Hepatocellular Carcinoma
GENERAL PRINCIPLES
HCC frequently occurs in patients with cirrhosis, especially when associated with viral hepatitis (HBV or HCV), alcoholic cirrhosis, #945;1AT deficiency, and hemochromatosis.
DIAGNOSIS
Clinical Presentation
• Clinical presentation is directly proportional to the stage of disease. HCC may present with right upper quadrant abdominal pain, weight loss, and hepatomegaly.
• Suspect HCC in a cirrhotic patient who develops manifestations of liver decompensation.
• Surveillance for HCC should be performed every 6 months with a sensitive imaging study. The combination of imaging with AFP is not recommended because it is unlikely to provide a gain in the detection rate. In patients with hepatitis B, surveillance should begin after age 40 years even in the absence of cirrhosis.
Diagnostic Testing
• AFP (see section “Evaluation of Liver Disease”).
• Liver ultrasound, triple-phase CT, and MRI with contrast are sensitive and often used for detection of HCC. Liver biopsy should be considered for patients at risk for HCC with suspicious liver lesions gt;1 cm with uncharacteristic imaging features (absence of arterial hypervascularity and venous or delayed phase washout).
TREATMENT
Surgical Management
• Hepatic resection is the treatment of choice in noncirrhotic patients.
• Liver transplantation is the treatment of choice for select cirrhotic patients who fall within Milan criteria (single HCC lt;5 cm or up to three nodules lt;3 cm).
• Milan criteria are used by the United Network for Organ Sharing for priority status (exception points) for liver transplantation candidacy in patients with HCC.
Locoregional Therapy
• Radiofrequency ablation (RFA) is a percutaneous ablation treatment using radiofrequency energy to produce a 3-cm area of necrosis. Sustained complete response and low complication rates were shown in very early HCC in patients with cirrhosis.
• Comparative effectiveness of other ablative techniques such as stereotactic body radiation and microwave ablation remains unclear.
• There are two transarterial embolization approaches available.
î Transarterial chemoembolization with conventional approach or doxorubicin-eluting beads improves survival in selected nonsurgical patients with large or multifocal HCC who do not have vascular invasion or metastatic disease.
î Transarterial radioembolization (TARE) with yttrium-90 may be considered in patients with HCC who are not candidates for resection or transplantation but data are still emerging.
• Selected patients with tumors beyond Milan criteria HCC can be bridged or downstaged to meet Milan criteria with TACE, RFA, and TARE prior to liver transplantation.
• The risk of hepatic decompensation because of locoregional therapy must be considered when selecting patients for bridging or downstaging.37
Medications
• Sorafenib is a small molecule that inhibits tumor cell proliferation and angiogenesis. In patients with advanced HCC and Child A cirrhosis, median survival and radiologic progression were 3 months longer for patients treated with sorafenib compared with placebo. The benefits of sorafenib in Child B cirrhosis with advanced HCC have not been established.38
• Phase III trials comparing lenvatinib (multikinase inhibitor against VEGFR1, VEGFR2, and VEGFR3) or nivolumab (human IgG4 anti-PD-1 monoclonal Ab) with sorafenib in advanced HCC with metastatic disease are ongoing.
Outcome and Prognosis
Early diagnosis is essential because surgical resection and liver transplantation can improve long-term survival. Liver transplantation has demonstrated, in patients meeting Milan criteria, a recurrence-free survival of 80%-90% at 3-4 years. Advanced HCC that is beyond Milan criteria has a dismal prognosis, with a 5-year survival of approximately 10%.37