Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

OBJECTIVE: To determine features of the clinical manifestation in patients with primary biliary cirrhosis (PBC), and to provide a scientific basis for diagnosis of PBC.
 METHODS: A total of 102 patients with PBC treated in the Second Xiangya Hospital, Central South University, from January 2013 to January 2015 were retrospectively analyzed. The patients' general condition, clinical manifestations, serum biochemical and immunological parameters were detected.
 RESULTS: Of the 102 PBC patients, 91 (89.21%) patients were female. The main symptoms in these patients were fatigue, poor appetite, dry mouth, nausea, vomiting, pruritus, stomachache, and abdominal distension. The major signs were jaundice, splenomegaly, hepatomegaly, edema, and ascites. The main features of serum biochemical parameters in these patients included the increase of alkaline phosphatase and gamma glutamyltranspeptidase (GGT), especially the GGT. The anti-mitochondrial antibodies-M2 (AMA-M2) in 81 and 21 patients was positive and negative, respectively. The differences between the AMA-MA positive and negative groups were not statistically significant (P>0.05). According to clinical manifestation, 102 patients were classified into 2 groups: A non-cirrhosis group (n=56) and a cirrhosis group (n=46). The positive rates in these 2 groups, such as ANA, AMA-M2, anti-gp210, anti-Sp100, anti-Ro52, anti-PML, were 54.35%, 89.13%, 41.30%, 13.04%, 43.38% and 10.87% vs 57.14%, 71.43%, 42.86%, 12.5%, 51.79% and 3.71%, respectively, with no significant difference between them (P>0.05). However, there was significant difference in the positive rate of anti-3E-EPO between the above 2 groups (86.78% vs 58.93%, P<0.05). The positive rates of AMA-M2 and anti-3E-EPO in 30 patients diagnosed by hepatic histopathological examination were higher than those of other antibodies.
 CONCLUSION PBC mainly affects middle-aged women, and its clinical manifestation is various. The autoantibody tests play an important role in diagnosis of PBC. Checking for AMA-A2 and anti-3E-BPO can improve the positive rate of PBC. Liver histopathological examination may provide useful information on disease severity, which can determine the histological stage when the patient's serum autoantibodies are negative.
Alkaline Phosphatase ; metabolism ; Autoantibodies ; blood ; Female ; Humans ; Liver Cirrhosis, Biliary ; diagnosis ; pathology ; Male ; Mitochondria ; Retrospective Studies ; gamma-Glutamyltransferase ; metabolism

OBJECTIVETo evaluate the expression of microRNA (miR)-let-7b in peripheral blood cells of patients with primary biliary cirrhosis (PBC) and investigate its relationship to clinical disease parameters.

METHODSPeripheral blood and serum samples were obtained for study from 60 PBC patients and 60 healthy controls. Peripheral blood cells were extracted and subjected to real-time PCR to measure miR-let-7b expression. Serum levels of interleukin (IL)-18, total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured by standard biochemical assays. The relationship between miR-let-7b expression and disease parameters was assessed by Spearman's rank correlation test.

RESULTSPBC patients showed significantly lower expression of miR-let-7b in peripheral blood cells than healthy controls (P less than 0.001); moreover, the miR-let-7b expression level decreased in parallel to increases in disease severity (stage I > II / III > IV). In PBC patients, the miR-let-7b expression was significantly correlated with Mayo risk scores (r = -0.4930, P less than 0.001), IL-18 (r = -0.4643, P less than 0.001) and ALP (r = -4119, P less than 0.001), but not with TBIL or GGT.

CONCLUSIONDecreased expression of miR-let-7b may be associated with development and progression of PBC, and this miRNA may represent a novel target of improved diagnostic and preventive strategies for PBC.

Adult ; Aged ; Alkaline Phosphatase ; blood ; Bilirubin ; blood ; Case-Control Studies ; Female ; Humans ; Interleukin-18 ; blood ; Liver Cirrhosis, Biliary ; blood ; Male ; MicroRNAs ; metabolism ; Middle Aged ; gamma-Glutamyltransferase ; blood

OBJECTIVETo evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy.

METHODSThe clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test.

RESULTSThere was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05).

CONCLUSIONSP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Adult ; Aged ; Antibodies, Antinuclear ; blood ; Antigens, Nuclear ; immunology ; Autoantibodies ; blood ; Autoantigens ; immunology ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Adult ; Bilirubin ; blood ; Biomarkers ; blood ; Disease Progression ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; blood ; drug therapy ; etiology ; Liver Function Tests ; Male ; Middle Aged ; S-Adenosylmethionine ; therapeutic use ; Ursodeoxycholic Acid ; therapeutic use

OBJECTIVETo observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage.

METHODSSixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years.

RESULTSAfter 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological

CONCLUSIONCombined therapy of Tongdan Decoction and UDCA showed a better therapeutic effect: than UDCA monotherapy on PBC, especially in improving immunological indices and histopathological hepatic changes.

