HBV Hepatitis Research Articles

Molecular Epidemiology, Drug-Resistant Variants, and Therapeutic Implications of Hepatitis B Virus and Hepatitis D Virus Prevalence in Nigeria: A National Study.

Information on circulating HBV (sub-)genotype, variants, and hepatitis D virus (HDV) coinfection, which vary by geographical area, is crucial for the efficient control and management of HBV. We investigated the genomic characteristics of HBV (with a prevalence of 8.1%) and the prevalence of HDV in Nigeria. We utilised 777 HBV-positive samples and epidemiological data from the two-stage sampled population-based, nationally representative Nigeria HIV/AIDS Indicator and Impact Survey conducted in 2018. We assessed 732 HBV DNA-extracted samples with detectable viral loads (VLs) for (sub-)genotypes and variants by whole-genome pre-amplification, nested PCR of the s-and pol-gene, and BigDye Terminator sequencing. We conducted HDV serology. In total, 19 out of the 36 + 1 states in Nigeria had a high prevalence of HBV (≥8%), with the highest prevalence (10.4%) in the north-central geopolitical zone. Up to 33.2% (95% CI 30.0-36.6) of the participants had detectable VLs of ≥300 copies/mL. The predominant circulating HBV genotype was E with 98.4% (95% CI 97.1-99.1), followed by A with 1.6% (95% CI 0.9-2.9). Drug-resistant associated variants and immune escape variants were detected in 9.3% and 0.4%, respectively. The seroprevalence of HDV was 7.34% (95% CI 5.5-9.2). Nigeria has subtype E as the major genotype with many variants.

Effects of SARS-CoV-2 Spike S1 Subunit on the Interplay Between Hepatitis B and Hepatocellular Carcinoma Related Molecular Processes in Human Liver

Background: This study addresses a particular aspect of the biological behavior of the Spike subunit S1 of SARS-CoV-2. Researchers observed S1 acting freely in the human organism during and after COVID-19 and vaccination. One of its properties is that it interacts one-to-one with human proteins. S1 interacts with 12 specific human proteins in the liver. Methods: We used these proteins as seeds to extract their functional relationships from the human proteome through enrichment. The interactome representing the set of metabolic activities in which they are involved shows several molecular processes (KEGG), including some linked to HBV (hepatitis B) and HCC (hepatocellular carcinoma) with many genes/proteins involved. Reports show that, in some COVID patients, HBV reactivated or progressed to cancer. Results: We analyzed the interactome with several approaches to understand whether the two pathologies have independent progressions or a common progression. All our efforts consistently showed that the molecular processes involving both HBV and HCC are significantly present in all approaches we used, making it difficult to extract any useful information about their fate. Through BioGRID, we extracted experimental data in vivo but derived it from model cell systems. The lack of patient data in STRING results prevents diagnosis or prediction of real disease progression; therefore, we can consider them “aseptic” model data. Conclusion: The interactome tells us that genes involved in HCC and HVB-related pathways have the potential to activate disease processes. We can consider them as a gold standard. It is the comparison with similar molecular interactions found in individual human phenotypes that shows us whether the phenotype favors or hinders their progression. This also suggests how to use these features. These sets of proteins constitute a molecular “toolkit”. In fact, if we compare them with similar molecular sets of the patient, they will provide us with information on the level of the phenotypic state that is driving the disease. The information derived from the composition of an entire group of proteins is broader and more detailed than a single marker. Therefore, these protein compositions can serve as a reference system with which doctors can compare specific cases for personalized molecular medicine diagnoses.

Two Concepts of Hepatitis B Core-Related Antigen Assay: A Highly Sensitive and Rapid Assay or an Effective Tool for Widespread Screening.

Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B patients in whom serum HBV DNA or hepatitis B surface antigen is undetectable. The HBcrAg measurement system was developed based on two concepts. One is a fully-automated and highly-sensitive HBcrAg assay (iTACT-HBcrAg) and the other is a point-of-care testing (POCT) that can be used in in resource-limited areas. iTACT-HBcrAg is an alternative to HBV DNA for monitoring HBV reactivation and predicting the development of hepatocellular carcinoma. This validated biomarker is available in routine clinical practice in Japan. Currently, international guidelines for the prevention of mother-to-child transmission recommend anti-HBV prophylaxis for pregnant women with high viral loads. However, over 95% of HBV-infected individuals live in countries where HBV DNA quantification is widely unavailable. Given this situation, a rapid and simple HBcrAg assay for POCT would be highly effective. Long-term anti-HBV therapy may have potential side effects and appropriate treatment should be provided to eligible patients. Therefore, a simple method of determining the indication for anti-HBV treatment would be ideal. This review provides up-to-date information regarding the clinical value of HBcrAg in HBV management, based on iTACT-HBcrAg or POCT.

Combined "Test and Treat" Campaigns for Human Immunodeficiency Virus, Hepatitis B, and Hepatitis C: A Systematic Review to Provide Evidence to Support World Health Organization Treatment Guidelines.

Worldwide, more than 39 million individuals are living with human immunodeficiency virus (HIV), 296 million with chronic hepatitis B (HBV), and 58 million with chronic hepatitis C (HCV). Despite successful treatments for these blood-borne viruses (BBVs), >1.7 million people die per annum. To combat this, the World Health Organization recommended implementing triple testing for HIV, HBV, and HCV. This systematic review aims to provide evidence for this policy, by identifying the prevalence of these BBVs and discussing the costs of available triple tests. Medline, Embase, and Global Health were searched to identify articles published between 1 January and 24 February 2023. Included studies reported the prevalence of HIV (anti-HIV 1/2 antibodies), HBV (hepatitis B surface antigen) and HCV (anti-HCV antibodies). Results were stratified into risk groups: blood donors, general population, healthcare attendees, individuals experiencing homelessness, men who have sex with men, people who use drugs, pregnant people, prisoners, and refugees and immigrants. One hundred seventy-five studies sampling >14 million individuals were included. The mean prevalence of HIV, HBV, and HCV was 0.22% (standard deviation [SD], 7.71%), 1.09% (SD, 5.80%) and 0.65% (SD, 14.64%) respectively. The mean number of individuals testing positive for at least 1 BBV was 1.90% (SD, 16.82%). Therefore, under triple testing, for every individual diagnosed with HIV, another 5 would be diagnosed with HBV and 3 with HCV. Testing for all 3 viruses is available for US$2.48, marginally more expensive than the lowest-priced isolated HIV test ($1.00). This article highlights a potential avenue for healthcare improvement by implementing combination testing programs. Hopefully, this will help to achieve the Sustainable Development Goal of elimination of these BBV epidemics by 2030.

Renal outcomes in adults with HBV, HIV and HBV/HIV coinfection after 3 years of antiviral therapy in urban Tanzania.

An enhanced understanding of renal outcomes in persons with chronic HBV, HIV, and HBV/HIV coinfection is needed to mitigate chronic kidney disease in regions where HBV and HIV are endemic. To investigate changes in estimated glomerular filtration rate (eGFR) in adults with HBV, HIV or HBV/HIV enrolled in a 3 year prospective cohort study of liver outcomes in Dar es Salaam, Tanzania and initiated on antiviral therapy. We compared eGFR between and within groups over time using mixed-effects models. Four hundred and ninety-nine participants were included in the analysis (HBV: 164; HIV: 271; HBV/HIV: 64). Mean baseline eGFRs were 106.88, 106.03 and 107.18 mL/min/1.73 m2, respectively. From baseline to Year 3, mean eGFR declined by 4.3 mL/min/1.73 m2 (95% CI -9.3 to 0.7) and 3.7 (-7.8 to 0.5) in participants with HBV and HIV, respectively, and increased by 5.1 (-4.7 to 14.9) in those with HBV/HIV. In multivariable models, participants with HBV had lower eGFRs compared with those with HIV or HBV/HIV and, after adjusting for HBV DNA level and hepatitis B e antigen (HBeAg) status, significantly lower eGFRs than those with HBV/HIV at all follow-up visits. In this Tanzanian cohort, coinfection with HBV/HIV did not appear to exacerbate renal dysfunction compared with those with either infection alone. Although overall changes in eGFR were small, persons with HBV experienced lower eGFRs throughout follow-up despite their younger age and similar baseline values. Longer-term studies are needed to evaluate continuing changes in eGFR and contributions from infection duration and other comorbidities.

