Liver transplantation (LT) is an established therapy for patients with end-stage primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). In this report, we describe the health status and quality of life (QOL) in patients with these cholestatic liver diseases before and after LT. A QOL questionnaire was completed by 157 adult patients with PBC or PSC before and 1 year after liver transplantation at the Mayo Clinic or Baylor University Medical Center. This questionnaire measured four aspects of QOL, including symptoms; physical, social, and emotional functioning; health perceptions; and overall QOL. Changes in these QOL parameters before and after LT were described, and regression analysis was used to assess the relationships between clinical and QOL factors. There were no differences in QOL parameters between patients with PBC and PSC. QOL following transplantation was substantially better than before transplantation. This was observed in all four aspects of QOL. The degree of improvement as measured by effect size (difference in mean scores divided by the pretransplantation standard deviation) was 0.53 for symptoms (P F .01), 1.16 for function (P F .01), 2.37 for health satisfaction (P F .01), and 1.16 for overall QOL (P F Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are cholestatic liver diseases of unknown etiology with distinctive clinical and epidemiological features. These diseases are characterized by a slow and usually progressive course that, over time, leads to cirrhosis, portal hypertension, and, eventually, liver failure. Patients with liver failure from end-stage PBC or PSC are potential candidates for orthotopic liver transplantation (LT). Between 1988 and 1994, these patients accounted for approximately 17% of LT recipients. 1 Following LT, these patients have an improved prognosis, with 2-year survival rates reported to be over 90%. 2 It is not known how rapidly or completely LT reverses the devastating symptoms of severe PBC or PSC, or how well these patients adapt to the drug regimens necessary to maintain their grafts. Information about these benefits and consequences of LT taken from the patient' s perspective can improve clinicians' understanding of the recovery process and enable clinicians to better prepare these patients and their families for LT. Furthermore, this information may identify important issues for long-term survivors and contribute to the evaluation of new therapies to enhance LT outcomes. Information of this type, about the effects of an illness and its consequent therapy on a patient' s health and well-being as perceived by the patient, is termed quality of life (QOL), or more specifically, health-related QOL. 3 While a number of studies have described the QOL outcomes of heterogeneous series of LT recipients, 4-8 QOL findings specific to patients with cholestatic liver disorders are very limited. 9 Patients with PBC or PSC form a distinct subgroup of LT patients in terms of their demographics, symptomatology, and complications of...

patients with most advanced disease, resulting in a longer We studied the outcome of 436 patients with primary waiting time for less advanced patients. The clinical status biliary cirrhosis (PBC) or primary sclerosing cholangitis of these patients inevitably deteriorates as their waiting time (PSC) who underwent orthotopic liver transplant (OLT) lengthens. 3 Since the postoperative course of patients who at three major liver transplant centers. Univariate preare end-stage at the time of transplantation is characterized dictors of outcome included age, Karnofsky score, by higher mortality, morbidity, and cost 3-6 ; this deferral of Child's class, Mayo risk score, United Network for Organ all patients until their status is terminal has a negative imSharing (UNOS) status, nutritional status, serum albupact upon liver transplantation outcome. Recognizing that min, serum bilirubin, international normalized ratio, not every patient can be transplanted, there is a need for and the presence of ascites, encephalopathy, renal failmethods which will allow transplantation physicians to preure (serum creatinine ú 2 mg/dL), and edema refractory dict which patients will most benefit from transplantation. to diuretics. Using these predictors, we developed a fourFor the referring physicians, the knowledge of factors that variable mathematical prognostic model to help the lead to poor OLT outcome may enable them to better plan liver transplant physician predict the following: 1) the their referrals. amount of intraoperative blood loss; 2) the number of This paper reports the predictors of post-OLT morbidity, days in the intensive care unit (ICU); and 3) severe comas the survival of transplanted patients has improved and plications after surgery. The model uses age, renal failbecome medically acceptable. 2 Indeed, the risk factors for paure, Child's class, and United Network for Organ Shartient and graft survival could not be assessed as there were ing status. This study is the first to model the outcome not enough events for adequate modeling. We studied the of liver transplant in patients with a specific etiology of outcome of 436 patients who received a liver transplant for chronic liver disease (PBC or PSC). The model may be primary biliary cirrhosis (PBC) or primary sclerosing cholanused to help select patients for OLT and to plan the timgitis (PSC). First, we examined the relationship between seing of their transplantation. (HEPATOLOGY 1997;25:672-lected preoperative variables and intraoperative blood loss, 677.) and postoperative morbidity (intensive care unit [ICU] stay and major complications after OLT). Second, we developed a In the early 1980s, orthotopic liver transplant (OLT) was mathematical prognostic model, containing four inexpensive recognized to prolong survival in patients with chronic liver and easily obtained variables, that the liver transplant physidisease; today it is accepted therapy for end-stage liver dis-cian can use to calculate a score for predicting the patient's ease due to a variety of etiologies....

Benzodiazepine receptors were studied in rats with hepatic encephalopathy due to fulminant hepatic failure induced by galactosamine. [3H]-Diazepam binding studies on brain synaptic membranes of rats with mild and severe encephalopathy show a significant increase in the number of receptors in both stages of coma. [3H]Diazepam binding to synaptic membrane preparations from rats in the mild or severe stage of encephalopathy hyper-responded to the stimulatory effect of gamma-aminobutyric acid (GABA) applied in vitro at doses which for control rat preparations were in a subthreshold range. The effect of GABA was shown to be specific, since it was blocked by bicuculline methiodide. The sensitivity of benzodiazepine receptors in hepatic encephalopathy to nanomolar concentrations of GABA, which induced a significant increase in their affinity, seems to indicate a functional supersensitivity of benzodiazepine receptors in vivo in both mild and severe stages of encephalopathy. The phenomena described may be attributed to a partial degeneration of nerve terminals in hepatic encephalopathy, leading to a supersensitivity of benzodiazepine receptors, which parallels the previously described denervation supersensitivity of GABA receptors present in this animal model of fulminant hepatic failure. These findings may account for the brain hypersensitivity to sedatives administered to patients with liver diseases. The administration in vivo of a benzodiazepine antagonist, 2-phenylpyrazolo[4,3-c]-quinolin-3(5H)-one, counteracted the hypersensitivity of benzodiazepine receptors in the mild stage of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

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