Hepatocellular Carcinoma: From Prevention to Treatment

SUMMARY:

Primary liver cancer is the third leading cause of cancer related deaths in the United States. The majority of primary liver cancers are due to hepatocellular carcinoma (HCC) in the setting of cirrhosis or chronic hepatitis infections. Any disease process that contributes to cirrhosis formation increases the risk of HCC regardless of the underlying etiology, and patients with cirrhosis have an annual risk of roughly 2% of developing HCC. In the United States most cases of cirrhosis and HCC occurrence are due to chronic hepatitis infection (HCV | HBV), alcohol use and metabolic dysfunction-associated steatotic liver disease. Incidence and mortality of HCC have both declined since their peak in 2010, likely due to improved prevention, screening and treatment strategies. The American Association for the Study of Liver Diseases (AASLD) has created a practice guideline to assist healthcare professionals in the prevention of HCC.

Prevention

Primary prevention strategies focus on treating and preventing disease processes that contribute to cirrhosis formation before cirrhosis occurs
- Hepatitis B Virus (HBV): Universal vaccination for babies and high-risk adults who have not been immunized | HBV anti-viral therapy for viral suppression
- Hepatitis C Virus (HCV): Anti-viral therapy to eradicate infection
- Lifestyle recommendations: Maintain healthy weight | Avoid tobacco | Limit alcohol use | Treat co-morbid metabolic syndrome conditions (e.g., Diabetes | Hyperlipidemia) | Eat a balanced diet
Emerging strategies that require further study for the prevention of HCC in patients with chronic liver disease (CLD) include
- Coffee consumption
- Pharmacotherapy: ASA | Statin | Metformin
Secondary prevention strategies focus on screening and early diagnosis of HCC to reduce disease impact and improve treatment success

Screening

HCC surveillance should be done in all high-risk patients
- High risk groups include patients with: Child-Pugh A–B cirrhosis | Child-Pugh C cirrhosis AND transplant candidate | Non-cirrhotic chronic hepatitis B
Patients listed for liver transplant should undergo HCC screening every 6 months
- Diagnosis of early-stage HCC can change the patient’s position on liver transplant list
Target screening to patients who could benefit from and would be eligible for HCC therapy
- Avoid screening in patients with life-limiting comorbid conditions that cannot be treated (e.g., Life expectancy less than 1 to 2 years)
AASLD recommends against routine surveillance in patients with advanced fibrosis but without progression to cirrhosis
Screening includes semiannual (e.g., roughly every 6 months) measurement of AFP AND liver ultrasound
- CT and MRI-based technology should not be routinely used for screening, but may be considered in select patients when ultrasound-based surveillance is suboptimal
Screening findings and adequacy of ultrasound visualization (e.g., VIS score A through C) can alter timing of follow up surveillance
- Normal AFP + VIS score A + no lesions seen on US: Repeat screening in 6 months
- Normal AFP + VIS score B or small lesion on US (e.g., < 1cm): Repeat screening in 3 to 6 month and if lesion is growing proceed with diagnostic CT/MRI
- VIS score C (e.g., Poor visualization on US): Proceed with screening contrast enhanced MRI or multi-phase CT
- Lesion ≥ 1 cm on US or AFP ≥ 20 ng/mL or AFP increasing: Proceed with diagnostic contrast enhanced CT or MRI
If diagnostic CT or MRI is negative for HCC and AFP is low patients may return to semiannual US/AFP screening

Diagnosis

Diagnosis of HCC is generally done with imaging findings using the LI-RADS criteria
- LI-RADS criteria do not apply in patients with liver nodules in the absence of cirrhosis or HBV infection, and pathologic diagnosis should be obtained
- Sensitivity of liver biopsy drops in smaller nodules, and a negative biopsy does not rule out HCC
- If findings are inconclusive liver biopsy should be repeated
LI-RADS scores of 4 or greater indicate likely HCC and multidisciplinary team should be engaged to determine next steps of care
- These patients will often proceed with biopsy for further histological and immunohistochemical analyses
Patients with confirmed HCC should undergo further staging with: High-quality multiphase CT or contrast-enhanced MRI for assessment of tumor extent | Non-contrast CT chest to assess for lung metastasis
- PET scan and bone scans should be avoided due to low sensitivity for HCC

Treatment

Patients with HCC should be cared for by a multidisciplinary team including: Hepatology | Surgery | Oncology | Transplant surgery | Palliative care
Surgical resection is the treatment of choice for localized HCC in the absence of cirrhosis or in patients with limited tumor burden and well compensated cirrhosis
- Surveillance for HCC should resume post-operatively with repeat CT or MRI imaging every 3 to 6 months to monitor for recurrence
In patients with early-stage HCC and decompensated cirrhosis, liver transplantation is the treatment of choice in transplant eligible patients
- Surveillance for HCC should resume post-transplant with CT or MRI imaging, though optimal timing is uncertain in this population
Other treatment options include: Ablation | Targeted radioembolization | EBRT | Transarterial chemoembolization | Chemotherapy | Immunotherapy
Advanced care planning should be offered to all patients receiving palliative-intent therapy or best supportive care for HCC

KEY POINTS:

Hepatocellular carcinoma is a primary liver cancer that typically occurs in the setting of cirrhosis or chronic hepatitis B infection
Incidence and mortality of HCC have decreased in the past decade due to improved awareness and implementation of prevention and screening strategies
Patients with cirrhosis or chronic HBV infection should undergo semiannual screening for HCC with AFP measurement and liver US
Patients with concerning findings for HCC on screening should obtain further imaging with CT or MRI to help diagnose HCC
Once HCC is confirmed, a multidisciplinary team should be engaged to develop a treatment plan