A new clinical and prognostic characterization of the patterns of decompensation of cirrhosis.

BACKGROUND & AIMS: The prognostic impact of acute decompensation (AD), i.e. the development of complications that require hospitalization, has recently been assessed. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as in the recently defined non-acute decompensation (NAD). Nevertheless, there is no data regarding the incidence and prognostic impact of NAD. The aim of the study was to evaluate the incidence and the prognostic impact of NAD and AD in outpatients with cirrhosis. METHODS: A total of 617 outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were enrolled from January 2003 to June 2021 and followed prospectively until the end of the study, death or liver transplantation. The complications registered during follow-up were considered as AD if they required hospitalization, or NAD if managed at the outpatient clinic. RESULTS: During follow-up, 154 patients (25.0% of total patients) developed complications, 69 patients (44.8%) developed NAD and 85 (55.2%) developed AD, while 29 patients with NAD (42.0%) developed a further episode of AD during follow-up. Sixty-month survival was significantly higher in patients with no decompensation than in patients with NAD or AD. On multivariable analysis, AD (hazard ratio [HR] 21.07, p <0.001), NAD (HR 7.13, p <0.001), the etiological cure of cirrhosis (HR 0.38, p <0.001) and model for end-stage liver disease score (HR 1.12, p = 0.003) were found to be independent predictors of mortality. CONCLUSIONS: The first decompensation is non-acute in almost 50% of outpatients, though such events are still associated with decreased survival compared to no decompensation. Patients who develop NAD must be treated with extreme care and monitored closely to prevent the development of AD. IMPACT AND IMPLICATIONS: This multicenter study is the first to investigate the role of non-acute decompensation (NAD) in patients with cirrhosis. In fact, while the unfavorable impact of acute decompensation is well known, there is currently a dearth of evidence on NAD, despite it being a common occurrence in clinical practice. Our data show that almost half of decompensations in patients with cirrhosis can be considered NAD and that such events are associated with a higher risk of mortality than no decompensation. This study has important clinical implications because it highlights the need to carefully consider patients who develop NAD, in order to prevent further decompensation and reduce mortality.

Recompensation of cirrhosis in candidates of transplant: Tips and tricks for delisting.

Liver transplantation (LT) is the most successful treatment for patients with decompensated cirrhosis. The availability of effective and safe etiological treatments has altered the natural history of decompensated cirrhosis. Recently, the concept of recompensation has been defined. Patients who achieve recompensation may be removed from the waiting list for LT. Therefore, achieving an etiological cure is the cornerstone in the treatment of patients with decompensated cirrhosis. However, most patients improve their liver function after an etiologic cure, and only a proportion of patients achieve true recompensation after an etiological cure. Some patients maintain a condition of "MELD purgatory," that is, an improvement in the Model for End-Stage Liver Disease score without relevant clinical improvement that prevents delisting and may be even detrimental because lower Model for End-Stage Liver Disease score delays LT. Herein, we review the available evidence regarding recompensation and the management of recompensated patients on the waiting list for LT.

Diagnostic and prognostic performance of urinary neutrophil gelatinase-associated lipocalin in patients with cirrhosis and acute kidney injury.

BACKGROUND AND AIMS: Acute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) could help discriminate between different etiologies of AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI. APPROACH AND RESULTS: One hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml [95% CI 423-2105 ng/ml] vs. 109 ng/ml [95% CI 52-192 ng/ml]; p  < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p  < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR [aOR], 6.17; 95% CI 1.41-27.03; p  = 0.016). In multivariable analysis (adjusted for age, Model for End-Stage Liver Disease, acute-on-chronic liver failure, leukocytes, and type of AKI), uNGAL was an independent predictor of in-hospital mortality (aOR, 1.74; 95% CI 1.26-2.38; p  = 0.001). CONCLUSIONS: uNGAL is an adequate biomarker for making a differential diagnosis of AKI in cirrhosis and predicting the response to terlipressin and albumin in patients with HRS-AKI. In addition, it is an independent predictor of in-hospital mortality.

Impact of bacterial infections prior to liver transplantation on post-transplant outcomes in patients with cirrhosis.

Background & Aims: Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival. Methods: From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected. Results: A total of 466 LT recipients were identified (study group n = 108; control group n = 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p = 0.001) and of septic shock (8% vs. 2%, p = 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio = 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p = 0.579) and 5-year survival rates (76% vs. 75%, p = 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes. Conclusions: Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT. Impact and Implications: Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.

Haemophilus parainfluenzae endocarditis in a low-risk woman: a case report.

Haemophilus parainfluenzae endocarditis is a rare but dangerous disease. With this work, we intend to show the importance of early diagnosis and appropriate treatment in order to avoid complications. We also highlight the importance of local epidemiology to choose antibiotic prophylaxis for high-risk procedures in selected predisposed patients.