One of the key features of chronic hepatitis B virus (HBV) infection is the inability to mount sufficient and coordinated adaptive immune responses against HBV. Recent studies on HBV-specific B cells and antibody to hepatitis B surface antigen (anti-HBs) have shed light on their role in the pathogenesis of chronic hepatitis B (CHB). Anti-HBs is recognized as a protective immune marker, both for HBV infection clearance and following vaccination, and it is also considered an important indicator of functional cure for CHB. Notably, functional impairment of HBV-specific B cells may be reversible. The restoration of HBV-specific B cell function, along with the induction of an anti-HBs antibody response, is regarded as pivotal for terminating chronic HBV infection and achieving functional cure. This article reviews the significance of anti-HBs in both the infection and clearance of HBV, and discusses the potential of neutralizing antibodies and therapeutic vaccines as promising future strategies.

The aspartate aminotransferase-to-platelet ratio index (APRI) is an effective non-invasive marker for chronic liver dysfunction. Given that heat stroke patients often suffer from poor prognosis due to multi-organ involvement, with liver injury and coagulation dysfunction being of particular concern, this study aims to investigate whether APRI can comprehensively reflect liver injury and coagulation dysfunction in heat stroke patients and explore its relationship with 28-day mortality.

This retrospective study analysed electronic medical records from patients treated at 57 grade A tertiary hospitals in China from May 2005 to May 2024. The primary outcome was 28-day mortality, and the secondary outcome was 7-day mortality. Restricted cubic splines (RCS) were utilized to visualize the relationship between APRI and 28-day mortality risk. The independent association between APRI and outcomes was assessed using Cox proportional hazards models, with multivariable analyses controlling for confounding factors. The predictive ability of APRI for outcomes was evaluated using receiver operating characteristic (ROC) curves.

A total of 450 eligible patients were included, with 71 deaths occurring within 28 days. RCS analysis showed a positive correlation between APRI and 28-day mortality. Participants were divided into higher (APRI ≥ 15.14) and lower (APRI < 15.14) APRI groups. Cox proportional hazards models indicated that individuals with higher APRI had a significantly increased 28-day mortality rate (HR 5.322, 95% confidence interval [CI] 2.642-10.720, p < 0.0001). Subgroup and interaction analyses confirmed the robustness of the core findings. Additionally, the areas under the ROC (AUROC) for APRI predicting 28-day mortality was 0.823 (95% CI 0.772-0.875), significantly higher than the AST to ALT ratio (0.526, 95% CI 0.448-0.605) and total bilirubin (0.694, 95% CI 0.623-0.765).

APRI is an independent predictor of early mortality risk in heat stroke.

Acute hepatitis E infection could induce severe outcomes among chronic hepatitis B (CHB) patients. Between 2016 and 2017, an open-label study was conducted to evaluate the immunogenicity and safety of hepatitis E vaccine (HepE) in CHB patients, using healthy adults as parallel controls in China. Eligible participants who were aged ≥30 y were enrolled in the study. The CHB group included participants who had ever developed symptoms of hepatitis because of CHB but was currently at a clinically stable stage, which was defined as ALT ≤ 1.5 times of upper limit of the normal range (ULN) in this study. The control group included healthy adults who had hepatitis B surface antigen (HBsAg) negative. HepE was administered for 0, 1, 6 months for all participants. At 1 month after the third-dose vaccination (month 7), the seroconversion rates of anti-HEV IgG were >97% in both groups. The geometric mean concentration (GMC) of anti-HEV IgG in the CHB group was non-inferior to the healthy adult group (0.69 WU/mL, 95% CI 0.55-0.85). The proportion of the participants with adverse events ≥ grade 3 was similar in both groups (p = .99), and no vaccine-associated severe adverse events were identified. Changes in the liver function indicators were not of clinical significance. The HepE was highly immunogenic and well tolerated among clinically stable CHB patients and healthy adults.

Hepatitis B and C infections are an underdiagnosed global health problem. Measurement of HBV DNA or HCV RNA levels using nucleic acid-based molecular diagnostic assays has been established as the standard of care for assessing diagnosis, guiding the treatment decision, and evaluating responses to antiviral therapy. In the present study, we examined the performance of the cobas 5800 System for HBV DNA and HCV RNA quantification in a large series of patients chronically infected. Specificity of the cobas HBV and HCV Tests on the 5800 System was high (99.1 % and 100 %, respectively). Linearity using the AcroMetrix panels was excellent. Repeatability and intermediate precision coefficients of variation were within 5 %. Of the 334 clinical specimens tested in parallel on the cobas 5800 and cobas 4800 Systems for HBV and the m2000 RealTime or Alinity m Systems for HCV, only 12 (3.6 %) yielded discrepant results that were at or near the limit of quantification of the cobas 5800 assays. The correlation between viral load results was extremely high, and only weak bias were observed across the entire range of concentrations tested without clinical impact in patients who are eligible for antiviral therapy. This comparison study demonstrated equivalent performance of the new cobas 5800 System compared with other molecular platforms widely used in clinical practice for HBV DNA and HCV RNA quantification. The cobas 5800 System can be confidently used in clinical practice. A few clinical specimens with low viral loads may be missed. Further studies are warranted to confirm or refute this finding.

Nucleos(t)ide analogs (NAs) provide prolonged viral suppression with favourable clinical outcomes in chronic hepatitis B (CHB) patients. Characterisation of adverse hepatic events after NA cessation leading to liver transplantation (LT) is vital to the improvement of patient management and safety considerations. This is a retrospective case series of CHB patients who developed hepatic decompensation due to NA discontinuation and were referred for LT. Patients with hepatocellular carcinoma or coinfection were excluded. Of 11 CHB patients included (81.8% clinical jaundice, 63.6% ascites, 54.5% hepatic encephalopathy and 18.2% variceal bleeding), 45.5% underwent LT, 36.4% were waitlisted (1 active, 1 died, 2 delisted of whom 1 died), and 18.2% died after referral during the assessment period. Median age was 55.1 years, 81.8% were male, and 72.7% had cirrhosis at NA cessation. Reasons for NA withdrawal included nonadherence (81.8%) and physician discretion (18.2%). Median time from NA cessation to a decompensating event was 3.2 months, and from the decompensating event to referral was 16.0 days. This study shows that most patients experience decompensations soon after NA cessation and reinforces that patients should not discontinue treatment themselves. Physicians should very carefully select non-cirrhotic, adherent patients for NA withdrawal, after which close monitoring and timely retreatment are crucial.

