Furthermore, GCSs inhibit bone formation indirectly, by suppressing the synthesis of testosterone in gonads and by decreasing the production of growth hormone, IGF, and accordingly type 1 collagen, as well as directly by suppressing the function of osteoblasts[95,96]. PBC Rcan1 and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the FUBP1-CIN-1 disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis. Keywords: Primary biliary cirrhosis, Clinical criteria, Laboratory criteria, Immunological signs, Biochemical signs, Morphological signs Core tip: Primary biliary cirrhosis is a chronic autoimmune cholestatic liver disease. This review summarizes current literature data and our own experiences on clinical and laboratory criteria for the diagnosis of primary biliary cirrhosis. Thanks to advances in biochemistry, molecular biology and genetics, it became possible to present these data with regard to the pathophysiological mechanisms of their development. INTRODUCTION Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease characterized by a striking female predominance, high-titer serum antimitochondrial autoantibodies (AMAs), disease-specific antinuclear autoantibodies (ANAs), and an autoimmune-mediated progressive granulomatous destruction of small and medium-sized intralobular and septal intrahepatic bile ducts, leading to cirrhosis and ultimately liver transplantation or death[1-5]. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease[6]. Immunologically, PBC is distinguished by immune-mediated destruction of the intrahepatic bile ducts and the presence of high-titer antimitochondrial autoantibodies[3] directed against a highly specific epitope within the lipoic acid binding domain of the pyruvate dehydrogenase E2 subunit (PDC-E2)[7]. The natural history of the disease is 10 to 20 years[6]. According to the presence or absence of cirrhosis, the mean survival was 9.17 years (95%CI: 6.79-11.56) and 10.7 years (95%CI: 9.27-12.14), respectively (= 0.03)[8]. Mortality from PBC is 2.2% of FUBP1-CIN-1 all deaths due to liver cirrhosis[9]. History of PBC In 1851, Addison et al[10] were the first to observe an association of skin changes with liver disease in women. Elevated serum cholesterol levels in these patients and the presence of cutaneous xanthelasmas served as a basis for employing the term xanthomatous biliary cirrhosis to denote this disease[11,12]. Almost 100 years ago, its clinical picture was described in detail and the term primary biliary cirrhosis was FUBP1-CIN-1 offered[11,12]. In 1965, a group of morphologists under the supervision of H. Popper proposed the term chronic non-purulent destructive cholangitis[13]. Epidemiology of PBC PBC is encountered in all parts of the world among people of all races and nationalities[14,15]. No differences were observed in the geographical distributions of the disease[15]. According to different authors, the prevalence of PBC is 4-14 cases per 100000 population[15-17]. PBC is mostly found in patients in Northern Europe, the United Kingdom, and the northern United States. The prevalence of familial PBC was later reported to be 6.4% in United Kingdom[18], and between 3.8% and 9.0% in a number of studies from FUBP1-CIN-1 North America, Europe, and Japan[5]. In Asia, Japan is the only country with a known prevalence of PBC, at 27-54 per million[19,20]. The annual incidence rates range between 0.7 and 49 cases per million persons, while the global prevalence rates range between 6.7 and 402 cases per million persons[3,5,6,20-24]. A study conducted by Gershwin et al[25] indicated that having a first-degree relative with PBC was significantly associated with increased risk of PBC, with an odds ratio of 10.7. This is supported by the high concordance rate of PBC among first-degree relatives and homozygous twins (approximately 60%)[26,27]. A pairwise concordance rate of 0.63 for PBC in monozygotic twin pairs has been published, which is one of the highest reported in autoimmunity[28]. Specifically, the high concordance for PBC in monozygotic twins, family clustering, and female predominance suggest that genetic factors may play an important role in the development of PBC[29-31]. PBC is a typical female disease that occurs from 40-60 years of age[32,33]. Much less is logged PBC in persons under the age of 25 years[34,35]. There is a high female:male incidence ratio (8:1), with suggestions of a significant role for X chromosome defects.