Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a reconstructed individual patient data meta-analysis.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/.

Retrospective study of hepatitis C screening and seroprevalence in the GHU Paris.

OBJECTIVES: The prevalence of hepatitis C virus (HCV) has been estimated to be approximately ten times higher in patients with psychiatric disorders, but European data are rare and only two French studies have recently been published on the subject. Our objective was to determine the HCV screening rate and the prevalence of HCV in adult patients hospitalised in the largest French psychiatric hospital. METHODS: We conducted a retrospective study of all adult patients hospitalised at GHU Paris, from 2019 to 2022, including age, gender, HCV screening, HCV serological status, and the existence of an ICD-10 diagnosis of psychoactive substance use disorder. Descriptive statistics used means±standard deviations and percentages. Bivariable comparisons used Student's t test and Chi-square test. RESULTS: The overall HCV screening rate was 55.4% and increased over the four years from 37.1% in 2019 to 69.4% in 2022. Patients screened were significantly younger people and with a substance use disorder than unscreened patients. The prevalence of HCV over this 4-year period was 2.8% and remained stable. The HCV-positive patients were significantly more male, older and more likely to have substance use disorders than the HCV-negative patients. CONCLUSIONS: We found a prevalence rate of HCV ten times higher than the prevalence in the general population, in line with findings in many other European countries. The eradication of HCV will not be possible without the elimination of this "forgotten reservoir" of the virus. Efforts must be made in psychiatric hospitals to test all patients in order to treat patients suffering from hepatitis C with direct-acting antivirals.

Investigation of Mother-to-Child Transmission of Hepatitis B in Yinchuan, China: Cross-Sectional Survey Study.

BACKGROUND: Hepatitis B poses a significant global public health challenge, with mother-to-child transmission (MTCT) being the primary method of hepatitis B virus (HBV) transmission. The prevalence of HBV infection in China is the highest in Asia, and it carries the greatest burden globally. OBJECTIVE: This study aims to critically evaluate the existing local strategies for preventing MTCT and the proposed potential enhancements by analyzing the prevalence of hepatitis B among pregnant women and their neonates in Yinchuan. METHODS: From January 2017 to December 2021, 37,557 prenatal screening records were collected. Among them, 947 pregnant women who tested positive for hepatitis B surface antigen (HBsAg) near delivery and their 960 neonates were included in an HBV-exposed group, while 29 pregnant women who tested negative and their 30 neonates were included in an HBV-nonexposed group. HBV markers in maternal peripheral blood and neonatal cord blood were analyzed using the least absolute shrinkage and selection operator (LASSO) regression, logistic regression, chi-square test, t-test, and U-test. Additionally, to further evaluate the diagnostic value of HBsAg positivity in cord blood, we conducted an additional follow-up study on 103 infants who tested positive for HBsAg in their cord blood. RESULTS: The prevalence of HBV among pregnant women was 2.5% (947/37,557), with a declining trend every year (χ²4=19.7; P=.001). From 2018 to 2020, only 33.0% (35/106) of eligible pregnant women received antiviral medication treatment. Using LASSO regression to screen risk factors correlated with HBsAg positivity in cord blood (when log [λ] reached a minimum value of -5.02), 5 variables with nonzero coefficients were selected, including maternal hepatitis B e-antigen (HBeAg) status, maternal hepatitis B core antibody (HBcAb) status, maternal HBV DNA load, delivery method, and neonatal birth weight. Through univariate and multivariate logistic regression, delivery by cesarean section (adjusted odds ratio [aOR] 0.52, 95% CI 0.31-0.87), maternal HBeAg positivity (aOR 2.05, 95% CI 1.27-3.33), low maternal viral load (aOR 2.69, 95% CI 1.33-5.46), and high maternal viral load (aOR 2.69, 95% CI 1.32-5.51) were found to be strongly associated with cord blood HBsAg positivity. In the additional follow-up study, 61 infants successfully completed the follow-up, and only 2 were found to be infected with HBV. The mothers of both these infants had detectable HBV DNA levels and should have received standard antiviral therapy. The results of the hepatitis B surface antibody (HBsAb) positivity rate and titer test indicated a gradual decline in the immunity of vaccinated infants as the interval after vaccination increased. CONCLUSIONS: The clinical relevance of HBV marker detection in cord blood is restricted within the current prevention measures for MTCT. There is an emphasis on the significance of public education regarding hepatitis B and the reinforcement of postnatal follow-up for the prevention of MTCT.

