Search

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). [ABSTRACT FROM AUTHOR]

Background and Aim: To identify individuals with metabolic dysfunction‐associated steatohepatitis (MASH) or "at‐risk" MASH among patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), three noninvasive models are available with satisfactory efficiency, which include magnetic resonance imaging [MRI]‐ AST (MAST), FibroScan‐AST (FAST score), and magnetic resonance elastography [MRE] plus FIB‐4 (MEFIB). We aimed to evaluate the most accurate approach for diagnosing MASH or "at‐risk" MASH. Methods: We included 108 biopsy‐proven MASLD patients who underwent simultaneous assessment of MRE, MRI proton density fat fraction (MRI‐PDFF), and FibroScan scans. Compared with the histological diagnosis, we analyzed the AUC of each model and assessed the accuracy. Results: Our study cohort consisted of 64.8% of MASH and 25.9% of "at‐risk" MASH. When analyzing the performance of each model for the diagnostic accuracy of MASH, we found that the AUC [95% CI] of MAST was comparable to FAST (0.803 [0.719–0.886] vs 0.799 [0.707–0.891], P = 0.930) and better than MEFIB (0.671 [0.571–0.772], P = 0.005). Similar findings were observed in the "at‐risk" MASH patients. The AUCs [95% CI] for MAST, FAST, and MEFIB were 0.810 [0.719–0.900], 0.782 [0.689–0.874], and 0.729 [0.619–0.838], respectively. The models of MAST and FAST had comparable AUCs (P = 0.347), which were statistically significantly higher than that of MEFIB (P = 0.041). Additionally, the cutoffs for diagnosis of MASH were lower than "at‐risk" MASH. Conclusion: MAST and FAST performed better than MEFIB in diagnosing "at‐risk" MASH and MASH using lower cutoff values. Our findings provided evidence for selecting the most accurate noninvasive model to identify patients with MASH or at‐risk MASH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Worldwide, viral hepatitis remains the most common cause of chronic liver disease.1 In this context, hepatitis B virus (HBV) infection and its complications are responsible for a tremendous clinical burden related to cirrhosis and hepatocellular carcinoma.1 In contrast, long-term HBV suppression can improve hepatic fibrosis and clinical outcomes.2 [ABSTRACT FROM AUTHOR]

Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context. [ABSTRACT FROM AUTHOR]

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 better managing mothers with hepatitis B. We aim to assess the frequency of postpartum ALT flares and predictors for such events. 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 infection (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted to prevent Mother-to-child transmission (MTCT) but discontinued at delivery if there is 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 objective is the proportion of patients with postpartum ALT flares. The secondary objectives are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers. Discussion: The current study focuses on the incidence of postpartum ALT flares in mothers with chronic hepatitis B including subgroup analysis based on HBeAg status. The data will have several clinical implications, such as providing evidence for an appropriate monitoring schedule in CHB mothers after delivery. Further analyses on predictors of such events may assist clinicians in identifying mothers who might develop severe postpartum ALT flares. The data generated from healthy mothers have the potential to identify the patterns of ALT changes during pregnancy and postpartum, so we can gain a better understanding of the normal range of ALT in this subpopulation. Trial Registration Number at the Chinese Clinical Trial Registry: ChiCTR2200061130. [ABSTRACT FROM AUTHOR]

Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease <10 and/or liver function tests within Child-Pugh Class A (albumin >35 g/L, international normalised ratio <1.50 and total bilirubin <34 μmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation. [Display omitted] • This is the first prospective validation of the Baveno VII recompensation definition in patients with HBV-related cirrhosis. • A stable improvement of liver function tests was defined as MELD <10 and/or ALB & INR & TBIL within Child-Pugh A. • On-treatment MELD scores may be more predictive of the probability of recompensation than baseline MELD scores. • Prompt antiviral therapy is effective for patients with HBV-related cirrhosis, even under severe conditions. [ABSTRACT FROM AUTHOR]

Background and Aims: The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices.Methods: Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated.Results: Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices.Conclusion: Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar. [ABSTRACT FROM AUTHOR]

Importance: Standard care for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in highly viremic mothers consists of maternal antiviral prophylaxis beginning at gestational week 28 combined with an HBV vaccine series and HBV immune globulin (HBIG) at birth. However, HBIG is unavailable in some resource-limited areas., Objective: To determine whether initiating tenofovir disoproxil fumarate (TDF) at gestational week 16 combined with HBV vaccinations for infants is noninferior to the standard care of TDF at gestational week 28 combined with HBV vaccinations and HBIG for infants in preventing MTCT in mothers with HBV and high levels of viremia., Design, Setting, and Participants: An unblinded, 2-group, randomized, noninferiority clinical trial was conducted in 7 tertiary care hospitals in China. A total of 280 pregnant individuals (who all identified as women) with HBV DNA levels greater than 200 000 IU/mL were enrolled between June 4, 2018, and February 8, 2021. The final follow-up occurred on March 1, 2022., Interventions: Pregnant individuals were randomly assigned to receive either TDF starting at gestational week 16 with HBV vaccinations for the infant or TDF starting at gestational week 28 with HBV vaccinations and HBIG administered to the infant., Main Outcomes and Measures: The primary outcome was the MTCT rate, defined as detectable HBV DNA greater than 20 IU/mL or hepatitis B surface antigen positivity in infants at age 28 weeks. Noninferiority was established if the MTCT rate in the experimental group did not increase by more than an absolute difference of 3% compared with the standard care group, as measured by the upper limit of the 2-sided 90% CI., Results: Among 280 pregnant individuals who enrolled in the trial (mean age, 28 years; mean gestational age at enrollment, 16 weeks), 265 (95%) completed the study. Among all live-born infants, using the last observation carried forward, the MTCT rate was 0.76% (1/131) in the experimental group and 0% (0/142) in the standard care group. In the per-protocol analysis, the MTCT rate was 0% (0/124) in the experimental group and 0% (0/141) in the standard care group. The between-group difference was 0.76% (upper limit of the 2-sided 90% CI, 1.74%) in all live-born infants and 0% (upper limit of the 2-sided 90% CI, 1.43%) in the per-protocol analysis. Both comparisons met the criterion for noninferiority. Rates of congenital defects and malformations were 2.3% (3/131) in the experimental group and 6.3% (9/142) in the standard care group (difference, 4% [2-sided 95% CI, -8.8% to 0.7%])., Conclusions and Relevance: Among pregnant women with HBV and high levels of viremia, TDF beginning at gestational week 16 combined with HBV vaccination for infants was noninferior to the standard care of TDF beginning at gestational week 28 combined with HBIG and HBV vaccination for infants. These results support beginning TDF at gestational week 16 combined with infant HBV vaccine to prevent MTCT of HBV in geographic areas where HBIG is not available., Trial Registration: ClinicalTrials.gov Identifier: NCT03476083.

