What are the potential causes and treatment options for a patient with abdominal pain, elevated liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)), hyperbilirubinemia (elevated total, direct, and indirect bilirubin), and leukocytosis (elevated white blood cell count)?

Differential Diagnosis and Management of Abdominal Pain with Elevated Liver Enzymes, Hyperbilirubinemia, and Leukocytosis

This clinical presentation demands immediate evaluation for acute cholangitis, acute cholecystitis, or hepatic abscess, as these life-threatening conditions require urgent intervention and can rapidly progress to sepsis and death if untreated.

Immediate Diagnostic Approach

Essential First-Line Laboratory Tests

• Fractionated bilirubin (direct and indirect) is mandatory to determine if hyperbilirubinemia is conjugated or unconjugated, as this fundamentally changes the differential diagnosis 1
• Complete hepatic panel including ALT, AST, alkaline phosphatase (ALP), albumin, and prothrombin time/INR to assess synthetic liver function and pattern of injury 1
• Inflammatory markers (CRP, procalcitonin) should be obtained immediately given the leukocytosis and abdominal pain, as this combination with elevated bilirubin suggests cholangitis or hepatic abscess 1
• Confirm GGT elevation is hepatobiliary in origin rather than from other sources 1

Critical Imaging Strategy

• Right upper quadrant ultrasound with Doppler is the mandatory first-line imaging to detect biliary dilation, gallstones, cholecystitis, focal hepatic lesions, hepatic vascular abnormalities, and ascites 1
• CT abdomen with IV contrast (triphasic) should be performed urgently if ultrasound is inadequate, if malignancy is suspected, or if there is concern for hepatic abscess, as ultrasound has 90% sensitivity for amoebic liver abscess but can miss high liver lesions 2, 1
• MRCP is indicated for detailed biliary tree evaluation if cholestatic pattern exists without obvious obstruction on ultrasound 1

Most Likely Differential Diagnoses

Acute Biliary Obstruction with Cholangitis (Highest Priority)

• Choledocholithiasis with ascending cholangitis presents with fever, right upper quadrant pain, jaundice (Charcot's triad), and leukocytosis 2
• Elevated conjugated bilirubin with elevated ALP indicates obstructive biliopathy 2
• This requires urgent ERCP if confirmed, as mortality increases significantly without prompt biliary decompression 1

Acute Calculous Cholecystitis

• Gallstones causing cystic duct obstruction lead to gallbladder inflammation, presenting with right upper quadrant pain, fever, and leukocytosis 2
• Elevated transaminases (ALT/AST) can occur with acute cholecystitis, though typically less pronounced than in hepatocellular injury 2
• Murphy's sign on ultrasound (sonographic Murphy's sign) has high specificity for acute cholecystitis 2

Hepatic Abscess (Pyogenic or Amoebic)

• Combination of fever, elevated right hemidiaphragm on chest X-ray, and hepatomegaly should raise suspicion for amoebic liver abscess, which presents with abdominal pain (72-95%), fever (67-98%), and hepatomegaly (43-93%) 2
• Neutrophil leukocytosis >10 × 10⁹/L, raised inflammatory markers, and deranged liver function tests (particularly raised alkaline phosphatase) are common 2
• Pyogenic abscess is the main differential diagnosis and is more likely to be multiple in older age groups 2
• Ultrasound or CT will demonstrate the abscess; if diagnostic uncertainty exists, percutaneous aspiration is warranted 2

Acute Viral or Drug-Induced Hepatitis

• Hepatic inflammation from acute hepatitis (hepatitis A, B, C, D, E, Epstein-Barr virus) can disrupt transport of conjugated bilirubin 2
• Medication-induced liver injury from common drugs including acetaminophen, penicillin, oral contraceptives, estrogenic or anabolic steroids can result in abnormal liver function tests with hyperbilirubinemia 2
• Review all medications and supplements that may cause hepatotoxicity and rule out abnormal liver enzymes from development or progression of liver metastases 2

