Background: In chronic hepatitis B virus (HBV) patients, fluctuations in HBV DNA serve as a “gray area” and impede the accurate identification of inactive carriers. We aimed to assess if such fluctuations impact the presence of significant hepatic fibrosis (Metavir F2-4) in chronic HBV patients. Methods: Consecutive, untreated HBeAg-negative carriers (n = 234) with fluctuating HBV DNA (n = 73) above or below a level of 2000 IU/mL were included and compared to those without fluctuations (n = 161). Patients without fluctuating HBV DNA were further analyzed based on those with persistently low (<2,000 IU/mL, n = 137) and higher HBV DNA (2,000–20,000 IU/mL, n = 24). Hepatic fibrosis (assessed by transient elastography) was correlated with virologic and biochemical profiles. Results: The mean age of the overall cohort was 47.8 ± 11.1 years, of whom 107 (45.7%) were male. During a median of 60 months (interquartile range [IQR] 34–82) of follow-up, 73 (31.2%) patients had a mean of 1.6 ± 0.9 fluctuations in HBV DNA. The median time to the first fluctuation was at 14.5 (IQR 5.0–33.7) months. Patients with fluctuating viremia had higher log₁₀ qHBsAg (3.1 ± 0.8 vs. 2.7 ± 1.0, P = 0.022) and HBV DNA (3.4 ± 0.5 vs. 2.7 ± 0.8, P < 0.001) compared to those without fluctuations. Patients with fluctuant viremia were less likely to have F2-4 fibrosis (8.2%) compared to those without fluctuant viremia (18.2%, odds ratio [OR]: 0.407, 95% confidence interval [CI]: 0.161–1.030; P = 0.052). Males tended to have less fluctuation constituting 37.0% of patients with fluctuating HBV DNA (P = 0.071). Fluctuations occurred more frequently in those with predominantly higher HBV DNA levels (26.0%) compared to those without fluctuations (14.9%; P = 0.030). Conclusions: Fluctuating HBV DNA levels occur frequently but are not associated with significant fibrosis. Minor fluctuations in HBV DNA levels are unlikely to be of clinical relevance.

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Therapeutic drug monitoring (TDM) is the measurement of serum drug concentrations and anti-drug-antibodies (ADA) for biologic therapies used to treat inflammatory bowel disease (IBD). The aim of this article is to review the current literature concerning reactive and proactive TDM for both adults and children with IBD. Although optimal trough concentration windows for some of these medications are not well defined, there is mounting evidence to suggest that reactive TDM is associated with favorable therapeutic outcomes, including less immunogenicity, greater drug exposure, and a decreased risk of treatment failure. Moreover, while the exact mechanism of loss of response is not fully elucidated, the vast majority of studies have reported a decreased incidence of nonresponse and secondary loss of response when TDM is implemented. Proactive TDM, while even less understood in the literature, employs a schedule of preemptive analysis of serum trough concentrations to accordingly adjust the patient's biologic dosage. Proactive TDM may decrease the need for IBD-related surgery/hospitalization, and therefore merits future studies of investigation.

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Background: Early screening and treatment of esophageal cancer (EC) is particularly important for the survival and prognosis of patients. However, early EC is difficult to diagnose by a routine endoscopic examination. Therefore, convolutional neural network (CNN)-based artificial intelligence (AI) has become a very promising method in the diagnosis of early EC using endoscopic images. The aim of this study was to evaluate the diagnostic performance of CNN-based AI for detecting early EC based on endoscopic images. Methods: A comprehensive search was performed to identify relevant English articles concerning CNN-based AI in the diagnosis of early EC based on endoscopic images (from the date of database establishment to April 2022). The pooled sensitivity (SEN), pooled specificity (SPE), positive likelihood ratio (LR+), negative likelihood ratio (LR−), diagnostic odds ratio (DOR) with 95% confidence interval (CI), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) for the accuracy of CNN-based AI in the diagnosis of early EC based on endoscopic images were calculated. We used the I² test to assess heterogeneity and investigated the source of heterogeneity by performing meta-regression analysis. Publication bias was assessed using Deeks' funnel plot asymmetry test. Results: Seven studies met the eligibility criteria. The SEN and SPE were 0.90 (95% confidence interval [CI]: 0.82–0.94) and 0.91 (95% CI: 0.79–0.96), respectively. The LR+ of the malignant ultrasonic features was 9.8 (95% CI: 3.8–24.8) and the LR− was 0.11 (95% CI: 0.06–0.21), revealing that CNN-based AI exhibited an excellent ability to confirm or exclude early EC on endoscopic images. Additionally, SROC curves showed that the AUC of the CNN-based AI in the diagnosis of early EC based on endoscopic images was 0.95 (95% CI: 0.93–0.97), demonstrating that CNN-based AI has good diagnostic value for early EC based on endoscopic images. Conclusions: Based on our meta-analysis, CNN-based AI is an excellent diagnostic tool with high sensitivity, specificity, and AUC in the diagnosis of early EC based on endoscopic images.

