Soluble immune checkpoints are elevated in patients with primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronically progressive liver disease mediated by an autoimmune response. The aetiology and pathogenesis of PBC are not fully understood and may be related to immune disorders caused by genetic factors and their interaction with environmental factors. Immune checkpoints play an important role in preventing the occurrence of autoimmunity. However, the level of immune checkpoints in PBC has not been reported. Here, we aimed to identify the serum levels of soluble checkpoints in patients with PBC. METHODS: Soluble checkpoint levels were evaluated using enzyme-linked immunosorbent assay in 60 patients with PBC and 20 healthy controls (HCs). The expression of immune checkpoints was compared in liver biopsy tissue samples using immunohistochemistry. Receiver operating characteristic (ROC) curves and area under the curve (AUCs) were used to determine the diagnostic performance of soluble checkpoints and laboratory indexes between patients with PBC and HCs and patients with mild and advanced PBC. A logistic regression was performed for advanced PBC. RESULTS: sCD134, sLAG-3, sPD-1, sPD-L1, and sTIM-3 levels were significantly increased in patients with PBC compared with those in healthy controls. Additionally, the levels of sCD134, sPD-1, sPD-L1, and sTIM-3 were positively associated with disease progression. Moreover, soluble checkpoints were correlated with immunoglobulin and liver functions. ROC analyses between patients with PBC and HCs showed that the AUCs of sOX40, sPD-1, and sPD-L1 were 0.967, 0.922, and 0.971, respectively. The optimal cut-off values of sOX40, sPD-1, and sPD-L1 for PBC diagnosis were 89.15, 213.4, and 68, respectively. ROC analyses between mild and advanced patients with PBC revealed that the AUCs of sOX40 and sTIM-3 were 0.767 and 0.765, respectively. The optimal cut-off values for predicting PBC stage ≥ III were 199.45 and 361.5, respectively. In univariate analysis, age, ALB, and sOX40 were associated with advanced PBC. Further, the expression of CD134 and TIM-3 was upregulated in the liver of patients with PBC. CONCLUSIONS: Our study results indicate that the serum titer of soluble checkpoints is increased in Chinese patients with PBC.

Cost-effectiveness evaluation of risk-based breast cancer screening in Urban Hebei Province.

To evaluate the implementations of Cancer Screening Program in Urban Hebei and to model the cost-effectiveness of a risk-based breast Cancer Screening Program. Women aged 40-74 years were invited to participate the Cancer Screening Program in Urban Hebei form 2016 to 2020 by completing questionnaires to collect information about breast cancer exposure. Clinical screening including ultrasound and mammography examination were performed. We developed a Markov model to estimate the lifetime costs and benefits, in terms of quality-adjusted life years (QALY), of a high-risk breast Cancer Screening Program. Nine screening strategies and no screening were included in the study. The age-specific incidence, transition probability data and lifetime treatment costs were derived and adopted from other researches. Average cost-effectiveness ratios (ACERs) were estimated as the ratios of the additional costs of the screening strategies to the QLYG compared to no screening. Incremental cost-effectiveness ratios (ICERs) were calculated based on the comparison of a lower cost strategies to the next more expensive and effective strategies after excluding dominated strategies and extendedly dominated strategies. ICERs were used to compare with a willingness-to-pay (WTP) threshold. Sensitivity analysis was explored the influence factors. A total of 84,029 women completed a risk assessment questionnaire, from which 20,655 high-risk breast cancer females were evaluated, with a high-risk rate of 24.58%. There were 13,392 high-risk females completed the screening program, with participation rate was 64.84%. Undergoing ultrasound, mammography and combined screening, the suspicious positive detection rates were 15.00%, 9.20% and 19.30%, and the positive detection rates were 2.11%, 2.76% and 3.83%, respectively. According to the results by Markov model, at the end of 45 cycle, the early diagnosis rates were 55.53%, 60.68% and 62.47% underwent the annual screening by ultrasound, mammography and combined, the proportion of advanced cancer were 17.20%, 15.85% and 15.36%, respectively. Different screening method and interval yield varied. In the exploration of various scenarios, annual ultrasound screening is the most cost-effective strategy with the ICER of ¥116,176.15/QALY. Sensitivity analyses demonstrated that the results are robust. Although it was not cost effective, combined ultrasound and mammography screening was an effective strategy for higher positive detection rate of breast cancer. High-risk population-based breast cancer screening by ultrasound annually was the most cost-effective strategy in Urban Hebei Province.