Despite having the highest Hepatitis B Virus (HBV)-related mortality globally, sub-Saharan Africa (SSA) has been slow in its disease elimination campaign. We describe a 5-year experience in HBV management at a large facility in Uganda and how it can inform future management strategies. HBV-related patient data were abstracted from clinic records. Of 2664 patients, 1828 (68.6 %) had documented chronic HBV infection. Participants were young, mean age (±SD) 31.3 (±10.6) and equally split by gender. Overall, 423 (23.1 %) were on antiviral medications including 158/229 (69.0 %) with a sonographic diagnosis of cirrhosis and 130/282 (46.1 %) with Aspartate aminotransferase to Platelet Ratio Index (APRI) score ≥0.5.48/1828 (2.6 %) had Hepatocellular Carcinoma (HCC). In multivariable analysis, APRI score ≥0.5 [OR (95 % CI) = 1.76 (1.26-2.46), p < 0.01], elevated alanine aminotransferase (ALT) [OR (95 % CI) = 2.25 (1.35-4.47), p = 0.04], and HBV viral load ≥2,000IU/mL [OR (95 % CI) = 2.97 (1.68-5.22), p < 0.01] were predictors of cirrhosis/HCC. Also, an APRI score of ≥0.5 [OR (95 % CI) = 1.62 (1.19-2.22), p = 0.01], elevated ALT [OR (95 % CI) = 2.60 (1.23-5.49), p = 0.02], cirrhosis [OR (95 % CI) = 21.65 (9.26-50.59), p < 0.01], and viral load ≥2,000IU/mL [OR (95 % CI) = 6.62 (3.93-11.15), p < 0.01] were associated with antiviral use. Cirrhosis/HCC apparently occur at lower APRI scores in SSA suggesting need for urgent adoption of the 2024 WHO guidelines which provide for earlier initiation of anti-HBV therapy.

Circulating HBsAg, HBV RNA, and hepatitis B core-related antigen (HBcrAg) are potential biomarkers for the response to nucleos(t)ide analog (NA) treatment discontinuation in patients with chronic hepatitis B (CHB). We retrospectively investigated the long-term kinetics of HBsAg, HBV RNA, and HBcrAg in HBeAg-negative patients treated with NA for up to 14 years in a prospective cohort study.

Ninety-six patients (mean age 65 y, 77% male, 52% with cirrhosis, all HBV genotype D) who were undergoing first (n=33, group A) or second-line (n=63, group B) treatment with tenofovir disoproxil fumarate were included. HBV biomarkers collected during tenofovir disoproxil fumarate treatment were measured in 384 serum samples stored at -20 °C. The combined biomarker endpoints associated with functional cure following NA discontinuation included HBsAg <1000 IU/mL, HBV RNA <54 copies/mL, and HBcrAg <2 log U/mL.

Before NA treatment, HBV RNA and HBcrAg were detectable in 85% (mean 3.9±2.3 [range, 0-9.2] log10 copies/mL) and 80% (mean 4.3±1.9 [2-8.9] log10 U/mL), respectively, of the patients in group A. In groups A and B, the percentages of patients with detectable HBV RNA levels decreased to 53% and 34%, respectively, during years 8-10 of NA treatment, and to 29% in group B during years 11-14 to 29%. HBcrAg could be quantified in 2% of patients in group B NA treatment years 8-10. Combined biomarker endpoints were met at baseline and at years 1-4, 5-7, 8-10, and 11-14 of treatment by 3.3%, 12% and 14%, 13% and 38%, 26% and 29%, and 41% of patients, respectively.

HBV biomarker endpoints are associated with functional cure after the discontinuation of NA increase during long-term NA treatment.

HDV infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a US-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with HBV infection.

In a national cohort of 4817 veterans infected with HBV tested for HDV (99.6% US-born, 3.3% HDV-positive) over a 23-year period, we used multivariable models to identify the factors associated with a composite outcome of HCC, decompensation, and liver-related mortality, and all-cause mortality of patients with HDV compared to HBV mono-infection. HDV coinfection (vs. HBV mono-infection) was associated with a significantly higher incidence of composite liver-related outcomes at both 5 (23.84 vs. 7.98, p < 0.001) and 10 years (19.14 vs. 10.18, p < 0.001), respectively. The most common cause of death was liver-related (33.8% for HDV vs. 24.7% for HBV), followed by nonhepatic malignancies (15.6% vs. 14.8%), cardiac (11.7% vs. 15.2%), and lung disease (5.2% vs. 3.7%). In multivariable models, HDV was associated with an increased risk of composite liver outcomes (adjusted hazard ratio: 2.57, 95% CI: 1.87-3.52, p < 0.001) and all-cause mortality (adjusted hazard ratio: 1.52, 95% CI: 1.20-1.93, p < 0.001).

In a predominantly US-born cohort of veterans, HDV coinfection was associated with an increased risk of liver-related outcomes and all-cause mortality. Our findings support widespread testing for early identification of HDV.

Current international guidelines recommend close monitoring and evaluation of patients with chronic hepatitis B (CHB) in the indeterminate phase, and treatment of patients at high risk of adverse outcomes. Clinical outcomes and the effect of antiviral therapy on the indeterminate phase remain unclear. We performed a systematic review and meta-analysis to study the incidence of adverse clinical outcomes including hepatocellular carcinoma (HCC), cirrhosis, and hepatic decompensation, and the effect of antiviral therapy, in the indeterminate phase.

Two investigators independently searched Embase, MEDLINE, Web of Science and China National Knowledge Infrastructure from 1/1/2007 to 31/12/2023. Three investigators independently assessed study eligibility and quality. We included cohort studies and a randomised-controlled trial, allowing for calculation of the incidence rate of adverse clinical outcomes, and cross-sectional studies that reported the prevalence of moderate-to-severe inflammation and different degrees of fibrosis. Incidence rates and prevalence were pooled using generalised linear mixed-effects models and random-effects models, respectively.

