rifampin and Liver-Cirrhosis

To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011.. There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011.. It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.. Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.. This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.. Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.. Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant. In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO. Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.. Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.. Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Topics: Acetogenins; Acute Disease; Acute Kidney Injury; Administration, Intravenous; Aged; Albumins; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; alpha-Glucosidases; Anemia; Animals; Anthozoa; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Antigens, Bacterial; Antihypertensive Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascites; Asthma; Bacteria; beta-Lactamases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding Sites; Biological Availability; Biomass; Borderline Personality Disorder; Brain; Brucella abortus; Brucella melitensis; Brucellosis; Calcium; Carbapenems; Case-Control Studies; Caseins; Cattle; CD8-Positive T-Lymphocytes; Ceftaroline; Cell Line; Cell Line, Tumor; Cell Physiological Phenomena; Cell Proliferation; Cephalosporins; Chemotherapy, Adjuvant; China; Chitin; Chlorella; Chlorophyll; Chlorophyll A; Chlorophyta; Cholangiocarcinoma; Cisplatin; Conotoxins; Contrast Media; Conus Snail; Cross-Sectional Studies; Cytokines; Decapodiformes; Deoxycytidine; Diagnostic and Statistical Manual of Mental Disorders; Dietary Fiber; Diterpenes; DNA Methylation; Dogs; Double-Blind Method; Drug Design; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Epidermis; Escherichia coli; Escherichia coli Infections; Extraintestinal Pathogenic Escherichia coli; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Volatile; Feasibility Studies; Feces; Female; Ferritins; Fluorodeoxyglucose F18; Gastrectomy; Gastrointestinal Microbiome; Gemcitabine; Glomerular Filtration Rate; Glucose; Glycerol; Granulocyte-Macrophage Colony-Stimulating Factor; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Immunoassay; Immunoglobulin G; India; Infant, Newborn; Infertility; Inflammation; Intensive Care Units; Iron; Iron Deficiencies; Kidney; Lacticaseibacillus rhamnosus; Laurencia; Leukocytes; Lipids; Liver Cirrhosis; Long Interspersed Nucleotide Elements; Longitudinal Studies; Male; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Mice; Microalgae; Microbial Sensitivity Tests; Microscopy; Middle Aged; Minerals; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Nephropidae; Nicotinic Antagonists; Nitrogen; Obesity; Oxaliplatin; Paclitaxel; Panax; Pancreatic Neoplasms; Pancreatitis; Personality; Personality Disorders; Personality Inventory; Photobioreactors; Plant Extracts; Plasmalogens; Plasmids; Polymorphism, Genetic; Polynesia; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prebiotics; Predictive Value of Tests; Prognosis; Prolyl-Hydroxylase Inhibitors; Rabbits; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Nicotinic; Recombinant Proteins; Retrospective Studies; Rifampin; Risk Factors; RNA, Ribosomal, 16S; Salinity; Seaweed; Sensitivity and Specificity; Sepsis; Sesquiterpenes; Severity of Illness Index; Shock, Septic; Silicones; Single Photon Emission Computed Tomography Computed Tomography; Skin; Snails; Solubility; Solvents; Sputum; Staphylococcal Infections; Stomach Neoplasms; Stramenopiles; Structure-Activity Relationship; Technetium Tc 99m Exametazime; Technology; Terpenes; Tuberculosis; Tuberculosis, Multidrug-Resistant; Urinary Catheters; Urinary Tract Infections; Vascular Endothelial Growth Factor A; Virulence Factors; Water; Wound Healing

Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.

Topics: Antitubercular Agents; Ethambutol; Humans; Immune System Diseases; Isoniazid; Latent Tuberculosis; Liver; Liver Cirrhosis; Liver Diseases; Liver Failure; Liver Function Tests; Liver Transplantation; Prevalence; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Multidrug-Resistant

