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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.

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.

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.

Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.

Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-ProcessOther Non-Indexed Citations, Scopus, and Web of Science from inception.Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI,87.7 to210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI,2.8 to177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI,5.1 to51]; moderate certainty).Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.

Patients with decompensated cirrhosis are well known to experience morbidity and mortality.We assessed clinical characteristics, health-care utilization, and economic burden according to the type, number, and combination of decompensation-related complications.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).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.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.

Whether hemostatic status was correlated with the diverse types of acute kidney injury in cirrhotic patients is unclear. The present study aimed to investigate the relationship between hemostatic markers and the diverse types of acute kidney injury (AKI) in liver cirrhosis. Cirrhotic patients with consecutive treatment at the First Affiliated Hospital of Medicine School, Zhejiang University, were pooled in a cohort. Their demographic and clinical data, biochemistry parameters and hemostatic markers were assessed to identify risk factors for the development and prognosis of AKI. A total of 773 cirrhotic patients were included in this cohort. Patients with hepatorenal syndrome (HRS) had significantly higher D-Dimer than those with the other types of AKI. In univariate COX regression, APTT, TT, INR, D-Dimer and Fib were correlated with the development of AKI, HRS and acute tubular necrosis (ATN), however, only D-Dimer remained independently associated with the development of AKI and HRS in multivariate COX regression. The area under the ROC curve of D-Dimer was 0.755 (95%CI, 0.718–0.793) in predicting the development of AKI, 0.879 (95%CI, 0.791–0.967) in predicting the development of HRS, respectively. D-Dimer was used for diagnosis of HRS with a sensitivity of 87.3% and specificity of 72.9% at the cutoff of 3.7 (mg/L FEU). Survival rates differed significantly between groups by D-Dimer level. Hemostatic markers were significantly associated with the diverse types of AKI. D-Dimer was an independent risk factor for HRS and correlated with a poor outcome in cirrhotic patients.

The effect of pretransplant hepatorenal syndrome (HRS) on the outcomes of living-donor liver transplantation (LDLT) recipients with special reference to the recovery of HRS before LDLT was investigated.The rate of HRS was 43.9% (125/285) among the cohort, and the subjects were divided into three groups: those without HRS (No-HRS group, n = 160), those with HRS but recovered following pretransplant renal function restoration treatment (Responders group, n = 55), and those with persistent HRS (Non-responders group, n = 70).While the 1-, 3-, and 5-year patient survival rates were comparable between those with and without HRS (89.6%, 84.7%, and 84.7% vs 95.6%, 92.2%, and 87.5%), the cumulative incidence of the development of posttransplant chronic kidney disease (CKD) was significantly higher in those with HRS (P .001). In addition, there was a significant difference between Responders and Non-responders in the development of CKD (P = .01). In the Cox regression model, Non-responders (P = .032, HR 1.79 [95% C.I. 1.05-3.03]) and recipient age (P = .014, HR 1.62 [95% C.I. 1.10-2.37]) were independent predictors for the development of CKD after LDLT.Living-donor liver transplantation is safe and effective for patients with HRS, and CKD progression could be reduced among those with HRS who responded to renal restoration treatment.

Albumin has been used primarily as a plasma expander, since it leads to an increase in the circulating blood volume. Current generally recommended indications for albumin therapy in cirrhotic patients are the prevention of circulatory dysfunction after large-volume paracentesis, the prevention of hepatorenal syndrome (HRS) in patients with spontaneous bacterial peritonitis (SBP), and the management of HRS in combination with vasoconstrictors. Yet, new indications for albumin have been tested in the recent years and are outlined in this short review.New data show that albumin both supports the circulation and reduces systemic inflammation. In addition, to its oncotic function, it acts as an antioxidant, radical scavenger, and immune modulator. These nononcotic properties explain why long-term albumin administration in patients with decompensated cirrhosis may be useful in the prevention of associated complications (acute-on-chronic liver failure, infections). New data show that long-term albumin therapy in patients with cirrhosis and ascites improves survival, prevents complications, simplifies ascites management, and lowers hospitalization rates. The so-called disease-modifying effects of long-term albumin therapy may have a favorable effect on the course of the disease. Nevertheless, the optimal dosage and administration intervals have not yet been finally defined.Albumin therapy is effective in the indications already recommended by the guidelines. A possible extension of the indication for albumin administration in non-SBP infections and as long-term therapy is promising, but should be confirmed by further studies.

