Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan

BACKGROUND Little is known about the engagement in hepatitis C virus(HCV)care and completion of HCV treatment in people living with human immunodeficiency virus(HIV)(PLWH)who have HCV coinfection in the Asia-Pacific region.Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH.AIM To investigate the care cascade of incident HCV infections among PLWH in Taiwan.METHODS PLWH with incident HCV infections,defined as HCV seroconversion,were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018.All PLWH with incident HCV infections were followed until December 31,2019.The care cascade of HCV examined included all incident HCV-infected patients,the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care,plasma HCV RNA load tested,HCV RNA positivity diagnosed,referral to treatment assessment made,anti-HCV treatment initiated,and sustained virologic response achieved.Those who had HCV seroconversion during the interferon(IFN)era(2011–2016)and the direct-acting antiviral(DAA)era(2017–2018)were analyzed separately.The duration of HCV viremia—from the date of seroconversion to viral clearance by treatments or until the end of observation—and the incidence of sexually transmitted infections(STIs)during the HCV viremic period were estimated.RESULTS During the study period,287 of 3495(8.2%)PLWH(92.3%being men who have sex with men)who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples.Of the 287 incident HCV infections,277(96.5%)had anti-HCV antibodies detected by HIV-treating physicians,270(94.1%)had plasma HCV RNA determined and 251(87.5%)tested positive for HCV RNA.Of those with HCV viremia,226(78.7%)were referred to treatment assessment,215(74.9%)initiated anti-HCV treatment,and 202(70.4%)achieved viral clearance.Compared with that in the IFN era,the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era{179 d[interquartile range(IQR)87-434]vs 92 d(IQR 57-173);P<0.001}.The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up(PYFU)and 38.5 per 100 PYFU,respectively,with an incidence rate ratio of 1.31(95%confidence interval 0.96-1.77),while the duration of HCV viremia was 380 d(IQR 274-554)and 735 d(IQR 391-1447)(P<0.001),respectively.CONCLUSION While anti-HCV therapies are effective in achieving viral clearance,our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.

Laparoscopic treatment of perforated appendicitis

The use of laparoscopy has been established in improving perioperative and postoperative outcomes for patients with simple appendicitis. Laparoscopic appendectomy is associated with less wound pain, less wound infection, a shorter hospital stay, and faster overall recovery when compared to the open appendectomy for uncomplicated cases. In the past two decades, the use of laparoscopy for the treatment of perforated appendicitis to take the advantages of minimally invasiveness has increased. This article reviewed the prevalence, approaches, safety disclaimers, perioperative and postoperative outcomes of the laparoscopic appendectomy in the treatment of patients with perforated appendicitis. Special issues including the conversion, interval appendectomy, laparoscopic approach for elderly or obese patient are also discussed to define the role of laparoscopic treatment for patients with perforated appendicitis.

Prospective,randomized,and active controlled study of the efficacy of alginic acid and antacid in the treatment of patients with endoscopy-negative reflux disease

瞄准：与内视镜检查法否定的倒流疾病(ENRD ) 在病人与相等力量的解酸药(Nacid ) 相比加解酸药(Topaal ) 估计复合包含藻酸的功效和安全。方法：有 ENRD 的 121 个病人的一个总数被使随机化收到 Topaal (65 个病人) 或 Nacid (56 个病人) 6 个星期，与咨询每 3 个星期。主要端点评价是在在 6 个星期用视觉模拟规模(管) 评估了的心痛的严厉的变化。第二等的端点评价是在 3 个星期的 VAS，倒流症状的频率的变化，生命和不利效果的质量的变化。结果：除了 Topaal 组包括了更多的男性之外，在每个治疗组的使随机化的题目的人口分布是可比较的。在这些组之间的基线特征是类似的。在 6 星期治疗以后，心痛的管的减小在 Topaal 组(-6.29 厘米对 -4.11 厘米) 是更突出的。在第三个星期， Topaal 为心痛(P=0.0016 ) 组织管的显示出的更大的减小，流回(P=0.0006 ) ，呕吐(P=0.0373 ) ，并且打嗝(P【0.0001 ) 。Topaal 组的病人在 6 星期的治疗经期的结束有心痛(P=0.0015 ) 和疼痛(P=0.0163 ) 的低频率。从医生的观点， Topaal 组也在心痛(P=0.0020 ) 的严厉显示出重要减小，流回(P=0.0081 ) ，呕吐(P=0.0182 ) ，并且打嗝(P=0.0018 ) 在治疗的结束。生命的质量的改进在在 6 星期的治疗经期(P【0.0001 ) 的结束的 Topaal 组是更显著的。为不利效果，在两个没有差别这些组。结论：Topaal 是比为病人与 ENRD 介绍的症状的治疗的 Nacid 更有效的。

Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer

Pancreatic cancer is highly lethal. Current research that combines radiation with targeted therapy may dramatically improve prognosis. Cancerous cells are characterized by unstable genomes and activation of DNA repair pathways, which are indicated by increased phosphorylation of numerous factors, including H2 AX, ATM, ATR, Chk1, Chk2, DNA-PKcs, Rad51, and Ku70/Ku80 heterodimers. Radiotherapy causes DNA damage. Cancer cells can be made more sensitive to the effects of radiation(radiosensitization) through inhibition of DNA repair pathways. The synergistic effects, of two or more combined non-lethal treatments, led to coadministration of chemotherapy and radiosensitization in BRCA-defective cells and patients, with promising results. ATM/Chk2 and ATR/Chk1 pathways are principal regulators of cell cycle arrest, following DNA doublestrand or single-strand breaks. DNA double-stranded breaks activate DNA-dependent protein kinase, catalytic subunit(DNA-PKcs). It forms a holoenzyme with Ku70/Ku80 heterodimers, called DNA-PK, which catalyzes the joining of nonhomologous ends. This is the primary repair pathway utilized in human cells after exposure to ionizing radiation. Radiosensitization, induced by inhibitors of ATM, ATR, Chk1, Chk2, Wee1, PP2 A, or DNA-PK, has been demonstrated in preclinical pancreatic cancer studies. Clinical trials are underway. Development of agents that inhibit DNA repair pathways to be clinically used in combination with radiotherapy is warranted for the treatment of pancreatic cancer.

Management of early hepatic artery occlusion after liver transplantation with failed rescue

Hepatic artery thrombosis is a serious complication after liver transplantation which often results in biliary complications, early graft loss, and patient death. It is generally thought that early hepatic artery thrombosis without urgent re-vascularization or retransplantation almost always leads to mortality, especially if the hepatic artery thrombosis occurs within a few days after transplantation. This series presents 3 cases of early hepatic artery thrombosis after living donor liver transplantation, in which surgical or endovascular attempts at arterial re-vascularization failed. Unexpectedly, these 3 patients survived with acceptable graft function after 32 mo, 11 mo, and 4 mo follow-up, respectively. The literatures on factors affecting this devastating complication were reviewed from an anatomical perspective. The collective evidence from survivors indicated that modified nonsurgical management after liver transplantation with failed revascularization may be sufficient to prevent mortality from early hepatic artery occlusion. Re-transplantation may be reserved for selected patients with unrecovered graft function.

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.

Epigenetic states and expression of imprinted genes in human embryonic stem cells

AIM: To investigate the epigenetic states and expres- sion of imprinted genes in five human embryonic stem cell (hESC) lines derived in Taiwan. METHODS: The heterozygous alleles of single nucleo- tide polymorphisms (SNPs) at imprinted genes were analyzed by sequencing genomic DNAs of hESC lines and the monoallelic expression of the imprinted genes were confirmed by sequencing the cDNAs. The expres- sion profiles of 32 known imprinted genes of five hESC lines were determined using Affymetrix human genome U133 plus 2.0 DNA microarray. RESULTS: The heterozygous alleles of SNPs at seven imprinted genes, IPW , PEG10 , NESP55 , KCNQ1 , ATP10A ,TCEB3C and IGF2 , were identified and the monoallelic expression of these imprinted genes except IGF2 were confirmed. The IGF2 gene was found to be imprinted in hESC line T2 but partially imprinted in line T3 and not imprinted in line T4 embryoid bodies. Ten imprinted genes, namely GRB10 , PEG10 , SGCE, MEST , SDHD , SN- RPN , SNURF , NDN , IPW and NESP55 , were found to be highly expressed in the undifferentiated hESC lines and down-regulated in differentiated derivatives. The UBE3A gene abundantly expressed in undifferentiated hESC lines and further up-regulated in differentiated tissues. The expression levels of other 21 imprinted genes were relatively low in undifferentiated hESC lines and five of these genes (TP73 , COPG2 , OSBPL5 , IGF2 and ATP10A ) were found to be up-regulated in differentiated tissues. CONCLUSION: The epigenetic states and expression of imprinted genes in hESC lines should be thoroughly studied after extended culture and upon differentiation in order to understand epigenetic stability in hESC lines before their clinical applications.

