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In this Editorial, we highlight the possible role that metabolism dysfunction-associated steatotic liver disease (MASLD) may play in the future, regarding liver disease in patients with transfusion-dependent β-thalassemia (TDBT). MASLD is characterized by excessive accumulation of fat in the liver (hepatic steatosis), in the presence of cardiometabolic factors. There is a strong correlation between the occurrence of MASLD and insulin resistance, while its increased prevalence parallels the global epidemic of diabetes mellitus (DM) and obesity. Patients with TDBT need regular transfusions for life to ensure their survival. Through these transfusions, a large amount of iron is accumulated, which causes saturation of transferrin and leads to the circulation of free iron molecules, which cause damage to vital organs (primarily the liver and myocardium). Over the past, the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C, for which modern and effective treatments have been found, resulting in successful treatment. Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths, and an increase in their life expectancy. This increased survival makes them vulnerable to the onset of diseases, which until recently were mainly related to the non-thalassemic general population, such as obesity and DM. There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence. However, it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia (Padeniya et al, BJH), that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis. These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence, the risk factors, and the effect of MASLD on these patients.

UNASSIGNED: Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed to relate to central sensitization in humans, that is, Human Assumed Central Sensitization (HACS). The aims of this systematic review were to identify non-invasive objective markers of HACS and the instruments to assess these markers in patients with fibromyalgia (FM).
UNASSIGNED: A systematic review was conducted with the following inclusion criteria: (1) adults, (2) diagnosed with FM, and (3) markers and instruments for HACS had to be non-invasive. Data were subsequently extracted, and studies were assessed for risk of bias using the quality assessment tools developed by the National Institute of Health.
UNASSIGNED: 78 studies (n= 5234 participants) were included and the findings were categorized in markers identified to assess peripheral and central manifestations of HACS. The identified markers for peripheral manifestations of HACS, with at least moderate evidence, were pain after-sensation decline rates, mechanical pain thresholds, pressure pain threshold, sound \'pressure\' pain threshold, cutaneous silent period, slowly repeated evoked pain sensitization and nociceptive flexion reflex threshold. The identified markers for central manifestations of HACS were efficacy of conditioned pain modulation with pressure pain conditioning and brain perfusion analysis. Instruments to assess these markers are: pin-prick stimulators, cuff-algometry, repetitive pressure stimulation using a pressure algometer, sound, electrodes and neuroimaging techniques.
UNASSIGNED: This review provides an overview of non-invasive markers and instruments for the assessment of HACS in patients with FM. Implementing these findings into clinical settings may help to identify HACS in patients with FM.

This study aimed to evaluate the quantitative measurement of Mac-2 binding protein glycosylation isomer (M2BPGi) levels using the new chemiluminescent enzyme immunoassay.
The data of a total of 347 patients with hepatitis C virus (HCV) infection and 150 health volunteers from 13 locations in Japan were evaluated. The quantitative system for measuring M2BPGi-Qt levels was based on a new chemiluminescent enzyme immunoassay. We evaluated the reproducibility and quantitation range in quantitative M2BPGi-Qt measurement. We also investigated the confidence ratio of M2BPGi-Qt levels measured by the new quantitative system to M2BPGi levels measured by the current semi-quantitative system for validating the clinical utility of the new method.
The reproducibility of M2BPGi-Qt in HCV samples with negative, positive 1+, and positive 2+ was 0.77 ± 0.02 AU/mL, 2.25 ± 0.03 AU/mL, and 6.55 ± 0.21 AU/mL, respectively, and the corresponding coefficient of variation (CV)s were 2.1%, 1.3%, and 3.2%, respectively. The range of quantification assessment resulted that all CVs showed less than 5% in investigated range. Sample stability testing found that the mean percentage difference between the pre- and post-storage values of 6 samples ranged between 96.2 and 103.9%. The correlation coefficient between M2BPGi and M2BPGi-Qt in patients with HCV and the healthy volunteers was 0.986 and 0.991, respectively. M2BPGi-Qt could be quantitatively assessed in a patient with over 20 C.O.I.
Compared with qualitative methods, the M2BPGi quantitative measurement system could provide a numerical value unaffected by interpretation bias, and measurements are more precise at high M2BPGi levels.

BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers.
METHODS: The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference.
RESULTS: In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8-87.9) and 92.6% (88.2-95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5-90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9-93.4) for the detection of moderate to severe AG at any location.
CONCLUSIONS: This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG.
CONCLUSIONS: Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis.

OBJECTIVE: Identifying significant fibrosis is crucial to evaluate the prognosis and therapeutic interventions in patients with nonalcoholic fatty liver disease (NAFLD). We assessed the performance of acoustic radiation force impulse (ARFI) elastography, APRI, FIB-4, Forns, NFS and BARD scores in determining liver fibrosis in severe obesity.
METHODS: A prospective study included 108 patients undergoing bariatric surgery. Liver biopsy specimens were obtained intraoperatively and classified according to the NAFLD Activity Score. Patients were assessed with serological markers and shear wave velocity of the liver was measured with the Siemens S2000 ultrasound system preoperatively. Optimal cut-off values were determined using the area under the receiver operating characteristic curves (AUROC).
RESULTS: In the entire cohort prevalence of NAFLD was 80.6%, steatohepatitis 25.9% and significant fibrosis 19.4%. The best tests for predicting significant fibrosis were FIB-4 and Forns scores (both AUROC 0.78), followed by APRI (AUROC 0.74), NFS (AUROC 0.68), BARD (AUROC 0.64) and ARFI (AUROC 0.62). ARFI elastography was successful in 73% of the patients. Higher body mass index (BMI) correlated with invalid ARFI measurements. In patients with BMI < 42 kg/m2, ARFI showed 92.3% sensitivity and 82,6% specificity for the presence of significant fibrosis, with AUROC 0.86 and cut-off 1.32 m/s.
CONCLUSIONS: FIB-4 and Forns scores were the most accurate for the prediction of significant fibrosis in bariatric patients. Applicability and accuracy of ARFI was limited in individuals with severe obesity. In patients with BMI < 42 kg/m2, ARFI elastography was capable for predicting significant fibrosis with relevant accuracy.

Aim To assess concordance of eight frequently used serology-based scoring indices for liver fibrosis and cirrhosis with transient elastography (TE) in chronic hepatitis C (CHC) patients in order to determine serum indices with the highest concordance and clinical usability in clinical practice. Methods In this prospective study, 63 CHC patients were included and TE results were compared with eight non-invasive indices. The diagnostic performance of these tests was assessed using receiver operating characteristic curves with kappa index calculated for the concordance analysis. Results Median age of 63 patients was 54 years (interquartile range: 42 to 63); 27 (42.9%) were females. According to areas under the Receiver Operating Characteristics (AUROC), the best performing serum markers for significant liver fibrosis (METAVIR ≥F2), advanced liver fibrosis (≥F3) and cirrhosis (F4) determined by TE measurements (≥7.1kPa, ≥9.5kPa and ≥12kPa, respectively) were Fibrotest (AUROC=0.727 for ≥F2) and FIB-4 score (AUROC=0.779 for ≥F3 and AUROC=0.889 for F4). Fibrotest cut-off at >0.50 was concordant with TE for presence of significant fibrosis in 30 (out of 45; 66.7%), FIB-4 cut-off at <1.45 was concordant for absence of significant fibrosis in 13 (out of 18; 72.2%) and Goeteborg University Cirrhosis Index (GUCI) cut-off at >1 was concordant for presence of cirrhosis in 16 (out of 22; 72.7%) patients, but not for exclusion of cirrhosis. Conclusion Serology-based scoring indices had moderate overall concordance with TE. We propose that FIB-4 score, Fibrotest and GUCI be used in routine practice to exclude and diagnose significant fibrosis and diagnose cirrhosis, respectively.

