Case Report: Pulmonary tuberculosis and raised transaminases without pre-existing liver disease- Do we need to modify the antitubercular therapy?

We report a case of an adult female with pulmonary tuberculosis who had biochemical evidence of liver injury during the presentation manifested as raised transaminases, but without clinically obvious pre-existing liver disease nor a history of hepatotoxic drug use. This is a fairly common scenario seen in tuberculosis endemic areas; however, this is an under reported condition in the literature and guidelines for its management has not been established. Many clinicians including the authors have treated such cases with modified liver friendly regimens in fear of increasing the hepatotoxicity with standard antitubercular drugs. However, the modified regimens may not be optimal in treating the underlying tuberculosis. In this report, we gave full dose standard drugs, and the liver injury resolved as evidenced by normalization of transaminases. Further research is required in this regard, but the presence of transaminitis with no obvious common underlying etiology may not warrant a modification of standard antitubercular regimen.

Case Report: Treating pulmonary tuberculosis with transaminitis with standard antitubercular four drugs therapy

We report a case of pulmonary tuberculosis with transaminitis during the presentation but without any pre-existing liver disease or hepatotoxic drug use. This is a fairly common scenario seen in tuberculosis endemic areas; however, this is an under reported condition in the literature and guidelines for its management has not been established. Many clinicians including the authors have treated such cases with modified liver friendly regimens in fear of increasing the hepatotoxicity with standard drugs. However, the modified regimens may not be optimal in treating the underlying tuberculosis. In this report, we gave full dose standard antitubercular drugs, and the liver injury resolved evidenced by normalization of transaminases.

Nevirapine Biotransformation Insights: An Integrated In Vitro Approach Unveils the Biocompetence and Glutathiolomic Profile of a Human Hepatocyte-Like Cell 3D Model

The need for competent in vitro liver models for toxicological assessment persists. The differentiation of stem cells into hepatocyte-like cells (HLC) has been adopted due to its human origin and availability. Our aim was to study the usefulness of an in vitro 3D model of mesenchymal stem cell-derived HLCs. 3D spheroids (3D-HLC) or monolayer (2D-HLC) cultures of HLCs were treated with the hepatotoxic drug nevirapine (NVP) for 3 and 10 days followed by analyses of Phase I and II metabolites, biotransformation enzymes and drug transporters involved in NVP disposition. To ascertain the toxic effects of NVP and its major metabolites, the changes in the glutathione net flux were also investigated. Phase I enzymes were induced in both systems yielding all known correspondent NVP metabolites. However, 3D-HLCs showed higher biocompetence in producing Phase II NVP metabolites and upregulating Phase II enzymes and MRP7. Accordingly, NVP-exposure led to decreased glutathione availability and alterations in the intracellular dynamics disfavoring free reduced glutathione and glutathionylated protein pools. Overall, these results demonstrate the adequacy of the 3D-HLC model for studying the bioactivation/metabolism of NVP representing a further step to unveil toxicity mechanisms associated with glutathione net flux changes.

Gambaran bilirubin dan urobilinogen urin pada pasien tuberkulosis paru dewasa di RSUP Prof. Dr. R. D. Kandou Manado

Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Antituberculosis drugs prescribed to TB patients is hepatotoxic drug. Liver damage caused by side effects of the drugs will cause an alteration in urinary bilirubin and urobilinogen level. This study was aimed to obtain the profile of urinary bilirubin and urobilinogen in adult pulmonary tuberculosis patients at Prof. Dr. R. D. Kandou Hospital Manado from October to November 2016. This was an observational descriptive study. Samples obtained by using random sampling urine from all pulmonary tuberculosis patient that met the inclusion criteria. The results showed that according to urinary bilirubin and urobilinogen examination in 30 patients, most of them were in normal level. Only 6 out of 30 patients has bilirubinuria in this urinary bilirubin examination. In urinary urobilinogen examination, all results is in normal level. Conclusion: Urinary bilirubin and urobilinogen examination in this research was normal in general, bilirubinemia was found only in some patients.Keywords: pulmonary tuberculosis, urinary bilirubin, urinary urobilinogen Abstrak: Tuberkulosis (TB) merupakan penyakit menular yang disebabkan oleh basil Mycobacterium tuberculosis. Obat antituberkulosis yang diberikan pada pasien TB bersifat hepatotoksik. Kerusakan hepar yang disebabkan oleh efek samping obat tersebut akan menyebabkan perubahan pada kadar bilirubin dan urobilinogen urin. Tujuan penelitian untuk mengetahui gambaran bilirubin dan urobilinogen urin pada pasien tuberkulosis paru dewasa di RSUP Prof. Dr. R. D. Kandou Manado. Jenis penelitian ialah deskriptif observasional, untuk mendapatkan data tentang bilirubin dan urobilinogen urin pada pasien tuberkulosis paru dewasa di RSUP. Prof. Dr. R. D. Kandou Manado pada Oktober-November 2016. Sampel penelitian adalah sampel urin sewaktu dari semua pasien tuberkulosis paru yang memenuhi kriteria inklusi. Hasil penelitian memperlihatkan berdasarkan pemeriksaan bilirubin dan urobilinogen urin pada 30 pasien, sebagian besar kadarnya normal. Hanya 6 dari 30 pasien yang mengalami bilirubinuria pada pemeriksaan bilirubin urin. Pada pemeriksaan urobilinogen urin semua hasil dalam batas normal. Simpulan: Pemeriksaan bilirubin dan urobilinogen urin pada umumnya normal, hanya beberapa pasien yang mengalami bilirubinuria.Kata kunci: tuberkulosis paru, bilirubin urin, urobilinogen urin

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.