How best to manage chronic cholestasis

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Applied Evidence

How best to manage chronic cholestasis

J Fam Pract. 2018 July;67(7):E9-E15

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From The Journal of Family Practice | 2018;67(7):E9-E15.

References

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Bile acid administration counters the cytotoxic effect of hydrophobic bile salts. Although it seems that UDCA might improve biochemical and histologic features of the disease at earlier stages (I-II), it fails in patients with more advanced disease.²⁷ In addition, monitoring and defining response to UDCA is inconsistent, partly because of variations in guideline criteria.^28,29

Despite progress in diagnostic techniques, life expectancy and quality of life for patients with advanced cholestatic conditions remain poor.

Recently a new molecule, obeticholic acid (OCA), has been approved by the FDA. A farnesoid X receptor agonist, OCA is indicated for treating patients who do not tolerate UDCA or as an adjunct to UDCA in those with a partial response to UDCA, defined as lowering ALP levels by <1.5 times the baseline value after 12 months of treatment.

Treating PSC is more complex. Combination therapy with prednisone and azathioprine is recommended only when there is an overlap syndrome between PSC and autoimmune hepatitis.⁴ UDCA at a high dosage (15-20 mg/kg/d) is used to facilitate long-lasting biochemical remission. These patients also need to be monitored for inflammatory bowel diseases, which affect up to 75% of patients,³⁰ and for cholangiocarcinoma, which is a life-limiting complication because of a lack of therapy options. Finally, these patients might need endoscopic-guided dilatation of the biliary tree when they have evidence of dominant fibrotic strictures of the greater bile ducts.^14,31

Addressing the systemic effects of intrahepatic cholestasis

Pruritus. A number of potential pruritogens, including bile salts, endogenous opioids, histamine, serotonin, and lisophosphatidic acid (LPA), can be targeted to relieve pruritus.

Bile acid resin binders such as cholestyramine are the first step for treating pruritus. UDCA also can be useful, mainly for intrahepatic cholestasis during pregnancy. Rifampicin, 300 mg/d, improves cholestatic pruritus, but is associated with hepatotoxicity and a number of severe reactions, such as nausea, loss of appetite, hemolytic anemia, and thrombocytopenia.³¹
Most evidence favors a role for opioids in relieving itch, and micro-opioid receptor antagonists (naltrexone, naloxone, nalmefene) that exert an antipruritic effect can be effective.
Sertraline (a selective serotonin reuptake inhibitor), 50 to 75 mg/d, usually is well tolerated in patients with chronic cholestasis and exerts a beneficial effect on pruritus in approximately 40% of patients.³²
Extracorporeal albumin dialysis removes albumin-bound pruritogens and has been found to be effective in patients with liver failure. Steroids and UV light also can be used in select patients.
The potent neuronal activator LPA and its converting enzyme autotaxin have been identified in the serum of patients with cholestatic pruritus; experimental modalities using LPA antagonists are ongoing for treating pruritus in patients who do not respond to other medications.³³

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