In patients with acute-on-chronic liver failure (ACLF), type 1 hepatorenal syndrome (HRS) is a critical organ failure complication that resulted in rapid mortality. There are no efficient parameters to predict HRS in hepatitis B virus (HBV)-related ACLF. To assess HBV-ACLF risk factors and evaluate the association between mean arterial pressures (MAP), HRS and survival in patients with HBV-ACLF.A total of 420 ACLF patients were screened from June 2015 to June 2016, and 57 HBV-ACLF patients were included in the study. Clinical data and MAP measurements of these patients were collected. Multivariate analyses, Cox proportional hazards regression and receiver operator characteristic (ROC) curves were used to analyze.In a 30-day study period, 43 (75.44%) patients survived. Patients in the HRS group were older and had higher Model for End-Stage Liver Disease (MELD) scores than patients in the non-HRS group. A MAP drop of ≥9.5 mmHg was an independent predictor of HRS with a sensitivity and specificity of 92.86 and 69.77%, respectively. The baseline MELD score was also an independent risk factor of HRS. MAP drop (OR, 1.582; P = 0.000), prothrombin time, HRS, MELD and FIB were independent prognostic factors for 30-day mortality. The area under the ROC curve of MAP drop was 0.808 (P = 0.001).A decrease in MAP was a valuable predictor of HRS in patients with HBV-related ACLF. MAP drop ≥9.5 mmHg may be useful for predicting patient prognosis and exploring new treatment measures in patients with HBV-related ACLF.

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.

Acute kidney injury (AKI) is common in advanced cirrhosis. Prerenal azotemia, hepatorenal syndrome, and acute tubular necrosis are the main causes of AKI in patients with cirrhosis. Evaluation of renal function and differentiation between functional and structural kidney injury are important issues in the management of cirrhosis. However, AKI in cirrhosis exists as a complex clinical spectrum rather than concrete clinical entity. Based on current evidence, changes in serum creatinine (Cr) levels remain the most appropriate standard for defining AKI in cirrhosis. However, serum Cr has a limited role in assessing renal function in this population. This review examines previous studies that investigated the ability of recent biomarkers for AKI in cirrhosis from the perspective of earlier and accurate diagnosis, classification of AKI phenotype, and prediction of clinical outcomes. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin have been extensively studied in cirrhosis, and have facilitated improved diagnosis and prognosis prediction in patients with AKI. In addition, urine N-acetyl-β-D-glucosaminidase, interleukin 18, and kidney injury molecule 1 are other promising biomarkers for advanced cirrhosis. However, the clinical significance of these markers remains unclear because there are no cut-off values defining the normal range and differentiating phenotypes of AKI. In addition, AKI has been defined in terms of serum Cr, and renal biopsy—the gold standard—has not been carried out in most studies. Further discovery of innovate biomarkers and incorporation of various markers could improve the diagnosis and prognosis prediction of AKI, and will translate into meaningful improvements in patient outcomes.

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) of40U/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.

One of the most dreaded complications of end stage liver disease is hepatorenal syndrome AKI (HRS-AKI; formally known as hepatorenal syndrome 1 [HRS-1]). HRS-AKI carries a high mortality, and treatment options are limited. Guidelines recommend terlipressin as the first-line treatment of HRS-AKI

BACKGROUND Hepatorenal syndrome (HRS) is a life-threatening condition among patients with advanced liver disease. Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited. AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States. METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014 (weighted sample of 23973 admissions). The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality. We estimated odds ratios from multi-level mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality. RESULTS Overall hospital mortality was 32%. Hospital mortality decreased from 44% in 2005 to 24% in 2014 (P < 0.001), while there was an increase in the rate of liver transplantation (P = 0.02), renal replacement therapy (P < 0.001), length of hospital stay (P < 0.001), and hospitalization cost (P < 0.001). On multivariable analysis, older age, alcohol use, coagulopathy, neurological disorder, and need for mechanical ventilation predicted higher hospital mortality, whereas liver transplantation, transjugular intrahepatic portosystemic shunt, and abdominal paracentesis were associated with lower hospital mortality. CONCLUSION Although there was an increase in resource utilizations, hospital mortality among patients admitted for HRS significantly improved. Several predictors for hospital mortality were identified.

