Jorge Findor

Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study

BACKGROUND/AIMS To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis. METHODS Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or placebo for 2 weeks. Subsequently, a 1-week washout period ensued and patients were crossed over to the other therapy for 2 additional weeks. Pruritus was assessed daily with a visual analogue scale (VAS) from 0 to 10. Patients whose pruritus decreased >50% of basal with naltrexone received naltrexone 50 mg/day for 2 additional months. RESULTS Mean basal VAS was similar in both groups. VAS showed greater and more significant changes with naltrexone than with placebo (P<0.0003). In nine out of 20 patients (45%) receiving naltrexone, pruritus decreased >50% compared to basal value, including five whose pruritus disappeared completely. No significant changes were observed in serum biochemistry. Most of the adverse events that occurred during the first 48 h of naltrexone therapy were consistent with opioid withdrawal-like phenomena and spontaneously disappeared 2 days after starting treatment. CONCLUSIONS Naltrexone can be considered as an alternative option to treat pruritus of cholestasis. In the current study, side effects were transient and did not require specific medication.

Primary biliary cirrhosis and hepatocellular carcinoma

The findings by epidemiological studies on the link between PBC and HCC are in general agreement with the notion that cirrhosis is a risk factor for HCC development. From the clinical perspective, this implies that in PBC patients with cirrhosis, the screening for HCC should be considered for evaluating prognosis as well as therapeutic options. At this time, it is not possible to determine whether any PBC-specific risk factors other than cirrhosis per se exist for the development of HCC. Identification of such risk factors may point to new mechanisms involved in the carcinogenesis of HCC. In order to answer the question whether the underlying mechanisms for PBC are risk factors for HCC, more aggressive clinical studies with larger patient populations are needed. Such studies should include patients with PBC as well as patients with cirrhosis of other etiologies, both have to be carefully matched for patient characteristics including race, gender, age, disease stage and period of follow-up. On the other hand, the resolution of this issue also relies on a better understanding of the molecular pathogenesis of PBC itself.

Erythrocytapheresis with Recombinant Human Erythropoietin in Hereditary Hemochromatosis Therapy: A New Alternative

Background and Objectives: The purposes of this study were to evaluate the tolerance, efficacy and safety of isovolemic erythrocytapheresis (EA) in nonanemic patients with hereditary hemochromatosis (HH), and to assess the usefulness of recombinant human erythropoietin (rHuEPO) associated with EA to reduce treatment duration. Materials and Methods: In 10 asymptomatic patients with serum ferritin >400 μg/l, transferrin saturation >50%, and GPT elevation, EA with rHuEPO and folic acid was performed. Results: Red cell indices, serum ferritin, and other iron metabolism parameters (serum iron, transferrin, and transferrin saturation); GPT and other laboratory data were considerably improved. Conclusion: This method offers better results in less time than traditional phlebotomy. EA with rHuEPO is an effective therapeutic alternative for patients with HH.

Isoenzymes of γ-glutamyl transpeptidase in liver diseases

SummaryA new method for the separation of isoenzymes ofγ-glutamyl-transpeptidase is described, using electrophoresis on acetate cellulose gel and a developing solution composed byγ-glutamylβ-naphthylamide, and a colored diazonium compound.The method permits the separation of up to four different isoenzymes, which we calledγ-GT1,γ-GT2,γ-GT3,γ-GT4, the first two showing an electrophoretic migration similar to that ofα1- andα2-globulins and the other two to that ofβ-globulins.The present technique has proved its usefulness in detecting isoenzymes in serum with values of totalγ-glutamyl-transpeptidase higher than 80 U/L.The application of this method in 52 patients with different types of biliary obstruction and hepatocellular damage has shown that it provides new possibilities in differential diagnosis.ZusammenfassungEine neue elektrophoretische Trenn-Methode für die Isoenzyme derγ-Glutamyl-Transpeptidase (γ-GT) wird beschrieben. Als Träger dient Cellulose-acetat, als Entwicklungslösung y-Glutamyl-β-Naphthylamid und eine gefärbte Diazo-Verbindung.Mit dieser Methode lassen sich 4 Isoenzyme differenzieren (γ-GT1—γ-GT4).γ-GT1 undγ-GT2 wandern mit den α1- und α2-Globulinen,γ-GT3 und y-GT4 im Bereich derβ-Globuline.Die beschriebene Technik erlaubt die Trennung der y-GT-Isoenzyme in Seren, deren Gesamt-γ-GT-Aktivität 80 U/l übersteigt.Die Anwendung der Methode bei 52 Seren von Patienten mit verschiedenartigen Gallenabflußbehinderungen und Leberparenchymzellschädigungen hat gezeigt, daß sie neue differential-diagnostische Möglichkeiten eröffnet.

Intensive plasmapheresis as an alternative therapy for intractable pruritus of primary biliary cirrhosis

Primary biliary cirrhosis is a chronic disease of presumed autoimmune etiology, generally associated with other systemic abnormalities such as scleroderma, characteristic of Sjogrens syndrome and Raynauds syndrome, for which pruritus is the most troublesome symptom. Treatment of this disease is a major unsolved problem. Although the use of cholestyramine has been effective, a considerable number of cases are refractory to the drug and to other agents such as corticosteroids, azathioprine and penicillamine. Plasma exchange has proven to be a useful option in four female patients with primary biliary cirrhosis--two with grade III histology and the other two with grade IV disease and intractable pruritus. The procedure was well tolerated and no side effects were observed. There was a temporary but significant attenuation of pruritus and improvement of melanoderma. Intensive plasma exchange is proposed as an alternative therapy in primary biliary cirrhosis with refractory pruritus.