Liver transplantation is a well-established treatment for liver failure. Prolongation in survival is accepted, but long-term effects of liver transplantation on cognitive and psychological outcome are unclear. In the present study, psychological data were prospectively collected for 164 patients who were assessed for liver transplantation. Memory impairment, psychomotor slowing, anxiety, and depression were commonly observed. Severity of liver disease at assessment was significantly associated with slowing of reaction time. Memory impairment distinguished those who were not listed for transplantation because of illness severity. One year posttransplantation, follow-up data from transplant recipients showed significant improvement in most psychological domains relative to both healthy comparison participants and patients with chronic liver disease who did not undergo transplantation. Immunosuppression (cyclosporine versus tacrolimus) did not have differential effects on quality of life, fatigue, or affective status, although those administered cyclosporine showed greater improvements at 1-year follow-up on simple and choice reaction times. Elevated levels of anxiety and neuroticism at pretransplantation assessment were associated with worse psychosocial outcome at 1 year posttransplantation. Severity of liver disease was not related to psychological outcome at 1 year. Good psychological outcome at 1 year was maintained at the 3-year follow-up. (Liver Transpl 2003;9:712-720.)
The World Health Organization has recently produced a generic quality of life measure--the WHOQOL-100, together with an abbreviated version, the WHOQOL-BREF. Preliminary data suggest that the WHOQOL BREF provides a valid and reliable alternative to the lengthier WHOQOL-100. In the present study, the sensitivity to change of both versions was tested pre- and 3 months post liver transplantation in fifty patients and also in twenty-one non-transplanted liver disease controls. Quality of Life domains on both measures were highly correlated, and were sensitive to change following transplant and remained stable on repeat assessment in non-transplanted control patients. However, the sensitivity to change was significantly reduced for the Social domain in the WHOQOL BREF. It is concluded that the WHO-QOL-BREF is a useful alternative to the WHOQOL-100 in evaluating quality of life improvement following major therapeutic interventions for Physical, Psychological and Environmental domains of life quality. However, researchers interested in measuring the Social aspects of life quality may be best advised to use the lengthier WHOQOL-100.
Hepatic encephalopathy is a neuropsychiatric syndrome that can complicate acute and chronic liver disease. Recent research has focused on the role benzodiazepine-like substances play in the pathogenesis of this disorder. It has been proposed that potentiation of the action of the neuroinhibitory transmitter γr-aminobutyric acid (GABA) through the binding of endogenous benzodiazepine agonists to the benzodiazepine receptor binding site accounts for the clinical and biochemical features of this condition.Increased levels of endogenous benzodiazepine-like substances have been noted in animal models of hepatic encephalopathy. In human studies, levels of these substances of up to 10 times those found in the body fluids of nonencephalopathic controls have been reported. The existence of such markedly elevated levels cannot be satisfactorily explained with reference to possible pharmaceutical or dietary origins.Further support for the role of benzodiazepines in the mediation of hepatic encephalopathy comes from the therapeutic effect reported after administration of the benzodiazepine receptor antagonist flumazenil. Improvements in the severity of hepatic encephalopathy have been documented in rats with fulminant hepatic failure given flumazenil, although results have been inconsistent according to the dose of flumazenil used and the procedure employed to induce the encephalopathy. Transient, but distinct, improvements in the grade of hepatic encephalopathy have also been documented in several human studies. In a placebo-controlled study involving patients with mild hepatic encephalopathy, a low dose of flumazenil (0.2 mg/kg) resulted in a significant improvement in reaction time.Research now needs to identify whether the beneficial effect of flumazenil is due to its antagonistic or inverse agonistic properties, and also to clarify the mechanisms by which the differential response to the drug in animal models of fulminant hepatic failure is mediated.
There is an increasing focus on the importance of quality-of-life (QOL) factors in evaluating the efficacy of medical and surgical interventions. There are a wide number of instruments currently available, and the aim of the present study was to evaluate the relative sensitivity to change of three widely used QOL measures, the WHOQOL-100, the SF-36 and the Rotterdam Symptom Checklist, focusing on psychological and physical components of life quality. Fifty patients were assessed pre- and 3 months post-liver transplantation. In addition, 21 patients with liver disease but who were not transplanted were assessed twice, separated by a 3-month interval, in order to serve as a comparison group. All QOL measures showed significant improvement following liver transplantation, whereas the control group showed no significant within-subject change on any measure. We employed the Standardised Response Mean (SRM) effect size as our index of clinically meaningful change in QOL measures. Large SRM effect sizes were obtained following liver transplantation for WHOQOL-100 and SF-36 summary measures, and for the Rotterdam physical subscale. In contrast, the traditional SF-36 scale scores and Rotterdam psychological subscale exhibited only moderate sensitivity to change.
PTSD in a sample of patients who survived life-threatening variceal haemorrhage is much rarer than might reasonably have been anticipated. Possible reasons for this low prevalence of PTSD are discussed.
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