UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis

Background & Aims: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate). Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021. Results: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P <.05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P <.001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P <.001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P =.121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline. Conclusion: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment

Erythrocytic nuclear abnormalities in Cyprinus carpio L. cultivated in water bodies of agroecosystems

Agrochemicals contaminate water bodies in agroecosystems, which affects the health of fishes. We assessed erythrocytic nuclear abnormalities (ENA) in Cyprinus carpio reared in uncontaminated and contaminated water bodies. We recorded micronucleus, notched nucleus, lobed nucleus, kidney bean-shaped nucleus, bi-nucleated, blebbed nucleus, karyopyknosis, nuclear shift, ooze out nucleus, and elongated nucleus at higher incidences in fish reared in the contaminated site. We observed a high percent incidence of ENA and micronucleus in fish from the contaminated site. The analysis of heavy metals with atomic absorption spectroscopy revealed that all heavy metals (Mn, Zn, Ni, Pb, Cd, Fe) were high in the contaminated site except for Cu in water and Cu and Cr in sediments. Correlation matrix analysis showed that total ENA increased with Cu (r = 0.996, p < 0.0001), Mn (r = 0.942, p < 0.0001), Zn (r = 0.517, p = 0.07), and Cr (r = 0.997, p = 0.0001). Compared to the uncontaminated site, the incidence of micronuclei was 20 times higher in the fish from the contaminated site, and this was influenced by the Cu, Mn, Zn, and Cr contents in the sediments. This study indicated that the heavy metal contamination of a water body located in an agroecosystem contributed to nuclear abnormalities in C. carpio