Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.

The present patients with positive GFAP-immunoglobulin G are highly similar to autoimmune GFAP astrocytopathy, described in a recent report. The features of the neuropathology and immunopathology of GFAP astrocytopathies were perivascular inflammation and loss of astrocytes and neurons.

Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease of the nervous system first defined in 2016. GFAP autoantibody, especially IgG that binds to GFAPα, has been reported in the cerebrospinal fluid (CSF) and serum of patients with GFAP astrocytopathy. The positive predictive value of GFAP antibody in the CSF is higher than in the serum. Tissue-based assay (TBA) and cell-based assay (CBA) are both recommended methods for the detection of GFAP antibody. GFAP astrocytopathy is accompanied by neoplasms, but the relationship between virus infection and GFAP astrocytopathy is unclear. GFAP antibody itself does not induce pathological changes; it is only a biomarker for the process of immune inflammation. The pathology of GFAP astrocytopathy in humans is heterogeneous. GFAP astrocytopathy is commonly diagnosed in individuals over 40 years old and most patients have an acute or subacute onset. Clinical manifestations include fever, headache, encephalopathy, involuntary movement, myelitis, and abnormal vision. Lesions involve the subcortical white matter, basal ganglia, hypothalamus, brainstem, cerebellum, and spinal cord. The characteristic MRI feature is brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Currently, there are no uniform diagnostic criteria or consensus for GFAP astrocytopathy and coexisting neural autoantibodies detected in the same patient make the diagnosis difficult. A standard treatment regimen is yet to be developed. Most GFAP astrocytopathy patients respond well to steroid therapy although some patients are prone to relapse or even die.

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