Minocycline-induced liver injury.

Tetracycline may cause fatty infiltration of the liver; more recently, it has been reported to cause intrahepatic cholestasis with bile duct depletion. However, minocycline, a derivative of tetracycline, is not generally recognized to be hepatotoxic. We report a series of six cases of presumed minocycline-induced liver injury; five of these patients had acute hepatitic illness, whereas one had a more prolonged course with histological evidence of chronic hepatitis. In addition, three patients demonstrated abnormal anti-nuclear antibody levels, and one had positive double-stranded DNA.

Efficacy of cisapride therapy in functional dyspepsia.

AIM: To assess the efficacy of cisapride therapy in relieving symptoms of functional dyspepsia. METHODS: After a 2-week placebo run-in period, 61 out of 74 patients were eligible to enter a 4-week double-blind treatment phase, consisting of treatment with cisapride (10 mg) or placebo tablets t.d.s. Gastric emptying was assessed scintigraphically at entry to the study. Patients were stratified before treatment into those with or without active chronic (Helicobacter pylori) gastritis. Patients were also classified retrospectively into those with 'reflux-like' dyspepsia (n = 29) and those with 'motility-like' dyspepsia (n = 32). RESULTS: At the end of the active treatment phase, there was a similar significant (P < 0.001) reduction in total symptom score from baseline in both cisapride (8.9 +/- 0.5 to 5.8 +/- 0.6) and placebo (9.7 +/- 0.6 to 5.5 +/- 0.6) groups. Scores for heartburn and continual bloating were significantly reduced in the cisapride but not the placebo group; improvement was attributable to patients with normal, rather than delayed, rates of gastric emptying. For continual bloating, significant improvement also occurred in the cisapride subgroup without gastritis, but not in the subgroup with gastritis (mean symptom score reduction 0.48 +/- 0.18, P = 0.03). For global evaluation by the investigator and by the patient, the overall improvement rates were not statistically different between cisapride and placebo groups. In those with normal gastric emptying, however, there was a significant (P = 0.01) improvement in general well-being in the cisapride but not in the placebo group. CONCLUSIONS: We were unable to show major differences in the short-term efficacy of cisapride and placebo in functional dyspepsia. There were indications, however, of beneficial effects of cisapride over placebo in those with 'reflux-like' dyspepsia, and in those without gastroparesis.

Intragastric distribution and gastric emptying of solids and liquids in functional dyspepsia. Lack of influence of symptom subgroups and H. pylori-associated gastritis.

The relative contributions of altered gastric motor function and Helicobacter pylori-associated active chronic gastritis to the pathogenesis of functional dyspepsia are controversial. We therefore evaluated scintigraphically the intragastric distribution and gastric emptying of a mixed solid-liquid meal in 75 patients with functional dyspepsia; patients were subdivided on the basis of both specific symptom clusters and the presence or absence of H. pylori gastritis. Twenty-one (28%) patients displayed abnormal solid and/or liquid gastric emptying, with prolonged solid lag time the most prominent alteration detected. The number of patients with abnormal scintigraphic patterns increased to 36 (48%) when intragastric distribution parameters (fundal half-emptying time and antral maximal fraction) were examined. Although patients with reflux-like dyspepsia (N = 36) demonstrated significantly slower rates of liquid emptying at 45 and 70 min and a higher prevalence of abnormal liquid intragastric distribution when compared to patients with motility-like dyspepsia (N = 39) or to controls (N = 34), the absolute differences were small and unlikely to be of clinical significance. Patients without H. pylori gastritis (N = 50) demonstrated a significantly more prolonged solid lag time when compared to those with H. pylori gastritis (N = 25), but the difference was small and there were no other differences between these two subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy.

The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.

Prolonged hepatic cholestasis after flucloxacillin therapy.

A severe prolonged illness that was characterized by deep jaundice and debilitating pruritus occurred in five patients after the use of flucloxacillin. The symptoms and signs of liver disease took at least two months to resolve; after four- to nine-months' follow-up, liver enzyme activities have remained abnormal in all patients. Examination of liver biopsy specimens showed severe cholestasis in all cases, with evidence of significant bile-duct injury in three cases. In one patient, in whom symptoms have persisted for nine months, examination of a liver biopsy specimen showed marked bile-duct depletion. All patients were seen during a four-month period and it is felt that flucloxacillin-induced liver disease probably has been under-diagnosed and underreported. The use of flucloxacillin has been increasing rapidly and it is anticipated that more cases of flucloxacillin hepatotoxicity will occur in the future.

The prevalence of serological markers for hepatitis B virus infection in Australian Naval personnel.

In order to determine the prevalence of hepatitis B virus infection in Royal Australian Navy personnel and to formulate policies for their education, screening and vaccination, a voluntary survey was undertaken. Seven hundred and forty-eight subjects completed a questionnaire that provided details of age, sex, rank, ethnic origin, service abroad, length of service, history of tattooing, liver disease and blood transfusions. Serum was assayed by radioimmunoassay for the presence of hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (antiHBs) and antibody to hepatitis B core antigen (antiHBc). The presence of markers of hepatitis B virus infection was correlated with "risk factors" by means of the chi 2 test of independence. Fourteen (74%) of 19 personnel from the Pacific Islands, Asia and Africa who were excluded from analysis showed one-or-more such markers. The prevalence of any marker of hepatitis B virus infection was 4.4% (95% confidence interval [CI], 2.9%-5.9%). The individual markers HBsAg, antiHBs and antiHBc were found in 0.4% (95% CI, 0.1%-1.2%), 3.6% (95% CI, 2.2%-4.9%) and 3.9% (95% CI, 2.5%-5.3%) of subjects, respectively. The annual attack rate was estimated to be less than 1%. Factors which had a significant correlation with an increased prevalence of markers of hepatitis B virus infection included tattooing (especially if this had been performed in Asia), age, the duration of service and service abroad. Based on these data, and given the reduced cost of hepatitis B vaccines, vaccination now is considered worth while. A policy of vaccinating all personnel who may be required for service at sea, and others at risk, now is in effect. Educational programmes that are aimed at minimizing the risk of exposure to hepatitis B and other viral infections have been instituted.