Hepatitis B vaccination status among patients with end-stage kidney disease on haemodialysis in Ethiopia: a multi-center cross-sectional study.

BACKGROUND: Chronic kidney disease patients, especially those on hemodialysis, are at increased risk of developing hepatitis B virus (HBV) infection. Guidelines suggest that all patients with chronic kidney disease patients should be vaccinated against HBV, but these guidelines are sub-optimally implemented. Notably, there is a lack of studies in Ethiopia examining the hepatitis B vaccination status among patients with end-stage renal disease. OBJECTIVE: To assess the vaccination status of hepatitis B and associated factors among people with end-stage renal disease who were on hemodialysis. METHODS: A multi-center cross-sectional observational study was conducted in six randomly selected dialysis centers in Ethiopia, from May 2023 to September 2023. Logistic regression analysis was used to evaluate factors associated with vaccination status. A person is considered to be vaccinated against hepatitis B if he/ she has taken at least one dose of HBV. Vaccination status was determined by patient's recall and verification from medical record. RESULTS: Only 16% of patients with end-stage renal disease on hemodialysis were vaccinated against hepatitis B virus (16.6%; with CI = 12.18, 21.83), of which 30% had received one dose, 57.5% had two doses, 12.5% had three doses, and only five had a booster dose. Post-secondary education (AOR = 5.47; 95% CI = 1.41, 21.2; P < 0.014) and dialysis for more than three years (AOR = 19.75; 95% CI = 4.06, 96.1; P < 0.001) were significant factors associated with having received hepatitis B vaccination. CONCLUSION: Only a small minority of Ethiopian hemodialysis patients have received hepatitis B vaccination. The level of education of patients and the duration of time on dialysis were significant associated factors that affected the vaccination status of patients with end-stage renal disease. So, strong intervention is needed according to the identified factors to raise the vaccination status of patients.

Management of occupational exposure to blood and body fluids in primary care.

Primary care workplaces where occupational exposure to blood and body fluids may occur should have policies and procedures in place to manage such incidents. All healthcare workers should be immunised against hepatitis B and ideally should have documentation of their antibody response to vaccination. Knowledge of hepatitis B immune status helps streamline the response to any exposure. Most occupational exposures carry a low risk of transmission of bloodborne viruses, and management can often be undertaken in general practice. Urgent risk assessment and management is crucial. If postexposure prophylaxis for hepatitis B or HIV is required, the earlier it is given, the more likely it is to be effective. Two-drug HIV postexposure prophylaxis is now more accessible because generic formulations of the drug combination are available, and general practitioners can prescribe this on a private prescription.

Acute hepatitis A with haemophagocytic lymphohistiocytosis: G-6PD deficiency-induced haemolytic anaemia and bile cast nephropathy.

Hepatitis A virus (HAV) infection typically presents as a self-limiting illness but it can cause debilitating symptoms and rarely fulminant hepatitis (acute liver failure), which is often fatal. WHO estimates that in 2016, 7134 persons died from hepatitis A worldwide (accounting for 0.5% of the mortality due to viral hepatitis). Fulminant hepatic failure is observed in less than 1% of cases of acute viral hepatitis A. Haemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of excessive inflammation and tissue destruction owing to abnormal immune activation. Acquired HLH due to viral infections (also known as virus-associated haemophagocytic syndrome) is most commonly associated with Epstein-Barr virus and cytomegalovirus (CMV). HAV-associated HLH has been rarely reported. Haemolysis of mild to moderate degree is not unheard of in cases of hepatitis A, which is often immune-mediated. Here, we present the case of a man in his 30s, with G6PD deficiency unmasked by acute viral hepatitis A, which later on progressed to hyperacute liver failure, HLH and renal failure.

