ABSTRACT
Objective To investigate the expression level of neutrophil extracellular traps (NET) in the peripheral blood and liver tissue of primary biliary cholangitis (PBC) patients and its correlation with clinical biochemical parameters. Methods A total of 24 PBC patients who were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine, from August 2016 to August 2020 were enrolled, as well as 8 patients with primary sclerosing cholangitis (PSC) and 19 patients with autoimmune hepatitis (AIH) matched for age, and 19 healthy individuals were enrolled as healthy control group (HC group). The serum level of myeloperoxidase (MPO) was measured, and its correlation with clinical indices were analyzed. Immunofluorescence assay was used to measure the expression of NET in the liver of PBC patients, and an in vitro experiment was to compare the ability of peripheral blood neutrophils to produce NET between PBC patients and healthy controls. Normally distributed continuous data were expressed as mean±standard deviation, and the independent samples t -test was used for comparison between two groups; for the non-normally distributed continuous data expressed as M ( P 25 - P 75 ), the Kruskal-Wallis H test was used for comparison between multiple groups, and the Mann-Whitney U test was used for comparison between two groups. A correlation analysis was performed for MPO level and liver-related laboratory markers, and the Spearman's correlation coefficient was calculated. Results The serum level of MPO in the PBC group was increased to 811.21 (450.67-1 216.20) ng/mL, which was significantly higher than that in the AIH group [468.58 (142.63-812.43) ng/mL] and the HC group [357.54 (203.52-811.21) ng/mL] ( P < 0.05), suggesting that there was a significant increase in the production of NET in peripheral blood of PBC patients. The PSC patients had a serum MPO level of 763.56 (489.59-1 633.14) ng/mL, which was significantly higher than that in the HC group ( P < 0.05). MPO level was positively correlated with alkaline phosphatase ( r =0.500, P < 0.05), gamma-glutamyl transpeptidase ( r =0.426, P < 0.05), alanine aminotransferase ( r =0.521, P < 0.05), and aspartate aminotransferase ( r =0.547, P < 0.01). Confocal immunofluorescence showed colocalization of H3Cit and MPO in the liver of PBC patients. In vitro experiment showed that compared with the HC group, the PBC group had an increase in NET produced by peripheral blood neutrophils after in vitro stimulation and an increase in spontaneous production of NET. Conclusion There is an increase in NET in peripheral blood and liver of PBC patients, and the content of peripheral blood NET is positively correlated with biochemical parameters of liver function. NET may become a novel biomarker for assessing the severity of PBC.
ABSTRACT
Autoimmune hepatitis (AIH) is an immune-mediated liver disease with hepatocytes as the main target cells. It is characterized by the high immunoglobulin G level and the presence of autoantibodies, and histological observation shows interface hepatitis at the portal area caused by a large amount of lymphoplasmacytic infiltration. The pathogenesis of AIH has not been fully elucidated. At present, glucocorticoid combined with azathioprine is mainly used as non-specific immunosuppressive therapy, and most patients tend to have good response; however, rebound or relapse is often observed during dose reduction or after drug withdrawal, so most patients need long-term maintenance therapy. This article briefly reviews the advances in the pathogenesis of AIH and the potential new targets for clinical intervention, in order to provide a reference for clinical translational research.
ABSTRACT
Primary biliary cholangitis (PBC) is an autoimmune-mediated chronic cholestatic liver disease, with the typical biochemical manifestation of significantly elevated alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT), with or without mild-to-moderate elevation of aminotransferases. ALP and GGT play an important role in the diagnosis and monitoring of PBC. With a deeper understanding of PBC, the significance of elevated aminotransferases in diagnosis and treatment has attracted more and more attention. This article briefly summarizes the significance of elevation of aminotransferases in PBC patients.
