A Preliminary Study on Clinical Characteristics of Patients With Autoimmune Liver Following Coronavirus Disease 2019

Objective To explore the clinical characteristics of liver function of patients with autoimmune liver disease (AILD) complicated with gallbladder stone (GS), so as to guide clinical practice. Methods From November 2009 to October 2018, at General Hospital of Tianjin Medical University, the clinical data of 386 patients with AILD were retrospectively analyzed. According to the relevant diagnostic criteria, 208 cases of autoimmune hepatitis (AIH), 129 cases of primary biliary cholangitis (PBC) and 49 cases of PBC-AIH overlap syndrome were screened out. The incidence, clinical characteristics and the changes of laboratory indicators including albumin, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of AILD patients complicated with GS were analyzed. Chi-square test, t test and rank sum test were performed for statistical analysis. Results There was no significant difference in the incidence between AILD, AIH, PBC and PBC-AIH overlap syndrome patients complicated with GS (32.9%, 127/386; 28.8%, 60/208; 36.4%, 47/129 and 40.8%, 20/49; respectively; P>0.05). Gallstones of AILD patients complicated with GS mostly were multiple and small stones with maximum diameter <1 cm (45.7%, 58/127 and 57.7%, 60/104, respectively). The age of initial diagnosis, the proportion of liver cirrhosis at inital diagnosis and the levels of ALP and GGT were higher in AILD patients complicated with GS than those of AILD patients without GS ((60.5±11.5) years vs. (57.6±11.5) years; 53.5%, 68/127 vs. 42.1%, 109/259; 154.00 U/L (89.00 U/L, 257.00 U/L) vs. 125.00 U/L (86.00 U/L, 212.00 U/L); 169.00 U/L (79.00 U/L, 343.00 U/L) vs. 128.60 U/L (48.00 U/L, 284.00 U/L); respectively); however the albumin level was lower than that of AILD patients without GS ((36.46±7.30) g/L vs. (38.34±7.58) g/L), and the differences were statistically significant (t=-2.361, χ2=4.506, Z=-2.192, -2.443, t=2.322; all P<0.05). The incidence of GS in AILD patients≥60 years old was higher than that AILD patients<60 years old (37.6%, 73/194 vs. 28.1%, 54/192), and the difference was statistically significant (χ2=3.948, P=0.047). The incidence of GS in AILD patients and AIH patients complicated with liver cirrhosis was higher than that in patients without liver cirrhosis (38.4%, 68/177 vs. 28.2%, 59/209; 35.7%, 35/98 vs. 22.7%, 25/110; respectively), and the differences were statistically significant (χ2=4.506 and 4.259, P=0.034 and 0.039). Conclusions AILD patients complicated with GS are common, most are multiple and small stones. When complicated with GS, the initial diagnosis may be delayed and the rate of liver cirrhosis at initial diagnosis may increase. The incidence of GS is high in AILD patients with older age and liver cirrhosis. Key words: Liver cirrhosis; Autoimmune liver disease; Gallbladder stone; Liver function; Age

The antibody and B cell responses after inactivated SARS-CoV-2 vaccination have not been well documented in patients with autoimmune liver disease (AILD). Therefore, we conducted a prospective observational study that included AILD patients and healthy participants as controls between July 1, 2021, and September 30, 2021, at the Second Affiliated Hospital of Chongqing Medical University. All adverse events (AEs) after the COVID-19 vaccination were recorded and graded. Immunoglobulin (Ig)-G antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG) and neutralizicadng antibodies (NAbs) were tested following full-course vaccination (BBIBP-CorV or CoronaVac). In addition, SARS-CoV-2-specific B cells were detected by flow cytometry. In total, 76 AILD patients and 136 healthy controls (HCs) were included. All AEs were mild and self-limiting, and the incidences were similar between the AILD and HCs. The seropositivity rates of anti-RBD-IgG and NAbs in AILD were 97.4% (100% in HCs, p = 0.13) and 63.2% (84.6% in HCs, p < 0.001), respectively. The titers of anti-RBD-IgG and NAbs were significantly lower in AILD patients than those in HCs. After adjusting for confounders, immunosuppressive therapy was an independent risk factor for low-level anti-RBD-IgG (adjusted odds ratio [aOR]: 4.7; 95% confidence interval [CI], 1.5-15.2; p = 0.01) and a reduced probability of NAbs seropositivity (aOR, 3.0; 95% CI, 1.0-8.9; p = 0.04) in AILD patients. However, regardless of immunosuppressants, the SARS-CoV-2-specific memory B cells responses were comparable between the AILD and HC groups. Our results suggest that inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) are safe, but their immunogenicity is compromised in patients with AILD. Moreover, immunosuppressants are significantly associated with poor antibody responses to the SARS-CoV-2 vaccines. These results could inform physicians and policymakers about decisions on screening the populations at higher risk of poor antibody responses to SARS-CoV-2 vaccines and providing additional vaccinations in patients with AILD.

Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic.

Background Early detection is crucial for the prognosis of patients with autoimmune liver disease (AILD). Due to the relatively low incidence, developing screening tools for AILD remain a challenge. Aims To analyze clinical characteristics of AILD patients at initial presentation and identify clinical markers, which could be useful for disease screening and early detection. Methods We performed observational retrospective study and analyzed 581 AILD patients who were hospitalized in the gastroenterology department and 1000 healthy controls who were collected from health management center. Baseline characteristics at initial presentation were used to build regression models. The model was validated on an independent cohort of 56 patients with AILD and 100 patients with other liver disorders. Results Asymptomatic AILD individuals identified by the health check-up are increased yearly (from 31.6% to 68.0%, p < 0.001). The cirrhotic rates at an initial presentation are decreased in the past 18 years (from 52.6% to 20.0%, p < 0.001). Eight indicators, which are common in the health check-up, are independent risk factors of AILD. Among them, abdominal lymph node enlargement (LN) positive is the most significant different (OR 8.85, 95% CI 2.73-28.69, p < 0.001). The combination of these indicators shows high predictive power (AUC = 0.98, sensitivity 89.0% and specificity 96.4%) for disease screening. Except two liver or cholangetic injury makers, the combination of AGE, GENDER, GLB, LN, concomitant extrahepatic autoimmune diseases, and familial history also shows a high predictive power for AILD in other liver disorders (AUC = 0.91). Conclusion Screening for AILD with described parameters can detect AILD in routine health check-up early, effectively and economically. Eight variables in routine health check-up are associated with AILD and the combination of them shows good ability of identifying high-risk individuals.

BackgroundThe association of autoimmune liver disease (AILD) and inflammatory bowel disease (IBD) is well documented. IBD affects about 45% of children with autoimmune sclerosing cholangitis (AISC) and about 20% of...

The influence of exercise at high temperature on adult males' routine blood indexes and biochemical indexes and the expression of HSP72 in peripheral blood lymphocytes (PBLs) was studied in order to provide theoretical ground for health supervision of adults receiving exercise at high temperature. 180 adult males were selected and divided into exercise group and control group, in which the exercise group was subdivided into subgroup 1 and subgroup 2 receiving exercise at high temperature in the afternoon and in the morning, respectively. Peripheral venous blood was phlebotomized before and after the exercise to examine routine blood indexes and blood biochemical indexes. The expression levels of HSP72 in PBLs were detected by flow cytometry. The results showed that the routine blood indexes and biochemical indexes in each group were within the range of normal values of male adults. There was no significant difference between each exercise group and control group in indexes before exercise. After exercise, the expression levels of HSP72 in PBLs in exercise groups were higher than those before exercise, and HSP72 expression levels in subgroup 1 were obviously higher than those in subgroup 2 and control group. The contents of ALT, urea, Na+, Cl-, Ca2+ and K+ in subgroups 1 and 2 were lower than those in control group, but CK level was higher than in control group (P<0.05). The contents of Na+ and Cl- in subgroup 1 were relatively lower than those in subgroup 2 (P<0.05). It was concluded that while receiving exercise at high temperature, adult males' HSP72 levels in PBLs could be increased and the biochemical indexes changed. Attention should be paid to health supervision to avoid obvious body injuries at high temperature.

Background: A high prevalence of autoimmune thyroid disease (AITD) has been observed in patients with autoimmune liver disease (AILD); however, data on the clinical relationship between AILD and AITD remain scant. We aimed to evaluate the relationship between AILD and AITD.Methods: We performed a retrospective study using medical records from 324 patients with AILD, 113 of whom had concurrent AITD.Results: Patients with autoimmune hepatitis (AIH) were more likely to develop AITD (45.8%), followed by autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC OS) (39.5%) and PBC (22.6%). Patients with concurrent AILD and AITD showed higher levels of immunoglobulin G (IgG) (21.5 g/L vs 16.3 g/L, p < .0001) and gamma globulin (γ-globulin) (27.1% vs 21.9%, p < .0001). IgG was positively correlated with thyroid antibodies [thymoglobulin antibody (TGAb) and thyroperoxidase antibody (TPOAb)] (r = 0.396, 0.322; p < .0001, p = .002, respectively). TPOAb positivity was highest in PBC patients with concurrent AITD (83.9%). Patients with concurrent PBC and AITD were significantly older than those with PBC alone (p = .0004). Patients with concurrent AIH and AITD had a higher homogenous nuclear pattern of antinuclear antibody positivity compared to those with AIH alone (p = .019). Thyroid dysfunction in AILD patients with concurrent AITD was principally characterized by Hashimoto’s thyroiditis (65.5%), and diffuse lesions were mainly found by thyroid ultrasound (53.1%).Conclusions: The high incidence of AILD concomitant with AITD, the higher levels of serum IgG and γ-globulin, and the strong correlation between thyroid antibodies and IgG suggest that close screening for AITD and accurate physical examinations should be performed for all patients with AILD.

