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Background and Aims: Hepatitis B virus (HBV) infection continues to threaten millions of lives across the globe, despite universal vaccination efforts. Current guidelines for screening, vaccination, and treatment are complex and have left too many people undiagnosed or improperly managed. Antiviral therapy has been shown to significantly reduce the incidence of liver-related complications, including liver cancer. However, the complexity of existing guidelines can make it difficult to identify which patients to target for treatment, and recommendations that are difficult to implement in real-world settings pose a barrier to eligible patients to receive therapy and contribute to health disparities in HBV care. The goal of this global expert panel was to gain consensus on a streamlined approach to HBV care to facilitate implementation of HBV intervention and treatment, especially in the primary care setting. Methods: A group of 8 liver and infectious disease specialists attended a meeting in January 2021 with the objective of gaining consensus on a streamlined algorithm for HBV care that would encourage implementation of HBV intervention and treatment. Results: We have created a comprehensive perspective highlighting screening optimization, diagnostic workup, treatment, and monitoring. This treatment algorithm is designed to provide a streamlined visual pathway for risk stratification and management of patients with HBV that can be adapted in various care settings. Conclusion: Simplification of guidelines will be critical to achieving health equity to address this public health threat and achieve HBV elimination.

Background and Aims: Type 1 hepatorenal syndrome (HRS) is a rapid deterioration in kidney function in patients with cirrhosis. Data on efficacy of vasoconstrictors for type 1 HRS have shown mixed results. Methods: Literature searched for randomized controlled trials comparing pharmacological therapy for HRS vs placebo or another drug for HRS. Primary outcome was HRS reversal (serum creatinine

Abstract Real‐world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real‐world outcomes with other first‐line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen–negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR

Introduction: Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival. Materials and methods: We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was < 15 IU/mL prior to transplant. At screening, 6 patients were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients underwent transplant prior to completing assigned treatment, with 4 treated for < 12 weeks. The primary endpoint was posttransplant virologic response 12 weeks after transplant (pTVR12) in patients with HCV RNA < 15 IU/mL at their last measurement prior to transplant. Results: Overall, 94% (16/17) achieved pTVR12. All who achieved pTVR12 received at least 11 weeks of treatment. The single patient who did not achieve pTVR12 discontinued study drug on day 21 and underwent liver transplant the following day. The patient had HCV RNA < 15 IU/mL at post-transplant week 2 but died 15 days post-transplant because of multi-organ failure and septic shock. Conclusion: Among a small population of HCV patients with decompensated cirrhosis, virologic response to ledipasvir / so-fosbuvir plus ribavirin prior to liver transplantation was maintained after transplantation, even if treatment was stopped early. Administration of ledipasvir / sofosbuvir plus ribavirin before liver transplant can prevent post-transplant HCV recurrence.

Background and aimsTransjugular intrahepatic portosystemic shunt (TIPS) may be placed to treat complications of portal hypertension by creating a conduit between the hepatic and portal vein. The diagnosis of hepatocellular carcinoma (HCC) is typically made by multiphasic imaging studies demonstrating arterial enhancement with washout on arterial, portal venous, and delayed phase imaging. The aim of our study was to determine how the presence of TIPS would affect the imaging diagnosis of HCC.MethodsThis was a single-center electronic database review of all patients who underwent multiphasic imaging with MRI or CT scan for HCC screening between January 2000 and July 2017 and who were subsequently diagnosed with HCC. Data collected included patient demographics, liver disease characteristics including CPT score, MELD-Na, AFP, type of imaging, tumor stage, and lab values at the time of HCC diagnosis. The diagnosis of HCC was made using LI-RADS criteria on contrast-enhanced CT or MR imaging and confirmed by chart abstraction as documented by the treating clinician. Demographic and imaging characteristics for HCC patients with and without TIPS were compared.ResultsA total of 279 patients met eligibility criteria for the study, 37 (13.2%) of whom had TIPS placed prior to diagnosis of HCC. There was no significant difference in demographics or liver disease characteristics between patients with and without TIPS. Compared to cirrhotic patients with no TIPS prior to HCC diagnosis, patients with TIPS had significantly more scans with a longer duration of surveillance until HCC diagnosis. However, LI-RADS criteria and stage of HCC at diagnosis were not significantly different between both groups. There were no differences in outcomes including liver transplant and survival.ConclusionThe presence of TIPS does not lead to a delayed diagnosis of HCC. It is associated, however, with greater duration of time from first scan to diagnosis of HCC.

