Extrahepatic production of the lignocaine metabolite monoethylglycinexylidide (MEGX).

The extrahepatic production of monoethylglycinexylidide (MEGX) from lignocaine was measured in a 20-year-old female rendered anhepatic while awaiting liver transplantation 4 days after a paracetamol overdose. Following hepatectomy and during continuous arteriovenous dialysis, cardiac stability and control over rising intracranial pressure was restored. Lignocaine (1 mg kg body weight-1 intravenously over 2 min) reached a subtherapeutic peak serum concentration of 0.89 mg l-1 and was rapidly and exponentially cleared, reaching the lower limit of detection after 5 h (cf. around 2 h in normal subjects). There was significant production of MEGX at extrahepatic sites with serum concentrations rising from undetectable levels to 15 micrograms l-1 at 15 min and to a peak of 30 micrograms l-1 at 2 h and falling thereafter. MEGX concentrations were similar in arterial, venous, and pulmonary arterial blood, suggesting minimal MEGX production in the heart, lungs or skeletal muscle. Extrahepatic production of MEGX may contribute to total MEGX formation and should be considered when interpreting test results.

Diclofenac hepatitis.

We report five cases of biopsy-proven hepatitis developing between six and 20 weeks after administration of diclofenac. In one patient jaundice had previously developed following use of ibuprofen. In another the clinical, biochemical and histopathological features were those of chronic active hepatitis and treatment with corticosteroids was required. All patients recovered from their liver injury without sequelae. Resolution of symptoms occurred between three and 12 weeks following cessation of the drug, while liver function tests returned to normal between seven and 16 weeks after drug withdrawal, except in the patient with chronic active hepatitis who remained biochemically abnormal for eight months. Three of the five patients developed transient circulating autoantibodies, suggesting immune mechanisms may be important in the pathogenesis of this injury. The incidence of severe hepatic dysfunction related to the use of diclofenac appears low and is probably in the order of one case per 50-100,000 prescriptions.

Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic haemochromatosis from alcoholic liver disease complicated by alcoholic haemosiderosis.

The hepatic tissue iron index proposed by Bassett et al was evaluated in 35 patients with homozygous genetic haemochromatosis, 67 patients with alcoholic liver disease, and 18 patients with other forms of chronic liver disease with and without cirrhosis. In patients with cirrhosis hepatic tissue iron concentration reliably differentiated alcoholic liver disease from genetic haemochromatosis. Although mean iron concentration was greater in patients with prefibrotic haemochromatosis than in those with prefibrotic alcoholic liver disease, some overlap occurred and complete differentiation of the two conditions was not possible. This overlap was particularly evident in some young patients with haemochromatosis in whom the tissue iron concentration grade fell in the range commonly seen in alcoholic haemosiderosis. Inability to differentiate early genetic haemochromatosis from alcoholic liver disease complicated by haemosiderosis was also a problem with standard Perls's staining. When the hepatic tissue iron index was calculated (hepatic tissue iron concentration/patient's age in years), clear differentiation of genetic haemochromatosis from both alcoholic liver disease and other forms of chronic liver disease was obtained in both cirrhotic and precirrhotic patients. This study confirms that the hepatic tissue iron index is a useful means of differentiating patients with genetic haemochromatosis from those with alcoholic liver disease. We suggest that biochemical estimation of tissue iron concentration and calculation of the tissue iron index in all patients in whom genetic haemochromatosis is a possible diagnosis will reduce the likelihood of misdiagnosing this as alcoholic liver disease.