Managing multiorgan failure in Acute on chronic liver failure (ACLF).

Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grade 2-3 as a potentially life-saving treatment. When transplant is not indicated, palliative care should be considered after 3-7 days of full organ support in patients with at least 4 organ failures or a CLIF-C ACLF score >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.

Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial.

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

Psychometric properties of the Quiet Ego Scale (iQES) within the Italian cultural context.

Introduction: The quiet ego indicates a more compassionate conception of self-identity that integrates others into the self by lowering the intensity of the ego and enhancing the awareness of the present moment. The Quiet Ego Scale (QES) is a 14-item self-report measure of quiet ego, and it is composed of the following four psychological domains: detached awareness, inclusive identity, perspective taking, and growth. The present study aimed to test the psychometric properties of the Quiet Ego Scale within the Italian cultural context (iQES). Methods: A total of 160 Italian university students aged between 20 and 42 years, with a mean age of 22.85 years (SD = 3.41), completed the measures of the iQES and of other psychological dimensions. The psychometrics properties of iQES were assessed based on its internal consistency, test-retest reliability, and construct validity through comparisons with other correlated psychological measures. Results: Analyses confirmed the psychometrics properties of iQES. As in previous studies, the quiet ego was positively associated with the indicators of resilience (p < 0.01), happiness (p < 0.05), self-esteem (p < 0.01), and psychological wellbeing (p < 0.01). Discussion: The study discussed the possible uses of the iQES in the field of mental health, specifically focusing on improving adherence to psychological therapies and enhancing psychological and social well-being. The results indicated strong psychometric properties of the iQES in measuring the quiet ego construct. Our findings enrich the literature on the validity of the iQES and highlight the multidimensional nature of the quiet ego construct.

The Role of Transjugular Intrahepatic Portosystemic Shunt for the Management of Ascites in Patients with Decompensated Cirrhosis.

The development and progression of ascites represent a crucial event in the natural history of patients with cirrhosis, predisposing them to other complications and carrying a heavy impact on prognosis. The current standard of care for the management of ascites relies on various combinations of diuretics and large-volume paracenteses. Periodic long-term albumin infusions on top of diuretics have been recently shown to greatly facilitate the management of ascites. The insertion of a transjugular intrahepatic portosystemic shunt (TIPS), an artificial connection between the portal and caval systems, is indicated to treat patients with refractory ascites. TIPS acts to decrease portal hypertension, thus targeting an upstream event in the pathophysiological cascade of cirrhosis decompensation. Available evidence shows a significant benefit on ascites control/resolution, with less clear results on patient survival. Patient selection plays a crucial role in obtaining better clinical responses and avoiding TIPS-related adverse events, the most important of which are hepatic encephalopathy, cardiac overload and failure, and liver failure. At the same time, some recent technical evolutions of available stents appear promising but deserve further investigations. Future challenges and perspectives include (i) identifying the features for selecting the ideal candidate to TIPS; (ii) recognizing the better timing for TIPS placement; and (iii) understanding the most appropriate role of TIPS within the framework of all other available treatments for the management of patients with decompensated cirrhosis.

Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis.

BACKGROUND & AIMS: The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. METHODS: We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. RESULTS: A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. CONCLUSIONS: The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. IMPACT AND IMPLICATIONS: The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.

Association between Albumin Alterations and Renal Function in Patients with Type 2 Diabetes Mellitus.

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.

Predictors of clinical trajectories of patients with acutely decompensated cirrhosis. An external validation of the PREDICT study.