To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011.. There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011.. It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.. Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.. This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.. Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.. Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant. In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO. Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.. Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.. Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Topics: Acetogenins; Acute Disease; Acute Kidney Injury; Administration, Intravenous; Aged; Albumins; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; alpha-Glucosidases; Anemia; Animals; Anthozoa; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Antigens, Bacterial; Antihypertensive Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascites; Asthma; Bacteria; beta-Lactamases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding Sites; Biological Availability; Biomass; Borderline Personality Disorder; Brain; Brucella abortus; Brucella melitensis; Brucellosis; Calcium; Carbapenems; Case-Control Studies; Caseins; Cattle; CD8-Positive T-Lymphocytes; Ceftaroline; Cell Line; Cell Line, Tumor; Cell Physiological Phenomena; Cell Proliferation; Cephalosporins; Chemotherapy, Adjuvant; China; Chitin; Chlorella; Chlorophyll; Chlorophyll A; Chlorophyta; Cholangiocarcinoma; Cisplatin; Conotoxins; Contrast Media; Conus Snail; Cross-Sectional Studies; Cytokines; Decapodiformes; Deoxycytidine; Diagnostic and Statistical Manual of Mental Disorders; Dietary Fiber; Diterpenes; DNA Methylation; Dogs; Double-Blind Method; Drug Design; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Epidermis; Escherichia coli; Escherichia coli Infections; Extraintestinal Pathogenic Escherichia coli; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Volatile; Feasibility Studies; Feces; Female; Ferritins; Fluorodeoxyglucose F18; Gastrectomy; Gastrointestinal Microbiome; Gemcitabine; Glomerular Filtration Rate; Glucose; Glycerol; Granulocyte-Macrophage Colony-Stimulating Factor; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Immunoassay; Immunoglobulin G; India; Infant, Newborn; Infertility; Inflammation; Intensive Care Units; Iron; Iron Deficiencies; Kidney; Lacticaseibacillus rhamnosus; Laurencia; Leukocytes; Lipids; Liver Cirrhosis; Long Interspersed Nucleotide Elements; Longitudinal Studies; Male; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Mice; Microalgae; Microbial Sensitivity Tests; Microscopy; Middle Aged; Minerals; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Nephropidae; Nicotinic Antagonists; Nitrogen; Obesity; Oxaliplatin; Paclitaxel; Panax; Pancreatic Neoplasms; Pancreatitis; Personality; Personality Disorders; Personality Inventory; Photobioreactors; Plant Extracts; Plasmalogens; Plasmids; Polymorphism, Genetic; Polynesia; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prebiotics; Predictive Value of Tests; Prognosis; Prolyl-Hydroxylase Inhibitors; Rabbits; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Nicotinic; Recombinant Proteins; Retrospective Studies; Rifampin; Risk Factors; RNA, Ribosomal, 16S; Salinity; Seaweed; Sensitivity and Specificity; Sepsis; Sesquiterpenes; Severity of Illness Index; Shock, Septic; Silicones; Single Photon Emission Computed Tomography Computed Tomography; Skin; Snails; Solubility; Solvents; Sputum; Staphylococcal Infections; Stomach Neoplasms; Stramenopiles; Structure-Activity Relationship; Technetium Tc 99m Exametazime; Technology; Terpenes; Tuberculosis; Tuberculosis, Multidrug-Resistant; Urinary Catheters; Urinary Tract Infections; Vascular Endothelial Growth Factor A; Virulence Factors; Water; Wound Healing

The possible existence of kinetic interactions between rifampicin and isoniazid and the effect of the concomitant presence of an impaired liver function were investigated in man. In a first study normal healthy subjects and patients with chronic liver disease received, on three different occasions, a single dose of 600 mg rifampicin or isoniazid and of rifampicin and isoniazid associated in randomized sequences. The results have shown that in both groups the serum levels, half-life values, and urinary excretion of each drug given alone are not significantly different from those observed when the other drug is associated. Serum levels and half-life of rifampicin and isoniazid were significantly higher in patients with chronically impaired liver. In a second study, rifampicin and isoniazid were given in combination at the same doses as in the first study over a period of one week. The results have shown a trend to decrease in the serum levels of rifampicin of the healthy subjects and a trend to increase in the patients with chronic liver disease on day 7 of treatment. In both groups a reduction in the half-life of rifampicin was also observed. No changes in serum isoniazid concentrations were observed between day 1 and day 7 in the healthy subjects, whereas a significant increase was observed in the patients. No significant changes in the half-life of isoniazid were observed.