Postpartum elevation of alanine aminotransferase (ALT) in mothers with chronic hepatitis B (CHB) presents a significant clinical challenge. However, the existing literature demonstrates inconsistencies regarding its incidence and predictors in mothers infected with the hepatitis B virus (HBV). Recent advancements in antiviral prophylaxis against mother-to-child transmission of HBV and postpartum cessation of antiviral therapy further complicate this issue. Our literature review, spanning PubMed, and two Chinese-language databases (CNKI and Wanfang) from 1 January 2000 to 31 December 2023 aimed to consolidate and analyse available data on the frequency and severity of postpartum ALT flares, identify risk factors, and propose a management algorithm. Data from 23 eligible studies involving 8,077 pregnant women revealed an overall incidence of postpartum ALT elevation: 25.7% for mild cases, 4.4% for moderate cases, and 1.7% for severe cases. In the subgroup of mothers who were HBeAg-positive and on antiviral prophylaxis for preventing mother-to-child transmission, postpartum intermediate and severe ALT elevations were reported with pooled rates of 5.9% and 0.8%, respectively. Importantly, none resulted in mortality or necessitated liver transplantation. Identified risk factors for postpartum ALT flares in mothers with CHB included HBV DNA levels, ALT levels during pregnancy, postpartum cessation of antiviral treatment, and HBeAg status. By leveraging this evidence and recent data on predictors of intermediate or severe postpartum ALT flares, we propose a risk-stratified algorithm for managing postpartum ALT elevation and selecting therapy in mothers with CHB, tailoring different approaches for treatment-naive vs treatment-experienced populations. These recommendations aim to provide guidance for clinical decision-making and enhance patient outcomes., Competing Interests: C.Q.P. received institutional research grants from Gilead Sciences and Wuxi Hisky Medical Technologies Co., Ltd. Other authors have no financial interests to be disclosed., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Introduction: This systematic scoping review aimed to synthesize existing research findings on the clinical manifestations in patients with nonalcoholic fatty liver disease (NAFLD) and sarcopenia., Methods: Adhering to scoping review guidelines, we comprehensively searched five databases for literature on sarcopenia's clinical manifestations in NAFLD patients from December 2013 to December 2023, meticulously compiling and synthesizing the findings., Results: A total of 312 articles were identified, with 9 studies included in the final review. Of these, 90% were cross-sectional investigations, with 70% from Asian cohorts. Comparative analysis between patients solely afflicted with NAFLD and those additionally experiencing sarcopenia revealed discernible trends. Individuals with both conditions tended to be older, have a higher body mass index, and show a higher prevalence among females, underscoring the influence of unhealthy lifestyles and obesity. Furthermore, comorbidities like metabolic syndrome, hypertension, and diabetes have been implicated in sarcopenia manifestation among NAFLD patients. Nonetheless, the lack of standardized diagnostic criteria and patterns poses an ongoing clinical challenge for this subgroup., Conclusions: Our review highlights distinct clinical characteristics evident in NAFLD patients with sarcopenia. However, comprehensive investigations remain scarce, impeding accurate early detection and intervention. Future research should prioritize bridging these gaps and fostering enhanced clinical management strategies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent hepatitis B virus (HBV) mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the 2 regimens are lacking., Design: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to 31 March 2024 and extracted data from cohort studies and randomized controlled trials (RCTs) in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups., Results: We included 31 studies with 2588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval [CI] .07-.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval .16-7.61). Network meta-analysis showed equal efficacy of the 2 regimens in reducing MTCT (risk ratio: 1.09, 95% CI .15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: .77 vs .72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens., Conclusions: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers., Competing Interests: Potential conflicts of interest . C. Q. P. received an institutional research grant from Gilead Sciences. A. S. Y. serves as a speaker for Gilead Sciences, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB)., Aims: Here, we report the studies' final 8-year results., Methods: CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping., Results: Among 1298 patients randomised to double-blind TAF (n = 866) or double-blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing-equals-failure analysis) and 95%, 94% and 97% (missing-equals-excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft-Gault method; eGFR CG ) and hip/spine bone mineral density (BMD) remained stable in patients receiving double-blind/OL TAF, with only small declines at year 8. Decreases in eGFR CG and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF., Conclusion: Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance., Clinicaltrials: gov numbers NCT01940341 and NCT01940471., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Achieving a sustained virologic response (SVR) through direct-acting antivirals for hepatitis C virus (HCV) infection significantly reduces the long-term risk of hepatocellular carcinoma (HCC), particularly in patients with advanced fibrosis (F3) or cirrhosis (F4). However, despite this