BACKGROUND AND AIMS: The PREDICT study recently showed that acutely decompensated (AD) patients with cirrhosis can present three different clinical phenotypes in the 90 days after admission: (1) pre-ACLF, developing acute-on-chronic liver failure (ACLF); (2) unstable decompensated cirrhosis (UDC), being re-admitted for AD without ACLF and (3) stable decompensated cirrhosis (SDC), not presenting readmission or ACLF. This study aimed to externally validate the existence of these three distinct trajectories and to identify predictors for the occurrence of each trajectory. METHODS: Baseline data, 3-month ACLF and readmission incidence and 1-year survival were analysed in a prospective cohort of patients admitted for AD. A multinomial multivariable model was used to evaluate the association between baseline features and clinical trajectories. RESULTS: Of the 311 patients enrolled, 55% met the criteria for SDC, 18% for UDC and 27% for pre-ACLF, presenting a significantly different 1-year mortality: pre-ACLF 65%, UDC 46%, SDC 21% (p < .001). The presence of hepatic encephalopathy (HE) was associated with UDC (p = .043), while the absence of ascites to SDC (p = .017). Among laboratory parameters, an increase in MELD-Na (p = .001) and C-reactive protein (p = .009) and a decrease in haemoglobin (p = .004) and albumin (p = .008) levels were associated with pre-ACLF. CONCLUSION: The present study confirms that AD patients have three different clinical trajectories with different mortality rates. Besides the severity of cirrhosis, the association with C-reactive protein supports the predominant role of systemic inflammation in ACLF pathophysiology. Finally, HE is associated with the UDC phenotype highlighting the need for better management of this complication after discharge.

Development and internal validation of a multivariable model for the prediction of the probability of 1-year readmission to the emergency department for acute alcohol intoxication.

To develop and internally validate a multivariable logistic regression model (LRM) for the prediction of the probability of 1-year readmission to the emergency department (ED) in patients with acute alcohol intoxication (AAI). We developed and internally validated the LRM on a previously analyzed retrospective cohort of 3304 patients with AAI admitted to the ED of the Sant'Orsola-Malpighi Hospital (Bologna, Italy). The benchmark LRM employed readmission to the same ED for AAI within 1 year as the binary outcome, age as a continuous predictor, and sex, alcohol use disorder, substance use disorder, at least one previous admission for trauma, mental or behavioral disease, and homelessness as the binary predictors. Optimism correction was performed using the bootstrap on 1000 samples without replacement. The benchmark LRM was gradually simplified to get the most parsimonious LRM with similar optimism-corrected overall fit, discrimination and calibration. The 1-year readmission rate was 15.7% (95% CI 14.4-16.9%). A reduced LRM based on sex, age, at least one previous admission for trauma, mental or behavioral disease, and homelessness, performed nearly as well as the benchmark LRM. The reduced LRM had the following optimism-corrected metrics: scaled Brier score 17.0%, C-statistic 0.799 (95% CI 0.778 to 0.821), calibration in the large 0.000 (95% CI - 0.099 to 0.099), calibration slope 0.985 (95% CI 0.893 to 1.088), and an acceptably accurate calibration plot. An LRM based on sex, age, at least one previous admission for trauma, mental or behavioral disease, and homelessness can be used to estimate the probability of 1-year readmission to ED for AAI. To begin proving its clinical utility, this LRM should be validated in external cohorts.

Albumin administration in internal medicine: A journey between effectiveness and futility.

Albumin is the most abundant circulating protein and provides about 70% of the plasma oncotic power. The molecule also carries many other biological functions (binding, transport and detoxification of endogenous and exogenous compounds, antioxidation, and modulation of inflammatory and immune responses). Hypoalbuminemia is a frequent finding in many diseases, representing usually only a biomarker of poor prognosis rather than a primary pathophysiological event. Despite that, albumin is prescribed in many conditions based on the assumption that correction of hypoalbuminemia would lead to clinical benefits for the patients. Unfortunately, many of these indications are not supported by scientific evidence (or have been even disproved), so that a large part of albumin use is nowadays still inappropriate. Decompensated cirrhosis is the clinical area where albumin administration has been extensively studied and solid recommendations can be made. Besides prevention and treatment of acute complications, long-term albumin administration in patients with ascites has emerged in the last decade has a potential new disease-modifying treatment. In non-hepatological settings, albumin is widely used for fluid resuscitation in sepsis and critical illnesses, with no clear superiority over crystalloids. In many other conditions, scientific evidence supporting albumin prescription is weak or even absent. Thus, given its high cost and limited availability, action is needed to avoid the use of albumin for inappropriate and futile indications to ensure its availability in those conditions for which albumin has been demonstrated to have a real effectiveness and an advantage for the patient.

