Which one of the following treatments is effective in primary biliary cirrhosis?
Correct Answer: Ursodeoxycholic acid
Description: Management The hydrophilic bile acid ursodeoxycholic acid (UDCA), at a dose of 13-15 mg/kg/day, improves bile flow, replaces toxic hydrophobic bile acids in the bile acid pool, and reduces apoptosis of the biliary epithelium. Clinically, UDCA improves LFTs, may slow down histological progression and has few side-effects; it is therefore widely used in the treatment of PBC and should be regarded as the optimal first-line treatment. Its use is recommended in all clinical guidelines. A significant minority of patients either fail to normalise their LFTs with UDCA or show an inadequate response, and such individuals have an increased risk of developing end-stage liver disease compared to those showing a full response. Obeticholic acid (OCA) is a second-generation bile acid therapeutic that acts as an agonist for the nuclear farnesoid X receptor. It reduces hepatocyte synthesis of bile acids and was approved in 2016 for use in patients showing an inadequate response to UDCA. Immunosuppressants, such as glucocoicoids, azathioprine, penicillamine and ciclosporin, have all been trialled in PBC. None shows overall benefit when given to unselected patients. It is unclear whether these drugs offer benefit to the specific subgroup of patients who do not respond to UDCA and require second-line approaches to treatment. Liver transplantation should be considered once liver failure has developed and may be indicated in patients with intractable pruritus. Serum bilirubin remains the most reliable marker of declining liver function. Transplantation is associated with an excellent 5-year survival of over 80%, although the disease will recur in over one-third of patients at 10 years. Pruritus This is the main symptom requiring treatment. The cause is unknown, but up-regulation of opioid receptors and increased levels of endogenous opioids may play a role. First-line treatment is with the anion-binding resin colestyramine, which probably acts by binding potential pruritogens in the intestine and increasing their excretion in the stool. A dose of 4-16 g/day orally is used. The powder is mixed in orange juice and the main dose (8 g) taken before and after breakfast, when maximal duodenal bile acid concentrations occur. Colestyramine may bind other drugs in the gut (most obviously UDCA) and adequate spacing should be used between drugs. Colestyramine is sometimes ineffective, especially in complete biliary obstruction, and can be difficult for some patients to tolerate. Alternative treatments include rifampicin (150 mg/day, titrated up to a maximum of 600 mg/day as required and contingent on there being no deterioration in LFTs), naltrexone (an opioid antagonist; 25 mg/day initially, increasing up to 300 mg/day), plasmapheresis and a liver suppo device (e.g. a molecular adsorbent recirculating system, MARS). Fatigue Fatigue affects about one-third of patients with PBC. The cause is unknown but it may reflect intracerebral changes due to cholestasis. Unfounately, once depression, hypothyroidism and coeliac disease have been excluded, there is currently no specific treatment. The impact on patients' lives can be substantial. Ref Davidson edition23rd pg888
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