The Difference of Urinary Neutrophil Gelatinase-Associated Lipocalin Level between Liver Cirrhosis Patients with and without Hepatorenal Syndrome

Objective: To determine differences of urinary Neutrophil Gelatinase-Associated Lipocalin level in liver cirrhosis patients with or without Hepatorenal Syndrome (HRS). Methods: This study was conducted on 46 liver cirrhosis patients (20 patients without hepatorenal syndrome, 26 patients with hepatorenal syndrome). Diagnosis of HRS was based on International Ascites Club criteria. Urinary NGAL was examined using ELISA method. Data analysis was performed with p<0,05 stated as statistically significant. Result: This study showed more HRS cases was found in male than female, with an average age of 53,95 years old for hepatic cirrhosis without HRS, and 57,35 with HRS. The most common cause of this study is Hepatitis B virus, and the highest grade of severity is in Child Pugh-C. The average urinary NGAL level in liver cirrhosis with HRS is 59,39 ± 58,98 ng/ml and 130,78 ± 45,14 ng/ml in liver cirrhosis without HRS. Conclusion: There was a significant higher urinary NGAL level in liver cirrhosis with HRS (p = 0.000), with the cut-off of urinary NGAL to differentiate cirrhosis patients with and without HRS was 95,115 ng/ml. Keywords: NGAL, HRS, hepatorenal syndrome, neutrophil gelatinase-associated lipocalin.

Predictors of the development of hepatorenal syndrome

Objective. To identify the predictors of the development of hepatorenal syndrome in patients with liver cirrhosis.Materials and methods. We analyzed the medical records of 79 patients diagnosed with liver cirrhosis. The laboratory research included general and biochemical blood tests. The general blood test measured erythrocyte and leukocyte counts. The biochemical blood test measured the content of ALT (U/L), AST (E/L), total bilirubin (μmol/L), direct bilirubin (μmol/L), indirect bilirubin (μmol/L), alkaline phosphatase (U/L), albumin (g/L), urea (mmol/L), creatinine (mmol/L), cholesterol (mmol/L).Viral hepatitis markers were determined for all the patients.Results. The predictors of the development of hepatorenal syndrome were identified: increased leukocyte count, increased total and indirect bilirubin levels, urea level and decreased erythrocyte count and albumin level. The most specific predictors were the amount of indirect bilirubin (98 %) and the content of albumin in the serum (89.8 %), and the most sensitive predictors were AST (96.7 %) and the content of red blood cells and creatinine (73.3 %).Conclusion. The most significant predictors of the development obtained will contribute to the diagnosis of the development of hepatorenal syndrome in patients with liver cirrhosis.

Safety And Efficacy of Terlipressin In Acute-On-Chronic Liver Failure With Acute Kidney Injury – A Prospective Cohort Study

Background: Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF.Methods: We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying either EASL or APASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, and differential treatment response in EASL and APASL subgroups. Results: Of the 116 patients, 51 satisfied EASL criteria, and 65 satisfied APASL criteria. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. Response to terlipressin was higher in EASL (78.43%) than APASL subgroup (53.84%;P=0.006). Terlipressin non-response predicted mortality in EASL (aHR,6.35[1.15-35.13];P=0.03) and APASL subgroups (aHR,3.07[1.47-6.4];P=0.003).Conclusion: ACLF patients who develop terlipressin adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

