Integrated network pharmacology and metabolomics to study the potential mechanism of Jiawei Yinchenhao decoction in chronic hepatitis B.

Chronic hepatitis B infection (CHB) is a major risk factor for the development of hepatocellular carcinoma (HCC) globally and continues to pose a significant global health challenge. Jiawei Yinchenhao decoction (JWYCH) is a modified version of Yinchenhao decoction (YCHD), which is widely used to treat liver diseases including icteric hepatitis, cholelithiasis, and hepatic ascites. However, the effectiveness and underlying mechanism of JWYCH on CHB are still unclear. This study aimed to investigate the impact of JWYCH on CHB and explore the underlying mechanism via network pharmacology and metabolomics. C57BL/6 mice were administered rAAV-HBV1.3 via hydrodynamic injection (HDI) to establish the CHB model. The infected mice were orally administered JWYCH for 4 weeks. HBsAg, HBeAg, HBV DNA, the serum liver function index, and histopathology were detected. In addition, network pharmacology was used to investigate potential targets, whereas untargeted metabolomics analysis was employed to explore the hepatic metabolic changes in JWYCH in CHB mice and identify relevant biomarkers and metabolic pathways. JWYCH was able to reduce HBeAg levels and improve liver pathological changes in mice with CHB. Additionally, metabolomics analysis indicated that JWYCH can influence 105 metabolites, including pipecolic acid, alpha-terpinene, adenosine, and L-phenylalanine, among others. Bile acid metabolism, arachidonic acid metabolism, and retinol metabolism are suggested to be potential targets of JWYCH in CHB. In conclusion, JWYCH demonstrated a hepatoprotective effect on a mouse model of CHB, suggesting a potential alternative therapeutic strategy for CHB. The effect of JWYCH is associated mainly with regulating the metabolism of bile acid, arachidonic acid, and retinol. These differentially abundant metabolites may serve as potential biomarkers and therapeutic targets for CHB.

Trends and multi-model prediction of hepatitis B incidence in Xiamen.

Background: This study aims to analyze the trend of Hepatitis B incidence in Xiamen City from 2004 to 2022, and to select the best-performing model for predicting the number of Hepatitis B cases from 2023 to 2027. Methods: Data were obtained from the China Information System for Disease Control and Prevention (CISDCP). The Joinpoint Regression Model analyzed temporal trends, while the Age-Period-Cohort (APC) model assessed the effects of age, period, and cohort on hepatitis B incidence rates. We also compared the predictive performance of the Neural Network Autoregressive (NNAR) Model, Bayesian Structural Time Series (BSTS) Model, Prophet, Exponential Smoothing (ETS) Model, Seasonal Autoregressive Integrated Moving Average (SARIMA) Model, and Hybrid Model, selecting the model with the highest performance to forecast the number of hepatitis B cases for the next five years. Results: Hepatitis B incidence rates in Xiamen from 2004 to 2022 showed an overall declining trend, with rates higher in men than in women. Higher incidence rates were observed in adults, particularly in the 30-39 age group. Moreover, the period and cohort effects on incidence showed a declining trend. Furthermore, in the best-performing NNAR(10, 1, 6)[12] model, the number of new cases is predicted to be 4271 in 2023, increasing to 5314 by 2027. Conclusions: Hepatitis B remains a significant issue in Xiamen, necessitating further optimization of hepatitis B prevention and control measures. Moreover, targeted interventions are essential for adults with higher incidence rates.

Hepatitis B virus infection and vaccination among people who use drugs in Xi'an, China.

BACKGROUND: While hepatitis B virus (HBV) infection in children has declined dramatically in China due to the vaccination strategy for newborns, HBV infection in high-risk adults is receiving an increasing attention. The number of people who use drugs (PWUD) in China is huge, but their status of HBV infection and vaccination is less reported, especially from large samples. The related knowledge can help decision makers develop the further strategy of HBV prevention and control. METHODS: A seroepidemiological survey was conducted in all four compulsory isolated detoxification centers (CIDCs) and all eight methadone maintenance treatment (MMT) clinics located in Xi'an, China. All PWUD who were undergoing detoxification or treatment in these settings were included. A questionnaire was designed to obtain the information of HBV vaccination history of participants, and sociodemographic and behavioral data of participants were obtained from the registration records of their respective CIDCs or MMT clinics. RESULTS: A total of 4705 PWUD participated in the survey. Positive rates of HBsAg (current infection) and HBsAg or anti-HBc (current/past infection) were 5.50% and 58.02%, notably higher than those reported for the general adult population in the same province during the same period. As age increased, the anti-HBc positive rate increased with statistically significant trend. The all-negative for HBsAg, anti-HBc, and anti-HBs accounted for 28.82%. Only 18.49% were identified by the questionnaire as having received HBV vaccine. The logistic regression found that compared with identified vaccinated PWUD, those unsure if having been vaccinated and those identified non-vaccinated had a significantly higher HBV current/past infection rate, with an increasing trend. CONCLUSION: PWUD are a high-risk adult group of HBV infection in China. Of them, more than half have not received HBV vaccine, and a significant portion are susceptible to HBV. Catch-up vaccination is need for this population to prevent and control HBV transmission.

