Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCVposMCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCVposMCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCVposMCV. The prevalence of HBsAg seroclearance was 48% within 123 HCVposMCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCVposMCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCVposMCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCVposMCV in male CHC patients.

In recent decades, microRNAs (miRNAs) have emerged as key regulators of gene expression, and the identification of viral miRNAs (v-miRNAs) within some viruses, including hepatitis B virus (HBV), has attracted significant attention. HBV infections often progress to chronic states (CHB) and may induce fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The presence of HBV can dysregulate host miRNA expression, influencing several biological pathways, such as apoptosis, innate and immune response, viral replication, and pathogenesis. Consequently, miRNAs are considered a promising biomarker for diagnostic, prognostic, and treatment response. The dynamics of miRNAs during HBV infection are multifaceted, influenced by host variability and miRNA interactions. Given the ability of miRNAs to target multiple messenger RNA (mRNA), understanding the viral-host (human) interplay is complex but essential to develop novel clinical applications. Therefore, bioinformatics can help to analyze, identify, and interpret a vast amount of miRNA data. This review explores the bioinformatics tools available for viral and host miRNA research. Moreover, we introduce a brief overview focusing on the role of miRNAs during HBV infection. In this way, this review aims to help the selection of the most appropriate bioinformatics tools based on requirements and research goals.

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.

Hepatitis B remains a significant global clinical problem, despite the implementation of safe and effective vaccination programs. The prevalence of hepatitis B virus (HBV) in patients with inflammatory bowel disease (IBD) largely follows the regional epidemiologic status. Serological screening with hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B surface (anti-HBs) and core (anti-HBc) proteins is a key element in the management of IBD patients and, ideally, should be performed at IBD diagnosis. Stratification of individual cases should be done according to the serologic profile and the IBD-specific treatment, with particular emphasis in patients receiving immunosuppressive regimens. In patients who have not contracted HBV, vaccination is indicated to accomplish protective immunity. Vaccination in immunosuppressed patients, however, is a challenging issue and several strategies for primary and revaccination have been proposed. The risk of HBV reactivation in patients with IBD should be considered in both HBsAg-positive and HBsAg-negative/anti-HBc-positive patients, when immunosuppressive therapies are administered. HBV reactivation is preventable via the administration of prophylactic nucleot(s)ide analogues and should be the standard approach in HBsAg-positive patients. HBsAg-negative/anti-HBc-positive patients represent a non-homogeneous group and bear a significantly lower risk of HBV reactivation. Biochemical, serological and molecular monitoring is currently the recommended approach for anti-HBc patients. Acute HBV infection is rarely reported in IBD patients. In the present review, we outline the problems associated with HBV infection in patients with IBD and present updated evidence for their management.

Blood safety is a non-negotiable issue worldwide, specifies the World Health Organization (WHO). Africa is both an entity and a multiplicity of situations within and cross-borders. Indeed, most African countries have recent borders and political organizations, after gaining independence in the 60's. Many such countries have maintained various types of links and cooperation programs with former European countries of influence, e.g. France and Belgium among others, which is the case for several countries from the francophone Central and West Africa. Besides, borders do not delineate ethnic groups as many of them migrate, with spread North to South and East to West across several countries, each having representations, ethnologically speaking. Transfusion is an essential supportive healthcare that requires medicine, technicity and logistics. Cooperation can be provided to Francophone Africa though at the expense of recruiting donors upon criteria that do not completely overlap with e.g. those put forward in France and other high-income countries, despite WHO claims for the universal model of Voluntary Non-Remunerated Blood Donation system. Next, the patient profile in intertropical Africa-of which the various francophone African countries-stringently differs from the profile now seen in France, with its younger (but strongly social network-connected) populations and the importance of anemia of all causes but frequently infectious in nature. The frequency of antigens defining blood groups also significantly differs from that in France and the rest of Europa. Last, the carriage of blood transmissible infectious pathogens in sick but also apparently healthy populations seriously complicates the build up of suitable blood component inventory. In the present review, we discuss the universality of blood donation, the specificities of inter-continent cooperation and report on experiences of such cooperation. The French Blood Establishment EFS has taken over earlier initiatives of regional blood services and provides technology and scientific transfer and support to many countries for several decades; the National Institute for Blood transfusion, an education and research institute, has set up collaborative research in several domains but mostly in the domain of blood transmissible infections. We next also present a theoretical view of support named ALEASE, that can be pursued, based on collaborative experiences carried out in the Mediterranean Northern and Eastern areas. ALEASE promotes benchmark between participants. If there is general agreement that cooperation between economically wealthy countries and low-income, developing, countries in the domain of blood and blood transfusion safety, promotion of blood donation, blood component manufacturing, transfusion technology, hemovigilance, etc., tools to achieve this goal can be periodically reviewed based on specific needs for countries and professionals. That also comprise of adapted, sometimes specific, education programs.