improvement, the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate. This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively, especially at advanced fibrosis (F3), and the unclear cost-effectiveness, modality, frequency, and duration of HCC surveillance in individuals with SVR but without cirrhosis. These factors contribute to significant variations in surveillance guidelines recommended by different professional societies. Therefore, there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians. This review article evaluates the existing data, addresses ongoing controversies, and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV., Competing Interests: All authors have completed the ICMJE uniform disclosure form and have no other conflicts of interest to declare. C.Q.P. received institutional research grants from Gilead Sciences and Wuxi Hisky Medical Technologies Co., Ltd. Table 1.Recommendations from international guidelines on HCC surveillance after DAA therapyPre-DAA assessmentAASLDEASLAPASLF0–F2N/AN/AUS+tumor markersa every 6 months for 2 years, followed by annually indefinitelyF3NoUS±AFP every 6 months indefinitelyUS+tumor markersa every 6 months indefinitelyF4US±AFP every 6 months indefinitelyUS±AFP every 6 months indefinitelyUS+tumor markersa every 6 months indefinitelyAASLD = American Association for the Study of Liver Diseases, EASL = European Association for the Study of Liver, APASL = Asian Pacific Association for the Study of Liver, SVR = sustained virologic response, DAA = direct acting antiviral agents,  TE = transient elastography, FIB-4 = Fibrosis-4 index, US = ultrasound, N/A = not available, AFP = alpha-fetoprotein, AFP-L3 = lens culinaris agglutinin-reactive AFP isoform, DCP = des gamma carboxy-prothrombin.aTumor markers: AFP, AFL-L3, DCP., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Competing Interests: C.Q.P. received institutional research grants from Gilead Sciences and Wuxi Hisky Medical Technologies Co., Ltd. The other authors have no conflicts of interest to disclose.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al , the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores., Competing Interests: Conflict-of-interest statement: Calvin Q Pan received institutional research grants from Gilead Sciences, Inc. and Wuxi Hisky Medical Technologies Co., Ltd. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p  < 0.0001. HBV marker consistency test results show perfect consistency between the two analyzers, with Kappa values ranging from 0.854 to 1.000. For specific samples, including Hepatitis B patients with Genotype C, chronic hepatitis B, hepatitis B-related cirrhosis, and hepatocellular carcinoma, spearman correlation analysis showed HBsAg correlation coefficients ranging from 0.8532 to 0.9745, p  < 0.001 in both analyzers. In conclusion, Autolumo A2000Plus diagnostic performance in consistency and correlation is comparable to Abbott Architect i2000 when detecting markers of hepatitis B infection. The Autolumo A2000Plus system can be used as a reliable instrument for HBV marker detection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background & Aims: Hepatic recompensation may be achieved in patients with decompensated cirrhosis due to chronic hepatitis B (CHB) upon effective suppression of viral replication by nucleos(t)ide analogues (NAs). However, the optimal timing and predictors of recompensation and the subsequent clinical course of patients with CHB with vs. without recompensation are not well-defined., Methods: This study was a retrospective extension of a multi-centre prospective cohort, focusing on patients with CHB and decompensated cirrhosis treated with entecavir. We followed patients beyond treatment week 120 until a second decompensation event or June 2023. We identified the optimal timing and predictors of recompensation by week 120, evaluated durability of recompensation in patients fulfilling recompensation criteria by week 120 and examined late recompensation in those who did not fulfil it by week 120., Results: At treatment week 24, serum albumin ≥34 g/L predicted recompensation by week 120. The Brec-PAS model offered good predictive ability for recompensation by week 120. Of the 283 patients who finished 120 weeks of therapy, 175 were followed beyond week 120 (median follow-up: 240 weeks). Among the 106 patients achieving recompensation by week 120, 92 (86.8%) maintained recompensation for another 120 (72-168) weeks. Among the 69 patients without recompensation by week 120, 40.6% attained late recompensation during the subsequent 120 (72-168) weeks. Additionally, hepatocellular carcinoma incidence was lower in the recompensated group (5.0% vs. 16.13%, p  = 0.002)., Conclusions: A serum albumin ≥34 g/L at treatment week 24 predicted recompensation by week 120. Recompensation achieved by week 120 of NA treatment is maintained in >80% of patients in the long term. Some patients may achieve recompensation only after >120 weeks of NA treatment. The incidence of hepatocellular carcinoma was reduced but not completely abolished after recompensation., Impact and Implications: Our research provides a meaningful contribution to understanding the long-term prognosis of recompensation in patients with chronic hepatitis B and decompensated cirrhosis, as well as to evaluating the predictive value of serum albumin levels, offering a comprehensive view of clinical outcomes after recompensation. The significance of early biomarkers in guiding therapeutic decisions is highlighted, shedding light on the continued benefits and possible risks after recompensation. This enhances the capability for more precise prognostic evaluations and informed therapeutic strategies. For healthcare providers, these insights afford a detailed perspective on patient monitoring and intervention planning, underscoring the need for ongoing assessment past the initial recompensation phase., (© 2024 The Authors.)