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Background: Screening endoscopy for varices may be deferred when the calculated EVendo score is ≤3.90. This novel score has not been validated in an external cohort. This study aimed to assess the performance of the EVendo score and compare it with the Baveno VI criteria. Methods: We identified and calculated this score in all cirrhotic patients who underwent screening endoscopy for the first time with laboratory tests and liver stiffness measurements within 6 months of the endoscopy date. Results: In total, 103 patients were included. An EVendo score of ≤3.90 identified patients with no gastroesophageal varices (GEV) and varices needing treatment (VNT) with sensitivities of 82% and 83% and specificities of 57% and 34%, respectively. The negative predictive value for VNT was 94%. A comparison with the Baveno VI criteria in Child–Turcotte–Pugh-A patients showed spared endoscopy and missed VNT rates with EVendo score cutoffs of ≤3.9 and ≤4.5 and the Baveno VI criteria of 25%, 33%, and 16.6% and 1.7%, 1.7%, and 0%, respectively. Conclusions: EVendo score is reliable in clinical practice for predicting GEV and VNT. The number of spared endoscopies was higher than that with the Baveno VI criteria; however, there were more missed VNT cases.

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Background: Patients with sleep disturbances have gastrointestinal symptoms. Breath hydrogen (H₂) and methane (CH₄) indicating small intestinal bacterial overgrowth (SIBO) might be related with these symptoms. The study was conducted to assess the link between breath profiles and untreated obstructive sleep apnea (OSA). Methods: This prospective study enrolled consecutive patients with OSA using polysomnography. Heart rate variability (HRV) was used as a measurement for the balance of autonomic nervous system during polysomnography. Glucose breath test (GBT) to evaluate breath H₂ and CH₄ and bowel symptom questionnaire to investigate associated intestinal symptoms were performed. Results: Among 52 patients with OSA, 16 (30.8%) showed positivity to GBT. Although no significant difference was shown in GBT positivity between patients with healthy controls and patients with OSA (13.3% vs 30.8%, P = 0.109), breath H₂ and CH₄ levels in the OSA group were significantly higher than those in controls (P < 0.05). Flatulence was significantly common in OSA groups with GBT positivity than those without GBT positivity. Multivariate analysis demonstrated that waist-to-hip ratio (odds ratio = 12.889; 95% confidence interval (CI): 1.257–132.200; P = 0.031) and low-to-high-frequency ratio of HRV (odds ratio = 1.476; 95% CI: 1.013–2.151, P = 0.042) are independently related to GBT positivity in patients with OSA. Conclusion: Elevated breath H₂ or CH₄ after glucose load might not be an uncommon finding in patients with untreated OSA. Abdominal obesity and autonomic imbalance dysfunction are significantly associated with GBT positivity in OSA patients. SIBO could be considered as target for therapeutic management in OSA patients.

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Background: Diagnosis of malignant pancreatic cystic lesions (PCLs) is challenging as there is no investigation that offers both high diagnostic sensitivity and specificity for a definite diagnosis. Accurate diagnosis of cyst type is vital in order to not miss opportunities for early treatment of potentially malignant lesions and to avoid unnecessary surgeries. Serine protease inhibitor Kazal type I (SPINK1) and glucose are promising cyst fluid markers for differentiation of mucinous from non-mucinous cysts. We aim to validate the value of SPINK1 and glucose in detecting potentially malignant PCLs. Methods: A prospective study was conducted on 80 patients presenting with PCLs. Endoscopic ultrasound (EUS) evaluation of detailed cyst morphology and EUS with fine needle aspiration (FNA) were done. Fluid analysis for carcinoembryonic antigen (CEA), glucose and SPINK1 and cytopathology were done. We compared these data with the final diagnosis based on cytopathological and postoperative histopathological examination. Results: Cyst fluid SPINK1 was significantly higher in malignant or potentially malignant cysts compared to benign cysts (0.91 vs 0.47 ng/ml; P = 0.001). Also, glucose was significantly lower in malignant or potentially malignant cysts compared to benign cysts (21.5 vs 68.5 mg/dl; P = 0.0001). Glucose and SPINK1 had the best sensitivity and specificity for differentiating mucinous from non-mucinous cysts with 84.78% and 73.53% (AUC 0.76; 95% CI [0.65–0.88]; cutoff value = 42 mg/dl), and 70.59% and 65.22% (AUC 0.72; 95% CI [0.64–0.86]; cutoff value = 0.58 ug/L) respectively. CEA level >192 ng/ml, high SPINK1 level and lymph node enlargement were the independent predictors of malignant cysts. Conclusion: Cyst fluid SPINK1 and glucose are promising diagnostic markers for the diagnosis of potentially malignant PCLs.

