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The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group ( p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group ( p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse. [ABSTRACT FROM AUTHOR]

In order to assess the effects of acute ethanol intoxication on bone, 45 female Sprague-Dawley rats were studied. Five rats were sacrificed at baseline. The remainder received either ethanol (2 g/kg of body weight) intraperitoneally or isotonic saline. Rats were sacrificed in groups of 10 (5 intoxicated and 5 placebo) at 1, 4, 8, and 24 hours after injection. At the time of sacrifice, a blood sample was obtained and the 4th vertebra was excised for histomorphometric analysis of undecalcified bone. Effect of ethanol was assessed by an analysis of variance test using a Scheffé procedure. In ethanol-treated rats we observed (mean +/- SD, ethanol versus controls, maximum difference point, P value) a significant decrease in osteiod surface with osteoblasts (42.86 +/- 15.61% versus 64.57 +/- 6.24%, P < 0.05); osteoclast number (0.05 +/- 0.02 n/mm2 versus 0.17 +/- 0.09 n/nm2, P < 0.05), and osteocalcin (36.9 +/- 2.21 ng/ml versus 45.8 +/- 5.1 ng/ml, P < 0.05). Osteoclast surface was initially reduced (0.129 +/- 0.09% versus 0.425 +/- 0. 26%, P < 0.01) but showed a subsequent increase (0.765 +/- 0.24% versus 0.226 +/- 0.17%, P < 0.01) attributable to alcohol. There was also a significant decrease in serum Ca (8.51 +/- 0.23 mg/dl versus 9.10 +/- 0.29 mg/dl, P < 0.01) and parathyroid hormone values (23.51 +/- 5.72 pg/ml versus 76.39 +/- 11.66 pg/ml, P < 0.001). We conclude that acute alcohol intoxication in rats induces early striking changes in bone histology and analytical parameters, not completely reversed after 24 hours. These data are consistent with a toxic effect induced by alcohol on bone. [ABSTRACT FROM AUTHOR]

The study of bone mass in experimental animals usually requires invasive techniques. Dual energy X-ray absorptiometry (DEXA) may be an alternative as a non-invasive method (1). Bone mineral density (BMD) and bone mineral content (BMC) of 62 vertebrae of Sprague Dawley rats (SDr) measured by DEXA densitometry were compared with histomorphometric bone volume measurements, and a statistically significant correlation was found (r = 0.79 and 0.75, respectively, p < 0.001). In conclusion, DEXA is an accurate and feasible technique for the study of trabecular bone mass in SDr. [ABSTRACT FROM AUTHOR]