Liver and inflammatory bowel disease.

Liver disease is exceptional in patients with inflammatory bowel disease. The most common manifestation, sclerosing cholangitis, characterized by inflammation and fibrosis of the intra- and\or extrahepatic bile ducts, is unusual in patients with inflammatory bowel disease. Conversely, inflammatory bowel disease (mainly chronic ulcerative colitis) is not infrequent in patients with sclerosing cholangitis. Gallstone disease, portal vein thrombosis, and hepatic abscesses are complications directly related to inflammatory bowel disease. Drugs prescribed for the treatment of inflammatory bowel disease can be the cause of rare but potentially serious hepatic manifestations which must be recognized and detected early. Recent studies have demonstrated the role of purine analogues in the development of nodular regenerative hyperplasia. Because of the poor prognosis, patients taking purine analogues should be monitored regularly to search for inaugural signs such as an elevation of serum alkaline phosphatase or low platelet counts (which may not necessarily reach thrombopenia). The risk of methotrexate-induced fibrosis is exceptional in inflammatory bowel disease. Patients should be monitored with non-invasive tests to recognize the development of fibrosis. Finally, because of the risk of viral reactivation, patients should be screened for hepatitis B virus surface antigen before introducing infliximab; chronic carriers should be given preventive treatment with nucleoside or nucleotide analogues.

[Imaging features of iatrogenic drug disorders]. / Imagerie de la pathologie iatrogène médicamenteuse.

Iatrogenic drug disorders should be considered when presented with a number of imaging findings mainly involving the nervous, musculoskeletal, gastrointestinal or genitourinary system. Care should be used when differentiating between imaging findings related to the underlying pathology and imaging findings related to drug-related complications: examples include the impact of steroid therapy on bones and the impact of triple-drug anti-HIV therapy and its impact of fatty tissue. Knowledge of the necessary imaging surveillance protocol is implied.

[Cholestatic icterus induced by the administration of fusidic acid in a cirrhotic patient]. / Ictère cholestatique induit par la prise d'acide fucidique chez un patient cirrhotique.

INTRODUCTION: Fucidic acid is an antibiotic essentially used to treat staphylococcal infections. Its chemical structure is very similar to that of bilary acids and hence implies competitive mechanisms between their elimination and metabolization. OBSERVATION: A patient with a past history of alcohol-induced cirrhosis was treated with fucidic acid for a Staphylococci aureus urinary infection. On day 2 of treatment a conjugate bilirubine icterus appeared. There was no argument to suggest a decompensation of the icterus. The icterus disappeared on suspension of fucidic acid. COMMENTS: The occurrence of an icterus in a cirrhotic patient may evoke decompensation of the hepatopathy and an extensive exploration must be made. A thorough survey of all drug administration must be made. Notably, the possibility of the occurrence of a connective bilirubin icterus during treatment with fucidic acid must be known. The icterus always regresses on withdrawal of treatment and this etiology must be evoked before conducting invasive examinations.

Postdischarge adverse drug reactions in primary care originating from hospital care in France: a nationwide prospective study.

OBJECTIVE: To describe and estimate the incidence and preventability of postdischarge adverse drug reactions (ADRs) detected in primary care in France. DESIGN: Prospective study of patients referred to hospital by participating general practitioners (GPs). These GPs reported all cases of an adverse reaction to a drug instituted in hospital among patients who consulted them within 30 days of discharge. SETTING: 305 general practices from all French regions. PATIENTS: 7540 patients referred by GPs to private or public hospitals. MAIN OUTCOME MEASURES: The incidence for postdischarge ADRs in primary care, and their preventability. RESULTS: 30 cases of postdischarge ADR were detected in 29 re-consulting patients, yielding a minimal incidence for France of 0.4 per 100 admissions (95% confidence interval 0.3 to 0.6). The ADRs were assessed as serious in 60% of cases. The main drug classes implicated were cardiovascular drugs (8 ADRs), oral anticoagulants (6), psychoactive drugs (4), antidiabetics (3), and opioid analgesics (3). Patients experiencing a postdischarge ADR were older than patients not experiencing one (median age: 77 vs 68 years; p = 0.004). Detected ADRs were considered preventable in 59% of cases. CONCLUSIONS: Physicians and patients should be aware of the possible occurrence of postdischarge ADRs. Patient information in hospital, close postdischarge follow-up of patients at risk, and appropriate transmission of information between hospital physicians and GPs can help to prevent them.

[Drug-induced hepatic diseases]. / Atteintes hépatiques médicamenteuses.

