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Objective: To reveal the regional division of the spatial structure of NASH fibrosis and the communication relationship between cells in different regions and to analyse specific marker genes as potential therapeutic targets for NASH fibrosis. Methods: The liver sections of healthy controls, NAFL patients and NASH patients were measured by spatial transcriptomics, and integration analysis was performed with single-cell RNA-seq. Differential expression, functional pathway prediction, and deconvolution analysis revealed lineage-specific changes in gene expression, subpopulation composition and intercellular communication in NASH and identified key genes involved in HSC activation. The role of key genes in NASH fibrosis was verified in vitro and in vivo. Result: Descending and clustering analysis of 4114 nuclei from liver tissues of healthy controls, NAFL, and NASH showed that the distribution of cluster5 (fibrotic region) is dominated by lobules, and a small amount of fibrosis can be seen in the sink area. Functional analysis suggested that differentially expressed genes of cluster5 were concentrated in ECM structural components and signalling molecules. Six cell types were obtained by integrating the single-cell sequencing dataset (GSE189175). Compared with the healthy control and NAFL groups, the NASH group had significantly increased proportions of HSCs and myofibroblasts, which were distributed in the lobule and the portal area around the fibrotic area. Simultaneously, the infiltration of Kupffer cells around the fibrotic area also increased. The cell communication analysis showed that diffusive cell communication was the main type, including endocrine, paracrine and autocrine communication, followed by ECM-receptor cell communication. According to the analysis of differentially expressed genes in the subsets, AEBP1 and DPT are relatively highly expressed in cluster5, as well as in HSCs and myofibroblasts. SCENIC analysis found that AEBP1+ and DPT+ myoblasts were involved in the activation of HSCs and fibrosis formation. Immunohistochemistry verified the high expression of AEBP1 and DPT in patients with NASH fibrosis. After transfection of AEBP1 and DPT interference fragments in LX2 cells in vitro, the mRNA level of Collagen Ⅰ in cells was significantly lower than that of the siRNA-NC group and blank control group. Conclusion: Our study is the first to reveal lineage-specific changes in gene expression, subpopulation composition and cell communication in NASH fibrosis, providing new directions for potential therapeutic targets for NASH fibrosis.

Background The majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15% − 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. The clinical features and ALT flare patterns in HBeAg-positive mothers versus HBeAg-negative mothers are not fully explored. Thus, we design a cohort study to investigate the aforementioned area and generate data to assist healthcare providers in the better management of mothers with hepatitis B. Method This study is a single-center and prospective cohort study (n = 360) that consists of two groups of patients including HBsAg-positive mothers (n = 120) and healthy mothers without HBV infections (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted for the prevention of MTCT but discontinued at delivery if no further indication for the treatment. Mothers are enrolled at the gestational weeks of 12–24. After delivery, both mothers and their infants will be followed up until postpartum week 24. Clinical and laboratory data are collected every 4 weeks during the study except there are no follow-up visits at the postpartum weeks 16 and 20. The primary assessment is the proportion of patients with postpartum ALT flares. The secondary assessments are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers. Discussion We will assess the incidence of postpartum ALT flares in mothers with chronic hepatitis B with subgroup analysis based on HBeAg status, and evaluate the normal range of postpartum ALT in healthy mothers without hepatitis B. In mothers with hepatitis B, the independent risk factors for predicting postpartum ALT flares are also investigated. Trial Registration Number at the Chinese Clinical Trial Registry: ChiCTR2200061130

Objective To assess the clinical and histological features of metabolic associated fatty liver disease (MAFLD) in non-lean population. Methods Current study enrolled consecutive non-lean (Body Mass Index (BMI) > 23 kg/m2) patients with MAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23 ~ 1) were also analysed through the logistic regression model. Results Among 184 non-lean patients with MALFD enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-Glutamyl transpeptidase (GGT), higher levels of platelet (PLT), Glucose (Glu), prothrombin time (PT), and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group vs the overweight group (19.33% vs 40.00%, P = 0.002). Multivariate logistic regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT) and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with MAFLD. Compared with the traditional FIB-4 (AUC = 0.77) and APRI (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT and CHOL was more accurated in predicting moderate to severe fibrosis in non-lean patients with MAFLD (AUC = 0.87). Conclusions Clinical and histological features differed between obesity and overweight patients with MAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT and CHOL provides a better model to predictor moderate to severe fibrosis in non-lean patients with MAFLD.

