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Concurrent severe hepatitis and acute pancreatitis in dengue fever: A rare case of dengue-associated hepatopancreatitis with extreme hyper-transaminasemia
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Received: ,
Accepted: ,
How to cite this article: Vihari J, Patnaik S, Pati GK, Narayan J. Concurrent severe hepatitis and acute pancreatitis in dengue fever: A rare case of dengue-associated hepatopancreatitis with extreme hyper-transaminasemia. Adesh Univ J Med Sci Res. doi: 10.25259/AUJMSR_104_2025
Abstract
Dengue infection is well known to cause liver dysfunction, but acute pancreatitis is a rare complication. The simultaneous involvement of both organs is exceptionally rare and may mimic fulminant hepatitis, leading to delays in recognition and management. We report the case of a 34-year-old male who, on the 7th day of dengue illness, developed progressive jaundice, pruritus, and severe epigastric pain. Laboratory evaluation showed markedly elevated transaminases (aspartate aminotransferase 10,083 IU/L; alanine aminotransferase 2,665 IU/L), direct hyperbilirubinemia (3.54 mg/dL), thrombocytopenia (87 × 109/L), coagulopathy with an International Normalized Ratio (INR) 2.78, and a significant elevation in serum lipase (396 IU/L). Dengue NS1 antigen was positive, while other viral, autoimmune, and metabolic causes were excluded. Abdominal ultrasonography revealed hepatomegaly with fatty change and a mildly bulky pancreas, without biliary obstruction. A diagnosis of dengue-associated acute hepatopancreatitis with dengue-related coagulopathy was made. The patient was treated with intravenous fluids, proton pump inhibitors, analgesics, fresh-frozen plasma, and close monitoring of metabolic parameters. Clinical improvement was seen with resolution of jaundice, abdominal pain, and normalization of liver enzymes, lipase, and INR over the course of 5 days, after which he was discharged in stable condition. This case emphasizes the need to consider pancreatitis in dengue patients presenting with abdominal pain, even in the absence of conventional risk factors, as early recognition of this dual-organ involvement can prevent unnecessary interventions and improve outcomes.
Keywords
Acute pancreatitis
Coagulopathy
Dengue fever
Hepatopancreatitis
Transaminases
INTRODUCTION
Dengue fever is a globally prevalent mosquito-borne viral infection, with an estimated 390 million cases occurring each year, particularly in tropical and subtropical regions.[1] The clinical spectrum of dengue is broad, ranging from mild febrile illness to life-threatening complications such as dengue hemorrhagic fever and dengue shock syndrome. Hepatic involvement is a well-recognized manifestation of dengue, observed in up to 60% of affected individuals.[2] This can range from mild, transient elevations in liver enzymes (transaminitis) to severe forms such as acute hepatitis and, rarely, fulminant hepatic failure. In contrast, pancreatic involvement in dengue is exceedingly rare, with fewer than 100 cases of acute pancreatitis attributed to dengue infection reported in the literature to date.[3] The simultaneous occurrence of both acute hepatitis and acute pancreatitis in a patient with dengue is an unusual and diagnostically challenging scenario. Such dual organ involvement can closely mimic severe viral hepatitis or other systemic illnesses, potentially leading to delays in diagnosis and management. Here, we report a rare and intriguing case of dengue-associated acute hepatopancreatitis in a young adult, characterized by strikingly elevated aminotransferase levels. We discuss the diagnostic dilemmas, underlying pathophysiological mechanisms, and key considerations in the management of this uncommon clinical entity.
CASE REPORT
A 34-year-old male from Phulbani, Odisha, with no prior history of alcohol use, gallstone disease, or metabolic disorders, presented to our hospital with complaints of progressive yellowish discoloration of the eyes and urine, generalized pruritus, and mild, persistent epigastric pain for the past week. The abdominal pain was dull, non-radiating, and not related to food intake. He denied any vomiting or gastrointestinal bleeding.
On examination, the patient was afebrile (37.2°C), with stable vitals (blood pressure 118/72 mmHg, heart rate 88 bpm, SpO2 98% on room air). Icterus was evident, but there was no rash, lymphadenopathy, or peripheral edema. Abdominal examination revealed mild epigastric tenderness without guarding or rigidity. The liver was palpable 2 cm below the right costal margin, and there was no palpable splenomegaly. Bowel sounds were normal, and there was no evidence of ascites or peritonitis.
