Cervera, Marta

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

AbstractWhether 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.

Abstract Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non‐alcoholic fatty liver disease and alcohol‐related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at‐risk populations. Thus far, a limited number of population‐based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%‐in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

OBJECTIVES: Hepatic encephalopathy (HE) is common in advanced cirrhosis and is characterized by marked neuropsychiatric abnormalities. However, despite its severity and effects on brain function, the impact of HE on psychological status of patients has not been adequately assessed. The aim of this study was to evaluate the effect of HE on psychological status of patients and their informal caregivers. METHODS: Fifteen patients with cirrhosis and episodic or persistent HE and their corresponding informal caregivers were included. Semistructured interviews were performed in patients and caregivers. Quality of life (QoL) was assessed by the short-form 36 in both patients and caregivers, and the Zarit burden score was measured in caregivers. The analysis of interviews was performed using qualitative methodology. RESULTS: HE causes a major psychological impact on patients with HE. The first episode of HE caused a very significant impact that was reported with deep feelings, mainly of fear, anger, misery, anxiety, and sorrow, which persisted with time. Symptoms causing more psychological impact on patients were impaired ability to walk and speak. All effects were associated with a marked impairment in QoL. The psychological impact was also marked in caregivers who had a major burden, as assessed by the Zarit score. Moreover, QoL, particularly the mental component score, was markedly impaired in caregivers in intensity similar to that of patients. DISCUSSION: HE has a profound psychological impact on patients and their informal caregivers, associated with a marked negative influence on QoL. The psychological effects of HE on patients and caregivers should be evaluated and treated.

Cirrhosis is a complex disease that is associated with disturbances in different organs besides the liver, including kidneys, heart, arterial circulation, lungs, gut, and brain. As a consequence, patients develop a number of complications that result in frequent hospital admissions and high morbidity and mortality. Patients with cirrhosis require constant and rigorous monitoring both in and outside the hospital. In this context, the role of nurses in the care of patients with cirrhosis has not been sufficiently emphasized and there is very limited information about nursing care of patients with cirrhosis compared with other chronic diseases. The current article provides a review of nursing care for the different complications of patients with cirrhosis. Nurses with specific knowledge on liver diseases should be incorporated into multidisciplinary teams managing patients with cirrhosis, both inpatient and outpatient. Conclusion: Nurses play an important role in the management and prevention of complications of the disease and improvement in patients’ quality of life and bridge the gap between clinicians and families, between primary care and hospital care, and provide medical education to patients and caregivers.