BackgroundIncreased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10 and treatment response in patients with CHC treated with direct-acting antiviral agents (DAAs) therapy.MethodsWe measured the dynamic changes of IP-10 in samples from 90 patients with CHC. The serum IP-10 levels, intrahepatic expressions of IP-10 mRNA, and protein were determined, respectively. For the in vitro experiments, the expression changes of IP-10 in hepatitis C virus (HCV)-replicating Huh-7 cells with or without non-structural protein 5A (NS5A) inhibitor were analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting.ResultsPatients with chronic hepatitis C had increased baseline IP-10 levels, intrahepatic IP-10 mRNA, and protein expression. After initiating DAAs therapy, serum IP-10 levels decreased gradually in patients who achieved cure, whereas in patients who failed the therapy, IP-10 levels did not change significantly or recovered from the initial decline. Multivariate logistic regression analysis confirmed that baseline IP-10 level ≤ 450 pg/ml and decline >30% at 12 weeks independently predicted the SVR in patients with CHC who received DAAs. In vitro, the expression of IP-10 mRNA and protein in HCV-replicating Huh-7 cells increased significantly. However, such activities were downregulated by NS5A inhibitor, followed by the reduction of HCV RNA levels and a decline in IP-10 levels.ConclusionIP-10 interfered with HCV replication in hepatocytes and the dynamic decline in IP-10 levels during DAA treatment predicted the SVR in patients with CHC.

Data that assess maternal and infant outcomes in hepatitis C virus (HCV)-infected mothers are limited.To investigate the frequency of complications and the associated risk factors.We performed a cohort study to compare pregnancy and fetal outcomes of HCV-viremic mothers with those of healthy mothers. Risk factors were analyzed with logistic regression.Among 112 consecutive HCV antibody-positive mothers screened, we enrolled 79 viremic mothers. We randomly selected 115 healthy mothers from the birth registry as the control. Compared to healthy mothers, HCV mothers had a significantly higher frequency of anemia [2.6% (3/115)Maternal HCV infections may associate with pregnancy and obstetric complications. We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference, suggesting fetal growth restriction.

Background. To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. Method. We performed a single-center prospective cohort study to analyze changes of NK cells at weeks 12 and 24 from baseline in CHB patients who received PEGylated-interferon- (PEG-IFN-) α-2a versus entecavir. The frequencies of NK, CD56bright, CD56dim, IFNAR2+, NKp46+, NKp46bright, and NKp46dim NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. Results. In PEG-IFN-α-treated patients, posttreatment CD56bright NK cell frequency increased, but CD56dim NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56bright and CD56dim NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56bright NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-α responders from baseline, while changes were absent in PEG-IFN-α nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46bright and IFNAR2+ NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions. In CHB patients, PEG-IFN-α treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.

Adenovirus‐mediated herpes simplex virus thymidine kinase gene therapy (ADV‐TK) in combination with interventional treatment could relieve the symptoms in patients with widespread splenic metastasis., Adenovirus‐mediated herpes simplex virus thymidine kinase gene therapy (ADV‐TK) in combination with interventional treatment could relieve the symptoms in patients with widespread splenic metastasis

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 60 ml/mi/1.7 m

Decompensated cirrhotic patients with hepatitis C (HCV) are often under-represented in clinical trials. We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir (SOF)-based regimens in these patients.We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020. Outcomes of interest were sustained virologic response (SVR) and safety of SOF-based regimens in decompensated HCV patients. Two reviewers independently performed the study selection and data extraction.We included 33 studies that enrolled 5,302 HCV patients. The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1% (95% CI: 82.8-87.3). Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR (91.0%, 95% CI: 87.7-93.9) than that of SOF/ledipasvir±ribavirin [(86.3%, 95% CI: 84.6-87.8);The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy, with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.