From Viral Infections to Alzheimer's Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics.

BACKGROUND: Emerging evidence suggests that viral infections may contribute to Alzheimer's disease (AD) onset and/or progression. However, the extent of their involvement and the mechanisms through which specific viruses increase AD susceptibility risk remain elusive. METHODS: We used an integrative systems bioinformatics approach to identify viral-mediated pathogenic mechanisms, by which Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A Virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could facilitate AD pathogenesis via virus-host protein-protein interactions (PPIs). We also explored potential synergistic pathogenic effects resulting from herpesvirus reactivation (HSV-1, HCMV, and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility. RESULTS: Herpesviridae members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-ß (Aß) formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction, they also affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress, and Aß formation. CONCLUSIONS: These findings underscore the complex link between viral infections and AD development. Viruses impact AD-related processes through shared and distinct mechanisms, potentially influencing variations in AD susceptibility.

Tackling a worrisome rate of lost to follow-up among migrants with hepatitis B in French Guiana.

OBJECTIVES: Management of Hepatitis B virus (HBV)-infected patients, whether they are receiving treatment or not, necessitates long-term follow-up. This study evaluated the rate of lost to follow-up (LTFU) among HBV-infected patients and the feasibility of a callback strategy to re-engage these patients in HBV care. PATIENTS AND METHODS: We conducted a retrospective study involving HBV-infected patients attending the outpatient clinic at Cayenne Hospital, French Guiana. LTFU was defined as patients who had not attended the clinic for more than 18 months. A callback strategy was implemented to re-engage LTFU patients in HBV care. RESULTS: Between 1st January 2015 and 31st December 2018, 203 HBV-infected patients were referred to the outpatient clinic; 95/203 (46.8 %) were LTFU, resulting in a crude LTFU rate of 2.6 (95 % CI, 2.1-3.2) per 100 person-years. At baseline, patients aged 30-40 years (aOR, 0.48; 95 %CI, 0.24-0.95) and those who initiated treatment (aOR, 0.26; 95 %CI, 0.10-0.60) were less likely to be LTFU. Through application of the callback strategy, 55/95 (58 %) patients were successfully contacted, and 46/55 (84 %) attended the outpatient clinic for a liver assessment. The EASL criteria for treatment eligibility were met by 3/46 (4 %) patients. Compared to non-LTFU patients, LTFU patients were more likely to be in informal employment (p = 0.03) and to be receiving state medical assistance (p < 0.01), and had lower levels of knowledge about their condition (p < 0.01). CONCLUSIONS: The callback strategy to re-engage LTFU patients in HBV care is feasible and effectively identifies those eligible for antiviral therapy.

Pollutants-mediated viral hepatitis in different types: assessment of different algorithms and time series models.

