Progress in the management of patients with cholestatic liver disease: Where are we and where are we going?

Medical Xpress / Xia & He Publishing Inc. / Journal of Clinical and Translational Hepatology ^ | July 12, 2024 | Xin Luo et al

[ConservativeMind]

Cholestatic liver diseases (CLDs) are a group of disorders characterized by the impairment of bile formation, secretion, or excretion.

Chronic cholestasis can lead to liver fibrosis and cirrhosis. The most common types of CLDs are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

CLDs are classified into intrahepatic and extrahepatic types based on their etiology. Intrahepatic cholestasis is mainly caused by immune dysfunction, viral infections, drug-induced injury, and alcohol-related damage, whereas extrahepatic cholestasis often results from bile duct stones, tumors, or strictures.

Pharmacological treatment of PBC include:

Ursodeoxycholic acid (UDCA): UDCA is the first-line treatment for PBC. It improves biochemical responses, delays histological progression, and extends transplant-free survival.

Obeticholic acid (OCA): For patients unresponsive to UDCA, OCA, a farnesoid X receptor (FXR) agonist, has shown efficacy in improving biochemical responses and delaying disease progression.

Fibrates: Bezafibrate and fenofibrate have demonstrated improved biochemical responses. Clinical trials have shown that fibrates can significantly reduce ALP levels and improve patient outcomes.

Budesonide: Budesonide has shown potential in normalizing ALP levels in PBC patients.

Currently, there are no approved pharmacological treatments for PSC. UDCA is used off-label.

New treatment avenues for CLDs are being explored, including:

Fibroblast growth factor 19 (FGF19): Reduces bile acid synthesis and shows promise in early clinical trials for both PBC and PSC.

S-adenosyl-L-methionine (SAM-e): Enhances hepatocyte protection and may improve liver function in cholestatic conditions.

Steroid drugs: Anti-inflammatory properties help manage symptoms, particularly in autoimmune-related cholestasis.

Farnesoid X receptor agonists: Inhibit bile acid synthesis and promote bile flow, offering a new therapeutic target for various cholestatic conditions.

Significant progress has been made in understanding and managing cholestatic liver diseases. While UDCA remains the cornerstone of PBC treatment, new therapies like OCA, fibrates, and budesonide offer additional options for patients with poor responses to standard treatments.

[ConservativeMind]

People with these disorders have new “approved” option, but can benefit from off-label use and even an over the counter supplement, like SAM-e.

Talk with your doctor about ways to enhance your own therapy, perhaps by going over items mentioned above.

[ConservativeMind]

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[Extremely Extreme Extremist]

Yes! There’s hope for me!!

[ConservativeMind]

That should read, “People with these disorders have no “approved” option…”

[telescope115]

I had a liver biopsy done in 2005 due to elevated liver enzymes. I had (still have) long standing Ulcerative Colitis. I was taking ursodiol for a while back then, then the doc took me off of it. Fast forward to 2017, I was told I had end stage liver disease, and put back on ursodiol for a time. It was intended to slow down the inevitable, but I was put on the transplant list. I received a new liver in 2021. I had PSC and Sarcoidosis. Doing great now.

Anything new they can come up with to arrest progression of liver disease would be wonderful.