Serum qAnti-HBc combined with ALT and HBsAg predicts significant hepatic inflammation in HBeAg-positive immune active patients.

BACKGROUND AND AIM: Quantitative hepatitis B core antibody (qAnti-HBc) level has been reported to predict significant liver inflammation in treatment-naïve chronic hepatitis B patients. However, little evidence has been revealed that qAnti-HBc alone or with other serum parameters in predicting moderate to severe hepatic inflammation in HBeAg-positive immune active patients treated with entecavir (ETV). METHODS: A total of 142 patients with HBeAg-positive immune active hepatitis were recruited in our study. Serum liver biochemistry, qAnti-HBc, hepatitis B virus markers, and liver inflammation were evaluated during 48-week ETV treatment. The association between liver inflammation grades and serum markers was systematically analyzed. RESULTS: The patients with moderate to severe inflammation (≥ G2) had a significantly higher level of qAnti-HBc compared with those with no to mild liver inflammation patients (< G2). The levels of qAnti-HBc and alanine transaminase (ALT) were positively correlated with hepatic inflammation grades, and qAnti-HBc had a better correlation than ALT, whereas HBsAg was negatively correlated with hepatic inflammation grades before treatment. After 48-week ETV treatment, no correlation was observed between hepatic inflammation grades and qAnti-HBc, ALT, or HBsAg. The combination of qAnti-HBc, ALT, and HBsAg had better performance in predicting significant liver inflammation (≥ G2) than qAnti-HBc alone or its combination with ALT. CONCLUSION: Serum qAnti-HBc levels were positively correlated with hepatic inflammation grades before treatment, but no positive correlation between them was observed after 48-week treatment. The level of qAnti-HBc combined with ALT and HBsAg may serve as a more reliable marker for identifying significant liver inflammation before treatment in HBeAg-positive immune active patients.

[Research Progress on Lung Cancer Screening].

Lung cancer is the most common malignant tumor in the world. The five-year survival rate is 19.7%, which seriously threatens human health. Lung cancer screening is an effective measure to reduce lung cancer mortality. Existing studies have shown that screening with low-dose computed tomography (LDCT) can reduce lung cancer deaths by 20%. Currently, lung cancer screening is recommended internationally and nationally. Studying the development status of lung cancer screening helps us to identify the high-risk groups of lung cancer, explore reasonable screening programs, improve the cost-effectiveness of screening and reduce the economic burden. Therefore, this article summarizes the current status of lung cancer screening, the cost-effectiveness of lung cancer screening and the existing problems as follows.
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High prevalence of Clonorchis sinensis infections and coinfection with hepatitis virus in riverside villages in northeast China.

In China, the prevalence of Clonorchis sinensis (C. sinensis) infections is only evaluated at the provincial level by national sampling surveys, and data from villages and counties are still lacking. In this study, we conducted a cross-sectional survey in 10 villages located along the Lalin River in northeast China. Clonorchiasis was diagnosed using a modified Kato-Katz method that detects the C. sinensis egg in stools. A total of 3,068 persons were screened and 2,911 were recruited for the study. Overall, the prevalence of C. sinensis infection was 29.3%. Among 175 participants who were cured after antiparasitic treatment, 54 (30.86%) were re-infected in this survey. After calibration of potential confounders, male gender, occupation as a farmer, smoking, and occasionally or frequently eating raw fish were independent risk factors for C. sinensis infection. The results of laboratory examinations in the C. sinensis/hepatitis B or C virus co-infection group were similar to those in the hepatitis B or C virus mono-infection groups. In conclusion, C. sinensis is highly endemic in villages along the Lalin River, and the primary route of infection is the consumption of raw freshwater fish. Co-infection with C. sinensis did't aggravate the clinical manifestations of viral hepatitis in this cross-sectional study.