Laboratory investigations on admission revealed severe transaminitis (aspartate aminotransferase [AST] 10,083 IU/L, alanine aminotransferase [ALT] 2,665 IU/L), direct hyperbilirubinemia (total bilirubin 4.62 mg/dL, direct 3.54 mg/dL), coagulopathy (international normalized ratio [INR] 2.78), and thrombocytopenia (platelets 87 × 109/L). Notably, serum lipase was markedly elevated (396 IU/L), and amylase was mildly raised (112 IU/L). Electrolyte analysis showed mild hyponatremia and hypokalemia. Dengue NS1 antigen was strongly positive (16.0 index), while serologies for hepatitis A, E, B, C, and human immunodeficiency viruses were negative [Table 1]. Serum calcium, triglycerides, and autoimmune markers were within normal limits.
| Parameter | Day 7 | Day 10 |
|---|---|---|
| Hemoglobin (g/dL) | 15.0 | 13.9 |
| Platelets (×109/L) | 87 | 103 |
| Sodium (mmol/L) | 133 | 136 |
| Potassium (mmol/L) | 2.77 | 3.52 |
| Total bilirubin (mg/dL) | 4.19 | 4.62 |
| Direct bilirubin (mg/dL) | 3.52 | 3.54 |
| AST (IU/L) | 10,083 | 1,177 |
| ALT (IU/L) | 2,665 | 711 |
| ALP (IU/L) | 174 | 146 |
| Serum albumin (g/dL) | 3.29 | 3.38 |
| INR | 2.78 | 1.25 |
| Serum lipase (IU/L) | 396 | - |
| Serum amylase (IU/L) | 112 | - |
AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, ALT: Alanine transaminase, ALP: Alkaline phosphatase, INR: International normalized ratio
Imaging with abdominal ultrasonography on day 7 revealed hepatomegaly with moderate fatty infiltration and a mildly bulky, heterogeneous pancreas. There was no evidence of cholelithiasis, biliary obstruction, or peripancreatic fluid collection.
The diagnosis of acute pancreatitis was established based on the revised Atlanta classification (2012), with the patient meeting all three diagnostic criteria: (1) acute onset of persistent epigastric pain, (2) serum lipase elevation to 6.6 times the upper limit of normal (ULN) (396 IU/L; ULN 60 IU/L), and (3) imaging evidence of a mildly bulky, heterogeneous pancreas on ultrasonography. The severity was classified as mild acute pancreatitis, given the absence of organ failure or local/systemic complications. Alternative etiologies, including gallstone disease, alcohol, metabolic causes, and other viral infections were systematically excluded, establishing dengue as the causative agent.
Hospital course and management
The patient was managed with intravenous (IV) fluids, proton pump inhibitors, and opioid-sparing analgesics. Four units of fresh-frozen plasma were administered to correct coagulopathy. Hypokalemia was addressed with IV potassium supplementation. Given the risk of bacterial translocation in severe hepatitis, a third-generation cephalosporin was started empirically. The patient remained hemodynamically stable throughout his hospital stay, and his abdominal pain resolved within 48 h. Serial laboratory monitoring showed a rapid decline in transaminases and improvement in coagulation parameters. By day 10, AST had decreased to 1,177 IU/L, ALT to 711 IU/L, and INR to 1.25. Despite a mild transient increase in total bilirubin from Day 7 to Day 10 (4.19–4.62 mg/dL), consistent with the typical lag in bilirubin clearance following acute hepatocellular injury, the patient demonstrated significant clinical improvement with a marked reduction in transaminases and normalization of coagulation parameters. The patient was discharged on day 11 with advice for adequate hydration, a low-fat diet, and close outpatient follow-up.
At a 4-week review, the patient was asymptomatic, and repeat liver and pancreatic enzyme levels had normalized.
Noteworthy aspects
This case is remarkable for the extreme elevation of aminotransferases, the simultaneous occurrence of acute hepatitis and pancreatitis in a dengue NS1-positive patient, and the rapid clinical and biochemical recovery with supportive care alone. The absence of traditional risk factors for pancreatitis and the exclusion of other viral and metabolic causes further strengthen the association with dengue infection.