The escalating frequency of environmental pollution incidents has raised significant concerns regarding the potential health impacts of pollutant fluctuations. Consequently, a comprehensive study on the role of pollutants in the prevalence of viral hepatitis is indispensable for the advancement of innovative prevention strategies. Monthly incidence rates of viral hepatitis from 2005 to 2020 were sourced from the Chinese Center for Disease Control and Prevention Infectious Disease Surveillance Information System. Pollution data spanning 2014-2020 were obtained from the National Oceanic and Atmospheric Administration (NOAA), encompassing pollutants such as CO, NO2, and O3. Time series analysis models, including seasonal auto-regressive integrated moving average (SARIMA), Holt-Winters model, and Generalized Additive Model (GAM), were employed to explore prediction and synergistic effects related to viral hepatitis. Spearman correlation analysis was utilized to identify pollutants suitable for inclusion in these models. Concurrently, machine learning (ML) algorithms were leveraged to refine the prediction of environmental pollutant levels. Finally, a weighted quantile sum (WQS) regression framework was developed to evaluate the singular and combined impacts of pollutants on viral hepatitis cases across different demographics, age groups, and environmental strata. The incidence of viral hepatitis in Beijing exhibited a declining trend, primarily characterized by HBV and HCV types. In predicting hepatitis prevalence trends, the Holt-Winters additive seasonal model outperformed the SARIMA multiplicative model ((1,1,0) (2,1,0) [12]). In the prediction of environmental pollutants, the SVM model demonstrated superior performance over the GPR model, particularly with Polynomial and Besseldot kernel functions. The combined pollutant risk effect on viral hepatitis was quantified as ßWQS (95% CI) = 0.066 (0.018, 0.114). Among different groups, PM2.5 emerged as the most sensitive risk factor, notably impacting patients with HCV and HEV, as well as individuals aged 35-64. CO predominantly affected HAV patients, showing a risk effect of ßWQS (95% CI) = - 0.0355 (- 0.0695, - 0.0016). Lower levels of PM2.5 and PM10 were associated with heightened risk of viral hepatitis incidence with a lag of five months, whereas elevated levels of PM2.5 (100-120 µg/m3) and CO correlated with increased hepatitis incidence risk with a lag of six months. The Holt-Winters model outperformed the SARIMA model in predicting the incidence of viral hepatitis. Among machine learning algorithms, SVM and GPR models demonstrated superior performance for analyzing pollutant data. Patients infected with HAV and HEV were primarily influenced by PM10 and CO, whereas SO2 and PM2.5 significantly impacted others. Individuals aged 35-64 years appeared particularly susceptible to these pollutants. Mixed pollutant exposures were found to affect the development of viral hepatitis with a notable lag of 5-6 months. These findings underscore the importance of long-term monitoring of pollutants in relation to viral hepatitis incidence.

Altered blood microbiome in patients with HCV-related Child-Pugh class B cirrhosis.

BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.

Rare presentation of hepatic alveolar echinococcosis mimicking hepatocellular carcinoma.

A complex liver lesion presents a significant challenge in terms of diagnosis and management. This case is an illustrative example, highlighting the steps involved in managing such complex scenarios. This patient, in her early 20s, presented with a fever associated with worsening abdominal pain, as well as a background history of chronic abdominal pain, anorexia, vomiting, constipation and weight loss. The radiology revealed an irregular complex cyst in the liver with biliary and vascular invasion, raising concerns about hepatocellular carcinoma. The diagnosis was changed to alveolar echinococcosis after the infectious diseases consultant gave helpful advice, and echinococcosis antibodies were found. We subsequently started the patient on albendazole therapy. Following prudent advice from hepatobiliary surgeons and given the complexity of the hepatic lesion, a liver transplant was considered the best management option due to the extensive involvement of the biliary and venous systems. The combined approach of albendazole and a liver transplant marked a transformative phase for this patient, putting an end to her prolonged suffering.

Peer-Assisted Telemedicine for Hepatitis C (PATHS): Process evaluation results from a State Opioid Response-funded program.

INTRODUCTION: The opioid crisis and the hepatitis C virus epidemic perpetuate and potentiate each other in a syndemic with escalating morbidity. Policy-driven funding can help resolve the syndemic through collaborative solutions that rapidly translate evidence-based interventions into real-world applications. METHODS: We report development and programmatic evaluation of Peer-Assisted Telemedicine for Hepatitis C (PATHS), which utilizes State Opioid Response (SOR) funding to scale-up a positive randomized trial of peer-assisted telemedicine HCV treatment. PATHS employs staff within an academic medical center and partners with people with lived experience of drug use, "peers," to recruit rural-dwelling people who use drugs living with HCV. PATHS staff record patient data by abstracting clinical records or directly communicating with patients and peers. Peers are funded by a separate SOR-supported program administered through the state health authority. Peers support patients through HCV screening, treatment initiation via telemedicine, adherence, and cure. RESULTS: Between March 2021 and June 2024, PATHS expanded to 18 of Oregon's 36 counties. In that time, PATHS diagnosed 198 rural PWUD with HCV. One hundred sixty-seven (84.3 %) linked to telemedicine and of these, 145 (86.8 %) initiated treatment. Of those who initiated treatment, 91 (62.8 %) completed treatment, of which 61 (67.0 %) are cured. CONCLUSIONS: By rapidly translating a clinical innovation in HCV treatment to achieve highly effective real-world results, PATHS models how policy-driven funding can facilitate collaboration between community partners, academic medical centers, and state health departments to end the opioid-HCV syndemic.

Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has increased in recent clinical practice; however, the relationship between CHB and hepatic steatosis (HS) remains controversial. AIM: To shed light on the potential association between NAFLD and hepatitis B virus (HBV) infection. METHODS: We conducted a systematic literature search using multiple databases, including PubMed, the Cochrane Library, Web of Science, and EMBASE, to identify relevant studies. Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis. RESULTS: Comprehensive meta-analysis software was used for statistical analysis, which covered 20 studies. The results indicated a lower NAFLD susceptibility in HBV-infected individuals (pooled OR = 0.87; 95%CI = 0.69-1.08; I 2 = 91.1%), with diabetes (P = 0.015), body mass index (BMI; P = 0.010), and possibly age (P = 0.061) as heterogeneity sources. Of note, in four studies (6197 HBV patients), HBV-infected individuals had a reduced NAFLD risk (OR = 0.68, 95%CI = 0.51-0.89, P = 0.006). A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients, along with specific biochemical indicators, including BMI, creatinine, uric acid, fasting blood glucose, and homeostasis model assessment of insulin resistance. CONCLUSION: HBV infection may provide protection against HS; however, the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.

mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.

Currently, chronic hepatitis B virus infection is still one of the most serious public health problems in the world. Though current strategies are effective in controlling infection and slowing down the disease process, it remains a big challenge to achieve a functional cure for chronic hepatitis B in a majority of patients due to the inability to clear the cccDNA pool. The mammalian target of rapamycin (mTOR) integrates nutrition, energy, growth factors, and other extracellular signals, participating in gene transcription, protein translation, ribosome synthesis, and other biological processes. Additionally, mTOR plays an extremely important role in cell growth, apoptosis, autophagy, and metabolism. More and more evidence show that HBV infection can activate the mTOR pathway, suggesting that HBV uses or hijacks the mTOR pathway to facilitate its own replication. Therefore, mTOR signaling pathway may be a key target for controlling HBV infection. However, the role of the central cytokine mTOR in the pathogenesis of HBV infection has not yet been systematically addressed. Notably, mTOR is commonly activated in hepatocellular carcinoma, which can progress from chronic hepatitis B. This review systematically summarizes the role of mTOR in the life cycle of HBV and its impact on the clinical progression of HBV infection.

Clinical and economic value of bulevirtide in the treatment of chronic hepatitis D.

BACKGROUND/AIMS: Bulevirtide (Hepcludex®) is the first drug approved for the treatment of chronic hepatitis D (CHD), unlike the current off-label treatment (PEG-IFN-α), limited in clinical practice and associated with post-treatment relapses. In a hypothetical cohort of CHD patients in Spain, the study aim was to compare the efficiency of bulevirtide with PEG-IFN-α in terms of clinical events avoided and associated cost savings. METHODS: A validated economic model reflecting the natural history of the disease was used to project lifetime liver complications and costs for two hypothetical cohorts treated with bulevirtide or PEG-IFN-α. The model considered progression to complications such as decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplantation (LT), and death. The efficacy rates used at 24 and 48 weeks were defined as the combined response rate for bulevirtide and undetectable HDV RNA to PEG-IFN-α. The numbers of clinic events and associated costs were evaluated from the perspective of the National Healthcare System. RESULTS: In a hypothetical cohort of 3,882 patients, bulevirtide reduced the numbers of complications events in comparison to PEG-IFN-α (152 DCC, 113 HCC, 11 LT, and 321 deaths over a lifetime). This was associated with a reduction of event-related costs of euro 11,837,044 (DCC euro1,138,059; HCC euro1,503,583; LT euro7,834,291; and death euro1,361,111). CONCLUSION: In patients with CHD, bulevirtide could prevent a significant number of clinical events compared to PEG-IFN-α and contribute to cost savings through these reduction in liver complications. Further testing for hepatitis D virus is needed so that more patients can benefit from bulevirtide.