BackgroundLiquid biopsies based on blood samples have been widely accepted as a diagnostic and monitoring tool for cancers, but extremely high sensitivity is frequently needed due to the very low levels of the specially selected DNA, RNA, or protein biomarkers that are released into blood. However, routine blood indices tests are frequently ordered by physicians, as they are easy to perform and are cost effective. In addition, machine learning is broadly accepted for its ability to decipher complicated connections between multiple sets of test data and diseases.ObjectiveThe aim of this study is to discover the potential association between lung cancer and routine blood indices and thereby help clinicians and patients to identify lung cancer based on these routine tests.MethodsThe machine learning method known as Random Forest was adopted to build an identification model between routine blood indices and lung cancer that would determine if they were potentially linked. Ten-fold cross-validation and further tests were utilized to evaluate the reliability of the identification model.ResultsIn total, 277 patients with 49 types of routine blood indices were included in this study, including 183 patients with lung cancer and 94 patients without lung cancer. Throughout the course of the study, there was correlation found between the combination of 19 types of routine blood indices and lung cancer. Lung cancer patients could be identified from other patients, especially those with tuberculosis (which usually has similar clinical symptoms to lung cancer), with a sensitivity, specificity and total accuracy of 96.3%, 94.97% and 95.7% for the cross-validation results, respectively. This identification method is called the routine blood indices model for lung cancer, and it promises to be of help as a tool for both clinicians and patients for the identification of lung cancer based on routine blood indices.ConclusionsLung cancer can be identified based on the combination of 19 types of routine blood indices, which implies that artificial intelligence can find the connections between a disease and the fundamental indices of blood, which could reduce the necessity of costly, elaborate blood test techniques for this purpose. It may also be possible that the combination of multiple indices obtained from routine blood tests may be connected to other diseases as well.

Coeliac disease in autoimmune liver disease: A cross-sectional study and a systematic review

Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper.

This study aims to explore the clinical effect of Arbidol (ARB) combined with adjuvant therapy on patients with coronavirus disease 2019 (COVID‐19). The study included 62 patients with COVID‐19 admitted to the First Hospital of Jiaxing from January to March 2020, and all patients were divided into the test group and the control group according to whether they received ARB during hospitalization. Various indexes in the two groups before and after treatment were observed and recorded, including fever, cough, hypodynamia, nasal obstruction, nasal discharge, diarrhea, C‐reactive protein (CRP), procalcitonin (PCT), blood routine indexes, blood biochemical indexes, time to achieve negative virus nucleic acid, and so on. The fever and cough in the test group were relieved markedly faster than those in the control group (P < .05); there was no obvious difference between the two groups concerning the percentage of patients with abnormal CRP, PCT, blood routine indexes, aspartate aminotransferase, and alanine aminotransferase (P > .05); the time for two consecutive negative nucleic acid tests in the test group were shorter than that in the control group; the hospitalization period of the patients in the test group and control group were (16.5 ± 7.14) days and (18.55 ± 7.52) days, respectively. ARB combined with adjuvant therapy might be able to relieve the fever of COVID‐19 sufferers faster and accelerate the cure time to some degree, hence it's recommended for further research clinically.

Prevalence and heterogeneity of antinuclear antibody patterns in adult Italian patients with autoimmune liver diseases: Our experience

