naloxone and Liver-Cirrhosis--Biliary

Primary biliary cirrhosis (PBC), autoimmune cholangitis (AIC = AMA-negative PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholestatic liver diseases. Overlap syndromes combine characteristics of cholestatic liver diseases and autoimmune hepatitis. In PBC, alkaline phosphatase and gamma-glutamyl transferase are elevated, to a lesser degree aminotransferases. Histology shows bile duct lesions. Anti-mitochondrial antibodies are typical. Ursodeoxycholic acid (UDC) is established therapy that slows or even stops the disease progression, at least in early stages of the disease. In non-responders immunosuppression is recommended. PSC is mostly associated with chronic inflammatory bowel diseases. P-ANCA are frequent. Bile duct lesions revealed by retrograde cholangiography are characteristic. UDC is given as therapy. Bile duct strictures or bacterial cholangitis may be late sequelae and should be treated by antibiotics or bile-duct dilatation. Cirrhosis may ultimately develop in PBC and PCS. In progressed PBC or PSC liver transplantation is indicated.

Topics: Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Anticholesteremic Agents; Antipruritics; Autoimmune Diseases; Bile Ducts; Cholagogues and Choleretics; Cholangiography; Cholangitis; Cholangitis, Sclerosing; Cholestasis; Cholestyramine Resin; Clinical Enzyme Tests; Diagnosis, Differential; Hepatitis, Autoimmune; Humans; Immunosuppression Therapy; Inflammatory Bowel Diseases; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Transplantation; Naloxone; Naltrexone; Narcotic Antagonists; Ondansetron; Plasmapheresis; Ursodeoxycholic Acid

To test the hypothesis that opioid agonist activity contributes to the pruritus of cholestasis, a placebo-controlled single-blinded trial of naloxone, an opioid antagonist, was conducted in eight patients with primary biliary cirrhosis. After discontinuation of all conventional antipruritic medications, one or two continuous (24-hour) IV infusions of naloxone (0.2 micrograms.kg-1.min-1) and placebo solution were administered consecutively in an order that was not predetermined. Pruritus was assessed subjectively by means of four hourly recordings of a visual analogue score. In addition, objective measurements of scratching activity that were independent of gross body movements were continuously recorded using an apparatus specifically designed to measure the frequencies associated with this activity. No side effects associated with naloxone infusions were observed. Only scratching activity data obtained for the same periods of day and night during both naloxone and placebo infusions were compared. Naloxone infusions were consistently associated with a decrease in values of the scratching activity index. In addition, in 50% of the patients the infusions were associated with a decrease in visual analogue score. The mean decrease in scratching activity ranged from 29% to 96% (mean, 50%; P less than 0.001). These findings imply that increased opioid agonist activity contributes to scratching activity in cholestatic patients.

Topics: Adult; Aged; Chronic Disease; Female; Humans; Infusions, Intravenous; Liver Cirrhosis, Biliary; Middle Aged; Motor Activity; Naloxone; Pilot Projects; Pruritus; Single-Blind Method

Topics: Adult; Antipruritics; Clinical Trials as Topic; Double-Blind Method; Humans; Liver Cirrhosis, Biliary; Male; Naloxone; Pruritus; Sodium Chloride

Topics: Fatigue; Female; Humans; Liver Cirrhosis, Biliary; Middle Aged; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Female; Humans; Infusions, Parenteral; Liver Cirrhosis, Biliary; Middle Aged; Naloxone; Narcotic Antagonists; Pruritus