Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. The key to preventing mortality is to diagnose HCC at an early stage when curative therapies can be offered. Candidacy for hepatic resection or liver transplantation is an early decision. Embolization and ablation procedures are important therapeutic modalities. Patients at high risk for HCC are recommended to participate in surveillance programs. Effective imaging is critical to patients with chronic liver disease given their risk of HCC. Imaging allows early identification and diagnosis with ongoing monitoring capabilities, and patients are given the best option for pursuit of cure from HCC.
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with more than 800,000 deaths worldwide.1 Most cases of liver cancer are related to hepatitis B virus (HBV) infection or occur in the setting of cirrhosis from any etiology. Although hepatitis C virus (HCV) treatment is highly effective, many patients were cured after they had developed cirrhosis and remain at risk for HCC.2 Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is a rising cause of cirrhosis and will soon be the most common reason for liver transplantation in the United States. Patients at high risk for HCC are recommended to participate in surveillance programs. The key to preventing mortality is to diagnose HCC at an early stage when curative therapies can be offered. Current society guidelines recommend the ultrasound and serum alphafetoprotein for surveillance.3,4 When these studies are abnormal, imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is recommended to establish the diagnosis. Imaging criteria for HCC have been recognized by the hepatology community as the best option for the diagnosis of HCC. Biopsy of a liver mass carries risk of complication but also the risk of false negative biopsy. A normal or benign biopsy result might reflect an incorrect needle location. Biopsy is reserved for lesions with atypical imaging features or concerning for metastatic disease. Imaging criteria algorithms often lead to indeterminate nodule designation, and repeat imaging is often required for patients.5
When HCC is diagnosed at an early stage, an initial consideration will be candidacy for resection. Liver resection is effective, but unfortunately few patients are eligible for this option. Patients considered for resection should have disease confined to the liver without significant portal hypertension. Patients with portal hypertension are at risk for rapid deterioration to liver failure with resection. If resection is not an option, another important consideration will be liver transplantation.3 Patients are eligible for liver transplantation if they have established HCC that is considered low risk for recurrence. Patients are considered low risk for recurrence according to the Milan criteria if they have one lesion less than 5 centimeters in diameter or 3 lesions all less than 3 centimeters.6 Once listed for transplantation, patients often undergo local-regional therapies such as embolization or ablation to keep control of the HCC until the time of transplantation. These patients then require ongoing imaging to monitor for recurrence. If patients have tumor burden beyond the Milan criteria, they may be eligible for transplantation following effective local-regional therapy to the HCC followed by a period of stability on imaging. Local-regional therapies can also considered first-line therapy for patients with HCC. While an option for those without access to liver transplantation, these ablation and embolization procedures are offered to those ineligible for transplantation as well as those patients who prefer not to pursue transplantation.3
Although variations are noted in liver transplant allocation systems around the world, they share similar approaches that consider the severity of liver disease and risk of mortality. The model for end stage liver disease (MELD) is used for this purpose, and the most recent version assigns a score using the serum creatinine, total bilirubin, sodium and prothrombin time–international normalized ratio (INR).7 Most patients with HCC do not have high MELD scores and therefore gain access through exception criteria that require definitive diagnosis from imaging or biopsy. Whether listed for HCC or for complications of portal hypertension, patients listed for liver transplantation require interval imaging to look for new HCC development or lack of recurrence in previously treated lesions.
Effective imaging is critical to the care of patients with chronic liver disease given their risk for the development of HCC. Imaging allows early identification and diagnosis with ongoing monitoring capabilities. In this way, patients are given the best option for pursuit of cure from HCC.
REFERENCES
1. Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol 2017; 3:1683.
2. Lok AS, Seeff LB, Morgan TR, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 2009; 136:138.
3. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018; 8:723-7.
4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69:182-88.
5.Konerman M, Verma A, Zhao B, et al. Frequency and Outcomes of Abnormal Imaging in Patients With Cirrhosis Enrolled in a Hepatocellular Carcinoma Surveillance Program. Liver Transplantation 2019; 25 369‒379.
6. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996 Mar 14; 334(11):693-9.
7. Wiesner, R, Edwards, E, Freeman, R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 2003; 124:91-7.