Tanzania has a high prevalence (7.17%) of chronic hepatitis B infection. Mother to Child transmission is very common, resulting in high rate of chronic infections. Currently, there is no screening program for HBV in pregnant women. This study investigated the prevalence and risk factors for chronic HBV infection in pregnant women in a tertiary hospital in Mwanza, Tanzania.

Seven hundred and forty-three women attending antenatal care and/or delivering at the Bugando Medical Centre were enrolled. All answered a questionnaire on sociodemographic and other risk factors and were tested for HBsAg using a rapid test. In HBsAg positive mothers, maternal blood and umbilical cord blood samples collected after delivery were analyzed for serological (HBsAg, HBeAg and anti-HBe) and virologic (HBV-DNA viral load and genotype) markers. All their babies were vaccinated within 24 h of delivery. The children were followed up at 3 years of age. Data was analyzed using the Mann-Whitney U-test, independent sample T-test and logistic regression.

Of the 743 participants, 22 (3%) were positive for HBsAg, and 2 (9%) had detectable HBe-antigen. Low condom use was the only statistically significant risk factor for chronic HBV infection (OR = 3.514, 95%CI = 1.4-8.0). Of 14 maternal blood samples genotyped, 10 (71%) were genotype A and 4 (29%) were genotype D. HBV-DNA was detected in 21/22 samples, with a median of 241 IU/ml (range: 27.4-25.9 × 107 IU/ml). Five (33%) of 15 available cord blood samples were positive for HBsAg and 10 (67%) were negative. At follow-up, one child showed chronic HBV infection characteristics, one had anti-HBs level of 7 mIU/ml and 5/7(71%) had protective anti-HBs levels (> 10 mIU/ml).

This cohort of pregnant women showed a lower-intermediate prevalence of HBV of 3%. In the 3 years follow-up only 1 out of 7 children showed evidence of chronic HBV infection. The child's mother with high viral load (25.9 × 107 IU/ml), was positive for HBeAg with a high degree of sequence similarity suggesting vertical transmission. These results highlight a need for improved diagnosis and treatment of HBV infection in pregnant women in Tanzania, in order to prevent vertical transmission.

To identify blood donors with occult hepatitis B infections (OBIs), determine the prevalence of antibody to hepatitis B core antigen (anti-HBc) positivity and estimate the impact of anti-HBc screening on donor deferral at CETS-Veracruz (Mexico).

Hepatitis B virus infection is a major concern in transfusion medicine. Mexican regulations only mandate screening for hepatitis B surface antigen (HBsAg), and there are no requirements regarding testing for anti-HBc or use of a nucleic acid test (NAT). There is, therefore, limited information about the prevalence of anti-HBc positivity and occult hepatitis B among blood donors in Mexico.

This retrospective study examined individuals who donated blood to CETS-Veracruz from June 2014 to June 2017. All donors were serologically examined according to Mexican health regulations, and the prevalence of anti-HBc positivity was determined. A NAT was used to identify individuals with OBIs.

We analysed the data of 28 016 blood donors. Over 4 years, the average prevalence of anti-HBc positivity was 1.05%. The risk factors for anti-HBc positivity were low education and age over 50 years. There were nine donors with OBIs.

The presence of donors with OBIs in CETS-Veracruz and other Mexican blood banks highlights the need to mandate the implementation of anti-HBc screening in Mexico.

Occult hepatitis B virus infection (OBI) carries a risk of hepatitis B virus (HBV) transmission and hepatocellular carcinoma. As previous studies have had a limited sample size, the characteristics of OBI with genotype B and C (OBI_B and OBI_C) mutations relating to hepatitis B surface antibody (anti-HBs) elicited by vaccination or a limited host immune response to HBV have not been fully explored.

In this study, the occurrence of OBI_B or OBI_C strains associated with envelope protein (pre-S/S) amino acid substitutions obtained from 99 blood donors stratified according to anti-HBs carriage were characterized extensively.

According to the presence of anti-HBs within each genotype, the number and frequency of substitution sites specific for anti-HBs(-) OBI_B were higher than those specific for anti-HBs(+) OBI_B strains (67 vs 31; 117 vs 41), but the reverse pattern was found in OBI_C strains (3 vs 24; 3 vs 26). Mutations pre-s₁T68I and sQ129R/L were found uniquely in 15-25% of anti-HBs(+) OBI_B carriers and mutation pre-s₁A54E was found preferentially in anti-HBs(+) OBI_C, while 17 substitutions were found preferentially in 11-38% of anti-HBs(-) OBI_B strains. In the major hydrophilic region (MHR) region, mutations sS167 in OBI_B, sT118 in OBI_C, and sA166 in both genotypes were possibly immune-induced escape mutation sites.