РАСПРОСТРАНЕННОСТЬ И ГЕНОТИПЫ ВИРУСА ГЕПАТИТА В И С СРЕДИ ВИЧ ИНФИЦИРОВАННЫХ

Viruses of parenteral hepatitis HBV, HCV and human immunodeficiency (HIV) are characterized by similar transmission routes and risk groups, in which the probability of acquiring two or more of these infections at once is increased. The aim of the research is to study the prevalence and determine the genotypes of hepatitis B and C virus circulating among HIV-infected people. The results of the studies show a high prevalence of HCV markers (HCV – 45% and HBV- 16%) among HIV-infected people. Co-infected patients had high viral replication of HBV (60%) and HCV (62.7%). Аlso by molecular genetic method, HBV DNA was detected among HBsAg negative and HCV RNA in the absence of anti- HCV. Among those co-infected with HIV+HCV, genotype 1b of hepatitis C virus prevailed so the proportion of the total number was 45.7%. Among those co-infected with HIV+HBV, genotype D of the hepatitis B virus prevailed, which amounted to 70%. The genetic diversity of variants of hepatitis B and C viruses among HIV-infected people is similar to the diversity observed in the general population of the republic.

Correlation between Hepatic Enzymes and Viral Load of HBV in Hepatitis B patients

Background: Hepatitis B virus is a causative agent of hepatitis B, and it is a severe global health issue. Aim: To investigate the increased level of aminotransferases and its association with viral load of HBV infected patients and to find the most sensitive and reliable technique for identification of HBV infection. Methods: This cross-sectional study included 198 patients of HBV. Blood samples were collected from these patients in serum tubes for detection of HBV by different techniques such as Immunochromatographic (ICT), Enzyme linked immunosorbent assay (ELISA), and whole blood was collected which was further processed for DNA extraction and real time PCR. Results: There were 64 female and 134 males in this study. All the patients were positive for HBV by the ICT method and also by ELISA method but for the RT-PCR out of these 198 patients 89(45%) were positive and 109 (55%) were negative. This study demonstrates no significant correlation between liver enzymes with viral load. The ICT test method is active and simple but not a precise and unique test also has no statistical correlation with viral load, but ELISA is correlated with viral load recognized by real time PCR. (P value=˂0.001, 95% Cl=0.40-0.69, r value =0.56). Conclusion: Our results concluded that the immunochromatographic technique is fast and easily available but not a precise and definitive test and has no statistical correlation with viral load, but ELISA is associated with viral load proved by RT-PCR. Real time polymerase chain reaction is the gold standard test for the detection of Hepatitis B virus infection. The practical implication of this study is that ICT technique is no longer a reliable technique for the diagnosis of HBV infection and the patients positive on ICT should be confirmed for HBV in PCR for both diagnostic and prognostic purposes. Keywords: Hepatitis B Virus, Liver enzymes, Immunochromatographic, Viral load, Enzyme linked immunosorbent assay

Use of HBV RNA and to predict change in serological status and disease activity in CHB.