ABSTRACT
Primary biliary cholangitis (PBC) is an autoimmune-mediated chronic cholestatic liver disease, with the typical biochemical manifestation of significantly elevated alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT), with or without mild-to-moderate elevation of aminotransferases. ALP and GGT play an important role in the diagnosis and monitoring of PBC. With a deeper understanding of PBC, the significance of elevated aminotransferases in diagnosis and treatment has attracted more and more attention. This article briefly summarizes the significance of elevation of aminotransferases in PBC patients.
ABSTRACT
Autoimmune hepatitis (AIH) is a liver inflammatory disease mediated by autoimmune response and may progress to liver failure and liver cirrhosis without treatment. The goal of AIH treatment is to achieve biochemical remission and histological remission. Currently immunosuppressant therapy is the standard therapy for AIH, i.e., prednisone/prednisolone alone or combined with azathioprine. For the patients who do not tolerate or have poor response to the standard therapy, second-line treatment regimen, including mycophenolate mofetil, can be considered. Recent studies have shown that various factors participate in the development and progression of AIH, such as immune function, gut microbiota, vitamin D, and mental state, which may become the potential therapeutic targets for AIH. This article reviews related studies on the standard therapies for AIH and highlights the potential therapeutic targets for AIH treatment.
ABSTRACT
Autoimmune hepatitis (AIH) is a chronic persistent liver inflammatory disease associated with autoimmune response. AIH is commonly seen in women, and those without intervention may progress to liver cirrhosis and liver cancer. The main histological feature of AIH is moderate to severe interfacial hepatitis with lymphocyte-plasma cell infiltration. The clinical manifestations of AIH have obvious heterogeneity, and it is difficult to differentiate AIH from other liver diseases with similar clinical, biochemical, serological, and histological features. Misdiagnosis may seriously affect the prognosis of patients. This article reviews the key points in the diagnosis and differential diagnosis of AIH, hoping to provide help for clinical diagnosis and treatment.
ABSTRACT
Autoimmune hepatitis (AIH) is an autoimmune liver disease induced by environmental factors in individuals with genetic susceptibility, with the main features of positive serum autoantibody, hypergammaglobulinemia, elevated transaminases, and interface hepatitis. The pathogenesis of AIH remains unknown, high heterogeneity is observed in clinical diagnosis and treatment, and thus it is of great importance to establish individualized precise diagnosis and treatment. Therefore, this article reviews the research advances and difficult issues in this field.
ABSTRACT
Autoimmune liver disease is a group of hepatobiliary injuries mediated by abnormal immunity. It mainly includes autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. Recently, an advancement of diagnostic technology has improved the detection and treatment of autoimmune hepatitis. However, it is easy to be confused with other liver diseases. Thus, the standardization of diagnosis and treatment of autoimmune liver diseases has become a main concern. Moreover, new progress has been made in basic research and clinical treatment of autoimmune liver diseases since 2018. In this review, we have introduced the latest research advances for the diagnosis and treatment of autoimmune liver diseases.
ABSTRACT
IgG4-relaed hepatobiliary diseases (IgG4-HBD) are the hepatobiliary manifestations of IgG4-related disease, a multisystem fibro-inflammatory disorder. Previous studies on the pathogenesis of genetics and immunology have provided significant assistance in understanding the disease, rational diagnosis and treatment, but there are still many unknowns and challenges. The current research progress summarizes several factors influencing fibrosis and inflammation in the pathogenesis of disease.
