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Background Enhanced drug elimination in alcoholics remains largely indefinable. In contrast, the reduced elimination of drugs in patients with advanced alcoholic liver disease ( ALD) is normally owing to hepatic end-stage disease such as cirrhosis. We here study the mRNA expression of various hepatic drug metabolizing enzymes and transporters in association with liver stiffness ( LS) being a novel noninvasive parameter for the assessment of cirrhosis to unravel the dynamic relationship between ALD and determinants of pharmacokinetics such as drug metabolizing enzymes and transporters. Methods We quantified mRNA expression levels of various cytochrome P-450 isoenzymes ( CYPs) and drug transporters in 26 liver specimens of chronic alcoholics and 5 controls by quantitative polymerase chain reaction. In addition, liver histology, clinical data, and LS evaluated by transient elastography ( Fibroscan) were obtained. Results Eighteen patients had a normal or moderate LS < 8 kPa (69.2%), while in the remaining 8 patients (30.7%) advanced F3 or F4 fibrosis could be established with an LS > 8 kPa. Overall, CYP3A4, CYP2E1, and solute carrier organic anion transporter 1 B1 ( SLCO1B1) were negatively correlated with increasing LS. CYPs and drug transporters tended to be up-regulated in alcoholics without advanced fibrosis ( LS < 8.0 kPa) compared to healthy controls supporting data of boosted drug elimination in alcoholics without advanced ALD. However, in alcoholics with severely increased LS (>8 kPa), expression levels of CYP2E1, SLC22A2, and SLCO1B1 were significantly lower. Conclusions In conclusion, CYPs and drug transporters seem to be induced in chronic alcoholics without irreversible liver damage but decline in case of manifest cirrhosis. Our study also suggests that noninvasive measurements of LS could be useful for pharmacokinetic predictions and individualized pharmacotherapy. [ABSTRACT FROM AUTHOR]

Aim: To study liver stiffness (LS) during pregnancy and its association with complications during pregnancy., Methods: In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device (Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women (controls) while preeclampsia and intrahepatic cholestasis of pregnancy (ICP) developed in 22 and 40 women, respectively., Results: In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa ( P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index (BMI). In women with pregnancy complications, LS was significantly higher as compared to controls ( P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05 (1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa ( P < 0.001)., Conclusion: During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent non-invasive predictor., Competing Interests: Conflict-of-interest statement: The authors have declared no conflicts of interest.