"To our knowledge, this is the first population-based study to evaluate the epidemiology and natural history of cirrhosis in a large diverse cohort of North American women. This data shows that the burden of cirrhosis is increasing in women in North America, driven largely by NAFLD and ALD and will account for around 95 percent of all cirrhosis cases in women by the year 2040," says study co-author Jennifer Flemming, MD, FRCP(C), MAS, associate professor of medicine at Queen's University in Kingston, Ontario.
Disproportionally Affecting Young Women
"ALD cirrhosis is disproportionally affecting young women," Flemming said, "while the risk of NAFLD is, and will be, highest for women in the post-menopausal state. Clearly, a heightened recognition of these key drivers of cirrhosis is essential for both primary care providers and specialists alike and should influence the development and evaluation of public health initiatives."
When it comes to chronic liver diseases like ALD and NAFLD, epidemiological sex differences are widely recognized. This study, supported by a research award from AASLD Foundation, looked at the contemporary risk factors of cirrhosis and liver-related complications in women to learn more about sex-specific prevention and treatment approaches. The researchers also wanted to project the cirrhosis disease burden out to 2040 to look at the long-term impact of chronic liver disease.
"Historically, cirrhosis has been considered a chronic disease predominantly affecting men," says Dr. Flemming. "However, over the past decade, data has consistently highlighted the existence of differences in the natural history and outcomes of chronic liver disease, cirrhosis and liver transplantation in women as compared to men. Our understanding of both the current and future burden of cirrhosis in the female population has been limited."
New Strategies Needed
"This is important to appreciate from a clinical standpoint, as this information will be key to the development of strategies to identify and manage chronic liver diseases and cirrhosis in females, given the large contribution of lifestyle and environmental influences driving liver disease and the differential utilization of healthcare between sexes." This data may lead to new, sex-specific management strategies and therapeutics, she adds.
Researchers used comprehensive administrative healthcare data from Ontario, Canada, for the study. They identified a population-based cohort of adult female patients with cirrhosis from Jan. 1, 2000 to Dec. 31, 2017. They characterized the patients as having either hepatitis C (HCV), hepatitis B (HBV), ALD, NAFLD, autoimmune liver disease (AI) or other based on a combination of viral serology and diagnostic codes.
They also characterized patients with hepatocellular carcinoma (HCC) and non-malignant liver deterioration based on administrative codes. Additionally, researchers looked at the impact of cirrhosis on mortality using data from a provincial death registry, and calculated age standardized incidence rates (IR) stratified by both etiology and generational birth cohorts.
Greater Increase Anticipated
The study included 65,217 women who were followed for a median five years. Their median age at diagnosis was 57. Patients included 63 percent with NAFLD, 16 percent with ALD, ten percent with HCV, six percent with AI, five percent with HBV and one percent with other diseases.
The change in IR was greatest for women with ALD born after 1980 and women with NAFLD born between 1945-1964. Hepatocellular carcinoma IR was highest in women with HCV and AI. Hepatic decompensation and death were highest in women with ALD.
When looking at the potential future impact of liver disease on women, the researchers project that by 2040, cirrhosis IR will rise by eight percent due to increases in ALD and NAFLD with declines anticipated in HCV, HBV and AI or other diseases. The study also shows that by 2040, the highest increase in cirrhosis incidence will be seen in women with ALD who were born after 1980.
Source: Flemming, JA, et al. "NAFLD and Alcohol-Related Liver Disease Are Primary Drivers of Current and Future Causes of Cirrhosis Among Women in North America." Hepatology 1 October 2020.