DISCUSSION
Dengue fever, a globally prevalent arboviral infection, is well known for its hepatic involvement, but acute pancreatitis remains a rare and under-recognized complication. The simultaneous occurrence of both hepatic and pancreatic injury, as seen in our patient, presents a diagnostic and therapeutic challenge. Our case, along with a review of published literature, highlights the clinical spectrum, diagnostic approach, and evolving understanding of the pathogenesis of dengue-associated acute pancreatitis.
Comparative analysis
To contextualize our findings, we compared our case with seven previously published reports of dengue-associated acute pancreatitis [Table 2]. Most patients were young- to middle-aged adults, with a slight male predominance. All cases presented with fever and abdominal pain, often accompanied by vomiting and myalgia. Thrombocytopenia and elevated pancreatic enzymes were universal findings, and imaging (ultrasound or computed tomography) confirmed pancreatitis in all cases. Notably, hepatic enzyme elevation was common, reflecting the dual organ involvement. Management was predominantly supportive, including IV fluids, bowel rest, and analgesia, with antibiotics reserved for select cases. The prognosis was excellent in all cases, with full recovery and no recurrence on follow-up.
| Case (Ref) | Age/ sex | Comorbidities | Dengue diagnosis | Clinical presentation | Platelets (lowest,/ mm≥) | Amylase (IU/L) | Lipase (IU/L) | AST/ ALT (IU/L) | Imaging findings | Complications | Management | Hospital Stay (days) | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case 1 | 28/ Male | None | IgM/IgG positive, NS1 negative | Fever, severe epigastric pain, vomiting | 23,000 | 229 | 258 | 747/509 | Enlarged liver, hypoechoic pancreas, mild ascites | Mild pleural effusion | IV fluids, NPO, low-fat diet | 8 | Full recovery |
| Case 2 | 32/ Female | None | IgM/IgG positive | Fever, gingivorrhagia, epigastric pain | 88,000 | 225 | 917 | 138/105 | Normal USG, no biliary pathology | Rash, pruritus | IV fluids, antihistamines | 7 | Full recovery |
| Case 3 | 21/ Male | None | NS1 positive | Fever, diffuse abdominal pain, vomiting | 32,000 | 325 | 3,250 | 210/180 | Bulky pancreas, peripancreatic fluid (CT) | Minimal ascites | IV fluids, antibiotics, NPO | 8 | Full recovery |
| Case 4 | 35/ Male | None | NS1 positive | Fever, abdominal pain, vomiting | 45,000 | 410 | 1,200 | 320/290 | Bulky pancreas, mild hepatomegaly | None | IV fluids, PPI, analgesics | 6 | Full recovery |
| Case 5 | 27/ Female | None | NS1 positive | Fever, severe epigastric pain, myalgia | 50,000 | 380 | 1,100 | 400/350 | Mildly bulky pancreas, normal liver | None | IV fluids, NPO, supportive | 7 | Full recovery |
| Case 6 | 30/ Male | None | IgM/IgG positive | Fever, epigastric pain, bloating, vomiting | 40,000 | 654 | 780 | 80/90 | Fatty liver, enlarged pancreas, minimal ascites | Renal insufficiency | TPN, IV fluids, antibiotics | 11 | Full recovery |
| Case 7 | 56/ Male | None | Serology positive (after admission) | Severe abdominal pain, then high fever | 60,000 | 350 | 1,000 | 100/90 | Bulky pancreas, peripancreatic fat stranding (CT) | None | Supportive, IV fluids | 8 | Full recovery, no recurrence at 1 year |
AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, IV: Intravenous, TPN: Total parenteral nutrition, USG: Ultrasound, IgM: Immunoglobulin M, IgG: Immunoglobulin G, CT: Computed tomography, NPO: Nil Per Os (Latin: “nothing by mouth”), PPI: Proton pump inhibitor, NS1: Non-Structural Protein 1
Comprehensive differential diagnosis of extreme hyper-transaminasemia
The extreme elevation of transaminases in our patient (AST 10,083 IU/L; ALT 2,665 IU/L) represents a rare and clinically significant finding, with AST exceeding 250 times the ULN. The AST/ALT ratio of 3.78:1 reflects the characteristic AST predominance seen in dengue hepatitis, attributed to mitochondrial injury and multi-organ involvement. A comprehensive differential diagnosis was systematically evaluated, including viral hepatitis (Hepatitis A Virus, Hepatitis B Virus, Hepatitis C Virus, Hepatitis E Virus—all serology negative), drug-induced liver injury (no hepatotoxic medication history), ischemic hepatitis (patient hemodynamically stable throughout), autoimmune hepatitis (negative autoimmune markers), and other metabolic or toxic causes. The positive dengue NS1 antigen (16.0 index), clinical timeline (Day 7 of illness), concurrent pancreatitis, and rapid improvement with supportive care alone confirmed dengue as the causative etiology. While extreme transaminase elevation in dengue is associated with severe disease classification and increased bleeding risk, most of the patients achieve complete recovery without progression to fulminant hepatic failure, as demonstrated in our case.
