Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of tuberculosis has grown seriously in the last ten years and so have the risks due to drug toxicity of Ethambutol, Isoniazid, Pyrazinamide, Rifampicin. One of the questions is whether a careful monitoring of liver function during anti-tubercular chemotherapy could be useful, given that once severe organ toxicity initiates the survival rate remains under 10% if organ transplant is not available. International literature shows a clear prevalence of this event in Asiatic populations which are now well represented in Italy owing to incoming migrations. A case of fulminant hepatitis in a young Chinese man under treatment for TBC arrived at our ICU with a drug-induced acute hepatitis is reported.
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PMID:[Fulminant liver failure caused by antitubercular drugs. Report of a clinical case]. 1083 75

To assess epidemiological and clinical significance of drug hepatotoxicity in the setting of liver diseases consultation, ten thousand and three hundred forty two prospectively designed clinical records from patient cared for in our Liver Unit in the period 1988-1998 were incorporated into the study; 58 out of 10,342 (prevalence = 5.6%) fulfilled at least the first three of the following causality requirements: 1.--Liver injury associated in time to drug exposition; 2.--Negative evaluation of more common other etiologies; (alcohol, viruses, immunologic, metabolic, etc) 3.--Favourable response to drug withdrawal (ALT < 50% of baseline in 8 to 30 days in acute hepatitis type, and alkaline phosphatase and/or total bilirubin < 50% of baseline up to 6 months, in acute cholestasis) 4.--Inadverted or rarely prescribed positive challenge. Acute hepatitis type of injury were considered when serum ALT rise 8 times or more above normal superior level with alkaline phosphatase (APh) below 3 times; "pure" cholestasis when APh rise 3 times or more above normal with ALT below 8 times; mixed acute injury or cholestatic hepatitis when both ALT and APh were elevated above 8 and 3 times respectively, and indeterminate type when both enzymes were below the referred levels. Chronic injury were considered when six or more month of evolution and compatible liver histology happens. Clinical severity were expressed as mild (absence of major clinical complications, serum bilirubin < 5 mg/dl and prothrombin concentration > 75%), moderate (presence of clinical complications, bilirubin > 5 mg/dl and prothrombin concentration between 50-75%), and severe (major clinical complications with bilirubin > 5 mg/dl and prothrombin concentration < 50%). Female/male ratio was 1.4:1, with age average 39 years (R = 15-77) and major concentration of cases above 40. More than 50% of cases received 2 or more drugs. Jaundice was present in 60.4%, and systemic manifestations of hypersensibility (fever, adenomegalies, rush, mononucleosis like syndrome, eosinophilia) in 29.3%. Acute injury represented 91.4% of the cases: 41.4% acute hepatitis, 15.5% "pure" cholestasis, 24.1% cholestatic hepatitis, and 10.3% indeterminate type. Four patients (4.5% of acute injury cases) were presented as severe acute liver failure, leading to liver transplant in one of them, drug association (INH-rifampicin and carbamazepine-phenobarbital) and inadverted challenge (sulphonamides and pemoline) were associated to clinical severity. Chronic injury were found in five patient (8.6%), four of them associated to chronic hepatitis and the other one to a ductopenic syndrome. Six drugs represented 53.4% of our cases; oral contraceptives (7 cases), INH alone or combined with rifampicin (6 cases), sulfonamides and clorpropamida (5 cases each), carbamazepine and amiodarone (4 cases each). Normalization of liver enzymes after drug suppression took 2 to 8 weeks in acute hepatitis type (X = 4 weeks), 4 to 20 in "pure" cholestasis (X = 12 weeks) and 8 to 24 weeks in cholestatic hepatitis or mixed type (X = 16 weeks). Two cases of chronic hepatitis normalize the histological activity index in 20 and 18 month respectively, one case remains as chronic hepatitis at 10 month and the other one progress to cirrhosis; the ductopenic syndrome normalize histology in 19 months receiving urso-deoxicolic acid, 10 mg/k/day.
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PMID:[Clinic-epidemiological significance of drug hepatotoxicity in liver disease consultation]. 1092 31

Isoniazid and pyrazinamide are both well-known hepatotoxic drugs. When isoniazid is used, the hepatic lesion appears before than when pyrazinamide is used. This paper intends to relate a case of a 5-month-old patient who had lungs' and meningeal tuberculosis and who developed toxic hepatitis accomplished by hepatic failure while he was being treated with isoniazid, pyrazinamide and rifampicin. The clinic manifestations and the laboratory alterations were detected in the fifth day of treatment and the recovery was fast; and almost complete by the end of the first week, in which the use of isoniazid had been suspended. Although it was necessary to take the patient to the intensive care unit, he had a good recovery, without sequels.
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PMID:[Isoniazid-induced hepatic failure. Report of a case]. 1096 32

Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuberculosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597 patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of 154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33; 5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8; 1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance.
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PMID:[Clinical study on the cases in which INH or RFP was discontinued during treatment for pulmonary tuberculosis]. 1144 98

Antituberculosis drug-induced hepatitis is one of the most prevalent drug-induced liver injuries. Isoniazid is the major drug incriminated in this hepatotoxicity. Isoniazid is mainly metabolized to hepatotoxic intermediates by N-acetyltransferase (NAT). However, the association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is debatable. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2 in 224 incident tuberculosis patients who received antituberculosis treatment. Antituberculosis drug-induced hepatitis was diagnosed based on a positive isoniazid rechallenge test and exclusion of viral hepatitis. Acetylator status was determined by genotyping NAT2 in patients using a polymerase chain reaction with restriction fragment length polymorphism. Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. Thirty-three patients (14.7%) were diagnosed with antituberculosis drug-induced hepatitis. Slow acetylators had a higher risk of hepatotoxicity than rapid acetylators (26.4% vs. 11.1%, P =.013). Among patients with hepatotoxicity, slow acetylators had significantly higher serum aminotransferase levels than rapid acetylators. Logistic regression showed that slow-acetylator status (odds ratio [OR], 3.66; 95% CI, 1.58-8.49; P =.003) and age (OR, 1.09; 95% CI, 1.04-1.14; P <.001) were the only 2 independent risk factors for antituberculosis drug-induced hepatitis. In conclusion, slow-acetylator status of NAT2 is a significant susceptibility risk factor for antituberculosis drug-induced hepatitis. Additionally, slow acetylators are prone to develop more severe hepatotoxicity than rapid acetylators. Regular monitoring of serum aminotransferase levels is mandatory in patients receiving antituberculosis treatment, especially in slow acetylators.
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PMID:Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. 1191 35

Forty-nine AIDS patients, most of who were antiretroviral therapy (ARV) naive, with active tuberculosis, were treated with Rifampin 600 mg, Isoniazid 400 mg and Pirazinamide 2 g daily. They also received ARV, consisting of Efavirenz (600 mg/day) plus 2 NRTIs. All patients were prospectively followed for at least 24 months. Baselines were: male/female ratio 2:1, mean age 34.7 +/- 9.4 yrs; weight 51 +/- 9.0 kg, viral load 5.6 +/- 0.6 logs, CD4 cell count 101 +/- 128 cells/ mm3. Follow up mean values of data logs of VL and CD4+ cell /mm3 counts were: VL 1.7 and CD4+ 265; VL 1.3 and CD4+ 251; VL 1.4 and CD4+ 326 at 6, 12 and 24 months, respectively. Weight gain changes were: 5 +/- 9.9 +/- 12 and 21 +/- 16 kg respectively at 6, 12 and 24 months. A non-concomitant ARV regimen was introduced at least three weeks after TB treatment initiation. Severe adverse reactions included rash (two), toxic hepatitis (six), Immune Reconstitution Syndrome (seven), and four deaths. We conclude that Efavirenz at a daily dose of 600 mg is sufficient and safe to treat HIV/TB patients using a Rifampin containing regimen.
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PMID:Efficacy and safety of Efavirenz in HIV patients on Rifampin for tuberculosis. 1547 53

The purpose of this study was to clarify the various clinical presentations, incidence, and complications associated with tuberculosis (TB), as well as patient survival in heart transplantation (HTx) recipients. A retrospective review of 177 case records of HTx recipients from May 1989 to April 2003 were evaluated for their clinical course, diagnostic procedures, treatment, and survival. TB was diagnosed by culture. TB was proven in five (2.8%) patients. There were three pulmonary lesions and two extrapulmonary lesions. TB was diagnosed at 3.5 to 85 months after HTx. Pulmonary lesions were detected by cultures of sputum, bronchoalveolar lavage, or pleural effusion. For extrapulmonay lesions, one subject had neck lymphadenopathy shown by biopsy and culture to be TB; another suffered from swelling of the finger joints which upon culture of the aspirate proved to be TB. Treatment consisted of isoniazid (INH), rifampin (RIF), ethambutol, pyrazinamide, streptomycin (STR), ciprofloxacin (Ciproxin), and levofloxacin (Cravit). During the use of RIF, the daily dosage of cyclosporine (CsA) or tacrolimus was increased to maintain appropriate levels. Because of severe hepatotoxicity and interference with CsA, RIF was withdrawn and STR given in the last three patients. In addition, ciprofloxacin was given in the patient with miliary TB. Levofloxacin was given to the other two patients. All patients survived the TB infection under treatment with at least three drugs. There were five clinical presentations of TB in our HTx recipients. Because of the high incidence of hepatitis and severe drug interaction with CsA or tacrolimus on RIF treatment, avoiding the use of RIF but treatment with at least three drugs is recommended.
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PMID:Various clinical presentations of tuberculosis in heart transplant recipients. 1556 Dec 61