Abstract The Chinese Government has promulgated the “Belt and Road Initiative” (BRI) to increase trade flows and integrate goods markets between China and BRI countries. The validity of purchasing power parity (PPP) implies well‐integrated goods markets, a precondition for further economic convergence, and the next stage of economic integration in factor, service, and financial markets. Our study aims to examine the validity of the PPP and the extent of goods market integration between China and selected BRI countries in Africa. Since the functional form of the cointegrating relationship may not be exact or linear, we adopt the nonparametric rank tests for analysis without prior knowledge and specification of the functional form. We also address the rank problems that occur in multivariate rank tests. Our empirical results provide strong evidence of an unrestricted PPP relationship with reasonably strong evidence of nonlinearity in the data. We also find that some African BRI countries have experienced goods market integration with China during the second‐half period only. This indicates that the introduction of the BRI in 2013 and China's active involvement in African economic development through BRI projects are leading to enhanced goods market integration between China and Africa. The results indicate favorable prospects of closer economic cooperation in the factor, service, and financial markets to build a free trade area or common markets with BRI countries in Africa.

Abstract Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of − 0.11 (95% CI − 0.15, − 0.07, Z = 5.45; P

The aim of this review is to explore the potential of new regenerative medicine approaches in the treatment of cholestatic liver fibrosis. Cholestatic liver diseases, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and biliary atresia (BA), due to the accumulation of bile, often progress to liver fibrosis, cirrhosis, and liver failure. When the disease becomes severe enough to require liver transplantation. Deeply understanding the disease’s progression and fibrosis formation is crucial for better diagnosis and treatment. Current liver fibrosis treatments mainly target the root causes and no direct treatment method in fibrosis itself. Recent advances in regenerative medicine offer a potential approach that may help find the ways to target fibrosis directly, offering hope for improved outcomes. We also summarize, analyze, and discuss the current state and benefits of regenerative medicine therapies such as mesenchymal stem cell (MSC) therapy, induced pluripotent stem cells (iPSCs), and organoid technology, which may help the treatment of cholestatic liver diseases. Focusing on the latest research may reveal new targets and enhance therapeutic efficacy, potentially leading to more effective management and even curative strategies for cholestatic liver diseases.

Abstract Hirschsprung disease is characterized by the absence of enteric neurons caused by the defects of enteric neural crest cells, leading to intestinal obstruction. Here, using induced pluripotent stem cell-based models of Hirschsprung and single-cell transcriptomic analysis, we identify a gene set of 118 genes commonly dysregulated in all patient enteric neural crest cells, and suggest HDAC1 may be a key regulator of these genes. Furthermore, upregulation of RNA splicing mediators and enhanced alternative splicing events are associated with severe form of Hirschsprung. In particular, the higher inclusion rate of exon 9 in PTBP1 and the perturbed expression of a PTBP1-target, PKM, are significantly enriched in these patient cells, and associated with the defective oxidative phosphorylation and impaired neurogenesis. Hedgehog-induced oxidative phosphorylation significantly enhances the survival and differentiation capacity of patient cells. In sum, we define various factors associated with Hirschsprung pathogenesis and demonstrate the implications of oxidative phosphorylation in enteric neural crest development and HSCR pathogenesis.

