Role of Infections in Acute-on-Chronic Liver Failure

Abstract

Patients with cirrhosis are prone to developing bacterial infections. Moreover, bacterial infection is the most common identifiable trigger of acute-on-chronic liver failure (ACLF), which is characterized by organ failures and a high risk of death. There is evidence of an excessive immune response of the host as a major mechanism leading to the development of organ failures in patients with cirrhosis. However, a role for direct tissue damage caused by bacterial toxins and virulence factors cannot be excluded. Failed tolerance mechanisms may also contribute to organ failures, although the involved mechanisms are unclear. A proportion of patients with infection-related ACLF have a prolonged stay in the intensive care unit. These patients have immune suppression, increased risk of superinfection and poor outcome. Immune suppression might be a consequence of the first infection episode that has led patients to be admitted to hospital.

The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis

“…Patients with cirrhosis are susceptible to infections that may contribute to and elicit severe complications including renal failure and sepsis . From a haemodynamic point of view, there are many similarities between full‐blown sepsis and advanced cirrhosis since both conditions are characterized by a hyperdynamic circulatory failure and signs of inflammation .…”

Regeneration in acute-on-chronic liver failure – the phantom lost its camouflage

“…Our current knowledge emphasizes the special role of bacterial infections which, among all other confounding factors, have the worst impact on the disease course. Infections are among the most frequent (>30% patients) precipitating events 13 of ACLF and more than 50% of patients with ACLF develop an infection during their hospital stay, increasing their death rate from 34% to 71%. 14,15 Infections have a sustained negative effect on patients' outcome even if successfully treated, as the 1-year mortality increases by the factor 3.75 compared to non-infected patients with cirrhosis.…”

Management of Infectious Complications Associated with Acute-on-Chronic Liver Failure

“…The constant translocation of bacteria and their products sensitizes the immune system so that invading pathogens cause an overwhelming inflammatory response [23,24]. Circulating bacterial products are recognized by pattern-recognition receptors (PRR), which typically belong to the Toll-like receptor (TLR) and NOD-like receptor families [23,24], and its binding induces the transcriptional upregulation of a battery of proinflammatory genes specifically coding for cytokines such as interleukin-6 (IL6) and tumor necrosis factor alpha (TNFα).…”

“…Circulating bacterial products are recognized by pattern-recognition receptors (PRR), which typically belong to the Toll-like receptor (TLR) and NOD-like receptor families [23,24], and its binding induces the transcriptional upregulation of a battery of proinflammatory genes specifically coding for cytokines such as interleukin-6 (IL6) and tumor necrosis factor alpha (TNFα). Thus, circulating levels of proinflammatory cytokines are higher in patients with cirrhosis than in healthy liver subjects [25,26], and increase with the severity of liver disease [27], which is an indicator that the intensity of bacterial translocation correlates with the degree of liver dysfunction.…”

“…Patients who survived either an ACLF-related infection or prolonged intensive care unit stay migrate into an immunosuppressive state [24,30]. Monocytes and other phagocyting cells are less active with a reduced expression of human leukocyte antigen-antigen D related (HLA-DR), and as a consequence show an impaired response to LPS stimulation [31].…”