HCV ‘Cures’ Came Too Late for Some Veterans

By Annette M. Boyle

hcv-graphicSEATTLE — For the VA, the combination of effective treatment options and much lower prevalence of HCV in younger veterans may offer a light at the end of the tunnel — and a turning point in the steady rise of HCV-associated complications such as cirrhosis and hepatocellular carcinoma (HCC) in only a few years.

The VA estimates that 233,000 veterans have HCV, with about 180,000 of them having received a diagnosis. The bulk of HCV-infected veterans come from the “baby boomer” cohort born between 1945 and 1965, with the oldest of these now reaching their 70th birthday.

For many veterans, the length of time they have been infected has already led to development of HCV-related cirrhosis and hepatocellular cancer. Up to 20% of individuals with chronic HCV infection develop cirrhosis over a period of 20-30 years, while between 1% and 5% will die from cirrhosis of hepatocellular carcinoma, according to the Centers for Disease Control and Prevention (CDC).

“We have a relatively narrow window of time in which to treat and cure HCV to prevent current HCV-infected patients from developing complications of liver disease, such as cirrhosis, hepatocellular carcinoma, liver failure or death,” said George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System and associate professor at the University of Washington School of Medicine in Seattle.

Ioannou and other VA researchers analyzed the rise in cirrhosis and HCC at the VA from 2001 to 2013 to better understand current trends and estimate the trajectory of the two conditions in the future. They presented a summary of their study at the recent American Association for the Study of Liver Diseases annual meeting in November and published the results in Gastroenterology.1

During the period studied, the prevalence of cirrhosis nearly doubled, from 664 to 1,058 per 100,000 veterans, with a total of 60,553 in treatment by 2013. Mortality rates rose more than 50%, from 83 to 126 per 100,000 patient-years. In 2013, 48% of cirrhosis cases were HCV-related, up from 38% in 2001.

At the same time, the incidence of HCC rose from 17 to 45 per 100,000 patient-years, and HCC mortality rates nearly tripled, increasing from 13 to 37 per 100,000 patient-years, with HCV as a primary cause in 67% of cases. In 2013, the VA was treating 7,670 veterans with HCC.

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) were the next two most significant factors in the rise of HCC and cirrhosis.

Based on the current trends, “we expect cirrhosis prevalence to peak in 2021,” Ioannou told U.S. Medicine.

From 2010 to 2013, the researchers found that cirrhosis mortality rose by five deaths per year, reaching 126 in 2013. The researchers assumed that the incidence of cirrhosis remained stable at the 2012 rate of 167 per 100,000 patient-years. Using similar calculations restricted to cirrhosis caused by HCV infection found that the peak would be reached by 2020.

The researchers said they could not identify a clear a turning point for HCC. “The prevalence of cirrhosis is still rising but appears to be leveling off. The burden of HCC is rising dramatically, with no sign of a slowdown. HCV is driving these trends, with alcoholic liver disease and NAFLD making up the majority of other cases,” said lead author Lauren Beste, MD, of the VA Puget Sound Health Care System and the University of Washington in Seattle. “All other causes, combined, accounted for just 7% of cirrhosis and 7% of HCC.”

Previous studies had predicted that the incidence of HCV-related HCC would top out in 2020. The current study noted that “with regard to HCC, we found an increasing incidence and mortality (both overall and HCV-specific) through 2013, with no sign of decline in the annual rate of increase.” Consequently, “our results do not allow us to predict when HCC rates might start declining but suggest that the HCC epidemic may be greater and more protracted then predicted by previous studies,” they wrote.

Because of the rise in NAFLD associated with the epidemics of obesity and diabetes, determining when HCC would level off became more challenging. NAFLD accounted for 15% of HCC cases in 2012.

“The role of NAFLD in absolute terms is already increasing, but HCV-related cirrhosis and HCC is currently increasing at an even faster rate,” Ioannou said.

That balance will change as HCV-infected baby boomers die, and the burden attributed to HCV will inevitably decline, according to the authors. The incidence of new HCV infections in the U.S. in the 1980s reached about 380,000 infections per year, dropping to approximately 38,000 per year in the 1990s and about 18,000 per year after 2000.

“All three of the leading causes of liver disease — HCV, alcoholic liver disease, and NAFLD — are potentially treatable. We have an opportunity to mitigate the effects of these underlying diseases if we invest now in treating them,” Beste said.

1 Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in Burden of Cirrhosis and Hepatocellular Carcinoma by Underlying Liver Disease in US Veterans, 2001-2013. Gastroenterology. 2015 Nov;149(6):1471-1482.e5. doi:10.1053/j.gastro.2015.07.056. Epub 2015 Aug 5. PubMed PMID: 26255044.