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.

More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome.

New criteria for acute kidney injury (AKI) in cirrhosis have been proposed, but its prognostic significance is unclear. This study aims to evaluate the prognostic significance of the AKI criteria in cirrhotic patients hospitalized for acute decompensation.

This is a prospective cohort study. AKI was defined as an increase in creatinine (Cr) levels ≥ 0.3 mg/dL in 48 h or ≥ 50% of the basal value in the last 7d. AKI was divided into stages 1 (elevation: < 2x basal), 2 (2 or 3x), and 3 (> 3x).

In this study, 227 patients aged 53.9 ± 11.5 years were included, of whom 37% had AKI (28% AKI1, 5% AKI2, and 4% AKI3). Thirty percent of the patients died or were transplanted within 90 days from causes related to the presence of ascites at hospital admission and higher values of Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scores, but not to the presence of AKI. In a regression analysis conducted to assess the effect of the final Cr level in patients with AKI, 90-day mortality was associated with ascites, higher CLIF-SOFA score, and AKI with final Cr level ≥ 1.5 mg/dL. The patients with AKI with Cr levels ≥ 1.5 mg/dL showed lower transplant-free survival rates than those without AKI, and those with AKI1 with final Cr level < 1.5 mg/dL.

Early AKI was frequent and associated with 90-day mortality or transplantation only when the final Cr level was ≥ 1.5 mg/dL. Distinct approaches are needed for patients with AKI1 according to final Cr.

Renal involvement in hepatitis B occurs in various spectrums and its knowledge is important for clinicians in management of patients. The renal diseases most commonly associated with hepatitis B virus (HBV) infection include membranous nephropathy, membranoproliferative glomerulonephritis and Polyarteritis nodosa. The widespread use of hepatitis B vaccination has decreased the incidence of HBV-related renal diseases. The incidence of HBV infection in dialysis patients has significantly decreased over the past few decades because of screening of blood products for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, implementation of infection control measures and hepatitis B vaccination. The definition of acute kidney injury has been recently modified in cirrhotic population, helping in prognosis and prediction of mortality. The most common etiologies of acute kidney injury in this cirrhotic population, which account for 80% to 90% of all cases, include volume depletion, acute tubular necrosis and hepatorenal syndrome. Treatment with oral nucleoside/tide analogues (NA) brought a new paradigm in the management of HBsAg positive glomerulonephritis, kidney transplant recipients and dialysis patients, resulting in effective viral suppression, reduced hepatic complications and improved patient survival, without compromising renal allograft outcome. NAs are cleared by the kidneys and therefore their dosage has to be adjusted in all patients with impaired renal function. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related glomerulonephritis and discusses the management of hepatitis B in patients on dialysis, kidney transplant recipients and cirrhotics, which is continuously evolving.

Patients with cirrhosis who are awaiting liver transplantation (LT) are at high risk for developing critical illnesses. Current liver allocation policies that dictate a "sickest first" approach coupled with a mismatch between need and availability of organs result in longer wait times, and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well-compensated cirrhosis may suffer acute deterioration; the syndrome of acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction and a marked increase in associated short-term morbidity and mortality. For patients on transplant waiting lists, the development of multisystem organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (eg, infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo LT. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and to describe our approach management in critically ill patients awaiting LT in our centers. Liver Transplantation 23 1465-1476 2017 AASLD.

Acute kidney injury is common in patients with liver disease and associated with significant morbidity and mortality. Besides bacterial infections, fluid loss, and use of nephrotoxic drugs AKI in liver disease may be triggered by tubular toxicity of cholephiles. Cholemic nephropathy, also known as bile cast nephropathy, supposedly represents a widely underestimated but important cause of renal dysfunction in cholestasic or advanced liver diseases with jaundice. Cholemic nephropathy describes impaired renal function along with characteristic histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed towards distal nephron segments. The underlying pathophysiologic mechanisms are not entirely understood and clear defined diagnostic criteria are still missing. This review aims to summarize (i) the present knowledge on clinical and morphological characteristics of cholemic nephropathy, (ii) available preclinical models, (iii) potential pathomechanisms especially the potential role of bile acids, and (iv) future diagnostic and therapeutic strategies for cholemic nephropathy. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

To assess the prognostic accuracy of absolute serum creatinine (sCr) changes ('Delta-sCr') on the long-term outcomes in cirrhotic patients, and evaluate the performance of the 'Delta-sCr' approach to stage acute kidney injury (AKI), compared with the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

We conducted a retrospective analysis of 333 hospitalized patients. We classified AKI stages using two methods: 1) KDIGO AKI criteria; 2) 'Delta-sCr' system, defined by the difference between the baseline and the peak sCr value during the hospitalization. The end point was the hazard of 1-year death.