One hundred and three studies (70 case-control studies [18,739 patients], 32 cohort studies [15,118 patients], and one RCT [160 patients]) were included. The annual incidence rate of HCC in patients in the indeterminate phase was 0.32% (95% CI 0.21-0.48%, I2 = 85.7%), and those of cirrhosis and hepatic decompensation were 0.67% (95% CI 0.30-1.49%, I2 = 94.3%) and 0.34% (95% CI 0.17-0.69%, I2 = 51.8%), respectively. The pooled prevalence of moderate-to-severe liver inflammation, significant fibrosis, advanced fibrosis, and cirrhosis was 40.7%, 39.7%, 17.9%, and 7.2%, respectively. Use of antiviral therapy was associated with a lower risk of HCC in patients in the indeterminate phase (adjusted incidence rate ratio 0.38, 95% CI 0.18-0.79, p = 0.009).

Patients in the indeterminate phase are at risk of developing advanced liver disease and HCC. Although inherent heterogeneity across studies limited the evidence to support expanding treatment to all patients in the indeterminate phase, antiviral therapy may reduce the risk of HCC development in high-risk subgroups.

Current international guidelines recommend close monitoring and evaluation of patients with chronic hepatitis B (CHB) in the indeterminate phase, in whom antiviral treatment is not always indicated. Based on the systematic review and meta-analysis with significant heterogeneity across studies, patients in the indeterminate phase are at risk of developing hepatocellular carcinoma, cirrhosis, and hepatic decompensation. Meta-regression findings on platelet count, positive HBeAg, and age highlighted the importance of liver fibrosis assessment, accurate phase classification, and timely detection of phase transition to identify antiviral treatment indications, supporting current guideline recommendations. Antiviral treatment may reduce the risk of hepatocellular carcinoma in the high-risk subgroups of patients in the indeterminate phase.

CRD42024537095.

Tenofovir alafenamide (TAF) is recommended for chronic hepatitis B (CHB) treatment in international guidelines according to its efficacy and safety. However, in phase III study, an increased LDL-c was observed in those who were switched from Tenofovir disoproxil fumarate (TDF) to TAF. Limited data exists on whether lipid profiles change only in individuals who switched to TAF from TDF or from any nucleoside/nucleotide analogues (NUC). We investigated how switching to TAF affected lipid and cardiovascular outcomes in Thai CHB patients.

We conducted a prospective observational study including CHB patients who had to switch from their prior NUC to TAF according to the national reimbursement policy in late 2022. All enrolled patients had lipid tests and transient elastography (TE) done at 0 and 48-week post-switch to TAF. Demographic data, prior NUC, liver biochemistry, controlled attenuated parameter (CAP) and liver stiffness (elastic modulus; E) data measured by TE were collected. The changes in lipid, Thai cardiovascular (CV) risk score, and TE results between 0 and 48-week were compared.

A total of 110 patients who were switched to TAF and completed 48-week follow-up were analyzed. The prior NUCs were as follows: 47 Lamivudine (LAM), 22 Entecavir (ETV), and 41 TDF-based. Baseline characteristics were similar between the three groups except for underlying hypertension was more frequent and baseline total cholesterol was lower in the TDF-based group. At 48-week post-switch, the median LDL-c changes were -2.45, -5.9 and +8.8 mg/dL (p<0.001), and total cholesterol changes were -4.5, -4 and +17 mg/dL (p<0.001), in the ETV, LAM, and TDF-based group, respectively. Whereas the changes in hepatic steatosis (measured by CAP), and liver stiffness (measured by E) as well as Thai CV risk score were not significantly different. No cardiovascular events occurred during follow-up.

Significant increase in LDL-c and total cholesterol after switching to TAF were observed only in patients with prior TDF, but not in those with prior ETV or LAM. Careful monitoring of lipids after the switch may not be universally needed. Data regarding long-term cardiovascular outcomes are warrant.

To identify clinical and viral indicators for the development of a new model to accurately differentiate the stages of chronic hepatitis B virus (HBV) infection based on histopathological changes in the liver.

Clinical and liver pathology data from chronic hepatitis B (CHB) patients who underwent liver biopsy were retrospectively collected. The patients were allocated into test and validation groups. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated to idneitfy the optimal diagnostic value for differentiating the stages of chronic HBV infection.

A total of 118 patients and 73 patients who met the diagnostic and inclusion criteria were selected as the test group and validation group, respectively. Multivariate analysis revealed that HBeAg was independently correlated with the IT and IC stages. The cutoff value of HBeAg used to quantitatively differentiate between IT and IC was 1335 S/CO. The AUC values were 0.921 (95% confidence interval (CI): 0.836-0.971) and 0.846 (95% CI: 0.726-0.967) in the test and validation groups, respectively. A new prediction model of the IT stage was established by using three indicators, namely, HBeAg, HBsAg and HBV DNA. The AUC values were 0.923 (95% CI: 0.864-0.982, p < 0.001) and 0.89 (95% CI: 0.787-0.994, p < 0.01) in the test and validation groups, respectively, when this prediction model was used. For the new model, CMA guidelines (2019 version), EASL guidelines (2017 version) and AASLD guidelines (2018 version), the error rates in the test group were 4.65%, 11.62%, 23.26%, and 46.51%, respectively, while the errors rates in the validation group were 20.0%, 25.0%, 40.0%, and 45.0%, respectively.

High levels of HBeAg, rather than HBeAg positivity, may serve as a predictor of the IT stage. A predictive model for the immune tolerance stage was established by combining three indicators. Compared with the recommended standards from multiple current guidelines, the new prediction model has a significantly lower error rate.

Chronic hepatitis B (CHB) with indeterminate phase comprises a heterogeneous group of patients. We determined the prevalence of indeterminate CHB overall and characterised novel types and phase transition probabilities of novel types of indeterminate CHB.