A new prognostic histopathologic classification of nasopharyngeal carcinoma

Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.

Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

AIM: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori(H pylori)-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT lymphoma.METHODS: Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less after H pylorieradication were classified as H pyloridependent; others were classified as H pylori-independent.The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry.RESULTS: There were 16 H pylori-dependent and 10H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 Hpyiori-dependent cases but in none of 10 Hpylori-independent cases (P = 0.001).H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8±1.4% vs 1.1±0.8%; P = 0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+)NK cells compared to CD86-negative cases (2.9±1.1% vs1.4±1.3%; P= 0.005).CONCLUSION: These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT lymphomas.

Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

Sorafenib is the current standard treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However,efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2,hepatocyte growth factor,insulin-like growth factor-1,and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response,dynamic contrast-enhanced magnetic resonance imaging,and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC.

Pathophysiological mechanisms of death resistance in colorectal carcinoma

Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks ofunlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contri-butes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways(i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

Effects of Helicobacter pylori infection in gastrointestinal tract malignant diseases:From the oral cavity to rectum

Helicobacter pylori(H.pylori)has infected approximately fifty percent of humans for a long period of time.However,improvements in the public health environment have led to a decreased chance of H.pylori infection.However,a high infection rate is noted in populations with a high incidence rate of gastric cancer(GC).The worldwide fraction of GC attributable to H.pylori is greater than 85%,and a high H.pylori prevalence is noted in gastric mucosa-associated lymphoid tissue lymphoma patients.These results indicate that the majority of GC cases can be prevented if H.pylori infection is eliminated.Because H.pylori exhibits oral-oral or fecal-oral transmission,the relationship between this microorganism and other digestive tract malignant diseases has also attracted attention.This review article provides an overview of H.pylori and the condition of the whole gastrointestinal tract environment to further understand the correlation between the pathogen and the host,thus allowing improved realization of disease presentation.

Evaluation of myocardial infarction patients after coronary revasculation by dual-phase multi-detector computed tomography:Now and in future

Multidetector-row computed tomography(MDCT) has become one of the major tools in diagnosing and evaluating patients with coronary artery disease in recent years.In selected patients,MDCT has been shown to provide more reliable accuracy in detection of stent patency than invasive coronary angiography.Chiou et al reported a delicate infarcted myocardium at-risk score.According to their results,the MDCT-based myocardium at-risk score had a good correlation with the thallium 201 ST-segment elevation myocardial infarction-based summed difference score(r = 0.841,P < 0.001).They claimed that dual-phase MDCT is useful in detecting different patterns of obstructive lesions and the extent of myocardium at risk.In this commentary,we discuss the current status of the clinical application of MDCT in patients with myocardial infarction in relation to evaluating the myocardial perfusion defect,detecting reversible myocardial ischemia,assessing myocardial viability,estimating target lesion restenosis,and calculating of fractional flow reserve from MDCT.

Hypofractionated particle beam therapy for hepatocellular carcinoma–a brief review of clinical effectiveness

Hepatocellular carcinoma(HCC)is the fifth most common malignancy and the second leading cause of cancer mortality worldwide.The cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local treatment.Although radiotherapy has not been considered a preferred treatment modality for HCC,charged particle therapy(CPT),including proton beam therapy(PBT)and carbon ion radiotherapy(CIRT),possesses advantages(for example,it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation)and has emerged as an alternative treatment option for HCC.With the technological advancements in CPT,various radiation dosages of CPT have been used for HCC treatment via CPT.However,the efficacy and safety of the evolving dosages remain uncertain.To assess the association between locoregional control of HCC and the dose and regimen of CPT,we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical outcomes.Overall,CPT provides a better local control rate compared with photon beam therapy,ranging from 80%to 96%,and a 3-year overall survival ranging from 50%to 75%,and it results in rare grade 3 toxicities of the late gastrointestinal tract(including radiation-induced liver disease).Regarding CPT for the treatment of locoregional HCC,conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary tract.In contrast,the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.