The prevalence of AKI in cirrhotic patients was 18.01% by the KDIGO criteria, and 25.22% by the 'Delta-sCr' system. On multivariable Cox hazard analysis, both of the two methods were independent predictive factors of death ('Delta-sCr' system: OR=2.911, p<0.001), (KDIGO criteria: OR=2.065, p<0.001). However, the 'Delta-sCr' system provided a modest improvement in classification over the KDIGO criteria with a net reclassification improvement (NRI) of 28.7% (p<0.001) and integrated discrimination improvement (IDI) of 7.5% (p=0.03). And the predictive value of the 'Delta-sCr' system could be significantly improved (p=0.006), when combined with age and MELD score.

The Delta-sCr is associated with the 1-year mortality. And the 'Delta-sCr' system may optimize the discrimination of risk prediction.

Renal dysfunction is a common complication of liver cirrhosis and of utmost clinical and prognostic relevance. Patients with cirrhosis are more prone to developing acute kidney injury (AKI) than the non-cirrhotic population. Pre-renal AKI, the hepatorenal syndrome type of AKI (HRS-AKI, formerly known as 'type 1') and acute tubular necrosis represent the most common causes of AKI in cirrhosis. Correct differentiation is imperative, as treatment differs substantially. While pre-renal AKI usually responds well to plasma volume expansion, HRS-AKI and ATN require different specific approaches and are associated with substantial mortality. Several paradigms, such as the threshold of 2.5 mg/dL for diagnosis of HRS-AKI, have recently been abolished and novel urinary biomarkers are being investigated in order to facilitate early and correct diagnosis and treatment of HRS-AKI and other forms of AKI in patients with cirrhosis. This review summarizes the current diagnostic criteria, as well as pathophysiologic and therapeutic concepts for AKI and HRS-AKI in cirrhosis.

Hepatorenal syndrome (HRS) represents a severe form of renal injury in cirrhotic patients with ascites in the absence of certain triggers.

Patients with cirrhosis and ascites were longitudinally screened for renal dysfunction. HRS was diagnosed by an increase in serum creatinine (SCr) by ≥100% to ≥1.5 mg/dl. If specific triggers (i.e. nephrotoxins, parenchymal kidney damage, hypovolaemia, infections) were found, these cases were defined as specifically triggered acute kidney injury (sAKI).

Four hundred ninety-seven cirrhotic patients were screened for AKI and we identified 71 patients with HRS and 84 with sAKI. The most common triggers of sAKI were parenchymal damage in 33%, nephrotoxins in 30% and hypovolaemia in 29%. sAKI patients showed significantly more often complete remission than HRS patients (51% vs. 13%, P < 0.001), whereas persisting impairment of renal function was more common in HRS than in sAKI (56% vs. 37%, P = 0.006). Short-term (30 days) mortality was significantly higher in HRS than in sAKI (62% vs. 45%, P = 0.038). Remission rates and mortality varied between sAKI triggers. Transplant-free survival (TFS) was not significantly, but numerically lower in HRS than in sAKI [14 (IQR: 2-99) vs. 36 (IQR: 5-371) days; P = 0.102].

Patients with HRS show worse outcome and higher 30-day mortality than patients with severe triggered AKI. Different triggers of sAKI seem to influence prognosis. Prospective data are needed to implement effective screening and treatment algorithms for kidney injury in patients with cirrhosis and ascites.

Renal dysfunction is prevalent in patients with advanced cirrhosis and decompensation. The presence of type 1 hepatorenal syndrome (HRS) has traditionally been defined by a set of stringent criteria based on serum creatinine levels. These diagnostic criteria have been found to be too stringent to be widely applicable to patients with cirrhosis, leading to underdiagnosis of renal failure in this population. Acute kidney injury (AKI) has now been proposed to characterize renal dysfunction in patients with cirrhosis and is defined as an increase in serum creatinine by 0.3 mg/dl in <48 h or an increase in serum creatinine by 50% from a stable baseline reading within 3 months. Type 1 HRS is renamed HRS-AKI. Stage 1 AKI is defined by 0.3 mg/dl serum creatinine or a 50% increase, stages 2 and 3 AKI are defined by a two-fold and three-fold increase in serum creatinine levels, respectively. Data collected so far suggests that even stage 1 AKI is associated with worse prognosis in patients with cirrhosis. The progression of AKI usually indicates substantially worse outcomes. A panel of biomarkers, including inflammatory markers, are envisaged to complement and enhance our current diagnostic criteria in the future and provide aetiology of the AKI.