The 2023 South Sudanese outbreak of Hepatitis E emphasizes ongoing circulation of genotype 1 in North, Central, and East Africa.

In April 2023, an outbreak of acute hepatitis was reported in the Nazareth internally displaced persons camp in South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis.

Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.

A consistent feature of chronic liver diseases and the hallmark of pathologic repair is the so-called ductular reaction. This is a histological abnormality characterized by an expansion of dysmorphic cholangiocytes inside and around portal spaces infiltrated by inflammatory, mesenchymal, and vascular cells. The ductular reaction is a highly regulated response based on the reactivation of morphogenetic signaling mechanisms and a complex crosstalk among a multitude of cell types. The nature and mechanism of these exchanges determine the difference between healthy regenerative liver repair and pathological repair. An orchestrated signaling among cell types directs mesenchymal cells to deposit a specific extracellular matrix with distinct physical and biochemical properties defined as portal fibrosis. Progression of fibrosis leads to vast architectural and vascular changes known as liver cirrhosis. The signals regulating the ecology of this microenvironment are just beginning to be addressed. Contrary to the tumor microenvironment, immune modulation inside this "benign" microenvironment is scarcely known. One of the reasons is that both the ductular reaction and portal fibrosis have been primarily considered a manifestation of cholestatic liver disease, whereas this phenomenon is also present, albeit with distinctive features, in all chronic human liver diseases. Novel human-derived cellular models and progress in "omics" technologies are increasing our knowledge at a fast pace. Most importantly, this knowledge is on the edge of generating new diagnostic and therapeutic advances. Here, we will critically review the latest advances, in terms of mechanisms, pathophysiology, and treatment prospects. In addition, we will delineate future avenues of research including innovative translational opportunities.

Examining the evolving landscape of liver cancer burden in the United States from 1990 to 2019.

INTRODUCTION: Liver cancer (LC) is frequently preceded by cirrhosis and poses a significant public health challenge in the United States (US). Recent decades have seen notable shifts in the epidemiological patterns of LC, yet national data guiding the optimal allocation of resources and preventive efforts remain limited. This study aims to investigate the current trends, risk factors, and outcomes of LC in the US. METHODS: This study utilized the Global Burden of Disease (GBD) dataset to collect data on the annual incident cases, deaths, Disability-Adjusted Life Years (DALYs), age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized DALY rates of primary LC and its etiologies and risk factors, between 1990 and 2019. Percentage changes in incident cases, DALYs, and deaths and the estimated annual percentage change (EAPC) in ASIR and deaths rates of LC were calculated to conduct temporal analysis. Linear regression was applied for the calculation of EAPCs. Correlations of EAPC with socio-demographic index (SDI) were separately evaluated by Pearson correlation analyses. RESULTS: We observed a marked increase in the ASIR of LC, increasing from 2.22 (95% CI: 2.15-2.27) per 100,000 people in 1990 to 5.23 (95% CI: 4.28-6.29) per 100,000 people in 2019, a percentage change of 135.4%. LC due to hepatitis C followed by alcohol use were the primary factors driving this increase. The ASIR and age-standardized death rates of LC showed a significant average annual increase of 3.0% (95% CI: 2.7-3.2) and 2.6% (95% CI: 2.5-2.8), respectively. There was a significant negative correlation between the SDI and the EAPC in ASIR (ρ = -0.40, p = 0.004) and age-standardized death rates (ρ = -0.46, p < 0.001). In 2019, drug and alcohol use, followed by elevated body mass index (BMI) were the primary risk factors for age-standardized DALY rates attributable to LC. CONCLUSION: The increased burden of LC in the US highlights the need for interventions. This is particularly important given that LC is mostly influenced by modifiable risk factors, such as drug and alcohol use, and elevated BMI. Our findings highlight the urgent need for public health interventions targeting socio-economic, lifestyle, and modifiable risk factors to mitigate the escalating burden of LC.