Predicting changes in disease activity and serological endpoints is necessary for the management of patients with chronic hepatitis B (CHB). We examined whether HBV RNA and hepatitis B core-related antigen (HBcrAg), two specialized virological markers proposed to reflect the activity of covalently closed circular DNA, may improve the ability to predict not sustained inactive carrier phase, spontaneous alanine aminotransferase (ALT) flare, HBeAg loss, and HBsAg loss. Among eligible participants enrolled in the North American Hepatitis B Research Network Adult Cohort Study, we evaluated demographic, clinical, and virologic characteristics, including HBV RNA and HBcrAg, to predict not sustained inactive carrier phase, ALT flare, HBeAg loss, and HBsAg loss through a series of Cox proportional hazard or logistic regression models, controlling for antiviral therapy use. Among the study population, 54/103 participants experienced not sustained inactive carrier phase, 41/1006 had a spontaneous ALT flare, 83/250 lost HBeAg, and 54/1127 lost HBsAg. HBV RNA or HBcrAg were predictive of all 4 events. However, their addition to models of the readily available host (age, sex, race/ethnicity), clinical (ALT, use of antiviral therapy), and viral factors (HBV DNA), which had acceptable-excellent accuracy (e.g., AUC = 0.72 for ALT flare, 0.92 for HBeAg loss, and 0.91 for HBsAg loss), provided only small improvements in predictive ability. Given the high predictive ability of readily available markers, HBcrAg and HBV RNA have a limited role in improving the prediction of key serologic and clinical events in patients with CHB.

What will it take to cure hepatitis B?

The current treatment of chronic HBV infection, pegylated interferon-α (pegIFNα) and nucleos(t)ide analog (NA), can suppress HBV replication, reverse liver inflammation and fibrosis and reduce the risks of cirrhosis, HCC, and HBV-related deaths, but relapse is common when the treatment is stopped before HBsAg loss. There have been major efforts to develop a cure for HBV, defined as sustained HBsAg loss after a finite course of therapy. This requires the suppression of HBV replication and viral protein production and the restoration of immune response to HBV. Direct-acting antivirals targeting virus entry, capsid assembly, viral protein production and secretion are in clinical trials. Immune modulatory therapies to stimulate adaptive or innate immunity and/or to remove immune blockade are being tested. NAs are included in most and pegIFNα in some regimens. Despite the combination of 2 or more therapies, HBsAg loss remains rare in part because HbsAg can be derived not only from the covalently closed circular DNA but also from the integrated HBV DNA. Achievement of a functional HBV cure will require therapies to eliminate or silence covalently closed circular DNA and integrated HBV DNA. In addition, assays to differentiate the source of circulating HBsAg and to determine HBV immune recovery, as well as standardization and improvement of assays for HBV RNA and hepatitis B core-related antigen, surrogate markers for covalently closed circular DNA transcription, are needed to accurately assess response and to target treatments according to patient/disease characteristics. Platform trials will allow the comparison of multiple combinations and channel patients with different characteristics to the treatment that is most likely to succeed. Safety is paramount, given the excellent safety profile of NA therapy.

Liver-related mortality among people with hepatitis B and C: Evaluation of definitions based on linked healthcare administrative datasets.

Routinely collected and linked healthcare administrative datasets could be used to monitor mortality among people with hepatitis B (HBV) and C (HCV). This study aimed to evaluate the concordance in records of liver-related mortality among people with an HBV or HCV notification, between data on hospitalization for end-stage liver disease (ESLD) and death certificates. In New South Wales, Australia, HBV and HCV notifications (1993-2017) were linked to hospital admissions (2001-2018), all-cause mortality (1993-2018) and cause-specific mortality (1993-2016) datasets. Hospitalization for ESLD was defined as a first-time hospital admission due to decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC). Consistency of liver death definition of mortality following hospitalization for ESLD was compared with two death certificate-based definitions of liver deaths coded among primary and secondary cause-specific mortality data, including ESLD-related (deaths due to DC and HCC) and all-liver deaths (ESLD-related and other liver-related causes). Of 63,292 and 107,430 individuals with an HBV and HCV notification, there were 4478 (2.6%) post-ESLD hospitalization deaths, 5572 (3.3%) death certificate liver disease deaths and 2910 (1.7%) death certificate ESLD deaths. Between 2001 and 2016, among HBV post-ESLD hospitalization deaths (n= 891), 63% (562) had death certificate ESLD recorded, and 83% (741) had death certificate liver disease recorded. Between 2001 and 2016, among HCV post-ESLD hospitalization deaths (n= 3587), 58% (2082) had death certificate ESLD recorded, and 87% (3135) had death certificate liver disease recorded. At least one-third of death certificates with DC and HCC as cause of death had no mention of HBV, HCV or viral hepatitis. Our study identified limitations in estimating and tracking HBV and HCV liver disease mortality using death certificate-based data only. The optimum data for this purpose is either ESLD hospitalisations with vital status information or a combination of these with cause-specific death certificate data.