The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we investigated the expression of CD200 and CD200R on T and B lymphocytes and the serum level of soluble CD200 (sCD200) using flow cytometry and ELISA, respectively. Peripheral blood samples were collected from 54 female patients and 20 healthy, age-matched controls. Results were tested for correlation with disease severity and selected clinical parameters. We demonstrated that the differences in sCD200 levels (p = 0.001), the frequencies of CD200-positive T and B lymphocytes (p < 0.001 and p = 0.004, respectively), and the frequencies of CD200R-positive T and B lymphocytes (p < 0.001 for all comparisons) in the study group correlated positively with disease severity. Receiver operating characteristic (ROC) analysis indicated that aberrant expression of CD200/CD200R might serve as a marker to distinguish between EMS cases. Finally, negative co-stimulatory factors may contribute to the induction and persistence of inflammation associated with EMS. It seems that it is essential to determine whether alteration in the CD200/CD200R pathway can be therapeutically targeted in EMS.

BACKGROUND: The prognostic value and non-invasive predictors of splenomegaly in cirrhotic patients with hepatocellular carcinoma (HCC) after curative resection remain unknown.
OBJECTIVE: To investigate the prognostic value and non-invasive predictors of splenomegaly in cirrhotic patients with HCC after curative resection.
METHODS: The medical records of 78 patients with HCC and liver cirrhosis who underwent curative resection were retrospectively reviewed. The influence of spleen size, measured with clinically routine ultrasonography (USG), on overall and disease-free survival was evaluated using univariate and multivariate analyses. The efficiency of some frequently used blood-derived liver function parameters and non-invasive fibrosis markers to predict splenomegaly was also assessed.
RESULTS: It was shown that tumor size >5 cm, the presence of microvascular invasion, tumor-node metastasis (TNM) stage III-IVA of the tumor, spleen size >11.45 cm, and age ≤52 years were associated with poor overall survival and/or disease-free survival in univariate analyses (all p < 0.05). In multivariate analyses, spleen size was identified as an independent predictor for both overall and disease-free survival (p < 0.001 and p = 0.012, respectively). On the other hand, platelet count, aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 index (FIB-4) scores were significantly different between small and large spleen groups (p = 0.026, 0.003 and 0.003, respectively), while statistical differences for albumin, alanine aminotransferase (ALT), AST, total bilirubin, AST to ALT ratio (AAR), and age-platelet index (API) were not found. Using receiver operating characteristic (ROC) curves, high powers of platelet count, APRI and FIB-4 in splenomegaly prediction were confirmed.
CONCLUSIONS: Splenomegaly, which can be predicted by some non-invasive variables, serves as a strong determinant for postresectional prognoses of cirrhotic patients with HCC.

At least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is based largely on lifestyle modifications, which are difficult to achieve, and therapeutic options are urgently needed. Maraviroc (MVC), through antagonism of CCR5 receptors, may reduce hepatic fibrosis progression and could be an effective treatment for NAFLD. However, dosing is usually two times per day, unlike most currently recommended antiretroviral therapies. This study will investigate the feasibility and acceptability of addition of MVC to combination antiretroviral therapy in PLWH and NAFLD as a treatment for NAFLD.
This is a phase IV, randomised, open-label, non-invasive feasibility study. Sixty individuals with well-controlled HIV-1 and NAFLD will be recruited from UK HIV clinics and randomised 1:1 to receive either optimised background therapy (OBT) plus MVC or OBT alone. Follow-up will be every 24 weeks for 96 weeks. The primary outcome measures will include recruitment and retention rates, adverse events and adherence. Secondary outcomes will include changes in markers of hepatic fibrosis, including the Enhanced Liver Fibrosis score, median liver stiffness measurement and controlled attenuation parameter scores on Fibroscan, and quality of life assessments. Analyses will be performed according to intention-to-treat principles. For secondary outcomes, estimated differences and 95% CIs between the groups using a t-method will be presented for continuous variables and as exact 95% binomial CIs for categorical variables.
Ethical approval was obtained through the London Dulwich UK Research Ethics Committee (reference 17/LO/2093). Results will be disseminated both through community groups and peer-reviewed scientific literature.Trial registration number SRCTN31461655. EudraCT number 2017-004141-24; Pre-results.