ABSTRACT
Objective@#To compare and analyze patient’s general condition, laboratory testing and therapeutic responses of isolated immunoglobulin G4- related sclerosing cholangitis (IgG4-SC) and immunoglobulin G4 sclerosing cholangitis combined autoimmune pancreatitis (IgG4-SC/AIP).@*Methods@#A retrospective study was conducted on IgG4-SC patients who attended outpatient and inpatients department of our hospital from April 2014 to March 2018 and their demographic characteristics, laboratory testing, and therapeutic responses were statistically analyzed. Normal distribution of continuous variables was compared with t-test, non-normal distribution of continuous variables was compared using the Mann-Whitney U test, and the categorical variables were compared with χ 2 test.@*Results@#29 IgG4-SC patients were included, including 19-isolated IgG4-SC and 10 IgG4-SC combined AIP (IgG4-SC/AIP). The average age of onset in the isolated IgG4-SC group was (46.06±19.03) years which was lower than IgG4-SC/AIP group (62.60±15.11), t = -2.360, P < 0.05. The median IgG4 in IgG4-SC/AIP patients is higher than that in isolated IgG4-SC, respectively 10.87 (3.73 ~ 20.13) and 3.14 (2.37 ~ 4.78)g/L(U = 159.000, P < 0.05). IgG4/IgG ratio is higher in IgG4-SC/AIP, than that in isolated IgG4-SC, respectively 0.62(0.23 ~ 0.86) and 0.16(0.10 ~ 0.21), U = 130.000, P < 0.05. Liver cirrhosis was more common in isolated IgG4-SC group (47%) than the IgG4-SC/AIP group (0), χ 2 = 9.637, P < 0.05. The median biochemical response time of isolated IgG4-SC group was 3.00 (2.00 to 4.00) months, which was longer than 1.00 (1.00 to 1.25) months of IgG4-SC/AIP group, U = 30.000, P < 0.05. The biochemical recurrence rate of isolated IgG4-SC group was 32%, which was lower than that of IgG4-SC/AIP (χ 2 = 6.461, P < 0.05).@*Conclusion@#Serum IgG4 level and IgG4/IgG ratio were higher in patients with IgG4-SC/AIP group, and therapeutic responses in isolated IgG4-SC patients were worse than that of IgG4-SC/AIP patients. The efficacy of glucocorticoid monotherapy and immunosuppressive agents combined with glucocorticoid therapy demonstrated no considerable difference in IgG4-SC patients.
ABSTRACT
IgG4-associated hepatobiliary diseases are group of autoimmune diseases characterized by lymphoplasmacytic infiltrates with an elevated serum IgG4 levels, affecting pancreas and biliary tract. In addition, it mainly includes IgG4-related sclerosing cholangitis, IgG4-related autoimmune pancreatitis and IgG4-related autoimmune hepatitis. An accurate diagnosis helps to avoid unnecessary surgery. Notably, an early diagnosis and treatment can improve the prognosis and enhance the quality of life. This review will focus on research advances and difficulties encountered in the study of IgG4 related hepatobiliary diseases.
ABSTRACT
Autoimmune liver diseases include autoimmune hepatitis (AIH),primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)and so on. The simultaneous presence of features of AIH,PBC or PSC called overlap syndrome,usually has a progressive course toward cirrhosis and liver failure if without prompt management. Early diagnosis and treatment can significantly improve the prognosis. This article summarized the advances in diagnosis and treatment of autoimmune liver diseases overlap syndrome in recent years.
ABSTRACT
Autoimmune hepatitis (AIH)is a chronic progressive immune-mediated inflammatory liver disease. Both adults and children could be involved and women are more often affected. AIH is characterized by elevation of serum IgG/hypergammaglobulinemia,autoantibodies and interface hepatitis with diverse clinical spectrum. The incidence of AIH is increasing in recent years. If not treated timely,it may lead to cirrhosis and liver failure. Immunosuppressive therapy is crucial for improving patients'survival rate. This article summarized the advances in diagnosis and treatment of AIH.
ABSTRACT
Autoimmune liver diseases (AILDs),including mainly autoimmune hepatitis (AIH),primary biliary cholangitis (PBC),primary sclerosing cholangitis (PSC),IgG4-related sclerosing cholangitis (IgG4-SC),and overlap syndromes,are characterized by circulating autoantibodies,inflammatory liver histology,and increased level of serum immunoglobulins. Early diagnosis and management can significantly improve the prognosis of patients and their quality of life. This editorial focused on the research progress and difficulties encountered in studies on AILDs in China.