Topics: Adult; Bilirubin; Chronic Disease; Half-Life; Humans; Isoniazid; Kinetics; Liver Cirrhosis; Male; Rifampin; Statistics as Topic; Time Factors

Periprosthetic joint infections (PJI) are a major complication in joint-arthroplasty. Rifampicin is often used as an additional agent to treat PJI, because it penetrates bacterial biofilms. However, rifaximin, belonging to the same antibiotic class as rifampicin, is frequently used to prevent episodes of hepatic encephalopathy in patients with cirrhosis and may induce resistance to rifampicin. The aim of this study was to examine the microbial pattern of periprosthetic joint infections in cirrhotic patients and to test the hypothesis that intake of rifaximin increases the rate of resistance to rifampicin in periprosthetic joint infections.. A cohort of cirrhotic patients and PJI (n = 25) was analysed on the characteristics of bacterial isolates from sonication and tissue analysis. In a second step a subgroup analysis on the development of rifampicin resistant bacterial specimens, depending on the intake of rifaximin (8 rifaximin intake patients vs. 13 non rifaximin intake patients) was performed.. Intestinal bacteria were found in 50% of the specimens, which was significantly more frequent than in a control cohort. By comparison of the single bacterial isolates, rifampicin resistance was detected in 69.2% (9/13) of the rifaximin-intake samples. In contrast, the non-rifaximin-intake isolates only were resistant to rifampicin in 22.2% (4/18) of the cases (p = 0.01). The odds ratio for developing a rifampicin-resistance through rifaximin intake was calculated as OR = 13.5.. Periprosthetic joint infections have a high incidence of being caused by enteric bacteria in cirrhotic patients. Due to this change in microbial pattern and the innate resistance to rifampicin of most of gram-negative bacteria, the therapy with rifampicin should be carefully considered. The association between the use of rifaximin and developed resistance to rifampicin has a major impact on the treatment of PJI.

Topics: Arthritis, Infectious; Bacteria; Enterobacteriaceae; Gastrointestinal Microbiome; Humans; Liver Cirrhosis; Prosthesis-Related Infections; Rifampin; Rifaximin

Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients.. A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1-7 weeks after treatment), and period 2 (8-16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing.. A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2.. About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined.

Topics: Aged; Drug Resistance, Microbial; Female; Humans; Liver Cirrhosis; Male; Microbial Sensitivity Tests; Middle Aged; Rifampin; Rifamycins; Rifaximin; Staphylococcus

The objective of this study was to evaluate the association between the use of anti-tuberculosis (anti-TB) agents, isoniazid (INH), rifampicin (RIF), and their combination (INH + RIF), and the risk of hepatocellular carcinoma (HCC) in cirrhotic patients. This population-based case-control study was conducted using a research database of Taiwan's National Health Insurance program. Cirrhotic patients first diagnosed with HCC between 1996 and 2011 (n = 50,351), among whom 4,738 were anti-TB medication users, were evaluated. Cirrhotic patients who did not develop HCC within the same period, frequency-matched according to age, sex, and index year, were evaluated as the control group (n = 47,488). The adjusted odds ratio (OR) of HCC was 1.34 [95 % confidence interval (CI), 1.20-1.50] in INH + RIF users compared with non-INH + RIF users. Long-term (>12 months) use of INH, RIF, and INH + RIF was significantly associated with increased risk of HCC, with an adjusted OR of 3.51 (95 % CI, 2.11-5.84), 4.17 (95 % CI, 2.76-4.31), and 7.17 (95 % CI, 4.08-12.6), respectively, after adjusting for age, sex, and comorbidities. An average dose of INH + RIF >16,050 mg/year was associated with increased risk of HCC in cirrhotic patients, with an adjusted OR of 1.48 (95 % CI, 1.27-1.73). Our results indicate that cirrhotic patients with long-term or high-dose INH and RIF treatment, particularly their combination, are associated with increased risk of HCC development.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Carcinoma, Hepatocellular; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Isoniazid; Liver Cirrhosis; Male; Middle Aged; Rifampin; Risk; Risk Assessment; Taiwan; Tuberculosis; Young Adult

