Harjit Singh

Drug-induced liver injury (DILI) remains an active field of clinical research and investigation with more than 4700 publications appearing in 2023 relating to hepatotoxicity of all causes and injury patterns. As in years past, we have attempted to identify and summarize highlights and controversies from the past year’s literature. Several new and novel therapeutic agents were approved by the US Food and Drug Administration (FDA) in 2023, a number of which were associated with significant hepatotoxicity. Updates in the diagnosis and management of DILI using causality scores as well as newer artificial intelligence-based methods were published. Details of newly established hepatotoxins as well as updated information on previously documented hepatotoxic drugs is presented. Significant updates in treatment of DILI were also included as well as reports related to global DILI registries.

Hepatic amyloidosis is a rare condition that leads to progressive liver dysfunction. Diagnosis is often challenging since clinical presentation may be highly varied and is dependent upon the extent of liver involvement, underlying etiology of amyloid deposition, as well as concomitant extrahepatic manifestations. Ascites, although uncommon, can be a presenting feature of hepatic amyloidosis and pose diagnostic challenges as it can occur in a variety of liver and nonliver‐related conditions. Herein, we present a case of hepatic amyloidosis in a patient with recurrent ascites, emphasizing the importance of considering this condition in the differential diagnosis of individuals presenting with unexplained ascites.

Statin-induced liver injury has been widely described. However, cases of clinically significant liver injury are rare. We present a 56-year-old woman who developed atorvastatin-induced grade III acute liver injury with concurrent rhabdomyolysis that worsened after rechallenging, which highlighted the need for pharmacovigilance with statins. The Roussel Uclaf Causality Assessment Method and Revised Electronic Causality Assessment Method both showed that atorvastatin was highly probable in causing hepatotoxicity. To our knowledge, this is the first reported case of concurrent drug-induced liver injury and rhabdomyolysis after a positive rechallenge with atorvastatin.

Ectopic varices are an infrequent yet fatal complication resulting from the progression of liver cirrhosis. Duodenal varices pose a significant challenge to clinicians as they are not easily visualized on endoscopy due to their submucosal location and lack of red color signs. Identification of duodenal varices is important given the risk of massive and life-threatening bleeding that is difficult to control. Patients may present in hemorrhagic shock requiring immediate resuscitation; however, confirmation of the bleeding source as variceal or non-variceal is critical in determining the optimal therapeutic intervention. Here, we report an unusual case of a duodenal ulcer that eroded into an ectopic varix resulting in hemorrhagic shock.

Aim: Formulation, optimization and anticancer activity of spray-dried Doxorubicin loaded folic acid conjugated Gelatin nanoparticles (DOX-FA-GN). Methods: Doxorubicin loaded gelatin nanoparticles (DOX-GN) were prepared by the Coacervation phase separation method, optimized using DoE and then conjugated with folic acid by covalent coupling to formulate Doxorubicin loaded folic acid conjugated nanoparticles (DOX-FA-GN). The formulated nanoparticles were characterized to evaluate its physicochemical properties. Cellular uptake and cell viability studies were carried out using MTT assay and biodistribution studies were carried out in Wistar rats. Results: Particle size, PDI and entrapment efficiency for optimized DOX-GN were found to be 152.3 ± 9.3 nm 0.294 ± 0.1 and 86.9± 3.4% while for DOX-FA-GN, 193.9 ± 12.3 nm 0.247 ± 0.2 and 84 ± 3.6%. The cytotoxic studies showed a cell viability of 75.1% for DOX-GN and 29.5% DOX-FA-GN. Biodistribution studies were found to be statistically insignificant for conjugated nanoparticles with excellent flow properties. Significantly higher DOX distribution in the lungs was observed in the case of DOX-FA-GN. Conclusions: There was a higher uptake of DOX on HeLa cells with DOX-FA-GN compared to DOX-GN. Also, the biodistribution of Dox in the lungs of Wistar rats was higher in conjugated nanoparticles as compared to unconjugated nanoparticles.