Cost-benefit analysis of serological and nucleic acid testing for hepatitis B virus in blood donors in southern China.

BACKGROUND: Most Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine blood donor screening for HBV infection since 2015, and a few centers upgraded MP to individual donation (ID) NAT screening recently, raising urgent need for cost-benefit analysis of different screening strategies. In an effort to prevent transfusion-transmitted infections (TTIs) for HBV, cost-benefit analyses of three different screening strategies: HBsAg alone, HBsAg plus MP NAT and HBsAg plus ID NAT were performed in blood donors from southern China where HBV infection was endemic. METHODS: MP-6 HBV NAT and ID NAT were adopted in parallel to screen blood donors for further comparative analysis. On the basis of screening data and the documented parameters, the number of window period (WP) infection, HBV acute infection, chronic hepatitis B infection (CHB) and occult hepatitis B infection (OBI) was evaluated, and the potential prevented HBV TTIs and benefits of these three strategies were predicted based on cost-benefit analysis by an estimation model. RESULTS: Of 132,323 donations, the yield rate for HBsAg-/DNA + screened by ID NAT (0.12%) was significantly higher than that by MP NAT (0.058%, P < 0.05). Furthermore, the predicted transfusion-transmitted HBV cases prevented was 1.25 times more by ID NAT compared to MP-6 NAT. The cost-benefit ratio of the universal HBsAg screening, HBsAg plus ID NAT and HBsAg plus MP NAT were 1:58, 1:27 and 1:22, respectively. CONCLUSIONS: Universal HBsAg ELISA screening in combination with HBV ID NAT or MP-6 NAT strategies was highly cost effective in China. To further improve blood safety, HBsAg plus HBV DNA ID NAT screening should be considered in HBV endemic regions/countries.

Epidemiology of hepatitis B virus infection among pregnant women in Africa: a systematic review and meta-analysis.

BACKGROUND: Although hepatitis B infection is highly endemic in Africa, information on its epidemiology among pregnant women in the region is limited. Therefore, this systematic review provided up-to-date information on the epidemiology of hepatitis B virus (HBsAg) infection among pregnant women in Africa. METHODS: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews. The Web of Science, Scopus, PubMed, Google Scholar, and African journals online were searched to identify relevant studies published between January 1, 2015, and May 21, 2024, on hepatitis B virus infection in pregnant women living in Africa. The Joanna Briggs Institute tool was used to assess the methodological qualities of the included studies. The random effects model was used to estimate the pooled prevalence of HBV infection. I2 assessed the amount of heterogeneity. Publication bias was assessed using Egger's test and a funnel plot. RESULTS: We included 91 studies from 28 African countries. The pooled prevalence of hepatitis B infection among pregnant women in Africa was 5.89% (95% CI: 5.26-6.51%), with significant heterogeneity between studies (I2 = 97.71%, p < 0.001). Family history of hepatitis B virus infection (AOR = 2.72, 95%CI: 1.53-3.9), multiple sexual partners (AOR = 2.17, 95%CI: 1.3-3.04), and sharing sharp materials were risk factors for hepatitis B infection. CONCLUSION: An intermediate endemic level of hepatitis B virus infection (2-7%) was observed among pregnant women in Africa. To prevent disease transmission, interventions should focus on pregnant women with a family history of hepatitis B infection, multiple sexual partners, and sharing sharp materials.

Sex-specific associations of Notch signaling with chronic HBV infection: a study from Taiwan Biobank.

BACKGROUND: Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA. METHODS: We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis. RESULTS: We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women. CONCLUSION: According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women.

Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV). It can lead to long-term liver damage and cancer. We looked at differences in how the virus affects men and women in Taiwan. We analyzed data from over 72,000 people in the Taiwan Biobank. The study individuals were divided into two groups­those who had the hepatitis B virus (cases) and those who did not (controls). We looked for genetic differences between the two groups and found that the specific genetic risk factors for hepatitis B differed between men and women. We found three genetic risk factors in men and eight in women. This suggests that the way the hepatitis B virus interacts with our genes may differ between the sexes. We found that in women, the most significant genetic risk factors were all located on chromosome 6. However, in men, the significant risk factors were spread across different chromosomes, including chromosome 3. Finally, we looked at how these genetic differences might affect the way the body processes the hepatitis B virus. We found that two specific genes, called POGLUT1 and HIST1H2BC, were only linked to hepatitis B risk in men, not in women. This indicates that the biological pathways involved in hepatitis B infection may differ between males and females. Understanding these differences could lead to more effective, personalized treatment strategies for those affected by the virus.

