What is the appropriate initial work‑up and management for a patient presenting with epigastric pain and elevated liver enzymes?

Initial Work-Up and Management of Epigastric Pain with Elevated Liver Enzymes

Obtain an ECG within 10 minutes and order CT abdomen/pelvis with IV contrast immediately, while simultaneously starting high-dose PPI therapy (omeprazole 20–40 mg once daily) and checking complete blood count, comprehensive metabolic panel, lipase, and C-reactive protein. 1

Immediate Life-Threatening Exclusions

The first priority is ruling out cardiac and surgical emergencies that masquerade as gastrointestinal disease:

• Obtain an ECG within 10 minutes to exclude myocardial infarction, which presents with isolated epigastric pain in 10–20% of cases, especially in women, diabetics, and elderly patients, and carries 10–20% mortality if missed. 1, 2
• Measure serial troponins at 0 and 6 hours—a single troponin is unreliable for excluding NSTEMI. 1
• Check vital signs immediately for tachycardia ≥110 bpm, fever ≥38°C, or hypotension, which predict perforation, anastomotic leak, or sepsis with high specificity and 30% mortality if treatment is delayed. 3, 2

Essential Laboratory Work-Up

Order the following tests immediately to differentiate hepatobiliary, pancreatic, and peptic causes:

• Complete blood count to detect anemia (an alarm feature mandating urgent endoscopy). 3, 1
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin) to characterize the pattern of liver enzyme elevation. 1, 4
• Serum lipase or amylase (≥3× upper limit of normal has 80–90% sensitivity/specificity for acute pancreatitis, which characteristically causes epigastric pain radiating to the back). 2
• C-reactive protein and serum lactate to assess for inflammatory or ischemic processes. 3

The pattern of liver enzyme elevation guides further work-up: predominant transaminase elevation suggests hepatocellular injury (viral hepatitis, drug-induced liver disease, Wilson's disease, hemochromatosis); predominant alkaline phosphatase/GGT elevation indicates cholestasis requiring ultrasound to distinguish intra- from extrahepatic obstruction; isolated GGT elevation suggests fatty liver disease or infiltrative processes. 4

Diagnostic Imaging Strategy

• CT abdomen and pelvis with IV contrast is the gold standard when diagnosis remains unclear, identifying pancreatitis, perforation (97% sensitivity for extraluminal gas), vascular emergencies, and biliary obstruction. 1, 2
• Right upper quadrant ultrasound should be performed if biliary pathology is suspected (cholelithiasis, cholecystitis, biliary obstruction), with 89.8% sensitivity and 88.0% specificity for cholelithiasis. 5, 6
• Chest and abdominal X-rays can be obtained as an initial screen for free intraperitoneal air if CT is unavailable, though CT is far superior. 3

Immediate Therapeutic Measures

While awaiting diagnostic results:

• Start high-dose PPI therapy immediately: omeprazole 20–40 mg once daily before meals, which achieves 80–90% healing of duodenal ulcers and 70–80% healing of gastric ulcers. 3, 1
• For nausea/vomiting: ondansetron 8 mg sublingual every 4–6 hours (obtain baseline ECG due to QTc prolongation risk), promethazine 12.5–25 mg orally/rectally every 4–6 hours, or prochlorperazine 5–10 mg every 6–8 hours. 3, 2

Helicobacter Pylori Testing

• Test all patients for H. pylori using ^13^C-urea breath test or stool antigen (serology is not recommended), as eradication eliminates mortality risk from peptic ulcer disease. 3, 1
• If H. pylori-positive, initiate triple therapy: omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 10 days. 1

Indications for Urgent Endoscopy (2-Week Wait)

Refer immediately if any of the following alarm features are present:

• Age ≥55 years with new-onset dyspepsia or epigastric pain. 3, 1
• Unintentional weight loss (requires objective documentation). 3
• Anemia on CBC. 3, 1
• Dysphagia (sensation of food sticking at a specific level). 3
• Persistent vomiting (a red-flag that excludes functional dyspepsia and signals organic disease). 3, 1
• Hematemesis or melena. 3
• Palpable epigastric mass. 3
• Epigastric tenderness on examination (suggests organic pathology rather than functional disease and warrants investigation regardless of age). 3, 1

Non-Urgent Endoscopy Indications (4–8 Weeks)

• Symptoms persist beyond 8 weeks despite optimized PPI therapy (omeprazole 20–40 mg daily). 3, 1
• H. pylori-positive with ongoing symptoms after successful eradication. 3
• Treatment-resistant dyspepsia in patients ≥25 years. 3

Specific Management by Diagnosis

Acute Pancreatitis

• Use non-aggressive IV fluid resuscitation (<10 mL/kg/hour)—aggressive fluid protocols triple mortality in non-severe cases. 2

Perforated Peptic Ulcer

• Immediate surgical consultation for laparoscopic or open repair with omental patch; perforation is a surgical emergency with 30% mortality if treatment is delayed. 2

Biliary Obstruction

• MR cholangiopancreatography (MRCP) achieves high accuracy for choledocholithiasis when ultrasound and CT are indeterminate. 6

Critical Pitfalls to Avoid

• Never delay endoscopy in patients with alarm features—missing gastric cancer or advanced peptic ulcer complications leads to poor outcomes. 3, 1
• Never dismiss cardiac causes based on age or "atypical" presentation—myocardial infarction can present with isolated epigastric pain. 1, 2
• Never rely on a single troponin measurement—serial measurements at least 6 hours apart are mandatory to exclude NSTEMI. 1
• Never attribute persistent vomiting to functional dyspepsia—it is a red-flag for organic disease. 3, 1
• Never use aggressive fluid resuscitation in acute pancreatitis unless severe disease with persistent organ failure is present. 2

Follow-Up Strategy

• If symptoms resolve within 4–8 weeks, consider tapering PPI and using on-demand therapy for recurrence. 3
• Confirm H. pylori eradication with repeat stool antigen or breath test 4 weeks after completing therapy. 3
• Re-evaluate for newly emerging alarm features (weight loss, anemia, persistent vomiting)—their presence upgrades the indication to urgent endoscopy. 3