Dengue fever is the most rapidly spreading mosquito-borne viral illness worldwide, particularly affecting tropical and subtropical regions. [1] India has witnessed recurrent dengue outbreaks with increasing disease burden. While dengue primarily presents as a febrile illness, hepatic involvement is increasingly recognized as a frequent and clinically relevant manifestation. [2] Liver dysfunction in dengue infection is attributed to direct viral cytopathic effects, immune-mediated injury, and hemodynamic compromise. [3] Elevation of serum transaminases is the most common hepatic abnormality reported, often with higher AST than ALT levels, distinguishing dengue-related hepatitis from viral hepatitis. [4,5] Severe hepatic involvement is more frequently observed in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).[6] Despite increasing recognition, regional data on the pattern of hepatic dysfunction in dengue remain limited. This study was conducted to evaluate the spectrum of liver function abnormalities in adult dengue patients and to compare hepatic involvement across different clinical severities.

Study Design and Setting A prospective observational study was conducted in the Department of General Medicine, Jhalawar Medical College and SRG Hospital, Jhalawar, Rajasthan, over a period of one year (November 2018–October 2019). Study Population Adult patients aged ≥18 years admitted with serologically confirmed dengue infection were included. Inclusion Criteria • Serologically confirmed dengue infection (NS1 antigen and/or IgM/IgG ELISA positive) • Classification into DF, DHF, or DSS as per WHO criteria Exclusion Criteria • Pre-existing chronic liver disease • Alcoholic liver disease • Drug-induced hepatotoxicity • Acute viral hepatitis, malaria, typhoid, or other co-infections • Non-alcoholic fatty liver disease Data Collection Clinical data were collected using a pre-structured proforma. Laboratory investigations included complete blood count, hematocrit, dengue serology, and liver function tests (bilirubin, AST, ALT, ALP, albumin). Imaging studies included ultrasonography and chest radiography where indicated. Statistical Analysis Data were analyzed using SPSS version 23. Continuous variables were expressed as mean ± standard deviation and categorical variables as frequencies and percentages. Comparisons across dengue severity groups were performed using Chi-square test and ANOVA/Kruskal-Wallis test. A p-value <0.05 was considered statistically significant. Ethical Considerations Institutional Ethics Committee approval was obtained. Written informed consent was taken from all participants.

In table 1 a total of 91 adult patients with serologically confirmed dengue infection were included. The mean age of the study population was 32.86 years, with the majority of patients (44.0%) belonging to the 21–30-year age group. The age distribution showed a predominance of young adults, reflecting the working-age population being most affected. Sex distribution was nearly equal, with 46 males (50.5%) and 45 females (49.5%), resulting in a male-to-female ratio of 1.02:1. Table 1. Demographic Characteristics of Study Population (n = 91) Variable Number (%) Age (years) 18–20 16 (17.6) 21–30 40 (44.0) 31–40 12 (13.2) 41–50 10 (11.0) 51–60 8 (8.8) >60 5 (5.5) Mean ±SD 32.86 ± 16.28 Sex Male 46 (50.5) Female 45 (49.5) Clinical Severity of Dengue Infection In figure 1 based on WHO criteria, 63 patients (69.2%) were diagnosed with dengue fever (DF), 25 patients (27.5%) with dengue hemorrhagic fever (DHF), and 3 patients (3.3%) with dengue shock syndrome (DSS). Figure 1. Distribution of Dengue Severity Dengue Serological Profile In table 2 NS1 antigen positivity was observed in 86 patients (94.5%), indicating early presentation in the majority of cases. IgM positivity was seen in 24.2%, while IgG positivity was observed in 5.5%, suggesting a smaller proportion of secondary dengue infections. Table 2. Dengue Serological Profile Serology Number (%) NS1 antigen positive 86 (94.5) IgM positive 22 (24.2) IgG positive 5 (5.5) NS1 + IgM 17 (18.7) NS1 + IgG 4 (4.4) NS1 + IgM + IgG 1 (1.1) Hepatic Dysfunction in Dengue Serum Bilirubin Abnormal serum bilirubin levels (>1.2 mg/dL) were observed in 15 patients (16.5%). The frequency of hyperbilirubinemia increased with disease severity: • DF: 9.5% • DHF: 24.0% • DSS: 100% All patients with DSS demonstrated abnormal bilirubin levels. Table 3. Distribution of Abnormal Bilirubin Levels by Dengue Severity Dengue Category Normal n (%) Abnormal n (%) DF (n=63) 57 (90.5) 6 (9.5) DHF (n=25) 19 (76.0) 6 (24.0) DSS (n=3) 0 (0) 3 (100) Total (n=91) 76 (83.5) 15 (16.5) Figure 2. Abnormal Bilirubin Levels Across Dengue Severity Serum Transaminases Elevation of serum transaminases was the most common hepatic abnormality. AST elevation predominated over ALT across all categories of dengue. The magnitude and frequency of enzyme elevation increased progressively from DF to DHF and DSS. • Mild to moderate elevations were common in DF • Higher elevations were observed in DHF • Markedly raised transaminases were seen in DSS Table 4. Pattern of Hepatic Involvement Across Dengue Severity Parameter DF (%) DHF (%) DSS (%) Elevated AST High Very high Universal Elevated ALT Moderate High Universal AST > ALT pattern Predominant Predominant Predominant Hypoalbuminemia Low Moderate High