Although gut dysbiosis appears in 20%–75% of cirrhotic patients, there are limited data on microbiota profiles in viral hepatitis cirrhotics and its role in progression to cirrhosis. Further understanding on the relationship between gut dysbiosis and cirrhosis presents a unique opportunity in not only predicting the development of cirrhosis but also discovering new therapies. Recent advances have been made on identifying unique microbiota in viral hepatitis cirrhotics and adopting the microbiota index to predict cirrhosis. Therapeutic intervention with microbiome-modulating has been explored. Cirrhosis from viral infection has unique bacterial or fungal profiles, which include increased numbers of Prevotella, Streptococcus, Staphylococcaceae, and Enterococcus, as well as decreased Ruminococcus and Clostridium. In addition, the gut microbiota can stimulate liver immunity, effectively helping hepatitis virus clearance. In clinical settings, CDR, GDI, Basidiomycota/Ascomycota, specific POD, and so forth are efficient microbiota indexes to diagnose or prognosticate cirrhosis from viral hepatitis. FMT, probiotics, and prebiotics can restore microbial diversity in cirrhotic patients with viral hepatitis, decrease ammonia serum or endotoxemia levels, prevent complications, reduce rehospitalization rate, and improve prognosis. Cirrhotics from viral hepatitis had unique bacterial or fungal profiles, associated with specific metabolic, immune, and endocrinological statuses. Such profiles are modifiable with medical treatment. The role of gut archaea and virome, implementation of FMT, microbiota metabolites as adjuvant immunotherapy, and microbiota indexes for prognostication deserve attention.

Although hepatitis B virus (HBV) reactivation has been reported in hepatitis C patients who received interferon therapy, rare cases of HBV reactivation occur in the context of direct-acting antiviral (DAA) agent therapy for treatment of hepatitis C virus (HCV) infection. Recent studies observed that the reactivations were predominantly in hepatitis B surface antigen (HBsAg) positive patients, but reactivation can rarely occur in patients who are HBsAg negative and hepatitis B core antibody (HBcAb) positive. The severity of an HBV flare varies. In some cases, severe liver injury or fulminant hepatic failure may occur. HBV reactivation may occur regardless of HCV genotype and type of DAA regimens. The onset of HBV reactivation can range from 4 to 48 weeks after initiating DAA therapy. These patients may have undetectable levels of HBV deoxyribonucleic acid (DNA) prior to DAA treatment. Pre-emptive antiviral therapy for HBV should be considered in HBsAg-positive patients with high levels of viremia who are not receiving HBV treatment. If HBV DNA viral load is less than the guideline criteria for HBV treatment, one should consider pre-emptive HBV antiviral versus HBV DNA monitoring during DAA therapy. For patients who are HBsAg negative but HBcAb positive, close monitoring of serum alanine aminotransferase (ALT) levels during/post-treatment is highly recommended. The current review summarizes the recommendations of different society guidelines and discusses the appropriate management strategies in various patient profiles. Keywords: Co-infection, Treatment induced flares, Hepatitis B exacerbation, Hepatitis C therapy, Prevention of disease reactivation

Background Appropriate passive-active immunoprophylaxis effectively reduces mother-to-child transmission (MTCT) of hepatitis B virus (HBV), but the immunoprophylaxis failure was still more than 5% under the current strategy. The study objective was to investigate the effects of high dose of HB vaccine on MTCT and immune response for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. Methods This was a prospective, multicenter, large-sample cohort study in four sites of China, and 955 pairs of HBsAg-positive mothers and their infants were enrolled in our investigation. The infants were given 10 μg or 20 μg HB vaccine (at age 0, 1, and 6 months) plus HB immunoglobulin (at age 0 and 1 month). Serum HBsAg, antibody to HBsAg (anti-HBs), and/or HBV DNA levels in the infants were determined at age 12 months. The safety of 20 μg HB vaccine was evaluated by adverse events and observing the growth indexes of infants. Results Thirteen of 955 infants were HBsAg-positive at 12 months. Stratification analysis showed that immunoprophylaxis failure rates in the 20 μg group were not significantly different from the 10 μg group, whatever maternal HBV load was high or not. But the high dose of HB vaccine significantly reduced low-response rate (anti-HBs 10–100 IU/L) (P = 0.002) and middle-response rate (anti-HBs 100–1000 IU/L) (P = 0.022) and improved high-response rate (anti-HBs ≥ 1000 IU/L) (P 10 IU/mL. For infants born to mothers with HBV DNA ≥ 5 log10 IU/mL, 20 μg HB vaccine did not present these above response advantages. The 20 μg HB vaccine showed good safety for infants. Conclusions The 20 μg HB vaccine did not further reduce immunoprophylaxis failure of infants from HBsAg-positive mothers, but increased the high-response and decreased low-response rates for infants born to mothers with HBV DNA 10 IU/mL. Trial registration Chinese Clinical Trial Registry, ChiCTR-PRC-09000459