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Background: The ¹³C-urea breath test (¹³C-UBT) is preferred for non-invasive detection of Helicobacter pylori (H. pylori); however, its accuracy drops when results fall between 2‰ and 6‰ (called the gray zone). This study aimed to evaluate the accuracy of ¹³C-UBT (cut-off point 4‰) between 2‰ and 6‰, find a more appropriate gray zone, and identify the factors influencing ¹³C-UBT. Methods: Patients with ¹³C-UBT results 2‰–6‰, over an eight-year period, were studied. H. pylori infection was diagnosed if patients were positive for either Warthin–Starry staining or quantitative real-time polymerase chain reaction (real-time PCR), and excluded if both were negative. Accuracy of ¹³C-UBT under different cut-off points was calculated, and the factors affecting ¹³C-UBT were analyzed. Results: A total of 208 patients were included, of whom 129 were H. pylori–positive. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ¹³C-UBT were 71.32%, 83.54%, 64.08%, and 87.62%, respectively. When the cut-off point was changed to 2.15‰, the NPV of ¹³C-UBT reached a maximum (76.47%); when the cut-off point was changed to 4.95‰, PPV reached its maximum (93.22%). Therefore, the original gray zone (2‰–6‰) was adjusted to 2‰–4.95‰. Gastric antral intestinal metaplasia (OR = 3.055, 95% CI: 1.003–9.309) was an independent risk factor for false-negative ¹³C-UBT. Conclusions: Accuracy of ¹³C-UBT over 2‰–6‰ was poor, and the gray zone was changed to 2‰–4.95‰. ¹³C-UBT results over 2‰–4.95‰ should be interpreted with caution during mass screening of H. pylori, especially for patients with gastric antral intestinal metaplasia.

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Background: NOP2 nucleolar protein plays a crucial role in early embryo development and cell proliferation. The role of NOP2 in human gastric adenocarcinoma has not been elucidated. In the present study, we aimed to examine the expression levels of NOP2 and dissected whether NOP2 expression was associated with aggressive clinicopathological outcomes of patients with gastric adenocarcinoma. Methods: Clinicopathological analysis was performed in patients with gastric adenocarcinoma. Expression of NOP2 was tested by immunohistochemistry staining and quantitative RT-PCR. The prognostic role of NOP2 in gastric adenocarcinoma patients was assessed by univariate and multivariate analysis. The effect of NOP2 on cell proliferation was examined through cellular experiments and mice models. Results: NOP2 expression was elevated in gastric adenocarcinoma tissues compared to normal gastric tissues. High expression of NOP2 was significantly correlated with tumor size, invasion depth, and lymph node metastasis. Moreover, patients with high NOP2 expression had poorer overall survival, and NOP2 was identified as an independent prognosis factor. Using the gastric adenocarcinoma cells, we found that NOP2 can promote tumor cell proliferation both in vitro and in vivo. Conclusions: Overexpression of NOP2 significantly correlates with a poorer prognosis of gastric adenocarcinoma patients and suggested the potential of NOP2, which may serve as a novel prognostic biomarker in gastric adenocarcinoma.

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Background: We aimed to validate the predictive value of the cirrhosis, age, male sex, and diabetes (CAMD) score and age, albumin, sex, and liver cirrhosis (AASL) score for chronic hepatitis B (CHB) patients, treated with nucleos(t)ide analogues (NUCs) in Northeast China. Methods: From January 2009 to June 2020, 945 patients diagnosed with CHB who received NUC therapy at China-Japan Union Hospital of Jilin University were included. Comprehensive medical records were retrospectively analyzed, and the predictive values of the CAMD score and AASL score for hepatocellular carcinoma (HCC) were evaluated. Results: A total of 58 patients (5.94%) were diagnosed with HCC. Multivariate analysis revealed that age [odds ratio (OR) = 1.041, 95% confidence interval (CI) 1.009–1.073, P < 0.011] and cirrhosis (OR = 3.297, 95% CI 1.383–7.861, P < 0.007) were independent predictors of HCC. Either the CAMD or AASL score was significantly higher in the HCC group compared to the non-HCC group. The area under the receiver operating characteristic (ROC) curve (AUC) of CAMD and AASL was 0.721 (95% CI 0.663–0.780) and 0.718 (95% CI 0.662–0.774), respectively. Risk stratification using either CAMD or AASL revealed significant differences in the one-, three-, and five-year cumulative incidence rates of HCC between the low-, intermediate-, and high-risk groups (all P < 0.001, log-rank test). Conclusions: Both CAMD and AASL scores have predictive value for HCC risk of CHB patients in Northeast China. In future, the optimal monitoring frequency and methods should be personalized.

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