Introduction: The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years., Methods: Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, and serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses., Results: Of 1,298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA <29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median estimated glomerular filtration rate (by using Cockcroft-Gault) declined <2.5 mL/min, and mean declines of <1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF., Discussion: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles., Aim: To evaluate how these changes affect cardiovascular risk., Methods: This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks. Patients who fulfilled the American College of Cardiology criteria (age 40-79 years, high-density lipoprotein [HDL] 20-100 mg/dL, total cholesterol [TC] 130-320 mg/dL and systolic blood pressure 90-200 mmHg) required to assess 10-year atherosclerotic cardiovascular disease (ASCVD) risk with baseline lipid data and at least one post-baseline measurement were included in the ASCVD-risk population. The 10-year ASCVD risk was calculated for patients in this population, and changes from baseline to Week 96 were assessed using intermediate- (≥7.5%) and high-risk (≥20%) cut-offs., Results: Among 1632 patients, 620 (38%) met the criteria for the ASCVD-risk population. At Week 96, fasting levels of all lipids, except TC:HDL ratio, were lower with TDF than TAF. No significant increase was observed in overall ASCVD risk or in any ASCVD-risk categories during the 96-week treatment period compared with baseline. A similar proportion of patients in the TAF and TDF treatment groups (1.3% and 2.3%, respectively; p = 0.34) reported cardiovascular events., Conclusion: Despite on-treatment differences in lipid profiles with TAF and TDF, predicted cardiovascular risk and clinical events were similar for both groups after 96 weeks., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Pyrrolizidine alkaloids induced hepatic sinusoidal obstruction syndrome (PA-HSOS) often occurs after consuming herbs or a dietary supplement containing the plant Tu-San-Qi. Limited data exists to identify patients with fatal outcomes for early interventions. We aimed to analyze the predictors for 3-month survival. We retrospectively enrolled PA-HSOS patients in 5 hospitals and extracted data from the onset of PA-HSOS to 36 months. Outcome measurements were 3-month and 36-month survival rates, baseline prognostic predictors for survival, and the effects of anticoagulant therapy. Among 49 enrollees, the median age was 60 and 49% male. At the onset of PA-HSOS, patients with Child-Turcotte-Pugh (CTP) class of A, B, or C were 8.2% (4/49), 42.8% (21/49) and 49.0% (24/49), respectively. None of them received a transjugular intrahepatic portosystemic shunt or a liver transplant. The 3-month and 36-month survival rates were 86% and 76%, respectively. Compared to the CTP class A or B, class C at baseline independently predicted lower survival rates at both 3 and 36 months. However, anticoagulation therapy treatment within the first 3 months independently predicted significantly higher survival rates at both time points. CTP class C and anticoagulant therapy were the independent predictors for short-term and long-term survival. Anticoagulant therapy could decrease mortality rate of CTP class C patients. The greatest benefit of anticoagulant evaluated by 3-month survival rate was in patients with CTP class C compared with those without treatment (93% vs 40%, P = .009). There were no bleeding complications reported in patients treated with the anticoagulant., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: CWS has received speaker fees from GILEAD Sciences and Abbott. CP received research funding and is a speaker for Gilead. PCM supervises a doctoral student with funding support from GSK. SH has received funding from Gilead for HCV Micro-elimination programs. HR has received research funding and speaker’s honoraria from Gilead Sciences, AbbVie and Pfizer and is a board member of the CDA foundation. SW has received research funding from Gilead Sciences, and honoraria from Prime Inc, and is on the Board of Directors for the Hepatitis B Foundation, World Hepatitis Alliance, and serves in the patient advisory group and HBV special interest group for the AASLD. FR has received consulting fees from Sanofi Pasteur. GD has received consulting fees and speaker fees from Gilead Sciences, has participated on Data Safety Monitoring Board/Advisory Board for janssen, Glaxo Smith Kline, Arbutus, Aligos, Vir and has roles in the National Medical Research Council Singapore and the World Health Organisation Pediatric Working Group on Viral Hepatitis. Please refer to the accompanying ICMJE disclosure forms for further details.

