SAN DIEGO – The U.S. incidence of hepatocellular carcinoma continues to soar, and will likely remain on that trajectory for at least a couple of decades, fed in large part by the obesity and type 2 diabetes epidemics, as well as by infections with hepatitis virus types C and B.

"I think rates will increase for another 10-20 years," predicted Dr. Alita Mishra, one of two researchers who reported results at the meeting from independent studies that documented increased rates of U.S. hepatocellular carcinoma (HCC) cases during the 2000s.

Greater vigilance is therefore needed to spot incident cases early, she said in an interview. While patients infected with hepatitis C virus who develop cirrhosis usually undergo routine, serial ultrasound screening for liver lesions, regular surveillance occurs less often in patients with cirrhosis who are infected with hepatitis B virus, or those with cirrhosis due to non-alcoholic fatty liver disease (NAFLD) secondary to obesity or type two diabetes. "Patients with cirrhosis should undergo regular HCC screening regardless of the underlying cause," Dr. Mishra said at the annual Digestive Disease Week.

One analysis, based on data collected by the Surveillance Epidemiology and End Results (SEER) registry of the National Cancer Institute, showed that U.S. HCC rates rose three-fold from 1975-2007, including a 33% rise during 1998-2007, Jessica A. Davila, Ph.D. reported at the meeting.

The second analysis, using data collected by the Nationwide Inpatient Sample (NIS), showed that the number of patients hospitalized with HCC per 100,000 hospital discharges jumped from 148 in 2005 to 213, said Dr. Mishra, a hospitalist at Inova Farifax (Va.) Hospital.

"HCC is rising because of hepatitis C viral infection, especially in people born during 1945-1965," Dr. Mishra said in an interview. Many of these people don’t know they are infected, and it usually takes decades for them to develop HCC.

The second big factor is the rising prevalence of obesity and type 2 diabetes. "Hepatitis C infections are now falling, so perhaps the rise in new HCC cases will eventually peak, but not if other factors like obesity and type 2 diabetes continue to push it up," she said.

"What is driving a lot of the increase is hepatitis C virus, and the high prevalence of hepatitis B virus in foreign-born Asians," said Dr. Davila, a clinical epidemiologist at the Houston VA Medical Center and Baylor College of Medicine in Houston.

"A lot also has to do with obesity and type 2 diabetes and their association with non-alcoholic fatty liver disease, especially in middle-aged, Hispanic women. I think we’ll see the greatest increase in HCC in women during the next 2 decades," Dr. Davila said. She also predicted increasing numbers of hepatitis C virus-driven HCC cases in the short term "as the [infected] cohort ages, increasing numbers will develop advanced fibrosis and eventually HCC," she said.

Dr. Davila’s study used data from SEER, which the National Cancer Institute began in 1973 to collect data on cancer cases from about 14% of the U.S. population in selected states and metropolitan areas. During 1975-2007, SEER tallied a total of 21,472 HCC cases, about 80% of which occurred in people aged 50-79 years, and about three-quarters of cases in men.

HCC incidence rose from 1.6 cases per 100,000 people during 1975-1977 to 4.8 per 100,000 in 2005-2007. Roughly a tripling of cases during the three decades occurred in both men and in women. The greatest increase occurred among people aged 50-59 years, which jumped nearly fivefold, from 2.6 per 100,000 in 1975-1977 to 12.6 per 100,000 in 2005-2007. The smallest rise was 2.4-fold among people aged 70-79 years.

By 2005-2007, the highest rate was among Asians, 10.3 per 100,000, followed by 8.2 per 100,000 in Hispanics, 7.5 per 100,000 in blacks, and 3.7/100,000 in whites (see table).

Dr. Mishra’s study used data collected in NIS by the federal Agency for Healthcare Research and Quality from about 1,000 hospitals in 44 states. The number of patients hospitalized with HCC (not confined to incident cases) rose from 9,537 in 2005 to 13,689 in 2009. During the 5-year period, in-hospital mortality of HCC cases dropped from 120 per 1,000 cases in 2005 to 95 per 1,000 cases in 2009, and the median length of stay fell by about 0.5 days.

Despite reduced hospitalized time, median hospital charges for each HCC hospitalized case rose from about $21,000 in 2005 to nearly $29,000 in 2009. Paralleling this increase was an uptick in the percent of cases having "major" or "extreme" illness, from 52% in 2005 to 63% in 2009, and the average number of comorbidities also rose steadily during the 5 years studied.

Hospitalized patients with HCC "are getting sicker, more complicated, and have more comorbidities," Dr. Mishra said. She also noted that the rate of liver transplants remained "very low" during the period studied.

Dr. Davila and Dr. Mishra reported having no conflicts of interest.

Liver Cancer Rates Continue to Rise, Vigilance Warranted