Primary biliary cirrhosis after long-term practolol administration.

Abstract

1591Clostridium tetani, however, have been found in up to 40%/o of samples of human faeces.' Another of our patients developed postoperative tetanus, which was attributed to self-contamination, after removal of a tumour of the buttock. Since rubber-band ligation of haemorrhoids produces an avascular area, and since this is in contact with a potential source of Cl tetani, the tetanus in this case may reasonably be attributed the operation. Certainly the time relationship fits in with the incubation period of tetanus. Case reportsA 76-year-old man developed pruritus after four years' continuous treatment with practolol 300 mg daily for angina of effort. He had an eczematous rash with palmar erythema; dryness of the eyes was confirmed by Schirmer filter paper testing. Smooth, non-tender hepatomegaly was noted. The following measurements were made: serum bilirubin 25 ,tmol/l (1.5 mg/100 ml) (normal 1-7-17,tmol/l (0.1-1.0 mg/100 ml)), alkaline phosphatase (liver isoenzyme) 405 IU/l (normal 20-90), serum aspartate transaminase (SGOT) 12 IU/I (normal 4-20), serum albumin 36 g/l, serum total globulin 40 g/l, serum IgM 2 2 g/l (0-7-2 0), IgG 11-6 g/l (9-5-16 5). Hepatitis B antigen was absent. Antinuclear factor was present (titre 1/80) as was smooth muscle antibody (1/20) and mitochondrial antibody (1/80). Liver scan and histological examination of a needle biopsy specimen confirmed the presence of cirrhosis.He remained well after practolol was stopped, but liver function tests showed persisting cholestasis. The development of cervical lymphadenopathy two years later, however, led to the diagnosis of nodular sclerosing Hodgkin's lymphoma. Despite radiotherapy he died after six months. Patent bile ducts were found at necropsy, and histology of tissue obtained a few minutes after death confirmed advanced cirrhosis with proliferating bile ducts and lymphocyte aggregates consistent with primary biliary cirrhosis. Staining with orcein and rubeanic acid showed hepatocytic metalloprotein complex as found in PBC.3 Typical sclerosing peritonitis affecting the jejunum was also present.A 57-year-old man was treated with practolol 300 mg/day for angina. After seven months he developed a psoriasiform rash and two months later he complained of dryness of the eyes. Liver function was not tested until 16 months after discontinuing the drug. Findings were: serum bilirubin concentration 50 ,imol/l (3 0 mg/100 ml), alkaline phosphatase concentration 144 IU/l, and SGOT 15 IU/I. Serum protein and immunoglobulins were normal as were autoantibody tests except mitochondrial antibody, which was positive to a titre of 1/160. A needle biopsy specimen of the liver showed normal lobular architecture, but near bile ducts were large epithelioid granulomata with surrounding lymphocytes (fig calculate the probability of men with PBC being exposed to practolol. By making several assumptions, an estimate of the figure may be obtained from the number of prescriptions for practolol and the number of certified deaths from PBC a year. Two cases of PBC expos...

Long‐term follow‐up of patients with mild to moderate drug‐induced liver injury

“…The clinical relevance of slightly abnormal liver tests, many years after the diagnosis of DILI, is unclear at the present time. However, the chronic evolution of DILI associated with continuing therapy reported by others [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and confirmed by the results of the current study demonstrates that the prompt recognition of drugs as responsible for the liver injury is of major importance in the management of these patients.…”

“…A number of drugs associated with cholestatic (CS) type of injury have been associated with the development of vanishing bile duct syndrome with long-term persistent CS injury, mostly presented as case reports. [10][11][12] Chronic liver disease, even including the development of liver cirrhosis, has been reported with a suspect causality to a number of different drugs [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] (Table 1).…”

“…Drugs with a suspect causality reported to have caused chronic liver disease, including the development of liver cirrhosis[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] …”

Review article: drug‐induced liver injury in clinical practice

“…However, chronic liver disease, even including the development of liver cirrhosis, has been reported with a number of different drugs. A number of case reports have been published reporting chronic liver injury following DILI 1, 1–13, 13–72 (Table 3).…”