CHB patients were enrolled retrospectively from 24 centres (9 countries/regions). Indeterminate phase was defined based on the AASLD 2018 guidance.

The cohort included 8375 patients with a mean age of 45.0 ± 13.7 years, 22.5% HBeAg-positive, and median ALT and HBV DNA of 30 U/L and 4.3 ± 2.2 log10IU/mL, respectively. Of the total cohort, half (47.2%) were in the indeterminate phase; and of these, the most prevalent group among HBeAg-positive patients was Type 2 (ALT 1-2 × ULN, HBV DNA≥ 20,000 IU/mL; 12.6%), while in HBeAg-negative patients it was Type 6 (ALT

CONCLUSIONS

Indeterminate CHB can be classified into 10 types, with the most prevalent type being those with HBeAg-negative, HBV DNA ≥ 2000 IU/mL and ALT Collapse

Key Words

• HBV
• grey zone
• longitudinal
• long‐term follow‐up
• phase transition
• prevalence

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Affiliation(s)

Rui Huang Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
Ai-Thien Do Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA Digestive Health Associates of Texas, Dallas, Texas, USA The University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA
Hidenori Toyoda Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
Jie Li Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
Satoshi Yasuda Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
Pei-Chien Tsai Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Ming-Lun Yeh Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Huy Trinh San Jose Gastroenterology, San Jose, California, USA
Angela Chau Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA Weill Cornell Medical College, New York, New York, USA
Daniel Q Huang Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Eiichi Ogawa Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
Takanori Ito Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Ritsuzo Kozuka Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
Masanori Atsukawa Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
Sebastián Marciano Liver Unit Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Takashi Honda Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Tsunamasa Watanabe Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
Norio Itokawa Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
Carmen Monica Preda Department of Gastroenterology and Hepatology, Clinic Fundeni Institute, University of Medicine and Pharmacy "Carol Davila", Romania
Cheng-Hao Tseng Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
Ana Barreira Liver Unit, Hospital Universitari Valle D'hebron and Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD del Instituto Carlos III, Spain
Kaori Inoue Liver Center, Saga University Hospital, Saga, Japan
Hirokazu Takahashi Liver Center, Saga University Hospital, Saga, Japan Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
Haruki Uojima Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
Keigo Kawashima National Institute of Infectious Diseases, Tokyo, Japan
Yao-Chun Hsu Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
Raluca Ioana Marin Department of Gastroenterology and Hepatology, Clinic Fundeni Institute, University of Medicine and Pharmacy "Carol Davila", Romania
Irina Sandra Department of Gastroenterology and Hepatology, Clinic Fundeni Institute, University of Medicine and Pharmacy "Carol Davila", Romania
Masatoshi Ishigami Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Jiayi Li Palo Alto Medical Foundation, Mountain View Division, Mountain View, California, USA
Jian Zhang Chinese Hospital, San Francisco, California, USA
Son Do The University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA
Mayumi Maeda Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
Dong-Hyun Lee Division of Gastroenterology, Department of Internal Medicine, Good Gang-An Hospital, Busan, South Korea
Wan-Long Chuang Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Chia-Yen Dai Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Jee-Fu Huang Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Chung-Feng Huang Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Ramsey Cheung Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA Gastroenterology and Hepatology, The Palo Alto Veterans Affairs Health Care System, Palo Alto, California, USA
Maria Buti Liver Unit, Hospital Universitari Valle D'hebron and Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD del Instituto Carlos III, Spain
Yasuhito Tanaka Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
Man-Fung Yuen Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
Masaru Enomoto Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan Department of Transfusion Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
Adrian Gadano Liver Unit Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Seng Gee Lim Director of Hepatology, Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
Ming-Lung Yu Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Chao Wu Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
Mindie H Nguyen Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA

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The long-term clinical benefits of interferon (IFN)-based therapy compared to nucleos(t)ide analogue (NA) monotherapy in HBeAg-positive chronic hepatitis B (CHB) have not been well defined. This study aimed to evaluate the cumulative incidence of new-onset cirrhosis, serological responses, and hepatocellular carcinoma (HCC) development between these treatment strategies.

Two independent cohorts of non-cirrhotic, HBeAg-positive CHB patients were analyzed: a treatment-naïve cohort (n = 686) and an NA-experienced cohort (n = 531). Patients received either IFN-based therapy or NA monotherapy. Propensity score matching (PSM) was employed to minimize intergroup heterogeneity. The primary endpoint was the cumulative incidence of new-onset cirrhosis.

After PSM, the 10-year cumulative incidence of new-onset cirrhosis was significantly lower in the IFN-based therapy group compared to the NA monotherapy group in both the treatment-naïve (3.3 % vs 20.0 %, p = 0.005) and NA-experienced (4.9 % vs 20.9 %, p = 0.034) cohorts. IFN-based therapy also resulted in significantly higher serological response rates across both cohorts, including HBeAg loss (treatment-naïve: 84.7 % vs 55.6 %; NA-experienced: 60.4 % vs 43.6 %, both p < 0.001) and HBsAg loss (treatment-naïve: 14.3 % vs 5.7 %, p = 0.006; NA-experienced: 10.2 % vs 1.3 %, p < 0.001). Subgroup analysis showed that patients receiving IFN-based therapy who achieved HBeAg loss within 96 weeks had the greatest long-term benefits, with lower cirrhosis incidence and higher HBsAg loss rates. Although the incidence of HCC was lower in the IFN-based group, the difference did not reach statistical significance (both p > 0.05).

IFN-based therapy provides superior long-term benefits over NA monotherapy in reducing cirrhosis risk and enhancing serological responses in HBeAg-positive CHB patients.

Hepatitis B surface antigen (HBsAg) clearance is an achievable treatment endpoint for chronic hepatitis B virus (HBV)-infected patients. Pegylated interferon-α (PEG-IFN-α) induces higher rate of HBsAg clearance than nucleos(t)ide analogues. However, the influencing factors associated with HBsAg recurrence have not been fully elucidated. The aim of this study was to evaluate the risk factors for recurrence in chronic HBV-infected patients who achieved functional cure with PEG-IFN-α-2b-based treatment.

