Predictors of infection in viral-hepatitis related acute liver failure

<p><b>Objective:</b> Infections are common and associated with complications and mortality in acute liver failure (ALF). The temporal relationship between ammonia and infection in ALF patients is unclear. We aimed to evaluate the predictors of infection and its relationship with arterial ammonia levels.</p> <p><b>Materials and methods:</b> Consecutive ALF patients hospitalized between January 2004 and December 2015, without signs of infection at/within 48 h of admission, were included. Occurrence of infection after 48 h was documented and ammonia levels were estimated for five consecutive days. Multivariate logistic regression analysis was used to assess factors associated with development of infection. Generalized estimating equations (GEE) were used to evaluate five-day time trend of ammonia in patients with and without infection.</p> <p><b>Results:</b> Of 540 consecutive patients, 120 were infected at admission/within 48 h and were excluded. Of the rest 420 patients, 144 (34.3%) developed infection after 48 h and 276 (65.7%) remained non-infected. Infected patients had higher mortality than non-infected patients (61.8% vs 40.0%, <i>p</i> < .001). On multivariate analysis, presence of cerebral edema(HR 2.049; 95%CI, 1.30–3.23), ammonia level on day 3 of admission (HR 1.006; 95%CI, 1.003–1.008), and model for end stage liver disease (MELD) score (HR 1.051; 95%CI, 1.026–1.078) were associated with development of infection. GEE showed group difference in serial ammonia values between infected and non-infected patients indicating lack of ammonia decline in infected patients.</p> <p><b>Conclusions:</b> Cerebral edema, elevated ammonia on day 3, and higher MELD score predict the development of infection in ALF. Ammonia persists at high levels in infected patients, and elevated ammonia on day 3 is associated with complications and death.</p

Baseline characteristics of patients and controls.

<p>Baseline characteristics of patients and controls.</p

Baseline characteristics of patients with Intestinal Tuberculosis (ITB), Crohn’s disease (CD) and controls.

<p>Baseline characteristics of patients with Intestinal Tuberculosis (ITB), Crohn’s disease (CD) and controls.</p

Comparison of peripheral CD4⁺CD25⁺ CD127^- FOXP3⁺ T cells are increased in ITB patients.

<p>Intracellular expression of FOXP3 gated on CD4⁺CD25⁺ CD127^- T cells were analysed by flow cytometry in (A) Controls, CD and UC populations (B) CD and UC in remission and relapse (C) Controls and ITB pre-therapy patients and (D)CD, UC and ITB pretherapy patients (E) Frequency of CD4⁺CD25^-FOXP3⁺ T cells analysed by Flow cytometry and (F) Total FOXP3 mRNA expression were evaluated in Controls, CD, UC and ITB pre-therapy patients. * P<0.05, ** P<0.001, *** P<0.0001.</p

Receiver operating characteristics (ROC) curve plotted according to percentage of CD4⁺CD25⁺ CD127^- FOXP3⁺ cells from blood samples of ITB and CD patients.

<p>Receiver operating characteristics (ROC) curve plotted according to percentage of CD4⁺CD25⁺ CD127^- FOXP3⁺ cells from blood samples of ITB and CD patients.</p

Comparison of clinical phenotypes and treatment outcomes in CD patients with and without MAP infection.

<p>Comparison of clinical phenotypes and treatment outcomes in CD patients with and without MAP infection.</p

Comparison of MAP positivity between CD, ITB and control subjects.

<p>Comparison of MAP positivity between CD, ITB and control subjects.</p

CD4⁺ CD25⁺ FOXP3⁺ T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn’s disease - Fig 1

<p>Representative photomicrographs (40X objective at 400 magnifications) of colonic biopsy showing increased frequency of CD4⁺FOXP3⁺ dual positive cells in all diseased groups as compared to control: a) control, b) ulcerative colitis, c) Crohn’s disease, d) intestinal tuberculosis. Scale: 40X objective; 400 magnification.</p

Clinical characteristics of patients with intestinal TB and Crohn’s disease.

<p>Clinical characteristics of patients with intestinal TB and Crohn’s disease.</p

Peripheral blood frequency of FOXP3 cells in various disease groups and controls.

<p>Peripheral blood frequency of FOXP3 cells in various disease groups and controls.</p