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.

Time interval distribution of hepatitis B vaccine immunization among infants in China from 2017 to 2021.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third doses is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from the Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28 and 61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61 and 214 days after the second dose 87,067 (64.1%) infants were vaccinated with the third dose between 151 and 180 days after the second dose. The time interval distribution varied across the four provinces or municipalities (p < .001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine and training for obstetricians and related personnel.

Immune checkpoint inhibitors in infectious disease.

Following success in cancer immunotherapy, immune checkpoint blockade is emerging as an exciting potential treatment for some infectious diseases, specifically two chronic viral infections, HIV and hepatitis B. Here, we will discuss the function of immune checkpoints, their role in infectious disease pathology, and the ability of immune checkpoint blockade to reinvigorate the immune response. We focus on blockade of programmed cell death 1 (PD-1) to induce durable immune-mediated control of HIV, given that anti-PD-1 can restore function to exhausted HIV-specific T cells and also reverse HIV latency, a long-lived form of viral infection. We highlight several key studies and future directions of research in relation to anti-PD-1 and HIV persistence from our group, including the impact of immune checkpoint blockade on the establishment (AIDS, 2018, 32, 1491), maintenance (PLoS Pathog, 2016, 12, e1005761; J Infect Dis, 2017, 215, 911; Cell Rep Med, 2022, 3, 100766) and reversal of HIV latency (Nat Commun, 2019, 10, 814; J Immunol, 2020, 204, 1242), enhancement of HIV-specific T cell function (J Immunol, 2022, 208, 54; iScience, 2023, 26, 108165), and investigating the effects of anti-PD-1 and anti-CTLA-4 in vivo in people with HIV on ART with cancer (Sci Transl Med, 2022, 14, eabl3836; AIDS, 2021, 35, 1631; Clin Infect Dis, 2021, 73, e1973). Our future work will focus on the impact of anti-PD-1 in vivo in people with HIV on ART without cancer and potential combinations of anti-PD-1 with other interventions, including therapeutic vaccines or antibodies and less toxic immune checkpoint blockers.

Cigarette Smoking Is Associated With Lower Chance of Hepatitis B Surface Antigen Seroclearance and Altered Host Immunity.

Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow-up data was retrieved in 7833 antiviral-treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB-infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death-1 (PD-1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV-specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFß) production in undepleted PBMCs and Treg-depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow-up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57-0.87). PD-1 expression was increased in CD4+T cells, CD8+T cells and CD20+B cells among smokers compared to non-smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV-specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non-smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD-1 expression on lymphocytes, and impairment of effector functions of HBV-specific T cells in CHB.

Hepatitis B surface antigen impairs TLR4 signaling by upregulating A20 expression in monocytes.

Toll-like receptors (TLRs) play a crucial role in eliminating viral infection. Conversely, viruses have evolved various strategies to disrupt TLR signaling during chronic infection. In the case of hepatitis B virus (HBV), we previously reported that plasma hepatitis B surface antigen (HBsAg) is closely associated with impaired TLR responses in peripheral blood mononuclear cells from chronic hepatitis B (CHB) patients, but the reasons remain unclear. In this study, we investigated the mechanism by which HBsAg suppresses TLR4 signaling in monocyte cell lines. The monocyte cell line THP-1 was pretreated with HBsAg, followed by lipopolysaccharide (LPS) stimulation. Levels of proinflammatory cytokines and the activation of NF-κB, c-JNK, and ERK were examined. We found that HBsAg did not influence the LPS-induced activation of p65, but it disrupted NF-κB promoter activity through the ectopic expression of myeloid differentiation factor 88 (MyD88) and TAK1, suggesting that HBsAg can block downstream TLR4 signaling. Furthermore, we proved that LPS-induced polyubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) and the formation of the TRAF6-TAB2 complex were inhibited in HBsAg-pretreated cells. Interestingly, HBsAg led to a significant upregulation of A20, a ubiquitin-editing enzyme. Correspondingly, downregulation of A20 using siRNA restored LPS-mediated cytokines production, reflecting its crucial role in HBsAg-mediated inhibition of TLR4 signaling. These results demonstrated a novel mechanism by which HBsAg disrupts TLR4 signaling through the upregulation of A20, suggesting that targeting A20 may be a potential strategy to help restore monocyte functions. IMPORTANCE: Clearance HBsAg indicates a functional cure of HBV infection, but in chronic hepatitis B (CHB), it is hard to achieve. HBsAg has been found to regulate anti-viral immune responses, such as the activation of TLR. Our previous jobs proved that HBsAg negatively correlates with TLR2/4 activation in monocytes from CHB patients and blocks TLR2 ligand-indcuced IL-12 production in monocytes. However, how TLR4 signaling is affected by HBsAg remains unknown. In this study, we not only observed impaired TLR4 activation after pretreated monocytes with HBsAg but also identified HBsAg-induced A20 play a role in this impairment, which suggests that targeting A20 may be a viable strategy to restore monocyte functions in CHB.

