What is the optimal management for a patient with newly diagnosed hepatocellular carcinoma, impaired consciousness (low Glasgow Coma Scale) on high‑flow oxygen and palliative‑care referral who now presents with melena indicating an upper gastrointestinal bleed, acute kidney injury out of proportion to the bleed, and hypercalcemia?

Management of HCC Patient with UGIB, Impaired Consciousness, and Palliative Status

In this patient with newly diagnosed HCC, poor Glasgow Coma Scale, palliative care referral, and now upper GI bleeding with AKI and hypercalcemia, the priority is comfort-focused symptom management without invasive interventions, as curative or life-prolonging treatments are contraindicated by the patient's poor performance status and decompensated state.

Immediate Management Priorities

Avoid Invasive Endoscopy and Resuscitation

• Do not pursue urgent endoscopy or aggressive resuscitation in this palliative patient with poor GCS. The patient's impaired consciousness (poor GCS) indicates ECOG performance status ≥2, which is an absolute contraindication to TACE and other HCC-directed therapies 1.
• Endoscopy in HCC patients with UGIB is typically performed to identify variceal versus non-variceal bleeding sources, but in 53% of HCC patients with UGIB, the source is non-variceal (most commonly duodenal ulceration), and direct tumor invasion into the GI tract occurs in only a small minority 2.
• Given the palliative goals of care and poor functional status, invasive diagnostic procedures will not change management and may worsen patient comfort 1.

Address Hypercalcemia Symptomatically

• Hypercalcemia in HCC is a paraneoplastic syndrome associated with poor prognosis and should be managed with bisphosphonates only if symptomatic relief is achievable. 3
• Zoledronic acid 4 mg IV over 15 minutes can reduce serum calcium in malignancy-associated hypercalcemia, though renal toxicity is a concern 4.
• However, given the concurrent AKI, zoledronic acid is relatively contraindicated. The FDA label specifies that zoledronic acid should be avoided in patients with advanced kidney dysfunction, and this patient has disproportionate AKI 4.
• Focus instead on hydration (if tolerated and not causing volume overload) and symptom management for hypercalcemia-related confusion, nausea, and pain 3.

Manage AKI Conservatively

• The AKI with disproportionate urea/creatinine ratio suggests pre-renal azotemia from GI bleeding, but avoid nephrotoxic agents. 5
• Do not administer contrast for imaging or zoledronic acid, as both worsen renal function 4, 5.
• Gentle volume resuscitation with crystalloids may be appropriate if consistent with palliative goals, but avoid aggressive fluid resuscitation that could precipitate pulmonary edema in a patient on high-flow oxygen 1.

Why HCC-Directed Therapies Are Contraindicated

TACE Is Not an Option

• TACE or TAE should not be used in patients with decompensated liver disease, advanced kidney dysfunction, or ECOG performance status ≥2. 1
• This patient meets multiple absolute contraindications: impaired consciousness (ECOG ≥2), AKI (advanced kidney dysfunction), and likely decompensated cirrhosis given the clinical presentation 1.

Systemic Therapy Is Not Appropriate

• Atezolizumab plus bevacizumab, the first-line systemic therapy for advanced HCC, requires careful assessment for contraindications including recent GI bleeding. 1
• Active UGIB is a contraindication to bevacizumab due to bleeding risk, and the patient's poor performance status precludes systemic therapy 1.
• Alternative oral agents (sorafenib, lenvatinib) are also inappropriate given the patient's palliative status and poor functional capacity 1.

Avoid Ineffective Therapies

• Do not use tamoxifen, which has been definitively shown to be ineffective for HCC and should be regarded as a placebo drug. 6

Palliative and Comfort-Focused Care

Optimize Symptom Control

• Prioritize minimizing pain and avoiding opioid-induced constipation, which is particularly important in patients with GI bleeding. 1
• Use non-opioid analgesics where possible; if opioids are necessary, co-prescribe laxatives prophylactically 1.

Manage GI Bleeding Conservatively

• Consider early adjunctive iron support, including parenteral iron, if the patient survives the acute bleeding episode and transfusion is consistent with goals of care. 1
• Proton pump inhibitors (PPIs) can be used empirically for suspected peptic ulcer disease, which is the most common non-variceal cause of UGIB in HCC patients 2.
• Avoid nasogastric tube placement unless the patient explicitly requests this intervention and other measures have failed, as it adds discomfort without improving outcomes in palliative patients 1.

Address Underlying Liver Disease Complications

• If ascites develops or worsens, manage with sodium restriction, spironolactone plus furosemide, and large-volume paracentesis when indicated, rather than tumor-directed therapy 6.
• The presence of ascites is a poor prognostic indicator and reflects advanced liver disease requiring focus on liver-function preservation and symptomatic management 6.

Prognosis and Goals of Care Discussion

Clarify Code Status and Treatment Limitations

• For patients with ≥70% risk of death within 1 year (which this patient clearly meets), ensure palliative care involvement is active and goals of care are clearly documented. 1
• The combination of newly diagnosed HCC, poor GCS, UGIB, AKI, and hypercalcemia indicates extremely poor prognosis, likely measured in days to weeks 1, 3.

Focus on Quality of Life

• Remote monitoring of patient-reported outcome measures and treatment to optimize symptoms and quality of life should be the primary focus. 1
• Avoid interventions that prolong suffering without meaningful benefit, including ICU admission, mechanical ventilation, or dialysis 1.

Common Pitfalls to Avoid

• Do not reflexively pursue endoscopy or imaging "to complete the workup" in a patient with established palliative goals. These interventions cause discomfort and will not change management 1.
• Do not administer zoledronic acid for hypercalcemia in the setting of AKI, as renal toxicity is significantly increased 4.
• Do not attempt TACE or systemic therapy in a patient with poor performance status and decompensated disease, as this violates guideline contraindications and will worsen outcomes 1.
• Recognize that direct tumor invasion into the GI tract is rare (only 3/55 patients in one series), so the bleeding is more likely variceal or peptic ulcer disease, but this distinction does not alter palliative management 2.