Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis

Asghar, Kashif; Ashiq, Mehvish; Zulfiqar, Bilal; Mahroo, Amnah; Nasir, Kaenat; Murad, Sheeba

doi:10.3892/etm.2014.2146

Cited by 18 publications

(15 citation statements)

References 36 publications

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“… 27 , 28 Increased activity of the KP as measured by the ratio of Kyn to Trp in plasma (KT ratio) has also been associated with progressive AIDS 9 and liver cirrhosis in hepatitis C virus (HCV) infection. 29 …”

Section: Trp Metabolism In Health and Disease: A Complex Interplay Bementioning

confidence: 99%

Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

Mehraj

Routy

2015

Int J�Tryptophan�Res

104

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l-Tryptophan (l-Trp) is an essential amino acid that possesses diverse metabolic, neurological, and immunological roles spanning from the synthesis of proteins, neurotransmitter serotonin, and neurohormone melatonin, to its degradation into immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor (AhR), play an important role in antimicrobial defense and immune regulation. IDO/AhR acts as a double-edged sword by both depleting l-Trp to starve the invaders and by contributing to the state of immunosuppression with microorganisms that were not cleared during acute infection. Pathogens experiencing Trp deprivation by IDO-mediated degradation include certain bacteria, parasites, and less likely viruses. However, chronic viral infections highjack the host immune response to create a state of disease tolerance via kynurenine catabolites. This review covers the latest data involving chronic viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their cellular interplay with Trp catabolites. Strategies developed by viruses to escape immune control also represent new avenues for therapeutic interventions based on Trp metabolism.

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Section: Trp Metabolism In Health and Disease: A Complex Interplay Bementioning

confidence: 99%

Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

Mehraj

Routy

2015

Int J�Tryptophan�Res

104

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“… 24 High Trp catabolism has also been demonstrated within the livers of individuals with HCV-induced liver cirrhosis. 25 Indeed, all these data suggest an important role for IDO in both HIV and HCV monoinfection.…”

Section: Introductionmentioning

confidence: 97%

Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients

Jenabian

Mehraj

Costiniuk

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background:We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)–associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism.Methods:Trp catabolism and inflammatory soluble markers were assessed in plasma samples from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional coinfected patients with sustained virological response (SVR) were assessed longitudinally 6 months after completion of interferon-α/ribavirin treatment.Results:HIV/HCV patients had higher Trp catabolism compared with HIV-monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV patients with liver fibrosis correlated with the prognostic aspartate aminotransaminase to platelet ratio (APRI scores) and insulin levels. Furthermore, HIV/HCV patients had elevated levels of disease progression markers interleukin-6 and induced protein 10 and shared similar levels of markers of microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy individuals. Successful HCV treatment improved APRI score and markers of disease progression and microbial translocation although elevated Trp catabolism remained unchanged 6 months after SVR.Conclusion:ART-treated HIV/HCV-coinfected patients had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV-treated patients, which did not normalize after SVR. These findings suggest that a necroinflammatory liver syndrome persists through inflammation by Trp catabolism after 6 month of SVR.

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“…approximately this value. In patients with type C chronic liver disease, increases in serum kynurenine levels, expression of indoleamine 2,3-dioxygenase (IDO) as an enzyme producing kynurenine, and the serum kynurenine/tryptophan ratio have all been demonstrated [15,16]. When HCC develops in chronic hepatitis C, kynurenine production is considered to be further promoted.…”

Section: Plos Onementioning

confidence: 99%

Serum kynurenine levels are a novel biomarker to predict the prognosis of patients with hepatocellular carcinoma

et al. 2020

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Background We examined serum kynurenine levels in patients with chronic hepatitis C virus infection, and the relationship between serum kynurenine and prognosis in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C. Methods We retrospectively analyzed 604 patients with HCC diagnosed between January 1999 and December 2015, and 288 patients without HCC who were seen at the National Hospital Organization Nagasaki Medical Center between October 2014 and November 2017. The association between serum kynurenine and prognosis was evaluated using the Cox's proportional hazards regression analysis. Results Patients with HCC had significantly higher values of serum kynurenine than patients without HCC (median: 557.1 vs. 464.2 ng/mL, p<0.001). Five-year survival rates of HCC patients with serum kynurenine �900 (n = 65), 600-899 (n = 194), and <600 ng/mL (n = 345) were 30.6%, 47.4%, and 61.4%, respectively (p = 0.001, log-rank test). Multivariate analysis identified serum kynurenine as an independent predictor for prognosis of HCC patients. The hazard ratio of serum kynurenine �900, and 600-899 compared with serum kynurenine <600 ng/mL were 1.91 (p<0.001) and 1.37 (p = 0.015), respectively. Conclusions A high level of serum kynurenine correlated with poor prognosis of HCC. Serum kynurenine levels may be a novel biomarker to predict the prognosis of patients with HCC. The

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Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis

Cited by 18 publications

References 36 publications

Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients

Serum kynurenine levels are a novel biomarker to predict the prognosis of patients with hepatocellular carcinoma

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