Distribution and relevance of hepatitis B genotypes in the general population of Slovakia.

The aim of the presented study was to determine the distribution of HBV genotypes and their influence on selected parameters in patients in eastern Slovakia. The study includes 202 patients with confirmed chronic HBV infection or hepatitis. For each patient, basic demographic data, and serum samples were collected. The degree of liver fibrosis was determined by transient elastography. The obtained data were evaluated statistically. Out of a total of 202 patients, 96.0 % of the patients were from the EU region and 27 patients (13.4 %) self-identified as Roma ethnic group. The most common genotype among our patients was genotype A (n = 104; 51.5 %), followed by genotype D (n = 76; 37.6 %) and A/D (n = 13; 6.4 %). In patients from the EU region, genotypes A and D predominated statistically significantly (p < 0.0001). Due to a low number of patients with other genotypes, in the subsequent analysis, we only compared patients with HBV genotypes A or D. Patients with genotypes D and A/D significantly more often mention tattoos as a possible risk factor for disease transmission compared to patients with genotype A (p = 0.043). Subsequently, we divided patients into two groups - treated and untreated. The level of qHBsAg was significantly higher in untreated patients with genotypes A (p < 0.0001). The influence of HBV genotypes on other laboratory parameters was not confirmed in our study. This is the first HBV genotypes study from Slovakia. We suggest that HBV genotypes may play a role in the virus-host relationship Keywords: chronic hepatitis B, genotypes, hepatitis B virus, prognostic factors, distribution.

A Case of Chlamydia Psittacosis with Severe Pneumonia Combined with Acute Hepatitis B and Literature Review

Chlamydia psittaci infection can lead to severe clinical manifestations in humans, including rapidly progressive severe pneumonia, adult respiratory distress syndrome (ARDS), sepsis, multiple organ dysfunction, and even death. Here, we reported a 47-year-old man who presented with shortness of breath, fever and diarrhea. His chest CT showed right pneumonia with consolidation, and severe psittacosis pneumonia was confirmed by metagenomic sequencing of bronchoalveolar lavage fluid. The condition continued to worsen under ventilator treatment, and ARDS occurred. VV-ECMO was used to support for five days to improve hypoxia. In the middle and late stage of the disease course, the ALT of the patient showed an upward trend, and the HBV DNA and hepatitis B surface antigen were positive. Considering the medical history, it might be acute hepatitis B, and antiviral therapy was given. After three weeks of combined therapy, the patient recovered and was discharged from the hospital. Chlamydia psittacosis pneumonia is prone to misdiagnosis and misdiagnosis when the symptoms are not typical, and high-throughput sequencing is needed for definite diagnosis. Short-term use of ECMO in severe pneumonia of Chlamydia psittaci can help shorten the course of the disease and reverse the disease. The route of viral hepatitis B infection is unknown. If acute hepatitis B co-infection with other pathogens initiates antiviral therapy, it may prevent its transformation to chronic.

Anti-hepatitis B virus activity of lithospermic acid, a polyphenol from Salvia miltiorrhiza, in vitro and in vivo by autophagy regulation

Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, Danshen in Chinese), a traditional Chinese medicine, has been clinically used to prevent and treat various diseases, such as cardiovascular and cerebrovascular diseases, diabetes, and hepatitis B, in China and some other Asian countries. Lithospermic acid (LA), a polyphenol derived from S. miltiorrhiza, has been reported to exhibit multiple pharmacological properties, such as anti-inflammatory, anti-HIV, and anti-carbon tetrachloride-induced liver injury activities. However, little is known about the anti-hepatitis B virus (HBV) activity of LA. The study was projected to investigate the anti-HBV activity of LA in vitro (HepG2.2.15 and pHBV1.3-transfected HepG2 cells) and in vivo (pAAV-HBV1.2 hydrodynamic injection [HBV-HDI] mice) and explore the potential mechanism as well. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) contents were detected by ELISA kits. HBV DNA and hepatitis B core antigen (HBcAg) levels were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry assay, respectively. The proteins in autophagy process, lysosomal acidic function, and autophagy-related signaling pathways were examined by Western blot. Transmission electron microscopy was used to observe the number of autophagosomes and autolysosomes. Confocal microscopy was applied to analyze the autophagic flux and lysosomal acidification, using mCherry-enhanced green fluorescent protein (EGFP)-microtubule-associated protein light chain (LC)3 and lysosomal probes, respectively. LA exhibited anti-HBV activity by inhibiting HBV DNA replication in HepG2.2.15 and pHBV-transfected HepG2 cells in dose- and time-dependent manners and hampering HBsAg and HBeAg levels in HepG2.2.15cells to a certain extent. LA reduced HBV DNA, HBsAg/HBeAg, and HBcAg levels in the serum/liver tissues of HBV-HDI C57BL/6 mice during the 3-week treatment and suppressed the withdrawal rebound of HBV DNA and HBsAg in the mice serum. LA increased LC3-II protein expression and the number of autolysosomes/autophagosomes and promoted the degradation of sequestosome 1(p62) protein in vitro and in vivo. LA enhanced the co-localization of LC3 protein with autolysosomes, further confirming the ability of LA to induce a complete autophagy. Knockdown of autophagy-related gene (Atg) 7 or 5 in vitro and administration of 3-methyladenine (an autophagic inhibitor) in vivo disabled the inhibitory efficacy of LA on HBV DNA replication, suggesting that the anti-HBV efficacy of LA depended on its ability of inducing autophagy. LA could enhance lysosomal acidification and improve the function of lysosomes by promoting the protein expression of lysosomal-associated membrane protein (LAMP)-1, LAMP-2, and mature cathepsin D, which may contribute to the autophagic induction of LA. LA inhibited the activation of AKT and mammalian target of rapamycin (mTOR) induced by HBV, which was reversed by IGF-1 (an agonist of the PI3K/AKT/mTOR signaling pathway), indicating that LA elicited autophagy through hampering the PI3K/AKT/mTOR signaling pathway. We revealed the anti-HBV activity and mechanism of LA in vitro and in vivo. This study facilitates a new understanding of the anti-HBV potent components of S. miltiorrhiza and sheds light on LA for further development as an active constituent or candidate used in the therapy against HBV infection.

Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos(t)ide analogue in chronic hepatitis B.

We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg). Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU. Twenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8-18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661-0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596-0.982). Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.

Three Effects of Β-Catenin Factors in Liver Cancer and Its Treatment

Liver cancer is a typical malignant tumor and the fourth most typical cancer in the Earth. Clinically, more than 90% of patients with primary liver cancer are caused by hepatocellular carcinoma. Epidemiological and experimental data show that human infection with HBV and HCV hepatitis virus is firmly connected with the occurrence of liver cancer. In the past 20 years, the level of diagnosis and cure of liver cancer in China has been greatly improved, but little progress has been made in the study of liver cancer markers. For then, with the understanding of Wnt signal transduction pathway, it is found that β-catenin, as a key molecule in Wnt signal transduction pathway, is closely associated to the incidence of HCC. Recently, more and more studies have shown that the abnormal activation of classical Wnt signal pathway plays a compelling part in the occurrence and advancement of hepatocellular carcinoma. Hepatocytes because of hidden onset, early rise can be no clinical symptoms, so the clinical discovery is mostly late, the mortality rate is high. At present, the clinical methods for the treatment of hepatocellular carcinoma are liver transplantation, radiotherapy and chemotherapy. However, hepatocellular carcinoma is easy to metastasize and has a high recurrence rate, so the mortality rate of hepatocellular carcinoma is still high. Wnt/β-catenin signal pathway has become major topic of debate in cancer research. In this paper, we begin with the classification of liver cancer and some pathogenic mechanisms. The effects of β-catenin protein on the occurrence, metastasis and immune regulation of hepatocellular carcinoma were also discussed. Under the background of the popular "signal transduction therapy" in recent years, to explore the therapeutic effect of targeted drugs targeting Wnt/β-catenin signal pathway in hepatocellular carcinoma. Because of the high degree of malignancy and limited treatment of hepatocellular carcinoma, we will mainly discuss the effect of Wnt signal pathway on the metastasis of hepatocellular carcinoma and its effect on the differentiation of immune cells. Abnormal activation of Wnt signaling pathway in hepatocellular carcinoma.

