Immune Dysfunction in Cirrhosis

Abstract

Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in antiinflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of noncirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates. Citation of this article: Noor MT, Manoria P. Immune dysfunction in cirrhosis.

Deleterious effect of proton pump inhibitors on the disease course of cirrhosis

“…As a result, prolonged high serum concentration of the drug potentiates acid suppression and may increase a PPI associated side effects [44]. Immune suppressive effects can be more harmful in patients with cirrhosis known to be immunocompromised with a multifactorial state of systemic immune dysfunction [45]. The unnecessarily high dose of the drug further enhances negative effects of PPI.…”

The effect of variceal bleeding on T-cell subsets in patients with cirrhosis

“…Nourieta et al demonstrated a broad defect of T cells and hyperactivity of B cells in patients with alcoholic liver disease. Specifically, these patients have circulating IgG and T lymphocytes that recognize epitopes against lipid peroxidation derived antigens and are associated with an increase in hepatic production of proinflammatory cytokines and chemokines.Doi et al reported that memory CD27+ B cells were reduced in the peripheral blood of pa- tients with cirrhosis, independent of etiology, and that this reduction led to impaired TNF-b and IgG production, vaccine hyporesponsiveness and susceptibility to bacterial infection [9].…”

Hepatic Encephalopathy and Nutrition Influences: A Narrative Review

“…Cirrhotic patients experience immune dysfunction due to alterations in both innate and acquired immunity including impaired phagocytic activity and lymphocyte derangement . BCAA supplementation in cirrhotic patients restores the phagocytic activity of neutrophils, increases the number of intrahepatic lymphocytes, and augments the natural killer activity of lymphocytes .…”