascites (MNB)), may also have different prognoses. Therefore, the study aimed to investigate the microbial pattern and the predictors of short-term outcomes in patients with SBP. (2) Methods: Patients discharged with a diagnosis of the first episode of SBP between January 2006 and July 2017 were enrolled. Patients' clinical, demographic, hematological, and biochemical data were obtained at diagnosis, and the model for end-stage liver disease (MELD)-based scores were calculated accordingly. Patients were followed up until February 2018 or until death. (3) Results: A total of 327 patients were analyzed. The prevalence of classic SBP was nearly equivalent to CNNA. As for the microbial pattern, Gram-negative bacillus (GNB) remained more prevalent than GPC (75 vs. 25%), with E. coli being the most common bacterial species, followed by K. Pneumoniae and then Staphylococcus. The percentage of ESBL strain in culture-positive patients was 10.9%. By univariable and multivariable logistic regression survival analysis, there was no significant difference in predicting short-term mortality among the three SBP types, neither between GNB vs. GPC nor between ESBL- and non-ESBL-producing bacteria. Only bacteremia (sepsis), hepatorenal syndrome (HRS), and serum creatinine (Cr) were independent predictors of in-hospital and 3-month mortality, whereas HRS and Cr were independent predictors of 6-month mortality. (4) Conclusions: SBP types, Gram stain result, and ESBL strain did not affect survival. Only bacteremia (sepsis), HRS, and serum Cr independently predicted the short-term mortality in patients with SBP.

Patients admitted with decompensated cirrhosis who develop acute kidney injury (AKI) tend to experience poor outcomes, even if provided with increased organ support such as renal replacement therapies. We assessed the association of albumin administered ≤24 hours of admission with hospital length of stay (LOS) and in-hospital mortality.

The Cerner Health Facts Database was queried for hospitalized patients with cirrhosis who had >0.3 mg/dL increase in serum creatinine within 48 hours and received diuretics following admission between January 2009 and April 2018. This study received institutional review board exemption through federal regulation 45CFR46. Albumin infusion was "timely" if administered ≤24 hours after admission and "nontimely" if administered >24 hours after admission or not at all. Two subgroups were assessed: the AKILOS subgroup (patients who survived to discharge) and the AKIMORTALITY RISK subgroup (patients with the highest risk of mortality, ie, AKI stage 3).

A total of 4135 hospitalizations with cirrhosis and AKI were grouped into AKILOS (n = 3321) and AKIMORTALITY RISK (n = 609) subgroups. Albumin administration occurred in 59.7% of the AKILOS subgroup and 77.8% of the AKIMORTALITY RISK subgroup, but timely treatment only occurred in 25.9% and 35.8% of encounters within these subgroups, respectively. Risk-adjusted analysis showed timely albumin administration to be associated with a 15.5% reduction (P < .01) in LOS in the AKILOS subgroup and a 49% reduction in the odds of death (adjusted odds ratio: 0.51; P < .01) in the AKIMORTALITY RISK subgroup, when compared to the nontimely group.

Among patients with cirrhosis and AKI, treatment with albumin ≤24 hours after admission was associated with a shorter LOS and lower risk of death in patients with stage 3 AKI.

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.

Spontaneous bacterial peritonitis (SBP) is a feared complication of ascites that affects 10%-30% of hospitalized patients with cirrhosis with an associated mortality rate of approximately 20%.1-3 Although efforts have been undertaken to encourage prompt evaluation and treatment of SBP, outcomes have generally remained dismal.3 There is significant interest in identifying factors that can reliably predict mortality among individuals with SBP.

Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients.

An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis.

The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27mg to 22mg and from 236g to 144g, respectively, after the institution of the protocol. This was not associated with higher mortality.

The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals.

