Published online Sep 7, 2020. doi: 10.3748/wjg.v26.i33.4983
Peer-review started: May 15, 2020
First decision: June 4, 2020
Revised: June 17, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: September 7, 2020
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.
To identify prognostic predictors of ALF and death in patients with dengue-induced severe hepatitis (DISH).
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.
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).
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.
Core tip: Acute liver failure (ALF) from dengue infection is rare, but it results in high mortality rate not only due to impairment in synthesis and detoxification functions of the liver but also because ALF indicates a state of severe inflammatory response to dengue; hence, early identification of patients who are at risk of ALF and prompt treatment are keys to improving clinical outcomes. Both Model for End-Stage Liver Disease (MELD) score and international normalized ratio (INR) level were excellent prognostic predictors for dengue patients with severe hepatitis. MELD score was the best predictor of ALF, while baseline INR level was the best predictors of mortality.