HOUSTON — VA researchers expect complications from chronic hepatitis C virus (HCV) in women veterans to continue to rise for a decade or longer after rates begin to decline in men. Worldwide, similar trends might require different approaches to communication about the disease and its treatment.

Chronic HCV has been viewed as a disease that primarily affects men, who are 1.7 times more likely to have the infection and more likely to experience complications such as hepatocellular carcinoma, hepatic fibrosis, cirrhosis and decompensated liver disease than women. That understanding might change, however, as the baby boom generation—which accounts for three-quarters of HCV cases in the U.S.—ages.

Some of the biological protection afforded women wanes after menopause and progression to fibrosis may happen more quickly in older women than in men. In a study published in the Journal of Viral Hepatitis, researchers from the Michael DeBakey VAMC in Houston determined that rising rates of complications and lower mortality rates in women will combine to substantially increase the impact of women infected with HCV starting in 2020.1

While the researchers used data from the VA Corporate Data Warehouse from January 2000 to December 2013 to project the trends in development of complications from HCV in men and women in veterans and the general U.S. population, they note that access to direct-acting antivirals has the potential to “stem the rising tide of HCV complications.”

In the VA, broad screening for and treatment of chronic HCV might already have changed the trajectory of the disease. The VA ramped up treatment for HCV starting in 2011 with the introduction of the first direct-acting antivirals and committed to treating all veterans with the disease in 2014, when second generation direct-acting antiviral agents with greater than 90% cure rates came on the market. This spring, the VA projected that every willing and eligible veteran with HCV will have been treated by the end of 2018.

“Our hope is that we will see rates for HCV complications falling after the introduction of direct-acting agents,” explained lead author Jennifer Kramer, an investigator with the VA’s Epidemiology and Comparative Effectiveness Program, Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center and assistant professor in the Department of Medicine, Section of Health Services Research at the Baylor College of Medicine in Houston.

“Studies from another research group using VA data suggest that this will be the case. We plan to examine this formally as well,” she told U.S. Medicine.

Curative treatment can head off development of HCV complications. “Veterans with minimal to no liver disease when treated should not continue to develop complications,” Kramer explained, but “a decent proportion of veterans already have cirrhosis when they got treated and cured of HCV. We need to continue to monitor these patients.”

As the VA serves more individuals with HCV than any healthcare organization in the world and few, if any, other healthcare systems have offered such broad access to curative therapy, the trends observed at the VA have significant implications for HCV care in the United States and abroad.

The study identified 264,409 veterans with HCV treated by the VA between 2000 and 2013, including 7,162 women. Women had an average age of 48.0, while men had an average age of 53.4. At the time of the study, less than one-quarter of men and women in the study had received antiviral treatment for HCV.

While men had higher incidence rates for cirrhosis, decompensated cirrhosis and hepatocellular carcinoma during the study period, women had a higher rate of increase for all three complications. During the period, the average annual percent change in cirrhosis was 13.1 for men and 15.2 for women. Decompensated cirrhosis rose at an average annual percent rate of 15.6 and 16.9 for men and women, respectively. The average annual percentage change in hepatocellular carcinoma had the greatest difference between men and women, 21.0 and 25.3, respectively.

Surprise Over Rates

The similarity in rates surprised the researchers. “The rate of complications in women rose in parallel to that of men,” Kramer said. “We had hypothesized that the increase would actually have been greater in women in recent years due to having a slower progression of liver disease, in general, but we did not see that in this study.”

The annual prevalence of cirrhosis rose from 3.2% in women and 4.9% in men at the start of the study to 13.8% in women and 20.5% in men at the end. Similarly, decompensated cirrhosis rose from 1.6% and 2.4% in 2000 to 7.3% and 11.5% in 2013 for women and men, respectively. While the prevalence of hepatocellular carcinoma did not rise appreciably in women during the study (0% in 2000 and 0.7% in 2013), it increased from 0.1% to 2.5% for men. Women with HCV had about 40% the all-cause mortality risk of men, 15.5% vs. 28.7%, with most of the difference attributed to patients under age 65.

Kramer attributed the sharp increase in complications to the lag between HCV infection and liver injury. “Also, the increased screening measures implement in the VA in the early 2000s have led to more patients being diagnosed. These patients are now experiencing complications from decades of HCV infection,” she said.

“With cure from HCV now becoming a reality, most of the projected burden of HCV is potentially preventable. With the availability of multiple proven treatment options for chronic HCV infection, there must be an increased focus on screening and treating patients with this disease,” Kramer said.

While the VA had screened 83% of baby boomers for HCV as of last year, women have not received treatment at the same rate as men, the authors noted. They cited a previous study of 4,084 veterans that showed a tendency toward lower treatment acceptance rate among women, a finding also seen in community-based studies in the U.S., France and Australia. Women are also less likely to receive liver transplantation.

The authors concluded that “These and our recent data suggest that the degree of undertreatment may be greater in women than in men and may fuel the rising tends of HCV complications and suboptimal outcomes in women with HCV.”

1Kramer JR, El-Serag HB, Taylor TJ, White DL, Asch SM, Frayne SM, Cao Y, Smith DL, Kanwal F. Hepatitis C virus-related complications are increasing in women veterans: A national cohort study. J Viral Hepat. 2017 Nov;24(11):955-965. doi: 10.1111/jvh.12728. Epub 2017 Aug 16.