Background and aims: The clinical course of liver cirrhosis is classically divided into two phases, compensated and decompensated cirrhosis, the latter characterized by the onset of complications (ascites, hepatic encephalopathy, bleeding from portal hypertension) and a worse prognosis. Recently, the observations resulting from the PREDICT study highlighted the role of Acute Decompensation (AD), i.e. the development of complications of cirrhosis that require hospitalization. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as is the case of slow and progressive development of ascites or mild grade 1 or 2 hepatic encephalopathy. This type of decompensation has recently been defined as Non Acute Decompensation (NAD). At present time, there is no information regarding the incidence and prognostic impact of NAD and whether it has a different prognosis than that of patients with AD. The aim of the study was therefore to evaluate the incidence and characteristics of NAD and AD in a group of outpatients with liver cirrhosis and the prognostic impact of these two decompensation patterns. Patients and Methods: 749 outpatients with cirrhosis were enrolled and consequently followed up until the end of the study (August 2021) or until death or liver transplantation. Clinical and biochemical data at inclusion were collected, as well as the development of complications of cirrhosis (ascites, hepatic encephalopathy or gastrointestinal bleeding), which were considered as AD if they resulted in hospitalization or NAD if they were managed at our outpatient clinic. Results: 379 patients (50.6%) did not develop any decompensation, while in 163 patients (21.8%) the first decompensation was NAD (144 with ascites, 57 hepatic encephalopathy, 2 gastrointestinal bleeding) and in 207 (27.6%) it was AD (77 ascites, 87 hepatic encephalopathy and 43 bleeding). During follow up, 216 patients (28.8%) died and 145 (19.4%) were transplanted. Survival at 120 months was significantly higher in patients who did not develop any decompensation (79.6%) than in patients who developed NAD or AD (33.7% and 21.3%, respectively; p <0.001). Survival in patients with NAD was slightly higher than that observed in patients with AD (p =0.03). Eighty-three patients with NAD (50.9%) subsequently developed AD. There was no significant difference in 120-month survival between patients who developed AD after NAD and those who only had AD, while both of these groups showed shorter survival than patients who had only NAD. All three decompensation patterns (only NAD, NAD followed by AD and AD) had significantly shorter survival than non-decompensated patients. At multivariate analysis, age (HR 1.05, 95% CI 1.03-1.06), MELD (HR 1.10, 95% CI 1.06-1.15), the presence of varices at inclusion (HR 1.48, 95% CI 1.03- 2.11), albumin (HR 0.94, 95% CI 0.92-0.97), MAP (HR 0.98, 95% CI 0.97-0.99), having received effective etiological treatment (HR 0.38, 95% CI 0.27-0.58 ) and the development of NAD (HR 2.65, 95% CI 1.70-4.11) or AD (HR 3.51, 95% CI 2.28-5.38) were independent predictors of mortality. Conclusions: In more than one out of five outpatients with liver cirrhosis, the first decompensation is a NAD, which often precedes AD and is associated with a decreased survival. Patients who develop NAD must be treated with extreme care and monitored closely to prevent any development of AD. The etiological treatment of cirrhosis has been confirmed as the most important predictor of prevention of decompensation of cirrhosis.
Il decorso clinico della cirrosi epatica è classicamente suddiviso in due fasi, la cirrosi compensata e quella scompensata, che è caratterizzata dalla comparsa delle complicanze della cirrosi (ascite, encefalopatia epatica, sanguinamento da ipertensione portale) e da peggior prognosi. Recentemente le osservazioni derivanti dallo studio PREDICT hanno posto l’attenzione sull’Acute Decompensation (AD), cioè lo sviluppo di complicanze della cirrosi che richiedono il ricovero ospedaliero. Tuttavia, le complicanze della cirrosi non sempre richiedono ricovero ospedaliero e possono svilupparsi in modo progressivo, come nel caso della formazione di ascite o una lieve encefalopatia epatica; questa tipologia di scompenso è stata definita Non Acute Decompensation (NAD). Al momento non esistono informazioni riguardo all’incidenza e all’impatto prognostico della NAD e se questa presenti una prognosi differente rispetto a quella dei pazienti con AD. L’obiettivo dello studio è stato quindi la valutazione dell’incidenza e delle caratteristiche di NAD e AD in un gruppo di pazienti con cirrosi epatica seguiti ambulatorialmente e l’impatto prognostico di questi due pattern di scompenso. Sono stati arruolati consecutivamente 749 pazienti cirrotici seguiti ambulatorialmente, che sono stati seguiti fino alla fine del follow up (Agosto 2021) oppure fino alla morte o al trapianto di fegato. Sono stati raccolti i dati clinici e bioumorali all’inclusione, così come lo sviluppo di complicanze della cirrosi (versamento ascitico, encefalopatia epatica o sanguinamento gastrointestinale), che sono stati considerati come AD qualora determinassero un ricovero ospedaliero o NAD nel caso venissero gestiti ambulatorialmente. 379 pazienti (50.6%) non hanno sviluppato alcun episodio di scompenso, mentre in 163 pazienti (21.8%) il primo scompenso è stato una NAD (144 con ascite, 57 encefalopatia epatica, 2 sanguinamento gastrointestinale) ed in 207 (27.6%) è stato una AD (77 sotto forma di ascite, 87 di encefalopatia epatica e 43 di sanguinamento). Durante il follow up, 216 (28.8%) pazienti sono deceduti e 145 (19.4%) sono stati trapiantati. La sopravvivenza a 120 mesi è risultata significativamente superiore nei pazienti che non hanno sviluppato scompenso (79.6%) rispetto sia ai pazienti che avevano sviluppato come primo scompenso NAD o AD (33.7% e 21.3%, rispettivamente; p<0.001). La sopravvivenza nei pazienti con NAD è risultata lievemente superiore rispetto a quella osservata nei pazienti con AD (p=0.03). 