150 N. Lampon & J. C. Tutor Table I. Results obtained in the patients treated with valproic acid in monotherapy according to its ceruloplasmin-speciﬁc oxidase activity. Speciﬁc oxidase activity <333(U/g) Speciﬁc oxidase activity ‡333(U/g) n (males/females) VPA Css (mg/L) VPA dose (mg/24h) Speciﬁc oxidase activity (U/g) Copper/ceruloplasmin ratio (mg/mg) Glucose (mg/dL) Cholesterol (mg/dL) Triglycerides (mg/dL) GGT (U/L) ALP (U/L) ChE (U/L) AST(U/L) ALT(U/L) AST/ALT ratio CRP (mg/L) APRI score FIB-4 score aSigniﬁcance: P < 0.01. 28 (18/10) 63.2 ± 4.0 (67.9) 1170.0 ± 93.1 (1200.0) 278.5 ± 6.8 (276.1)a 3.2 ± 0.1 (3.2)a 94.5 ± 5.1 (89.0) 191.0 ± 10.2 (199.0) 134.5 ± 13.2 (108.0) 31.6 ± 8.8 (12.6) 161.2 ± 11.3 (132.0) 7061.6 ± 407.4 (7250.0) 14.6 ± 1.1 (13.5) 19.2 ± 1.6 (20.0) 0.8 ± 0.1 (0.8) 3.4 ± 1.2 (1.4) 0.37 ± 0.06(0.30) 0.89 ± 0.12(0.80) 47 (21/26) 63.5 ± 2.7 (60.4) 1241.9 ± 86.1 (1000.0) 430.5 ± 13.0 (405.4) 3.9 ± 0.1 (3.8) 88.4 ± 2.0 (87.5) 175.5 ± 8.2 (171.0) 107.7 ± 8.9 (99.0) 17.2 ± 2.5 (10.0) 162.1 ± 3.7 (143.0) 7005.9 ± 229.4 (7050.0) 16.7 ± 1.9 (13.0) 22.1 ± 3.9 (14.5) 0.9 ± 0.1 (0.7) 6.6 ± 2.6 (1.4) 0.35 ± 0.05(0.30) 0.84 ± 0.12(0.60) with the exception of the data obtained for the copper/immunoreactive ceruloplasmin ratio, which was signiﬁcantly lower in the group of patients with ceruloplasmin-speciﬁc oxidase activities <333 U/g. Analogous results were obtained for the patients treated with VPA in polytherapy (Table II). In both cases, signiﬁcant differences were not achieved after a dichot- omy of the data according to the patient’s sex. No signiﬁcant correlations were obtained for the different variables assayed with the speciﬁc oxidase activity of ceruloplasmin or the copper/immunoreactive cerulo- plasmin ratio, which have a signiﬁcant correlation coefﬁcient between them (r = 0.550; P < 0.001). In our study, thrombocytopenia was deﬁned as a platelet count of less than 150 109/L, and 11 patients (10 in monotherapy and 1 in polytherapy ) had thrombocytopenia, with a platelet count of 115 ± 9.7 109/L (range 42–146 109/L), MPV of 9.5 ± 0.4 fL (range 7.6–11.5 fL), and PDW of 54.8 ± 2.4% (range 39.8%–63.8%). In accordance with previously published data on the discrimination of hypo-productive or hyper-destructive thrombocy- topenia using MPV and PDW platelet indices (26,27), the decreased platelet count may be due to a hyper-destruction of peripheral blood platelets in these patients. Furthermore, in the ﬁve patients (three in monotherapy and two in polytherapy) with a plate- let count greater than 400 109/L, the calculation of the residual PDW according to Osselaer et al. (28) suggests that the discrete thrombocytosis of 491.8 ± 37.7 109/L (range 409–601 109/L) was secondary or reactive. No signiﬁcant correlations of the platelet count with the daily dose or serum levels of VPA were found. Figure 1 shows the distribution of the values obtained for the APRI and FIB-4 liver ﬁbrosis indices in 50 healthy controls and the patients who were studied. The correlation coefﬁcient of the APRI index with the platelet count was r = –0.764 (P < 0.001), and with AST activity r = 0.635 (P < 0.001). The corre- lation of FIB-4 score with platelet count (r = –0.606; P < 0.001) was also greater than with AST (r = 0.348; P < 0.005). The ﬁrst-order partial correlation coefﬁ- cient of the APRI index with platelet count (main- taining AST as a constant) was r = –0.898 (P < 0.001), and with AST activity (maintaining platelet count as a constant) r = 0.849 (P < 0.001). The partial correla- tions of the FIB-4 score with the platelet count was r = –0.607 (P < 0.001), and with AST r = 0.350 (P < 0.005). Discussion It has been previously described that non-alcoholic fatty liver disease is present in 61% of the patients