Renal transplantation (RT) recipients are at a high risk of developing tuberculosis (TB) following transplantation. Effectiveness of isoniazid (INH) in preventing TB is well documented in immunocompetent as well as immunocompromised persons. There is paucity of data on role of INH prophylaxis in RT recipients. Thus, a prospective randomised trial of INH in RT recipients was carried out to determine the efficacy of daily INH monotherapy in the prevention of TB in these patients. Patients of end stage renal disease (ESRD) taken for RT formed the subjects of study. Patients with active TB and active hepatitis at the time of RT were excluded from the study. Patients were randomised to receive INH 300 mg with pyridoxine 20 mg daily from the day of RT. The duration of the treatment was planned for 1 year or till the development of TB, which ever was earlier. Between October 1998 and September 2000, 114 RT were done at our hospital. Of these, 24 (21%) patients had active TB at the time of RT and thus were excluded. Patients included were randomised with 1:2 ratio of treatment and control group. Of the 90 patients thus enrolled, 30 were randomised in treatment group and 60 in control group. Of the included patients five patients had very early graft loss (three in treatment and two in control group) within days and thus excluded from the analysis. Three of the 27 (11.1%) patients in treatment group and 15 (25.8%) in control group developed TB (P = 0.10). The risk ratio of (RR) of INH versus control group of TB was 0.36 (95% CI, 0.10-1.32) but the difference was not statistically significant (P = 0.12). Only one patient developed INH induced hepatitis. In conclusion, with INH prophylaxis, there was a trend towards protection from TB, though it was not statistically significant. Further, all patients tolerated INH and hepatotoxicity was not a major problem in this group of patients.
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PMID:Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient. 1578 19

Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity. The immunogenetics of antituberculosis drug-induced hepatotoxicity, especially inclusive of acetylaor phenotype polymorphism, have been increasingly unravelled. Other principal clinical risk factors for hepatotoxicity are old age, malnutrition, alcoholism, HIV infection, as well as chronic hepatitis B and C infections. Drug-induced hepatic dysfunction usually occurs within the initial few weeks of the intensive phase of antituberculosis chemotherapy. Vigilant clinical (including patient education on symptoms of hepatitis) and biochemical monitoring are mandatory to improve the outcomes of patients with drug-induced hepatotoxicity during antituberculosis chemotherapy. Some fluoroquinolones like ofloxacin/levofloxacin may have a role in constituting non-hepatotoxic drug regimens for management of tuberculosis (TB) in the presence of hepatic dysfunction. Isoniazid administration is currently the standard therapy for latent TB infection. Rifamycins like rifampicin or rifapentine, alone or in combination with isoniazid, may also be considered as alternatives, pending accumulation of further clinical data. During treatment of latent TB infection, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring for hepatic dysfunction. Monitoring of liver chemistry is also required for those patients at risk of drug-induced hepatotoxicity.
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PMID:Antituberculosis drugs and hepatotoxicity. 1705 97

There is very high incidence of tuberculosis (TB) in dialysis and renal transplant (RT) recipients in developing countries. Clinical manifestation of TB may be atypical or obscure in initial stages. Common clinical abnormalities include pyrexia, pulmonary infiltrates, exudative pleural effusion, and exudative ascites. Aggressive investigations must be done in patients with pyrexia, pulmonary abnormalities, scanty sputum, and weight loss. BAL and computed tomography (CT) scan of the chest should be done in such cases. Tuberculin skin test is not helpful in the majority of patients. New blood tests to quantitate PPD reactivity in vivo and tests to distinguish between latent M tuberculosis infection from BCG-induced reactivity have been devised recently. Side effects of anti-TB drugs, especially hepatitis, need close observation because of the frequent occurrence of viral hepatitis in such cases. Tests to confirm latent TB are desirable before starting chemoprophylaxis in RT recipients. INH prophylaxis cannot be recommended universally in all RT recipients.
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PMID:Challenge of tuberculosis in renal transplantation. 1744 91


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