rifampin and Hepatitis-C

Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear.. To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity.. Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV.. Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors.. The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.

Topics: Adult; Antitubercular Agents; Aspartate Aminotransferases; Brazil; Canada; Case-Control Studies; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Therapy, Combination; Female; Hepatitis C; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Multivariate Analysis; Rifampin; Risk Factors; Spain; United States

Topics: Antitubercular Agents; Hepatitis C; Humans; Rifampin; Tuberculosis, Multidrug-Resistant

Simeprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, displays nonlinear pharmacokinetics (PK) at therapeutic doses. Using physiologically based PK modeling, various drug-drug interactions were simulated with simeprevir as victim drug to identify whether saturation of the predominant metabolic enzyme (CYP3A4) or the active hepatic transporters (organic anion-transporting polypeptide (OATP)1B1/3) could account for the nonlinear PK. Interactions with ritonavir, a strong CYP3A4 inhibitor that does not affect OATP (at 100 mg dose), erythromycin, a moderate CYP3A4 inhibitor, and efavirenz, a moderate CYP3A inducer that does not affect OATP, demonstrated the involvement of CYP3A4. Interaction studies with low-dose cyclosporine confirmed the role of OATP. The interplay between hepatic uptake and CYP3A4 metabolism was verified by simulations with rifampicin, a potent CYP3A4 inducer and OATP1B1/3 inhibitor, and maintenance doses of cyclosporine. Saturation of gut and liver metabolism by CYP3A4, and saturation of hepatic uptake by OATP1B1/3, seem to account for the observed nonlinear PK of simeprevir.

Topics: Alkynes; Antiviral Agents; Benzoxazines; Cyclopropanes; Cyclosporine; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Erythromycin; Hepatitis C; Humans; Liver; Liver-Specific Organic Anion Transporter 1; Nonlinear Dynamics; Organic Anion Transporters; Rifampin; Ritonavir; Simeprevir; Viral Nonstructural Proteins

Socially anxious cannabis users are influenced by cannabis expectancies and normative perceptions. The present study examines the influence of psychosocial factors on cannabis use vulnerability factors as the result of interactions between norms perceptions, social anxiety, and expectancies.. Participants were 149 (36.2% female) current cannabis users aged 18-36 (. Among cannabis users with perceptions of greater injunctive norms, social anxiety was associated with greater cannabis craving when tension reduction expectancies were greater. However, social anxiety was unrelated to cannabis craving when expectances were low. This suggests that cannabis craving among socially anxious adults was greatest when cannabis use was viewed as acceptable and expected to reduce tension, and highlights the importance of considering norms, expectancies, and social anxiety in understanding cannabis-related behaviors.. The A876P-substitution bridges in vitro and in vivo studies using J6/JFH1-based recombinants. We provide the first in vivo evidence that HVR1 protects cross-genotype conserved HCV neutralisation epitopes, which advocates the possibility of using HVR1-deleted viruses as vaccine antigens to boost broadly reactive protective nAb responses.. We conclude that the photo-processing of eVSGs leads to the production of PAHs with attached aliphatic sidegroups that are revealed by the 3.4. De 4,331 publicaciones encontradas, 16 estudios cumplieron con los criterios de inclusión. El 50 % (8/16) de los estudios revisados fueron realizados en países de Sur América, Centro América y del Caribe. El diseño de casos y controles fue el más frecuente. El anterior sistema de clasificación de casos (OMS-1997) fue utilizado en todos los estudios incluidos en esta revisión.. El estrés oxidativo-nitrosativo se encuentra presente en el curso de la infección por virus dengue, demostrado por los cambios en las concentraciones plasmáticas de óxido nítrico, antioxidantes y marcadores de lipoperoxidación y de oxidación de proteínas. Por último, parece existir una asociación entre la elevación de los niveles plasmáticos de los carbonilos proteicos y malondialdehído con la severidad del dengue.