Pathogenesis
The pathogenesis of dengue-associated acute pancreatitis is multifactorial and remains incompletely understood. Viral infections, including dengue, can trigger an inflammatory response in the pancreas, but the precise mechanisms are still being elucidated.[4] Recent histopathological and ultrastructural studies of pancreatic tissue from fatal dengue cases have provided valuable insights. These studies demonstrate diffuse edema, mononuclear cell infiltrates (predominantly macrophages), and acinar necrosis, which are indicative with acute pancreatitis.[5] Increased vascular permeability, a hallmark of severe dengue, leads to plasma leakage and interstitial edema in the pancreas. Direct cytopathic effects of the dengue virus on acinar cells have also been proposed.[6,7]
Macrophages play a central role in both dengue pathogenesis and acute pancreatitis. They contribute to the cytokine storm and vascular leakage through the secretion of pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and High Mobility Group Box 1 (HMGB-1).[8] The detection of dengue NS3 protein within pancreatic macrophages by immunofluorescence strongly suggests active viral replication in these cells, further supporting their role in tissue injury. The intense inflammatory response is accompanied by increased levels of transforming growth factor-beta (TGF-β) and matrix metalloproteinase 9 (MMP-9), which are key modulators of fibrosis and tissue remodeling [Figure 1]. While TGF-β promotes collagen deposition and fibrosis, MMP-9 degrades extracellular matrix components, and their dysregulation may contribute to the fibrotic changes observed in severe cases.[9]
Other ultrastructural changes, such as loss of zymogen granules, dilatation of the rough endoplasmic reticulum, and acinar cell necrosis, further confirm the destructive process. The upregulation of TNF-α and MMP-9, along with low levels of anti-inflammatory cytokines (interleukin-10, TGF-β), creates a pro-inflammatory environment that perpetuates tissue injury and may link acute to chronic pancreatitis.[10] HMGB-1, a potent pro-inflammatory protein, is also elevated in dengue-infected pancreatic tissue and may amplify the inflammatory cascade through nuclear factor kappa activation.[9]
Therapeutic considerations: Antibiotic use and coagulopathy management
The use of empirical antibiotics in our case warrants discussion, as dengue is a viral infection, and routine antibiotic use is not recommended. However, patients with severe dengue and extreme hepatic dysfunction are at increased risk of bacterial co-infections, reported in 7–44% of severe dengue cases. The decision for empirical coverage was based on risk stratification, considering severe hepatitis, concurrent pancreatitis, coagulopathy, and the difficulty in distinguishing viral from bacterial complications in critically ill patients. The management of coagulopathy in dengue requires careful consideration, balancing bleeding risk against transfusion-related complications. Our patient’s severe coagulopathy (INR 2.78) with concurrent thrombocytopenia and multi-organ involvement justified fresh-frozen plasma administration per the World Health Organization guidelines, resulting in successful prevention of hemorrhagic complications and rapid INR improvement.
CONCLUSION
Our case and the reviewed literature underscore the importance of considering acute pancreatitis in dengue patients presenting with abdominal pain, especially when accompanied by elevated pancreatic enzymes and imaging findings. Early recognition and supportive management are crucial, as the prognosis is generally favorable. The pathophysiological overlap between hepatic and pancreatic injury in dengue highlights the need for a multidisciplinary approach and further research into the mechanisms of organ involvement. Reporting such cases enriches understanding of dengue’s protean manifestations and guides clinicians in endemic regions.
Acknowledgments:
We sincerely thank the Department of Medical Gastroenterology for their valuable guidance, support, and critical inputs during the preparation of this case report. Their contributions greatly improved the clarity and quality of the manuscript.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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