Little is known about the utility of transcatheter aortic valve implantation (TAVI) in patients with cirrhosis of the liver, and their outcomes have not been studied extensively in literature. We performed a retrospective analysis of patients with severe symptomatic aortic stenosis (AS) who underwent transfemoral TAVI with a SAPIEN 3 valve at our institution between April 2015 and December 2018. We identified 32 consecutive patients with evidence of cirrhosis of the liver on imaging (including ultrasound and/or computed tomography) and patients with severe symptomatic AS who underwent transfemoral TAVI with a SAPIEN 3 valve. Among 1,028 patients, 32 had cirrhosis of the liver and 996 constituted the control group without cirrhosis. Mean age in the cirrhosis group was 74.5 years compared with 81.2 years in the control group. Baseline variables were comparable between the groups. Compared with the noncirrhotic group, patients with cirrhosis had a similar 1-year mortality (12% vs 12%, p = 1), a lower 30-day new pacemaker after TAVI rate (6% vs 9%, p = 0.85), a higher 30-day and 1-year readmission rate for heart failure (11% vs 1% and 12% vs 5%, p = 0.12, respectively), and a similar 1-year major adverse cardiac and cerebrovascular event rate (15% vs 14%, p = 0.98). In conclusion, patients with severe AS with concomitant liver cirrhosis who underwent TAVI demonstrated comparable outcomes to their noncirrhotic counterparts.

Whether tubular injury develops in patients with acute kidney injury owing to hepatorenal syndrome (AKI-HRS) is controversial. We performed repeated measurements of biomarkers of tubular injury during a 14-day period in 60 patients with cirrhosis and AKI (34 with AKI-HRS meeting the classical definition of type 1 HRS and 26 with AKI owing to acute tubular necrosis, AKI-ATN). Nineteen of 34 patients had resolution of AKI-HRS, while the remainder had persistent AKI-HRS. The persistence of AKI-HRS was associated with remarkably high short-term mortality. There were no significant differences in urinary NGAL or IL-18 between patients with resolution vs those with persistent AKI-HRS throughout the 14-day period. By contrast, biomarker levels were significantly lower in AKI-HRS, even if persistent, compared to AKI-ATN. These findings are highly suggestive of lack of significant tubular injury in AKI-HRS and could be of value in the clinical decision between combined liver-kidney or liver transplantation alone in patients with cirrhosis and AKI candidates to transplantation.

Hepatorenal syndrome (HRS) contributes to significant morbidity and mortality in hospitalised patients with cirrhosis.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.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.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.

Terlipressin is widely used for treatment of hepatorenal syndrome and variceal bleeding in cirrhotic patients. However, it may be associated with side effects, especially those related to vasoconstriction, such as myocardial infarction or intestinal ischemia. This is a case report of a cirrhotic patient with nonvariceal upper gastrointestinal bleeding after duodenal necrosis due to the use of terlipressin, a novel side effect not yet described in literature to the best of our knowledge.A 51-year-old male patient, with alcoholic liver cirrhosis and hepatitis C virus infection, was admitted presenting oliguria associated with severe ascites and lower limb edema. His Model for End Stage Liver Disease-Sodium score was 19 and his serum creatine level was 2.12 mg/dL. Albumin infusion was performed for 48 hours, but his serum creatinine level reached 3.46 mg/dL. Terlipressin infusion was started in continuous infusion and serum creatinine levels progressively decreased. However, the patient presented hemorrhagic shock secondary to hematemesis after 7 days. Upper digestive endoscopy showed an extensive ulcerated lesion in the duodenal bulb, reaching 70% of its lumen, with hematic residues and necrotic foci. Terlipressin was suspended and proton pump inhibitors were started. Despite intensive care, the patient developed severe encephalopathy and reentrant seizures. He eventually died 10 days after the bleeding event.We described a case of nonvariceal upper gastrointestinal bleeding secondary to duodenal necrosis, which was caused by visceral ischemia induced by terlipressin. Given its fatality potential, this novel side effect should be remembered when using this medication in cirrhotic patients.

Case Presentation A 64-year-old man with a past medical history of alcoholic cirrhosis with resultant hepatorenal syndrome requiring kidney and liver transplantation 10 years previously sought treatment at the ED with progressive lower-extremity edema and dyspnea. After noting worsening shortness of breath and cough as an outpatient, he had been referred to a pulmonary clinic and was undergoing a workup for interstitial lung disease (ILD). He had been started on prednisone 40 mg/d after a lung biopsy 4 months before admission. He was also receiving chronic immunosuppression with tacrolimus and mycophenolate mofetil. He had noted worsening of edema since starting prednisone.

Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.

Introduction : Cystatin C (CysC) is biomarker for early detection of acute kidney injury (AKI). However, there is limited evidence in decompensated cirrhotic patients without AKI at admission. This study aimed to assess CysC as a predictor of 90-day mortality. Methods : Decompensated cirrhotic patients without AKI were prospectively enrolled. CysC and creatinine were measured within 24 hours of admission and compared between patients with in-hospital complications (AKI, hepatorenal syndrome (HRS), acute-on-chronic liver failure (ACLF)) vs. those without, and survivors vs. non-survivors. The AUROC and cut-off point of CysC in predicting 90-day mortality were determined. Results : Of 137 decompensated cirrhotic patients, 46 without AKI at admission were included (58.7% male, age 60.8 ± 11.2years, MELD 13.1 ± 5.1, ChildA / B / C 43.5% / 39.1% / 17.4%). The mean CysC level tended to be higher in patients with ACLF (1.52 ± 0.60 vs. 1.11 ± 0.28, p = 0.05), and significantly higher in non-survivors than survivors (1.61 ± 0.53 vs. 1.08 ± 0.28, p = 0.013). The 90-day mortality rate was 21.7%. After adjusting with age and bacterial infection on admission, CysC level ≥ 1.25 mg / L was significantly associated with 90-day mortality. The CysC cut-off level ≥ 1.25 mg / L provided 80% sensitivity and 75% specificity for predicting 90-day mortality. Conclusion : Plasma CysC within 24 hours could be used as a predictor for 90-day mortality and development of ACLF in decompensated cirrhotic patients. J. Med. Invest. 68 : 302-308, August, 2021.

Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. AKI is separated into two categories, non-HRS AKI and HRS-AKI. The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease. The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation. The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients; novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models. The overall management of non-HRS AKI and HRS-AKI requires a systematic approach. Although pharmacological treatments have shown mortality benefit, the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. This article reviews the current guidelines and recommendations of AKI in cirrhosis.

Vasoconstrictors are the treatment of choice for hepatorenal syndrome (HRS). We evaluate the real-life effectiveness of a sequential vasoconstrictor regimen of midodrine-octreotide followed by norepinephrine in a nonintensive care unit (non-ICU) setting in the United States, where terlipressin is not available. The diagnosis of HRS and definitions of response to therapy were based on 2015 guidelines from the International Club of Ascites. In adult patients with HRS without partial or full response to oral midodrine and subcutaneous octreotide, norepinephrine was administered at a starting dose of 5 mcg/minute, with a goal to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline. We assessed predictors of response and treatment outcomes. A total of 61 patients were administered midodrine and octreotide for the treatment of HRS, with a 28% response rate. The median MELD-Na (Model for End-Stage Liver Disease-sodium) score was 30 (interquartile range [IQR] 24-35). Responders were more likely to have alcohol-related liver disease and lower Acute-on-Chronic Liver Failure (ACLF) grade. Of the nonresponders, 20 were then administered norepinephrine, of whom 45% achieved full or partial response. Achieving an MAP increase of ≥10 mm Hg was associated with a greater probability of response. Patients who responded to norepinephrine experienced improved transplant-free survival at 90 days (88% versus 27%; P = 0.02); 5 of 20 patients experienced norepinephrine treatment-related adverse events, namely arrhythmias. Norepinephrine can be effectively used in a non-ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide. Based on these data, we propose a practical stepwise algorithm for vasoconstrictor therapy to manage HRS in situations where terlipressin is not an option.

Purpose of review Hepatorenal syndrome (HRS) is encountered frequently in patients with end-stage liver disease and remains an important cause of morbidity and mortality in this patient population. This review will focus and provide updates on pathophysiology, assessment of kidney function, new definitions, and treatment and prevention of HRS. Recent findings Pathophysiology of HRS has been elucidated more recently and in addition to hemodynamic changes, the role of systemic inflammatory response contributes significantly to this process. Assessment of kidney function in patients with liver cirrhosis remains challenging. Novel glomerular filtration rate equations have been developed in patients with liver disease to better estimate kidney function and changes made in the definition of acute kidney injury (AKI), which are more aligned with KDIGO criteria for AKI. Vasoconstrictors, especially terlipressin, along with albumin remain the mainstay of pharmacological treatment of HRS-AKI. Biomarkers have been useful in differentiating ATN from HRS at an early stage. Summary HRS remains a significant cause of morbidity and mortality for patients with end-stage liver disease. Newer understanding of mechanisms in development and pathophysiology of HRS have helped with elucidation of the disease process.

