Abstract and Introduction
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.
Introduction
Overt hepatic encephalopathy (OHE) complicates the course of cirrhosis occurring in up to one-third of patients at some point during their clinical course.[1] HE is also a major contributor to repeated hospital admissions in this cohort and has a massive impact on health-related quality of life for both the patients and their caregivers[2] and is associated with high mortality (36% survival rate at 1 year and 15% at 5 years).[3–5] Even higher mortality is observed in patients with acute-on-chronic liver failure (ACLF).[6] Overt HE may occur spontaneously or because of other precipitating events such as infection, gastrointestinal bleeding, dehydration, constipation, hypovolemia, shock, high dietary protein intake, hypokalaemia, alkalosis or medications such as opiates and benzodiazepines.[7,8]
Community-acquired and healthcare-related infections occur in more than 50% of hospitalised patients with cirrhosis[9] with an admission incidence of infection of 25%-35%, which is four- to fivefold greater than that for the general population.[10] The most common infections in the setting of cirrhosis are spontaneous bacterial peritonitis (SBP), urinary tract infections (UTI), pneumonia and cellulitis.[9,11] Some of these infections might be caused by multidrug-resistant organisms (MDROs), bearing in mind that antibiotic resistance is a growing complex issue among patients with advanced cirrhosis and can negatively affect their prognosis.[12] Infection is a common cause for hospital admission and is associated with progression to HE, other organ failures and mortality in patients with cirrhosis.[13–16] Those who develop one to three episodes of infection have an almost threefold risk of developing HE compared to patients without any infection.[17]
The high risk of infection in cirrhotic patients is partly explained by the impaired immunity, bacterial translocation from the intestinal lumen because of intestinal bacterial overgrowth, increased permeability and decreased motility.[18–20] However, despite the best available treatment for managing HE and intensive care support, the risk of mortality in patients with HE remains high.[21] Several studies in the neurology literature provide compelling data showing a strong interaction between acute disorders of the nervous system and immune dysfunction as exemplified by an increased risk of infection even in patients with silent stroke.[22] Ammonia, which is thought to be central in the pathophysiology of HE is also known to induce impairment in neutrophil phagocytosis.[23–25] In addition, elevated ammonia levels are associated with other organ failure and mortality in patients with cirrhosis and acute decompensation (AD).[26] These data support the hypothesis that the occurrence of HE may predispose to the development of de novo infection. Therefore, in this study, we aimed to determine whether the occurrence of overt HE defines the risk of developing "de novo infection" in patients with cirrhosis and AD.
Aliment Pharmacol Ther. 2022;55(6):722-732. © 2022 Blackwell Publishing
