To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022).With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden. 

pdf/guidelines-for-the-prevention-and-treatment-of-chronic-4ga3mhptdn.pdf

Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022)

Risk stratification and early detection biomarkers for precision hepatocellular carcinoma screening.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Early detection of HCC enables patients to avail curative therapies that can improve patient survival. Current international guidelines advocate for the enrollment of patients at high risk for HCC, like those with cirrhosis, in surveillance programs that perform ultrasound every 6 months. In recent years, many studies have further characterized the utility of established screening strategies and have introduced new promising tools for HCC surveillance. In this review, we provide an overview of the most promising new imaging modalities and biomarkers for the detection of HCC. We discuss the role of imaging tools like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) in the early detection of HCC, and describe recent innovations which can potentially enhance their applicability, including contrast enhanced ultrasound, low-dose CT scans, and abbreviated MRI. Next, we outline the data supporting the use of three circulating biomarkers (i.e., alpha-fetoprotein [AFP], AFP lens culinaris agglutinin-reactive fraction, and des-gamma-carboxy prothrombin) in HCC surveillance, and expand on multiple emerging liquid biopsy biomarkers, including methylated cell-free DNA (cfDNA), cfDNA mutations, extracellular vesicles, and circulating tumor cells. These promising new imaging modalities and biomarkers have the potential to improve early detection, and thus improve survival, in patients with HCC.

Current and Emerging Tools for Hepatocellular Carcinoma Surveillance.

The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10–20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients’ survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients.

https://www.mdpi.com/1422-0067/24/5/4286/pdf?version=1676973737

Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review

BACKGROUND The introduction of lumen-apposing metal stents (LAMS) for endoscopic ultrasound (EUS)-guided drainages has marked a turning point in the field of interventional ultrasound and it is gathering worldwide diffusion in different clinical settings. Nevertheless, the procedure may conceal unexpected pitfalls. LAMS misdeployment is the most frequent cause of technical failure and it can be considered a procedure-related adverse event when it hampers the conclusion of the planned procedure or results in significant clinical consequences. Stent misdeployment can be managed successfully by endoscopic rescue maneuvers to allow the completion of the procedure. To date, no standardized indication is available to guide an appropriate rescue strategy depending on the type of procedure or of misdeployment. AIM To evaluate the incidence of LAMS misdeployment during EUS-guided choledochoduodenostomy (EUS-CDS), gallbladder drainage (EUS-GBD) and pancreatic fluid collections drainage (EUS-PFC) and to describe the endoscopic rescue strategies adopted under the circumstance. METHODS We conducted a systematic review of the literature on PubMed by searching for studies published up to October 2022. The search was carried out using the exploded medical subject heading terms “lumen apposing metal stent”, “LAMS”, “endoscopic ultrasound” and “choledochoduodenostomy” or “gallbladder” or “pancreatic fluid collections”. We included in the review on-label EUS-guided procedures namely EUS-CDS, EUS-GBD and EUS-PFC. Only those publications reporting EUS-guided LAMS positioning were considered. The studies reporting a technical success rate of 100% and other procedure-related adverse events were considered to calculate the overall rate of LAMS misdeployment, while studies not reporting the causes of technical failure were excluded. Case reports were considered only for the extraction of data regarding the issues of misdeployment and rescue techniques. The following data were collected from each study: Author, year of publication, study design, study population, clinical indication, technical success, reported number of misdeployment, stent type and size, flange misdeployed and type of rescue strategy. RESULTS The overall technical success rate of EUS-CDS, EUS-GBD and EUS-PFC was 93.7%, 96.1%, and 98.1% respectively. Significant rates of LAMS misdeployment have been reported for EUS-CDS, EUS-GBD and EUS-PFC drainage, respectively 5.8%, 3.4%, and 2.0%. Endoscopic rescue treatment was feasible in 86.8%, 80%, and 96.8% of cases. Non endoscopic rescue strategies were required only in 10.3%, 16% and 3.2% for EUS-CDS, EUS-GBD, and EUS-PFC. The endoscopic rescue techniques described were over-the-wire deployment of a new stent through the created fistula tract in 44.1%, 8% and 64.5% and stent-in-stent in 23.5%, 60%, and 12.9%, respectively for EUS-CDS, EUS-GBD, and EUS-PFC. Further therapeutic option were endoscopic rendezvous in 11.8% of EUS-CDS and repeated procedure of EUS-guided drainage in 16.1% of EUS-PFC. CONCLUSION LAMS misdeployment is a relatively common adverse event in EUS-guided drainages. There is no consensus on the best rescue approach in these cases and the choice is often made by the endoscopist relying upon the clinical scenario, anatomical characteristics, and local expertise. In this review, we investigated the misdeployment of LAMS for each of the on-label indications focusing on the rescue therapies used, with the aim of providing useful data for endoscopists and to improve patient outcomes.