Very recently, we reported that an antituberculous agent, rifampicin, exerts potent inhibitory effects on hepatic tumors when administered orally at low doses. The in vitro effects of rifampicin to rapidly downregulate angiogenesis and mitogenesis-related genes in cultured endothelial cells are reminiscent of endostatin, one of the most well-studied angiogenesis inhibitors. However, rifampicin at the expected hepatobiliary concentrations after low oral doses showed more complete antiproliferative effects on endothelial cells, which make rifampicin favorable as an adjunct anticancer regimen. Since rifampicin undergoes hepatic accumulation resulting from the enterohepatic circulation, it may be especially beneficial for targeting hepatobiliary tumors. In the present paper, we extend our observations on the antiangiogenic properties of rifampicin and further elaborate on its direct antitumor effects on a variety of human cancer-derived cells.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Cell Line, Tumor; Humans; Liver Cirrhosis; Liver Neoplasms; Neovascularization, Pathologic; Rifampin

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

This study investigated the hepatoprotective effect of two Indian medicinal plants Tinospora cordifolia (Tc), Phyllanthus emblica (Pe), and their combination, in a rat model of isoniazid, rifampicin and pyrazinamide induced hepatic damage. Hepatic damage was assessed using a composite score assigned to histopathological findings of degeneration, necrosis and fibrosis. The antituberculosis treatment (ATT), when given for 90 days, induced significant degeneration and necrosis (score: 7.5; p < 0.01 vs vehicle) associated with morphological changes. However, no change was found in the serum bilirubin and liver enzymes. Co-administration of silymarin (positive control, 50 mg/kg) with ATT protected against necrosis (score: 1.5; p < 0.001 vs ATT). Tc (100 mg/kg) showed a reduction in liver damage (score: 6.5), which was not statistically significant. On the other hand, Pe (300 mg/kg) prevented the necrotic changes to a significant extent (grade 1.0; p < 0.05; score [corrected] 5.5). Combination of Tc and Pe in their therapeutic doses (1:3) significantly prevented the necrosis (score: 3.5; p < 0.001 vs ATT). Similar effects were seen even when the doses were halved and were comparable to the silymarin group. Thus, this study proves the synergistic protective effects exerted by the combination of Tc and Pe when co-administered with ATT.

Topics: Animals; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Isoniazid; Liver Cirrhosis; Liver Diseases; Male; Necrosis; Phyllanthus emblica; Phytotherapy; Plant Extracts; Pyrazinamide; Rats; Rats, Wistar; Rifampin; Tinospora

Patients with liver cirrhosis are likely to be susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of this study was to elucidate the clinical characteristics and treatment responses in TB patients with cirrhosis.. Cases were patients with TB detected during their follow up for liver cirrhosis over a 4-year period. Controls were randomly selected patients with TB but no liver disease, matched to cases by age and gender in a 3:1 ratio.. Thirty-six cases and 108 controls were enrolled. Extrapulmonary TB was more common in cases than controls (31% vs 12%, P = 0.02). Clinical and radiographic manifestations and response to treatment did not differ between the two groups. The frequency of hepatotoxicity was higher in the cases than in the controls who were treated with a regimen containing rifampicin and isoniazid, although the difference was not statistically significant (27% vs 10%, P = 0.079).. TB patients with liver cirrhosis show extrapulmonary involvement more frequently. Patients with pulmonary TB and cirrhosis usually respond well to anti-TB treatment although appear to present more frequently with treatment-related hepatotoxicity.

Topics: Adult; Aged; Antibiotics, Antitubercular; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Isoniazid; Liver; Liver Cirrhosis; Male; Middle Aged; Prognosis; Rifampin; Tuberculosis, Pulmonary

Treatment of latent tuberculosis infection with isoniazid (INH) or rifampin (RIF) is controversial in liver transplant candidates due to potential hepatotoxicity. In this study, treatment of latent tuberculosis during transplant candidacy period is explored, and relevant literature is reviewed.. Liver transplant candidates with latent tuberculosis infection by positive tuberculin skin test (>5 mm) were prospectively enrolled and treated with 9 months of INH or 4 months of RIF, and were monitored monthly for their liver enzyme profiles, adverse effects, compliance, and completion rate.. Four of nine patients with INH had asymptomatic, mild elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) versus none of five patients in the RIF group. Two cases of elevations were attributed to INH. Two other cases were attributed to alcoholism or active chronic hepatitis B virus infection. Only one patient in the INH group experienced symptoms possibly attributed to INH hepatotoxicity. Compliance was 100% per patient reporting. Completion rates were 79% for INH and 100% for RIF. No fulminant hepatic failure or death was observed.. Treatment of latent tuberculosis in liver transplant patients during their candidacy with INH or RIF appears to be a safe, viable option, if carefully monitored for adverse effects and liver enzymes.