Hepatorenal syndrome (HRS) is a type of acute kidney injury (AKI), occurring in patients with decompensated liver cirrhosis and is associated with high mortality. We aim to describe the predictors associated with the development of HRS in cirrhotic patients with AKI. We retrospectively analyzed 529 cirrhotic patient encounters with AKI across all Northwell Health institutions between 1 January 2015 and 31 December 2018. We performed multivariate analyses to determine independent predictors of development of HRS. Alcoholic cirrhosis was the most common identified etiology of cirrhosis. The mean Model for End-Stage Liver Disease Scorewas18 (±7). Ascites was the most commonly identified clinical feature of portal hypertension. Infection was identified in 38.4% of patients with urinary tract infection/pyelonephritis being the most common. Spontaneous bacterial peritonitis occurred in 5.9% of patients. The most common cause of AKI was pre-renal. Hepatorenal syndrome was identified in 9.8% of patient encounters. Predictors of HRS were history of ascites, serum creatinine >2.5 mg/dL, albumin <3 g/dL, bilirubin >2 mg/dL and spontaneous bacterial peritonitis. We demonstrate strong predictors for the development of HRS which can aid clinicians to attain an early diagnosis of HRS, leading to prompt and targeted management and improving outcomes.

Portal hypertensive bleeding is a major complication of portal hypertension (PHT) with high morbidity and mortality. A lot of advances have been made in our understanding of screening, risk stratification, and management strategies for portal hypertensive bleeding including acute variceal bleeding leading to improved overall outcomes in patients with PHT. A number of guidelines on variceal bleeding have been published by various societies in the past few years. The Indian Society of Gastroenterology (ISG) Task Force on Upper Gastrointestinal Bleeding (UGIB) felt that it was necessary to bring out a standard practice guidance document for the use of Indian health care providers especially physicians, gastroenterologists, and hepatologists. For this purpose, an expert group meeting was convened by the ISG Task Force to deliberate on this matter and write a consensus guidance document for Indian practice. The delegates including gastroenterologists, hepatologists, radiologists, and surgeons from different parts of the country participated in the consensus development meeting at Coorg in 2018. A core group was constituted which reviewed all published literature on portal hypertensive UGIB with special reference to the Indian scenario and prepared unambiguous statements on different aspects for voting and consensus in the whole group. This consensus was produced through a modified Delphi process and reflects our current understanding and recommendations for the diagnosis and management of portal hypertensive UGIB in Indians. Intended for use by the health care providers especially gastroenterologists and hepatologists, these consensus statements provide an evidence-based approach to risk stratification, diagnosis, and management of patients with portal hypertensive bleeding.

Content available: Author Audio Recording.

Hepatorenal syndrome (HRS) occurs in patients with cirrhosis or fulminant hepatic failure and is a kind of pre-renal failure due to intense reduction of kidney perfusion induced by severe hepatic injury. While other causes of pre-renal acute kidney injury (AKI) respond to fluid infusion, HRS does not. HRS incidence is 5% in children with chronic liver conditions before liver transplantation. Type 1 HRS is an acute and rapidly progressive form that often develops after a precipitating factor, including gastrointestinal bleeding or spontaneous bacterial peritonitis, while type 2 is considered a slowly progressive form of kidney failure that often occurs spontaneously in chronic ascites settings. HRS pathogenesis is multifactorial. Cirrhosis causes portal hypertension; therefore, stasis and release of vasodilator substances occur in the hepatic vascular bed, leading to vasodilatation of splanchnic arteries and systemic hypotension. Many mechanisms seem to work together to cause this imbalance: splanchnic vasodilatation; vasoactive mediators; hyperdynamic circulation states and subsequent cardiac dysfunction; neuro-hormonal mechanisms; changes in sympathetic nervous system, renin-angiotensin system, and vasopressin. In patients with AKI and cirrhosis, fluid expansion therapy needs to be initiated as soon as possible and nephrotoxic drugs discontinued. Once HRS is diagnosed, pharmacological treatment with vasoconstrictors, mainly terlipressin plus albumin, should be initiated. If there is no response, other options can include surgical venous shunts and kidney replacement therapy. In this regard, extracorporeal liver support can be a bridge for liver transplantation, which remains as the ideal treatment. Further studies are necessary to investigate early biomarkers and alternative treatments for HRS.

Spontaneous bacterial peritonitis (SBP) is a decompensation of cirrhosis with an in-hospital mortality ranging from 20% to 40%.

The purpose of this study is to analyze if EASL-CLIF definition of acute-on-chronic liver failure (ACLF) is able to predict mortality in cirrhotic patients with SBP.