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

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).

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a serious complication of severe liver disease with a clinically poor prognosis. Supportive care using vasoconstrictors and intravenous albumin are the current mainstays of therapy. Terlipressin is an efficacious vasoconstrictor that has been used for 2 decades as the first-line treatment for HRS-AKI in Europe and has demonstrated greater efficacy in improving renal function compared to placebo and other vasoconstrictors. One of the challenges associated with terlipressin use is monitoring and mitigating serious adverse events, specifically adverse respiratory events, which were noted in a subset of patients in the recently published CONFIRM trial, the largest randomized trial examining terlipressin use for HRS-AKI. In this article, we review terlipressin's pharmacology, hypothesize how its mechanism contributes to the risk of respiratory compromise and propose strategies that will decrease the frequency of these events by rationally selecting patients at lower risk for these events.

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.

BACKGROUND Acute-on-chronic liver failure (ACLF) patients have a high short-term mortality rate, and the severity evaluation of ACLF is necessary for prognostication. Therefore, it was meaningful to evaluate the association between type 2 diabetic mellitus (DM) and ACLF and further explore the feasibility of using DM as a prognostic indicator in ACLF patients. The association between type 2 DM and the prognosis of patients with severe liver disease remains unclear. AIM To examine the effect of type 2 DM on the prognosis of patients with ACLF. METHODS Clinical data from 222 ACLF patients were collected and analyzed. The patients were categorized into two groups depending on whether they had DM or not, and the clinical data of ACLF patients were measured within 48 h after admission. Complications of ACLF were documented during treatment, such as hepatic encephalopathy, hepatorenal syndrome, acute upper gastrointestinal hemorrhage, and spontaneous peritonitis (SBP). Values of laboratory parameters, complication rates, and hospital mortality rates were compared between two groups. RESULTS Among 222 ACLF patients, 38 cases were categorized into DM groups, the mean age was 56.32 years and 73.68% were male. The prognosis of ACLF patients was significantly correlated with DM in univariate [hazard ratio (HR) = 2.4, 95% confidence interval (CI) =1.5-3.7, P < 0.001] and multivariable analysis (HR = 3.17, 95%CI =1.82-5.523, P < 0.001). The incident of SBP (34.21% vs 13.59%, P = 0.038) and other infections like lung, urinary, blood, and cholecyst (44.74% vs 28.26%, P = 0.046) were higher in DM patients than non-DM counterparts. In addition, the ACLF patients with DM tended to have a high mortality rate (P < 0.001). Cumulative survival time was also significantly shorter in the ACLF patients with DM than non-DM. CONCLUSION A significant association between DM and the prognosis of ACLF patients was found in China. The ACLF patients with DM had higher incidence of hospital mortality and infection than those without DM.

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.

Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, in the setting of organ system failures. Given this prognosis, there is an urgent need to understand risk factors for this condition, for appropriate medical management of organ failures, and for selection criteria for patients who may benefit from liver transplantation (LT). Although several definitions exist to identify ACLF, all of them are designed to identify patients with uniquely high mortality. Currently, management of severe ACLF relies on best supportive care for specific organ failures. Thromboelastography should guide the evaluation of coagulation pathways and hyperfibrinolysis in ACLF; prophylactic blood product transfusions and thrombopoetin agonists are not recommended. Combination therapy with terlipressin and albumin has been shown to be efficacious in the management of the hepatorenal syndrome but should be administered with caution in patients with ACLF-3. Recent data have characterized the role of beta-blockers and transjugular intrahepatic portosystemic shunt placement in the management of ACLF. Investigational therapies such as extracorporeal liver support and hepatocyte stem cell therapies have shown promise; larger scale studies may better define the subpopulations of patients with ACLF mostly likely to benefit from these evolving therapeutics. Regarding LT in ACLF, data suggest that even patients with 3 or more organ system failures may have a 1-year survival >80%. However, further efforts are needed to understand the predictors of post-LT survival to facilitate LT criteria for this condition.

