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Pathologica Jun 2021Autoimmune cholestatic liver diseases are rare hepato-biliary disorders characterized by a progressive, inflammatory destruction of bile ducts. Primary biliary... (Review)
Review
Autoimmune cholestatic liver diseases are rare hepato-biliary disorders characterized by a progressive, inflammatory destruction of bile ducts. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. Both may evolve into secondary biliary cirrhosis and its complications. Therapeutic options are limited and liver transplantation remains the only definitive treatment for PBC and PSC. Most PBC and PSC patients have a typical presentation, which does not require liver biopsy. However, in routine clinical practice, important variants or specific subgroups that benefit from liver biopsy for proper management may be observed. Herein, we provide a general overview of clinical and pathological characteristic of PBC and PSC, highlighting the most important features for routine diagnostic practice.
Topics: Autoimmune Diseases; Cholangitis, Sclerosing; Humans; Liver Cirrhosis, Biliary
PubMed: 34294935
DOI: 10.32074/1591-951X-245 -
Hepatology (Baltimore, Md.) Jul 2009
Topics: Humans; Liver Cirrhosis, Biliary
PubMed: 19554543
DOI: 10.1002/hep.22906 -
Hepatology Communications Jun 2023Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked...
Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC vary widely in different regions and time periods, and although disproportionally more common among White non-Hispanic females, contemporary data show a higher prevalence in males and racial minorities than previously described. Outcomes largely depend on early recognition of the disease and prompt institution of treatment, which, in turn, are directly influenced by provider bias and socioeconomic factors. Ursodeoxycholic acid remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with ursodeoxycholic acid intolerance. Novel and repurposed drugs are currently at different stages of clinical development not only for the treatment of PBC but also for its symptomatic management. Here, we summarize the most up-to-date data regarding the epidemiology, prognosis, and treatment of PBC, providing clinically useful information for its holistic management.
Topics: Male; Female; Humans; Ursodeoxycholic Acid; Liver Cirrhosis, Biliary; Cholangitis; Prognosis; Cholestasis
PubMed: 37267215
DOI: 10.1097/HC9.0000000000000179 -
Aging May 2023Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also...
BACKGROUND
Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arises in biliary atresia (BA), the first cause of pediatric liver transplantation. Since alternatives to transplantation are needed, our aim was to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis.
METHODS
BA liver tissues were prospectively obtained at hepatoportoenterostomy (n=5) and liver transplantation (n=30) and compared to controls (n=10). Senescence was investigated through spatial whole transcriptome analysis, SA-β-gal activity, p16 and p21 expression, γ-H2AX and senescence-associated secretory phenotype (SASP). Human allogenic liver-derived progenitor cells (HALPC) or dasatinib and quercetin (D+Q) were administrated to two-month-old Wistar rats after bile duct ligation (BDL).
RESULTS
Advanced premature senescence was evidenced in BA livers from early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but also present in surrounding hepatocytes. HALPC but not D+Q reduced the early marker of senescence p21 in BDL rats and improved biliary injury (serum γGT and expression) and hepatocytes mass loss ().
CONCLUSIONS
BA livers displayed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced early senescence and improved liver disease in a preclinical model of BA, providing encouraging preliminary results regarding the use of senotherapies in pediatric biliary cirrhosis.
Topics: Humans; Rats; Animals; Biliary Atresia; Liver Cirrhosis, Biliary; Rats, Wistar; Liver; Hepatocytes; Cellular Senescence
PubMed: 37204430
DOI: 10.18632/aging.204700 -
Frontiers in Immunology 2023Observational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence...
BACKGROUND
Observational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence establishing a causal relationship between the two, and a clear mechanism explaining this association, remains elusive.
METHODS
We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between PBC and osteoporosis. This analysis utilized five MR methods: inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analyses were performed, employing various models and testing methods, to assess the impact of heterogeneity and pleiotropy on the results and to confirm their robustness.
RESULTS
A causal relationship between PBC and osteoporosis risk was established through IVW analysis (OR: 1.049, 95%CI: 1.017-1.082, =0.002). Three other MR analyses corroborated these findings. Conversely, osteoporosis was not found to causally affect PBC risk, as evidenced by IVW analysis (OR: 0.941, 95%CI: 0.783-1.129, =0.511). Across all MR analyses, no heterogeneity or horizontal pleiotropy was detected among the instrumental variables (IVs). Furthermore, the leave-one-out analysis indicated that no single SNP disproportionately influenced the results, affirming the reliability of the bidirectional MR findings.
CONCLUSION
This study establishes a positive causal relationship between PBC and the risk of osteoporosis, while no definitive causal link was found from osteoporosis to PBC. These findings offer new insights and guidance for managing bone health in PBC patients.
