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.

Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial

Background Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood. Methods This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated. Results During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group. Conclusions Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease. Graphic abstract

Prescription rates of common medications in patients with decompensated cirrhosis in Germany

Background Adequate pharmacological treatment is of pivotal importance to improve prognosis in patients with decompensated liver cirrhosis. We studied the adherence to recommended pharmacological treatments as secondary prevention in cirrhotic patients following a first decompensation in German primary care. Methods Using the Disease Analyzer Database, the current study sample included patients with liver cirrhosis who had an initial diagnosis of a first decompensation event between 2015 and 2018 (index date) and a follow-up time of at least 6 months after the index date. Pharmacological treatments following the 6 months after the index date were studied. Results The study included 1538 patients with a first decompensation event. The frequency of first-time complications of cirrhosis was 60% new onset of ascites, 25% overt hepatic encephalopathy (HE), 3% spontaneous bacterial peritonitis (SBP), and 12% acute variceal bleeding. The adherence to guideline-recommended treatment following the initial decompensation was highest for ascites, with 91.3% of patients receiving diuretics. Non-selective beta-blockers following an event of variceal bleeding were prescribed in 69.1% and lactulose and/or rifaximin in 59.1% after a bout of HE. The frequency of prescriptions of antibiotics after SBP was 60.4%. Potenzially harmful prescribed medications included non-steroidal anti-inflammatory drugs in 15.5%, benzodiazepines in 12.8%, opioids in 9.5%, and proton pump inhibitors in 73.7%. Conclusion Our findings underline the need for intensified efforts to distribute practice guidelines for liver cirrhosis and increase awareness of over-prescribing of potentially harmful medication.

Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts

Mitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutations in the nuclear or mitochondrial genome) manifest through a remarkable clinical variation of symptoms in affected individuals underlines the far-reaching implications of mitochondrial dysfunction. The study of mitochondrial function in genetic or non-genetic diseases therefore requires a multi-angled approach. Taking into account that the liver is among the organs richest in mitochondria, it stands to reason that in the process of unravelling the pathogenesis of liver-related diseases, researchers give special focus to characterizing mitochondrial function. However, mitochondrial dysfunction is not a uniformly defined term. It can refer to a decline in energy production, increase in reactive oxygen species and so forth. Therefore, any study on mitochondrial dysfunction first needs to define the dysfunction to be investigated. Here, we review the alterations of mitochondrial function in liver cirrhosis with emphasis on acutely decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF), the latter being a form of acute decompensation characterized by a generalized state of systemic hyperinflammation/immunosuppression and high mortality rate. The studies that we discuss were either carried out in liver tissue itself of these patients, or in circulating leukocytes, whose mitochondrial alterations might reflect tissue and organ mitochondrial dysfunction. In addition, we present different methodological approaches that can be of utility to address the diverse aspects of hepatocyte and leukocyte mitochondrial function in liver disease. They include assays to measure metabolic fluxes using the comparatively novel Biolog’s MitoPlates in a 96-well format as well as assessment of mitochondrial respiration by high-resolution respirometry using Oroboros’ O2k-technology and Agilent Seahorse XF technology.

Sex Specific Differences in Nosocomial Infections in Patients with Decompensated Liver Cirrhosis

Background and aims: There are considerable differences between males and females regarding the etiology, progression and outcome of liver diseases. Infections are a frequent and severe complication in these patients. This study aimed to examine sex specific differences in the incidence and clinical course of nosocomial infections in patients with decompensated liver cirrhosis.Methods: A number of 555 consecutive patients with decompensated liver cirrhosis and ascites were analyzed. The patients were followed up for the incidence of nosocomial infections, acute kidney injury (AKI), acute-on-chronic liver failure (ACLF) as well as liver transplantation and death (LTx-free survival). Results: A number of 285 patients (111 women and 174 men) developed a nosocomial infection. Incidence was numerically lower in men (p=0.076). While the frequency of a nosocomial spontaneous bacterial peritonitis was similar between males and females, the incidence of a nosocomial urinary tract infection was significantly higher in women (p<0.001). No sex specific differences were documented regarding the outcome of an infection as indicated by a similar incidence of, AKI, ACLF as well as LTx-free survival.Conclusion: There seem to be no major differences in the incidence and outcome of nosocomial infections between male and female patients.