A worry though is despite benefits in the biochemical pathways, pruritus was more intense and prevalent than the placebo. A titration strategy may help to mitigate pruritus, but FDA approval for obeticholic acid is currently unlikely. In fact, in February 2018, the FDA gave a black box warning for OCA. A recent study did find that if the drug is given with UDCA, the incidence for cirrhosis and liver transplants decreases.Another target that is being looked into is the All-trans retinoic acid (ATRA), an activator for the retinoid X receptor. In vitro and animal studies found ATRA had lowered the amount of bile acid and decreased hepatic inflammation. 24-norursodeoxycholic acid
A recent scientific breakthrough for cholestasis that has allowed us to evaluate a new treatment option is that a hydrophilic environment and bicarbonate production protects hepatocytes from bile acid. The novel agent norUDCA (24-norursodeoxycholic acid) can be passively absorbed by cholangiocytes. This leads to bicarbonate production and an environment that is less toxic. Mouse models have found promising results with norUDCA with the drug showing antiproliferative and anti-inflammatory properties. A recent clinical trial found norUDCA had significant dose-dependent reductions for ALP levels. This makes norUDCA a viable possibility to look into as it clearly plays a significant role in the treatment of cholestasis. Immunomodulatory treatments
In PBC, the liver is filled with T cells and B cells that contribute to a worsening condition. Therefore, some treatments are looking into targeting the antigens of these immune cells.
Nelsons syndrome is a disorder that occurs in about one in four patients who have had both adrenal glands removed to treat Cushings disease. In patients with pre-existing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, loss of adrenal feedback following bilateral adrenalectomy can trigger the rapid growth of the tumor, leading to visual symptoms (e.g. bitemporal hemianopsia) and hyperpigmentation. The severity of the disease is dependent upon the effect of ACTH release on the skin, pituitary hormone loss from mass compression, as well as invasion into surrounding structures around the pituitary gland.The first case of Nelsons syndrome was reported in 1958 by Dr. Don Nelson. Within the past ten to twenty years, improvements have been made with identification and care for patients with Cushings disease. Techniques such as pituitary radiation therapy, ACTH assay, transsphenoidal pituitary surgery, higher resolution MRIs, and sampling of the inferior petrosal sinus have allowed physicians to pursue routes for Cushings syndrome therapy prior to consideration of bilateral adrenalectomy.Nelsons syndrome is also referred to as post adrenalectomy syndrome, a possible result of adrenalectomy performed for Cushings disease. Symptoms and signs
The common symptoms include:
hyper-pigmentation of the skin
visual disturbances
headaches
abnormally high levels of beta-MSH and ACTH
abnormal enlargements of the pituitary gland,
interruption of menstrual cycles in women

Cause
Common causes include bilateral adrenalectomy for the treatment of Cushings disease, and hypopituitarism. The onset of the disease can occur up to 24 years after a bilateral adrenalectomy has been performed, with an average of up to 15 years after.