A multicenter retrospective study was conducted. All patients received PEG-IFN-α-2b-based therapy, achieved HBV DNA negativity and HBsAg clearance, and were followed-up for at least 48 weeks after discontinuation of medications. The demographic data, as well as virological, serological, and biochemical indicators, were collected at baseline, therapy cessation, and during followed-up. Logistic regression analysis was subsequently performed.

A total of 101 chronic HBV-infected patients who achieved HBsAg loss with PEG-IFN-α-2b-based therapy were enrolled. The median treatment time was 24.00 (14.50, 37.50) weeks, and the median consolidation time was 11.00 (0.00, 24.00) weeks. HBsAg recurrence was found in 16 patients after a median 70.00 (48.00, 96.00) week follow-up, with a cumulative recurrence rate of 15.84%. A higher platelet count was associated with a slightly increased HBsAg recurrence risk at therapy cessation, whereas a shorter consolidation time was associated with an elevated HBsAg recurrence risk during followed-up. The appearance of anti-HBs presented a robustly reduced HBsAg recurrence risk at both therapy cessation and followed-up. No HBV DNA positivity or occurrence of end-stage liver disease was observed during treatment or followed-up.

The cumulative HBsAg recurrence rate was 15.84% after discontinuation of medications in chronic HBV-infected patients who achieved functional cure with PEG-IFN-α-2b-based therapy. The presence of anti-HBs reduced the HBsAg recurrence risk.

This trial is a part of ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837) and a part of E-Cure Study (ClinicalTrials.gov, identifier NCT05182463).

Hepatocellular carcinoma (HCC) poses a significant global health burden, with escalating incidence rates and substantial mortality. The predominant etiological factors include liver cirrhosis (LC) and chronic hepatitis B infections (CHB). Surveillance primarily relies on ultrasound and Alpha-fetoprotein (AFP), yet their efficacy, particularly in early HCC detection, is limited. Hence, there is a critical need for accurate non-invasive biomarkers to enhance surveillance and early diagnosis. Extracellular vesicles (EVs) hold promises as stable carriers of signaling molecules, offering potential in tumor diagnosis. Our study developed a novel tidal microfluidic chip for label-free EV isolation, enabling rapid and efficient enrichment from small plasma volumes. Through transcriptome sequencing and single-cell analysis, we identified HMMR and B4GALT2 as promising HCC-associated biomarkers in EVs. In a comprehensive clinical evaluation, bi-mRNAs in EVs exhibited superior diagnostic performance over AFP, particularly in distinguishing early-stage HCC or AFP-negative cases from high-risk individuals (CHB/LC). Notably, our study demonstrated the potential of bi-mRNAs to complement imaging examinations, enabling early detection of HCC lesions. In conclusion, the tidal microfluidic chip offers a practical solution for EV isolation, with the integration of EV-based biomarkers presenting opportunities for improved early detection and management of HCC in clinical practice.

Chronic hepatitis B (CHB) patients who do not meet any immunostaging criteria are categorized as the "grey zone" (GZ). However, there are discrepancies in the definition of the GZ in different areas.

To investigate the prevalence and clinical characteristics of Chinese GZ patients and to validate the application value of three international guidelines.

Data from 807 naïve CHB patients with liver biopsies from seven Chinese centres were retrospectively collected. GZ patients were defined and compared across four guidelines: the Chinese guidelines, the American Association for the Study of Liver Diseases (AASLD) guidelines, the European Association for the Study of the Liver (EASL) guidelines, and the Asian Pacific Association for the Study of the Liver (APASL) guidelines.

When the Chinese guidelines were used, 38.79% of patients were categorized into the GZ, 78.91% of whom were indicated for antiviral therapy. The EASL guidelines yielded a greater proportion of GZ patients (50.56%) than did the APSAL (36.68%) and AASLD guidelines (33.21%). The APASL guidelines yielded a lower proportion of GZ patients who were indicated for antiviral therapy (42.57%) than did the AASLD (47.76%) and EASL guidelines (60.54%). According to the AASLD, EASL, APASL and Chinese guidelines, if liver biopsy was not performed, 13.06%, 31.86%, 0% and 64.54% of GZ patients were indicated for antiviral therapy, respectively.

GZ patients account for a significant proportion of CHB patients, with approximately half of them requiring antiviral therapy.

NCT06041022.

Little is known about the short-term and long-term outcomes of non-cirrhotic chronic hepatitis B (CHB) patients who experience hepatic decompensation. Therefore, this study aimed to investigate the clinical outcomes of decompensated non-cirrhotic CHB patients.

We conducted a retrospective study and enrolled a total of 304 decompensated non-cirrhotic CHB patients. Cox regression model was used to analyze factors associated with all-cause mortality. Additionally, the incidence of HBsAg seroclearance and its associated factors were estimated by the competing risk analysis.

The median follow-up time was 4.36 years (IQR 1.04-7.16). Out of the total enrolled patients, 63 (20.72 %) patients either died or underwent liver transplantation, and 14 patients achieved HBsAg seroclearance. Risk factors associated with 1-month, 3-month, and long-term all-cause mortality were the presence of ascites and hepatic encephalopathy, baseline HBV DNA levels, and MELD scores. The cumulative incidence of HBsAg seroclearance was 1.78 %, 3.72 %, 4.25 %, 5.68 %, 5.68 %, 8.28 %, and 8.28 % at the 1-year, 2-year, 3-year, 4-year, 5-year, 6-year, and 7-year follow-up, respectively. Independent predictors for HBsAg seroclearance were baseline alanine aminotransferase (ALT)≧ 25 times upper limit of normal (subdistribution hazard ratio [sHR] = 5.97; 95 %CI, 1.82-19.63; p = 0.0032) and HBV DNA <5 log10 IU/ml (sHR = 4.43; 95 %CI, 1.55-12.63; p = 0.0054).

The presence of ascites and hepatic encephalopathy, baseline HBV DNA levels, and MELD scores were associated with short-term and long-term all-cause mortality. Additionally, lower HBV DNA levels and higher ALT levels at baseline were independently predictive of sequential HBsAg seroclearance.

The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

Hepatitis B, hepatitis C, cytomegalovirus (CMV), and tuberculosis (TB) pose significant risks to patients with inflammatory bowel disease (IBD) receiving biological therapy. However, data on the prevalence of these infections in Syria are scarce.