Fibrinogen dysfunction and fibrinolysis state in patients with hepatitis B-related cirrhosis.

OBJECTIVE: To assess the fibrinogen function in patients with hepatitis B-related cirrhosis and explore the relationship between dysfibrinogenemia and bleeding and thrombotic events. METHODS: Medical records and laboratory data of the patients with hepatitis B-related cirrhosis were collected. Patients were categorized into three groups based on the Child-Pugh score. Fibrinogen activity and antigen, fibrinogen-bound sialic acid (FSA), fibrinogen polymerization and fibrinolysis kinetic analysis, thrombin-antithrombin complex (TAT) and plasmin-α2-antiplasmin complex (PAP) were detected. RESULTS: Eighty patients with seventeen, thirty-eight and twenty-five in Child-Pugh A, B and C, respectively, were included. Seventeen patients experienced bleeding events and eight patients had thrombotic events. Fibrinogen activity and antigen levels were reduced with the severity of cirrhosis. Twenty-two patients exhibited dysfibrinogenemia. The FSA levels in patients with non-dysfibrinogenemia and those with dysfibrinogenemia were increased to 1.25 and 1.37 times of healthy controls, negatively correlated with fibrinogen activity (ρ = -0.393, p = 0.006). Compared to healthy controls, the amount of clot formation was reduced (p < 0.001), the polymerization was delayed (p < 0.001) and the rate of fibrinolysis was reduced (p < 0.001). The TAT levels were significantly increased in the Child-Pugh C patients compared to the Child-Pugh B patients (p = 0.032) while the PAP levels were comparable among 3 groups (p = 0.361). CONCLUSION: Sialylation of fibrinogen is one of the main causes of modifications of fibrinogen in patients with hepatitis B-related cirrhosis. The polymerization and fibrinolysis functions of fibrinogen are impaired. The degree of impaired fibrinolysis function is more severe than that of polymerization function, and may be partly related to the occurrence of thrombotic events.

Effect of nucleos(t)ide analogue discontinuation on the prognosis of HBeAg-negative hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A propensity score matching analysis.

BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

Adult Hepatoblastoma and Concomitant Hepatitis B Infection.

We report a case of hepatoblastoma in a 26-year-old man with a background of type 2 diabetes mellitus and untreated hepatitis B, initially presenting with hematemesis and a recent diagnosis of hepatocellular carcinoma on computed tomography scan from a different hospital and recent referral to hospice. On presentation to our hospital, given atypical presentation for hepatocellular carcinoma, histological examination was made, revealing hepatoblastoma. Treatment included chemotherapy and management of hepatitis B, although complicated by chemotherapy-induced cytopenias and tumor progression, ultimately losing the patient to follow-up after 2 years.

Unusual extrahepatic metastatic site of hepatocellular carcinoma with post-therapy disseminating metastases presenting as a primary soft tissue sarcoma: case report.

Introduction and importance: Hepatocellular carcinoma (HCC) is a highly malignant primary hepatic tumor. However, extrahepatic metastatic sites of HCC with post-therapy dissemination of metastases mimicking primary soft tissue sarcomas with rib metastases are extremely rare. Case presentation: The authors report a unique case of hepatitis B virus (HBV)-positive HCC with bilateral lung involvement and widespread right-flank soft tissue and rib metastases. The pathological diagnosis after surgical resection confirmed extrahepatic HCC metastasis. Subsequently, adjuvant-targeted and immune-checkpoint inhibitor therapies were still initiated. Clinical discussion: Extrahepatic HCC metastasis, which initially presents at distant sites, is uncommon. HCC commonly metastasizes to the lungs, bones, lymph nodes, kidneys, adrenal glands, and peritoneum/omentum. HCC with aggressive post-scheduled adjuvant therapy to the lungs and hypochondriac soft tissue with rib metastasis is very rare and has a poor prognosis. Conclusion: Although most patients with HCC have disseminated extrahepatic metastases, primary HCC should still be treated. Thus, a review of the history and imaging, histopathology, and immunohistochemical findings is crucial for the definite and differential diagnosis of this tumor.

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/.

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.

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.