AIM:To compare the efficacy and safety of tenofovir disoproxil fumarate(TDF)in Asian and non-Asian chronic hepatitis B(CHB)patients.METHODS:The efficacy and safety of the initial 48wk of treatment with TDF was compare...AIM:To compare the efficacy and safety of tenofovir disoproxil fumarate(TDF)in Asian and non-Asian chronic hepatitis B(CHB)patients.METHODS:The efficacy and safety of the initial 48wk of treatment with TDF was compared in a posthoc analysis of combined data from 217 Asians and299 non-Asians included in Studies 102 and 103and a post-approval,open-label trial(Study 123).Patient groups were compared according to baseline hepatitis B e antigen(HBe Ag)status and viral load.The main outcome measures included the proportion of patients who achieved a hepatitis B virus(HBV)DNA level<400 copies/m L at Week 48 of treatment.Secondary measures included:HBV DNA and alanine aminotransaminase(ALT)levels over time;proportion of patients with normal ALT levels;proportion of patients with HBe Ag loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion;changes in liver histology.Safety and tolerability were evaluated by the occurrence of adverse events(AEs),serious AEs,laboratory abnormalities,discontinuation of the study drug due to AEs,or death.The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug.RESULTS:At week 48,similar proportions of Asians and non-Asians reached HBV DNA<400 copies/m L(96%of Asian and 97%of non-Asian patients with HBe Ag-negative CHB and 83%of Asian and 79%of non-Asian patients with HBe Ag-positive CHB had HBV DNA)and normal ALT(78%of Asian and 81%of nonAsian patients with HBe Ag-negative CHB and 71%of Asian and 74%of non-Asian patients with HBe Agpositive CHB had normal ALT).On-treatment HBV DNA decline rates were similar between Asians and nonAsians regardless of baseline HBe Ag status and viralload.HBV DNA decline during the first four weeks was2.9 log10 copies/m L in HBe Ag-negative Asians and nonAsians,and in HBe Ag-positive non-Asians,and 3.1log10 copies/m L in HBe Ag-positive Asians.HBe Ag loss and seroconversion was achieved in 14%of Asians vs 26%and 24%,respectively,in non-Asians.Liver histology improved in 77.2%of Asians and 71.5%of non-Asians.No resistance to TDF developed.No renal safety signals were observed.CONCLUSION:TDF demonstrated similar viral suppression,normalization of ALT,improvements in liver fibrosis,and no detectable resistance in Asian and non-Asian patients regardless of baseline HBe Ag status.展开更多
Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogen...Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis.The deregulation of epigenetic mechanisms,which maintain heritable gene expression changes and chromatin organization,is implicated in the development of multiple cancers,including HCC.This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC,with an emphasis on HCC mediated by chronic hepatitis B virus infection.This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers,and highlights the future potential of similar therapies in the treatment of HCC.展开更多
AIM: To investigate physicians' knowledge including chronic hepatitis B(CHB) diagnosis, screening, and management in various stages of their training.METHODS: A voluntary 20-question survey was administered in San...AIM: To investigate physicians' knowledge including chronic hepatitis B(CHB) diagnosis, screening, and management in various stages of their training.METHODS: A voluntary 20-question survey was administered in Santa Clara County, CA where Asian and Pacific Islanders(API) account for a third of the population. Among the 219 physician participants,there were 63 interns, 60 second-year residents, 26 chief residents and 70 attending physicians. The survey asked questions regarding respondents' demographics,general hepatitis B virus knowledge questions(i.e.,transmission, prevalence, diagnostic testing, prevention,and treatment options), as well as, self-reported practice behavior and confidence in knowledge.RESULTS: Knowledge about screening and managing patients with CHB was poor: only 24% identified the correct tests to screen for CHB, 13% knew the next steps for patients testing positive for CHB, 18% knew the high prevalence rate among API, and 31% knew how to screen for liver cancer. Wald chi-square analysis determined the effect of training level on knowledge; in all cases except for knowledge of liver cancer screening(p = 0.0032), knowledge did not significantly increase with length in residency training or completion of residency.CONCLUSION: Even in a high-risk region, both medical school and residency training have not adequatelyprepared physicians in the screening and management of CHB.展开更多
AIM To evaluate maternal hepatitis B virus(HBV) DNA as risk for perinatal HBV infection among infants of HBVinfected women in California.METHODS Retrospective analysis among infants born to hepatitis B surface antigen...AIM To evaluate maternal hepatitis B virus(HBV) DNA as risk for perinatal HBV infection among infants of HBVinfected women in California.METHODS Retrospective analysis among infants born to hepatitis B surface antigen(HBs Ag)-positive mothers who received post vaccination serologic testing(PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen(HBe Ag) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/ml,a 5:1 ratio of cases to controls and a two-sided confidence level of 95%.RESULTS A total of 17687 infants were born to HBs Ag positive mothers in California between Jan 1 2005 and Dec 31,2011. Among 11473 infants with PVST,only 125(1.1%) were found to be HBV infected. Among these infected infants,lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis(PEP) occurred in only 9 infants. However,PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBe Ag and HBV DNA level,case-control analysis found HBe Ag positivity(70.4% vs 28.9%,OR = 46.76,95%CI: 6.05-361.32,P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/ml(92.6% vs 18.5%,OR = 54.5,95%CI: 12.22-247.55,P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression,maternal HBV DNA level ≥ 2 × 107 IU/ml was the only significant independent predictor of perinatal HBV infection. CONCLUSION In California,transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/ml is associated with high risk of perinatal infection.展开更多