The contribution of drugs to hepatic disorders, long viewed as insignificant, is now widely recognized. Advances have been made over the last few years in our understanding of the mechanisms underlying drug-induced hepatic injury. Conversion of drugs to toxic or reactive metabolites has been demonstrated. Drugs can induce the full range of hepatic disorders, and the diagnostic approach is the same as for the other causes of liver disease. The evaluation of the hepatotoxicity of drugs requires use of available classification schemes for assigning causal relationships with drugs. Over 1000 drugs have been incriminated in the occurrence of hepatic lesions. Hepatox is a computerized database that has become vital to the storage of new information. Part of the contents of the Hepatox database is presented in this article.

Cyamamezine-induced acute hepatitis after unique massive intake: a case report.

Hepatotoxicity of cyamamezine, a phenothiazine structurally related to chlorpromazine, has been rarely documented. We report here a case of acute symptomatic hepatitis following a unique massive intake of cyamamezine in a suicide attempt and discuss the mechanisms of such injury.

Mesalazine (5-aminosalicylic acid) induced chronic hepatitis.

BACKGROUND: Treatment of ulcerative colitis or Crohn's disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported. CASE REPORT: A 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration. CONCLUSION: Contrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.

Atrium and paroxetine-related severe hepatitis.

Two cases of severe hepatitis in young women using Atrium and paroxetine are presented. Both patients presented jaundice, marked increase in aminotransferases activities, and pronounced prolongation in prothrombin time. In both cases, liver biopsy specimen examination revealed lesions compatible with drug-related injury. Other causes of hepatic injury were reasonably ruled out by complete careful screening. Outcome was marked by rapid complete recovery in one case and by slow recovery in the other. We suggest that simultaneous treatment with Atrium and paroxetine could increase each of these drugs' hepatotoxicity.

[Hepatotoxicity caused by therapeutic doses of paracetamol in alcoholics. Report of 2 cases of fatal hepatitis in cirrhosis]. / Toxicité hépatique du paracétamol à dose thérapeutique chez le sujet éthylique chronique. A propos de 2 cas d'hépatite mortelle chez des patients cirrhotiques.

Paracetamol is a widely used medication as it is an effective analgesic and antipyretic. Because of the absence of gastro-intestinal side effects, it has been used as the analgesic of choice for alcoholic patients. Hepatotoxicity is dose-related and generally occurs in patients who absorb more than 125 mg/kg/j. However, cases of severe liver damage have been reported after absorption of therapeutic doses of paracetamol in alcoholics. We report 2 cases with a fatal outcome and discuss the mechanisms of toxicity, the prognostic factors and treatment of such event.

Antibiotic-associated hepatitis: update from 1990.

OBJECTIVE: To review the literature on the recent available evidence of antibiotic-associated acute liver injury. DATA SOURCES: All published articles from January 1990 to July 1995 were extracted from the monthly updated HEPATOX database. Additional articles were found using MEDLINE, EMBASE, and PASCAL searches. Hepatic injuries associated with antituberculous, antimycotic, antiviral, antiprotozoal, and antiseptic compounds were excluded form this review. STUDY SELECTION: As the amount of literature was large, only case reports, series and epidemiologic data were used. Results from clinical trials were reviewed only when other information was available. DATA EXTRACTION: Original articles were reviewed to select relevant material. Information regarding the clinical description, histologic features, severity, outcome, and possible risk factors was extracted. Data on incidence were provided by epidemiologic studies or spontaneous reporting to regulatory agencies. DATA SYNTHESIS: Antibiotic-associated acute injury is rare, with an incidence not exceeding 1 case 10,000 users for most drugs. Among beta-lactams, amoxicillin/clavulanic acid and penicillinase-resistant penicillins are associated with predominant and sometimes protracted cholestasis. The hepatotoxic potential of all available erythromycin salts is confirmed, and recent evidence suggests that roxithromycin could be added to the list of antibiotic-induced liver injury. Among fluoroquinolones, only ciprofloxacin has been associated with serious hepatitis. Trimethoprim/sulfamethoxazole-induced hepatitis often reported, but trimethoprim alone also appears as a possible cause of acute liver injury. Finally, acute bile duct injuries and ductopenia have been described with several antibiotics. CONCLUSIONS: The most important recent information is the possibility of protracted liver cholestasis with bile duct injuries induced by several antibiotics, particularly penicillinase-resistant penicillins, and the identification of new potentially hepatotoxic antibiotics, namely, roxithromycin, ciprofloxacin, and trimethoprim.