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.
For intrahepatic cholestasis in pregnant women, S-adenosylmethionine has proven to be an effective treatment. Dexamethasone is a viable treatment in regards to the symptom of intensive itching. Research directions
Primary sclerosing cholangitis (PSC) is one of the most common cholestatic liver diseases, yet treatment options remain limited. Treatment for primary biliary cholangitis (PBC) is often done with ursodeoxycholic acid (UDCA) and with no other suitable alternative, it poses a problem for those that are not responsive to (UDCA). However, with advancing technology in the molecular biochemistry field and higher understanding of bile acid regulation, novel pharmacological treatments have been considered. For patients with primary biliary cholangitis, current guidelines recommend about 13–15 mg/kg of ursodeoxycholic acid as a first line treatment. This drug stimulates biliary bicarbonate secretion, improves survival without having to resort to a liver transplantation, and is very well tolerated— making it an ideal treatment. However, around 40% of patients with primary biliary cholangitis are not responsive to UDCA.Obeticholic acid has been approved by the US Food and Drug Administration for PBC in 2016 after experiments found beneficial improvements for the liver in half of patients with inadequate response to UDCA.Primary sclerosing cholangitis is a challenging liver disease as treatment options are limited. There is still uncertainty about the efficacy of ursodeoxycholic acid for PSC and researchers offer conflicting recommendations. One study found UDCA had improved biochemical functions but did lower the rate for death or transplant-free survival.