Alcohol-related liver disease (ALD) from excessive alcohol intake has a unique gut microbiota profile. The disease progression-free survival in ALD patients has been associated with the degree of gut dysbiosis. The vicious cycles between gut dysbiosis and the disease progression in ALD including: an increase of acetaldehyde production and bile acid secretion, impaired gut barrier, enrichment of circulating microbiota, toxicities of microbiota metabolites, a cascade of pro-inflammatory chemokines or cytokines, and augmentation in the generation of reactive oxygen species. The aforementioned pathophysiology process plays an important role in different disease stages with a spectrum of alcohol hepatitis, ALD cirrhosis, neurological dysfunction, and hepatocellular carcinoma. This review aims to illustrate the pathophysiology of gut microbiota and clarify the gut-brain crosstalk in ALD, which may provide the opportunity of identifying target points for future therapeutic intervention in ALD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Wang, Pan and Xing.)

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB., Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated., Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 ( p <0.001) vs. 0.56 ( p  = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 ( p <0.001) vs. 0.58 ( p  = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively)., Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis., Impact and Implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB., Clinical Trial Numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236., Competing Interests: AJH: There are no financial disclosures for this author. CP: Has served as a speaker for Gilead and received research grants from Gilead. DRS: There are no financial disclosures for this author. EG: Member of scientific advisory boards for AbbVie, Abbott Diagnostics, Aligos, Arbutus, Arrowhead, Assembly, Avalia, Clear B Therapeutics, Dicerna, Enanta, Gilead Sciences, GSK, Intellia, Janssen, Merck, Novartis, Genentech-Roche, Vaccitech, Ventorx, Vir Bio and Virion Therapeutics. FA: Gilead Sciences employee and stock ownership. HJ: Received grants from: AbbVie, Gilead Sciences, GSK, Janssen, Roche, Vir Biotechnology Inc. Is a consultant for: Aligos, Antios, Arbutus, Eiger, Gilead Sciences, GSK, Janssen, Merck, Roche, VBI Vaccines, Vir Biotechnology Inc., Viroclinics. HC: Has served as an advisor for Aligos, Arbutus, Hepion, Janssen, Gilead, GSK, Roche, Vaccitech, Vir Biotechnology, Virion Therapeutic, and as a speaker for Gilead, Roche, and Mylan. HW: Employee and stockholder for Gilead. JF: Employee and stockholder for Gilead. JK: Consultant for Abbvie, Abbott, Gilead Sciences, Roche and Sysmex. On speaker’s bureaus for Abbvie, Bristol-Myers Squibb, Gilead Sciences, and Fujirebio. JH: Has received consulting fee from AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Johnson & Johnson, Roche and received grants from Bristol Myers Squibb and Johnson & Johnson. KA: Aligos, Assembly, Bluejay, BMS, BI, DrugFarm, Gilead, GSK, Janssen, Merck, Roche, Sobi. LJY: Employee of Gilead Sciences and own stock in Gilead Sciences. MB: Has served as an advisor for Abbvie, Arbutus, Assembly, Janssen, Gilead, GSK, Roche, and as a speaker for Gilead and Abbvie. MBr: Speakers Bureau for AbbVie and Gilead. Advisory for AbbVie, Gilead, Janssen, Roche, EISAI-MSD. NI: There are no financial disclosures for this author. QN: Has served as a consultant for BMS, GSK, MSD, and Novartis. SHA: Has acted as advisors and investigator for Gilead, Janssen, AbbVie, Roche, Assembly Biosciences, Arbutus, Brii, Vaccitech, GSK, Inovio, Aligos, Vir Biotechnology, SL Vaxigen, GeneOne Life Science, GreenCross, Yuhan, Samil and Ildong. SF: Has received research support from Gilead. Consultant for Abbvie, Assembly Bio, Janssen, and Gilead. Teacher and speaking for Abbvie and Gilead. SGL: Speakers bureau for Gilead, Janssen, Roche, Sysmex. Advisory board for Gilead, Abbott, Roche, GSK, Janssen, Sysmex, Springbank, Arbutus, Assembly, Grifols, Eisai. Research support from Gilead, Abbott, Roche, Sysmex, Fibronostics, Merck. TTC: There are no financial disclosures for this author. WLC: Member of Advisory Board for Gilead, AbbVie, BMS, Roche, and PharmaEssentia. Speaker for Gilead, AbbVie, BMS, Roche, PharmaEssentia. WKS: Received speaker’s fees from Mylan and AstraZeneca, is an advisory board member of Abbott, is an advisory board member and received speaker’s fees from AbbVie, and is an advisory board member, received speaker’s fees and research funding from Gilead Sciences. YSL: Advisor/consultant/speaker for AbbVie, Assembly Biosciences, Bayer Healthcare, GlaxoSmithKline, Gilead Sciences, Janssen, Olix Pharmaceuticals, Roche, Vaccitech, and Vir Biotechnology; and received grant/research support from Gilead Sciences. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background: The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infections by 2030. However, the HBV prevalence in Western countries, where the historical prevalence is low and highly impacted by immigration trends, remains uncertain making planning difficult. We aimed to develop a more accurate estimate of HBV prevalence and identify key immigrant populations that need to be screened, vaccinated, and treated to achieve the elimination targets., Methods: US immigration data from 1900 forward and country-specific modeled prevalence by age and sex were used to estimate immigrated HBV infections entering the US, new infections in the US, mortality (all-cause and liver-related), and disease burden through 2030., Findings: Using a dynamic Markov model, we estimated 1.8 million (95% uncertainty interval: 1.3-2.6 million) HBV infections in 2020 in all ages, higher than the NHANES national serosurvey. Infections between ages 30-74 accounted for 82% of all cases. Furthermore, HBV infections were concentrated among immigrants. New decompensated cirrhosis, hepatocellular carcinoma, and liver related deaths are expected to increase by 20%, 31% and 25% respectively from 2019 to 2030 at current diagnosis and treatment rate., Interpretation: National serosurveys can underestimate total infections due to under-sampling in immigrant populations. To meet the WHO elimination targets, culturally appropriate screening and linkage to care programs in the immigrant populations are needed in the US. In their absence, there will be significant increases in the burden of HBV and the US will fail to meet the elimination targets by 2030., Funding: This analysis was funded by a research grant from Gilead Sciences (IN-US-988-5786) and made possible by grants from John C Martin Foundation (2019-G024), ZeShan Foundation (2021-0101-1-CDA-HEP-10), and EndHep2030 who supported country analyses., Competing Interests: Calvin Q. Pan: Consultant – Gilead, AbbVie; Advisory Board – Gilead, BMS, AbbVie; Research – Gilead, Merck. Homie Razavi: Employee – CDA Foundation, Advisory Board – Gilead, AbbVie, VBI Vaccine, Merck, Jansson, Roche; Research – Gilead, AbbVie, Assembly Biosciences, Intercept, Pfizer. Devin Razavi-Shearer, Ivane Gamkrelidze, Kathryn Razavi-Shearer, Sarah Blach, Chris Estes, Ellen Mooneyhan: Employee – CDA Foundation., (© 2023 The Author(s).)

Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits., Competing Interests: CWS has received speaker fees from GILEAD Sciences and Abbott. CP received research funding and is a speaker for Gilead. PCM supervises a doctoral student with funding support from GSK. SH has received funding from Gilead for HCV Micro-elimination programs. HR has received research funding and speaker’s honoraria from Gilead Sciences, AbbVie and Pfizer and is a board member of the CDA foundation. SW has received research funding from Gilead Sciences, and honoraria from Prime Inc, and is on the Board of Directors for the Hepatitis B Foundation, World Hepatitis Alliance, and serves in the patient advisory group and HBV special interest group for the AASLD. FR has received consulting fees from Sanofi Pasteur. GD has received consulting fees and speaker fees from Gilead Sciences, has participated on Data Safety Monitoring Board/Advisory Board for janssen, Glaxo Smith Kline, Arbutus, Aligos, Vir and has roles in the National Medical Research Council Singapore and the World Health Organisation Pediatric Working Group on Viral Hepatitis. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background and Aims: 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., Methods: 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., Results: 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); p =0.004)], or on SOF/daclatasvir±ribavirin (82.4%, 95% CI: 78.2-86.2%; p <0.001). Adding ribavirin to SOF-based regimens (pooled SVR 84.9%, 95% CI: 81.7-87.9) did not significantly increase the SVR [(83.8% (95% CI: 76.8-89.8%; p =0.76)] in decompensated patients, which was also true in subgroup analyses for each regimen within the same treatment duration. However, adding ribavirin significantly increased the frequency of adverse events from 52.9% (95% CI: 28.0-77.1) to 89.2% (95% CI: 68.1-99.9) and frequency of severe events. The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1% (95% CI: 1.5-5.0) and 4.6% (95% CI: 3.1-6.3), respectively. The overall heterogeneity was high. There was no publication bias., Conclusions: 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., Competing Interests: CQP is a speaker and consultant for Gilead Sciences. He also received a research grant from Gilead Sciences and Assembly Biosciences. The other authors have no conflict of interests related to this publication., (© 2023 Authors.)