Topics: Humans; Liver Cirrhosis, Biliary; Mendelian Randomization Analysis; Reproducibility of Results; Osteoporosis; Fractures, Bone
PubMed: 38162659
DOI: 10.3389/fimmu.2023.1269069 -
Frontiers in Immunology 2023Primary biliary cirrhosis (PBC) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms...
BACKGROUND
Primary biliary cirrhosis (PBC) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PBC and psoriasis remain poorly defined.
METHODS
In this study, we conducted bidirectional MR analysis to explore the causal relationship between PBC and psoriasis using four MR methods: inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results.
RESULTS
A causal relationship between the risk of PBC and psoriasis was identified, as confirmed by IVW analysis (OR: 1.081, 95%CI: 1.028~1.137, <0.05). The other three MR methods also produced similar results. However, psoriasis did not have a causal effect on PBC risk (OR: 1.022, 95%CI: 0.935~1.118, >0.05). The intercept of MR-Egger regression was 0.0013 (>0.05), indicating that genetic pleiotropy did not influence the results. Additionally, the leave-one-out analysis demonstrated the robustness of our MR findings.
CONCLUSION
This study reveals a causal relationship between PBC and psoriasis, with PBC increasing the risk of psoriasis, but not the reverse. This potential causal relationship offers a new perspective on the etiology of PBC.
Topics: Humans; Liver Cirrhosis, Biliary; Mendelian Randomization Analysis; Psoriasis; Genetic Pleiotropy; Nonoxynol
PubMed: 38239358
DOI: 10.3389/fimmu.2023.1264554 -
World Journal of Gastroenterology Jul 2015Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts,... (Review)
Review
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has been unknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author's findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC 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 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.
Topics: Autoantibodies; Biomarkers; Biopsy; Blood Chemical Analysis; Diagnosis, Differential; Diagnostic Imaging; Disease Progression; Genetic Markers; Genetic Predisposition to Disease; Humans; Liver Cirrhosis, Biliary; Liver Function Tests; Molecular Diagnostic Techniques; Phenotype; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors
PubMed: 26167070
DOI: 10.3748/wjg.v21.i25.7683 -
Clinical Reviews in Allergy & Immunology Jun 2015Primary biliary cirrhosis occurs more frequently in women, and previous studies indicated that the average age of primary biliary cirrhosis (PBC) onset makes pregnancy... (Review)
Review
Primary biliary cirrhosis occurs more frequently in women, and previous studies indicated that the average age of primary biliary cirrhosis (PBC) onset makes pregnancy in PBC patients uncommon. However, more recently, improved diagnostic testing has enabled detection of PBC in younger women, including those of childbearing age. This has led investigators to become increasingly interested in the relationship between the ontogeny of PBC and pregnancy. Published cases indicate that the typical age for pregnant women to be diagnosed with PBC is in the early 30s, and that during gestation, pruritus and jaundice are the most common symptoms. During gestation, susceptible women may experience onset of PBC resulting from the drastic changes in female hormones; this would include not only the mitochondrial damage due to accumulation of bile acids but also changes in the immune response during the different stages of pregnancy that might play an important role in the breakdown of self-tolerance. The mechanisms underlying the potential relationship between PBC and pregnancy warrant further investigation. For women first diagnosed with PBC during gestation, or those for whom first appearance of a flare up occurs during and postpartum, investigation of the immune response throughout gestation could provide new avenues for immunologic therapeutic intervention and the discovery of new treatment strategies for PBC.
Topics: Chimerism; Female; Humans; Liver Cirrhosis, Biliary; Pregnancy; Pregnancy Complications; Risk Factors; Sex Factors
PubMed: 25241227
DOI: 10.1007/s12016-014-8449-4 -
Orphanet Journal of Rare Diseases Jan 2008Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile... (Review)
Review
Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC.
Topics: Aged; Antibodies, Antinuclear; Autoimmune Diseases; Cholagogues and Choleretics; Female; Humans; Liver Cirrhosis, Biliary; Liver Transplantation; Male; Middle Aged; Sex Factors; Ursodeoxycholic Acid
PubMed: 18215315
DOI: 10.1186/1750-1172-3-1 -
British Journal of Hospital Medicine... Mar 2022Recent years have seen major advances in our understanding of primary biliary cholangitis, with the condition now renamed to reflect the majority of patients who do not... (Review)
Review
Recent years have seen major advances in our understanding of primary biliary cholangitis, with the condition now renamed to reflect the majority of patients who do not have cirrhosis. Data from large multicentre studies have greatly increased our knowledge of the natural history of primary biliary cholangitis, making the identification of higher risk patients clearer and facilitating the development of new medications. Recent guidelines have emphasised the importance of risk stratification, targeted treatment of symptoms and early prioritisation for second line therapies. The review summarises recent major developments in our understanding of primary biliary cholangitis and its management.
Topics: Humans; Liver Cirrhosis; Liver Cirrhosis, Biliary
PubMed: 35377202
DOI: 10.12968/hmed.2021.0450