Introduction Many individuals test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA after recovering from the coronavirus disease (COVID-19), but the incidence of reactivation is unknown. We, therefore, estimated the incidence of reactivation among individuals who had recovered from COVID-19 and determined its predictors. Methods In this retrospective cohort study, patients with COVID-19 were followed up for at least 14 days after two consecutive negative SARS-CoV-2 polymerase chain reaction test results obtained ≥24 hours apart, and the frequency of SARS-CoV-2 reactivation was assessed. Results Of the 109 patients, 29 (27%) experienced reactivation, and seven (24%) of these were symptomatic. The mean period for the real-time PCR tests for SARS-CoV-2 from negative to positive results was 17 days. Compared with patients without reactivation, those with reactivation were significantly younger and more likely to have a lymphocyte count of

We primarily quantified exposure patterns, transmission characteristics, and the clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection among household contacts of individuals with severe coronavirus disease‐2019 (COVID‐19). We conducted a retrospective cohort study of 20 index patients hospitalized with severe COVID‐19 and 79 of their household contacts. We determined the transmission frequency, range of manifestations of SARS‐CoV‐2 infection, and factors associated with infection in household settings. Of the 79 household contacts, 53 (67%) developed SARS‐CoV‐2 infection (49 [62%] symptomatic, 4 [5%] asymptomatic). Eight patients (10%) developed severe COVID‐19, and one died of COVID‐19 pneumonia (case‐fatality rate: 1.9%). The probability of SARS‐CoV‐2 infection was similar in children and adults (55% vs. 72%, p = .14), with children being less likely to develop the symptomatic disease (46% vs. 68%, p = .06). Handwashing ≥ 5 times/day was associated with reduced infection risk (52.8% vs. 76.9%, p = .04). SARS‐CoV‐2 has a high frequency of transmission among household contacts. Nonhospitalized individuals with SARS‐CoV‐2 infection should be quarantined in patient care facilities rather than at home to minimize spread, if possible, and frequent handwashing should be practiced to prevent transmission., Highlights The new coronavirus, SARS‐CoV‐2, is the cause of the COVID‐19 pandemic. It is readily transmitted and may cause severe pneumonia, but information on its infectivity and the full disease spectrum of the infection is limited because many infections are undiagnosed.The study followed a cohort of 79 household contacts of 20 unrelated index patients with severe COVID‐19 pneumonia. All household contacts had exposure to infection, and the complete cohort was followed‐up; thus, it was possible to determine the rates of transmission and the severity and complete clinical course of all infections. We were also able to determine the risk factors for transmission and severe disease and to compare the susceptibility of children and adults to infection and disease.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

Background/Purpose Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV. Methods In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA Results In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA Conclusions In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT.

To investigate whether IL-21 levels predict treatment outcomes of salvage therapy among patients with suboptimal response (SOR) to nucleos(t)ide analogues (NAs), serum IL-21 levels were measured in a prospective cohort of hepatitis B e antigen (HBeAg)-positive patients with SOR to antiviral therapy. The patients switched therapy to entecavir (ETV) with or without adefovir (ADV) for 104 weeks. IL-21 levels at treatment week 12 in patients who achieved HBeAg loss with undetectable levels of hepatitis B virus (HBV)-DNA at week 104 were the primary endpoint and the results were compared with those of corresponding patients without such an endpoint. Furthermore, IL-21 levels at treatment week 12 in patients who achieved an HBeAg-level decline at week 104 were assessed as the secondary endpoint. Among 24 enrolled patients with SOR to ADV (n=21), telbivudine (n=2) or ETV (n=1), the median (10-90th percentile) levels of HBeAg, HBV-DNA and ALT at baseline were 2.7 (0.2-3.1) log10 S/CO, 5.2 (3.5-7.5) log10 IU/ml and 0.9 (0.5-3.1) upper limit of normal, respectively. Comparison of the patients with and without HBeAg loss at week 104 indicated that their mean IL-21 levels did not significantly differ at week 12 (63.0±14.4 vs. 55.9±10.5 pg/ml; P=0.26). In the secondary endpoint analyses of patients with and without HBeAg level decline, the elevated levels of IL-21 at the first 12 weeks were significantly higher in the decline group (15.6±8.3 vs. 3.1±13.2 pg/ml; P=0.03). Following adjustment for confounding factors, the elevated levels of IL-21 from baseline to week 12 independently predicted an HBeAg level decline at week 104 (odds ratio=1.137, R2=0.23; P=0.047). In conclusion, the serum IL-21 levels at the first 12 weeks during the salvage therapy independently predicted HBeAg level decline at treatment week 104 in patients with SOR to NAs (ClinicalTrials.gov identifier: NCT01829685; date of registration, April 2013).