Background: Mother-to-child transmission (MTCT) of hepatitis B virus may occur in highly viremic mothers despite the infants receiving appropriate immunoprophylaxis. We aimed to review tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) data for preventing MTCT., Methods and Data Selection: We performed a systematic review between January 1, 2015 and December 31, 2021 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases. Data was extracted from randomized controlled trials or cohort studies in English or Chinese. The outcomes of interest included the efficacy and safety of TDF versus TAF or TDF/TAF versus placebo for preventing MTCT (PROSPERO registration: CRD42021256656)., Results: Data from forty-three studies (13 randomized controlled trials, 30 nonrandomized studies) were included in the review. All infants in the studies received appropriate immunoprophylaxis. Among 3656 highly viremic mothers treated with TDF, hepatitis B virus DNA suppression to the levels <200,000 IU/mL at delivery was achieved in 34% to 100% of mothers. MTCT rates were 0 to 5% and 2 to 83% in mothers treated with TDF and in those who received no treatment, respectively. Congenital malformation rates were 0 to 2.1% in the TDF groups, which did not differ from the nontreated groups. Similar findings were reported in 4 studies that enrolled 326 mothers for maternal TAF therapy, resulting in 0% of MTCT and 0% infant malformation. All studies observed that TDF or TAF maternal therapy reduced MTCT rates significantly without safety concerns when compared with untreated groups, except for 1 RCT that failed the therapeutic endpoint., Conclusions: TDF is well established for preventing MTCT in highly viremic mothers, whereas TAF may become an option as data emerges., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population., Methods: Current study enrolled consecutive non-lean (body mass index [BMI] &gt;23 kg/m2) patients with NAFLD 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∼&lt;28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage &gt;1) were also analyzed through the logistic regression model., Results: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, 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 versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics 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 NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87)., Conclusions: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Hepatitis C (HCV)-induced decompensated cirrhosis warrants liver transplantation (LT) as the only ultimate solution. These patients experience liver deterioration, while on the transplant waitlist. However, debate remains over the optimal timing for treating HCV relative to before or after LT., Methods: We performed a literature search between 1/2011 and 1/2022 on PubMed and OVID Medline. Data were extracted from direct antiviral agent (DAA) studies in English. The outcomes of interest included sustained virological response (SVR) rates from various cohorts as well as long- and short-term outcomes in the LT settings., Results: After screening, 54 studies were eligible and included into the review. In aligning with the EASL and AASLD guidelines and suggestions, many studies supported DAA therapy before LT in patients with Model for End-stage Liver Disease (MELD) scores < 18 and DAA therapy post-LT in MELD scores > 20 through SVR rates, long-term survival factors, liver deterioration, and incidences of severe adverse events. However, uncertainty still lies in the guideline recommendations and unsettled issues remain for various patient cohorts that may benefit from opposing the guideline cutoffs. Based on the recent studies on predictors of treatment outcomes in decompensated patients and the impact of DAA on the waiting list for LT, we proposed an algorithm to manage patients with MELD scores between 18 and 20., Conclusion: DAA therapy for decompensated patients must be personalized with consideration of different factors, particularly among those with MELD scores between the two cutoff-values proposed by the current associational guidelines., (© 2022. Asian Pacific Association for the Study of the Liver.)

Background and Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) has become one of the most common causes of chronic liver disease in the pediatric population. Recent advances have been made in developing non-invasive measures for NAFLD assessment. This review presents an analysis of these latest developments and also proposes an algorithm for screening pediatric patients at risk for NAFLD., Methods: A systematic literature search on PUBMED and EMBASE was conducted. Guidelines for clinical care of pediatric NAFLD were also reviewed., Results: In imaging tests, transient elastography (TE) combined with controlled attenuation parameter (CAP) is a promising, relatively low-cost method offering an intermediate level of accuracy on accessing patient's fibrosis and steatosis in a singular package. Liver biopsy remains the gold standard for diagnosis and/or evaluation of NAFLD, but with our proposed algorithm on utilizing non-invasive testing, the number of liver biopsies required could decrease. The current evidence supports the implementation of TE and CAP in an evaluation algorithm for pediatric NAFLD., Conclusions: Current data support the use of TE and CAP as a first-line tool in the diagnosis and evaluation of adolescent NAFLD, to better stratify high-risk patients and cut down on the number of liver biopsies needed., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Accumulating evidence shows that the intestinal microbiota is closely related to the pathophysiology and the disease progression of chronic hepatitis B virus (HBV) infection. The intestinal microbiota acts on the host through its metabolites. This review aimed to discuss the effects of gut microbiota metabolites on the disease progression of chronic HBV infection. A literature search on PubMed database and Wiley Online Library with pre-specified criteria yielded 96 unique results. After consensus by all authors, the contents from 86 original publications were extracted and included in this review. In liver disease with HBV infection, the intestinal microbiota changed in different stages and affected the production of bacterial metabolites. The abundance of bacteria producing short-chain fatty acids such as butyrate reduced, which was associated with bacterial translocation and the progression of liver disease. The intestinal microbiota-bile acid-host axis was destroyed, affecting the progression of the disease. Under the control of intestinal microbiota, tryptophan affected the gut-liver axis through three main metabolic pathways, among which the kynurenine pathway was closely related to the immune response of hepatitis B. The level of trimethylamine-N-oxide decreased in liver cancer with HBV infection and were used as a potential biomarker of liver cancer. Vitamin deficiencies, including those of vitamin D and vitamin A related to microbiota, were common and associated with survival. Hydrogen sulfide regulated by the intestinal microbiota was also closely related to the gut-liver axis. In liver disease with hepatitis B infection, the intestinal microbiota is imbalanced, and a variety of intestinal microbiota metabolites participate in the occurrence and development of the disease., (© 2021. Asian Pacific Association for the Study of the Liver.)