Malignancy-Related Obstruction

• Cholangiocarcinoma, gallbladder cancer, or pancreatic tumor can present with biliary obstruction, increasing direct bilirubin 2
• Elevated GGT with bilirubin may indicate biliary obstruction from cholangiocarcinoma or metastatic disease, particularly in older patients 1
• Diffuse malignancy such as lymphoma can cause extrinsic biliary compression 2

Treatment Algorithm Based on Etiology

If Cholangitis is Confirmed or Suspected

• Immediate broad-spectrum antibiotics (e.g., ceftriaxone and metronidazole) are required for patients with evidence of systemic inflammatory response syndrome 2
• Urgent biliary decompression via ERCP within 24-48 hours is life-saving 1
• Hospitalization is mandatory for monitoring and supportive care 2

If Acute Cholecystitis is Confirmed

• Broad-spectrum antibiotics covering gram-negative and anaerobic organisms 2
• Surgical consultation for cholecystectomy, ideally within 72 hours of symptom onset 2
• Supportive care including IV fluids, pain control, and NPO status 2

If Hepatic Abscess is Confirmed

• Empirical therapy with metronidazole 500 mg TDS orally for 7-10 days results in cure of over 90% for amoebic liver abscess 2
• Tinidazole 2 g daily for 3 days is an alternative with less nausea 2
• Broad-spectrum antibiotics (e.g., ceftriaxone and metronidazole) until diagnosis is confirmed, as pyogenic abscess is the main differential 2
• Most patients respond within 72-96 hours; surgical or percutaneous drainage is rarely required unless symptoms persist after 4 days of treatment or risk of imminent rupture 2
• Once treatment with tinidazole or metronidazole is complete, all patients should receive a luminal amoebicide (diloxanide furoate 500 mg orally TDS or paromomycin) to reduce risk of relapse 2

If Drug-Induced Hepatotoxicity is Suspected

• Stop all potentially hepatotoxic medications immediately 2
• If AST/ALT rises to five times normal or bilirubin level rises, stop rifampicin, isoniazid, and pyrazinamide if patient is on tuberculosis treatment 2
• Monitor liver function every 3 days if Grade 2 hepatic toxicity (AST/ALT 3.0 to 5.0 × ULN and/or total bilirubin 1.5 to 3.0 × ULN) 2
• Consider corticosteroids (0.5-1 mg/kg/day prednisone) if no improvement after 3-5 days in Grade 2 hepatic toxicity 2

If Viral Hepatitis is Confirmed

• Supportive care is the mainstay for acute viral hepatitis 3
• Antiviral therapy should be initiated if chronic hepatitis B or C is diagnosed 4
• Monitor for hepatic decompensation with serial INR/PT and albumin 1

Monitoring and Follow-Up Strategy

• Repeat testing within 2-3 days is necessary if bilirubin ≥2× ULN or if combined with ALT/AST >3× ULN 1
• Assess hepatic synthetic function with INR/PT and albumin to identify patients at risk for hepatic decompensation 1
• If patient is not improving within 72-96 hours, repeat imaging and consider alternative diagnoses 2

Critical Pitfalls to Avoid

• Do not assume direct bilirubin equals conjugated bilirubin, as delta bilirubin can cause persistent hyperbilirubinemia even after underlying cause resolves 1
• Do not delay imaging in a patient with this presentation, as acute cholangitis can rapidly progress to septic shock and death 1
• Do not miss hydatid disease in patients who have lived in the Middle East, Central Asia, or Horn of Africa; review hydatid serology prior to attempting aspiration 2
• Do not overlook malignancy, particularly in patients over 50 years old with new-onset symptoms 1
• Do not forget to check for hemolysis as a cause of unconjugated hyperbilirubinemia, which can result from sickle cell disease, thalassemia, hereditary spherocytosis, or glucose-6-phosphate dehydrogenase deficiency 2