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Hepatocellular carcinoma: Options for diagnosing and managing a deadly disease

Cleveland Clinic Journal of Medicine. 2013 October;80(10):645-653 | 10.3949/ccjm.80a.12163
October 1, 2013|Cleveland Clinic Journal of Medicine
Arvind R. Murali, MD;Carlos Romero-Marrero, MD;Federico Aucejo, MD;K.V. Narayanan Menon, MD
Author and Disclosure Information

Arvind R. Murali, MD
Department of Internal Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL

Carlos Romero-Marrero, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Federico Aucejo, MD
Department of Hepato-pancreatobiliary and Transplant Surgery, Digestive Disease Institute, Cleveland Clinic

K.V. Narayanan Menon, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Address: K.V. Narayanan Menon, MD, Department of Gastroenterology and Hepatology, A51, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: menonk@ccf.org

ABSTRACTHepatocellular carcinoma (HCC) is an important cause of death in patients with liver disease, and its incidence appears to be rising in the United States. Because early diagnosis improves the chances of survival, it is important to identify patients who would benefit from surveillance. Once HCC is suspected on surveillance, noninvasive diagnostic tests are available to make an accurate diagnosis. Treatment should be individualized, based on the characteristics of the tumor and the degree of liver dysfunction.

KEY POINTS

  • Surveillance for HCC is indicated in all patients with cirrhosis, regardless of the cause of the cirrhosis.
  • Liver biopsy is not needed to make the diagnosis if the findings on four-phase multidetector computed tomography or dynamic contrast-enhanced magnetic resonance imaging are typical of HCC (arterial hyperenhancement with venous-phase or delayed-phase washout).
  • Many treatments are available, including surgical resection, liver transplantation, ablative therapy, perfusion-based therapy, chemotherapy, and palliative therapy.

Hepatocellular carcinoma (HCC) is a common cause of death worldwide. However, it can be detected early in high-risk individuals by using effective screening strategies, resulting in the ability to provide curative treatment.

Here, we review the risk factors for HCC, strategies for surveillance and diagnosis, and therapies that can be used.

EPIDEMIOLOGY

HCC is the most common primary malignancy of the liver. Overall, it is the fifth most common type of cancer in men and the seventh most common in women.1

Cirrhosis is present in 80% to 90% of patients with HCC.

Male sex. The male-to-female ratio is from 2:1 to 4:1, depending on the region.2 In the United States, the overall male-to-female ratio has been reported2 as 2.4:1. In another report,3 the incidence rate of HCC per 100,000 person-years was 3.7 for men and 2.0 for women.

Reproduced from Altekruse SF, et al. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009; 27:1485–1491, with permission from the American Society of Clinical Oncology.
Figure 1. Annual age-adjusted incidence rates per 100,000 of hepatocellular carcinoma in the United States, based on data from the Surveillance, Epidemiology, and End Results registries. The arrow indicates a change in the overall trend.

Geographic areas with a high incidence of HCC include sub-Saharan Africa and eastern Asia, whereas Canada and the United States are low-incidence areas. The difference has been because of a lower prevalence of hepatitis B virus infection in North America. However, recent data show a downward trend in incidence of HCC in eastern Asia and an upward trend in North America (Figure 1).3,4

Viral hepatitis (ie, hepatitis B or hepatitis C) is the main risk factor for cirrhosis and HCC.

Diabetes mellitus can predispose to nonalcoholic steatohepatitis, which can subsequently progress to cirrhosis. Thus, it increases the risk of HCC.

Obesity increases the risk of death from liver cancer, with obese people (body mass index ≥ 30 kg/m2) having a higher HCC-related death rate than leaner individuals.5 And as obesity becomes more prevalent, the number of deaths from HCC could increase.

Other diseases that predispose to HCC include alcohol abuse, hereditary hemochromatosis, alpha-1-antitrypsin deficiency, and glycogen storage disease.

SURVEILLANCE OF PATIENTS AT RISK

Patients at high risk of developing liver cancer require frequent screening (Table 1).

Patients with cirrhosis. Sarasin et al6 calculated that surveillance is cost-effective and increases the odds of survival in patients with cirrhosis if the incidence of HCC exceeds 1.5% per year (which it does). In view of this finding, all patients with cirrhosis should be screened every 6 months, irrespective of the cause of the cirrhosis.

Hepatitis B carriers. Surveillance is also indicated in some hepatitis B carriers (Table 1), eg, those with a family history of HCC in a first-degree relative (an independent risk factor for developing the disease in this group).7 Also, Africans with hepatitis B tend to develop HCC early in life.8 Though it has been recommended that surveillance be started at a younger age in these patients,9 the age at which it should begin has not been clearly established. In addition, it is not clear if black people born outside Africa are at higher risk.

Benefit of surveillance

HCC surveillance has shown to lower the death rate. A randomized controlled trial in China compared screening (with abdominal ultrasonography and alpha-fetoprotein levels) vs no screening in patients with hepatitis B. It showed that screening led to a 37% decrease in the death rate.12 Studies have also established that patients with early-stage HCC have a better survival rate than patients with more-advanced disease.10,11 This survival benefit is largely explained by the availability of effective treatments for early-stage cancer, including liver transplantation. Therefore, early-stage asymptomatic patients diagnosed by a surveillance program should have a better survival rate than symptomatic patients.

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