Treatment of acetaminophen-induced hepatitis and fulminant hepatic failure with extracorporeal sorbent-based devices.

When a patient with acetaminophen overdose arrives in the emergency room more than 14 hours after ingestion, the value of N-acetylcysteine is unproven and patient mortality is at least 10%. Anecdotal case reports have indicated benefit of extracorporeal detoxification of these late-arriving patients with acetaminophen overdose. We identified 10 patients with serious acetaminophen overdose, 8 that arrived in the emergency room 16 to 44 hours after acetaminophen overdose with plasma levels predicting severe hepatic toxicity, and 2 that arrived in the emergency room 8 to 12 hours after overdose but with exceedingly high levels. All patients developed severe hepatitis (mean peak alanine aminotransferase, 4,052; mean peak protime, 25 seconds). At 16 to 68 hours after overdose, the patients were treated for 4 to 6 hours with the Liver Dialysis System (Hemocleanse Inc, W. Lafayette, IN), a single-access hemodiabsorption system indicated for treatment of serious drug overdose and for treatment of hepatic encephalopathy. Acetaminophen levels fell an average of 73% during treatment. Treatment was repeated 24 or 48 hours later if acetaminophen was still measurable in plasma. All 10 patients recovered intrinsic liver function and general health, with liver enzymes starting to normalize 24 hours after treatment, and were discharged 3 to 7 days after overdose. No patient required liver transplant. Because market introduction of Liver Dialysis, there have been 40 more patients with acetaminophen-induced hepatotoxicity treated with Liver Dialysis. All have recovered liver function without long-term sequelae. Though most of these patients with already established hepatic toxicity from acetaminophen would recover without extracorporeal blood therapy, treatment with the Liver Dialysis System should assure recovery from acute hepatic failure, and may shorten the clinical course of the illness.

Short course induction immunosuppression with thymoglobulin for renal transplant recipients.

BACKGROUND: The aim of this study was to demonstrate that 3-days of induction immunosuppression with thymoglobulin was as effective and safe as a 7-day course and reduced initial hospitalization after transplantation. METHODS: This was a prospective, nonrandomized trial of 40 consecutive patients receiving thymoglobulin induction for 3 days and followed for 1 year. An historical group of 48 patients that received 7 days of thymoglobulin served as controls. RESULTS: At 1 year, acute rejection (5 vs. 4%), graft survival (95 vs. 98%) and patient survival were similar; a composite end point of freedom from death, rejection, or graft loss, the event-free graft survival, was similar as was the safety profile. In the 3-day group, lymphocyte depletion was more sustained and initial hospitalization was significantly shorter (6 vs. 8 days). CONCLUSION: Three-day induction with thymoglobulin is as effective and safe as seven days, decreases initial hospitalization and causes more sustained lymphocyte depletion.

Variation in plasma leptin concentrations after unilateral nephrectomy.

The temporal changes in plasma leptin concentrations were studied in healthy adults who underwent unilateral nephrectomy. Another group who underwent abdominal surgery for repair of aneurysm or to relieve arterial stenosis, was also studied. Plasma leptin concentrations increased to 230% +/- 74% of prenephrectomy levels at 8 to 16 hours after surgery and then generally declined. Subjects with prenephrectomy leptin concentrations above 14 microL maintained elevated postnephrectomy levels, whereas subjects with low prenephrectomy concentrations had final leptin levels below prenephrectomy concentrations. Abdominal surgery subjects did not manifest the increase after surgery, but generally had declining concentrations throughout the convalescent period. Free and bound fractions of plasma leptin and leptin binding capacity were measured in the prenephrectomy and peak specimens (8 to 16 hours postnephrectomy) by high-performance liquid chromatography (HPLC). The increase in total leptin postnephrectomy largely affected the free fraction of leptin, without significant increase in bound leptin or leptin binding capacity. We conclude that (1) plasma leptin concentrations increase acutely after nephrectomy, consistent with the role of the kidneys in eliminating circulating leptin; (2) plasma leptin concentrations decline thereafter, suggesting activation of compensatory elimination capacity; and (3) the postnephrectomy peak in total leptin increases primarily free leptin.

In vitro T cell proliferation from kidney allograft biopsies with unremarkable pathology: new strategies for an old problem.

Acute rejection of renal allografts is mediated by infiltrating alloreactive T cells. The goals of this study were to correlate T cell proliferation with rejection and to determine whether T cell proliferation in the absence of rejection would predict future rejection episodes. Toward this, kidney biopsies (n=100) were cultured in the presence of interleukin-2. Cultures were examined at 4, 24, and 48 hr for T cell proliferation. A strong correlation was observed between T cell proliferation at any time point and rejection. There was not a significant correlation between T cell proliferation in biopsies with no rejection and the occurrence of a rejection episode within 2 months. However, T cell proliferation after 4 hr was a better predictor of the occurrence of rejection within 2 months compared with observations after 24 and 48 hr. Therefore, a subgroup of patients with unremarkable biopsies but T cell proliferation may be at risk for rejection and warrant closer observation and possible tailoring of immunosuppression.

Hepatocellular carcinoma in a patient with focal nodular hyperplasia.

BACKGROUND: Focal nodular hyperplasia is an uncommon liver tumour that typically requires no therapeutic intervention. CASE OUTLINE: A 43-year-old woman with a 20-year history of oral contraceptive use presented with symptomatic bilateral liver masses. Biopsy revealed hepatocellular carcinoma in the right hemiliver and focal nodular hyperplasia in the left hemiliver. At operation,t he patient was noted to have multiple liver nodules bilaterally, and all intraoperative biopsies were consistent with focal nodular hyperplasia including a biopsy taken from the region that demonstrated carcinoma preoperatively. Because of the earlier biopsy results and the patient's preoperative symptoms, a right hemihepatectomy was performed. Final pathology revealed hepatocellular carcinoma directly adjacent to an area of focal nodular hyperplasia, as well as multiple other areas of hyperplastic liver tumour. DISCUSSION: Although focal nodular hyperplasia is believed to be benign, few studies have followed patients with this tumour beyond three years. Longer-term follow-up studies are needed to determine the natural history of focal nodular hyperplasia, potentially focussing on a subset of patients with either diffuse tumours or prolonged oral contraceptive use.