Hepatology : official journal of the American Association for the Study of Liver Diseases
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We characterized expression and activity of the bile salt transporters Na(+)/taurocholate (TC) cotransporting polypeptide (Ntcp), and bile salt export pump (Bsep), and the expression of organic anion transporting polypeptides 1 and 2 (Oatp1 and 2) and multidrug resistance associated protein-2 (Mrp2) in pregnancy and throughout lactation in rats. The V(max) for Na(+)/TC cotransport in basolateral liver plasma membrane was increased 1.7-fold in 2 days postpartum relative to control and pregnant rats. This correlated well with an increase in Ntcp messenger RNA (mRNA) and a 2-fold increase in Ntcp protein. ⋯ Mrp2 mRNA was stable in pregnancy and postpartum, whereas Mrp2 protein expression decreased significantly in pregnancy, but returned to control levels postpartum. Organic anion transporting polypeptide 2 (Oatp2) mRNA was decreased in pregnancy and increased postpartum, but changes in Oatp2 protein were not significant. Oatp1 mRNA and protein were unchanged in pregnancy and postpartum.
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Comparative Study
Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites.
The diagnosis of refractory ascites in cirrhotic patients carries a poor prognosis and liver transplantation should always be considered in this situation. Identification of patients who will not respond to diuretic therapy usually requires several weeks of observation during which a trial of diuretics is instituted using stepwise increases in dosage in order to classify ascites as refractory. In the present study we evaluated the effect of a single dose of 80 mg intravenous furosemide on urinary sodium excretion over 8 hours in cirrhotic patients with ascites responsive to diuretic treatment (group 1; n = 14) and patients with refractory ascites (group 2; n = 15). ⋯ The effects of furosemide on 8-hour natriuresis was much higher in patients with responsive ascites as compared with patients with refractory ascites (125 +/- 46 vs. 30 +/- 16 mEq; mean +/- SD; P <.0001). A natriuresis lower than 50 mEq/8 hours was observed in all group-2 patients as compared with none from group 1. The present study shows that patients with refractory ascites can be identified quickly and accurately by using this simple furosemide-induced natriuresis test, which could be very useful to select patients for liver transplantation.
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Immune elimination of hepatitis B virus (HBV) during antiviral therapy depends on the activation of T-cell responses, which are generally impaired in chronic hepatitis B. HBV-specific T helper (Th)-cell reactivity has been assessed post-treatment in liver and peripheral blood of 18 anti-HBe-positive patients with chronic hepatitis B administered combined ribavirin/interferon alfa (IFN-alpha) therapy. The results showed that patients with undetectable HBV DNA by quantitative polymerase chain reaction under combination therapy were able to mount an HBV-specific CD4(+) Th-cell proliferative response and such T-cell reactivity is detectable 1 year after HBV DNA clearance. ⋯ However, HBV-specific IFN-gamma production in vitro in peripheral blood mononuclear cells augmented in 4 of 5 sustained responders and all 13 nonresponders, interleukin 10 (IL-10) production decreased in all 5 sustained responders but increased in 7 of 13 nonresponders. Furthermore, intrahepatic HBcAg plus HBeAg-specific Th-cell proliferation only occurred in sustained responders (2 of 3, 67%, vs. 0 of 9; P =.045) whose cells showed in vitro significantly increased productions in HBcAg/HBeAg-specific IFN-gamma and IL-12 compared with nonresponders in whom IFN-gamma and IL-12 productions decreased together with increased IL-10 secretion. In conclusion this study indicates that combined therapy with ribavirin and IFN-alpha for chronic hepatitis B not only significantly reduces viremia levels but also induces lasting CD4(+) T-cell proliferation and Th1 cytokine release at the site of infection, which may lead to sustained eradication of the HBV.