Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for nearly 1 million cases worldwide. HCC ranks as the sixth-most common cancer in the world and the third-leading cause of cancer-related death. In the United States, it was estimated that approximately 42,230 new cases would be diagnosed and 30,230 people would die from this disease in 2021.
The most significant risk factor for HCC is chronic liver disease or cirrhosis. Worldwide, the majority of HCC cases are confined to Sub-Saharan Africa and eastern Asia, where there is a high prevalence of hepatitis B virus (HBV) infection. In the U.S. and Europe, the primary risk factors for HCC are hepatitis C virus (HCV) infection and alcohol abuse.
More recently, the rise of non-alcoholic fatty liver disease has become an important risk factor for the development of cirrhosis and HCC in the western world. Additional risk factors include diabetes and metabolic syndrome, tobacco use and co-infection with human immunodeficiency virus (HIV).
Unfortunately, for many patients, the presence of cirrhosis is unknown until it reaches an advanced stage. It is imperative that at-risk populations seek testing to avoid the consequences of late-stage disease. Patients with a known history of HCV or HBV infection, prior IV drug use, unprotected sexual intercourse, alcohol abuse, obesity, diabetes or metabolic syndrome should request screening for liver disease with their primary care provider.
Unfortunately, HCC patients may experience no symptoms, especially when detected early in the disease, as part of a formal screening program. Other patients may experience abdominal pain, unexplained weight loss, weakness or fatigue, jaundice (yellowing of the skin or eyes) or a hard lump under the right rib cage, but these patients are the minority.
Once a patient is deemed at risk for HCC and is enrolled in a surveillance program, serial abdominal imaging and blood work are the mainstay of diagnosis. Typically, a screening ultrasound will be obtained yearly in at-risk patients. The tumor marker α-fetoprotein is also used as a screening tool to survey patients at high risk for HCC. Abnormalities in any of these tests will prompt further imaging, most importantly an abdominal MRI (preferred) or CT scan. HCC is typically diagnosed radiologically with a characteristic arterial enhancement and delayed washout, forgoing the need for a biopsy.
After confirming the diagnosis of HCC, the most important prognostic factor is the stage of the disease. HCC is staged according to the Barcelona Clinic Liver Cancer (BCLC) classification system, which is helpful to make recommendations on treatment options. The BCLC system categorizes HCC based on characteristics and size of the tumor, the patient’s native liver function and performance status, and cancer-related symptoms.
The BCLC stage groupings include:
- Very early stage (BCLC 0): Patients with a single tumor smaller than 2 centimeters, who have no underlying liver disease and whose performance status is excellent. Surgical resection is generally recommended. Average survival is typically over five years.
- Early stage (BCLC A): Patients with a single tumor or multiple tumors, each smaller than 3 centimeters with some liver dysfunction. Patients may be candidates for a liver transplant, surgical resection or locoregional treatments. Average survival is typically over five years.
- Intermediate stage (BCLC B): Patients with a large tumor or with multiple tumors and some liver dysfunction. Patients are candidates for regional therapies. Average survival is typically 2-3 years.
- Advanced stage (BCLC C): Patients with a tumor that has invaded the portal vein or spread to other parts of the body, such as the lymph nodes, lungs, and bones. Treatment is generally systemic. Average survival is typically one year.
The treatment for HCC is diverse and highly dependent on the BCLC stage of presentation, the patient’s performance status and the goals of treatment. Surgery (liver resection or transplantation) has long been the backbone of curative therapies for HCC, yielding the best outcomes, with a five-year survival of over 80 percent.
For patients who may not be appropriate surgical candidates, who have significant underlying liver disease, or who don’t fit the criteria for liver transplantation, various locoregional therapies may serve as a bridge to liver transplantation, palliative treatments or to prolong life. These include microwave or radiofrequency ablation, transarterial chemo- or radio-embolization or external beam radiation therapy.
Finally, systemic therapy for HCC has recently grown as our understanding of the molecular fingerprint of these tumors has improved, which has led to the development of biologic agents that includes monoclonal antibodies, molecular pathway inhibitors, and immunomodulators.
The treatment of HCC is complex and requires a comprehensive team of providers from various backgrounds, including hepatology, oncology, surgery, radiation oncology, diagnostic and interventional radiology and transplantation. Patients with HCC should be referred to a center that specializes in liver disease and liver transplantation.
At the Hartford Hospital Transplant Program and Comprehensive Liver Center, we work collaboratively to bring each patient state-of-the-art diagnostic and therapeutic options that encompass all facets of care, including the most efficient screening modalities, the latest locoregional therapies and minimally-invasive surgical techniques and the availability to participate in clinical trials that exploit new therapeutic targets in addition to standard of care treatment. Patients considered at risk for HCC should be followed closely with an active surveillance plan to improve the chances of detecting an early lesion.
Dr. Oscar K. Serrano is a liver transplant and hepatobiliary surgeon with the Hartford Hospital Transplant Program and Comprehensive Liver Center.