What is the treatment for a patient with hepatocellular carcinoma (HCC) presenting with hyperbilirubinemia and shivering?

Management of Hyperbilirubinemia and Shivering in HCC Patient

In an HCC patient presenting with high bilirubin and shivering, immediately rule out cholangitis with blood cultures and empiric broad-spectrum antibiotics (e.g., piperacillin-tazobactam or ceftriaxone plus metronidazole), while simultaneously addressing biliary obstruction with urgent ERCP or percutaneous transhepatic biliary drainage, and managing fever with acetaminophen up to 3 g/day—avoiding NSAIDs entirely due to bleeding and renal risks in cirrhotic patients. 1

Immediate Assessment and Infection Management

Shivering in an HCC patient with hyperbilirubinemia strongly suggests cholangitis or bacteremia, which requires urgent intervention:

• Obtain blood cultures immediately before starting antibiotics, as bacterial translocation and ascending cholangitis are common when biliary obstruction is present 1
• Start empiric broad-spectrum antibiotics covering gram-negative organisms and anaerobes within the first hour of presentation 1
• Monitor for sepsis indicators including hypotension, tachycardia, altered mental status, and rising lactate levels 1

Biliary Decompression Strategy

Hyperbilirubinemia in HCC typically indicates biliary obstruction from tumor compression or invasion, requiring urgent decompression:

• Bilirubin >2 mg/dL is a relative contraindication to chemoembolization unless segmental injections can be performed, making biliary drainage essential before considering locoregional therapies 2
• ERCP with stent placement is preferred for distal biliary obstruction when technically feasible 3
• Percutaneous transhepatic biliary drainage (internal-external drains) should be performed when ERCP fails or for proximal/central biliary obstruction 3
• Monitor bilirubin levels every 2-3 days after drainage to assess adequacy of decompression and guide treatment eligibility 1

Symptom Management Protocol

Fever and pain management must avoid hepatotoxic and nephrotoxic agents:

• Acetaminophen up to 3 g/day (not 4 g/day) orally or intravenously is first-line for fever and mild pain in cirrhotic patients 1
• Never use NSAIDs due to risks of gastrointestinal bleeding, ascites decompensation, and acute kidney injury in cirrhotic patients 1
• For moderate-to-severe pain unresponsive to acetaminophen, use opioids (tramadol or low-dose morphine) with mandatory co-prescription of osmotic laxatives (lactulose or polyethylene glycol) to prevent constipation-induced hepatic encephalopathy 1

Treatment Eligibility Assessment Based on Liver Function

Once infection is controlled and bilirubin improves, reassess HCC treatment options:

If Bilirubin Decreases to <2 mg/dL and Child-Pugh A:

• Consider TACE for intermediate-stage disease (BCLC B) if portal vein is patent and tumor nodules allow selective arterial access 2
• Evaluate for systemic therapy (atezolizumab plus bevacizumab or STRIDE regimen) for advanced-stage disease (BCLC C) with preserved liver function 2
• Sorafenib or lenvatinib remain alternatives if immunotherapy is contraindicated or unavailable 2, 4

If Bilirubin Remains >3 mg/dL Despite Drainage:

• Stereotactic body radiotherapy (SBRT) may be considered for localized tumor causing biliary obstruction, as it can be delivered safely despite hyperbilirubinemia and may allow subsequent treatment eligibility 3
• Best supportive care becomes primary focus if Child-Pugh C or persistent hepatic decompensation, with emphasis on symptom control, nutrition, and psychological support 2

Monitoring During Acute Phase

Close surveillance is essential during the first 2 weeks:

• Liver function tests every 2-3 days initially, then weekly once stable, monitoring ALT, AST, bilirubin, albumin, and INR 1
• Daily assessment for hepatic encephalopathy using clinical grading and ammonia levels if indicated 1
• Monitor for signs of hepatic failure including worsening coagulopathy, progressive jaundice, and altered mental status 1

Critical Pitfalls to Avoid

• Never delay antibiotics waiting for culture results when cholangitis is suspected—mortality increases significantly with each hour of delay 1
• Never use NSAIDs for pain or fever in cirrhotic patients regardless of Child-Pugh class 1
• Never prescribe opioids without concurrent laxatives as constipation can precipitate hepatic encephalopathy 1
• Never attempt TACE with bilirubin >2 mg/dL unless segmental injection is possible, as this significantly increases hepatotoxicity and mortality risk 2
• Never assume shivering is tumor-related fever without ruling out infection first, as untreated cholangitis or bacteremia can rapidly progress to septic shock 1

Antiviral Considerations

If underlying viral hepatitis is present:

• Start or continue potent nucleos(t)ide analogues (entecavir or tenofovir) immediately for HBV to prevent reactivation during HCC treatment, which occurs in 16-19% of patients and significantly worsens outcomes 1
• HBV reactivation prophylaxis should continue indefinitely throughout HCC treatment regardless of HBV DNA levels 1