The present prospective observational study evaluated hepatic dysfunction in 91 adult patients with serologically confirmed dengue infection and demonstrated that liver involvement is a frequent finding across the clinical spectrum of dengue. The study population predominantly comprised young adults, with a mean age of 32.86 years, and nearly equal gender distribution (50.5% males and 49.5% females), reflecting current epidemiological trends in dengue-endemic regions. Dengue fever constituted the majority of cases (69.2%, n = 63), while 27.5% (n = 25) had dengue hemorrhagic fever (DHF) and 3.3% (n = 3) presented with dengue shock syndrome (DSS). This distribution is comparable to previously published Indian studies reporting DHF prevalence ranging from 20% to 35% among hospitalized dengue patients. Hepatic dysfunction was commonly observed, with serum transaminase elevation being the predominant abnormality. Although precise enzyme cut-offs varied, AST elevation was consistently more frequent and pronounced than ALT elevation across all severity groups. This AST predominance aligns with earlier studies reporting AST elevation in 85–98% of dengue patients, compared to ALT elevation in 70–90%, and is thought to reflect combined hepatic and extra-hepatic (muscle) injury in dengue infection. Hyperbilirubinemia was observed in 16.5% (15/91) of patients overall. When stratified by disease severity, abnormal bilirubin levels were present in 9.5% of DF, 24.0% of DHF, and 100% of DSS patients. The universal presence of hyperbilirubinemia in DSS patients underscores the strong association between severe dengue and significant hepatic involvement. Similar trends have been reported by Nguyen et al. [3] and Goyal et al. [7], where bilirubin abnormalities ranged from 15% to 30% in severe dengue cases. The progressive increase in hepatic dysfunction from DF to DHF and DSS observed in this study supports the hypothesis that liver injury in dengue is multifactorial. Direct viral hepatocyte injury, immune-mediated inflammation, cytokine-induced endothelial dysfunction, and hypoxic damage secondary to plasma leakage and shock all likely contribute to worsening liver biochemistry in severe disease. Previous studies have shown that patients with DHF and DSS exhibit transaminase levels 2–5 times higher than those seen in uncomplicated dengue fever, consistent with the pattern observed in this study. [8,9] Despite biochemical evidence of hepatic involvement, clinically overt liver failure was not observed in this study. This finding is consistent with existing literature indicating that while mild to moderate hepatic dysfunction is common, fulminant hepatic failure remains rare, reported in <1–2% of dengue cases. The absence of liver failure in the present study may be attributed to early diagnosis, supportive management, and exclusion of patients with pre-existing liver disease. The predominance of young adults (44.0% aged 21–30 years) highlights the significant socioeconomic impact of dengue-related morbidity. Additionally, the nearly equal male-to-female ratio contrasts with older studies reporting male predominance, suggesting changing exposure patterns and improved healthcare access among women. Overall, the presence of hyperbilirubinemia in one-fourth of DHF patients and all DSS patients, along with widespread transaminase elevation, emphasizes that hepatic dysfunction is not merely incidental but closely linked to disease severity.

Hepatic dysfunction is a frequent and clinically relevant manifestation of adult dengue infection. Transaminase elevation, particularly AST predominance, is the most common abnormality and correlates with disease severity. Routine liver function monitoring is recommended in dengue patients, especially in those with severe clinical presentations. Limitations •Single-center study •Relatively small sample size •Lack of long-term follow-up of hepatic recovery

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