Regional differences in clinical presentation and prognosis of patients with post-sustained virologic response (SVR) hepatocellular carcinoma.

Background& Amis: Widespread use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has resulted in increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response ('post-SVR HCC') worldwide. Few data compare regional differences in presentation and prognosis of patients with post-SVR HCC.MethodsWe identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March, 2015 and October, 2021 from 30 sites in Europe, North America, South America, Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis.ResultsAmong 8,796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of detection by surveillance (range: 59.5-100%), median maximum tumor diameter (range: 1.8-5.0 cm), and proportion with multinodular HCC (range: 15.4-60.8%). Prognosis of patients highly varied by region (HR range: 1.82-9.92), with the highest survival in East Asia, North America, and South America, and lowest in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early-stage detection (BCLC stage 0/A: 71.0% vs. 21.3%, pConclusionsClinical characteristics, including early-stage detection, and prognosis of post-SVR HCC significantly differed across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally

Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients

It has been reported that hepatic flare (HF), attributable to the development of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients, occurs frequently after the start of anti-retroviral therapy (ART). We have observed several cases of hepatitis B surface antigen (HBsAg) loss after IRIS. However, the factors leading to HBsAg clearance remain unknown. We measured CD4+ and CD8+ T cells, cytokines and chemokines in 16 patients coinfected HIV-1 and HBV with IRIS, and analyzed the factors leading to HBsAg clearance after IRIS. There was no significant difference in the CD4+ and CD8+ T cell counts between the HBsAg clearance and non-clearance groups, while the serum concentrations of almost all cytokines and chemokines in the HBsAg clearance group were higher than in the HBsAg non-clearance group at any time of observation. In particular, IP-10 at the ALT peak, GM-CSF and IL-12 one month after the ALT peak and TNF-α and GM-CSF after the ALT concentrations fell to within normal limits, were significantly higher in the HBsAg clearance group. It seems that HBsAg loss after IRIS requires continued immune responses against HBV, involving Th1 cytokines

Increased levels of arginase in patients with acute hepatitis B suppress antiviral T cells

Background & Aims: During viral infection, the activities of virus-specific CD8 + T cells are carefully regulated to prevent severe damage of the infected organs. We investigated the mechanisms that control the functions of activated T cells. Methods: We measured the size of the population of activated and proliferating CD8 + T cells and the functional pattern of CD8 + T cells specific for the entire hepatitis B virus proteome and for selected heterologous virus (Epstein-Barr virus, human cytomegalovirus, and influenza virus) using blood samples from 18 patients with acute hepatitis B. We analyzed the effects of different modulatory mechanisms, such as inhibitory molecules, suppressive cytokines (interleukin-10), and arginase, on the activities of CD8 + T cells. Results: In patients with acute hepatitis B, the expansion of activated and proliferating (HLA-DR/CD38 +, Ki-67 +/Bcl-2 low) CD8 + T cells did not quantitatively match their specific functions ex vivo; virus-specific CD8 + T cells had functional impairments that were temporally restricted to the acute phase of viral hepatitis. These impairments in function were not limited to HBV-specific CD8 + T cells but were also observed in CD8 + T cells with specificities for other viruses. We investigated possible causes of antigen-independent CD8 + T cell inhibition and found that the increased levels of arginase observed in patients with acute hepatitis could suppress the function of activated, but not resting, CD8 + T cells. Conclusions: The increased level of arginase in patients with acute hepatitis B suppresses the functions of activated CD8 + T cells. This mechanism might limit the amount of liver damage caused by activated CD8 + T cells in patients with acute HBV infection. © 2012 AGA Institute

Predicting the success of endoscopic transpapillary gallbladder drainage for patients with acute cholecystitis during pretreatment evaluation

INTRODUCTION: Although endoscopic transpapillary gallbladder drainage (ETGBD) has been reported to be an effective treatment for acute cholecystitis, technical difficulties have precluded more widespread use of this technique. Case evaluations that can predict the occurrence of such difficulties should increase the acceptance of ETGBD for acute cholecystitis treatment

RIG-I functions as a dual effector against HBV

Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but not type I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.Supplemental materials are available on the publisher's website

