An environmental Gram-negative Alphaproteobacterium — Novosphingobium aromaticivorans has been associated with this disease, with several reports suggesting an aetiological role for this organism. The mechanism appears to be a cross-reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells. The gene encoding CD101 may also play a role in host susceptibility to this disease.A failure of immune tolerance against the mitochondrial pyruvate dehydrogenase complex (PDC-E2) is a primary cause, with shedding of the antigen into apoptotic bodies or "apotopes" leading to the anatomic localization. Such autoreactivity may also be the case with other proteins, including the gp210 and p62 nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients, and these proteins may be associated with prognosis. Diagnosis
Most patients are currently diagnosed when asymptomatic, having been referred to the hepatologist for abnormal liver function tests (mostly raised GGT or alkaline phosphatase) performed for annual screening blood tests. Other frequent scenarios include screening of patients with nonliver autoimmune diseases, e.g. rheumatoid arthritis, or investigation of elevated cholesterol, evaluation of itch or unresolved cholestasis post partum. Diagnosing PBC is generally straightforward. The basis for a definite diagnosis are:

Abnormalities in liver enzyme tests are usually present and elevated gamma-glutamyl transferase and alkaline phosphatase  are found in early disease. Elevations in bilirubin occur in advanced disease. Antimitochondrial antibodies are the characteristic serological marker for PBC, being found in 90–95% of patients and only 1% of controls.
Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer.Sonidegib is Hedgehog signaling pathway inhibitor (via smoothened antagonism). Approvals and indications
It was approved for medical use in the United States and in the European Union in 2015It is indicated for the treatment of adults with locally advanced basal-cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. Pharmacology
Sonidegib is administered by mouth. Common side effects include muscle spasms, hair loss, fatigue, abdominal pain, nausea, headache, and weight loss.Sonidegib binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway. Sonidegib is primarily metabolized by CYP3A and is eliminated hepatically. Development
It has been investigated as a potential treatment for:

Pancreatic cancer
Breast cancer
Basal cell carcinoma of the skin
Small cell lung cancer
Medulloblastoma
Advanced solid tumors (including ovarian, breast, pancreatic, stomach, oesophageal cancers and glioblastoma multiforme)
Acute leukemia and chronic myeloid leukemia
Myelofibrosis and essential thrombocythaemiaIt has demonstrated significant efficacy against melanoma in vitro and in vivo. It also demonstrated efficacy in a mouse model of pancreatic cancer. References
External links
"Sonidegib". Drug Information Portal. U.S. National Library of Medicine. "Sonidegib phosphate". Drug Information Portal. U.S. National Library of Medicine.