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 < 0.0001) in infants born to mothers with HBV DNA < 5 log 10 IU/mL. For infants born to mothers with HBV DNA ≥ 5 log 10 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 < 5 log 10 IU/mL., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-PRC-09000459., (© 2021. The Author(s).)

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 h 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 <1500/μL (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.12-0.94) and two or fewer symptoms (OR: 0.20, 95% CI: 0.07-0.55) during the initial episode., Conclusion: Risk-stratified surveillance should be conducted among patients who have recovered from COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hepatitis B virus (HBV) infection is a global health issue. Mother-to-child transmission (MTCT) is the most prominent route for chronic HBV infection in Asian countries. 1 Although standard immunoprophylaxis has been effective in preventing MTCT, a significantly higher rate of MTCT has been observed among mothers with high levels of viremia. 2 Tenofovir disoproxil, telbivudine (LdT), and lamivudine, used in third trimester, have been shown to significantly reduce MTCT of HBV for highly viremic mothers. 3 Although the efficacy and short-term safety of LdT in preventing MTCT have been demonstrated in several large cohort studies in recent years, fewer data exist on the safety assessment of infants' neurocognitive development after fetal exposure to LdT. 4-6 Therefore, we conducted a prospective cohort study to investigate the effect of LdT on infants' neurocognitive development., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Minority patients are under-screened for chronic hepatitis C (CHC) in the USA, and limited data exist for minority patients with advanced fibrosis., Methods: 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., Results: 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 < 0.001) and a higher percentage of late presenters (p < 0.001). In subgroup analyses, the mean fibrosis scores for Hispanic, Black and Asian patients were 2.58 ± 1.38, 2.28 ± 1.41 and 2.28 ± 1.40, respectively., Conclusions: Minority populations with CHC in the USA experience disparities in access to treatment in the early stages of liver fibrosis. Public health strategies are necessitated to address the inequality, as late presenters are at risk of hepatocellular carcinoma.

Introduction: We aimed to characterize postpartum disease flares among treatment-naive mothers with chronic hepatitis B (CHB). CHB mothers were enrolled and compared with non-infected mothers in terms of postpartum alanine aminotransferase (ALT) abnormalities., Methods: Demographic, virological, and biochemical parameters were collected up to postpartum week 16, with flares and exacerbations defined as ALT levels 5-10 and >10 times the upper limit of normal, respectively. Outcome assessments included ALT flares or exacerbation and their predictive parameters., Results: Among 4236 patients enrolled, 869 and 3367 had no infection (group A) and had CHB (group B), respectively. Infected mothers were further stratified into two subgroups by the presence (B1, n = 1928) or absence (B2, n = 1439) of detectable serum levels of hepatitis B virus (HBV) DNA (lowest level of quantitation, 100 IU/mL). A significantly higher frequency of abnormal ALT levels was observed in group B vs. group A (28.27 vs. 20.37%, p < 0.001). ALT events mainly occurred in group B1 (flares, 115/1928, 5.96%; exacerbations, 57/1928, 2.96%). The ALT levels had a bimodal pattern, with peaks at postpartum weeks 3-4 and 9-12. On multivariate analysis, elevated ALT levels and detectable levels of HBV DNA at delivery were independent risk factors for postpartum disease flares. Further subgroup analysis in group B1 demonstrated that a cut-off HBV DNA level of 5 log 10 IU/mL at delivery predicted ALT events (positive predictive value, 14.4%; negative predictive value, 98.2%)., Conclusions: Postpartum ALT level elevation is common in CHB patients. ALT flares or exacerbations are mainly observed in mothers with elevated ALT or HBV DNA levels ≥5 log 10 IU/mL at delivery.

Objective: To investigate the effect of antiviral therapy on the progression of liver cirrhosis and related predictive factors through a retrospective analysis of patients with compensated hepatitis C cirrhosis. Methods: The patients with compensated hepatitis C cirrhosis who were treated in our hospital from 2004 to 2015 were divided into sustained virologic response (SVR) group, non-SVR (NSVR) group, and untreated group. The baseline features of patients with or without liver cirrhosis were compared to identify the predictive factors for the progression of liver cirrhosis. The changes in platelet count, spleen sizes, Model for End-Stage Liver Disease (MELD) score, Sequential Organ Failure Assessment (SOFA) score, and Child-Turotte-Pugh (CTP) score were analyzed, and the incidence rate of liver cancer was compared between groups. A one-way analysis of variance, the Kruskal-wallis H test, the two-independent-sample t test, the chi-square test, and a multivariate logistic regression analysis were used for data analysis based on data type. Results: A total of 89 patients with compensated liver cirrhosis were enrolled, among whom 42 received the antiviral treatment with interferon and ribavirin (30 were treated with pegylated interferon-α and 12 were treated with ordinary interferon) and 47 did not receive any antiviral therapy. Among the patients who received the antiviral treatment with interferon and ribavirin, 20 achieved SVR and 22 did not achieve SVR. Compared with baseline values, platelet count in the SVR group and the NSVR group was increased by (44.93 ± 32.66)×10(9)/L and (9.73 ± 28.83)×10(9)/L, respectively, and platelet count in the untreated group was reduced by (19.76 ± 54.5)×10(9)/L; the three groups had a significant change in platelet count ( F = 14.731, P < 0.001). Spleen size was reduced by 0.91 ± 1.09 cm in the SVR group and increased by 0.20±0.84 cm and 1.11 ± 1.69 cm in the NSVR group and the untreated group, respectively; the three groups had a significant change in spleen size ( F = 14.943, P < 0.001). The three groups had no significant changes in MELD, SOFA, and CTP scores ( P > 0.05). One patient (5.00%) in the SVR group, 5 (22.73%) in the NSVR group, and 6 (12.77%) in the untreated group progressed to liver cancer ( χ (2) = 13.787, P = 0.001). The univariate analysis showed that SVR, HCV RNA, total bilirubin, and albumin were predictive factors for disease progression, and the multiple logistic regression analysis demonstrated that SVR and total bilirubin were predictive factors for disease progression. Conclusion: Interferon combined with ribavirin has a marked clinical effect in the treatment of compensated hepatitis C cirrhosis with good short- and long-term efficacy.