Lumen-apposing-metal stent misdeployment in endoscopic ultrasound-guided drainages: A systematic review focusing on issues and rescue management

Background and Aims: Therapeutic drugs that are used to treat cholestatic liver disease are limited; however, the results of clinical trials on primary biliary cholangitis treatment targeting peroxisome proliferator-activated receptors (PPARs) are encouraging. In this study, we aimed to identify the effects of MBT1805, a novel balanced PPARα/γ/δ agonist, on cholestasis induced by α-naphthylisothiocyanate (ANIT) and elucidate the underlying mechanisms through untargeted and bile acid-targeted metabolomic analysis. Methods: Levels of serum biochemical indicators (transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin) and liver histopathology were analyzed to evaluate the therapeutic effects of MBT1805 on ANIT-induced cholestasis in C57BL/6 mice. Untargeted and bile acid-targeted metabolomic analysis of liver tissues was performed using ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MC/MC). qRT-PCR and Western blot analysis were carried out to measure the expression of key enzymes and transporters regulating bile acid synthesis, biotransformation, and transport. Results: MBT1805 significantly improved abnormal levels of liver biochemical indicators and gallbladder enlargement induced by ANIT. Histopathological analysis showed that MBT1805 effectively relieved ANIT-induced necrosis, vacuolation, and inflammatory infiltration. Untargeted metabolomic analysis identified 27 metabolites that were involved in the primary biliary acid biosynthesis pathway. In addition, bile acid-targeted metabolomics showed that MBT1805 could alleviate the abnormal bile acid content and composition induced by ANIT. Furthermore, qRT-PCR and Western blot results confirmed that MBT1805 could effectively regulate bile acid synthesis, biotransformation, and transport which helps relieve cholestasis. Conclusions: MBT1805 is a potential candidate drug for cholestasis, with a balanced PPARα/γ/δ activation effect.

/pdf/metabolomic-analysis-reveals-the-therapeutic-effects-of-t7ylprnqkj.pdf

Metabolomic Analysis Reveals the Therapeutic Effects of MBT1805, a Novel Pan-Peroxisome Proliferator-Activated Receptor Agonist, on α-Naphthylisothiocyanate-Induced Cholestasis in Mice.

Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B.

Purpose GALAD is a statistical model for estimating the likelihood of having hepatocellular carcinoma (HCC) based on gender, age, AFP, AFP-L3, and PIVKA-II. We aimed to assess its performance and build new models in China, where hepatitis B virus (HBV) is the leading etiology of HCC. Patients and methods We built the GALAD-C model with the same five variables in GALAD, and the GAAP model with gender, age, AFP, and PIVKA-II, using logistic regression based on 242 patients with HCC and 283 patients with chronic liver disease (CLD). We also collected 50 patients with other malignant liver tumors (OMTs) and 50 healthy controls (HCs). A test dataset (169 patients with HCC and 139 with CLD) was used to test the performance of GAAP. Results The GALAD-C and GAAP models achieved comparable performance (area under the receiver operating characteristic curve [AUC], 0.922 vs 0.914), and both were superior to GALAD, PIVKA-II, AFP, and AFP-L3% (AUCs, 0.891, 0.869, 0.750, and 0.711) for discrimination of HCC from CLD for the entire dataset. The AUCs of the GALAD, GALAD-C and GAAP models were excellent for the hepatitis C virus (HCV) subgroup (0.939, 0.958 and 0.954), and for discrimination HCC from HCs (0.988, 0.982, and 0.979), but were relatively lower for the HBV subgroup (0.855, 0.904, and 0.894), and for HCC within Milan Criteria (0.810, 0.841, and 0.840). They were not superior to AFP (0.873) for discrimination of HCC from OMT (0.873, 0.809, and 0.823). GAAP achieved an AUC of 0.922 in the test dataset. Conclusion GALAD was excellent for discrimination of HCC from CLD in the HCV subgroup of a cohort of Chinese patients. The GAAP and GALAD-C models achieved better performance compared with GALAD. These three models exhibited better performance in patients with an HCV etiology than those with HBV.

/pdf/validation-of-the-galad-model-and-establishment-of-gaap-4k0vcll89d.pdf

Validation of the GALAD Model and Establishment of GAAP Model for Diagnosis of Hepatocellular Carcinoma in Chinese Patients.

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.

/pdf/high-prevalence-of-clonorchis-sinensis-infections-and-3qnpdql8yn.pdf

High prevalence of Clonorchis sinensis infections and coinfection with hepatitis virus in riverside villages in northeast China

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Metabolomic Analysis Reveals the Therapeutic Effects of MBT1805, a Novel Pan-Peroxisome Proliferator-Activated Receptor Agonist, on α-Naphthylisothiocyanate-Induced Cholestasis in Mice.

Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B.

Validation of the GALAD Model and Establishment of GAAP Model for Diagnosis of Hepatocellular Carcinoma in Chinese Patients.

High prevalence of Clonorchis sinensis infections and coinfection with hepatitis virus in riverside villages in northeast China