Secular decreasing trends in gastric cancer incidence in Taiwan:A population-based cancer registry study

BACKGROUND Gastric cancer remains a leading cause of cancer death worldwide.In Taiwan,gastric cancer is the sixth leading cause of cancer mortality in both males and females.AIM To evaluate secular trends in gastric cancer incidence according to age,sex,and Helicobacter pylori(H.pylori)treatment in Taiwan.METHODS In this population-based study,we used the national Taiwan Cancer Registry database.Annual percent changes in incidence rates were used to describe secular trends in incidence rates and sex ratios of gastric cancer in Taiwan.Pearson’s product-moment correlation coefficients were used to analyze the correlation between annual age-adjusted incidence rates and the annual number of patients treated with antibiotic therapy for H.pylori infection.RESULTS The annual percent changes showed continuously decreasing rates of gastric cancer among both males and females.However,the decreasing trends differed by sex,with an annual percent change of-2.58%in males and-2.14%in females.The age-specific incidence rates increased with age.Within the same age group,more recent time periods showed lower incidence rates than greater time periods.Similarly,the sex ratio was lower in later birth cohorts than in earlier birth cohorts.Age-adjusted incidence rates substantially decreased with increasing numbers of patients being treated with antibiotic therapy for H.pylori infection during 2005 to 2016(r=0.72).CONCLUSION We observed steadily decreasing trends with differential sex ratios in the incidence of gastric cancer in Taiwan.These results support H.pylori eradication programs in Taiwan.

Reappraisal of surgical decision-making in patients with splenic sclerosing angiomatoid nodular transformation:Case series and literature review

BACKGROUND Many clinicians and surgeons are unfamiliar with the sclerosing angiomatoid nodular transformation(SANT),which is gaining recognition as a benign splenic tumor.We challenge that SANT is rare and whether surgical intervention could be avoided through critical imaging review.AIM To evaluate the incidence of SANT among splenic tumors and the decisionmaking process of SANT management.METHODS Twenty hospitalized patients who underwent splenectomy in 2018 and 2019 in a tertiary university hospital were retrospectively reviewed,and their data on imaging,diagnosis,surgical indications,and courses were recorded.All pathology results were confirmed by pathologist.Discriminative features differentiating SANT from other non-SANT splenic tumors were descriptively analyzed in this case series.RESULTS Fourteen out of 20 patients who underwent splenectomy had splenic tumors,including 3 SANTs(21%splenic tumors),6 non-SANT benign lesions(43%),2 metastatic tumors,and 3 lymphomas.Hypointensity on T2-weighted magnetic resonance imaging(MRI),spoke wheel enhancing pattern in contrasted computed tomography or MRI,and cold spot(low fluorodeoxyglucose uptake)in positron emission tomography(PET)scan helped establish the diagnosis of SANT.Lymphoma,presenting with a hot spot on the PET scan were differentiated from SANT.Surgical indications were reformatted for splenic tumors.Splenectomy need not be performed in patients with typical imaging features of SANT.CONCLUSION SANT is not a rare disease entity in clinical practice.Splenectomy should not be routinely indicated as the only management option for SANT with typical imaging features.

Real-world effectiveness of direct-acting antivirals in people living with human immunodeficiency virus and hepatitis C virus genotype 6 infections

