Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda

Gastric cystica profunda(GCP)is an uncommon but underestimated gastric lesion.Its precancerous potential determines its significance.In addition to previous mucosa injury due to operations,biopsy or polypectomy,chronic active and atrophic gastritis may also lead to the development of GCPs.By carefully examining the stomach and taking biopsy samples from the susceptible regions,the stage of atrophy can be determined.Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation.GCPs frequently occur close to early gastric cancers(EGCs)or EGC can arise from the cystic glands.Endoscopic resection is an effective and minimally invasive treat-ment in GCP.

Chronic active Epstein-Barr virus infection treated with PEGaspargase: A case report

BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV(CAEBV),and hematopoietic stem cell transplantation is the only effective treatment.We here report a CAEBV patient treated with PEG-aspargase,who achieved negative EBV-DNA.CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017.EBV-DNA was positive with a high copy number.She was diagnosed with chronic active EB virus infection.PEGaspargase was administered at a dose of 1500 U/m2 at a 14-d interval,resulting in eradication of EBV for more than 6 mo.The effect of PEG-aspargase in this patient was excellent.CONCLUSION A chemotherapy regimen containing PEG-aspargase for CAEBV may be further considered.

Chronic Active Epstein–Barr Virus Infection

Chronic active Epstein-Barr virus(CAEBV)infection is a systemic Epstein–Barr virus(EBV)positive lymphoprolifetative disease characterized by fever,lymphadenopathy,splenomegaly,unusual pattern of antiEBV antibodies,and/or increased EBV genomes in affected tissues.Most cases are from Asia.So far,there is hardly any adult case reported from mainland of China.We herein presented a 33-year-old man with fever,facial erythema and rash,lymphadenopathy,lower limbs weakness,splenomegaly and liver lesion.EBV VCA,EA and EBNA were all positive.EBV DNA could be found in serum and PBMC.In situ hybridization of EBV encoded RNA in skin and liver biopsy was positive.Viral load in serum decreased under interferon alpha therapy.To our knowledge,it’s the first adult case reported from mainland of China.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.

Clinical analysis and follow-up study of chronic active Epstein-Barr virus infection in 53 pediatric cases

Background Chronic active Epstein-Barr virus infection （CAEBV） has been previously reported to be sometimes associated with an aggressive clinical course. The characteristics of CAEBV in Mainland Chinese pediatric patients are largely unreported. The main aims of this survey were to recognize the clinical features of CAEBV in children and to explore its diagnostic criteria and risk factors. Methods A retrospective study was performed on 53 pediatric patients （36 boys and 17 girls） with CAEBV who were admitted to Beijing Children＇s Hospital between 2003 and 2007. All their medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory data and outcome were collected. Independent-samples t test was used for statistical analysis. Results The age at onset of CAEBV was from 2 months to 14.6 years （mean （5.3_＋3.3） years）. At the time of onset, 43.4% patients had an infectious mononucleosis-like symptom. Most patients exhibited intermittent fever （92.5%, 49/53）, hepatomegaly （81.1%, 43/53） and splenomegaly （77.4%, 41/53）. Life-threatening complications including hemophagocytic syndrome （24.5%,13/53）, interstitial pneumonia （24.5%, 13/53）, hepatic failure （15.1%, 8/53） and malignant lymphoma （11.3%, 6/53） were also observed. The serum EBV DNA level in 23 patients with CAEBV was in the range of 5.05×10^2-4.60×10^6 copies/ml with a mean value of 103.7 copies/ml. Many patients with CAEBV generally had continuous symptoms during the observational period. Eleven out of 42 patients （26.2%） died 7 months to 3 years after onset. Deceased patients were more likely to have had lower platelet counts and albumin levels than the living patients （P 〈0.05 for all comparisons）. Conclusions The study reveals that CAEBV in Chinese pediatric patients has a severe clinical course and prognosis is poor. Thrombocytopenia and decreases in albumin might potentially be risk factors for a poor prognosis. EBV loads should be measured and tissue should be stained on hybridization probes for EBV-encoded small RNA （EBER） if a patient presents with the known symptoms of CAEBV.