Several mutations in pre-S/S of OBI appeared to be associated with carrier anti-HBs pressure, which might be risk factors for potential reactivation of viruses under anti-HBs selection in OBI carriers.

Hepatitis B surface antigen (HBsAg) is the primary marker for diagnosis of acute and chronic hepatitis B. Although HBsAg assays have undergone continuous improvement, gaps remain in the detection of early and late acute infection and occult hepatitis B infection (OBI).

The performance of a prototype, improved sensitivity HBsAg assay run on the ARCHITECT and Alinity instruments was evaluated for detection of early and late acute infection and OBI.

Seventy seven early acute samples [positive only for hepatitis B viral DNA (HBV DNA)], twelve seroconversion panels spanning late acute infection, and 101 occult samples (HBsAg negative, positive for HBV DNA and anti-HBc) were tested with the prototype assay and ARCHITECT HBsAg Qualitative II. HBsAg gene sequencing was performed to determine genotype and mutations in the immunodominant region.

Compared with ARCHITECT HBsAg Qualitative II, the prototype assay showed increased detection of NAT yield samples (28/77, 36.4%,), late acute samples (≥13 days longer detection of HBsAg for 6/12 panels), and OBI samples (11/101, 10.9%). HBsAg sequence data were obtained for 62 samples. Genotypes represented were A1, A2, B2, B4, C1, C2, C5, D3, E, and H. HBsAg escape mutations were found in 4.8% of NAT yield and 38.9% of OBI samples sequenced. Prototype assay values for 188 samples were equivalent on the ARCHITECT and Alinity instruments.

The new prototype HBsAg assay will be of diagnostic value in providing improved detection of early acute, late acute, and occult HBV infections.

The anti-HBc prevalence over a 14-years period (2004-2017), trends, infectivity, residual risk, and need for testing in blood donors (BD) of the Croatian Institute of Transfusion Medicine were assessed.

Anti-HBc was tested in 19,969 BD serum samples collected in 2004 (N=7561), 2013 (N=7318) and 2017 (N=5090). All serums were initially screened for HBsAg, anti-HCV, HIV Ag/Ab, and anti-TP. 2013 and 2017 samples were also tested by ID-NAT.

Over a 14-years period, the anti-HBc prevalence significantly decreased among Croatian BD (5.24% in 2004, 2.56% in 2013, and 1.32% in 2017). Similarly, the prevalence of anti-HBc-only profiles decreased from 0.62% in 2004, 0.25% in 2013, and 0.21% in 2017. The 4-time decreasing trend was observed in all age groups of BD from 2017 but mostly among repeat donors (5.90% to 1.38%). First-time donors showed no significant difference in anti-HBc prevalence probably due to their younger age (<29 years) and HBV vaccine status. However, similar anti-HBs carriage rates (80.56%, 87.57%, and 82.09%) were reported in anti-HBc positive donors over the study period. HBsAg and HBV DNA were not detected. No OBI infection was found in the study despite an OBI frequency of 1:10,900 donations previously reported in Croatia. A HBV decreasing residual risks of 68, 88, and 12 per million donations were estimated for years 2004, 2013, and 2017, respectively.

Anti-HBc testing is an additional measure of preventing HBV infection by transfusion. Implementation of anti-HBc testing will result in the deferral of 1.3% BD and should be supported by cost-benefit analyses.

Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in the liver and/or serum (&lt; 200 IU/mL) in HBsAgnegative patients with or without serologic markers of previous viral exposure. The clinical significance of OBI is of concern in posttransfusional hepatitis B infection, hepatitis B reactivation, chronic liver disease and hepatocellular carcinoma (HCC). The diagnosis of OBI relays on the use of highly sensitive and specific laboratory techniques. Herein, comments derived from a study analyzing the frequency and characteristics of OBI in HCC Japanese patients are stated. While OBI and other causes of HCC have been highly studied in Asia and Europe, research in Latin America in these topics is limited. Several findings such as population risk groups with high prevalence of overt and OBI infection, HBV genotype F in Argentinean HCC patients, and the clinical impact of the foreign A-D genotypes suggest the need of further investigation. Additionally, alcoholism, obesity, NASH and type 2 diabetes may override the presence of OBI. Therefore, OBI diagnosis is essential. It is known that anti-HBc alone is a predictive signal of potential OBI and given the fluctuations of the HBV infection markers, testing for HBsAg and anti-HBc at baseline and follow-up is recommended. In conclusion, OBI and other causes involved in the epidemiology of HCC in Latin America are unexplored risk factors. Genome-based research is required to decipher the role of gene-environmental interactions associated with chronic liver disease. Novel algorithms to detect OBI supported by basic/applied/clinical research are also needed.