Viral load 1 week after liver transplantation, donor age and rejections correlate with the outcome of recurrent hepatitis C.

BACKGROUND: Early identification of patients at a higher risk of rapidly progressive recurrent hepatitis post liver transplantation (LT) could help to tailor antiviral therapy. METHODS: We studied the correlation between early post-LT viral load and the histological and clinical outcomes of 49 consecutive patients (34 males, median age 55 years) in whom viraemia was monitored at days 0, 1, 7, 30, 180 and 365 after LT. RESULTS: Hepatitis C recurred at histology in 38 of 42 (90.5%) patients. Early viral load after LT was higher in patients with rapidly progressive hepatitis C recurrence (day 7 median HCV-RNA levels: 5.84 vs 4.93 Log(10) IU/ml, P=0.003). Day 7 HCV-RNA levels >/=2.5 x 10(5) IU/ml, donor age >60 years and rejection episodes were independently associated with progression to cirrhosis within one year post-LT [P=0.018, odds ratio (OR) 27.59; P=0.043, OR 13.85 and P=0.048, OR 9.95, respectively]. Day 7 viraemia and rejection episodes were independently associated with 5-years survival. Day 7 viraemia, in combination with acute hepatitis and/or donor age, showed 80% sensitivity, 94% specificity and 90.5% diagnostic accuracy to identify severe recurrence. CONCLUSIONS: Early post-LT HCV-RNA correlates with the severity of hepatitis C recurrence and in combination with donor age (>60 years) and rejections, identifies patients with a high risk of severe recurrence and candidates of cost-effective pre-emptive antiviral therapy.     

The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin

The relative importance of antithrombin and anti-factor Xa activities of heparin fractions required to achieve optimal antithrombotic effects is unknown. To study this, we measured the effects of standard heparin, an octasaccharide heparin fraction (anti-factor Xa activity only), and dermatan sulfate (antithrombin activity only) on the prevention of thrombosis and related this to their anticoagulant effects in vivo in rabbits. Thrombosis was measured as the incorporation of 125I- fibrinogen into tissue thromboplastin-induced thrombi using a Wessler- type model. Ex vivo changes in thrombin clotting time (TCT) were used as an index of antithrombin activity, and a chromogenic anti-factor Xa assay was used to measure anti-factor Xa activity. In addition, the ability of the three sulfated polysaccharides to simultaneously inhibit the generation of thrombin activity and to enhance the inactivation of the factor Xa added to initiate thrombin generation in plasma was determined. Standard heparin, in a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 90%, prolonged the TCT by two seconds, and resulted in an anti-factor Xa level of 0.32 U/mL. The octasaccharide heparin fraction, in a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 41%, had no effect on the TCT, and resulted in an anti-factor Xa level of 0.28 U/mL. Higher doses of the octasaccharide resulted in a further increase in the anti-factor Xa levels but had no further effect on thrombus formation. Dermatan sulfate, in a dose of 500 micrograms/kg, inhibited thrombus formation by 95%, but had no affect on the TCT. These results indicate that the antithrombotic effect achieved by inhibiting factor Xa is limited and that better antithrombotic effects are achieved by heparin or heparin- like substances capable of influencing the inactivation and/or the generation of thrombin.     

Three-dimensional study of the upper airway in different skeletal Class II malocclusion patterns

Objectives:To characterize upper airway volume and morphology in patients with different skeletal patterns of Class II malocclusion compared to Class I.Materials and Methods:A total of 197 individuals who had cone-beam computed tomography were allocated into groups according to ANB, SNA, and SNB angles (Class I, Class II maxillary protrusion, Class II mandibular retrusion), each subdivided into hypodivergent, normal, and hyperdivergent. Nasopharynx (NP), oropharynx (OP), and hypopharynx (HP) were assessed with three-dimensional image reconstruction software.Results:Intergroup comparison did not detect significant differences in volume and morphology of NP, OP, and HP. The males displayed larger OP and HP volume than the females. Positive correlations between age and NP, OP, HP volume and between craniocervical angle and OP and HP volume were observed. Linear regression analysis detected a tendency for OP and HP volume to increase as maxillary and mandibular length increased.Conclusions:Upper airway volume and morphology were similar in different skeletal patterns of Class II malocclusion. Actual upper and lower jaw lengths were more closely related to upper airway volume and morphology than the angles that reflected their position relative to the cranial base.