Dataset Information

Cytokine and autoantibody patterns in acute liver failure.

ABSTRACT: The mechanisms of idiosyncratic drug-induced liver injury (IDILI) are still a matter of dispute. Some of the characteristics of reactions that have been classed as metabolic idiosyncrasy could also be those of an immune-mediated reaction with an autoimmune component. Many auto-immune reactions appear to be mediated by T(H)17 cells, which are in part characterized by the production of interleukin (IL)-17. To test the involvement of T(H)17 cells in IDILI, we quantified a number of cytokines, chemokines, and autoantibodies in the serum of 39 patients with acute liver failure (ALF) due to IDILI and compared the values with those from 21 patients with acetaminophen-induced ALF and 10 patients with viral hepatitis-induced ALF. The IL-17 levels were elevated in 60% of patients with IDILI, but also in a similar number of patients with acetaminophen-induced ALF and occasionally in patients with viral hepatitis. Levels of other cytokines, such as IL-21, that are also produced by T(H)17 cells were higher in patients with IDILI, but again, there was overlap with acetaminophen DILI. Autoantibodies were more frequent in patients in the IDILI group but were absent in most patients. These data provide a picture of the cytokine/chemokine profile in patients with various types of ALF. The pattern varies from patient to patient and not specifically by etiology. This suggests that different underlying disease mechanisms may be at play in different individuals, even among those demonstrating injury from the same drug. Since cytokines may originate from more than one type of cell, interpretation of results of cytokine assays remains difficult in complex disease settings.

SUBMITTER: Li J

PROVIDER: S-EPMC4937798 | biostudies-literature | 2010 Jul-Sep

REPOSITORIES: biostudies-literature

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Cytokine and autoantibody patterns in acute liver failure.

Li Jinze J Zhu Xu X Liu Feng F Cai Ping P Sanders Corron C Lee William M WM Uetrecht Jack J

Journal of immunotoxicology 20100701 3

The mechanisms of idiosyncratic drug-induced liver injury (IDILI) are still a matter of dispute. Some of the characteristics of reactions that have been classed as metabolic idiosyncrasy could also be those of an immune-mediated reaction with an autoimmune component. Many auto-immune reactions appear to be mediated by T(H)17 cells, which are in part characterized by the production of interleukin (IL)-17. To test the involvement of T(H)17 cells in IDILI, we quantified a number of cytokines, chemo ...[more]

PMID: 20039781

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Project description:In patients with acute liver failure (ALF), elevated prothrombin time and thrombocytopenia can fuel a perception of a bleeding tendency. However, the incidence, site, risk factors, and clinical significance of bleeding complications have not been quantified in a large cohort of patients with ALF. We studied 1,770 adult patients enrolled in the ALF Study Group Registry between 1998 and 2016. Bleeding complications and blood component transfusions were collected for 7 days after admission. The relationship of bleeding complications to 21-day mortality was assessed. Despite a median international normalized ratio of 2.7 and platelet count of 96 × 109 /L on admission, bleeding complications were observed in only 187 patients (11%), including 173 spontaneous and 22 postprocedural bleeding episodes. Eighty-four percent of spontaneous bleeding episodes were from an upper gastrointestinal source and rarely resulted in red blood cell transfusion. Twenty patients experienced an intracranial bleed; half of these occurred spontaneously and half after intracranial pressure monitor placement, and this was the proximate cause of death in 20% and 50%, respectively. Bleeders and patients who received red blood cell transfusions were more acutely ill from extrahepatic organ system failure but not from hepatocellular failure. Consistent with this observation, bleeding complications were associated with lower platelet counts but not higher international normalized ratio. Transfusion of any blood component was associated with nearly 2-fold increased death or need for liver transplantation at day 21, but bleeding complications were the proximate cause of death in only 5% of cases. CONCLUSIONS:Despite a perceived bleeding diathesis, clinically significant bleeding is uncommon in patients with ALF; bleeding complications in patients with ALF are markers of severe systemic inflammation rather than of coagulopathy and so portend a poor prognosis. (Hepatology 2018;67:1931-1942).

Dataset Information

Cytokine and autoantibody patterns in acute liver failure.

Publications

Cytokine and autoantibody patterns in acute liver failure.

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