Awareness of the severity of liver disease re-examined using software-combined biomarkers of liver fibrosis and necroinflammatory activity

Abstract

Background: Effective antiviral treatment (direct-acting antiviral agents (DAAs)), the requirement for a fibrosis score to support DDA reimbursement and a screening strategy, such as the USA baby boomer campaign, should lead to an increased awareness of liver disease severity.

Objective: To compare the awareness of liver disease severity between the USA and France, two countries with similar access to hepatitis C virus (HCV) and hepatitis B virus (HBV) treatments, similar rules for treatment reimbursement and similar availability of validated fibrosis tests, but with different policies, as France has no screening.

Method: The global database of the FibroTest-ActiTest, including 1,085,657 subjects between 2002 and 2014, was retrospectively analysed. Awareness was defined as the test prescription rate and was compared between the USA and France, according to year of birth, gender and dates of DAA availability and screening campaign (2013-2014).

Results: In the USA 252,688 subjects were investigated for HCV, with a dramatic increase (138%) in the test rate in 2013-2014 (119,271) compared with 2011-2012 (50,031). In France 470,762 subjects were investigated (subjects with HCV and other disease) and the rates were stable. In USA 82.4% of subjects and in France 84.6% were classified as either the highest or lowest priority. The most striking difference was the higher test rate in women born between 1935 and 1944 in France 30,384/200,672 (15.1%) compared with the USA 8035/97,079 (8.3%) (OR=1.98 (95% CI 1.93 to 2.03) p<0.0001). This resulted in twice as many cases of cirrhosis being detected, 2.6% (5191/200,672 women) and 1.3% (1303/97,079), respectively, despite the same prevalence of cirrhosis in this age group (17.1% vs 16.2%) and without any clear explanation as to why they had not been included in the USA screening.

Conclusions: This study highlighted in the USA the association between awareness of liver disease and both the HCV campaign and DAA availability. In comparison with France, there was a dramatically lower awareness of cirrhosis in the USA for women born between 1935 and 1944.

Figure 1

Awareness of liver fibrosis according to the FibroTest in USA, France and in other countries. First column (main characteristics): number of subjects, median age, percentage of women and of subjects with cirrhosis. Second column (fibrosis stage spectrum): presumed METAVIR stage by the FibroTest—F0, no fibrosis; F1, minimal fibrosis; F2, few septa; F3, many septa; F4, cirrhosis. Cirrhosis F4.1 (red), compensated cirrhosis without risk of bleeding; F4.2 (violet), compensated cirrhosis with risk of bleeding; F4.3 (black), decompensated cirrhosis (cancer, bleeding, liver failure). Third column (baby boomer spectrum): number of subjects according to year of birth—before 1945 in orange, 1945–1965 in green, after 1965 in blue. Fourth column (fibrosis–age–gender): fibrosis density plots according to fibrosis presumed by FibroTest (y-axis) and year of birth (x-axis). All subjects are represented. The concentric black lines are density centiles, with the highest density being in the inner circle; subjects outside the outer line comprise <10% of the population. The two vertical black lines indicate the years of birth 1945 and 1965. The two crossing lines represented linear regression between FibroTest and date of birth, according to gender (men in blue and women in red). Fifth column (FibroTest (FT) prescription rate): number of subjects according to the test year between 2005–2006 (orange) and 2013–2014 (rose).

Figure 2

The extent of fibrosis according to activity grade as predicted by the ActiTest biomarker (see online supplementary data video 1 for the USA). First column: percentage of activity grade ranges presumed by the ActiTest, no activity (A0) and severe necroinflammatory activity (A3). Second column: among subjects without activity (A0), fibrosis density plots according to fibrosis presumed by FibroTest (y-axis) and year of birth (x-axis). Concentric black lines indicate centiles of density, with higher density in the inner circle; subjects outside the outer line comprise <10% of population. The two vertical black lines indicate the years of birth 1945 and 1965. Third column: fibrosis density plots among subjects with minimal activity (A1). Fourth column: fibrosis density plots among subjects with moderate activity (A2). Fifth column: fibrosis density plots among subjects with severe activity (A3). For all countries and all grades of activity there was a strong association between fibrosis severity, age and male gender. The 2 crossing lines represented linear regression between FibroTest and date of birth, according to gender (men in blue and women in red).