European Journal of Cardiovascular Medicine

Dengue fever, a mosquito-borne viral illness caused by the dengue virus (DENV), remains a major global public health challenge with an estimated 390 million infections annually. While typically self-limiting, severe manifestations such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) contribute to significant morbidity and mortality. Hepatic involvement has emerged as a critical prognostic indicator, with liver dysfunction observed in 60-90% of hospitalized cases [1,2]. Clinical manifestations range from asymptomatic transaminase elevation to fulminant hepatic failure, often presenting with hepatomegaly (43-100% of cases), abdominal pain, jaundice, and elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels [3-5].

The pathophysiology of dengue-associated liver injury involves both direct viral cytopathic effects and immune-mediated mechanisms, with DENV-2 serotype and secondary infections showing stronger hepatotropism[2,6]. Biochemical markers demonstrate AST elevation typically exceeding ALT, with levels correlating with disease severity – severe dengue cases show 10-fold higher transaminase levels compared to classical dengue fever [4,5]. Concurrent hematological alterations, including thrombocytopenia, rising hematocrit, and leukopenia, further complicate clinical management [6,7]. Recent studies highlight the prognostic value of early hematological parameters, where total leukocyte count ≥20,000/mL and platelet count ≤20,000/mL during initial presentation predict mortality odds ratios of 11.81 and 5.53 respectively [6].

Despite growing recognition of hepatic involvement, significant knowledge gaps persist regarding optimal monitoring protocols and early predictive biomarkers. Current diagnostic reliance on late-stage clinical manifestations often delays intervention, emphasizing the need for validated biochemical parameters that enable risk stratification during the critical febrile phase [6,7]. This study aims to systematically evaluate the temporal progression of hepatic dysfunction in relation to hematological parameters, identifying early predictive markers for severe dengue progression.

This observational, prospective study was conducted over a period of six months at Department of General Medicine, Sri Aurobindo Medical College & PG Institute, Hospital-Indore a tertiary care center in central India. A total of 100 adult patients (age ≥18 years) diagnosed with dengue fever were included in the study. Patients were enrolled consecutively during the study period based on clinical suspicion and laboratory confirmation of dengue infection.

Inclusion Criteria:

• Adults aged 18 years and above.
• Laboratory-confirmed dengue infection by NS1 antigen, IgM ELISA, or RT-PCR.
• Presentation within the first 7 days of illness.

Exclusion Criteria:

• Patients with a known history of chronic liver disease, alcohol use disorder, or other pre-existing hepatic conditions.
• Patients with coinfections such as malaria, leptospirosis, or viral hepatitis.

All patients underwent a detailed clinical evaluation at the time of presentation. Clinical data collected included demographic information, duration and pattern of fever, gastrointestinal symptoms, bleeding manifestations, and signs of hepatic involvement (such as right upper quadrant pain, hepatomegaly, jaundice, or altered mental status).

Relevant laboratory investigations included complete blood count, liver function tests (serum bilirubin, AST, ALT, ALP, and albumin), renal function tests, coagulation profile, and dengue serology. Hepatic involvement was defined by the presence of elevated transaminases (AST or ALT >2 times the upper limit of normal), hyperbilirubinemia, or clinical signs suggestive of liver dysfunction. Abdominal ultrasonography was performed where indicated to assess for hepatomegaly, ascites, gall bladder wall thickening, or other hepatic abnormalities.

All data were recorded using a structured proforma and analyzed to study the pattern of hepatic involvement and its association with other clinical and laboratory parameters. Ethical clearance was obtained from the Institutional Ethics Committee. Written informed consent was obtained from all participants prior to inclusion in the study.

Table 1: Demographic Profile of Study Population (N = 100)

This table outlines the basic demographic characteristics of the 100 adult dengue patients included in the study. The majority of patients were in the 31–45 age group (40%), followed by those aged 18–30 years (35%). Males constituted a slightly higher proportion (58%) compared to females (42%). Urban residents made up 60% of the cohort, indicating a slightly higher dengue prevalence or reporting from urban areas in this sample.

Table 2: Clinical Presentation of Dengue Patients

The clinical presentation table highlights the most common symptoms experienced by the patients. All patients presented with fever, consistent with dengue's typical onset. Myalgia (82%), headache (74%), and gastrointestinal symptoms like nausea/vomiting (55%) were frequently observed. Less common findings included rash (21%) and bleeding manifestations (12%). Hepatomegaly was observed in 26% of patients, and clinical jaundice in 8%, indicating early hepatic involvement in a subset of cases.