BACKGROUND Hepatitis C virus(HCV)genotype 6(HCV-6)infection is prevalent predominantly in Southeast Asia,and the data on the virologic response of HCV-6 to direct-acting antivirals(DAAs)are sparse in people living with human immunodeficiency virus(HIV)(PLWH).AIM To assess the virologic response of HCV-6 to DAAs in PLWH.METHODS From September 2016 to July 2019,PLWH coinfected with HCV-6 initiating DAAs were included.Laboratory investigations were performed at baseline,the end of treatment,and 12 wk off-therapy.RESULTS Of the 349 PLWH included(mean age 48.9 years,82.5%men),80.5%comprised people who inject drugs,18.1%men who have sex with men,and 1.4%heterosexuals.Coexistent hepatitis B virus infection was present in 12.3%of the included PLWH,liver cirrhosis 10.9%,hepatocellular carcinoma 0.9%,and previous HCV treatment experience 10.9%.The mean baseline plasma HCV RNA was 6.2 log10 IU/m L.Treatment with glecaprevir/pibrentasvir was initiated in 51.9%,sofosbuvir/ledipasvir 41.5%,sofosbuvir/velpatasvir 6.3%,and sofosbuvir/daclatasvir 0.3%.At DAA initiation,antiretroviral therapy containing tenofovir alafenamide was given in 26.4%,tenofovir disoproxil fumarate 34.4%,non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%,non-nucleoside reverse-transcriptase inhibitors 30.4%,protease inhibitors 4.0%,and integrase strand transfer inhibitors 66.8%;94.8%of the included patients had CD4 counts≥200 cells/mm3 and 96.0%had plasma HIV RNA<50 copies/m L.Overall,96.8%achieved undetectable plasma HCV RNA(<30 IU/m L)at end of treatment;and 92.3%achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis(93.5%in patients receiving sofosbuvir-based DAAs and 91.2%in those receiving glecaprevir/pibrentasvir).CONCLUSION Similar to the observation made in HIV-negative patients,sustained virologic response 12 wk offtherapy with DAAs is high in PLWH coinfected with HCV-6.

H1-antihistamine use and head and neck cancer risk in type 2 diabetes mellitus

This study aimed to examine the association between the use of H1-antihistamines(AHs)and head and neck cancer(HNC)risk in patients with type 2 diabetes mellitus(T2DM).Data from the National Health Insurance Research Database of Taiwan were analyzed for the period from 2008 to 2018.A propensity-score-matched cohort of 54,384 patients each in the AH user and nonuser groups was created and analyzed using Kaplan-Meier method and Cox proportional hazards regression.The results showed that the risk of HNC was significantly lower in AH users(adjusted hazard ratio:0.55,95%CI:0.48 to 0.64)and the incidence rate was also lower(5.16 vs.8.10 per 100,000 person-years).The lower HNC incidence rate in AH users(95%CI:0.63;0.55 to 0.73)suggests that AH use may reduce the risk of HNC in T2DM patients.

亚太地区慢性乙型肝炎治疗共识(2012最新版)

自2008年至今,有大量关于慢性HBV感染的自然史和治疗的最新数据不断涌现。其中包括慢性HBV感染的无症状感染者,以社区为基础的队列研究,HBV基因型的作用,非药物诱导的自然HBV变异型毒株,无创性肝纤维化评估方法的应用,HBsAg定量在临床中的应用,更有效的新治疗药物和新治疗方案等等。来自亚太地区的专家审查和评估了相关数据,并共同商讨了近年来报道的最有意义的发现,基于此,对2008年版的亚太地区慢性乙型肝炎治疗共识进行修订,同时对2008年版治疗指南定义的关键词组进行了修订。修订后的指南包括以下几方面内容:一般治疗,肝纤维化评价适应证,何时开始治疗或停药,初始抗病毒治疗药物的选择,如何监测治疗中和治疗后的患者。关于特殊人群的治疗建议中包括了对妊娠妇女,已发生耐药,合并其他病毒感染,肝功能失代偿,接受免疫抑制治疗、化疗,肝移植或肝细胞癌患者的具体治疗建议。

Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

Hepatitis B virus(HBV)infection is a leading cause of chronic hepatitis,liver cirrhosis,and hepatocellular carcinoma worldwide.Due to the shared modes of transmission,coinfection with HBV and human immunodeficiency virus(HIV)is not uncommon.It is estimatedthat 10%of HIV-infected patients worldwide are coinfected with HBV.In areas where an HBV vaccination program is implemented,the HBV seroprevalence has declined significantly.In HIV/HBV-coinfected patients,HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy(cART)is initiated,while HIV infection increases the risk of hepatitis events,cirrhosis,and end-stage liver disease related to chronic HBV infection.With the advances in antiviral therapy,concurrent,successful longterm suppression of HIV and HBV replication can be achieved in the cART era.To reduce the disease burden of HBV infection among HIV-infected patients,adoption of safe sex practices,avoidance of sharing needles and diluent,HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches.However,due to HIV-related immunosuppression,using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.