Topics: Adolescent; Adult; Alanine Transaminase; Antitubercular Agents; Aspartate Aminotransferases; Comorbidity; Female; Humans; Isoniazid; Liver Cirrhosis; Liver Transplantation; Male; Postoperative Complications; Preoperative Care; Rifampin; Safety; Treatment Outcome; Tuberculin Test; Tuberculosis

Topics: Adrenal Cortex Hormones; Antibiotics, Antitubercular; Drainage; Empyema, Tuberculous; Humans; Liver Cirrhosis; Pleural Effusion; Rifampin; Tuberculosis, Pleural

Urinary bile acids from 20 patients treated with chenodeoxycholate, 18 treated with ursodeoxycholate, 15 treated with rifampicin and 8 patients with advanced cirrhosis were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Occurrence rates and amounts of three so-called unusual trihydroxy bile acids, hyocholate, ursocholate and omega-muricholate, were increased in patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and decreased in cirrhotic patients as compared with those in untreated healthy adults. These data suggest that chenodeoxycholate and ursodeoxycholate are hydroxylated to produce unusual trihydroxy bile acids in bile acid-loaded humans and that this metabolism may be related to the induction of hepatic microsomal enzymes by rifampicin. In contrast, the hydroxylation of chenodeoxycholate and ursodeoxycholate may be impaired by severe hepatic damage. Because the urine is a secretory pathway for internal bile acids, the occurrence of unusual trihydroxy bile acids in the urine may be used as an indicator of hepatic ability to metabolize "hydrophobic" dihydroxy bile acids to their secretory forms.

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholelithiasis; Chromatography, Gas; Deoxycholic Acid; Gas Chromatography-Mass Spectrometry; Humans; Hydroxy Acids; Liver Cirrhosis; Rifampin; Ursodeoxycholic Acid

Investigation of the uptake and metabolism of drugs by organs such as the liver may allow assessment of specific aspects of organ function. Rifampicin, when orally administered, is transported into the hepatocyte from portal blood and thence passes, with its deacetylated metabolite, into the systemic circulation and into bile. This paper reports an investigation of the pharmacokinetics of a sub-therapeutic oral dose of rifampicin in healthy subjects, in patients with cirrhosis and in subjects with Gilbert's syndrome. The areas under the plasma concentration curves (AUC) in patients with cirrhosis were significantly greater than in healthy subjects. Subjects with Gilbert's syndrome had decreased AUCs compared with healthy subjects and were clearly distinguished from patients with cirrhosis. Rifampicin concentration in serum was measured by HPLC using a novel direct injection technique.

Topics: Acetylation; Administration, Oral; Adult; Bile; Biological Transport, Active; Chromatography, High Pressure Liquid; Female; Gilbert Disease; Half-Life; Humans; Kinetics; Liver; Liver Cirrhosis; Male; Rifampin

Normal subjects taking rifampicin regularly, show a fall in serum and urinary drug concentrations from enzyme induction and increased biliary excretion. In cirrhosis, hepatocellular dysfunction and impaired biliary excretion may prevent these changes, but there is little information on how the drug should be prescribed in such patients. Serum and urinary rifampicin concentrations were therefore measured in thirteen patients and five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower than on Day 1 (7.0 +/- 3.0 and 8.0 +/- 1.0 microgram/ml respectively) and this was also the case for nine cirrhotic patients with mild impairment of liver function (6.0 +/- 1.0 and 11.0 +/- 2.0 microgram/ml (p less than 0.02). In both groups there was an accompanying fall in urinary rifampicin excretion due to a decrease in desacetylrifampicin excretion. In the remaining four cirrhotic patients, peak serum rifampicin levels rose from 11.0 +/- 5.0 to 17.0 +/- 6.0 microgram/ml and urinary excretion of desacetylrifampicin did not fall. Although values for serum albumin and prothrombin time were of limited value in predicting drug accumulation, pretreatment levels of bilirubin exceeding 50 mumol/l were present in all four patients showing an increase in serum rifampicin concentration. Furthermore, only in this group was there a rise in serum bilirubin during treatment, almost certainly the result of competition between rifampicin and bilirubin for hepatic uptake and excretion. In all patients with cirrhosis, bilirubin concentrations exceeding 50 mumol/l should be an indication for reduction of rifampicin dosage.

