The key features of the algorithm include new guidance-informed suggestions for staging PBC using noninvasive testing (NIT), earlier assessment of lower thresholds to gauge ursodeoxycholic acid (UDCA) response after initiation of therapy, possible earlier initiation of second-line therapy with obeticholic acid (OCA) at lower levels of alkaline phosphatase (ALP) or bilirubin, avoidance of OCA in patients with cirrhosis complicated by portal hypertension or liver decompensation, and the safety and durability of response with long-term OCA therapy and off-label use of fibrates.

The algorithm is intended for use patients:

• With a PBC diagnosis confirmed by + antimicrobial antibodies (AMA), + antinuclear antibodies (ANA; sp100 Gp210) or biopsy.
• Confirmed PBC that is staged via vibration controlled transient elastography (VCTE) or magnetic resonance elastography (MRE)

All patients that quality, per the criteria above steps, should be started on UDCA 13-15 mg/kg/day for:

• 12 months with lower stage of fibrosis (VCTE or TE <10 kPa, MRE <4.3 kPa)
• 6 months with more advanced fibrosis (VCTE or TE ≥ 10kPa, compensated liver disease and no signs of portal hypertension)

Following this treatment, patients should be monitored for response to therapy and UDCA intolerance by following the steps in the algorithm.

Patients with PBC with an inadequate response to or intolerance of UDCA should be considered for second-line therapy with OCA. Second-line therapy consists of OCA, as reviewed in detail above, or off-label bezafibrate or fenofibrate in patients with an inadequate response and if there are no signs of decompensated liver disease or clinically significant portal hypertension.

• OCA
  • OCA therapy should not be used in patients with thrombocytopenia (i.e., in those with a platelet count < 120 x 109/L, ascites, esophageal varices, or hepatic encephalopathy), complications of cirrhosis (i.e., spontaneous bacterial peritonitis, hepatic encephalopathy, or variceal bleeding), or evidence of hepatic synthetic dysfunction or reduced liver function (prolonged prothrombin time, elevated serum bilirubin, or reduced serum albumin)
  • OCA should be stopped if any of the above develop while on treatment.
  • Patients with cirrhosis receiving OCA should be monitored closely for any evidence of clinical or laboratory decompensation, which would indicate need to discontinue therapy.
  • Given the evidence that OCA may increase the lithogenicity of bile, monitoring for symptomatic gallstones would also be appropriate
• Fibrates
• Because bezafibrate is not available in the United States, it is the opinion of the expert panel that fenofibrate could be considered as an alternative second-line therapy in the appropriate patient, at a low dose of 45-48 mg per day and titrated up as tolerated.

If the patient has not responded to the first second-line option (OCA or fibrate) after 3-6 months of therapy or the patient is unable to tolerate the selected second-line treatment, then the other second-line option should be considered.

Participation in clinical trials should be discussed and encouraged for appropriate patients who may need additional therapies beyond UDCA, OCA, and off-label fibrates

A referral for liver transplantation evaluation may be appropriate for patients with decompensated cirrhosis, portal hypertension, or significantly affected due to severe pruritus or fatigue even if the Model for End-Stage Liver Disease score is relatively low (< 15). Living donor liver transplants may be an option for some patients.