It is likely that fewer than 50% of patients with HCC undergo definitive treatment because of age, liver function, general medical condition, and patient refusal. The modalities outlined here are based on a literature review and do not represent official VA treatment guidelines for HCC. Of the available treatments, only surgical resection and transplantation are potentially curative; other treatments are palliative, although they may be used in combination with resection or transplantation. For the plain-language patient version, see the patient treatment options.

Surgical resection

Surgical resection may be curative if HCC is detected at an early stage. Patients who are younger than 65 years of age, have Child-Pugh Class A cirrhosis, and have only 1 or 2 tumors are the best candidates. However, recurrence after resection is very high, approaching 25% per year; once a liver has formed HCC it can be considered a premalignant organ. The 5-year recurrence-free survival rate after resection is only about 20%, and fewer than 20% of HCC patients are good candidates for resection. Anatomical resection can be performed safely only in noncirrhotic patients or cirrhotic patients with fully compensated liver function. Contraindications include decompensated liver disease, anatomically unresectable disease, extrahepatic and vascular spread, and comorbid conditions precluding major abdominal surgery.

Liver transplantation

Liver transplantation likely affords the best long-term survival to patients with localized HCC and is an option for good transplant candidates with small tumors. Traditional limits have been a solitary encapsulated tumor less than 5 cm, or no more than 3 lesions each less than 3 cm. In one study, patients meeting these criteria had a 75% survival rate at 4 years post-transplant. Many patients also undergo therapy for HCC prior to transplantation.

Transcatheter arterial chemoembolization (TACE)

TACE combines targeted chemotherapy and arterial embolization, producing selective ischemia and chemotherapeutic effects on HCC. It tends to be used in patients with several small tumors who cannot undergo resection, or immediately pre-transplant. TACE causes minimal damage to normal liver parenchyma because of the liver's dual blood supply: the hepatic artery supplies 80 to 100% of blood flow to liver tumors but only 20 to 30% to normal tissue. A cytotoxic agent such as doxorubicin or cisplatin can be mixed with iodized oil (Lipiodol) and injected into the artery supplying the tumor. Contraindications include advanced (Child-Pugh Class C) cirrhosis, portal vein thrombosis, hepatic encephalopathy, and biliary obstruction. TACE should not be the sole therapy for patients with operable HCC who are surgical or transplant candidates.

Percutaneous ethanol injection (PEI)

PEI injects high-concentration ethanol directly into HCCs and is most effective for smaller tumors, performed under direct tumor visualization (usually ultrasound), percutaneously or intraoperatively. Major complications are rare (about 1.3 to 2.4%). Compared with surgery, PEI causes minimal loss of normal liver tissue and can be repeated easily when new lesions appear. To achieve more complete necrosis of larger (greater than 3 cm) tumors, PEI has been combined with TACE.

Radiofrequency ablation (RFA)

RFA is a localized therapy, usually performed under sonographic guidance, in which an alternating electric current causes thermal injury around a needle electrode inserted into the tumor. The goal is to ablate the tumor plus a small margin of normal tissue. Effectiveness has been compared favorably with PEI for small tumors.

Hepatic artery chemotherapy

Chemotherapeutic agents can be delivered via hepatic arterial infusion through an implantable pump directly to HCCs, increasing local drug concentrations while minimizing systemic effects. Agents used include 5-fluorouracil (5-FU) and FUDR. Complications include impaired liver function, biliary sclerosis, liver abscess, and dislodged catheter tip.

Systemic therapy

Historically, no systemic chemotherapeutic strategy was shown to improve outcomes in HCC compared with localized therapies. As a single agent, 5-FU had an overall response rate around 10%, and doxorubicin appeared to be the most active single agent, with a response rate near 25%. Patients with advanced cirrhosis cannot tolerate cisplatin because associated portal hypertension and hypoalbuminemia preclude the intravascular volume expansion needed to prevent renal toxicity. Targeted and systemic agents (for example, sorafenib and newer therapies) are now used for advanced HCC; refer to current AASLD and ASCO guidance for present-day systemic therapy recommendations.

Guidelines and references

See Screening and Surveillance Guidelines for VA consensus pathways and the AASLD guidelines. References for this topic are listed on the Background and Epidemiology page.