The outbreak of coronavirus disease-2019 (COVID-19) impacts public health dramatically around the world. The demographic characteristics, exposure history, dates of illness onset and dates of confirmed diagnosis were collected from the data of 24 family clusters from Beijing. The characteristics of the cases and the estimated key epidemiologic time-to-event distributions were described. The basic reproductive number (R0) was calculated. Among 89 confirmed COVID-19 patients from 24 family clusters, the median age was 38.0 years and 43.8% were male. The median of incubation period was 5.08 days (95% confidence interval (CI) 4.17–6.21). The median of serial interval was 6.00 days (95% CI 5.00–7.00). The basic reproductive number (R0) was 2.06 (95% CI 2.02–2.08). The median of onset-to-care-seeking days and the median of onset-to-hospital admission days were significantly reduced after 23 January 2020, which implied the enhanced public health awareness among families. With epidemic containment measures in place, the results can inform health authorities about possible extent of epidemic transmission within families. Furthermore, following initiation of interventions, public health measures are not only important for curbing the epidemic spread at the community level but also improve health seeking behaviour at the individual level.

To compare the diagnostic utility of serum markers in nonalcoholic fatty liver disease (NAFLD) patients with chronic hepatitis B (CHB). This study enrolled 118 consecutive biopsy-proven NAFLD patients with or without CHB. Fibrosis scores of each marker were compared against histological fibrosis staging. Receiver operating characteristic curve (ROC) analysis helped assess the accuracy of each marker. In patients with both diseases, 12.96% (7/54) had advanced fibrosis on biopsy and aspartate aminotransferase (AST) to platelet ratio index was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC (95% confidence interval) for AST to platelet ratio index (APRI) were 0%, 93.62%, 0%, 86.27%, and 0.676 (0.524–0.828), respectively. The markers ranked as follows from highest to lowest with respect to their accuracy: APRI; BARD; fibrosis-4; and AST to ALT ratio. In patients without CHB, fibrosis-4 was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, PPV, NPV, and area under the ROC (95% confidence interval) for fibrosis-4 were 77.78%, 85.45%, 46.67%, 95.92%, and 0.862 (0.745–0.978), respectively. Serum markers are less reliable in predicting advanced fibrosis in NAFLD patients with CHB; APRI is the most accurate predictor of the absence of advanced fibrosis.

BACKGROUND Data on tenofovir alafenamide fumarate (TAF) for preventing mother-to-child transmission of hepatitis B virus (HBV) are lacking. AIMS To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother-to-child transmission. METHODS Mothers with chronic HBV infection, positive for hepatitis B e-antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother-to-child transmission were enrolled retrospectively from multiple centres with data collection on mother-infant dyads up to postpartum week 24-28. Primary measurements were the mother-to-child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. RESULTS Among 71 mothers enrolled, the mean (±SD) age was 30.3 (±2.2) years. TAF was initiated during the second or third trimester and continued to delivery with a mean (±SD) duration of 12.8 (±4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA

Background A critical aspect of liver transplantation in hepatitis B patients is to prevent graft reinfection with hepatitis B virus. The use of hepatitis B immune globulin after transplant was a significant milestone, which allowed prolonged graft and patient survival by controlling hepatitis B reinfection in liver grafts. The development of anti-viral treatments with oral nucleos(t)ide analogues, led to a further reduction in graft reinfection and improvement in patient survival. The combination of the aforementioned two therapies has been widely used in hepatitis B-associated liver transplants. Aims To address the post-transplant management of hepatitis B and provide updates on preventing graft reinfection. Methods We performed a literature search on Ovid and PubMed for randomised controlled trials or cohort studies in English, which investigated the effectiveness of hepatitis B immune globulin and anti-viral therapy on hepatitis B-associated transplants (1/2000-1/2020). Studies that met pre-established criteria were reviewed. Results Based on currently available evidence, an algorithm for post-transplant management with anti-viral therapy is proposed. Also, the management of recipients who received grafts from hepatitis B core antibody-positive donors is discussed. Conclusions The development of hepatitis B immune globulin and anti-viral treatments led to substantial improvement in graft and patient survival. The prevention of hepatitis B graft reinfection is complex and involves a broad interdisciplinary team.