We conducted a retrospective chart review of IBD patients receiving biologic therapy at Damascus Hospital and Ibn Al-Nafees Hospital, two major public institutions in Syria, between January 2021 and November 2024. A minimum sample size of 130 was estimated; however, all available records were reviewed.

Among 185 IBD patients (104 from Damascus and 81 from Ibn Al-Nafees), 51.4% had ulcerative colitis and 47.6% had Crohn's disease. The smoking prevalence was 9.2%, which was higher in Crohn's disease (5.9%) than in ulcerative colitis (3.2%). TST performed in 61.1% of patients, with 4.3% positivity, and interferon-gamma release assay (IGRA) in 8.7% (1.1% positive). Hepatitis B surface antigen (HBsAg) and anti-HBc antibodies were found in 2.7% and 5.4% of the patients, respectively, while hepatitis C seroprevalence was low (0.5%). CMV seropositivity was high in Damascus (50.8%), with two cases (1.1%) of CMV colitis. Biologic therapies included infliximab (42.7%), ustekinumab (24.3%), golimumab (10.8%), and adalimumab (6.5%). Data gaps, particularly in viral serology and TB screening, are notable.

This study identifies deficiencies in TB/hepatitis B screening (notably anti-HBs Ab) and elevated CMV seroprevalence among Syrian IBD patients receiving biologics, extending to immunosuppressed cohorts (rheumatology, dermatology, oncology). Insufficient screening heightens occult infection/reactivation risks, necessitating standardized pretreatment protocols to reduce morbidity in high-risk populations.

Not applicable.

This study aims to evaluate the prevalence of undiagnosed hepatitis delta in southern Spain (Andalusia) and assess the effectiveness and cost-efficiency of implementing reflex testing for hepatitis D detection in HBsAg-positive patients. A multicenter ambispective study was conducted in 17 Andalusian hospitals. The retrospective phase (January 2018-June 2022) analyzed diagnostic processes for hepatitis delta in HBsAg-positive patients. The prospective phase (October 2022-March 2023) implemented reflex testing, performing anti-HDV serology on all HBsAg-positive patients without prior testing. HDV RNA testing followed for those who tested anti-HDV-positive. In the retrospective phase, out of 18,583 HBsAg-positive patients, anti-HDV tests were performed on 3,436 (18%), identifying 205 (6%) positive cases. HDV RNA was tested in 158 (77%) anti-HDV-positive patients, with 69 (44%) testing positive. In the prospective phase, out of 2,384 HBsAg-positive patients without prior anti-HDV testing, 2,293 (96%) were tested, identifying 109 (4.7%) positive cases. HDV RNA was analyzed in 97 (89%) anti-HDV-positive patients, with 30 (31%) testing positive. Reflex testing increased anti-HDV detection by 77%, resulting in a fourfold increase in detecting anti-HDV-positive patients and a threefold increase in detecting HDV RNA-positive patients, reducing undiagnosed HDV RNA-positive cases to 4% compared to 45% with clinical practice. Cost analysis indicated a saving of €265,954 with reflex testing. Reflex testing improves HDV detection, reduces costs, and simplifies diagnosis, making it an efficient strategy for managing chronic hepatitis D patients.

The risk of mother-to-child transmission for pregnant women with chronic hepatitis B (CHB) still exists, especially for those with high HBV DNA levels. The guidelines for initiating prophylaxis for pregnant women with CHB vary across countries. We aimed to explore the latest prophylaxis initiation time for these women.

We collected the real-world clinical data of 328 pregnant women aged 20-49 with CHB, who were treated with telbivudine or tenofovir disoproxil fumarate, from July 2010 to December 2020 in China. A mathematical model was developed to describe the viral kinetics of HBV after prophylaxis. We calculated the time required to reduce viral load below the threshold value of 5.3 log10 IU/ml. We derived the prophylaxis initiation time by subtracting the required time to threshold from the childbirth gestational week.

The median time for 328 women to reduce HBV DNA levels below the threshold of 5.3 log10 IU/ml was 4.2 (range: 0.2-12.8) weeks, corresponding to a prophylaxis initiation time of no later than 35.1 (25.2-41.4) weeks. Specifically, for women with viral loads >8.0 log10 IU/ml, prophylaxis should be initiated before 33.9 (25.2-39.5) weeks, and even before the lower bound of 25.2 weeks, to maximize clinical safety. For women with viral load >7.0 to ≤8.0 log10 IU/ml, prophylaxis should be initiated before 35.5 (28.6-39.8) weeks, and for women with viral load >5.3 to ≤7.0 log10 IU/ml, prophylaxis should be initiated before 36.2 (28.3-41.4) weeks.

Pregnant women with HBV DNA levels >5.3 to ≤8.0 log10 IU/ml can initiate prophylaxis before 28 gestational weeks. However, women with HBV DNA >8.0 log10 IU/ml could consider initiating prophylaxis before 25 weeks.

This study investigates how long it takes to decrease maternal viral load below a threshold (5.3 log10 IU/ml) after receiving antiviral prophylaxis in pregnant women with different HBV DNA levels based on real-world clinical data and mathematical modelling, which provides quantitative evidence on the initiation time of antiviral prophylaxis. The results show that pregnant women with CHB infection at high HBV DNA levels (>8 log10 IU/ml) should initiate antiviral prophylaxis earlier to decrease the risk of mother-to-child transmission of HBV. Physicians can determine when to begin antiviral prophylaxis for those women according to their maternal HBV DNA levels. Our findings justify the initiation time of antiviral prophylaxis recommended by the Chinese guidelines and will offer new insights for other international guidelines.

The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study.

In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log 10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected 8 week) or to 4 weeks postpartum (expected 12 week) were randomly enrolled at a 1:1 ratio and followed until 6 months postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary end point was the safety of mothers and infants. The secondary end point was the HBV-MTCT rate of infants at the age of 7 months.

Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in 2 groups completed the study. Overall, TAF was well tolerated, no one discontinued the therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n = 231) and at 7 months (n = 222) was normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log 10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at the age of 7 months. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) vs 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the 2 groups had mildly elevated alanine aminotransferase levels at 3 months and 6 months postpartum, respectively ( P = 0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] vs 0% [0/120, 0%-3.1%]).

Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected 8-week prenatal duration is feasible. ClinicalTrials.gov , NCT04850950.

The relapse pattern following the discontinuation of tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to compare the 2-year incidences of virological and clinical relapses among patients who discontinued TAF versus those who discontinued tenofovir disoproxil fumarate (TDF) or entecavir (ETV).

This multicenter retrospective study enrolled noncirrhotic hepatitis B e antigen (HBeAg)-negative CHB patients who discontinued TAF, TDF, or ETV with undetectable HBV DNA at treatment cessation. For patients who switched from ETV or TDF to TAF, a minimum TAF exposure duration of 12 months was required for inclusion in the off-TAF group. Inverse probability of treatment weighting was employed to adjust for baseline differences.

A total of 162 patients (off-TAF: 37, off-TDF: 87, off-ETV: 38) were included in the primary analysis. The 2-year cumulative incidence of virological relapse was significantly higher in the off-TAF group (85.0%) compared to the off-TDF group (69.5%, p = 0.024) and the off-ETV group (51.5%, p = 0.010). Similarly, the 2-year cumulative incidence of clinical relapse was significantly higher in the off-TAF group (62.4%) compared to the off-TDF group (39.0%, p = 0.026) and the off-ETV group (22.5%, p = 0.024). Consistent results were observed in patients meeting the 2012 APASL stopping criteria.

HBeAg-negative patients who discontinue TAF face a higher risk of both virological and clinical relapses compared to those discontinuing TDF or ETV. These findings underscore the need for more intense monitoring in CHB patients after TAF cessation.

To identify factors influencing HBsAg seroclearance rates after stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB).

We conducted a comprehensive literature search in databases from inception to July 2024. Subgroup analyses and meta-regression were performed to determine factors associated with HBsAg seroclearance, including ethnicity, HBV genotype, NA therapy duration, end-of-treatment (EOT) qHBsAg levels, HBeAg status, cirrhosis status, and follow-up duration.

The meta-analysis included 62 studies (n = 9867) with a pooled HBsAg seroclearance rate of 10% (95%CI: 8%-12%, I2 = 92%) after NA cessation. HBeAg-negative patients showed significantly higher rates than HBeAg-positive patients (11% vs. 5%, p = 0.030). Subgroup analysis revealed higher seroclearance with follow-up of >5 years (18%, p = 0.004), showing significantly higher rates were observed in studies with longer follow-up periods. Caucasians showed a higher rate (12%) than Asians (9%, p = 0.067). Studies adhering to AASLD, EASL, or APASL stopping rules showed no significant differences in rates. Patients with EOT qHBsAg ≤2.0 log IU/mL had higher rates (23%) than those with >2.0 log IU/mL (11%). Re-treated patients had lower seroclearance (6%) compared to those not re-treated (17%, p = 0.178). Meta-regression identified ethnicity, HBeAg status, and follow-up duration as significant contributors to heterogeneity. Egger's test showed no evidence of publication bias (p = 0.1928).

Our meta-analysis highlights the role of ethnicity, EOT qHBsAg levels, HBeAg-status, and follow-up duration in determining HBsAg seroclearance rates. These findings stress the need for personalized NA discontinuation strategies and further research on HBV genotypes and biomarkers to improve treatment outcomes and predict seroclearance more accurately.

Chronic hepatitis B virus (HBV) infection is an etiology of HCC, but clinical trials using immune checkpoint inhibitors (ICIs) usually exclude patients with chronic active hepatitis B (serum HBV viral load > 2000 IU/mL). This study examined the safety and efficacy of concurrently administering the ICI and anti-HBV medications in this patient population.

In this single-arm phase 2 clinical trial, we enrolled patients with advanced HCC and untreated chronic active hepatitis B. Patients received 1500 mg of durvalumab every 4 weeks alone or in combination with 300 mg of tremelimumab on day 1 (the STRIDE regimen). Anti-HBV treatment with entecavir was simultaneously initiated. The primary endpoint was the rate of HBV reactivation.

We enrolled 30 patients, whose mean baseline HBV viral load was 770,986 IU/mL. No patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare was noted in 8 (26.7%) patients, but none of them were associated with HBV reactivation. The objective tumor response rate was 10% and 25% for the durvalumab treatment alone and the STRIDE regimen, respectively.

For patients with chronic active hepatitis B, ICI therapy could be promptly initiated as long as anti-HBV medications were administered simultaneously.

NCT04294498.

Viral hepatitis remains a global health challenge and immune status affects outcomes. In patients with haematological malignancies, including haematopoietic stem-cell transplantation recipients, viral hepatitis can be life-threatening due to the direct effects of the virus or the need to modify or delay chemotherapy. Additionally, haematopoietic stem-cell donors with past or current viral hepatitis infections might transmit the virus to recipients. The growing recognition of hepatitis E virus (HEV), advances in haematological therapies, and the availability of direct-acting antivirals for hepatitis C virus (HCV), led the 2022 9th European Conference on Infections in Leukaemia (ECIL-9) to update the 2013 ECIL-5 guidelines on viral hepatitis. The ECIL organising committee convened a panel of 13 impartial international experts (all authors of this Review) in viral hepatitis, both within and outside the fields of haematological malignancies and immunosuppression. The ECIL-9 panel conducted a review of the literature on hepatitis B virus (HBV), HCV, and HEV, grading the evidence based on the European Society for Clinical Microbiology and Infectious Diseases system. The panel identified key clinical questions and outcomes and built on the recommendations established during ECIL-5. A consensus conference was held in Sofia Antipolis, France, from Sept 15-17, 2022, bringing together 49 experts from 19 countries. The ECIL-9 panel presented the proposed recommendations, which were revised following expert discussions. A final consensus on updated guidelines was reached in a second plenary session. The updated ECIL-9 guidelines provide evidence-based recommendations on the prevention, screening, treatment, and long-term surveillance of viral hepatitis in patients with haematological malignancies and haematopoietic cell transplantation recipients.