Haploidentical hematopoietic stem cell transplantation for pediatric patients with chronic active Epstein-Barr virus infection:a retrospective analysis of a single center

Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr virus infection(CAEBV).Methods Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital,Capital Medical University,from October 2016 to June 2020 were analyzed retrospectively.Data relating to the clinical manifestations,engraftment,and prognosis of the children were extracted from medical records.Results Twenty-five patients,including 16 males and 9 females,with an onset age of 5.0±2.6 years and a transplantation age of 6.9±2.9 years,were enrolled irnhis study.The mean time from diagnosis to transplantation was 3.8(2.0-40.2)months.The mean observation time was 19.0±12.0 months.Three patients received the reduced intensity conditioning regimen,and the remaining patients all received the modified myeloablative conditioning regimen.By the end of the follow-up,23 patients were characterized by disease-free survival(DFS),22 were characterized by event-free survival(EFS).and two died.One of the patients died of thrombotic microangiopathy(TMA),and another died of graft versus host disease(GVHD);this patient discontinued the treatment for economic reasons.The 3-year overall survival(OS)rate was estimated to be 92.0%±5.4%,and the 3-year EFS rate was estimated to be 87.4%±6.8%.All active patients survived after HSCT event-free.Acute GVHD degrees 1-3 were observed in ten patients(40.0%),and degree IV was observed in six(24.0%),who were all cured except for one patient.Chronic GVHD was observed in nine(36.0%),and most of these cases were mild.The incidence of TMA and veno-occlusive disease(VOD)was 28.0%and 4.0%.Conclusions Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation.Patients with active disease before HSCT also benefited from haplo-HSCT.Haplo-HSCT requires careful monitoring for complications,such as GVHD and TMA.Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.

Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein–Barr virus infection

Importance:Allogeneic hematopoietic stem cell transplantation(alloHSCT)is considered the only effective treatment for chronic active Epstein–Barr virus infection(CAEBV).The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear.Objective:To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning(MAC)regimen for children with CAEBV and also the factors affecting the outcomes.Methods:We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children’s Hospital,Capital Medical University from October 2016 to June 2021.Data related to the clinical manifestations,engraftment,and outcome were extracted from the medical records.Results:The cohort comprised 41 patients(24 males,17 females)with a median transplantation age of 92.6(60.4,120.7)months and a median follow-up time of 28.2(15.3,40.2)months.Four patients(9.8%)died,among which three died from primary disease relapse,and one died from grade IV acute graft-versus-host diseases(aGVHD)after stopping treatment.The 3-year overall survival(OS)and 3-year event-free survival(EFS)rates were 88.8%±5.4%and 85.0%±5.7%,respectively.The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis(HLH)and the patient without HLH(87.7%±6.8%vs.91.7%±8.0%,P=0.790;85.0%±6.9%vs.84.6%±10.0%,P=0.921),or among the patients with complete remission,partial remission,and activity disease before HSCT(all P>0.05).Multivariate analysis showed that grade III–IV aGVHD was a risk factor for mortality(Hazards ratio:11.65,95%confidence interval:1.00,136.06;P=0.050).Interpretation:Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV.This treatment benefits patients with HLH or active disease.Patients with Grade III–IV aGVHD may be associated with worse outcomes.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

Epstein-Barr virus:Silent companion or causative agent of chronic liver disease?

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.