EFFICIENCY OF NORFLOXACIN IN THE PROPHYLAXIS OF HEPATORENAL SYNDROME

Purpose - to evaluate norfloxacin efficacy for the prevention of hepatorenal syndrome(HRS) development in patients with alcoholic liver cirrhosis and concomitant chronicpyelonephritis.Material and methods. In all, 157 patients, divided into two groups depending on themethod of HRS prevention, were examined: group 1 (n = 78) - received placebo; group 2(n = 79) - received norfloxacin. The main endpoint of the study was short-term survival.The probability curves were constructed using the Kaplan – Mayer method.Results. The rate of renal failure was much lower in group 2 (7 vs. 16 patients, p = 0.03).HRS was associated with bacterial infection in 4 patients of group 2 and in 6 patients ofgroup 1. HRS developed during the first 3 months of the follow-up period in 9 patientsin group 1 and only 1 patient in group 2 (p = 0.006). The incidence of HRS developmentduring the first 14 days was significantly lower in group 2. In all, 10 patients died ingroup 2 and 13 in group 1. The main cause of death in both groups was HRS (5 and8 patients, respectively). Mortality during the first 3 months was significantly higherin group 1 (10 vs. 2 patients, p = 0.02). Three-month (group 2 - 94%, group 1 - 62%)and annual survival (60% vs. 48%, respectively, p = 0.05) were significantly higher ingroup 2.Conclusions. Peroral antibiotic prophylaxis with norfloxacin almost 5 times reduces therisk of hepatorenal syndrome development type 1 in patients with alcoholic liver cirrhosisand concomitant chronic pyelonephritis, and increases their short-term survival.

Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacotherapy

Hepatorenal syndrome type 1 (HRS-1) is a serious form of acute kidney injury (AKI) that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. While the diagnostic criteria dictated by the International Club of Ascites (ICA) provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury (ATI) is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of ATI, distinguishing these 2 causes of AKI has direct implications in management. Therefore, the use if the ICA criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1 but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacological therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors and their use should be determined by availability, ease of administration and attention to optimal risk/benefit balance for each clinical scenario.

Predictors of Development of Hepatorenal Syndrome in Hospitalized Cirrhotic Patients with Acute Kidney Injury

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.

CHRONIC PYELONEPHRITIS AS A PRECIPITATING FACTOR OF HEPATORENAL SYNDROME IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS

Introduction. Most attempts to assess renal failure in alcoholic liver cirrhosis have so far focused on acute kidney injury and on the hepatorenal syndrome in particular. However, there are still limited data on the prevalence and clinical impact of chronic kidney disease in cirrhosis. Objectives. This study aimed to assess the influence of chronic pyelonephritis on the incidence of hepatorenal syndrome in patients with alcoholic liver cirrhosis. Material and methods. 165 patients with decompensated alcoholic liver cirrhosis and concomitant chronic pyelonephritis were enrolled in the study. They were divided into two groups according to the presence or absence of chronic pyelonephritis: group 1 had alcoholic liver cirrhosis only (n=82), group 2 had alcoholic liver cirrhosis + chronic pyelonephritis (n=83). Results. The general bacterial infections were more common in group 1 patients. The spectrum of the most frequent bacterial complications in the examined patients typical for alcoholic liver cirrhosis was as follows: the share of urinary tract infection made up 16.0% (95% confidence interval 14.4-27.9), pneumonia constituted 16.7% (95% confidence interval 10.5-22.7, bacteremia made up 4.0% (95% confidence interval 7.7-38.6), the share of skin infections (erysipelas) was 2.7% (95% confidence interval 0.7-6.6). Other infections including pulmonary tuberculosis, lung abscess, right leg abscess, osteomyelitis, bedsores, were less common (6.7%). Spontaneous bacterial peritonitis, taking into account all options, was found in 6 cases (10.5%, 95% confidence interval 4.0-21.5). As expected, the incidence of hepatorenal syndrome within 14 days of inpatient onset was almost twice higher in group 2 – 22 cases (27%), than in group2 – 13 cases (16%). The group 2 demonstrated a more severe course of alcoholic liver cirrhosis on the Child-Pugh scale compared with group I (class B - 29.9%; class C - 70.1% against class B - 46.4%; class C - 53, 6% ); the differences were statistically significant (χ2 = 4.30, p = 0.038). In patients of group 2, the lethal outcome in the hospital occurred in 6 (8.9%) cases. Conclusions: The results of the present study confirm the role of chronic pyelonephritis as one of the major precipitating factors of hepatorenal syndrome incidence in patients with alcoholic liver cirrhosis. This fact should be considered when making the treatment plan for these patients.