Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.

The pathogenesis of liver damage in dengue patients has not been clarified. In this study, we sought to identify the factors that are associated with dengue-induced liver damage and evaluate the associations of cytokines/chemokines, including platelets, neutrophils, activated endothelial cells and other inflammatory factors, with liver damage.

We collected and analysed clinical data from 106 hospitalized dengue patients and evaluated the serum levels of platelet (soluble P-selectin [sP-selectin] and soluble CD40 ligand [sCD40L]), neutrophil (neutrophil elastase [NE] and neutrophil myeloperoxidase [MPO]) and endothelial cell (soluble thrombomodulin [sTM]) activation markers, as well as inflammatory mediators, including C-X-C motif chemokine ligand 2 (CXCL2), interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor-α and interferon-γ (which are associated with liver damage), in 32 patients.

In total, 106 dengue patients were included in this study. The patients were categorized into dengue with warning signs (DwWS), dengue without warning signs (DwoWS) and severe dengue (SD). Twenty-four patients (22%) had DwWS and 1 patient (1%) had SD. Compared with the DwoWS group, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase levels in the DwWS/SD group were significantly greater (p<0.001, p<0.001 and p=0.001, respectively). A long time to onset (odds ratio [OR] 1.495 [95% confidence interval {CI} 1.063 to 2.101], p=0.021), thrombocytopenia (OR 4.166 [95% CI 1.11 to 15.629], p=0.034) and concomitant fatty liver (OR 6.326 [95% CI 1.57 to 25.493], p=0.009) were risk factors for dengue-related liver dysfunction. Compared with patients with normal liver enzyme levels, serum sP-selectin levels were significantly lower (p=0.012), sTM levels were higher (p=0.047), serum ALT and AST levels were positively correlated with sTM (r=0.411, p=0.02 and r=0.419, p=0.039; respectively) and AST levels were negatively correlated with sP-selectin levels (r=-0.441, p=0.011) in dengue patients.

Dengue fever with hepatic involvement is related to serum sTM and sP-selectin levels, thus suggesting that platelet and endothelial cell activation may be involved in the pathogenesis of liver damage and can be used as early predictors of dengue liver damage.

Dengue-associated acute liver failure (ALF) poses a significant risk for mortality, especially in regions lacking access to liver transplantation. Although Plasma Exchange (PLEX) is recognized as a potential therapeutic intervention for dengue-associated ALF, data on its efficacy remain limited. This systematic review aimed to comprehensively examine the literature on PLEX and other combination therapies for dengue-associated ALF. It focused on assessing their effectiveness, safety profile, and potential implications for therapeutic interventions.

In this study, we conducted a systematic review to assess the efficacy and safety of PLEX and other combination therapies in patients with dengue-associated ALF. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria were used to search the PubMed, Scopus, Embase, Ovid, and Google Scholar databases. Studies published in English between 2019 and May 2024 were included. The titles and abstracts were reviewed for discrepancies, and any differences were resolved through discussion.

Among the 713 studies assessed for review, 9 met the eligibility criteria. Studies have demonstrated that PLEX, both alone and in combination with other therapies, such as continuous renal replacement therapy (CRRT), improves liver function, survival rates, and neurological outcomes in patients with dengue virus. Both high- and low-volume plasma exchanges were effective.

This systematic review highlights the beneficial role of PLEX and the potential benefits of combination therapies in the treatment of rare and severe forms of dengue-associated ALF. However, given the limited sample sizes and the necessity for well-designed studies, further investigations are needed to determine the optimal volume of PLEX and the efficacy of additional therapeutic strategies.

Acute liver failure (ALF) in dengue is rare but fatal. Early identification of patients who are at risk of ALF is the key strategy to improve survival.

To validate prognostic scores for predicting ALF and in-hospital mortality in dengue-induced severe hepatitis (DISH).

We retrospectively reviewed 2532 dengue patients over a period of 16 years (2007-2022). Patients with DISH, defined as transaminases > 10 times the normal reference level and DISH with subsequent ALF, were included. Univariate regression analysis was used to identify factors associated with outcomes. Youden's index in conjunction with receiver operating characteristic (ROC) analysis was used to determine optimal cut-off values for prognostic scores in predicting ALF and in-hospital death. Area under the ROC (AUROC) curve values were compared using paired data nonparametric ROC curve estimation.