Chronic hepatitis B virus (HBV) remains a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Because chronic hepatitis B infection is rarely eradicated, preventing mother-to-child transmission (MTCT) is the most effective strategy to eliminate HBV globally. Although immunoprophylaxis strategy is widely available and effective for infants born to mothers with chronic hepatitis B infection, postnatal immunoprophylaxis fails in approximately 5-10 % of infants, and this failure rate goes up to 30 % in infants born to highly viremic mothers. Mothers with HBV DNA levels above 200,000 IU/mL should be managed aggressively with antiviral therapy because viral load is the strongest independent risk factor for immunoprophylaxis failure. Emerging data suggest that initiation of antiviral therapy in late pregnancy in highly viremic mothers can prevent immunoprophylaxis failure in their infants. Reducing viral load to target levels below 200,000 IU/mL at delivery is a practical approach to control MTCT. This review focuses on viral factors in mothers associated with MTCT.

Background: The novel prodrug tenofovir alafenamide delivers the nucleotide reverse transcriptase inhibitor tenofovir to target cells more efficiently at a lower dose than tenofovir disoproxil fumarate, thereby reducing systemic exposure. We compared the efficacy and safety of the two drugs in patients with HBeAg-negative chronic hepatitis B virus (HBV) infection in a non-inferiority study., Methods: In this ongoing randomised, double-blind, phase 3, non-inferiority study in 105 centres in 17 countries, patients with HBeAg-negative chronic HBV were randomly assigned (2:1) by a computer-generated allocation sequence (block size six), stratified by plasma HBV DNA concentration and previous treatment status, to receive once-daily oral doses of tenofovir alafenamide 25 mg or tenofovir disoproxil fumarate 300 mg, each with matching placebo. Participants, investigators, and those assessing outcomes were masked to group assignment. Eligible patients were aged at least 18 years with HBeAg-negative chronic HBV infection (with plasma HBV DNA concentrations of >20 000 IU/mL), serum alanine aminotransferase concentrations of greater than 60 U/L in men or greater than 38 U/L in women and at no more than ten times the upper limit of normal, and estimated creatinine clearance of at least 50 mL/min (by the Cockcroft-Gault method). The primary efficacy endpoint was the proportion of patients who had HBV DNA less than 29 IU/mL at week 48 in those who received at least one dose of study drug; the study was powered to show non-inferiority with a 10% efficacy margin of tenofovir alafenamide compared with tenofovir disoproxil fumarate. Bone and renal safety, and key secondary safety endpoints were assessed sequentially. The study will be conducted for a total of 3 years as a double-blind comparison to assess the longer term response to treatment. This study is registered with ClinicalTrials.gov, number NCT01940341., Findings: Between Sept 12, 2013, and Oct 31, 2014, 426 patients were randomly assigned (285 assigned to tenofovir alafenamide and 141 assigned to tenofovir disoproxil fumarate; one patient assigned to tenofovir disoproxil fumarate did not receive the treatment. 268 (94%) of 285 patients receiving tenofovir alafenamide had HBV DNA less than 29 IU/mL at week 48 versus 130 (93%) of 140 patients receiving tenofovir disoproxil fumarate (difference 1·8% [95% CI -3·6 to 7·2]; p=0·47), which demonstrates non-inferiority. Patients receiving tenofovir alafenamide had significantly smaller mean percentage declines in bone mineral density than those receiving tenofovir disoproxil fumarate (hip -0·29% [95% CI -0·55 to -0·03] vs -2·16% [-2·53 to -1·79], adjusted percentage difference 1·87% [95% CI 1·42 to 2·32; p<0·0001]; spine -0·88% [-1·22 to -0·54] vs -2·51% [-3·09 to -1·94], adjusted percentage difference 1·64% [95% CI 1·01 to 2·27]; p<0·0001). At week 48, mean change in serum creatinine was small in both groups (tenofovir alafenamide 0·01 mg/dL [95% CI 0·00 to 0·02] vs tenofovir disoproxil fumarate 0·02 mg/dL [0·00 to 0·04], adjusted percentage difference -0·01 mg/dL [95% CI -0·03 to 0·01]; p=0·32), but patients receiving tenofovir alafenamide had a smaller reduction in creatinine clearance (median change in estimated glomerular filtration rate -1·8 mL/min [IQR -7·8 to 6·0] vs -4·8 mL/min [-12·0 to 3·0]; p=0·004). Most adverse events were mild to moderate in severity in the two treatment groups. The most common adverse events overall were headache (tenofovir alafenamide 40 [14%] patients vs tenofovir disoproxil fumarate 14 [10%] patients), nasopharyngitis (30 [11%] vs 15 [11%]), and upper respiratory tract infection (35 [12%] vs ten [7%]). 14 (5%) patients receiving tenofovir alafenamide and nine (6%) patients receiving tenofovir disoproxil fumarate had serious adverse events, none of which was deemed by investigators to be related to study treatment; one patient in the tenofovir disoproxil fumarate group died, but this was not deemed to be related to study treatment., Interpretation: In patients with HBeAg-negative chronic HBV, the efficacy of tenofovir alafenamide was non-inferior to that of tenofovir disoproxil fumarate, and had improved bone and renal effects. Longer term follow-up is needed to better understand the clinical impact of these changes., Funding: Gilead Sciences., (Copyright © 2016 Elsevier Ltd. All rights reserved.)