Impact of the COVID-19 pandemic on hepatitis B and C elimination: An EASL survey

Background & AimsThe World Health Organization (WHO) HBV and HCV elimination targets, set in 2016 and based on projections to 2030, were unable to consider the impact of intervening factors. To evaluate the impact of the COVID-19 pandemic on viral hepatitis elimination programs, the European Association for the Study of the Liver (EASL) conducted a survey in liver centers worldwide in 2021.MethodsA web-based questionnaire was distributed (May-July 2021) to all EASL members representing clinical units providing HBV and HCV hepatitis care. Results are expressed as absolute numbers and reduction rates for each care activity.ResultsData were collected from 32 European and 12 non-European clinical centers. Between January 2019 (pre-pandemic) and December 2020 (during the pandemic), chronic HBV consultations decreased by 32% and 26%, new referrals by 38% and 39%, HBV testing rates by 39% and 21% (for HBsAg detection) and 30% and 22% (for HBV DNA detection), and new HBV treatments by 20% and 44% (p = 0.328) in European and non-European centers, respectively. With regard to HCV during the same time frame, the overall reductions were 39% and 50% for consultations, 49% and 49% for new referrals, 11% and 38% for HCV RNA detection, and 51% and 54% for new HCV antiviral treatments for European and non-European Centers, respectively (p = 0.071).ConclusionsAll steps in the viral hepatitis care cascade have been hampered by the COVID-19 pandemic, with a comparable impact across different centers. These data reaffirm the pandemic’s major effect on global viral hepatitis elimination programs and suggest that actions to achieve the WHO 2030 targets should be reconsidered and revised to account for each country's progress relative to pre-pandemic values.Lay summaryThe EASL multinational survey conclusively shows that viral hepatitis elimination programs, expected to provide control of hepatitis B and hepatitis C worldwide by 2030, have been held back by the COVID-19 pandemic in clinical centers from several European and non-European countries, with a comparable impact across centers. Limitations in the cascade of care for both HBV and HCV were linked to limited access to screening, consultations, specific testing, and actual treatment. As restrictions for COVID-19 begin to lift, efforts to diagnose and provide treatment for viral hepatitis should remain high on the list of priorities for public health officials to maintain the WHO elimination efforts. Measures that have been put in place to control the COVID-19 pandemic could be transferred to increasing the diagnosis and linkage to care of people with hepatitis.

Prevalence and Risk Factors of hepatitis B and C infections in general population of Tehsil Arifwala

According to the WHO, over 350 and 250 million individuals have been estimated as chronic carriers of HBV and HCV, worldwide. About 1.34 million deaths are attributed to HBV and HCV, globally. Objective: To estimate the seroprevalence of HBV and HCV-related hepatitis. Methods: For this purpose, a population of 300 individuals was screened for HBsAg and Anti-HCV antibodies. Data were collected from tested individuals included their age, gender, occupation. Prevalence of HBV and HCV was found at 10% and 14% respectively. Co-infection of both pathogens was observed in 1.33% of individuals. Male (18%) were more infected with these viruses as compared to females (6%). The highest percentage (75%) of HBV/HCV was in adult patients of age between 31-50 years. The various risk factor associated with the spread of viral hepatitis were also considered for a better understanding of the routes of spread of these viral infections. Results: Out of 300 screened individuals, 21% had a history of going through any dental procedure, followed by 17% with needle stick injuries. Only 7.6% of persons had a history of any blood transfusion. Conducting such type of seroprevalence studies can help the administration and health care authorities to take necessary control measures to minimize the chances of acquiring these infections by eliminating risk factors. Conclusion: Further, these surveillance studies can also play a significant role in the launch of vaccination programs in areas of high prevalence.