Felty’s syndrome (FS) is a disorder wherein patients with rheumatoid arthritis develop splenomegaly, neutropenia, and in some cases, portal hypertension without underlying cirrhosis. Esophageal variceal bleeding is a complication of FS in patients with portal hypertension. In contrast to splenectomy, few reports exist on the management of variceal bleeding with endoscopic therapy. Moreover, the long-term outcome has not been reported. We present a patient with esophageal variceal bleeding due to portal hypertension secondary to Felty’s syndrome. The patient was followed up for two years postendoscopy intervention. Literature review was performed and the histological features of portal hypertension in FS are discussed. The patient presented with a typical triad of rheumatoid arthritis (RA), splenomegaly, and neutropenia and was diagnosed as Felty’s syndrome in 2012. She was admitted to our hospital in September 2017 for esophageal variceal bleeding. At the time of admission, her liver function test was normal. Abdominal CT showed no signs of cirrhosis and portal vein obstruction. Liver biopsy further excluded diagnosis of cirrhosis and supported the diagnosis of porto-sinusoidal vascular disease (PSVD), which was previously named as noncirrhotic idiopathic portal hypertension (NCIPH). An upper abdominal endoscopy revealed gastric and esophageal varices. A series of endoscopies was performed to ligate the esophageal varices. The patient was followed up for two years and did not show rebleeding. In conclusion, comorbid PSVD might be a cause of portal hypertension in FS patients. The present case had excellent outcome in two years, which supported the use of endoscopic therapy for the management of variceal bleeding in FS patients. Further large prospective study is needed to confirm the findings.

Background Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). Methods A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Results Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. Conclusions TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.

BACKGROUND Data on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real-world setting are limited. AIM To investigate TDF for preventing vertical transmission of HBV in real-world practice. METHODS Hepatitis B e-antigen (HBeAg)-positive mothers with HBV-DNA >6 log10 IU/mL to receive TDF between gestational weeks 24-33 and delivery were prospectively enrolled and followed until post-partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother-to-child transmission rates. Secondary outcomes were maternal HBV-DNA level suppression (

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed drugs and can cause drug-induced liver injury. Although patients with drug-induced liver injury from NSAIDs often recover spontaneously, 3% of them required hospitalization and those with persistent cholestasis present a diagnostic challenge. Recently, a few cases of children with persistent jaundice reported have been linked to the vanishing bile duct syndrome. However, data on adult patients is limited. Case presentation We report herein a case of an adult patient who had persistent cholestasis with hyperlipidemia from the VBDS after ibuprofen use. We described a female patient with severe jaundice after taking ibuprofen, although she had no history of liver disease before. The drug-induced liver injury from ibuprofen was identified by clinical features and liver biopsy, which included the Roussel Uclaf Causality Assessment Method scores of 6 and pathological features of cholestasis with stage four drug-induced injury as well as loss of bile duct structures. The clinical course was featuring with persistently high levels of bilirubin associated with hyperlipidemia over the period of one month, although the laboratory abnormalities were slightly improved spontaneously after the cessation of ibuprofen. Her autoantibodies markers including AMA-M2 ASMA, RO-52, LKM, SLA, and anti-glycoprotein-210 were negative. The second liver biopsy was performed on day 213 due to persistent hyperbilirubinemia. Pathological findings were consistent with the diagnosis of vanishing bile duct syndrome. Conclusions A rare case of ibuprofen-associated vanishing bile duct syndrome in an adult female patient is presented. Clinicians need to be aware of vanishing bile duct syndrome as a serious consequence of ibuprofen use in adult patients, although ibuprofen is considered to be among the safest NSAIDs.

Background & Objective: Although data on the effects of liraglutide and semaglutide in patients with diabetes have been reviewed, their therapeutic outcomes in obese/overweight individuals without diabetes have not been summarized. We conducted a systematic review to evaluate their effects on the latter population. Methods: We searched the PubMed, EMBASE, Cochrane, CNKI, and Wanfang databases. Studies regarding obese/overweight adults without diabetes treated with liraglutide/semaglutide compared with other active agents or placebos were accessed. The primary outcomes were the proportions of adults with at least 5% and 10% weight reduction. The secondary outcomes included metabolic indicators and adverse events. Results: Eighteen studies with 10,938 obese/overweight adults without diabetes were included. When stratified by the categories of at least 5% and 10% weight loss, the pooled data showed medians 27.7% and 10.3% of control groups versus 65.3% and 30.7% of liraglutide 3 mg once daily, respectively; whereas medians 47.6% and 20.4% of control groups vs 86.6% and 75.3% of semaglutide 2.4 mg once weekly were found in the two categories, respectively. Both agents either improved or had no impact on lipid or glycemia. Liraglutide or semaglutide therapy had discontinuation rates of 2.4%–11.4% which overlapped with 0.7%–8.6% in control groups. The frequency of adverse events was comparable between the treatment groups and the control groups (66.5%–95.8% vs 46.9%–96.1%), which were mild to moderate graded by studies. Conclusion: Liraglutide and semaglutide therapy led to a clinically relevant (⩾5%) weight loss of 48.2%–88.7% among obese/overweight adults without diabetes. Both liraglutide and semaglutide are associated with weight loss and are well-tolerated.