Computational analysis of naturally occurring resistance-associated substitutions in genes NS3, NS5A, and NS5B among 86 subtypes of hepatitis C virus worldwide.

BACKGROUND AND OBJECTIVE: Direct-acting antivirals (DAA) facing resistance continue to be used in some areas worldwide. Thus, identifying hepatitis C virus (HCV) genotypes/subtypes and loci with certain prevalent resistance-associated substitutions (RASs) deserves attention. We investigated the global and regional frequencies of naturally occurring RASs among all confirmed HCV subtypes (n=86) and explored co-occurring and mutually exclusive RAS pairs within and between genes NS3, NS5A, and NS5B. METHODS: A total of 213,908 HCV sequences available as of July 10, 2019 were retrieved from the NCBI nucleotide database. After curation, 17,312 NS3, 8,478 NS5A, and 25,991 NS5B sequence fragments from DAA-naïve patients were screened for RASs. MEGA 6.0 was used to translate aligned nucleotide sequences into amino acid sequences, and RAS pairs were identified by hypergeometric analysis. RESULTS: RAS prevalence varied significantly among HCV subtypes. For example, D168E, highly resistanct to all protease inhibitors except voxilaprevir, was nearly absent in all subtypes except in 43.48% of GT5a sequences. RASs in NS3 exhibiting significantly different global distribution included Q80K in GT1a with the highest frequency in North America (54.49%), followed by in Europe (22.66%), Asia (6.98%), Oceania (6.62%), and South America (1.03%). The prevalence of NS3 S122G in GT1b was highest in Asia (26.6%) and lowest in Europe (2.64%). NS5A L28M, R30Q, and Y93H in GT1b, L31M in GT2b, and NS5B C316N in GT1b was most prevalent in Asia. A150V in GT3a, associated with sofosbuvir treatment failure, was most prevalent in Asia (44.09%), followed by Europe (31.19%), Oceania (24.29%), and North America (19.05%). Multiple mutually exclusive or co-occurring RAS pairs were identified, including Q80K+R155K and R155K+D168G in GT1a and L159F+C316N and R30Q (NS5A)+C316N (NS5B) in GT1b. CONCLUSION: Our data may be of special relevance for those countries where highly effective antivirals might not be available. Considering the specific RASs prevalence will help the clinicians to make optimal treatment choices. The RASs pairs would benefit anti-HCV drug development.

Epidemiological study of hepatitis B and hepatitis C infections in Northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study.

BACKGROUND: Viral hepatitis, mainly hepatitis B and C, is a serious public health problem worldwide. In China, the prevalence of hepatitis B virus (HBV) infection remains high, while that of hepatitis C virus (HCV) infection is controversial. This study investigated the epidemiology of HBV and HCV infections and assessed the beneficial effect of the vaccination strategy for hepatitis B in Northeastern China. METHODS: From June 2016 to August 2016, 6541 residents of Changchun in Northeastern China were recruited for this cross-sectional study. Demographic characteristics as well as HBV and HCV serological test results were reviewed and analyzed. RESULTS: Among all study participants, 3.8% and 0.36% tested positive for hepatitis B surface antigen (HBsAg) and anti-HCV, respectively. The HBsAg- and anti-HCV-positive rates were significantly higher in male participants (4.58% and 0.43%) than in female individuals (3.0% and 0.33%). Notably, among all age groups, the lowest rate of HBsAg positivity (0.2%) was found in children born after the implementation of the vaccination strategy for hepatitis B. Conversely, participants aged 40-49 years had significantly greater positive rates of HBsAg (5.9%) compared with those of other age groups. Furthermore, the highest rates of anti-HCV positivity (1.1%) were observed in participants aged 50-59 years. CONCLUSIONS: The rate of HBsAg-positivity declined significantly following successful implementation of the policy on hepatitis B vaccination, indicating a beneficial impact on the control of HBV infection. However, only a slight decrease was observed in the anti-HCV-positivity rate, identifying an area in need of improvement within viral hepatitis prevention and control programs in China.