Topics: Drug Administration Schedule; Humans; Liver Cirrhosis; Liver Function Tests; Rifampin

Topics: Adult; Aged; Antipyrine; Cytochrome P-450 Enzyme System; Enzyme Induction; Female; Glucaric Acid; Hepatitis; Histamine H1 Antagonists; Humans; Liver; Liver Cirrhosis; Male; Medroxyprogesterone; Middle Aged; Pharmaceutical Preparations; Phenobarbital; Phenytoin; Prednisolone; Rifampin

Fasting and postprandial serum bile acid concentrations were determined by gas-liquid chromatography in 20 consecutive individuals (14 normal subjects, 6 cirrhotics) before and after administration of rifampicin in a single dose of 900 mg, using each individual as his own control. In the normal subjects the 2-hr postprandial level was 2.9 +/- 0.2 microM (mean +/- 1 SEM) prior to drug administration. Following rifampicin, it was 7.7 +/- 0.5 microM (P less than 0.0005). In the patients with liver cirrhosis the 2-hr postprandial level increased from 30.2 +/- 3.5 before, to 105.0 +/- 27.7 microM after rifampicin (P less than 0.025). Twelve hours after drug administration the levels of serum bile acids were not significantly different with respect to the control values. Total serum bilirubin also showed a transient and parallel increase. These findings are compatible with the hypothesis that rifampicin inhibits the hepatic transport of bile acids.

Topics: Adult; Bilirubin; Eating; Fasting; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Rifampin

Topics: Aged; Female; Hepatic Encephalopathy; Humans; Jaundice; Liver Cirrhosis; Male; Rifampin

Topics: Humans; Liver; Liver Cirrhosis; Rifampin

Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggests that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.

Topics: Adult; Aged; Cholestasis; Female; Hexobarbital; Humans; Kinetics; Liver Cirrhosis; Male; Metabolic Clearance Rate; Middle Aged; Rifampin; Stimulation, Chemical; Time Factors; Tolbutamide

Topics: Adult; Aged; Fatty Liver; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Middle Aged; Rifampin

Topics: Bilirubin; Dose-Response Relationship, Drug; Half-Life; Hepatitis; Humans; Kinetics; Liver; Liver Cirrhosis; Liver Diseases; Rifampin; Time Factors

Liver function and serum concentrations of rifampicin, a highly cholephilic antibiotic, have been studied after ingestion of a single dose of 600 mg of rifampicin in 12 patients, six of them having a normal liver and six a cirrhotic, and during treatment with 600 mg of rifampicin per day for 17 days in eight patients, four of them having a normal liver and four a cirrhotic. Rifampicin produced competition for the elimination of bilirubin and bromsulphalein by the liver. This competition, which seemed to involve mainly the uptake by the liver cell, was always rapidly reversible when treatment was discontinued. It makes it impossible, however, to interpret a bromsulphalein test during treatment with rifampicin. In the eight patients treated for 17 days, apart from the competition already mentioned, no clinical, biological, or morphological abnormalities of the liver were ascertained. But in this limited number of patients it is not possible to exclude the fact that rifampicin could provoke jaundice by idiosyncrasy in a small percentage of cases. The serum concentrations of rifampicin were higher in cirrhotic patients than in patients with normal livers, especially after one or two weeks of treatment. It is suggested that efficient blood concentrations of rifampicin would be achieved with small doses in case of previous hepatocellular insufficiency.

Topics: Adult; Aged; Bilirubin; Humans; Jaundice; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Rifampin; Sulfobromophthalein

Topics: Alcoholism; Aspartate Aminotransferases; Bilirubin; Chronic Disease; Ethambutol; Humans; Liver Cirrhosis; Male; Melena; Middle Aged; Recurrence; Rifampin; Sputum; Thrombocytopenia; Tuberculosis, Pulmonary

Topics: Alcoholism; Chronic Disease; Humans; Liver Cirrhosis; Male; Middle Aged; Rifampin; Thrombocytopenia; Tuberculosis

Topics: Adult; Aged; Chronic Disease; Drug Combinations; Drug Resistance, Microbial; Ethambutol; Female; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Rifampin; Sputum; Tuberculosis, Pulmonary