BACKGROUND AND AIMS Patients with decompensated cirrhosis are prescribed numerous medications. Data are limited as to whether patients are receiving medications they need and avoiding those they do not. We examined a large national claims database (2010-2015) to characterize the complete medication profile as well as the factors associated with appropriate and potentially inappropriate medication use in 12,621 patients with decompensated cirrhosis. APPROACH AND RESULTS Clinical guidelines and existing literature were used to determine appropriate and potentially inappropriate medications in decompensated cirrhosis. The total medication days' supply was calculated from pharmacy data and divided by the follow-up period for each decompensation. Ascites was the most common (86.5%), followed by hepatic encephalopathy (HE; 37.8%), variceal bleeding (VB; 17.5%), hepatorenal syndrome (6.3%), and spontaneous bacterial peritonitis (SBP; 6.1%). For patients with ascites, 55.8% filled a diuretic. For patients with HE, 32.4% and 63.3% filled rifaximin and lactulose, respectively. After VB, 60.3% of patients filled a nonselective beta blocker, and after an episode of SBP, 48.0% of patients filled an antibiotic for prophylaxis. The minority (4.5%-17.3%) had enough medication to cover >50% follow-up days. Potentially inappropriate medication use was common: 53.2% filled an opiate, 46.0% proton pump inhibitors, 14.2% benzodiazepines, and 10.1% nonsteroidal anti-inflammatory drugs. Disease severity markers were associated with more appropriate mediation use but not consistently associated with less inappropriate medication use. CONCLUSIONS Patients with decompensated cirrhosis are not filling indicated medications as often or as long as is recommended and are also filling medications that are potentially harmful. Future steps include integrating pharmacy records with medical records to obtain a complete medication list and counseling on medication use with patients at each visit.

Calciphylaxis is a rare disease characterized by calcification of small- to medium-sized blood vessels in the dermis and subcutaneous fat, resulting in cutaneous necrosis. Although most commonly shown in patients with end-stage kidney disease, it has also been reported in patients with other diseases, including alcoholic cirrhosis and malignancies. Here, we report an unusual case of calciphylaxis in an orthotopic liver transplant recipient with acute kidney injury. The patient, a 43-year-old white female with a history of type 2 diabetes mellitus, alcoholic cirrhosis, and normal kidney function, presented with decompensated liver disease and hepatorenal syndrome; she no longer responded to medical treatment and required treatment with dialysis. Ten days after admission, she underwent liver transplant, resulting in improved liver function tests. She had acute tubular necrosis (creatinine peak: 325 μmol/L) from sustained hypotension during and after surgery, which required 4 sessions of dialysis over 2weeks. Six weeks after her transplant, she developed painful, nonulcerating, erythematous plaques over her shins and thighs. Skin biopsy of the lesions showed calciphylaxis, calcium deposits, and thrombotic vasculopathy. She also developed severe hypercalcemia (calcium level of 2.75 mmol/L) from immobility, which required treatment with a bisphosphonate and hemodialysis. The lesions improved 6 weeks later, and her renal function returned to normal. Calciphylaxis diagnosed in an orthotopic liver transplant recipient with acute kidney injury has not been previously reported. We hypothesize that her chronic inflammatory state caused down-regulation and low levels of fetuin A and protein C. She also had other risk factors, including hypoalbuminemia, obesity, systemic glucocorticoids, and alcoholic liver disease. Calciphylaxis can occur in patients with alcoholic cirrhosis and acute renal failure even after liver transplant. Further studies into the pathogenesis of this disease may help us understand why it develops in these patients and not others with the same risk factors.

OBJECTIVES Ascites is a pathologic buildup of fluid in the peritoneal cavity. Knowledge is lacking in clinical outcome in pediatric patients with ascites. We aim to identify and assess clinical variables, associated with morbidity and mortality in pediatric patients who are hospitalized with ascites. METHODS A retrospective cohort study was performed on patients ages 0 to 21 hospitalized at Johns Hopkins Hospital between 1983 and 2010 with an ICD-9 discharge diagnosis of ascites (789.5, 789.51, 789.59). A total of 518 pediatric patients were studied, all with a diagnosis of ascites during hospitalization. Study outcomes included hospital length of stay (LOS) as a proxy for morbidity and death at hospital discharge for mortality. Variables analyzed included demographic data, ascites etiology and grade, comorbidities, and laboratory markers. Variables were analyzed by log-linear regression and competing risk model. RESULTS Among the 3 age groups (0-5, 6-12, and 13-21), the 0 to 5 age group experienced significantly increased LOS (P

