Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study

Abstract

IntroductionAcute deterioration of cirrhosis is associated with high mortality rates particularly in the patients who develop organ failure (OF), a condition that is referred to as acute-on-chronic liver failure (ACLF), which is currently not completely defined. This study aimed to determine the role of predisposing factors, the nature of the precipitating illness and inflammatory response in the progression to OF according to the PIRO (predisposition, injury, response, organ failure) concept to define the risk of in-hospital mortality.MethodsA total of 477 patients admitted with acute deterioration of cirrhosis following a defined precipitant over a 5.5-year period were prospectively studied. Baseline clinical, demographic and biochemical data were recorded for all patients and extended serial data from the group that progressed to OF were analysed to define the role of PIRO in determining in-hospital mortality.ResultsOne hundred and fifty-nine (33%) patients developed OF, of whom 93 patients died (58%) compared with 25/318 (8%) deaths in the non-OF group (P < 0.0001). Progression to OF was associated with more severe underlying liver disease and inflammation. In the OF group, previous hospitalisation (P of PIRO); severity of inflammation and lack of its resolution (R of PIRO); and severity of organ failure (O of PIRO) were associated with significantly greater risk of death. In the patients who recovered from OF, mortality at three years was almost universal.ConclusionsThe results of this prospective study shows that the occurrence of OF alters the natural history of cirrhosis. A classification based on the PIRO concept may allow categorization of patients into distinct pathophysiologic and prognostic groups and allow a multidimensional definition of ACLF.

Acute-on-Chronic Liver Failure: A Portuguese Single-Center Reference Review

“…A variety of insults can precipitate ACLF, both of hepatic or extrahepatic origin; the main cause of acute decompensation of cirrhosis in this study was bacterial infection, which is described as the leading cause of hospitalization, decompensation, and mortality in cirrhosis [12] . The MELD score varied significantly between grade 1, grade 2, and grade 3 ACLF but less significantly between grade 2 and grade 3 ACLF.…”

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014

“…Hence, the prevailing theory of sepsis for many years was that it represented an uncontrolled inflammatory response [71][72][73]. However, the results of more than 30 trials of diverse anti-cytokine and anti-inflammatory drugs showed no benefit or even reduced survival rates [74].…”

“…According to the most accepted theory, both pro-inflammatory and antiinflammatory responses occur early and simultaneously in sepsis, although the net initial effect of these competing processes is typically manifested by an early, dominant, hyper-inflammatory phase characterized by shock, fever, and hyper-metabolism. Subsequently, this initial hyper-inflammatory phase evolves over several days into a more protracted immunosuppressive phase [71]. The robustness of the hyper-inflammatory phase depends on numerous factors, including preexisting comorbidities, nutritional status, microorganism load, and virulence factors [72].…”

Acute-on-chronic liver failure: recent update

“…Once the 'eye of the storm' resolves, there is an upregulation of compensatory anti-inflammatory processes, resulting in patients becoming immunocompromised and particularly susceptible to nosocomial infections, sepsis and further deterioration [35] . As previously mentioned, cirrhotic patients who improve following organ failure in hospital and are subsequently discharged have an almost universal threeyear mortality rate [13] . In addition, it has been found that patients who have been recently hospitalised (within 6 months) possess a significantly worse mortality than those without recent hospitalization (78% vs. 34%; respectively).…”

“…These results suggest that approximately half the cases of single organ dysfunction are reversible. However, it has also been found that patients who improve in intensive care following organ failure and are subsequently discharged possess a three-year mortality of almost 100%, implying that organ failure also has the ability to change the predicted progression of cirrhosis [13] . The CANONIC study produced similar results, demonstrating that approximately 50% of patients presenting with ACLF improve and return to a compensated state, while 20% deteriorate; clinical deterioration of ACLF is associated with a mortality of < 50%.…”