Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity

Dirchwolf, Melisa; Podhorzer, Ariel; Marino, Mónica; Shulman, Carolina; Cartier, Mariano; Zunino, Moira; Paz, Suzanne; Muñoz, Alberto; Bocassi, Andrea; Gimenez, J.; Pietro, Lucía Di; Romero, Gustavo; Fainboim, Hugo; Fainboim, Leonardo

doi:10.1016/j.cyto.2015.10.006

Cited by 96 publications

(85 citation statements)

References 43 publications

(49 reference statements)

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“…Recently, a study of immune function in patients with cirrhosis has reported increased serum levels of proinflammatory cytokines, including IL-8. In this study, IL-8, together with IL-6, was higher in both patients with stable and those with decompensated cirrhosis and stayed high after development of acute-on-chronic liver failure [16]. It has been also shown that IL-8 levels are increased intrahepatically and in the serum of patients with alcoholic liver disease, probably contributing to hepatic neutrophil accumulation and also exerting systemic actions [17].…”

Section: Discussionmentioning

confidence: 86%

Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases

Акберова

Kiassov

Абдулганиева

2017

Journal of Immunology Research

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Serum cytokine levels were explored in a combined group of patients with autoimmune liver diseases (AILDs) and separately in patients with autoimmune hepatitis (AIH) and overlap syndrome. Overall, 60 patients with AILD, among them 32 patients with AIH and 28 patients with overlap syndrome, were included in the cross-sectional study. Serum cytokine levels were measured at baseline and compared to those of 21 healthy controls. Patients with AILD had significantly higher levels of IL-6 (0.70 (range 0.17–99.86) in patients with AILD compared to 0.40 (range 0.14–2.65) in controls, p < 0.01), IL-8 (1.66 (0.45–34.58) versus 0.53 (0.35–2.38), resp., p < 0.01), and TNF-α (2.61 (0.23–120.88) versus 1.65 (0.21–7.54), resp., p < 0.01). Adjusted logistic regression analysis revealed a pronounced relation of IL-8 and AILD, 48.36 (3.63–643.60), as well as AIH, 18.54 (1.08–318.54), and overlap syndrome, 23.85 (2.37–240.23), while the associations between the level of other cytokines and AILD were assessed as nonsignificant. In the language of absolute numbers, the increase of IL-8 serum level by 1 pg/mL had increased the chance for a patient to find himself in a group of AILD by 48.36 times. Also, high IL-8 serum levels were strongly related to clinical parameters.

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Section: Discussionmentioning

confidence: 86%

Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases

Акберова

Kiassov

Абдулганиева

2017

Journal of Immunology Research

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“…Two pathways of hepatic CXCL-10 induction are known: (1) a direct signaling pathway where recognition of HCV RNA by pattern recognition receptors triggers transcription within the hepatocyte; and (2) indirect production in response to type I, II, and III IFNs produced by Kupffer cells, stellate cells, and sinusoidal epithelial cells (nonparenchymal cells [NPCs]) [26]. In decompensated cirrhosis, with a reduced hepatocyte mass and elevated IFN-γ levels [27], CXCL-10 production may be primarily driven by the production of IFNs by NPC. We also saw a significant elevation in CXCL-10 level at the end of treatment in nonresponders.…”

Section: Discussionmentioning

confidence: 99%

Immunological Predictors of Nonresponse to Directly Acting Antiviral Therapy in Patients With Chronic Hepatitis C and Decompensated Cirrhosis

Childs

Merritt

Considine

et al. 2017

Open Forum Infectious Diseases

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Background.Sustained virological response rates (SVRs) to directly acting antiviral (DAA) therapy for hepatitis C virus (HCV) are lower in decompensated cirrhosis. Markers of innate immunity predict nonresponse to interferon-based HCV treatment; however, whether they are associated with the response to DAAs in patients with decompensation is not known.Methods.Information on demographics, adherence, viral kinetics, and resistance were gathered prospectively from a cohort with decompensated cirrhosis treated with 12 weeks of DAAs. C-X-C motif chemokine-10 (CXCL-10) level and T-cell and natural killer (NK) cell phenotype were analyzed pretreatment and at 4 and 12 weeks of treatment.Results.Of 32 patients, 24 of 32 (75%) achieved SVR (responders). Eight of 32 (25%) experienced relapse after the end of treatment (nonresponders). There were no differences in demographics or adherence between groups. Nonresponders had higher CXCL-10; 320 pg/mL (179461) vs 109 pg/mL (88170) in responders (P < .001) and differential CXCL-10 dynamics. Nonresponders had lower NK cell frequency, higher expression of activation receptor NKp30, and lower frequency of the NK subset CD56−CD16+.Conclusions.Nonresponders to DAAs displayed a different NK phenotype and CXCL-10 profile to responders. Nonresponders did not have poorer adherence or baseline virological resistance, and this shows that immunological parameters are associated with treatment response to interferon-free treatment for HCV in individuals with decompensated cirrhosis.

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“…One case states the patient denies having risk factors for HIV [10]. Alcoholic liver cirrhosis is noted to be one of the conditions in one of the patients [9], which is a predisposing factor to infection as it leads to immune system dysfunction and relative immunoincompetence [11] ( refer to Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus intermediusCausing Necrotizing Pneumonia in an Immune Competent Female: A Case Report and Literature Review

Hannoodi

Ali

Sabbagh

et al. 2016

Case Reports in Pulmonology

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We report a case of a 52-year-old immunocompetent Caucasian female treated for necrotizing Streptococcus intermedius pneumonia and review available literature of similar cases. Our patient presented with respiratory failure and required hospitalization and treatment in the intensive care unit. Moreover, she required surgical drainage of right lung empyema as well as decortication and resection. The review of literature revealed three cases of S. intermedius pneumonia, one of which was a mortality. Comparison of the published cases showed a highly varied prehospital course and radiological presentations, with a symptomatic phase ranging from 10 days to five months. Radiological findings varied from an isolated pleural effusion to systemic disease with the presence of brain abscesses. Immunocompetence appears to correlate well with the overall prognosis. In addition, smoking appears to be an important risk factor for S. intermedius pneumonia. In 2 (50%) of cases, pleural fluid analysis identified S. intermedius. In contrast, no organism was found in our patient, necessitating the acquisition of lung tissue sample for the diagnosis. In conclusion, both medical and surgical management are necessary for effective treatment of S. intermedius pneumonia. The outcome of treatment is good in immunocompetent individuals.

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Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity

Cited by 96 publications

References 43 publications

Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases

Serum Cytokine Levels and Their Relation to Clinical Features in Patients with Autoimmune Liver Diseases

Immunological Predictors of Nonresponse to Directly Acting Antiviral Therapy in Patients With Chronic Hepatitis C and Decompensated Cirrhosis

Streptococcus intermediusCausing Necrotizing Pneumonia in an Immune Competent Female: A Case Report and Literature Review

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