Historical cohort study conducted in a public tertiary care teaching hospital. Data from medical records from January 2009 to July 2016 were obtained by searching the hospital electronic database for samples of ascites collected in the period. Electronic and physical medical records were analyzed and patients were included if they were over 18-years old, with cirrhosis and an ascites fluid compatible with SBP: 69 patients were included. Liver-specific scores were calculated and Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis.

All cause mortality was 44%, 56.5% and 74% for 28-, 90- and 365-day, respectively. The prevalence of ACLF was 58%. Of these, 65% grade 1, 17.5% grade 2 and 17.5% grade 3. In multivariate analysis, the use of proton-pump inhi-bitors, alanine transaminase lower than 40 U/L, hemoglobin higher than 9 g/dL, absence of ACLF and lower CLIF-SOFA and MELD scores were independently associated with higher survival for both 28- and 90-day interval.

The presence of ACLF and higher CLIF-SOFA scores were independently associated with higher 28- and 90-day mortality in cirrhotic patients admitted due to SBP.

The development of acute kidney injury (AKI) is one of the most frequent complications in patients with cirrhosis. AKI due to volume depletion is the most common etiology and hepatorenal syndrome (HRS) is the second most common cause of AKI in these patients. HRS is the extreme form of kidney injury in patients with cirrhosis, which is caused due to a reduction in renal blood flow unresponsive to volume expansion. The literature involving HRS is rapidly evolving and newer tests and updated definitions have been proposed which allows timely identification and treatment. Here, we will discuss the definition, pathophysiology, prevention, diagnosis, and treatment of HRS.

Cirrhosis is associated with dysregulated immune cell activation and immune dysfunction. These conditions modify gut flora, facilitate bacterial translocation, and increase susceptibility to bacterial peritonitis and consequent systemic infections by dramatically affecting long-term patient survival. Human amnion-derived mesenchymal stromal cells (hA-MSCs) exert immunomodulatory potential benefit, and have the ability to modulate their actions, especially in situations requiring immune activation through mechanisms not fully understood. In this study, we aimed to investigate, in vitro, the immunostimulant or immunosuppressive effects of hA-MSCs on cellular components of ascitic fluid obtained from cirrhotic patients with refractory ascites. We found that hA-MSCs viability is not affected by ascitic fluid and, interestingly, hA-MSCs diminished the pro-inflammatory cytokine production, and promoted anti-inflammatory M2 macrophage polarization. Moreover, we found that there was no simultaneous significant decrease in the M1-like component, allowing a continual phagocytosis activity of macrophages and NK cells to restore a physiological condition. These data highlight the plasticity of hA-MSCs' immunomodulatory capacity, and pave the way to further understanding their role in conditions such as spontaneous bacterial peritonitis.

Hepatorenal syndrome (HRS) is a serious complication of cirrhosis with high morbidity and mortality rates. Recently, the definition of HRS type 1 has been updated and is now called HRS-AKI. This new definition reduces the risk of delaying HRS treatment and eliminates the need to establish a minimum creatinine cut-off for the diagnosis of HRS-AKI. From a pathophysiological point of view, newly identified mechanisms involved in the development of HRS are related to the inflammatory response, conditioning the development of extrahepatic organ dysfunction in patients with cirrhosis. One of the main challenges for the diagnosis of HRS is the validation of new biomarkers to obtain an early and differential diagnosis of kidney injury (eg HRS vs. ATN). Treatment of HRS is based on the use of vasoconstrictive agents in combination with albumin and terlipressin is the most widely used vasoconstrictor drug, with a high response rate. The effects of a continuous infusion of terlipressin at a dose of 2-12 mg/day was similar to bolus administration, but with lower rates of adverse events. Finally, MELD/MELD-Na which includes creatinine as one of its main determinants gives AKI-HRS patients priority on the waiting list (WL) for liver transplant (LT). However, the MELD and MELD-Na scores are reduced in responding patients, resulting a longer waiting time in these patients than in non-responders. Thus, the initial MELD/MELD-Na score (pre-treatment value) should be used to prioritize patients on the WL for LT in these cases.

Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction. Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis, large-volume paracentesis and hepatorenal syndrome. Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients. We review the current literature on both the established and potential role of albumin, and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.

Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.

Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset.

Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death.

In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications.

