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Comorbidity with other autoimmune disease, familial incidence, past or present smoking habits, a history of urinary tract infection, and repetitive use of cosmetic products such as hair dyes are significant risk factors for developing PBC [13, 14, 16]. The clinical features and natural history of PBC range significantly from asymptomatic to progressive conditions [13]. Jaundice, pruritus derived from cholestasis, and general fatigue are typical symptoms in patients with PBC. However, up to 60% of patients may have no clinical symptoms (asymptomatic PBC). PBC represents approximately 1% of all cases of LC [34], potentially reflecting the relatively high frequency of asymptomatic cases. 2.2.3. Histopathological C646 cost Features of PBC With regard to the histopathological features of PBC, florid bile duct lesions, such as chronic, nonsuppurative, and destructive cholangitis, and epithelioid granuloma formation are well-known and useful histological findings in the diagnosis of PBC [13]. Other histopathological findings include portal inflammation, chronic cholestasis, hepatic changes (interface hepatitis or lobular hepatitis), and bile duct loss. The classifications by Scheuer or Ludwig are globally used for disease staging and are based on the histopathological findings of PBC. 2.2.4. [http://www.selleck.co.jp/products/atezolizumab.html http://www.selleck.co.jp/products/atezolizumab.html Atezolizumab clinical trial learn more Atezolizumab price] Diagnosis of PBC The diagnosis of PBC is established if two of the three objective criteria are present: (1) elevated serum alkaline phosphatase; (2) presence of AMA, which is useful for the serological selleck kinase inhibitor diagnosis of PBC (90%�C95% of patients with PBC being AMA-positive [25, 57]); and (3) liver histology findings (presence of chronic, nonsuppurative, and destructive cholangitis) [13]. 2.2.5. Prognosis of PBC The prognosis of PBC is often dependent on the development of portal hypertension or cirrhosis, indicating liver failure. However, disease progression may in some cases be significantly inhibited by treatment with ursodeoxycholic acid (UDCA) [13, 58]. Meanwhile, patients with end-stage liver failure require organ transplantation [34]. In such cases, prognostic models, such as Mayo risk scores and bilirubin levels, are useful to determine the appropriate timing of liver transplantation [58]. Although the incidence of hepatocellular carcinoma (HCC) with concomitant PBC is relatively low, several studies have reported incidence rates of