Background: Hepatitis delta virus (HDV) is a satellite RNA virus that relies on hepatitis B virus (HBV) for transmission. HIV/HBV/HDV coinfection or triple infection is common and has a worse prognosis than monoinfection. Objective: We aimed to reveal the epidemiological characteristics of HIV/HBV/HDV triple infection in the global population. Methods: A systematic literature search in PubMed, Embase, and the Cochrane Library was performed for studies of the prevalence of HIV/HBV/HDV triple infection published from January 1, 1990, to May 31, 2021. The Der Simonian-Laird random effects model was used to calculate the pooled prevalence. Results: We included 14 studies with 11,852 participants. The pooled triple infection rate in the global population was 7.4% (877/11,852; 95% CI 0.73%-29.59%). The results of the subgroup analysis showed that the prevalence of triple infection was significantly higher in the Asian population (214/986, 21.4%; 95% CI 7.1%-35.8%), in men (212/5579, 3.8%; 95% CI 2.5%-5.2%), and in men who have sex with men (216/2734, 7.9%; 95% CI 4.3%-11.4%). In addition, compared with people living with HIV, the HIV/HBV/HDV triple infection rate was higher in people with hepatitis B. Conclusions: This meta-analysis suggests that the prevalence of HIV/HBV/HDV triple infection in the global population is underestimated, and we should focus more effort on the prevention and control of HIV/HBV/HDV triple infection. Trial Registration: PROSPERO CRD42021273949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273949

Background and Aims: Hepatocellular carcinoma (HCC) poses a significant global health burden, with hepatitis B virus (HBV) being the predominant etiology in China. However, current diagnostic markers lack the requisite sensitivity and specificity. This study aims to develop and validate serum N-glycomics-based models for the diagnosis and prognosis of HCC in patients with chronic hepatitis B (CHB)-related cirrhosis. Approach and Results: This study enrolled a total of 397 patients with CHB-related cirrhosis and HCC for clinical management. N-glycomics profiling was conducted on all participants and clinical data were collected. First, machine learning-based models, HCC-GRF and HCC-GSVM, were established for early screening and diagnosis of HCC using N-glycomics. The AUC values in the validation set were 0.967 (95% CI: 0.930-1.000) and 0.908 (0.840-0.976) for HCC-GRF and HCC-GSVM, respectively, outperforming AFP [0.687 (0.575-0.765)] and PIVKA-II [0.665 (0.507-0.823)]. It also showed superiority in subgroups analysis and external validation. Calibration and decision curve analysis also showed good predictive performance. Additionally, we developed a prognostic model, the prog-G model, based on N-glycans to monitor recurrence in HCC patients after curative treatment. During the follow-up period, it was observed that this model correlated with the clinical condition of the patients and could identify all recurrent HCC cases (n=12) prior to imaging findings, outperforming AFP (n=7) and PIVKA-II (n=9), while also detecting recurrent lesions earlier than imaging. Conclusions: N-glycomics models can effectively predict the occurrence and recurrence of HCC to improving the efficiency of clinical decision-making and promoting the precision treatment of HCC. Export

Background: Liver cancer is a severe public health problem worldwide, and it creates a relatively higher disease burden in China than in the Western world. Despite achieving notable progress in China, potential differences in some aspects of medical services for liver cancer may persist across different regions and hospitals. This warrants serious consideration of the actual status of and barriers to liver cancer treatment. We intended to explore the present status of and obstacles in liver cancer treatment especially for advanced-stage liver cancer.Methods: In February 2021, a national multicenter cross-sectional study was conducted among 1500 doctors from 31 provinces of mainland China using a self-administered online questionnaire. Participants completed the questionnaire about their general information, perspectives on the current status of liver cancer treatment, and expectations for future treatment. Chi-square and logistic regression analyses were performed to explore the differences associated with the regions, doctors’ professional ranks, and hospital levels.Results: Treatment conditions, medications, and treatment strategies were inconsistent across different economic regions and hospital of different levels. With respect to obstacles in treatment, 76.6% of the doctors were unsatisfied with the current treatment for liver cancer. Important factors that influenced their satisfaction with the treatment for liver cancer included early diagnosis and the disclosure of true conditions to patients.Conclusions: There persists differences in the treatment of liver cancer in China, besides barriers to treatment. More attention should be paid to the detection and treatment of liver cancer and the propagation of novel progress among doctors in underdeveloped areas.

Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3X^ΔHep) mice and control (DDX3X^fl/fl) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury.

The rapid clearance of hepatitis C virus induced by direct-acting antivirals (DAAs) affects natural killer (NK) cells, but the reported results are not consistent, and the relative mechanism was unclear. This study focused on the dynamic changes of NK cells during and after DAA treatment and analyzed the reasons.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.