This study aimed to determine the seroprevalence of hepatitis B virus (HBV) among newly diagnosed cancer patients in Khartoum State, Sudan, prior to chemotherapy initiation and to identify associated risk factors.

A cross-sectional study was conducted from October 2022 to April 2023 at various oncology centers in Khartoum State. A total of 300 newly diagnosed cancer patients, aged 18 years and older, were included. Blood samples were screened for Hepatitis B surface antigen (HBsAg) using a rapid immunochromatographic test (ICT) and confirmed by enzyme-linked immunosorbent assay (ELISA). The study found that 31 patients (10.3%) were HBsAg positive. A significant association was observed between HBV positivity and patients' history of blood transfusions (41.9% of positive cases), as well as geographic origin, with higher rates among those from Western Sudan (44.7%) and Central Sudan (40.6%). Patients diagnosed with hematological malignancies exhibited the highest HBV prevalence. Statistical analysis revealed significant correlations between HBV positivity and factors such as age, gender, residence, and transfusion history, indicating these as key risk factors.

The study reveals a notable HBV seroprevalence among cancer patients in Khartoum, particularly linked to blood transfusion history and specific regions. These findings emphasize the need for routine HBV screening in oncology patients before chemotherapy to prevent reactivation and improve clinical outcomes.

Drug-induced liver injury (DILI) is becoming a worldwide emerging problem. However, few studies focus on the diagnostic performance of non-invasive markers in DILI. This study aims to develop novel integrative models to identify DILI-associated liver inflammation and fibrosis, and compare the predictive values with previously developed indexes.

A total of 72 DILI patients diagnosed as DILI through liver biopsy were enrolled in this study. Patients were divided into absent-mild (S0-S1, G0-G1) group and moderate-severe (S2-S4, G2-G4) group based on the histological severity of inflammation and fibrosis. We used the area under the receiver operating characteristics curves (AUC) to test the model performances. Backward stepwise regression, best subset and logistic regression models were employed for feature selection and model building. Prediction models were presented with nomogram and evaluated by AUC, Brier score, calibration curves and decision curve analysis (DCA).

For diagnosing moderate-severe inflammation and fibrosis, we calculated the AUC of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and fibrosis-5 index (FIB-5), which were 0.708 and 0.676, 0.778 and 0.667, 0.822 and 0.742, 0.831 and 0.808, respectively. Then, backward stepwise regression, best subset and logistic regression models were conducted for predicting significant liver inflammation and fibrosis. For the prediction of ≥G2 inflammation grade, the AUC was 0.856, 0.822, 0.755, and for the prediction of ≥S2 fibrosis grade, the AUC was 0.889, 0.889, 0.826. Through Brier score, calibration curves and DCA, it was further demonstrated that backward stepwise regression model was highly effective to predict both moderate-severe inflammation and fibrosis for DILI.

The backward stepwise regression model we proposed in this study is more suitable than the existing non-invasive biomarkers and can be conveniently used in the individualized diagnosis of DILI-related liver inflammation and fibrosis.

Chitinase 3-like protein 1 (CHI3L1) is a marker of liver fibrosis produced mainly by hepatic macrophages. However, few studies have assessed the relationship between CHI3L1 and liver fibrosis in autoimmune liver diseases (AILDs). We aimed to explore the diagnostic value of CHI3L1 for liver fibrosis in AILDs and to compare its application differences between AILDs and chronic hepatitis B (CHB) patients.

The fibrotic group was defined as liver stiffness measurement (LSM) > 9.70kPa. Serum CHI3L1 levels were measured by ELISA in 78 AILDs patients, 65 chronic hepatitis B patients. The diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve (AUROC).

Serum CHI3L1 levels in AILDs patients were positively correlated with LSM (r=0.750, p <0.001). The AUROC for serum CHI3L1 in identifying significant liver fibrosis was 0.939 (95% CI: 0.891 - 0.988), which was higher than that of other non - invasive fibrosis scores (APRI, FIB - 4, GPR, AAR, NLP, and PLR). At the optimal cutoff value of 86.84 ng/mL, the sensitivity and specificity were 92.9% and 83.3%, respectively. Furthermore, in patients with no significant difference in LSM, serum CHI3L1 levels were higher in the autoimmune liver disease group than in the CHB group.

Serum CHI3L1 is an effective non-invasive indicator for assessing liver fibrosis in AILDs patients and may vary in different etiologies.

Patients with chronic hepatitis B virus (HBV) infection and low serum HBV DNA level (<2000 IU/mL) are not indicated for anti-HBV therapy. Fortunately, anti-HBV therapy is recommended if co-infected with hepatitis C virus (HCV) by World Health Organization recently. Whether specific anti-viral therapy could facilitate the decline or the loss of hepatitis B surface antigen (HBsAg) in this clinical setting was investigated in the co-infected patients.

We retrospectively collected 60 patients with chronic HBV/HCV co-infection and low serum HBV DNA (<2000 IU/mL). All were positive for HBsAg and anti-HCV/HCV RNA >6 months. Among them, 26 patients didn't receive any anti-HBV or anti-HCV therapy (Group 1), 23 patients received peginterferon plus ribavirin therapy for HCV (Group 2) and 11 patients received DAA therapy for HCV (Group 3). Serum HBsAg levels at the end of 3-year follow-up was obtained retrospectively.

Serum HBsAg (log10 IU/mL) decline was found to be greatest in Group 2 patients, [median: log 0.605; Range 25 %-75 % [Range] = 0.272-1.476) and least in Group 3 patients, (log 0.340, -0.453-0.559). Statistically significant difference was found between Group 2 and 3 (P = 0.0489). Proportion of patient with >1 log decline in serum HBsAg was 26.9 %, 43.4 % and 9.1 % in Group 1, 2 and 3, respectively. Statistically significant difference was also found between Group 2 and 3 (P = 0.045).

In HBV/HCV co-infected patients with low serum HBV DNA, favorable HBsAg dynamics was found post-interferon/ribavirin therapy. These findings supported further investigations of interferon-based therapy in this clinical setting.