Combining liver stiffness with hyaluronic acid provides superior prognostic performance in chronic hepatitis C

Background Non-invasive methods are the first choice for liver fibrosis evaluation in chronic liver diseases, but few studies investigate the ability of combined methods to predict outcomes. Methods 591 chronic hepatitis C patients with baseline liver stiffness (LSM) by FibroScan and hyaluronic acid measurements were identified retrospectively. The patients were grouped by baseline LSM: < 10kPa, 10-16.9kPa, and 17-75kPa. Primary outcomes were all-cause mortality and liver-related mortality, analyzed using cox regression and competing risk regression models, respectively. Results Median follow-up was 46.1 months. Prevalence of cirrhosis at baseline was 107/591 (18.1%). Median LSM was 6.8kPa (IQR 5.3-11.6) and divided into groups, 404/591 (68.4%) had a LSM < 10kPa, 100/591 (16.9%) had a LSM between 10-16.9kPa and 87/591 (14.7%) had a LSM between 17-75kPa. There were 69 deaths, 27 from liver-related disease. 26 patients developed cirrhosis and 30 developed complications of cirrhosis. The mortality rate in the 17-75kPa group was 9.7/100 person-years, compared to 2.2/100 person-years and 1.1/100 person-years in the 10-16.9kPa and <10kPa groups (p<0.005). Liver-related mortality increased 10-fold for each group (p<0.005). Cirrhotic complications occurred almost exclusively in the 17-75kPa group, with an incidence of 10.3/100 person-years, compared to 1.8/100 person-years and 0.2/100 person-years in the 10-16.9kPa and <10kPa groups (p<0.005). Median hyaluronic acid in the 17-75kPa group was approximately 200ng/mL. Patients with a LSM 17-75kPa had significantly higher risks of death, liver-related death, and complications to cirrhosis if their hyaluronic acid measurement was more than or equal to 200ng/mL at baseline, with hazard ratios of 3.25 (95% CI 1.48-7.25), 7.7 (95% CI 2.32-28), and 3.2 (95% CI 1.35-7.39), respectively. Conclusions The combination of LSM and circulating hyaluronic acid measurements significantly improved prognostic ability, relative to LSM alone. Combined static and dynamic markers of liver fibrosis could provide superior risk prediction.