Background Encapsulating peritoneal sclerosis (EPS) is a rare condition in which the small intestine is covered by an inflammatory fibrocollagenous membrane; the exact etiology of EPS is unclear. Herein, we report the case of our patient who underwent hemodialysis and cell-free and concentrated ascites reinfusion therapy (CART) and was diagnosed with EPS. Case presentation A 64-year-old Japanese man visited our emergency department with a chief complaint of abdominal pain. He had a medical history of cirrhosis due to hepatitis C for 25 years. He had undergone partial resection of the small intestine 2 years earlier for an incarcerated hernia. One year earlier, he experienced renal failure due to hepatorenal syndrome and started hemodialysis three times a week and CART twice a month. Physical examination of the abdominal wall revealed a lack of peristalsis of the intestinal tract and strong tenderness on palpation. Because hernia of the small intestine was found on computed tomography, we suspected strangulation ileus, requiring emergency operation. When the abdomen was opened, the entire small intestine was found to be wrapped in a fibrous membrane and constricted by it. The patient was diagnosed with EPS; hence, during surgery, the fibrous membrane was excised, resulting in decompression of the intestinal tract and subsequent recovery. Conclusions EPS is thought to be related to various elements, but no case of EPS induced by CART has been reported to date. EPS should be considered in the differential diagnosis of small bowel obstruction in patients undergoing CART for refractory ascites.

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens clinical outcomes in patients with chronic liver diseases. It is a common complication in hospitalised patients with liver cirrhosis, especially those with decompensated cirrhosis, associated with a high mortality rate. Considering its impact on patient prognosis, efforts should be made to diagnose and tailor therapeutic interventions for AKI at an early stage. In the past decade, a significant progress has been made to understand the key events and define major prognostic factors for the onset and progression of AKI in the cirrhotic population leading hepatologists to redefine the classic definition of hepatorenal syndrome and renal failure in this specific population.

Liver failure has attracted attention in clinical work due to its high mortality, and the development of liver transplantation is restricted by various factors. Therefore, it is very important to carry out research on the mechanism of liver cell regeneration. This article has studied in depth the preparation of MED1 gene nanocarriers, collected human plasmids and cells through experimental materials and experimental instruments, and conducted comparative research on conventional culture. This question conducts a regeneration experiment on liver cells in chronic-onset acute liver failure, divides patients into an experimental group and a control group, and understands the recovery of liver function according to the screening of their plasma samples and separation of plasma. This article selects the commonly used clinical biological markers, such as Na+, AFP, Alb, CHE (serum cholinesterase) and other indicators to reflect the regeneration ability of liver function. The incidence of surgical complications in the control group, such as ascites, infection, bleeding, HE, hepatorenal syndrome, and hyponatremia were 71.3%, 87.4%, 16.1%, 41.4%, 19.5%, and 33.3%, respectively. Significantly higher than the experimental group, the difference was statistically significant (P 0.05)., Graphical Abstract