A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagno...A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of druginduced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.展开更多
基金Supported by Gilead SciencesEditorial support was provided by Carol Lovegrove,associated with Elements Communications(Westerham,United Kingdom),and funded by Gilead Sciences
文摘AIM:To compare the efficacy and safety of tenofovir disoproxil fumarate(TDF)in Asian and non-Asian chronic hepatitis B(CHB)patients.METHODS:The efficacy and safety of the initial 48wk of treatment with TDF was compared in a posthoc analysis of combined data from 217 Asians and299 non-Asians included in Studies 102 and 103and a post-approval,open-label trial(Study 123).Patient groups were compared according to baseline hepatitis B e antigen(HBe Ag)status and viral load.The main outcome measures included the proportion of patients who achieved a hepatitis B virus(HBV)DNA level<400 copies/m L at Week 48 of treatment.Secondary measures included:HBV DNA and alanine aminotransaminase(ALT)levels over time;proportion of patients with normal ALT levels;proportion of patients with HBe Ag loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion;changes in liver histology.Safety and tolerability were evaluated by the occurrence of adverse events(AEs),serious AEs,laboratory abnormalities,discontinuation of the study drug due to AEs,or death.The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug.RESULTS:At week 48,similar proportions of Asians and non-Asians reached HBV DNA<400 copies/m L(96%of Asian and 97%of non-Asian patients with HBe Ag-negative CHB and 83%of Asian and 79%of non-Asian patients with HBe Ag-positive CHB had HBV DNA)and normal ALT(78%of Asian and 81%of nonAsian patients with HBe Ag-negative CHB and 71%of Asian and 74%of non-Asian patients with HBe Agpositive CHB had normal ALT).On-treatment HBV DNA decline rates were similar between Asians and nonAsians regardless of baseline HBe Ag status and viralload.HBV DNA decline during the first four weeks was2.9 log10 copies/m L in HBe Ag-negative Asians and nonAsians,and in HBe Ag-positive non-Asians,and 3.1log10 copies/m L in HBe Ag-positive Asians.HBe Ag loss and seroconversion was achieved in 14%of Asians vs 26%and 24%,respectively,in non-Asians.Liver histology improved in 77.2%of Asians and 71.5%of non-Asians.No resistance to TDF developed.No renal safety signals were observed.CONCLUSION:TDF demonstrated similar viral suppression,normalization of ALT,improvements in liver fibrosis,and no detectable resistance in Asian and non-Asian patients regardless of baseline HBe Ag status.
文摘Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis.The deregulation of epigenetic mechanisms,which maintain heritable gene expression changes and chromatin organization,is implicated in the development of multiple cancers,including HCC.This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC,with an emphasis on HCC mediated by chronic hepatitis B virus infection.This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers,and highlights the future potential of similar therapies in the treatment of HCC.
文摘AIM: To investigate physicians' knowledge including chronic hepatitis B(CHB) diagnosis, screening, and management in various stages of their training.METHODS: A voluntary 20-question survey was administered in Santa Clara County, CA where Asian and Pacific Islanders(API) account for a third of the population. Among the 219 physician participants,there were 63 interns, 60 second-year residents, 26 chief residents and 70 attending physicians. The survey asked questions regarding respondents' demographics,general hepatitis B virus knowledge questions(i.e.,transmission, prevalence, diagnostic testing, prevention,and treatment options), as well as, self-reported practice behavior and confidence in knowledge.RESULTS: Knowledge about screening and managing patients with CHB was poor: only 24% identified the correct tests to screen for CHB, 13% knew the next steps for patients testing positive for CHB, 18% knew the high prevalence rate among API, and 31% knew how to screen for liver cancer. Wald chi-square analysis determined the effect of training level on knowledge; in all cases except for knowledge of liver cancer screening(p = 0.0032), knowledge did not significantly increase with length in residency training or completion of residency.CONCLUSION: Even in a high-risk region, both medical school and residency training have not adequatelyprepared physicians in the screening and management of CHB.
文摘AIM To evaluate maternal hepatitis B virus(HBV) DNA as risk for perinatal HBV infection among infants of HBVinfected women in California.METHODS Retrospective analysis among infants born to hepatitis B surface antigen(HBs Ag)-positive mothers who received post vaccination serologic testing(PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen(HBe Ag) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/ml,a 5:1 ratio of cases to controls and a two-sided confidence level of 95%.RESULTS A total of 17687 infants were born to HBs Ag positive mothers in California between Jan 1 2005 and Dec 31,2011. Among 11473 infants with PVST,only 125(1.1%) were found to be HBV infected. Among these infected infants,lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis(PEP) occurred in only 9 infants. However,PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBe Ag and HBV DNA level,case-control analysis found HBe Ag positivity(70.4% vs 28.9%,OR = 46.76,95%CI: 6.05-361.32,P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/ml(92.6% vs 18.5%,OR = 54.5,95%CI: 12.22-247.55,P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression,maternal HBV DNA level ≥ 2 × 107 IU/ml was the only significant independent predictor of perinatal HBV infection. CONCLUSION In California,transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/ml is associated with high risk of perinatal infection.
基金Supported by the Science and Technology Project of State Grid Corporation of China,No.SGHB0000AJJS1400182
文摘A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of druginduced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.
