Dengue hepatitis with acute liver failure: Clinical, biochemical, histopathological characteristics and predictors of outcome

Abstract

BackgroundHepatitis infection from non‐hepatotropic viruses such as dengue virus (DENV) is increasing worldwide. There is increasing recognition of the changing epidemiology and atypical presentations of DENV infection including acute liver failure (ALF). There is paucity of data regarding incidence, disease characteristics, and markers of prognosis in patients who develop DENV‐related ALF.MethodsWe aimed to study the incidence, clinical features, laboratory characteristics, and determinants of outcome in patients of DENV presenting with ALF. We reviewed all patients with DENV infection and focused on DENV‐related ALF from 2014 to 2017. Diagnosis of DENV and ALF was confirmed by serological tests and standard criteria, respectively.ResultsThirty‐six patients (20 men, mean age 32.3) developed ALF among 10 108 patients with DENV infection (0.35%). Twenty‐one patients died (58.3%). Although bilirubin, aspartate and alanine aminotransferase, and international normalized ratio were markedly elevated in all patients with DENV ALF, there was no statistically significant difference between survivors and non‐survivors. Lactate levels, pH at admission, and model for end‐stage liver disease (MELD) score were the only predictors of mortality. Lactate levels were significantly higher in non‐survivors (11.5 ± 4.2 mmol/L) than survivors (6.3 ± 3.6 mmol/L) (P < 0.001). MELD score in non‐survivors (26.7 ± 10.2) was significantly higher than in survivors (20 ± 7.2) (P = 0.039). Receiver operator characteristic curve showed lactate or pH to be a superior prognostic marker than MELD with an area under the curve of 0.80, 0.79, and 0.70, respectively.ConclusionDengue hepatitis progressed to ALF in 0.35%. Development of ALF was associated with a high mortality (> 50%). Lactate level, pH, and MELD score at admission were significant determinants of outcome.

Dengue hemorrhagic fever and the liver

“…In the liver, DENV infection occurred in hepatocytes and Kupffer cells but not in endothelial cells. Other studies reported the same pathological findings[ 34 , 38 , 39 ]. Recently, Win and colleagues reported that the prominent findings of the ultrastructure features of human liver specimens from patients who died of DHF were extensive cellular damage and steatosis.…”

“…Mean AST and ALT concentrations ranged from 2-fold to 5-fold rises, which demonstrated mild hepatitis with self-limited. The 10-fold elevation of AST and ALT was reported in 4%-15% of the patients associated with SDD and may deteriorate to be ALF[ 33 , 34 ]. The physical sign of hepatomegaly with hepatic tenderness did not predict the rising of AST and ALT[ 16 ].…”

“…However, the development of ALF is associated with a very high mortality rate. Lactate levels, pH, and model for end-stage liver disease (MELD) score at admission were the only predictors of mortality[ 34 ]. Recently, Teerasarntipan and colleagues conducted a retrospective study of 2311 serologically confirmed adult dengue patients to evaluate ALF and fatality rate incidence.…”

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

“…With a cut-off ≥ 15 points, the MELD score could predict ALF from DISH with an excellent performance (AUROC of 0.906, 88.2% sensitivity and 87.3% specificity). Overall, we suggest that the liver background and functional reserve after dengue infection are the main prognostic factors and have a stronger influence on the development of ALF than the severity of liver insults from the virus[ 23 ].…”

Epidemiology of liver failure in Asia‐Pacific region

“…More recently, many cases of denguerelated ALF were observed in both children and adults during the Indian seasonal epidemic, including cases of mixed infections. 70 In an Indian study, dengue hepatitis progressed to ALF in 0.35%. 71 The mean age of dengue-related ALF was 29 years.…”