Treatment of primary biliary cholangitis has two aims: to slow the destruction of the small bile ducts and so delay cirrhosis, and to relieve the symptoms, particularly pruritus, that come with chronic cholestasis.
First-line treatment
Ursodeoxycholic acid (UDCA) is the first-line drug, given orally at 13 to 15 mg/kg/day. It reduces liver damage, prolongs survival and delays the need for liver transplantation. AMA-negative PBC responds to UDCA in the same way as AMA-positive disease.
Response is judged from the biochemistry after at least 12 months of treatment: a response means the alkaline phosphatase has fallen to less than 1.5 to 2 times the normal range and the bilirubin has normalised. About 40% of patients do not reach this response; they may have more advanced disease and require liver transplantation within a few years, and they are the ones considered for second-line therapy.
Second-line treatment
Second-line drugs are the peroxisome proliferator-activated receptor (PPAR) agonists, added to UDCA or, in patients who cannot tolerate UDCA, used alone. Seladelpar, a PPAR-delta agonist, and elafibranor, a PPAR-alpha and delta agonist, reduce cholestasis in patients with an inadequate response to UDCA. Bezafibrate, a fibrate acting on PPAR-alpha, is an alternative where these are not available. Fibrates can raise aminotransferases and worsen renal function, so these are monitored, and PPAR agonists, including the fibrates, are avoided in decompensated cirrhosis. Obeticholic acid was previously used as a second-line agent, but it has been withdrawn from the market in the United States because of safety concerns.
Managing symptoms and complications
Pruritus is treated in steps. Cholestyramine, 4 to 16 g/day, is tried first; because it binds bile salts in the gut, it can worsen fat malabsorption, and it can also bind UDCA and reduce the absorption of other drugs, so UDCA and any affected medication should be taken at least 1 hour before or 4 hours after cholestyramine. If cholestyramine is not enough, rifampicin, naltrexone or sertraline can be tried. Fat-soluble vitamins (A, D, E and K) are supplemented when malabsorption is present, and osteoporosis is managed with calcium and vitamin D, weight-bearing exercise, and a bisphosphonate or raloxifene.
Liver transplantation
Liver transplantation is reserved for decompensated liver disease and has excellent results. The usual indications are a Model for End-Stage Liver Disease (MELD) score of 15 or more, uncontrolled variceal bleeding, refractory ascites, intractable pruritus and hepatic encephalopathy. AMA tend to persist after transplantation, and PBC recurs in the graft in about 15% of patients within a few years and in more than 30% by 10 years, usually with a benign course.