Chronic hepatitis B; HBeAg status; Viral genome variation Hepatitis B crónica; Estado de HBeAg; Variación del genoma viral Hepatitis B crònica; Estat de HBeAg; Variació del genoma viral Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants. These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to the negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype.

Minority patients are under-screened for chronic hepatitis C (CHC) in the USA, and limited data exist for minority patients with advanced fibrosis. In this cross-sectional study, CHC patients who were prescribed direct-acting antiviral agents were divided into White patients and minority patient groups. Primary measurements were the mean fibrosis scores and percentages of patients with stage III–IV fibrosis (late presenters) for the two groups. Among the 1421 patients with self-reported ethnicity, 697 were White patients, and 724 were minority patients (484 Hispanic, 175 Black, 65 Asians). Compared to the White, minority patients had significantly higher mean fibrosis score (p

Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV).In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28.At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups.In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).

Background TAF has shown less bone and renal effects with similar efficacy rates compared to TDF in Phase 3 studies after 96 weeks of double-blind (DB) treatment. We evaluated patients who completed 96 weeks of DB treatment with TAF or TDF and switched to open label (OL) treatment with TAF, including those with 1 year of data (through Week 144) to determine changes in bone mineral density (BMD), creatinine clearance (CrCL), and the maintenance of viral suppression. Methods 1298 CHB patients who were HBeAg-negative or HBeAg-positive were randomised and treated with TAF or TDF. At Week 96, 541 (42%; TAF 361; TDF 180) patients had completed DB treatment with TAF or TDF and switched to OL TAF. Analyses included subjects with values at Week 96 and at Week 144 for creatinine clearance (n=401), spine BMD (n=288) or hip BMD (n=287), HBV DNA (n=394) and ALT normalisation by AASLD criteria (n=398). Results CrCL improved in patients who switched from DB TDF to OL TAF at Week 144 compared to Week 96 (n=122, median (Q1, Q3) change=+3.6 (-4.2,+8.4) ml/min, p Conclusions Patients who switched from TDF to TAF demonstrated continued improvements in BMD and CrCL over 48 weeks of treatment, virologic control was maintained, and rates of ALT normalisation increased.

Background TAF, a novel prodrug of tenofovir, has demonstrated efficacy noninferior to that of TDF at Week 48 in patients with chronic HBV (CHB) with significantly reduced bone and renal effects. Here we evaluated the efficacy and safety of TAF vs TDF in the subset of patients of Chinese ethnicity enrolled in two overseas studies. Methods In 2 Phase 3 studies, HBeAg-negative (Study 108) and HBeAg-positive (Study 110) CHB patients were randomised 2:1 to TAF 25 mg QD or TDF 300 mg QD and treated for 96 weeks. In this analysis, the efficacy (HBV DNA). Results Of 1298 patients randomised and treated, 471 (36%) were of Chinese ethnicity; 156 (TAF 97; TDF 59) and 315 (TAF 207; TDF 108) patients were HBeAg-negative and HBeAg-positive, respectively. For the TAF and TDF groups within each study, baseline characteristics of the study populations were generally similar. Key efficacy results at Weeks 48 and 96 are presented in the Table (table 1). In both HBeAg-negative and HBeAg-positive patients of Chinese ethnicity, the antiviral efficacy of TAF was similar to that of TDF and results were comparable to those in the overall overseas population. Numerically higher percentages of patients treated with TAF achieved normalisation of serum ALT values and anti-HBe seroconversion at Weeks 48 and 96. The safety of TAF and TDF, including changes in renal and bone parameters, were similar to results previously reported in the overall overseas population. Conclusions In CHB patients of Chinese ethnicity, TAF 25 mg showed similar antiviral efficacy to TDF 300 mg, with less change in bone and renal parameters. Results in this subgroup were comparable to those in the overall population.

