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The Wnt/-Catenin signaling pathway plays crucial roles in HFs development, including growth cycle restart and maintenance and HF cells proliferation and differentiation (Ito et al., 2007

Abbreviations AAS: Antibiotic antimycotic solution -GST: Alpha-glutathione s-transferase ALT: Alanine aminotransferase ASGPR1: Asialoglycoprotein receptor 1 CD206: Mannose receptor CD32b: Fc fragment of IgG receptor IIb CYP3A4: Cytochrome P450 3A4 DILI: Drug-induced liver injury DMSO: Dimethyl sulfoxide IL: Interleukin KCs: Kupffer cells LDH: Lactate dehydrogenase LPS: Lipopolysaccharide LSECs: Liver sinusoidal endothelial cells LVX: Levofloxacin mBCI: Monochlorobimane MDMs: Monocyte-derived macrophages PBS: Phosphate buffered saline ROS: Reactive oxygen species RT: Room temperature TNF-: Tumor necrosis factor-alpha TVX: Trovafloxacin VPM: Vascular perfusion medium References Stevens, J

Important discussion points include: Medical history : Disclose any history of thyroid problems (especially MTC), MEN2, pancreatitis, gallbladder disease, kidney disease, gout, liver disease, or alcohol use Treatment goals : Clarify whether niacin therapy is necessary given current lipid management guidelines, which generally favor statins, ezetimibe, PCSK9 inhibitors, or other agents before niacin for cardiovascular risk reduction Glucose monitoring plan : Establish a clear schedule for blood glucose checks and hemoglobin A1c testing (typically every 3 months) to assess the combination's net effect on glycemic control Liver monitoring plan : Discuss the schedule for liver function tests if taking pharmacologic doses of niacin (baseline, 6-8 weeks during titration, and periodically thereafter) Pregnancy planning : If applicable, discuss contraception needs, as tirzepatide may reduce oral contraceptive effectiveness during initiation and dose escalation Symptom management : Review strategies for managing potential side effects from both medications, including the timing of niacin doses to minimize flushing and approaches to mitigate tirzepatide's gastrointestinal effects Patients should specifically ask about the expected timeline for therapeutic effects, warning signs that require immediate medical attention (severe abdominal pain, yellowing of skin/eyes, unusual fatigue, neck swelling), and whether any dose adjustments to existing diabetes medications may be necessary

doi: 10.1038/s41579-022-00722-z 183 MartinezS