Antigens, CD ; blood ; Biomarkers ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin G ; blood ; Inflammation ; blood ; complications ; Liver Cirrhosis, Biliary ; blood ; drug therapy ; immunology ; pathology ; Male ; Middle Aged ; Ursodeoxycholic Acid ; therapeutic use

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a slowly progressing autoimmune disease of the liver that is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Serum total bilirubin is one of the various prognostic factors that have been proposed. A recent study found that PBC with accompanying autoimmune hepatitis (AIH) carries a negative prognosis. This study examined the clinical characteristics of PBC and analyzed the factors that affect its prognosis. METHODS: Patients diagnosed with PBC between January 1998 and December 2010 based on clinical and histopathological findings were compiled and analyzed retrospectively. RESULTS: Among 27 patients, 24 (1 male and 23 females, ages 50.0+/-9.3 years) were followed up. The follow-up period was 8.6+/-0.9 years. Of the 24 patients, 9 patients progressed to liver cirrhosis (LC). Comparison between patients who did and did not progress to LC revealed statistically significant differences in the patients' serum total bilirubin (2.7+/-1.8 vs. 0.8+/-0.4, P=0.012), the Mayo risk score (5.1+/-0.7 vs. 3.9+/-0.6, P=0.001), the revised IAHG (International Autoimmune Hepatitis Group) score (9.2+/-2.3 vs. 5.4+/-3.0, P=0.004) and frequency of AIH overlap (5/9 [55.6%] vs. 0/15 [0%], P=0.001) at the time of diagnosis. CONCLUSIONS: We propose that serum total bilirubin, the Mayo risk score, and the revised IAHG score at the time of diagnosis are helpful for predicting PBC prognosis. In particular, since all of the patients with accompanying AIH progressed to LC, the presence of overlap syndrome at the time of diagnosis is helpful for predicting PBC prognosis and providing an adequate treatment.
Adult ; Aged ; Bilirubin/blood ; Female ; Follow-Up Studies ; Humans ; Liver Cirrhosis, Biliary/*diagnosis/pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; *Severity of Illness Index

Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In addition to typical clinical findings as fever, hepatosplenomegaly, and cachexia, VL is associated with autoimmune phenomena. To date, VL mimicking or exacerbating various autoimmune diseases have been described, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and autoimmune hepatitis (AIH). Herein, we presented a patient with VL who had overlapping clinical features with SLE, AIH, as well as antimitochondrial antibody (AMA-M2) positive primary biliary cirrhosis.
Adult ; Autoantibodies/blood ; Bone Marrow/pathology ; Cytological Techniques ; Diagnosis, Differential ; Female ; Hepatitis, Autoimmune/complications/*pathology ; Histocytochemistry ; Humans ; Leishmaniasis, Visceral/complications/*diagnosis/*pathology ; Liver/pathology ; Liver Cirrhosis, Biliary/complications/*pathology ; Lupus Erythematosus, Systemic/complications/*pathology

OBJECTIVETo investigate the correlation between ER-a in the liver and cytokines of T lymphocytes subsets and serum signatures in PBC patients.

METHODSThe research is performed with cross-sectional study. 80 PBC women patients without treatment were enrolled in PBC group, 10 healthy women as baseline-matched in healthy-control group, and 20 patients with non-autoimmune liver disease in non-PBC control group. The expression of IL-6, IL-8, IL-22, TNFa, IFNgamma, AMA-M2, Sp100 and gp210 were analyzed in Peripheral Blood using ELISA in all groups, and ER-a of patients were performed on tissues from liver biopsies in PBC group and non-PBC control group with immunohistochemistry. Spearman correlation test were performed on the indices to identified the association of all Parameters. numerical data were compared with Wilcoxon rank-sum test.

RESULTSCompared with healthy-control group, expression of serum cytokines are significantly higher in PBC and non-PBC groups (P less than 0.01), while no significant difference were observed between PBC and non-PBC groups. The positive rate of ER-a in PBC patients liver tissues in PBC group is higher than that in non-PBC group (Z=4.82, P less than 0.01). Expression of ER-a is positively correlated with positive rates of AMA-M2 antibody, Sp100 and gP210 of tissues of PBC patients ( r=0.898, 0.819, 0.814, P less than 0.01). ER-a is positive correlated with the expression of cytokines, among which the coefficient of correlation of IL-22, TNFa, IFNgamma is more than 0.7 (r=0.71, 0.89, 0.82, P less than 0.01), AMA-M2, Sp100, gp210 is negative in serum of non-PBC control group. No obviously correlations were indicated between the expression of ER-a and cytokines.

CONCLUSIONA high level of expression of cytokines in the serum might be one of the factors of etiopathogenesis of PBC.

Autoantibodies ; blood ; Biomarkers ; blood ; Case-Control Studies ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Interleukins ; blood ; Liver ; metabolism ; Liver Cirrhosis, Biliary ; blood ; immunology ; Middle Aged

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibody and histologic findings of nonsuppurative destructive cholangitis. Although the diagnosis is straightforward, it could be underdiagnosed because of its asymptomatic presentation, or underrecognition of the disease. UDCA in a dose of 13-15 mg/kg is the widely approved therapy which can improve the prognosis of patients with PBC. However, one-third of patients does not respond to UDCA therapy and may require liver transplantation. Every effort to diagnose PBC in earlier stage and to develop new therapeutic drugs and clinical trials should be made.
Autoantibodies/blood ; Autoimmunity/immunology ; Cholagogues and Choleretics/therapeutic use ; Humans ; Liver Cirrhosis, Biliary/*diagnosis/pathology/*therapy ; Liver Transplantation ; Ursodeoxycholic Acid/therapeutic use