Acute liver failure and death predictors in patients with dengue-induced severe hepatitis

Abstract

BACKGROUND Liver injury in patients with dengue infection is common. Most patients have mild and transient hepatitis. Acute liver failure (ALF) in dengue infection is rare but results in an extremely poor prognosis. AIM To identify prognostic predictors of ALF and death in patients with dengue-induced severe hepatitis (DISH). METHODS We retrospectively reviewed 2311 serologically confirmed adolescent and adult dengue patients who were hospitalized during a 12-year study period (between 2007 and 2019) at the university hospital of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients with DISH [ n = 134 (5.80%)], defined as a baseline transaminase > 10 times the normal reference cut-off level, and DISH with subsequent ALF as defined by the American Association for the Study of the Liver Diseases 2011 criteria [ n = 17 (0.74%)], were included. Predictors of ALF and in-hospital death were identified using logistic regression analysis. RESULTS Of the 151 dengue-infected patients with severe liver injury or ALF, 51% were female, with a mean age of 27.9 ± 14.5 years. Capillary leakage syndrome (CLS) occurred in 68.2% ( n = 103) of DISH and 100% of ALF patients. The mortality rate was low in DISH patients (0.8%) but was remarkably high if ALF developed (58.8%). In univariate analysis, age, sex, hematocrit, white blood count, atypical lymphocyte count, platelet count, international normalized ratio (INR), bilirubin, serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, alkaline phosphatase, albumin, creatinine, Model for End-Stage Liver Disease (MELD) score, presence of liver comorbidity and presence of CLS were identified as potential prognostic parameters for ALF or death. In multivariate analysis, the MELD score remained the only predictor of ALF with an adjusted odds ratio (aOR) of 1.3 [95% confidence interval (CI): 1.1-1.5; P = < 0.001]. An initial MELD score ≥ 15 was associated with ALF from DISH with an area under the receiver operating characteristic (AUROC) of 0.91, 88.2% sensitivity and 87.3% specificity. Regarding mortality prediction, the deterioration of liver function to ALF was the most significant factor related to death in DISH patients (aOR 108.5, 95%CI: 5.5-2145.4, P = 0.002). Other independent factors associated with death included baseline INR (aOR 10.4, 95%CI: 2.6-40.5, P = 0.001). An INR ≥ 1.5 predicted death from DISH with an AUROC of 0.83 (81.8% sensitivity and 86.8% specificity). CONCLUSION The MELD score is the best predictor of ALF in DISH patients, a complication from dengue that is associated with high mortality. The presence of ALF and the baseline INR level are independent markers of death in DISH patients.

Dengue hemorrhagic fever and the liver

“…The mortality rate of ALF was 10 of 17 SDD patients (58.82%). They concluded that the MELD score is the best predictor of ALF in dengue-induced severe hepatitis (DISH) patients[ 46 ].…”

Prognostic indicators associated with progresses of severe dengue

“…AKI in dengue patients may recover on its own, but may also require kidney replacement therapy [ 7 , 20 ]. Liver function damage is relatively common in dengue patients and can lead to acute liver failure [ 6 , 10 ]. Disorders of coagulation parameters such as APTT, PT, fibrinogen are common in patients with severe dengue [ 12 ], leading to severe bleeding, especially in prolonged shock [ 2 , 4 ].…”

“…This was either a result of direct viral toxicity or compromised immune response to the virus [ 25 ]. Although the bilirubin parameter was rarely suggested, however some studies have also recognized that bilirubin may be associated with severe dengue prognosis [ 10 ].…”

“…In recent years, in addition to shock syndrome, serious conditions such as severe bleeding, impaired organ function in dengue patients have been reported with an increase [ 3 – 5 ]. The serious situation of liver failure, acute kidney injury (AKI) has also become a concern [ 6 , 7 ] and affects treatment outcomes [ 5 , 8 – 10 ]. In many cases, organ failure in dengue patients can only be detected based on the laboratory results [ 5 , 9 , 11 ].…”

“…In many cases, organ failure in dengue patients can only be detected based on the laboratory results [ 5 , 9 , 11 ]. Therefore, in addition to hematocrit and platelet indices [ 2 ], some recent studies have suggested the use of biomarkers such as AST, ALT [ 11 – 14 ], aPTT [ 12 , 15 , 16 ], and INR [ 10 , 16 ] to predict severe or fatal dengue patients.…”