Hepatology : official journal of the American Association for the Study of Liver Diseases
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Portopulmonary hypertension represents a major risk factor for transplantation; therefore, preoperative detection is crucial. The aims of this study were to determine (1) whether Doppler echocardiography performed at evaluation is a reliable tool for detecting portopulmonary hypertension and (2) the incidence of acquired portopulmonary hypertension profile after evaluation. One hundred sixty-five patients had Doppler echocardiography and right heart catheterization at evaluation over a 9-year period. ⋯ In conclusion, Doppler echocardiography is a highly sensitive tool for detecting portopulmonary hypertension. However, because this technique has a poor positive predictive value, right heart catheterization is recommended for confirming portopulmonary hypertension. In addition, the absence of portopulmonary hypertension at evaluation does not exclude the occasional occurrence of acquired portopulmonary hypertension profile after listing.
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Ischemia/reperfusion (I/R) injury remains an important problem in clinical organ transplantation. There is growing evidence that T lymphocytes, and activated CD4+ T cells in particular, play a key role in hepatic I/R injury. This study analyzes the role of signal transducer and activator of transcription 4 (Stat4) and Stat6 signaling in liver I/R injury. ⋯ In contrast, HO-1 depression restored hepatic injury in otherwise I/R resistant Stat4 KOs. In conclusion, Stat4 signaling is required for, whereas Stat4 disruption protects against, warm hepatic I/R injury in mice. The cytoprotection rendered by Stat4 disruption remains HO-1-dependent.
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Acute liver failure (ALF) results in alterations of energy metabolites and of glucose-derived amino acid neurotransmitters in brain. However, the dynamics of changes in glucose metabolism remain unclear. The present study was undertaken using (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy to determine the rates of incorporation of glucose into amino acids and lactate via cell-specific pathways in relation to the severity of encephalopathy and brain edema in rats with ALF because of hepatic devascularization. ⋯ Furthermore, (13)C isotopomer analysis showed a selective increase of de novo synthesis of lactate from [1-(13)C]glucose resulting in 2.5-fold increased fractional (13)C enrichments in lactate at coma stages. [2-(13)C]glutamine, synthesized through the astrocytic enzyme pyruvate carboxylase, increased 10-fold at precoma stages but showed no further increase at coma stages of encephalopathy. (13)C-label incorporation into [4-(13)C]glutamate, synthesized mainly through neuronal pyruvate dehydrogenase, was selectively reduced at coma stages, whereas brain GABA synthesis was unchanged at all time points. In conclusion, increased brain lactate synthesis and impaired glucose oxidative pathways rather than intracellular glutamine accumulation are the major cause of brain edema in ALF. Future NMR spectroscopic studies using stable isotopes and real-time measurements of metabolic rates could be valuable in the elucidation of the cerebral metabolic consequences of ALF in humans.