860 June, 1992 (when he was referred to us) liver histology showed active cirrhosis. He has since been lost to follow-up. A girl, born in March, 1987, to an HBsAg-positive, anti-HBe-positive mother with chronic liver disease, has since birth been HBsAg positive, anti-HBe positive, and HBV-DNA positive on all occasions. ALT values were 2-7 times the upper limit of normal throughout the first 2 years of her life and liver histology in June, 1989, showed CAH. During the next 4 years ALT was 3-6 times normal, and when the patient was referred to us, in September, 1993, biopsy revealed active cirrhosis. Both patients were constantly anti-hepatitis C and anti-delta virus negative. HBV type was characterised by polymerase- chain-reaction amplification and direct sequencing of amplified DNA. Direct sequencing of the pre-C region revealed, in both children, an HBV strain with a point mutation at position 1896, creating a stop codon, in more than 95% of all molecules. Although hepatitis will usually resolve promptly in infants born to HBsAg positive, anti-HBe positive mothers, babies who acquire the pre-core mutant of HBV vertically can sometimes go on to chronic hepatitis and liver cirrhosis. Careful monitoring of such infants is therefore mandatory, and antiviral therapy should be tried if chronic liver disease is diagnosed. Sandro Vento, Giovanni Di Perri, Ercole Concia, Dante Bassetti Department of Infectious Diseases, Borgo Trento Hospital, University of Verona, 37100 Verona, Italy; and 1st Department of Infectious Diseases, University of Genoa Bentazepam-associated chronic liver disease SiR-Reports of hepatotoxicity secondary to treatment with benzodiazepines are rare.1 We have seen liver dysfunction associated with a histological picture of severe chronic active hepatitis in a patient who received oral bentazepam for anxiety. This report indicates that chronic liver disease can be associated with long-term bentazepam use. A 65-year-old man had a history of peptic ulcer (20 years previously), and chronic constipation and transient ischaemic attacks 2 years ago when cerebral arteriography showed a complete obstruction of the right carotid. Thromboendarterectomy was done and the antiaggregant agent triflusal was started, although it had to be stopped because of gastrointestinal bleeding. He had normal liver function. 6 months later he was prescribed bentazepam 25 mg three times daily (the manufacturer’s recommended dose) for severe anxiety. He had no toxic habits, and was taking no other drugs except oral lactulose. 4 months later he presented with abdominal discomfort and progressive asthenia, anorexia, and weight loss. Routine blood tests showed increased liver enzymes, and bentazepam was reduced to a daily dose of 25 mg with no improvement in symptoms. He had been taking the drug for 13 months when he decided to stop some days before his appointment. Physical examination showed a malnourished non-jaundiced patient without signs of chronic liver disease. Aspartate aminotransferase (AST) was 152 U/L (normal 0-37), alanine aminotransferase (ALT) 142 U/L (normal 0-40), total bilirubin 18-6 umol/L with direct bilirubin 6-8 umol/L, and y-glutarnyl transferase (y-GT) 109 U/L (normal 11-50). Values for gammaglobulin, alkaline phosphatase, serum copper and ceruloplasmin, serum iron, transferrin, and ferritin levels were all within the normal range. Serum thyroid hormones were also normal. The leucocyte and platelet counts were 3 x 109/L and 130 x 109/L, respectively. Serology ruled out viral hepatitis A, B, and C (3rd-generation enzyme-linked immunosorbent assay, Ortho Diagnostics Systems; Inno-Lia III HCV, Innogenetic, Ingelheim Biosystems, SA), cytomegalovirus, and Epstein-Barr virus. Antinuclear, antismooth muscle, and anti-liver-kidney microsomal-1 antibodies were all negative. An abdominal echography was normal. Sections of a percutaneous liver biopsy specimen showed expanded portal areas with a dense infiltrate (lymphocytes and monocytes) that disrupted the limiting plate, and surrounding clusters of swollen hepatocytes. Lymphoid aggregates (follicles) were seen in some portal tracts. There was marked portal-to-portal fibrosis and transition to cirrhosis was evident in some areas. A striking degree of parenchymal collapse was also seen. Shortly after he stopped taking bentazepam the patient’s clinical condition improved dramatically and by the eleventh week his serum AST had decreased to 66 U/L, ALT to 53 U/L, and y-GT to 85 U/L; leucocyte and platelet counts also returned to normal. Laboratory findings were normal at 4 months. Although many drugs commonly used can have toxic effects on liver, benzodiazepines appear to have a very low hepatotoxic potential,l cholestasis being reported in only a few patients who were taking chlordiazepoxide, diazepam, or flurazepam. Bentazepam is a benzodiazepine marketed in Spain since 1981 for anxiety disorders. The adverse effects noted by the manufacturer are gastrointestinal discomfort and dryness of the mouth. We think that a causal relation between the use of bentazepam and hepatic injury can confidently be established because alternative explanations have been ruled out and withdrawal of the drug was followed by a rapid improvement in the patient’s condition and return of laboratory findings to normal. For ethical reasons rechallenge was not attempted. The mechanism of drug-induced liver injury may be intrinsic (dose-dependent) or allergic (idiosyncratic), the symptoms usually appearing soon after exposure.2 Unpredictable hepatic injury may also result from a metabolic aberration rather than hypersensitivity, and usually develops after latency periods of 1 week to 12 months or longer, with no apparent signs of hypersensitivity. In addition, reproduction of the hepatic injury requires administraton of the drug for a period of days or weeks, rather than only one or two doses, presumably to allow the accumulation of toxic metabolites.3 In our patient the type of injury, the absence of hallmarks of drug allergy (rash, fever, eosinophilia, or granulomatous inflammation in the liver) and the long period of latency between drug intake and presentation suggest an idiosyncratic metabolic mechanism. Raul J Andrade, M Isabel Lucena, Ramiro Alcantara, Jose M Fraile Liver Unit, Department of Gastroenterology, and Clinical Pharmacology Service, University Hospital, School of Medicine, University of Malaga, 29080-Malaga, Spain 1 Bass NM, Ockner RK. Drug-induced liver disease. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. 2nd ed. Philadelphia: WB Saunders, 1990: 754-91. 2 Sherlock S. The spectrum of hepatotoxicity due to drugs. Lancet 1986; ii: 440-44. 3 Kaplowitz N, Yee T, Simon FR, Stolz A. Drug-induced hepatoxicity. Ann Intern Med 1986; 104: 826-39. Pulmonary eosinophilia associated with dapsone SiR-Pulmonary eosinophilia (Loeffler’s syndrome) can be caused by drugs such as sulphonamides, penicilllin, nitrofurantoin, hydralazine, or chlorpropamide and may be life-threatening.’ We report a case of pulmonary eosinophilia associated with dapsone. A 65-year-old woman with a history of tuberculosis at the age of 15 was treated with dapsone alone at a dose of 100 mg per day in September, 1992, for cicatricial pemphigoid. She was receiving no other medications. The initial eosinophil count