ABSTRACT
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapeutic drug for PBC and can delay disease progression, but as high as 40% of patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment. Other drugs such as fibrates, glucocorticoids, immunosuppressants, biological agents, and mesenchymal stem cells are gradually used in clinical practice and bring new hope to patients with refractory PBC.
ABSTRACT
Autoimmune liver diseases are a group of abnormal autoimmune-mediated inflammatory hepatobiliary injuries, mainly including autoimmune hepatitis(AIH), primary biliary cholangitis(PBC), and primary sclerosing cholangitis (PSC). The diagnosis and treatment of autoimmune liver diseases, an important type of non-viral liver disease, have become a prominent issue in hepatology. In 2016, many new advances have been achieved in the clinical and basic research on autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, the proposal of UK-PBC risk score, and the research on gut microbiota associated with PSC. This article reviews the research advances in the diagnosis and treatment of autoimmune liver diseases in 2016.
ABSTRACT
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving the interlobular bile ducts and can progress to liver cirrhosis and liver failure.Early diagnosis and management can significantly improve the prognosis of such patients and their quality of life.This article focuses on the achievements of PBC research and related difficult issues in China,with reference to the clinical practice guidelines for PBC by European Association for the Study of the Liver in 2017 and experience in clinical practice.
ABSTRACT
Background:Activation of hepatic stellate cells( HSCs)plays a pivotal role in development of liver fibrosis. Interleukin-17(IL-17)is the most important effector of T helper 17(Th17)cells that causes inflammatory cell infiltration and tissue damage. Preliminary studies showed that the number of IL-17-positive cells in liver tissue was positively correlated with the severity of liver fibrosis in patients with chronic hepatitis B and autoimmune hepatitis. However,the mechanism of IL-17 in liver fibrosis is not yet clarified. Aims:To investigate the effect of IL-17 on activation of human HSC cell line LX2 and collagen expression. Methods:Human HSC cell line LX2 was treated with different concentrations of IL-17. Viability of LX2 cells was measured by CCK-8 assay. mRNA expressions of α-smooth muscle actin(α-SMA), type Ⅰ collagen(Col-Ⅰ)and Col-Ⅲ were determined by real-time PCR. Protein expressions of α-SMA、Col-Ⅰ and Col-Ⅲ were detected by immunofluorescence. Results: Viability of LX2 cells increased with the increase of IL-17 concentration,but no significant differences were seen between any two groups(P > 0. 05). mRNA expressions of α-SMA, Col-Ⅰ and Col-Ⅲ in IL-17 treatment group(100 ng/ mL)were significantly higher than those in blank control group(P <0. 05). With the increase of IL-17 concentration,protein expressions of α-SMA,Col-Ⅰ and Col-Ⅲ gradually increased. Conclusions:IL-17 can promote the activation of HSCs and expressions of Col-Ⅰ and Col-Ⅲ,thereby contributing to the development of liver fibrosis.
ABSTRACT
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, cirrhosis, and even liver failure. At present, the only drug approved for the treatment of PBC is ursodeoxycholic acid (UDCA), but up to 40% of PBC patients have suboptimal response to UDCA, and the risk of related complications is increased. Nowadays, other drugs and treatment methods, such as fibrates, glucocorticoids, immunosuppressants, obeticholic acid, biological agents, and mesenchymal stem cells, have been gradually applied in clinical practice and have brought the hope for the treatment of these patients.
ABSTRACT
In recent years, autoimmune hepatitis (AIH) has attracted more and more attention due to its unique clinicopathological features. However, its incidence and clinical features remain unclear, and systematic and in-depth studies are still needed. This article reviews the epidemiology, etiology, pathogenesis, clinical features, and diagnosis and treatment of AIH and points out that clinical studies or animal models of AIH have proved the effects of TNF-α neutralizing antibody, rituximab, all-trans retinoic acid, and regulatory T cell transplantation in the treatment of AIH.