Objective: To analyze the chorological changes of diagnosis in patients with autoimmune liver disease (AILD) and related factors for early diagnosis. Methods: A total of 581 patients with age ranged from 16 to 81 were retrospectively analyzed, who were admitted to Tianjin Medical University General Hospital with AILD during January 2000 to December 2017. Age at diagnosis, diagnostic method and cirrhosis at diagnosis were compared in different groups according to admission period as 2000-2005, 2006-2011, 2012-2017. Results: The diagnostic rate of AILD showed an upward trend during the past near two decades. The proportion of AILD patients diagnosed via health examination was increasing year by year mainly by elevated transaminases (P<0.001). The mean age at diagnosis in our AILD patients were younger at present, especially in men (P=0.044). The proportion of cirrhosis at diagnosis was gradually reduced in three different periods respectively [77.78%(21/27), 41.58% (79/190), 25.00%(91/364), P<0.001], which were coincident in patients with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (P<0.001). The shrinking trend of cirrhosis at diagnosis was significantly correlated with the increasing application of health examination (r=-0.549, P<0.001). Conclusions: Extensive application of health examination expands the diagnostic rate of AILD. During the past 18 years, more young patients are diagnosed with AILD. The proportion of severe cases such as cirrhosis at diagnosis is decreasing. Screening of immunological examinations in patients with abnormal transaminases is needed and critical to the early diagnosis of asymptomatic AILD.

While the association between inflammatory bowel disease (IBD) and autoimmune liver disease (AILD) is well-established, prevalence estimates vary considerably across studies. In this study, a meta-analysis was performed to determine the pooled prevalence and characterize the bidirectional relationship between AILD and IBD. A systematic search was conducted in PubMed, Embase, and the Cochrane Library to identify observational studies reporting the prevalence between IBD and AILD. Data were extracted for eligible studies, and pooled prevalence estimates were derived using random effects models. Subgroup analyses were performed based on IBD and AILD subtypes, gender, race, geographical region, extent of IBD, and publication year. Of the 9347 citations, 172 studies involving 1 550 966 participants were included. The pooled prevalence of IBD among AILD patients, based on 65 studies, was 32.05% (95% CI 22.83%-42.94%; I2 = 100%, p < 0.001). Specifically, the prevalence of IBD in patients with primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cirrhosis (PBC) was 62.79% (95% CI 57.74%-67.57%), 3.54% (95% CI 2.08%-5.96%), and 1.99% (95% CI 1.05%-3.74%), respectively. The pooled prevalence of AILD among IBD patients, based on 109 studies, was 2.28% (95% CI 1.88%-2.76%; I2 = 100%, p < 0.001). Prevalence of PSC, AIH, and PBC in IBD patients was 2.24% (95% CI 1.85%-2.70%), 0.59% (95% CI 0.24%-1.47%), and 0.32% (95% CI 0.09%-1.13%), respectively. Subgroup analyses revealed significant variations in prevalence associated with gender, race, IBD extent, geographic region, and publication year. This study reveals a significant bidirectional association in the prevalence of AILD and IBD, supporting the gut-liver axis theory. Further research is needed to elucidate causal mechanisms.

Autoimmune liver disease (ALD) in children, when not diagnosed and treated timely, are characterised by a progressive course leading to liver cirrhosis. Monitoring the progression of the disease is crucial for evaluating the effectiveness of treatment in ALD patients. We believe that the use of ultrasound elastography is not only valuable for diagnosing liver fibrosis but also for monitoring the course of ALD in children, representing a promising research method. Purpose - to assess the feasibility of using shear wave elastography for diagnosing liver fibrosis and monitoring the course of ALD in children. Materials and methods. In 108 children with ALD aged 3-18 years, examined at the Department of Pediatric Hepatology of the SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O. Lukyanova of the National Academy of Medical Sciences of Ukraine», from 2019 to 2023, ultrasound shear wave elastography (2D-SWE) parameters were evaluated before treatment (baseline) and at 6, 12, 24, and 36 months of therapy, depending on the stage of liver fibrosis determined by histological method using the Metavir scoring system (F0-F4) in all children. Statistical analysis was performed using GraphPad Prism 9 version 10.0.0. Results. The mean age of the children was 11 years (range 8-13.8 years), with 91% (n=98) having liver fibrosis stage ≥F2 according to Metavir. There was a significant correlation between complete biochemical remission and median 2D-SWE at 12, 24, and 36 months of treatment (p=0.0002; p=0.002; p=0.0004, respectively). The area under the ROC curve (AUC) for diagnosing liver fibrosis stage ≥F3 and F4 at 0, 6, 12, 24 and 36 months of treatment was 0.81; 0.78; 0.67; 0.81; 0.75 and 0.80; 0.91; 0.84; 0.89; 0.92, respectively. The optimal cutoff value for median 2D-SWE was 10.1 kPa; 8.9 kPa; 9.1 kPa; 8.9 kPa; 7.0 kPa and 14.0 kPa; 10.5 kPa; 10.2 kPa; 9.7 kPa; 8.1 kPa, respectively. Conclusions. Shear wave elastography is an effective method for diagnosing fibrosis ≥F3 and cirrhosis in children with ALD. Reduction in 2D-SWE values in children with ALD during treatment is a predictor of its effectiveness. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.