Endoscopic Sphincterotomy before Fully Covered Metal Stent Placement Is Not Required for Distal Malignant Biliary Stricture due to a Pancreatic Head Tumor

Background/Aims. Endoscopic sphincterotomy (EST) is often performed before fully covered self-expandable metal stent (FCSEMS) placement in order to prevent pancreatitis. However, it is not clear whether EST prevents pancreatitis or affects other adverse events (AEs). This study is conducted to evaluate the necessity of EST before FCSEMS placement for distal malignant biliary strictures due to a pancreatic head tumor. Methods. This study included 68 patients who underwent FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor. Treatment outcomes and AEs were retrospectively compared between 32 patients with EST before FCSEMS placement (EST group) and 36 patients without EST (non-EST group). Results. The success rates of drainage for the EST and non-EST groups were 100% and 97.2%, respectively (P=0.95). The incidence of pancreatitis in the EST and non-EST groups was 3.1% and 0%, respectively (P=0.95). The incidence of hyperamylasemia in the EST and non-EST groups was 12.5% and 13.9%, respectively (P=0.85). The incidence of all AEs in the EST and non-EST groups was 15.6% (pancreatitis: 1, cholecystitis: 2, and stent migration: 2) and 13.9% (cholecystitis: 3, stent migration: 2), respectively (P=0.89). Conclusions. EST before FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor does not affect the successful drainage and incidence of adverse events. The necessity of EST to prevent pancreatitis before FCSEMS placement was deemed low

Diversidade e inclusão, sensibilizar para o outro que é diferente de mim

A sociedade atual evidencia-se cada vez mais pela diversidade e idiossincrasias dos seus indivíduos, o que responsabiliza todo o sistema educativo na promoção de uma educação orientada para valores e práticas inclusivas. Este estudo, de natureza qualitativa, integrado no âmbito da formação de professores, dá conta de como alguns desses valores, e consequentes práticas, podem ser promovidos desde muito cedo, nomeadamente na Educação Pré-escolar e no 1º Ciclo do Ensino Básico. Com base na metodologia dos testes sociométricos, através de placas com imagens fotográficas de crianças, a investigação foi desenvolvida com um grupo de 24 crianças, entre os três e quatro anos, e uma turma do 4º ano com 20 alunos. Da análise de dados evidenciam-se as médias percentuais das suas preferências sobre aspetos culturais, de género,cor da pele e deficiência. Dos resultados destacam-se aspetos particulares de eleição, de como percecioname o que pensam sobre outras crianças consideradas“diferentes”. De salientar o papel fundamental dos docentes na promoção e sensibilização para a aceitação da diferença e da diversidade

Genetic Association of Human Leukocyte Antigens with Chronicity or Resolution of Hepatitis B Infection in Thai Population

<div><p>Background</p><p>Previous studies showed that single nucleotide polymorphisms (SNPs) in the <i>HLA-DP</i>, <i>TCF19</i> and <i>EHMT2</i> genes may affect the chronic hepatitis B (CHB). To predict the degree of risk for chronicity of HBV, this study determined associations with these SNPs.</p><p>Methods</p><p>The participants for this study were defined into 4 groups; HCC (n = 230), CHB (n = 219), resolved HBV infection (n = 113) and HBV uninfected subjects (n = 123). The <i>HLA-DP</i> SNPs (rs3077, rs9277378 and rs3128917), <i>TCF19</i> SNP (rs1419881) and <i>EHMT2</i> SNP (rs652888) were genotyped.</p><p>Results</p><p>Due to similar distribution of genotype frequencies in HCC and CHB, we combined these two groups (HBV carriers). The genotype distribution in HBV carriers relative to those who resolved HBV showed that rs3077 and rs9277378 were significantly associated with protective effects against CHB in minor dominant model (OR = 0.45, <i>p</i><0.001 and OR = 0.47, <i>p</i><0.001). The other SNPs rs3128917, rs1419881 and rs652888 were not associated with HBV carriers.</p><p>Conclusions</p><p>Genetic variations of rs3077 and rs9277378, but not rs3128917, rs1419881 and rs652888, were significantly associated with HBV carriers relative to resolved HBV in Thai population.</p></div