Low haemoglobin level predicts early hospital readmission in patients with cirrhosis and acute decompensation.

Background & Aims: Patients with decompensated cirrhosis present frequent hospitalisations with a relevant clinical and socio-economic impact. This study aims to characterise unscheduled readmissions up to 1-year follow-up and identify predictors of 30-day readmission after an index hospitalisation for acute decompensation (AD). Methods: We performed a secondary analysis of a prospectively collected cohort of patients admitted for AD. Laboratory and clinical data at admission and at discharge were collected. Timing and causes of unscheduled readmissions and mortality were recorded up to 1 year. Results: A total of 329 patients with AD were included in the analysis. Acute-on-chronic liver failure was diagnosed in 19% of patients at admission or developed in an additional 9% of patients during the index hospitalisation. During the 1-year follow-up, 182 patients (55%) were rehospitalised and 98 (30%) more than once. The most frequent causes of readmission were hepatic encephalopathy (36%), ascites (22%), and infection (21%). Cumulative incidence of readmission was 20% at 30 days, 39% at 90 days, and 63% at 1 year. Fifty-four patients were readmitted for emergent liver-related causes within 30 days. Early readmission was associated with a higher 1-year mortality (47 vs. 32%, p = 0.037). Multivariable Cox regression analysis showed that haemoglobin (Hb) ≤8.7 g/dl (hazard ratio 2.63 [95% CI 1.38-5.02], p = 0.003) and model for end-stage liver disease-sodium score (MELD-Na) >16 at discharge (hazard ratio 2.23 [95% CI 1.27-3.93], p = 0.005), were independent predictors of early readmission. In patients with MELD-Na >16 at discharge, the presence of Hb ≤8.7 g/dl doubles the risk of early rehospitalisation (44% vs. 22%, p = 0.02). Conclusion: Besides MELD-Na, a low Hb level (Hb ≤8.7 g/dl) at discharge emerged as a new risk factor for early readmission, contributing to identification of patients who require closer surveillance after discharge. Impact and Implications: Patients with decompensated cirrhosis face frequent hospitalisations. In the present study, type and causes of readmissions were analysed during 1-year follow-up in patients discharged after the index hospitalisation for an acute decompensation of the disease. Early (30-day) liver-related readmission was associated with higher 1-year mortality. The model for end-stage liver disease-sodium score and low haemoglobin at discharge were identified as independent risk factors for early readmissions. Haemoglobin emerged as a new easy-to-use parameter associated with early readmission warranting further investigation.

A case of peri­stomal ectopic variceal bleeding in a patient with decompensated cirrhosis treated with TIPS placement.

Peri-stomal variceal bleeding is an underestimated complication in patients with colostomy and portal hypertension. Due to the small number of reported cases, there is currently no unified consensus on the best treatment and several options may be available. We report a case in which TIPS placement was effective.

Mortality and its association with chronic alcohol-related diseases in patients admitted to the emergency department for acute alcoholic intoxication: retrospective cohort study.