The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge.

Sudden damage to the kidneys is becoming more common in people who are hospitalized and have cirrhosis. Despite advances in cirrhosis care, those with damage to the kidneys remain at higher risk of dying.

Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment.

In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 μmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points.

The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326).

Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction.

NCT03846180 ( https://clinicaltrials.gov ).

Risk scoring for patients with cirrhosis has evolved greatly over the past several decades. However, patients with low Model for End-Stage Liver Disease-Sodium scores still suffer from liver-related morbidity and mortality. Unfortunately, it is not clear which of these low Model for End-Stage Liver Disease-Sodium score patients would benefit from earlier consideration of liver transplantation. This article reviews the literature of risk prediction in patients with cirrhosis, identifies which patients may benefit from earlier interventions, such as transplantation, and proposes directions for future research.

Hepatorenal syndrome (HRS), the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduction in renal blood flow and glomerular filtration rate. Hepatorenal syndrome is diagnosed when kidney function is reduced but evidence of intrinsic kidney disease, such as hematuria, proteinuria, or abnormal kidney ultrasonography, is absent. Unlike other causes of acute kidney injury (AKI), hepatorenal syndrome results from functional changes in the renal circulation and is potentially reversible with liver transplantation or vasoconstrictor drugs. Two forms of hepatorenal syndrome are recognized depending on the acuity and progression of kidney injury. The first represents an acute impairment of kidney function, HRS-AKI, whereas the second represents a more chronic kidney dysfunction, HRS-CKD (chronic kidney disease). In this review, we provide critical insight into the definition, pathophysiology, diagnosis, and management of hepatorenal syndrome.

Acute kidney injury is a common and life-threatening event in patients with liver cirrhosis occurring in approximately 20-50% of hospitalized patients of liver cirrhosis. Pre-renal acute kidney injury, the hepatorenal syndrome type of acute kidney injury and acute tubular necrosis represent the common causes. The aim of this study was to study the profile of acute kidney injury in patients with liver cirrhosis.

Consecutive patients of liver cirrhosis admitted in Liver unit of Bir Hospital were studied to see the presence of acute kidney injury in this hospital based descriptive cross-sectional study. Clinical and laboratory parameters along with various clinical outcome were compared between different groups categorized by the severity of liver disease and renal dysfunction.

Out of 302 liver cirrhosis patients, 56 (18.5%) had acute kidney injury among which 23 (46%) were found to have pre-renal acute kidney injury, 15 (30%) with hepatorenal syndrome- acute kidney injury and 12 (24%) with intrinsic renal disease. Patients with higher stages of acute kidney injury had longer duration of hospital stay and hepatorenal syndrome-acute kidney injury was seen in patients with higher grade of ascites and with hyponatremia.

Acute kidney injury is a common occurrence in patients with advanced liver cirrhosis with pre-renal acute kidney injury being the commonest cause. Median hospital stay is directly affected by the severity of acute kidney injury and hepatorenal syndrome-acute kidney injury was seen in patients with higher grade of ascites and hyponatremia. Early identification of patients at high risk for acute kidney injury may help to reduce mortality and contain costs.

AKI is known to be associated with increased risk of mortality, however limited information is available on how AKI impacts healthcare costs and resource utilization in hospitalized patients with cirrhosis. Previous studies have had variable definitions of AKI, resulting in inconsistent reporting of the true impact of AKI in patients with cirrhosis.

Data from the Nationwide Inpatient Sample (NIS) which contains data from 44 states and 4378 hospitals, accounting for over 7 million discharges were analyzed. The inclusion data were all discharges in the 2012 NIS dataset with a discharge diagnosis of cirrhosis.

A total of 32,605 patients were included in the analysis, incidence of AKI was 12.12% in patients with cirrhosis. Crude mortality was much higher for patients with cirrhosis and AKI (14.9% vs. 1.8%, OR 9.42, p<0.001) than for patients without AKI. In addition, mean LOS was longer (8.5 vs. 4.3 days, p<0.001) and median total hospital charges were higher for patients with AKI ($43,939 vs. $22,270, p<0.001). In multivariate logistic regression, controlling for covariates and mortality risk score, sepsis, ascites and SBP were predictors of AKI.