Jaundice in pregnancy.

The occurrence of hepatobiliary disease with or without jaundice during pregnancy provides both the hepatologist and obstetrician with an interesting and urgent diagnostic challenge. Advances in our understanding and management of liver disorders unique to pregnancy and hepatobiliary disease in general have resulted in a significant improvement in the outcome for both mother and fetus. Certain disorders such as acute fatty liver of pregnancy and hepatic haemorrhage associated with toxaemia should be considered medical emergencies and delay in diagnosis of these conditions will probably adversely affect maternal and fetal outcome. A careful clinical history, physical examination, appropriate laboratory tests and radiological investigations should allow a diagnosis within 24-48 hours of presentation. Liver biopsy is rarely required. A careful history may provide important information. Does the patient have pre-existent liver disease? Has there been contact with hepatitis, intravenous drug abuse or any other factor predisposing to acute viral hepatitis? Does the patient have a family history of pruritus and/or jaundice to suggest intrahepatic cholestasis of pregnancy? Is the patient's alcohol consumption excessive? Has the patient received any hepatotoxic medications? Has there been abdominal pain and/or fever to suggest gallstones, hepatic bleeding or acute fatty liver of pregnancy? Laboratory investigations may give valuable diagnostic clues. Marked aminotransferase elevation would suggest acute viral or 'ischaemic' hepatitis. Haematological features of microangiopathic haemolysis would point towards toxaemia or AFLP. Hepatitis A and B serological tests may be helpful in viral liver disease. Radiological investigations may be indicated depending on the clinical context. Abdominal ultrasonography may be useful in the diagnosis of gallstones, biliary obstruction, liver tumours or intrahepatic bleeding. Fatty infiltration of the liver may be diagnosed by ultrasonography but computed tomography (CT) of the abdomen is probably more reliable for a diagnosis of acute fatty liver of pregnancy as it allows measurement of liver density which is typically reduced by fatty infiltration. CT scanning is also probably more valuable than ultrasound in assessing the extent of capsular rupture and haemorrhage into the liver and peritoneal cavity.

Value of serum gamma-glutamyltransferase activity in the diagnosis of hepatobiliary disease.

Serum gamma-glutamyltransferase activity (GGT) has been measured in 150 patients with a variety of hepatobiliary disorders. GGT concentration was significantly higher in patients with "cholestatic" liver disease than in those with "hepatic" disorders, although there was considerable overlap. Measurement of GGT alone did not allow differentiation of intrahepatic cholestasis from extrahepatic cholestasis. However, GGT/serum bilirubin ratios were significantly higher in patients with intrahepatic cholestasis when compared with patients with extrahepatic biliary obstruction. Estimation of serum concentration of GGT appears to be a sensitive screening test both for alcohol consumption and for hepatobiliary disease. However, measurement of GGT concentration has only limited value in the differential diagnosis of hepatobiliary disease, although it may help in the differentiation of "hepatitic" and "cholestatic" liver disease.

Pseudo-metastases in the liver: a presentation of the Budd-Chiari syndrome.

Angiographic and scintigraphic findings closely mimicked vascular liver metastases in a young woman whose Budd-Chiari syndrome is probably the result of oral contraceptive use. Histological proof should be obtained before the diagnosis of hepatic neoplasm is accepted in patients with this syndrome.

Urinary and serum octopamine in patients with portal-systemic encephalopathy.

Urinary excretion and serum concentrations of octopamine were studied in seventeen controls, thirty-three patients with portal-systemic encephalopathy, and thirteen patients with liver disease without encephalopathy. No differences were detected between control subjects and patients without encephalopathy. Urinary excretion and serum concentrations of octopamine were significantly higher in patients with encephalopathy compared with those without encephalopathy. The presence and grade of portal-systemic encephalopathy seemed to correlate more closely with the serum-octopamine concentrations than with urinary octopamine excretion. It is postulated that octopamine may be involved in the pathogenesis of portal-systemic encephalopathy.

Impaired cardiovascular responsiveness in liver disease.

Cardiovascular responsiveness to reflex impaired in patients with cirrhosis compared with control subjects. Peripheral vascular responses to exogenous noradrenaline were also impaired in cirrhotic patients, but peripheral vascular responses to infused adrenaline and to angiotensin II were similar in both groups. Impaired cardiovascular reactivity in patients with chronic liver disease could predispose them to circulatory failure after haemorrhage or surgery and should be considered when prescribing drugs which affect autonomic activity.

Jaundice due to erythromycin estolate.

A 43-year-old male developed abdominal pain and jaundice after the administration of erythromycin estolate. The diagnosis was strongly suspected on clinical grounds, but ultimate confirmation depends upon the demonstration of biochemical and morphological alterations after challenge with the drug.

Use of bumetanide in the treatment of ascites due to liver disease.

Bumetanide is an effective diuretic for the treatment of ascites. Fifteen out of 17 patients with chronic liver disease responded satisfactorily and the incidence of hepatic encephalopathy and electrolyte disturbances was similar to that previously observed with frusemide. Colicky abdominal pain was reported in three patients but no other adverse effects were noted. An unexpected response was obtained in two patients who had diuresis without natriuresis.