We assessed long-term mortality and its association with chronic alcohol-related diseases in patients admitted to the emergency department (ED) because of acute alcoholic intoxication (AAI). A retrospective cohort study was performed at the ED of Sant'Orsola-Malpighi Hospital, Bologna, Italy. 3304 patients, corresponding to 6415 admissions for AAI, who accessed the ED from January 1, 2005, to December 31, 2017, were studied. The ED electronic registry system was used to assess living status on 08 May 2020 and to obtain the prespecified potential predictors, i.e., age at first admission, sex, alcohol use disorder (AUD), substance use disorder (SUD), more than 1 admission to ED for trauma, mental and behavioral disorders, neurological disorders, and cardiovascular disease. The median follow-up time was 9.3 years and the time on risk was 30,053 person years (PY) with a death rate corresponding to 4.42 (95% CI 3.74-5.26) per 1000 PY (n = 133 deaths). The death rate was higher in patients with AUD (17.30) than in those without AUD (1.98) and in those with SUD (13.58) than in those without SUD (3.80). Lastly, there was a clearly higher death rate among AUD+ SUD+ (20.89) compared to AUD-SUD-patients (1.74). At multivariable Cox regression, AUD, SUD, and liver cirrhosis were strong and independent predictors of time-to-death. Using standardized mortality ratios, a clear excess of mortality was evident for all the age bands from (40-45] to (60-65] years. Mortality is higher in AAI than in the general population and chronic alcohol-related diseases are strongly associated with it.

Medium and long-term efficacy of psychoeducational family intervention for bipolar I disorder: Results from a real-world, multicentric study.

OBJECTIVES: This study aims to explore the long-term efficacy of a psychoeducational family intervention (PFI) in bipolar I disorder at one and five years post-intervention in terms of improvement of: (1) patients' symptoms and global functioning and (2) relatives' objective and subjective burden and coping strategies. METHODS: This is a multicentre, real-world, controlled, outpatient trial. Recruited patients and key-relatives were consecutively allocated to the experimental intervention or treatment as usual. Patients were assessed at baseline, and after one and five years. RESULTS: One hundred and thirty-seventh number families have been recruited; 70 have been allocated to the experimental intervention, and 67 have been allocated to the control group. We observed an increasing positive effect of the PFI on patients' clinical status, global functioning and objective and subjective burden after one year. We also found a reduction in the levels of relatives' objective and subjective burden and a significant improvement in the levels of perceived professional support and of coping strategies. The efficacy of PFI on patients' clinical status was maintained at five years from the end of the intervention, in terms of relapses, hospitalizations and suicide attempts. CONCLUSIONS: The study showed that the provision of PFI in real-world settings is associated with a significant improvement of patients' and relatives' mental health and psychosocial functioning in the long term. We found that the clinical efficacy of the intervention, in terms of reduction of patients' relapses, hospitalization and suicide attempts, persists after 5 years. It is advisable that PFI is provided to patients with BD I in routine practice.

FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study.

Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in N = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17-46.56, p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02-0.75, p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726, p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.

Cognitive remediation for the treatment of neuropsychological disturbances in subjects with euthymic bipolar disorder: findings from a controlled study.

INTRODUCTION: Individuals with euthymic Bipolar Disorder (BD) can experience deteriorated cognitive functioning, with such deterioration being associated with functional impairment. Cognitive remediation (CR) is considered an effective add-on intervention for neuropsychological impairments, but relatively few CR controlled studies have been performed on BD. In the present study the efficacy of a CR intervention designed for the improvement of cognition and functioning in patients with euthymic BD was tested. METHODS: Patients (n = 54) with euthymic BD were assigned to receive active (n = 27) or control (n = 27) intervention. The active intervention (i.e. the Cognitive Remediation in Integrated Treatment - CRIIT - protocol) was made of 20 individual sessions focused on the treatment of attention, memory and executive functioning through the COGPACK software; each session was integrated with psychoeducation and rehabilitation interventions implemented through a metacognitive approach aimed at ameliorating personal agency. RESULTS: A significant (p ≤ 0.015) time x group interaction at repeated measures MANOVA was observed on Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Wisconsin Card Sorting Test, Trail Making Test, Visual Search, Life Skills Profile, and Barratt Impulsiveness Scale. LIMITATIONS: A single-blind approach was used. DISCUSSION: The results showed that patients undergoing active intervention improved in domains related to executive functions, attention, memory, functioning and impulsivity more significantly than patients undergoing control interventions. This study adds to the evidence that CR improves neurocognition in BD, and suggests that CRIIT protocol represents an add-on intervention of potential relevance to increase cognition and functioning in BD euthymic patients.