Topics: Acid-Base Imbalance; Acidosis, Renal Tubular; Aged; Air Pollution, Indoor; Amino Acid Substitution; Animals; Animals, Newborn; Anti-Bacterial Agents; Antibodies, Neutralizing; Apoptosis; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Bone Marrow Transplantation; Carbonic Anhydrase Inhibitors; Castleman Disease; Cat Diseases; Cats; Cell Proliferation; Cell- and Tissue-Based Therapy; Chemical and Drug Induced Liver Injury; Chemotaxis, Leukocyte; Clinical Trials as Topic; Coated Materials, Biocompatible; Diagnosis, Differential; Disease Models, Animal; Environmental Monitoring; Female; Gas Chromatography-Mass Spectrometry; Genotype; Granuloma, Foreign-Body; Heart Failure; Hepacivirus; Hepatitis C; Horse Diseases; Horses; Housing; Humans; Hypercalcemia; Hypokalemia; Immunophenotyping; In Vitro Techniques; Liver; Liver Function Tests; Lymphocytes; Macrophages; Male; Medicine, Chinese Traditional; Metabolomics; Mice; Mice, Inbred C57BL; Middle Aged; Models, Animal; Mutation; Myocardial Ischemia; Neovascularization, Physiologic; Neutrophil Infiltration; Ocular Hypertension; Ophthalmic Solutions; Parathyroid Hormone; Particulate Matter; Polyethylene Terephthalates; Prednisolone; Prospective Studies; Prosthesis Design; Prosthesis-Related Infections; Rats; Rats, Wistar; Reactive Oxygen Species; Rifampin; Saponins; Sepsis; Skin; Stem Cells; Stroke Volume; Sulfonamides; Texas; Thiophenes; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Viral Hepatitis Vaccines; Viral Nonstructural Proteins; Viral Proteins; Vitamin D; Wound Healing

Topics: Antimalarials; Antitubercular Agents; Chloroquine; Diagnosis, Differential; Drug Therapy, Combination; Feces; Hepatitis C; Humans; Iron Overload; Male; Middle Aged; Phlebotomy; Photosensitivity Disorders; Porphyria Cutanea Tarda; Porphyrins; Rifampin; Risk Factors; Skin Diseases, Vesiculobullous; Tuberculosis, Pulmonary

SCY-635 is a novel nonimmunosuppressive cyclosporine-based analog that exhibits potent suppression of hepatitis C virus (HCV) replication in vitro. SCY-635 inhibited the peptidyl prolyl isomerase activity of cyclophilin A at nanomolar concentrations but showed no detectable inhibition of calcineurin phosphatase activity at concentrations up to 2 microM. Metabolic studies indicated that SCY-635 did not induce the major cytochrome P450 enzymes 1A2, 2B6, and 3A4. SCY-635 was a weak inhibitor and a poor substrate for P-glycoprotein. Functional assays with stimulated Jurkat cells and stimulated human peripheral blood mononuclear cells indicated that SCY-635 is a weaker inhibitor of interleukin-2 secretion than cyclosporine. A series of two-drug combination studies was performed in vitro. SCY-635 exhibited synergistic antiviral activity with alpha interferon 2b and additive antiviral activity with ribavirin. SCY-635 was shown to be orally bioavailable in multiple animal species and produced blood and liver concentrations of parent drug that exceeded the 50% effective dose determined in the bicistronic con1b-derived replicon assay. These results suggest that SCY-635 warrants further investigation as a novel therapeutic agent for the treatment of individuals who are chronically infected with HCV.

Topics: Animals; Antiviral Agents; Cell Line; Cells, Cultured; Cyclophilin A; Cyclosporins; Dogs; Dose-Response Relationship, Drug; Enzyme Activation; Haplorhini; Hepacivirus; Hepatitis C; Hepatocytes; Humans; Immunosuppressive Agents; Interleukin-2; Jurkat Cells; Leukocytes, Mononuclear; Mice; Molecular Structure; Rats; RNA, Viral; Virus Replication

Angiogenesis is an important therapeutic target in cancer, and to fully exploit its therapeutic potential, combination chemotherapeutic/antiangiogenic regimens should be optimized and delivered earlier to more patients. Ideally, this could be done by a single potent oral agent with established safety. Rifampicin, a semisynthetic antibiotic derived from the rifamycins, is one of the most commonly used pharmaceutical compounds worldwide in the treatment of tuberculosis. Here, we present the effects of oral rifampicin on human cancer progression and its antiangiogenic properties, which were comparable to the angiogenesis inhibitor endostatin. Clinically, low-dose p.o. administration of rifampicin to six high-risk patients with hepatitis C virus-related liver cirrhosis resulted in a single occurrence of hepatocellular carcinoma during the follow-up period of 97.3 +/- 29.1 (mean +/- SD) months. Experimentally, rifampicin rapidly and markedly down-regulated the expression of a wide spectrum of angiogenesis-associated genes in growing human microvascular endothelial cells, thereby suppressing endothelial cell proliferation and migration. Rifampicin, at higher concentrations, also directly inhibited the growth of a variety of human cancer cells. P.o. administration of rifampicin significantly inhibited in vivo growth and metastases of subcutaneous human cancer xenografts. Thus, the potent antiangiogenic properties of oral rifampicin therapy were effective in suppressing cancer progression. It provides a promising new addition to antiangiogenic strategies for designing human cancer therapies. Considering the clinical pharmacokinetics of rifampicin, which enters the enterohepatic circulation and undergoes subsequent hepatic accumulation, it may be especially beneficial as an antitumor agent targeting hepatobiliary tumors.