Of 193 DISH patients, 20 developed ALF (0.79%), with a mortality rate of 60.0%. International normalized ratio, bilirubin, albumin, and creatinine were independent predictors associated with ALF and death. Prognostic scores showed excellent performance: Model for end-stage liver disease (MELD) score ≥ 15 predicted ALF (AUROC 0.917, sensitivity 90.0%, specificity 88.4%) and ≥ 18 predicted death (AUROC 0.823, sensitivity 86.9%, specificity 89.1%); easy albumin-bilirubin (ALBI) score ≥ -30 predicted ALF and death (ALF: AUROC 0.835, sensitivity80.0%, specificity 72.2%; death: AUROC 0.808, sensitivity 76.9%, specificity 69.3%); ALBI score ≥ -2 predicted ALF and death (ALF: AUROC 0.806, sensitivity 80.0%, specificity 77.4%; death: AUROC 0.799, sensitivity 76.9%, specificity 74.3%). Platelet-ALBI score also showed good performance in predicting ALF and death (AUROC = 0.786 and 0.699, respectively). MELD and EZ-ALBI scores had similar performance in predicting ALF (Z = 1.688, P = 0.091) and death (Z = 0.322, P = 0.747).

MELD score is the best predictor of ALF and death in DISH patients. EZ-ALBI score, a simpler yet effective score, shows promise as an alternative prognostic tool in dengue patients.

Dengue virus (DENV) infection causes various disease manifestations ranging from an asymptomatic state to severe, life-threatening dengue. Despite intensive research, the molecular mechanisms underlying the abnormal host responses and severe disease symptoms caused by evolved DENV strains is not fully understood. First, the spatial structure of mutant DENV was compared via in silico molecular modeling analysis. Second, employing single-nucleus and spatial RNA sequencing, we analyzed and verified transcriptome samples in uninfected, mild (NGC group), and severe (N10 group) liver tissues from murine models. In this study, we obtained a cumulatively mutated DENV-2 N10 with enhanced capability of replication and pathogenicity post 10 serial passages in Ifnra-/- mice. This variant caused severe damage in the liver, as compared with other organs. Furthermore, mutated DENV infection elicited stronger responses in hepatocytes. The critical host factor Nrg4 was identified. It dominated mainly via the activation of the NRG/ErbB pathway in mice with severe symptoms. We report on evolved N10 viruses with changes observed in different organisms and tissue. This evolutionary variant results in high replicability, severe pathogenicity, and strong responses in murine. Moreover, the host responses may play a role by activating the NRG/ErbB signaling pathway. Our findings provide a realistic framework for defining disturbed host responses at the animal model level that might be one of the main causes of severe dengue and the potential application value.

Although liver involvement has been observed in over two-third cases of dengue viral infection, less than 1% cases progress to dengue-related acute liver failure (D-ALF). Various aspects of management of this disease remain debated including the need and timing of liver transplantation (LT). Moreover, the outcomes of LT for D-ALF have been suboptimal. We present four contrasting cases of D-ALF, two managed with LT and the other two conservatively to highlight the management dilemmas concerning LT in D-ALF. Based on our 4 cases, we would consider dengue shock syndrome, multisystem involvement and neurological deficit not completely accounted for by the ALF as potential contraindications for LT. These would need to be revisited on a case-to-case basis till larger studies define objective selection criteria for LT in D-ALF.

Acute liver failure (ALF) is a devastating consequence of dengue infection. This systematic review and meta-analysis assessed the incidence of ALF in dengue infection and its associated mortality. We systematically searched the EMBASE and MEDLINE databases from inception to December 2023 for observational studies reporting ALF incidence and mortality in dengue patients. Twenty-one studies encompassing 26,839 dengue-infected patients were included. Meta-analysis revealed a pooled incidence of ALF in cases of general dengue infection of 2.0 % (95 % CI, 1.2-3.0 %), with 1.2 % (95 % CI, 0.6-2.1 %) in adults and 5.0 % (95 % CI, 1.5-10.2 %) in children. ALF incidence was 17.3 % (95 % CI, 6.5 %-31.5 %) in severe dengue and 7.4 % (95 % CI, 0.8-18.5 %) in dengue shock syndrome. The pooled mortality rate of dengue-associated ALF was 47.0 % (95 % CI, 32.9-61.2 %). These findings underscore the detrimental impact of dengue infection on the development of the relatively uncommon, albeit life-threatening, condition of ALF.

Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.

Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40 years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000 IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.