Acute kidney injury (AKI) is a common complication in patients with liver cirrhosis, and its impact on the clinical course is increasingly recognized. Diagnostic classification systems for AKI in cirrhosis have been suggested. The prognostic significance of the respective AKI stages remains to be evaluated in decompensated cirrhosis with ascites.

Data of consecutive patients with cirrhosis and ascites undergoing paracentesis at a tertiary care center were analyzed. AKI was defined as an increase in serum creatinine of ≥ 0.3 mg/dL or by ≥ 50% within 7 days after paracentesis, and classified according to (i) revised Acute Kidney Injury Network (AKIN) criteria and (ii) modified AKI criteria for cirrhosis (C-AKI). In contrast to AKIN, C-AKI stage A discriminates prognosis based on an absolute creatinine cut-off at < 1.5 mg/dL versus C-AKI stage B at ≥ 1.5 mg/dL.

The final study cohort included 239 patients. Median transplant-free survival was 768 days (95% confidence interval [CI]: 331-1205 days) without AKI, 198 (0-446) in AKI-1, 91 (0-225) in AKI-2, 19 (0-40) and in AKI-3, whereas it was 89 (20-158) days in C-AKI-A, 384 (0-1063) in C-AKI-B, and 22 (7-776) in C-AKI-C. Mild AKI was already associated with significantly increased 30-day mortality (AKI-1:26.4%, C-AKI-A:33.3%) as compared with patients without AKI (14.3%), even when serum creatinine remained within normal range (< 1.2 mg/dL) we observed a significant 30-day mortality.

AKIN criteria-considering small increases in serum creatinine rather than absolute thresholds-seem to be more accurate for estimating prognosis of AKI after paracentesis than C-AKI criteria. Even patients developing AKI-1 with "normal" serum creatinine are at increased risk for mortality.

Cirrhosis is the eighth leading cause of "years of lost life" in the United States and accounts for approximately 1% to 2% of all deaths in Europe. Patients with cirrhosis have a high risk of developing acute kidney injury. The clinical characteristics of hepatorenal syndrome (HRS) are similar to prerenal uremia, but the condition does not respond to volume expansion. HRS type 1 is rapidly progressive whereas HRS type 2 has a slower course often associated with refractory ascites. A number of factors can precipitate HRS such as infections, alcoholic hepatitis, and bleeding. The monitoring, prevention, early detection, and treatment of HRS are essential. This paper reviews the value of early evaluation of renal function based on two new sets of diagnostic criteria. Interventions for HRS type 1 include terlipressin combined with albumin. In HRS type 2, transjugular intrahepatic portosystemic shunt (TIPS) should be considered. For both types of HRS patients should be evaluated for liver transplantation.

Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker.

To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis.

We have searched through current literature and analyzed all significant full text articles on this topic.

NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.

Acute kidney injury (AKI) is frequent in patients with cirrhosis. AKI and hyponatraemia are major determinants of the poor prognosis in advanced cirrhosis. The hepatorenal syndrome (HRS) denotes a functional and potential reversible impairment of renal function. Type 1 HRS, a special type of AKI, is a rapidly progressive AKI, whereas the renal function in type 2 HRS decreases more slowly. HRS is precipitated by factors such as sepsis that aggravate the effective hypovolaemia in decompensated cirrhosis, by lowering arterial pressure and cardiac output and enhanced sympathetic nervous activity. Therefore, attempts to prevent and treat HRS should seek to improve liver function and to ameliorate arterial hypotension, central hypovolaemia and cardiac output, and to reduce renal vasoconstriction. Ample treatment of HRS is important to prevent further progression and death, but as medical treatment only modestly improves long-term survival, these patients should always be considered for liver transplantation. Hyponatraemia, defined as serum sodium <130 mmol/L, is common in patients with decompensated cirrhosis. From a pathophysiological point of view, hyponatraemia is related to an impairment of renal solute-free water excretion most likely caused by an increased vasopressin secretion. Patients with cirrhosis mainly develop hypervolaemic hyponatraemia. Current evidence does not support routine use of vaptans in the management of hyponatraemia in cirrhosis.