Background Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. Objective: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. Methods: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. Results: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. Conclusion: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment. RESUMO Contexto: A Síndrome Hepatorrenal (SHR) é a forma mais grave de lesão renal aguda em pacientes com cirrose avançada, estando diretamente associada a alta taxa de mortalidade. Normalmente é diagnosticada seguindo critérios definidos pela International Ascites Club (IAC). Atualmente, as terapias farmacológicas mais indicadas no tratamento da SHR são a combinação de vasoconstritores esplâncnicos (terlipressina ou norepinefrina) associados à albumina. Com o aumento progressivo dos gastos em saúde, torna-se relevante realizar uma análise de custo-efetividade do tratamento farmacológico em pacientes com diagnóstico de SHR. Objetivo: Realizar avaliação de custo-efetividade do uso da terlipressina associada à albumina no tratamento da SHR em pacientes com cirrose. Métodos: Avaliação econômica de custo-efetividade, com base em dados secundários de estudos publicados com resultado da eficácia da terapia com terlipressina, em comparação com norepinefrina combinada com albumina ou apenas albumina. A análise de custo-efetividade foi calculada usando a razão de custo-efetividade incremental (RCEI) e uma análise de sensibilidade foi desenvolvida variando os valores das terapias e probabilidades. O real foi a moeda utilizada na análise. Resultados: Após a seleção, elegibilidade e avaliação da qualidade das publicações, os resultados demonstraram que a administração da associação de terlipressina ou norepinefrina com albumina em pacientes diagnosticados com SHR tipo 1 possui eficácia comprovada. Os custos do tratamento com a terapia combinada de terlipressina com albumina foram de USD $1,644.06, administração de somente albumina USD $912.02 e norepinefrina mais albumina USD $2,310.78. Considerando as terapias combinadas com efetividade terapêutica comprovada, isto é, terlipressina e norepinefrina associada a albumina, o custo incremental foi de USD $666.73 e efetividade de 0,570 para o grupo da terlipressina associada a albumina e de 0,200 para o grupo da norepinefrina associada a albumina. A efetividade incremental foi de 0,370 e o valor da RCEI foi de USD $1,801.97. Assim, os fatores de incremento do custo por terapia e razão de custo-efetividade incremental definem que a terapia combinada de terlipressina mais albumina é custo efetiva quando comparada a administração de somente albumina ou norepinefrina no cenário do sistema único de saúde. Conclusão: O estudo demonstrou por meio de uma análise de custo-efetividade que a terlipressina associada à albumina quando administrada concomitantemente a pacientes com diagnóstico de SHR tipo 1 é custo-efetiva quando comparada à albumina sozinha e com norepinefrina associada à albumina administrada em um ambiente controlado.

This report describes a case of Autoimmune Hemolytic Anemia that was possibly induced by COVID-19 in a patient with history of Chronic Liver Disease and Diabetes Mellitus. Autoimmune responses like hemolytic anemia are known to be triggered by viral infections. COVID-19 is reported to be inducing Autoimmune Hemolytic Anemia in susceptible individuals. This is a case report of a 65 year old male with history of chronic alcoholism, who tested positive for COVID-19 infection which was treated as per protocols and was uncomplicated at the time of discharge. After about three months he presented with complaints of breathlessness which on laboratory evaluation revealed Direct Coombs test positive hemolytic anemia. Anemia improved with blood transfusion and steroid administration but patient eventually developed hepatorenal syndrome and expired.

When timely access to deceased-donor livers is not feasible, living-donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single-center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non-HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post-LT renal recovery. The HRS group had a higher death rate than the non-HRS group (17.5% vs. 8.6%, p 0.001). In the HRS group, post-LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non-recovery (5.7% vs. 43.6%, p 0.001). Multivariable analysis indicated that post-LT sepsis (p 0.001) and non-recovery of HRS (p 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre-LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post-LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post-LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post-LT renal recovery.

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.

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.

Background Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). Objective: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. Methods The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. Results: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). Conclusion: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease. RESUMO Contexto O impacto da doença é um indicador relacionado ao estado de saúde. Dados epidemiológicos norte-americanos e europeus mostraram que, nas últimas décadas, o impacto da doença hepática crônica tem aumentado significativamente. Não há estudos que avaliem o impacto das descompensações da doença hepática crônica na lista de espera para transplante hepático (TxH) com doador falecido. Objetivo: Determinar o impacto clínico e econômico das descompensações da doença hepática nos pacientes em lista de espera sob a perspectiva do centro transplantador. Métodos Foram analisados, retrospectivamente, os prontuários de 104 pacientes incluídos em lista de espera para TxH com doador falecido entre outubro de 2012 e maio de 2016 e acompanhados integralmente no centro transplantador. Dados clínicos foram obtidos do prontuário eletrônico, enquanto dados econômicos foram coletados através de software de gestão hospitalar. A apropriação dos custos médicos diretos foi realizada sob duas metodologias: custeio por absorção pleno e microcusteio. Resultados: A descompensação com maior incidência foi a ascite refratária (20,2%) seguida de encefalopatia portossistêmica (12,5%). A média de internações por paciente foi de 1,37±3,42. A hemorragia digestiva alta varicosa foi a descompensação com maior tempo mediano de internação (18 dias), seguida da síndrome hepatorrenal (13,5 dias). A descompensação mais onerosa foi a síndrome hepatorrenal (custo médio de US$ 3.565), seguida encefalopatia portossistêmica (US$ 2.576) e a hemorragia digestiva alta varicosa (US$ 1.530). Conclusão O impacto da doença hepática crônica inclui um custo importante para os sistemas de saúde. Além disso, é provável que seja ainda maior em decorrência do curso insidioso da doença.