Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.

Wilson disease (WD) is the most common genetic metabolic liver disease. Some studies have shown that comorbidities may have important effects on WD. Data on hepatitis B virus (HBV) infection in patients with WD are limited.

To investigate the prevalence and clinical impact of HBV infection in patients with WD.

The clinical data of patients with WD were analyzed retrospectively, and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.

Among a total of 915 WD patients recruited, the total prevalence of current and previous HBV infection was 2.1% [95% confidence interval (CI): 1.2%-3.0%] and 9.2% (95%CI: 7.3%-11.1%), respectively. The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B (CHB) infection. The diagnosis of WD was missed in all but two patients with CHB infection. The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo, which was significantly longer than that in patients with isolated WD (10.5 mo). The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD (63.1% vs 19.3%, P = 0.000 and 36.8% vs 4.1%, P < 0.001, respectively). Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection [odds ratio (OR) = 7.748; 95%CI: 2.890-20.774; P = 0.000)] or previous HBV infection (OR = 5.525; 95%CI: 3.159-8.739; P = 0.000) than in patients with isolated WD.

The total prevalence of current HBV infection in patients with WD was 2.1%. The diagnosis of WD in CHB patients is usually missed. HBV infection is an independent risk factor for severe liver disease in WD patients. The diagnosis of WD should be ruled out in some patients with CHB infection.

The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.

Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (p<0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (p<0.05). Positive anti-HBc results may predict OBI and also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression. This article is protected by copyright. All rights reserved.

Chronic hepatitis C infection is a major cause of liver cancer in the United States. Hawai'i's incidence of liver cancer consistently ranks among the highest in the US, due in part to the high prevalence of hepatitis B in the state. To better understand the factors associated with liver cancer among patients in Hawai'i with hepatitis C virus (HCV) infection, the patient database of Kaiser Permanente's Hawai'i region was used to identify a cohort of 3198 patients with a history of chronic HCV infection, of whom 159 (5%) were diagnosed with liver cancer between the years 2004-2020. Multiple logistic regression was used to identify factors independently associated with liver cancer. Male sex (AOR 2.02, 95% CI 1.34-3.06), Asian race (AOR 1.78, 1.16 - 2.74) and hepatitis B core antibody (HBCAB) positivity (AOR 1.76, 95% CI 1.25 - 2.49) emerged as independent predictors of liver cancer among patients with chronic HCV infection. A history of diabetes (AOR 1.56, 1.07 - 2.27) and older age at the time of HCV diagnosis (AOR 1.19, 1.09-1.29) also emerged as significant associations. HBCAB-positive individuals did not differ significantly from those who were HBCAB-negative in regards to demographics or 5-year survival rate. In this cohort of patients with chronic HCV, a positive HBCAB without evidence of active hepatitis B infection was associated with 1.76 increased odds of liver cancer compared to those with negative HBCAB. This finding may have important implications for screening algorithms among individuals with hepatitis C infection.

Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.

Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age.

A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ± 15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others.

This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.

Internal jugular vein stenosis (IJVS) has recently aroused increasing interests, whereas, the factors affecting its clinical outcomes are not clear. This study aims to explore the probable factors affected clinical prognosis by evaluating the IJVS with different etiologies and strategies.

Patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. One-year clinical outcomes of the IJVS cases enrolled in this study were assessed by outpatient and telephone follow-up using the Patient Global Impression of Change (PGIC) scores. According to the etiologies, patients were divided into thrombotic IJVS and non-thrombotic IJVS groups. And further, non-thrombotic IJVS group was divided into external compression and non-external compression subgroups. Outcomes of IJVS with different etiologies and strategies were compared and the probable prognostic factors were analyzed.

A total of 118 eligible patients enrolled in this study, including 76 females and 42 males, mean aged 55.07±14.61 years. The average follow-up duration after discharge was 13.22±3.80 months. According to the PGIC scores, we categorized patients as good outcome and poor outcome groups. For thrombotic IJVS, patients underwent standard anticoagulant obtained remarkable PGIC improvement (100.0% vs. 33.3%, P=0.038). For non-thrombotic IJVS, stenting showed benefit in non-external compression subgroup (26.9% vs. 3.3%, P=0.019) but not in external compression subgroup. In addition, we found that in this Chinese IJVS cohort, poor outcomes involved old age (P=0.004), type 2 diabetes mellitus (P=0.036), previous hepatitis B virus (HBV) infection (P=0.027), and head noises (P=0.002). Multivariate logistic regression analysis indicated that continuous head noises [P=0.045, odds ratio (OR): 2.412, 95% confidence interval (CI): 1.019-5.711], as a unique symptom of IJVS may be significantly related to poor outcomes.

In this Chinese cohort, elderly degenerative bone compression, type 2 diabetes mellitus, and previous HBV infection are the top-three probable etiologies of non-thrombotic IJVS and may involve poor outcome. Long-term head noises may predict IJVS and with poor outcome. Thrombosis-induced IJVS may get benefit from standard anticoagulation. Non-external compression IJVS can be corrected by stenting.

In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.

Coinfections involving viruses are being recognized to influence the disease pattern that occurs relative to that with single infection. Classically, we usually think of a clinical syndrome as the consequence of infection by a single virus that is isolated from clinical specimens. However, this biased laboratory approach omits detection of additional agents that could be contributing to the clinical outcome, including novel agents not usually considered pathogens. The presence of an additional agent may also interfere with the targeted isolation of a known virus. Viral interference, a phenomenon where one virus competitively suppresses replication of other coinfecting viruses, is the most common outcome of viral coinfections. In addition, coinfections can modulate virus virulence and cell death, thereby altering disease severity and epidemiology. Immunity to primary virus infection can also modulate immune responses to subsequent secondary infections. In this review, various virological mechanisms that determine viral persistence/exclusion during coinfections are discussed, and insights into the isolation/detection of multiple viruses are provided. We also discuss features of heterologous infections that impact the pattern of immune responsiveness that develops.