Abstract Background In addition to high vaccination levels, COVID-19 control requires uptake and continued adherence to personal hygiene and social distancing behaviors. It is unclear whether residents of a city with successive experience in worldwide pandemics such as SARS, would quickly adopt and maintain preventive behaviors. Methods A population-based, longitudinal telephone survey was conducted between in first local wave of the COVID-19 pandemic (April 2020) and third local wave (December 2020) (n = 403). The study examined factors associated with personal hygiene and social distancing behavior fatigue, as measured by reduced adherence. Results Over 9 months, face mask use increased (96.5–100%, p

Genetic mutations are critical factors leading to congenital surgical diseases and can be identified through genomic analysis. Early and accurate identification of genetic mutations underlying these conditions is vital for clinical diagnosis and effective treatment. In recent years, artificial intelligence (AI) has been widely applied for analyzing genomic data in various clinical settings, including congenital surgical diseases. This review paper summarizes current state-of-the-art AI-based approaches used in genomic analysis and highlighted some successful applications that deepen our understanding of the etiology of several congenital surgical diseases. We focus on the AI methods designed for the detection of different variant types and the prioritization of deleterious variants located in different genomic regions, aiming to uncover susceptibility genomic mutations contributed to congenital surgical disorders.

Abstract Background Assessing motor function is a simple way to track cognitive impairment. We analysed the associations between cognitive and motor function and assessed the predictive value of two motor function measuring tools for cognitive impairment in older adults with multimorbidity in primary care settings. Methods We conducted a prospective cohort study with a 1 year follow-up. Patients aged ≥60 years with ≥2 morbidities were recruited from four primary care clinics. Motor function was assessed using handgrip strength and a sarcopenia screening scale (SARC-F). Cognitive function was measured using the Hong Kong Montreal Cognitive Assessment (HK-MoCA). We defined cognitive impairment as an HK-MoCA score

Abstract Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear. We showed in this study that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

Abstract Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.8% of the population) was a carrier for one or more recessive conditions, and 1 in 12 individuals (8.30% of the population) was a carrier for treatable inherited conditions. In alignment with current American College of Obstetricians and Gynecologists (ACOG) pan-ethnic carrier recommendations, 1 in 26 individuals were identified as carriers of cystic fibrosis, thalassemia, and spinal muscular atrophy in the Southern Chinese population. When the >1% expanded carrier screening rate recommendation by ACOG was used, 11 diseases were found to meet the criteria in the Southern Chinese population. Approximately 1 in 3 individuals (35.5% of the population) were carriers of these 11 conditions. If the 1 in 200 carrier frequency threshold is used, and additional seven genes would meet the criteria, and 2 in 5 individuals (38.7% of the population) would be detected as a carrier. This study provides a comprehensive catalogue of the carrier spectrum and frequency in the Southern Chinese population and can serve as a reference for careful evaluation of the conditions to be included in expanded carrier screening for Southern Chinese people.

Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA.

Background Choledochal cysts (CC) are congenital bile duct anomalies with 6–30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients. Methods Liver organoids (n = 51) were generated from liver/bile duct biopsies of CC (n = 7; type I) and hepatoblastoma (n = 5; HB: non-tumor & tumor) for RNA sequencing. Bioinformatics analysis was conducted to identify differentially expressed cancer-related genes in CC and controls. We compared CC with non-cancerous and cancerous controls, normal adjacent non-tumor region of hepatoblastoma (HB) liver as non-cancerous control and tumor region as non-CC cancer control (HB-tumor). Reverse transcription real-time quantitative PCR (RT-qPCR) verification and immunohistochemistry of selected genes was conducted in additional CC and HB liver biopsies. Findings HB non-tumor and HB tumor organoids displayed distinct gene expression profiles. Expression profiling separated CC organoids into two clusters, one overlapping with HB non-tumor and the other one with HB tumor organoids. Genes selected based on their log2FoldChange values for RT-qPCR verification in 31 CC and 11 HB non-tumor liver tissues revealed significantly elevated expression of FGFR2 in 7 and CEBPB in 2 CC liver tissues (CC vs HB: 4.082 vs. 0.7671, pInterpretation The study identified dysregulated genes related to cancer pathways in CC patients suggesting cancer risk. The findings suggest that the elevated expression of FGFR2 and CEBPB in liver may contribute to cancer development in CC patients.

BackgroundBiliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown.MethodPlasma samples of 11 BA and 24 controls were collected for liver function test, Aβ40 and Aβ42 measurement by enzyme-linked immunosorbent assay (ELISA). Pearson's chi-squared test or Mann–Whitney U test was performed to assess differences between groups. Correlation between Aβ42/Aβ40 and liver function parameters was performed using Pearson analysis. The area under the receiver-operative characteristic (ROC) curve (area under curve; AUC) was measured to evaluate the diagnostic power of Aβ42/Aβ40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of Aβ42/Aβ40 combined with other hepatic function parameters.ResultsPlasma Aβ42/Aβ40 was elevated in BA patients. Aβ42 displayed a weak positive correlation with γ-glutamyl transpeptidase (GGT) (Pearson’s correlation = 0.349), while there was no correlation for Aβ40 with hepatic functions. Aβ42/Aβ40 was moderately correlated with GGT, total bile acid (TBA), direct bilirubin (DBIL) (Pearson’s correlation = 0.533, 0.475, 0.480), and weakly correlated with total bilirubin (TBIL) (Pearson’s correlation = 0.337). Aβ42/Aβ40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552–0.941), p

Abstract To evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literature reporting BA biomarkers published before August 2020. Screening, data extraction, and quality assessment were performed in duplicate. A total of 51 eligible studies were included in the systematic review, and data from 12 (4182 subjects) were extracted for meta-analysis regarding the following 2 domains: (1) serum matrix metallopeptidase-7 (MMP-7), interleukin33 (IL-33) and γ-glutamyl transferase (GGT) to differentiate BA from non-BA; (2) the aspartate aminotransferase to platelet ratio index (APRi) to predict post-KPE liver fibrosis/cirrhosis. The summary sensitivity, specificity and area under the curve (AUC) of MMP-7 for diagnosing BA were 96%, 91% and 0.9847, respectively, and those of GGT were 80%, 79% and 0.9645, respectively. The summary sensitivity and specificity of IL-33 for diagnosing BA were 77% and 85%, respectively. The summary sensitivity and specificity of APRi for predicting post-KPE liver fibrosis were 61% and 80%, respectively, and the summary sensitivity, specificity and AUC of APRi for predicting post-KPE cirrhosis were 78%, 83% and 0.8729, respectively. Moreover, good evidence was shown in investigations of serum IL-18 and IL-33 in distinguishing BA from healthy controls, serum IL-18 for prognosis of post-KPE persistent jaundice, and serum hyaluronic acid and MMP-7 for prognosis of post-KPE significant liver fibrosis. MMP-7, IL-33 and GGT are useful biomarkers to assist in the diagnosis of BA. APRi might be used to predict post-KPE significant liver fibrosis and cirrhosis. These noninvasive biomarkers can be integrated into the management protocol of BA.

Abstract We present a 37 years’ experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE). A retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. Outcome parameters were clearance of jaundice (COJ), native liver survival (NLS) and long-term complications. Factors affecting the operative outcomes were analyzed. The median duration of follow up was 17.5 (IQR: 13.5–22) years. Over 66% of patients became jaundice-freed at 1 year after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 (IQR: 4.3–8.4) years. The NLS rates at 10 and 20 years were 70.7% and 61.5% respectively with no significant change over the study period. The median age at KPE was 59 (IQR: 49–67) days. KPE performed before 70 days was associated with higher odd ratios for successful drainage but the age of KPE did not have an impact on the long-term NLS. Among all native liver survivors (n = 153), the median bilirubin level was 24 (IQR: 16–36) µmol/L. Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively. With a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long-term survival without LT. Although cholestasis, portal hypertension and recurrent cholangitis are common in long-term NLS, with a comprehensive follow management strategy, they do not always necessitate LT. Our study serves as an example for countries where deceased donor organs are scarce due to very low donation rate.