The acute inflammatory milieu in patients with acute liver failure (ALF) results in 'toxic' blood in these patients. In vitro experiments have shown that the plasma obtained from ALF patients is toxic to rabbit hepatocytes and inhibits regeneration of rat hepatocytes. Treatments such as plasma exchange and continuous renal replacement therapy to cleanse the blood have improved survival in ALF patients. In the liver microcirculation, the exchange of fluid across fenestrae in liver sinusoidal endothelial cells (LSECs) is vital for proper functioning of hepatocytes. Clogging of the liver filter bed by inflammatory debris and cells ('traffic jam hypothesis') impeding blood flow in sinusoids may in turn reduce the exchange of fluid across LSEC fenestrae and cause dysfunction and necrosis of hepatocytes in ALF patients. In mouse model of paracetamol overdose, disturbances in microcirculation in the liver preceded the development of injury and necrosis of hepatocytes. This may represent a reversible pathophysiological mechanism in ALF which may be improved by the anti-inflammatory effect of plasma exchange. Wider access to urgent plasma exchange is a major advantage compared to urgent liver transplantation to treat ALF patients worldwide, especially so in resource constrained settings. Continuous hemo-filtration or dialysis is used to reduce ammonia levels and treat cerebral edema in ALF patients. In this review, we discuss the different modalities to cleanse the blood in ALF patients, with an emphasis on plasma exchange, from a hepatology perspective.

Acute liver failure is a rare condition involving the rapid development, progression, and worsening of liver dysfunction, characterised by coagulopathy and encephalopathy, and has a high mortality unless liver transplantation is performed. Population-based studies are scarce, and most published data are from high-income countries, where the main cause of acute liver failure is paracetamol overdose. This Review provides an overview of the scanty literature on acute liver failure in low-income and middle-income countries, where patients are often admitted to primary care hospitals and viral hepatitis (especially hepatitis E), tropical infections (eg, dengue), traditional medicines, and drugs (especially anti-tuberculosis drugs) have an important role. We discuss incidence, cause, occurrence in children and pregnant women, prognostic factors and scores, treatment, and mortality. To conclude, we advocate for international collaboration, the establishment of central registries for the condition, and better diagnostics.

The World Health Organization (WHO) has revised dengue case classification in 2009 to better reflect the severity of the disease. However, there was no comprehensive meta-analysis of pooled routine blood parameters according to the age or the categories of the 2009 WHO classification. This study aimed to meta-analyze the routine blood parameters of dengue infected children and adults. Electronic search was performed with eligible articles included for review. Meta-analysis was conducted for six blood parameters stratified into children, adults and all ages, which were further grouped into the three 2009 WHO case classifications (dengue without warning signs, DwoWS; dengue with warning signs, DwWS; severe dengue, SD), non-severe dengue (non-SD) and 'All' cases. A total of 55 articles were included in the meta-analysis. Fifteen studies were conducted in the children's age category, 31 studies in the adult category and nine studies in all ages. The four selected pooled blood parameters for children were white blood cell (WBC) (×103/L) with 5.11 (SD), 5.64 (DwWS), 5.52 (DwoWS) and 4.68 (Non-SD) hematocrit (HCT) (%) with 36.78 (SD), 40.70 (DwWS), 35.00 (DwoWS) and 29.78 (Non-SD) platelet (PLT) (×103/µL) with 78.66 (SD), 108.01 (DwWS), 153.47 (DwoWS) and 108.29 (non-SD); and aspartate aminotransferase (AST) (/µL) with 248.88 (SD), 170.83 (DwWS), 83.24 (DwoWS) and 102.99 (non-SD). For adult, WBC were 4.96 (SD), 6.44 (DwWS), 7.74 (DwoWS) and 3.61 (non-SD); HCT were 39.50 (SD), 39.00 (DwWS), 37.45 (DwoWS) and 41.68 (non-SD); PLT were 49.62 (SD), 96.60 (DwWS), 114.37 (DwoWS) and 71.13 (non-SD); and AST were 399.50 (SD), 141.01 (DwWS), 96.19 (DwoWS) and 118.13 (non-SD). These blood parameters could not differentiate between each dengue severity according to the WHO 2009 classification, SD, DwoWS, DwWS and non-SD, because the timing of blood drawing was not known and there was an overlapping confidence interval among the clinical classification. Hence, these pooled blood parameter values could not be used to guide clinicians in management and did not correlate with severity as in previous scientific literatures and guidelines.

While dengue infection is common in India, there is scarce information on dengue hepatitis. The aim of this study was to analyze the incidence, spectrum and outcome of dengue hepatitis.

We retrospectively analyzed consecutive patients, who had hepatitis among those with dengue infection admitted to two tertiary care hospitals in western India from January 2016 to March 2021. Diagnosis of dengue infection was made by serology. Dengue hepatitis was diagnosed and the severity of dengue was categorized by standard criteria.