Long-Term Safety of Rituximab in DLBCL Patients With Hepatitis B-Related Cirrhosis: A Retrospective Case Series

ObjectiveChemotherapy regimens containing rituximab (RTX) have been extensively used to treat diffuse large B cell lymphoma (DLBCL). However, data looking at long-term safety of DLBCL patients with hepatitis B-related cirrhosis are still lacking. This study aims to report the safety and outcomes of RTX administration in DLBCL patients with hepatitis B-related cirrhosis.MethodsA retrospective case series was designed and implemented, using data from January 1, 2011 to December 31, 2020. Consecutive patients who were diagnosed with DLBCL and hepatitis B-related cirrhosis receiving RTX treatment were included. The primary outcomes included HBV reactivation, hepatitis flares or abnormal liver function. Survival status, the secondary outcome measure, was observed until death, loss to follow-up, or the end of follow-up, whichever occurred first.ResultsA total of 8 DLBCL patients combined with hepatitis B-related cirrhosis were included in this study [4 men; median age 62.5 years (range, 44–77 years); median RTX-containing regimen course 5 (range, 2–11)]. Of them, 6 patients had current HBV infection with HBsAg-positive and anti-HBc-positive, whereas 2 patients had previously resolved HBV infection with HBsAg-negative and anti-HBc-positive. The HBV reactivation was observed in only one patient, who received 11 courses of RTX-containing immunochemotherapies within 15 months. No hepatitis flares or abnormal liver function occurred in any patients included. All patients received standardized antiviral therapy for a lifelong time. Of 8 patients included, 3 patients died, and 1 patient was lost to follow-up, and the median overall survival among patients was 39 months (range, 7–82 months).ConclusionThe findings provide support for the concept that, on the premise of standardized and valid management strategy, RTX containing regimens may be a safe option for use as the treatment of DLBCL patients combined with hepatitis B-related cirrhosis.

Zero percent vertical transmission is achievable

Background and Aim: HBV infection is a global problem with nearly 350 million chronic carriers and over 50% of these carriers are believed to have acquired their infection vertically from their mothers, i.e. through mother - to - child transmission (MTCT). We studied a) to prevent MTCT of HBV by administrating antiviral drugs, as per indication to Hepatitis B positive pregnant mothers and mandatory HBV Vaccine and Hepatitis B immunoglobulin (HBIG) to newborn b) to evaluate vertical transmission to neonate

Sustained Antiviral and Liver Protection by a Nasal Therapeutic Vaccine (NASVAC, Containing Both HBsAg and HBcAg) in Patients with Chronic Hepatitis B: 2-Year Follow-Up of Phase III Clinical Trial.

A phase III clinical trial in treatment-naïve patients with chronic hepatitis B (CHB) revealed the safety and considerable therapeutic efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (NASVAC) at the end of treatment (EOT) and 24 weeks after EOT. Two years after EOT, we checked HBV DNA, alanine aminotransferase (ALT), and hepatitis B e antigen (HBeAg). The data reveal that 33 of 66 NASVAC-recipient CHB patients became negative for HBV DNA in the blood two years after EOT. The ALT levels were within the upper limit of normal (ULN) in 37 patients, although all 66 CHB patients had elevated ALT (above ULN) before the start of therapy. Out of the total twelve HBeAg-positive patients, eight patients became negative for HBeAg. None of the patients developed cirrhosis of the liver within this period. NASVAC is a finite treatment regimen with sustained antiviral and liver-protecting properties. This study is the first to report follow-up data of immune therapy for CHB. NASVAC, an immune therapy of finite duration, is endowed with sustained antiviral and liver protection properties in CHB patients.