Natural killer/T-cell lymphoma with intracranial infiltration and Epstein-Barr virus infection: A case report

BACKGROUND Because of atypical clinical symptoms,lymphoma is easily confused with infectious diseases.Extranodal nasal-type natural killer/T-cell lymphoma(NKTL)is more common,and there are few cases of eyelid site onset and intracranial infiltration,which increases the difficulty of diagnosis.This disease usually has a very poor prognosis and there are few reports of recovery.CASE SUMMARY A 3-year-old boy was admitted to our hospital due to an initial misdiagnosis of"eyelid cellulitis"and failed antibiotic treatment.He was characterized by fever,right eyeball bulging,convulsions,and abnormal liver function.His blood Epstein-Barr virus(EBV)DNA was positive(8.798×10^4 copies/mL),and remained positive for about half a year.The cranial imaging examination suggested a space-occupying lesion in the right eyelid,with the right temporal lobe and meninges involved.The boy underwent ocular mass resection.The pathological diagnosis was NKTL.He was diagnosed as having NKTL with intracranial infiltration,combined with chronic active EBV infection(CAEBV).Then he underwent systemic chemotherapy and intrathecal injection.The boy suffered from abnormal blood coagulation,oral mucositis,diarrhea,liver damage,and severe bone marrow suppression but survived.Finally,the tumor was completely relieved and his blood EBV-DNA level turned negative.The current follow-up has been more than 2 years and his condition is stable.CONCLUSION This case suggests that chemotherapy combined with intrathecal injection may have a good effect on intracranial infiltrating lymphoma and CAEBV,which deserves further study and discussion.

Efficacy observation of Yiguanjian decoction combined adefovir Dipivoxil tablet in treating HBeAg negative chronic viral hepatitis B active compensated liver cirrhosis patients

Objective To explore clinical efficacy of Yiguanjian Decoction(YD)combined Adefovir Dipivoxil Tablet(ADT)in treating HBe Ag negative chronic viral hepatitis B(CVHB)active compensated liver cirrhosis(LC)patients.Methods Totally 68 HBe Ag negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group

PLATELET ACTIVATION IN PATIENTS WITH CHRONIC PULMONARY HEART DISEASE EFFECT OF DIPYRIDAMOLE TREATMENT

Plasma levels of /f-thromboglobulin (/?-TG), platelet fac-tor 4(P and platelet aggregation rate (PAR) were measured in remission phase of 15 patients affected with chronic pulmonary heart disease (CPHD). 0-TG, /?-TG / PF4, PF4 and PAR were significantly higher in the patients than in controls (/3<0.01 and 0.05, respectively). After 10 days of treatment with Dipyridamole lOOtng tid, fi-TG, /?-TG / PF4 and PF4 decreased significantly compared with pretreatment values (/><0.01 and 0.05, respectively). The results suggest that in vivo platelet activation is indeed present in patients with CPHD and that dipyridamole can antagonize platelet activation in vivo.

Alanine Aminotransferase as the First Test Parameter for Wilson's Disease

Background and Aims: The liver is the first organ affected by toxic copper in the classical and severe hepatic forms of Wilson's disease(WD).Because their associated chronic liver damage is mostly asymptomatic,an intervention using a special test including serum alanine aminotransferase(ALT)activity is needed for detecting WD.Methods: Using the modified international criteria for the diagnosis of WD,45 patients were selected from the collective databases of our institutions,and 7 infants were reviewed from the literature.Two patients had the severe hepatic form,with nor-moceruloplasminemia and no mutations in ATP7B.The rapid ALT change during hemolytic anemia was adjusted for a baseline.The diagnostic potential of the ALT test was assessed from the age-dependent natural course of the liver damage of WD.Results: The natural course had three stages.ALTs were still low in some infants younger than 4 years-old.They were high in all children between the ages of 4 and 8 years-old;then,they reduced to low levels in some patients over 9 years of age.The high ALT stage represents chronic active hepatitis,and the sub-sequent low ALT stage is due to silent cirrhosis.The hepatic cop-per content is a reliable but invasive test,while urinary copper secretion is an alternative,non-invasive test for copper toxicosis of WD.The serum ceruloplasmin and ATP7B analyses are sub-type tests of WD.The response to anti-copper regimens is the final test result.Conclusions: ALTcould be the first parameter to test to detect WD in children between the ages of 4 and 8 years.