Overt hepatic encephalopathy is an independent risk factor for de novo infection in cirrhotic patients with acute decompensation

Abstract

Background:The occurrence of overt hepatic encephalopathy (OHE) is associated with increased mortality. HE is commonly precipitated by infection, but whether HE predisposes to new infection is unclear. This study aimed to test if OHE predisposes to de novo infection during hospitalisation and its association with short-term mortality.Aims and Methods: Seven hundred and fifty-nine consecutive patients were identified at two institutions from prospectively maintained clinical databases of cirrhotic patients admitted with acute decompensation (AD). Infection and HE data were collected on the day of admission, and the occurrence of de novo infections was assessed for 28 days after admission. EASL-CLIF organ failure criteria were used to determine the presence of organ failures. Multivariable analysis using the logistic regression model was used to assess predictors of 28-day mortality and de novo infection.Results: Patients were divided into four groups; no baseline OHE or infection (n = 352); OHE with no baseline Infection (n = 221); no OHE but baseline infection (n = 100) and OHE with baseline infection (n = 86). On multivariate analyses, OHE (OR, 1.532 [95% CI, 1.061-2.300, P = 0.024]), and admission to ITU (OR, 2.303 [95% CI, 1.508-3.517, P < 0.001]) were independent risk factors for de novo infection.28-day mortality was 25.3%, 60.2%, 55.0% and 72.1% in the 4-groups respectively.Age, INR and creatinine were independently predictive of mortality. The presence of overt HE, infection, coagulation, kidney, circulatory, respiratory and liver failures were significantly associated with higher mortality. Conclusion:OHE is an independent risk factor for de novo infection in cirrhotic patients with AD.

Letter: de novo infection in hepatic encephalopathy—The culprit or the victim? Authors' reply

“…We agree that it is difficult to be certain at the time of presentation whether the patient has an infection or not. However, there are many lines of evidence provided in our paper 2 that support our hypothesis of the link between OHE and risk of infection.…”

Editorial: infections and hepatic encephalopathy—does the chicken or the egg come first? A novel perspective at the horizon. Authors’ reply

“…The author's declaration of personal and funding interests are unchanged from those in the original article. 4 Declaration of personal interests: Rajiv Jalan has research collaborations with Takeda, and Yaqrit, and consults for Yaqrit. Rajiv Jalan is the founder of Yaqrit Limited, which is developing UCL inventions for the treatment of patients with cirrhosis.…”

“…We have already discussed the potential role of ammonia in the pathogenesis of HE in our paper. 4 Ammonia plays a role in the pathogenesis of HE through multiple mechanisms. In addition to the neurotoxic effect on astrocytes, ammonia impairs neutrophil function, which is mediated by activation of the p38 mitogenactivated protein kinase (p38 MAPK) pathway, leading to reactive oxygen species release, systemic inflammation, oxidative stress, high spontaneous oxidative burst, and decreased phagocytosis, significantly increasing the risk of infection, organ failure, and mortality.…”

“…We have already discussed the potential role of ammonia in the pathogenesis of HE in our paper 4 . Ammonia plays a role in the pathogenesis of HE through multiple mechanisms.…”

Editorial: infections and hepatic encephalopathy–does the chicken or the egg come FIRST? A novel perspective at the horizon

“…Minimal HE was also related to infections and reversible after resolution. 8 Alabsawy 9 proposed a different view from such well-established paradigm: namely that HE represent an important determinant for infections. In fact, the authors introduce an innovative concept according to which HE plays a decisive role in the pathogenesis of infections.…”