Tenofovir alafenamide (TAF) has shown equivalent efficacy and improved safety profiles for patients with chronic hepatitis B (CHB) compared to tenofovir disoproxil fumarate (TDF). However, limited data are available for its resistance profiles. In two clinical trials, 1,298 hepatitis E antigen-positive and -negative patients with CHB were randomized 2:1 and treated with TAF (n = 866) or TDF (n = 432). Baseline nucleos(t)ide analog resistance substitutions in HBV polymerase/reverse transcriptase (Pol/RT) were assessed using INNO-LiPA Multi-DR v2/v3. Resistance surveillance was conducted for patients with viremia (HBV DNA ≥ 69IU/ml) by HBV Pol/RT sequencing at week 96 or at discontinuation. In vitro phenotypic analysis was performed for patients with conserved site substitutions or virologic breakthrough while adherent to the study drug. At baseline, the majority of patients harbored virus with wild-type Pol/RT (89.2%), with 10.8% harboring resistance associated mutations. A similar percentage of patients in the TAF or TDF groups qualified for sequence analysis through week 96 (TAF, 11.1%; TDF, 10.9%). Of these, a small percentage of patients experienced virologic breakthrough (TAF, 2.8%; TDF, 3.2%) that was often associated with drug nonadherence (TAF, 30%; TDF, 50%). Across treatment groups, 132 patients qualified for sequence analysis through week 96, with nearly half having no sequence changes from baseline (43.2%). Most sequence changes occurred at polymorphic positions, and no isolates showed a reduction in susceptibility in vitro After 96 weeks, the proportion of patients achieving virus suppression (HBV DNA < 69 IU/ml) was similar across treatment groups, and no substitutions associated with resistance to TAF or TDF were detected. (These studies have been registered at ClinicalTrials.gov under identifiers NCT01940471 and NCT01940341.).

Background Entecavir (ETV) has been shown to be safe and efficacious in randomized controlled trials in highly selected patients with hepatitis B virus (HBV) infection.

Author(s): Tong, MJ; Pan, CQ; Han, S-HB; Lu, DS-K; Raman, S; Hu, K-Q; Lim, JK; Hann, HW; Min, AD | Abstract: BackgroundHepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide.AimTo generate recommendations for the management of Asian Americans infected with HBV.MethodsThese guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women.ResultsAsian American patients, HBeAg positive or negative, with HBV DNA levels g2000 IU/mL (g104 copies/mL) and ALT values above normal are candidates for anti-viral therapy. HBeAg negative patients with HBV DNA g2000 IU/mL and normal ALT levels but who have either serum albumin l3.5 g/dL or platelet count l130 000 mm3 , basal core promoter (BCP) mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life-long anti-viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life-long surveillance for HCC with alpha-fetoprotein (AFP) testing and abdominal ultrasound examination at 6-month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3-month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence.ConclusionsApplication of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.

Despite decreasing prevalence, new cases of hepatitis C in China are increasing recently with growing percentage of patients who are with advanced disease, aging, or not eligible for interferon-based treatments. Hepatitis C infection represents a serious public health burden. This review was based on expert's consensus during a medical forum on hepatitis sponsored by the Beijing Wu Jie-Ping Medical Foundation. The literature searches were conducted in PubMed and critical publications in Chinese journals. Data on hepatitis C prevalence, risk factors, viral or host features, and treatment modalities were extracted and reviewed. Recent large-scale surveys reported reducing prevalence of hepatitis C to approximately 0.4% in China, partly because of regulation changes to safer medical practices and illegalizing commercial blood donations. Patient demographics evolved from being dominated by former paid blood donors to include intravenous drug users and others. Although hepatitis C genotype 1 is the most common, other genotypes are emerging in prevalence. The current standard of care is interferon-based without direct acting antivirals. However, many patients failed therapy because of high treatment costs, substantial needs to manage side effects, difficulties with treatment monitoring in the rural areas, and growing populations of elderly and cirrhotic patients. The lack of high efficacy therapies with good safety profile and low disease awareness in China resulted in increasing public burden of advanced hepatitis C disease. Despite significant reduction of hepatitis C prevalence, iatrogenic, nosocomial, and community transmissions are still significant. In addition to promoting disease awareness, interferon-free regimens are needed to reduce the public health burden.