Of 1664 patients admitted with dengue fever during the study period, 199 patients had hepatitis (i.e. incidence of dengue hepatitis was 11.9%). Of the 199 dengue hepatitis patients (age: 29 [13 - 80] years, median [range], 67% males), 100 patients (50%) had severe dengue, 73 (36%) had severe dengue hepatitis, 32 (16%) had dengue shock syndrome and eight (4%) had acute liver failure. Forty-five patients (23%) had acute lung injury and 32 (16%) had acute kidney injury. The dengue hepatitis patients were treated with standard medical care, including vital organ support, as needed-166 (83%) patients survived, while 33 patients (17%) died (cause of death: multi-organ failure: 24 patients, septic shock: nine patients). The presence of shock independently predicted mortality (odds ratio 6.4, 95% confidence interval: 1.2 - 34). Among patients with dengue hepatitis, mortality rate was higher in those with severe dengue (23%), dengue shock syndrome (47%), severe dengue hepatitis (24%) and acute liver failure (38%).

In this large series of hospitalized patients with dengue infection, the incidence of dengue hepatitis was 11.9%. Among 199 dengue hepatitis, 17% died; multi-organ failure was the commonest cause for death and death rate was higher in patients with more severe disease. The presence of shock at presentation independently predicted mortality.

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.

The global burden of deaths caused by liver failure is substantial. The Asia-Pacific region is home to more than half of the global population and accounted for 62.6% of global deaths because of liver diseases in 2015. The aetiology of liver failure varies in different countries at different times. Viruses (Hepatitis A, B and E), drugs (herbs and anti-tuberculous drugs), toxins (alcohol use) and autoimmune flares are mainly responsible of majority of liver failure in individuals with normal liver (acute liver failure; ALF); else these may precipitate liver failure in those with chronic liver disease (acute-on-chronic liver failure; ACLF). Concomitant increases in alcohol misuse and metabolic syndrome in recent years are concerning. Ongoing efforts to address liver failure-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. In light of the ever-changing nature of liver disease epidemiology, accurate estimates for the burden of liver failure across the countries are vital for setting clinical, research and policy priorities. In this review, we aimed to describe the current as well as changing epidemiological trends of common liver failure syndromes, ALF and ACLF in the Asia-Pacific region.

Dengue hemorrhagic fever (DHF) is one of the most rapidly emerging infections of tropical and subtropical regions worldwide. It affects more rural and urban areas due to many factors, including climate change. Although most people with dengue viral infection are asymptomatic, approximately 25% experience a self-limited febrile illness with mild to moderate biochemical abnormalities. Severe dengue diseases develop in a small proportion of these patients, and the common organ involvement is the liver. The hepatocellular injury was found in 60%-90% of DHF patients manifested as hepatomegaly, jaundice, elevated aminotransferase enzymes, and critical condition as an acute liver failure (ALF). Even the incidence of ALF in DHF is very low (0.31%-1.1%), but it is associated with a relatively high mortality rate (20%-68.3%). The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis, immune-mediated hepatocyte injury induced hepatitis, and cytokine storm. Hepatic hypoperfusion is another contributing factor in dengue shock syndrome. The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.

Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue (SD), which is potentially lethal and involves vascular permeability changes, severe hemorrhage and organ damage. The involvement of the liver is a fairly common feature in DEN, and alterations range from asymptomatic elevation of transaminases to acute liver failure. Since its introduction in Brazil in 1990, two strains of Dengue virus (DENV) serotype 2 (DENV-2) have been detected: Lineage I, which is responsible for an outbreak in 1991, and Lineage II, which caused an epidemic greater than the previous one and had a different epidemiological profile. To date, studies on different strains of the same serotype/genotype and their association with disease severity are scarce. In addition, one of the greatest challenges regarding the study of DEN pathogenesis and the development of drug and vaccine therapies is the absence of an animal model that reproduces the disease as it occurs in humans. The main goals of this study were to assess BALB/c mouse susceptibility experimentally infected by two distinct DENV-2 strains and characterize possible differences in the clinical signs and alterations induced in the liver resulting from those infections. Mice infected by the two DENV-2 lineages gained less weight than uninfected mice; however, their livers were slightly heavier. Increased AST and AST levels were observed in infected mice, and the number of platelets increased in the first 72 h of infection and subsequently decreased. Mice infected with both lineages presented leukocytosis but at different times of infection. The histopathological changes induced by both lineages were similar and comparable to the changes observed in DEN fatal cases. The viral genome was detected in two liver samples. The results demonstrate the susceptibility of BALB/c mice to both DENV-2 lineages and suggest that the changes induced by those strains are similar, although for some parameters, they are manifested at different times of infection.

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.