Topics: Administration, Oral; Aged; Angiogenesis Inhibitors; Animals; Carcinoma, Hepatocellular; Cells, Cultured; Drug Delivery Systems; Female; Follow-Up Studies; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Nude; Middle Aged; Rats; Rats, Wistar; Rifampin

Topics: Adult; Antitubercular Agents; Cholestasis, Intrahepatic; Diagnostic Errors; Hepatitis B; Hepatitis C; HIV Infections; Humans; Isoniazid; Male; Medicine in the Arts; Mercury Poisoning; Pyrazinamide; Rifampin; Television; Tuberculosis

An alternative regimen for the treatment of latent tuberculosis infection is 2 months of rifampin and pyrazinamide, but some patients have died of hepatitis associated with this therapy. One hundred fourteen patients received rifampin/pyrazinamide in Wake County, North Carolina, between December 1999 and May 2002; 60.5% of these patients were homeless, and at least 17% drank alcohol to excess. Seventy-seven patients (67.5%) completed a full 2-month course. Nine patients had a history of viral hepatitis or chronic liver disease. Four of 114 (3.5%; 95% confidence interval, 1.0-8.7%) patients developed hepatitis on therapy, and another two had symptoms consistent with hepatitis but did not report for laboratory testing (total confirmed plus suspected hepatitis rate 5.3%; 95% confidence interval, 2.0-11.1%). No patient who developed hepatitis had a history of viral hepatitis or liver disease, and none had been previously treated with isoniazid. No patients died or were hospitalized due to drug side effects. Rifampin/pyrazinamide was associated with a significantly higher rate of hepatitis than previously described with isoniazid therapy for latent tuberculosis but resulted in a high completion rate. The rifampin/pyrazinamide regimen for latent tuberculosis infection may be useful for high-risk, traditionally nonadherent patient groups, but careful monitoring for toxicity is required.

Topics: Adolescent; Adult; Aged; Alcoholism; Antibiotics, Antitubercular; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cohort Studies; Comorbidity; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Hepatitis B; Hepatitis C; Humans; Ill-Housed Persons; Infant; Liver Diseases; Male; Middle Aged; North Carolina; Pyrazinamide; Rifampin; Safety; Treatment Outcome; Tuberculosis

Department of Chest Diseases, Gazi University Faculty of Medicine and Atatürk Chest Diseases Hospital, Ankara, Turkey.. The primary purpose of this study was to assess the contributory role of viral hepatitis in antituberculosis drug hepatotoxicity.. Serologic markers for viral hepatitis were studied in 57 patients who developed acute hepatitis during antituberculosis therapy with rifampicin and isoniazid.. Among 705 adult tuberculous patients, 57 (8.1%) developed acute hepatitis during therapy with rifampicin and isoniazid. Serologic markers confirmed the presence of hepatitis B in 6 (10.5%) and hepatitis C in 4 (7%) of the 57 patients. Acute hepatitis A was not diagnosed in any of the patients.. Hepatitis occurring during antituberculosis therapy may not be drug-induced in all patients. Apart from the other factors mentioned above the endemicity of viral hepatitis in developing countries could be responsible for the higher incidence of antituberculosis-drug hepatitis.

Topics: Acute Disease; Adolescent; Adult; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Drug Therapy, Combination; Female; Hepatitis B; Hepatitis C; Hepatitis, Viral, Human; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Rifampin

Serologic markers for hepatitis viruses were studied in 40 children who developed acute hepatitis during antituberculosis therapy with rifampin and isoniazid, with the aim of assessing the contributory role of these viruses toward producing hepatic injury. Hepatitis A and B were confirmed in 7.5 and 35% patients, respectively, by IgM antibodies. Epidemiologic evidence suggested the possibility of non-A, non-B hepatitis in at least a few of the remaining 23 children. Hepatitis B was seen more often in children with severe tubercular disease (72%) and was largely (92.8%) parenterally transmitted. The study highlights that the endemicity of viral hepatitis in developing countries, among other factors, could also be responsible for the reported higher incidence of hepatotoxicity from developing countries and also for the increased risk of hepatotoxicity seen in severe tubercular disease.

Topics: Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Hepatitis A; Hepatitis B; Hepatitis C; Humans; Infant; Isoniazid; Liver; Male; Rifampin; Tuberculosis