Acute on Chronic Liver Failure and Immune Dysfunction: A Mimic of Sepsis

Abstract

Both the adaptive and innate arms of immunity are altered in patients with cirrhosis, which have both prognostic and clinical implications. Acute on chronic liver failure (ACLF), defined as decompensated cirrhosis with associated organ failure, carries a high risk of 28-day mortality and is marked by a significant inflammatory response. Patients with decompensated chronic liver disease display a shift from a chronic low-grade inflammatory state to one of intense inflammation, followed by the development of immunoparalysis. Considerable heterogeneity exists depending on the nature of the inciting cause and duration of ACLF. In this review, we will highlight the changes that immune cell populations in the liver undergo during decompensated liver disease, underscoring the immunological paradox between inflammation and increased susceptibility to infection that occurs during ACLF and progressive cirrhosis, as well as provide future perspectives regarding potentially useful biomarkers and possible avenues for treatment.

Gut Microbiota, Prebiotics, Probiotics, and Synbiotics in Gastrointestinal and Liver Diseases: Proceedings of a Joint Meeting of the Brazilian Society of Hepatology (Sbh), Brazilian Nucleus for the Study of Helicobacter Pylori and Microbiota (Nbehpm), and Brazilian Federation of Gastroenterology (Fbg)

“…Elevated levels of inflammatory cytokines are observed in ACLF, even in the absence of infections (121) . Paradoxically, these patients also have marked immunosuppression that is related to the occurrence of secondary infections (122) . Changes in the gut microbiota are expected in cases of advanced organ dysfunction in cirrhotic patients, either as a contributing cause or as a consequence of profound immune changes.…”

Expression and Clinical Significance of Decoy Receptor 3 in Acute-on-Chronic Liver Failure

“…The pathological feature of ACLF is the massive hepatocyte death resulting from an excessive immune response targeting liver cells [27]. This inflammatory response not only is localized in the liver, but also spreads to the whole body system, leading to a systemic inflammatory, similar to sepsis [7, 8, 28]. Excessive and uncontrollable inflammation might further deteriorate liver injury [27].…”

“…Tumor necrosis factor (TNF) induced apoptosis plays an important role in the development of liver failure [5, 6]. The surge of proinflammatory cytokines in ACLF patients, such as TNF- α and interleukin 6 (IL-6), is comparable to those described in sepsis [5, 7, 8].…”

The Matrisome, Inflammation, and Liver Disease

“…Inflammation plays a central role in chronic liver diseases, and comprises components of both the innate and adaptive immune responses. 53,54 The net result is a chronic, low-grade inflammatory condition, in which innate immune cells are activated, and surveillance and tolerance by adaptive immune cells are dysregulated. [55][56][57][58][59] It is this vicious cycle of cell damage/death and inflammation, when it overwhelms the repair/recover responses of the liver, which leads to the chronicity of liver diseases.…”