Table 3: Liver Function Test Abnormalities

This table summarizes the liver function abnormalities indicative of hepatic involvement. Elevated AST and ALT levels were observed in 88% and 81% of patients respectively, with AST values tending to be higher than ALT—an enzyme pattern typical of viral hepatitis, including dengue. Hyperbilirubinemia was present in a smaller proportion of patients, with 19% showing raised total bilirubin and 12% elevated direct bilirubin. Hypoalbuminemia was found in 23% of patients, suggesting mild hepatic dysfunction or capillary leakage.

Table 4: Hematological Parameters

The hematological profile shows key laboratory abnormalities associated with dengue infection. Leukopenia was observed in 76% of patients, and thrombocytopenia was highly prevalent, affecting 91% of the cohort—consistent with dengue pathophysiology. A smaller proportion showed anemia (18%) and elevated hematocrit (14%), the latter suggesting hemoconcentration and plasma leakage in more severe cases. These hematological markers are important for diagnosis and monitoring of disease progression.

Table 5: Severity Stratification Based on WHO Criteria

This table categorizes patients based on the World Health Organization’s classification for dengue severity. Nearly half of the patients (46%) had dengue without warning signs, while 42% presented with warning signs such as abdominal pain, mucosal bleeding, or persistent vomiting. A smaller yet significant subset (12%) developed severe dengue, characterized by complications like shock, severe bleeding, or organ impairment, underscoring the need for close monitoring of such patients.

The present study highlights the early hepatic involvement and clinical-laboratory profile of adult dengue patients, offering valuable insights into the disease's spectrum in our setting. The demographic analysis revealed a predominance of cases among young to middle-aged adults (31–45 years: 40%), with a slight male preponderance (58%) and higher urban representation (60%). These findings align with previous studies from India and Southeast Asia, which also reported higher dengue incidence in young adults and urban populations, likely due to greater exposure to vector habitats and increased healthcare access [8,9].

Clinically, fever was universal, while myalgia (82%) and headache (74%) were prominent, consistent with the classic dengue presentation described in the literature [10,11]. Gastrointestinal symptoms such as nausea/vomiting (55%) and abdominal pain (37%) were also common, reflecting the systemic nature of dengue infection. Hepatomegaly (26%) and jaundice (8%) indicated early hepatic involvement, comparable to rates reported by Kuo et al. (hepatomegaly: 21%, jaundice: 7%) and Kumar et al. (hepatomegaly: 28%) [12,13]. The relatively lower frequency of rash (21%) and bleeding manifestations (12%) mirrors the variable cutaneous and hemorrhagic presentations observed in other cohorts [10,14].

Liver function test abnormalities were notable, with elevated AST (88%) and ALT (81%) in most patients, and AST predominance-a pattern characteristic of dengue-related hepatitis [12,15]. These enzyme elevations are in agreement with studies by Trung et al. and Parkash et al., who also reported high rates of transaminitis in dengue (AST: 80–90%, ALT: 70–85%) [15,16]. Hyperbilirubinemia (19%) and hypoalbuminemia (23%) were less frequent but underscore the potential for hepatic dysfunction and capillary leakage, as highlighted in previous reports [15,17].

Hematologically, thrombocytopenia (91%) and leukopenia (76%) were highly prevalent, corroborating the established diagnostic criteria for dengue and findings from studies by Kalayanarooj et al. and Srikiatkhachorn et al. [18,19]. Anemia (18%) and elevated hematocrit (14%) were observed in a minority, the latter suggesting plasma leakage and risk for severe disease (3,11).

Severity stratification revealed that 46% of patients had dengue without warning signs, 42% with warning signs, and 12% developed severe dengue. These proportions are similar to those reported by World Health Organization surveillance data and studies by Gupta et al., where 10–15% of hospitalized patients progressed to severe dengue [10,20]. The observed hepatic and hematological abnormalities were more pronounced in patients with severe disease, emphasizing the importance of early recognition and monitoring [15,19].

This study underscores the high prevalence of hepatic and hematological abnormalities in dengue patients, with elevated transaminases—particularly AST—and thrombocytopenia emerging as the most common findings. Hepatic involvement was evident in a significant proportion, even during early illness, highlighting its importance as a prognostic marker. The correlation between abnormal liver function tests and severe disease emphasizes the need for early biochemical monitoring. Notably, severe dengue occurred in 12% of patients, reinforcing the utility of WHO severity criteria in risk stratification. Early identification of hepatic dysfunction and hematological derangements can aid timely intervention and potentially reduce dengue-related morbidity and mortality.

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