Deferasirox-induced liver injury and Fanconi syndrome in a beta-thalassemia major male

A 33-year-old male presenting with subacute abdominal pain was found to have hyperbilirubinaemia, hypokalaemia and hyponatraemia. This was in the setting of transitioning between deferasirox iron chelator formulations, from dispersible tablets to film-coated tablets for ongoing treatment of chronic iron overload secondary to transfusion requirement for beta-thalassemia major. A liver biopsy demonstrated acute cholestasis with patchy confluent hepatocellular necrosis and mild to moderate microvesicular steatosis. Based on the histological, biochemical and clinical findings, the diagnosis of hepatotoxicity and Fanconi-like syndrome was made. The patient improved clinically and biochemically with cessation of the deferasirox film-coated tablets and supportive management. To our knowledge, this is the first case report of hepatotoxicity and Fanconi-like syndrome occurring due to deferasirox film-coated tablets with previous tolerance of dispersible deferasirox tablets. It is important to raise clinical awareness of this potentially severe complication.

PATHOMORPHOLOGICAL STRUCTURE OF INTRAHEPATIC DUCTS AND CHOLEDOCH IN PATIENTS WITH ACUTE AND CHRONIC CHOLANGITIS.

The morphological status of bile duct cells was studied in patients with acute and chronic cholangitis at different terms of the disease.All patients (32) were divided into 4 groups: up to 5 days, 12-14 days, 28-30 days and 10-12 months. The control group included 12 patients without clinical manifestations of choledocholithiasis. Acute cholestasis is registered in the intrahepatic bile ducts, the maximal severity of which is on first two weeks. In the period of 28-30 days the residual phenomena of acute cholangitis and the growth of connective tissue in the duct walls and around them are registered. In patients with cholangitis, the largest changes in the wall of the choledochus are recorded in 3-5 days from the onset of the disease in the form of edema-desquamative and epithelium necrosis. On 12-14 days marked "attenuation" and demarcation of the inflammatory process, and on 28-30 there’s the appearance of connective tissue in the wall of the choledoch. Patients operated on for chronic recurrent cholangitis for 1 year are documented on the background of the development of choledoch stricture, cholestasis, cholangiosclerosis, and biliary cirrhosis, as a complication.

Clinical features and management of painless biliary type sphincter of Oddi dysfunction

Objective The objective of this study was to clarify the characteristics and management of painless biliary type sphincter of Oddi dysfunction (SOD). Methods From June 2002 to July 2018, 12 patients who had recurrent liver dysfunction with a dilated bile duct or acute cholestasis of unknown cause without biliary pain (painless SOD) were included in this study. These patients’ characteristics were compared with those of 36 patients with biliary type SOD based on the conventional definition (criteria-based SOD). Results Patients with painless SOD had significantly more prominent bile duct dilation than patients with criteria-based SOD (13.9 vs. 12.2 mm, respectively). Prophylactic biliary drainage was performed significantly more often in patients with painless SOD than criteria-based SOD (67% vs. 11%, respectively). The short-term effectiveness rate of endoscopic sphincterotomy, the symptom recurrence rate, and the incidence of adverse events were not significantly different between the two groups. Conclusions Painless SOD is a specific subtype of biliary SOD that causes recurring liver dysfunction or acute cholestasis without biliary pain. Endoscopic sphincterotomy was effective in the present study, but the relapse rate was as high as that in typical SOD.

Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury

The objective of this study was to evaluate the hepatoprotective and metabolic effects of rosmarinic acid (RA) in rats. RA [100 mg/kg body weight (BW)] was intragastrically (i.g.) administered to Sprague-Dawley (SD) rats once a day for seven consecutive days. The rats were then i.g. administered α-naphthylisothiocyanate (ANIT) (80 mg/kg once on the 5th day) to induce acute intrahepatic cholestasis after the last administration of RA. Blood samples were collected at different time points (0.083 h, 0.17 h, 0.33 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 20 h) after administration, and the levels of RA were estimated by HPLC. Plasma and bile biochemical analysis, bile flow rate, and liver histopathology were measured to evaluate the hepatoprotective effect of RA. The PK-PD curves showed obviously clockwise (AST and ALT) or anticlockwise (TBA, TBIL). Pretreatment with RA at different doses significantly restrained ANIT-induced pathological changes in bile rate, TBA, TBIL, ALT, AST (p < 0.05 or p < 0.01). The relationship between RA concentration and its hepatoprotective effects on acute cholestasis responses was assessed by PK-PD modeling.