83 pazienti con NAD (50.9%) hanno successivamente sviluppato una AD. Non si sono evidenziate differenze significative in termini di sopravvivenza a 120 mesi tra i pazienti che hanno sviluppato una AD dopo NAD e quelli che hanno avuto solo AD, mentre entrambi questi gruppi hanno dimostrato una sopravvivenza inferiore ai pazienti che avevano presentato solo una NAD. Tutti e 3 i pattern di scompenso (solo NAD, NAD seguito da AD e AD) hanno presentato una sopravvivenza significativamente inferiore rispetto ai pazienti non scompensati. All’analisi multivariata, l’età (HR 1.05, 95% CI 1.03-1.06), il MELD (HR 1.10, 95% CI 1.06-1.15), la presenza di varici all’inclusione (HR 1.48, 95% CI 1.03-2.11), l’albumina (HR 0.94, 95% CI 0.92-0.97), la MAP (HR 0.98, 95% CI 0.97-0.99), l’aver ricevuto un trattamento eziologico efficace (HR 0.38, 95% CI 0.27-0.58) e lo sviluppo di NAD (HR 2.65, 95% CI 1.70-4.11) o di AD (HR 3.51, 95% CI 2.28-5.38) sono risultati predittori indipendenti di mortalità. In più del 20% dei pazienti con cirrosi epatica lo scompenso della cirrosi si manifesta inizialmente come NAD, spesso precede l’AD e si associa ad una riduzione di sopravvivenza. I pazienti che sviluppano NAD devono essere trattati con estrema attenzione e monitorati strettamente per prevenire eventuali sviluppi di AD. Il trattamento eziologico della cirrosi si è confermato il più importante predittore di prevenzione dello scompenso.
CARATTERIZZAZIONE CLINICA E PROGNOSTICA DEI PATTERNS DI SCOMPENSO DELLA CIRROSI EPATICA / Tonon, Marta. - (2022 Mar 03).
CARATTERIZZAZIONE CLINICA E PROGNOSTICA DEI PATTERNS DI SCOMPENSO DELLA CIRROSI EPATICA
TONON, MARTA
2022
Abstract
Background and aims: The clinical course of liver cirrhosis is classically divided into two phases, compensated and decompensated cirrhosis, the latter characterized by the onset of complications (ascites, hepatic encephalopathy, bleeding from portal hypertension) and a worse prognosis. Recently, the observations resulting from the PREDICT study highlighted the role of Acute Decompensation (AD), i.e. the development of complications of cirrhosis that require hospitalization. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as is the case of slow and progressive development of ascites or mild grade 1 or 2 hepatic encephalopathy. This type of decompensation has recently been defined as Non Acute Decompensation (NAD). At present time, there is no information regarding the incidence and prognostic impact of NAD and whether it has a different prognosis than that of patients with AD. The aim of the study was therefore to evaluate the incidence and characteristics of NAD and AD in a group of outpatients with liver cirrhosis and the prognostic impact of these two decompensation patterns. Patients and Methods: 749 outpatients with cirrhosis were enrolled and consequently followed up until the end of the study (August 2021) or until death or liver transplantation. Clinical and biochemical data at inclusion were collected, as well as the development of complications of cirrhosis (ascites, hepatic encephalopathy or gastrointestinal bleeding), which were considered as AD if they resulted in hospitalization or NAD if they were managed at our outpatient clinic. Results: 379 patients (50.6%) did not develop any decompensation, while in 163 patients (21.8%) the first decompensation was NAD (144 with ascites, 57 hepatic encephalopathy, 2 gastrointestinal bleeding) and in 207 (27.6%) it was AD (77 ascites, 87 hepatic encephalopathy and 43 bleeding). During follow up, 216 patients (28.8%) died and 145 (19.4%) were transplanted. Survival at 120 months was significantly higher in patients who did not develop any decompensation (79.6%) than in patients who developed NAD or AD (33.7% and 21.3%, respectively; p <0.001). Survival in patients with NAD was slightly higher than that observed in patients with AD (p =0.03). Eighty-three patients with NAD (50.9%) subsequently developed AD. There was no significant difference in 120-month survival between patients who developed AD after NAD and those who only had AD, while both of these groups showed shorter survival than patients who had only NAD. All three decompensation patterns (only NAD, NAD followed by AD and AD) had significantly shorter survival than non-decompensated patients. At multivariate analysis, age (HR 1.05, 95% CI 1.03-1.06), MELD (HR 1.10, 95% CI 1.06-1.15), the presence of varices at inclusion (HR 1.48, 95% CI 1.03- 2.11), albumin (HR 0.94, 95% CI 0.92-0.97), MAP (HR 0.98, 95% CI 0.97-0.99), having received effective etiological treatment (HR 0.38, 95% CI 0.27-0.58 ) and the development of NAD (HR 2.65, 95% CI 1.70-4.11) or AD (HR 3.51, 95% CI 2.28-5.38) were independent predictors of mortality. Conclusions: In more than one out of five outpatients with liver cirrhosis, the first decompensation is a NAD, which often precedes AD and is associated with a decreased survival. Patients who develop NAD must be treated with extreme care and monitored closely to prevent any development of AD. The etiological treatment of cirrhosis has been confirmed as the most important predictor of prevention of decompensation of cirrhosis.File | Dimensione | Formato | |
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