Roles and application of exosomes in the development,diagnosis and treatment of gastric cancer

As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.

Early endoscopic management of an infected acute necrotic collection misdiagnosed as a pancreatic pseudocyst: A case report

BACKGROUND Infected acute necrotic collection(ANC)is a fatal complication of acute pancre-atitis with substantial morbidity and mortality.Drainage plays an exceedingly important role as the first step in invasive intervention for infected necrosis;however,there is great controversy about the optimal drainage time,and better treatment should be explored.CASE SUMMARY We report the case of a 43-year-old man who was admitted to the hospital with severe intake reduction due to early satiety 2 wk after treatment for acute pancre-atitis;conservative treatment was ineffective,and a pancreatic pseudocyst was suspected on contrast-enhanced computed tomography(CT).Endoscopic ultra-sonography(EUS)suggested hyperechoic necrotic tissue within the cyst cavity.The wall was not completely mature,and the culture of the puncture fluid was positive for A-haemolytic Streptococcus.Thus,the final diagnosis of ANC in-fection was made.The necrotic collection was not walled off and contained many solid components;therefore,the patient underwent EUS-guided aspiration and lavage.Two weeks after the collection was completely encapsulated,pancreatic duct stent drainage via endoscopic retrograde cholangiopancreatography(ERCP)was performed,and the patient was subsequently successfully discharged.On repeat CT,the pancreatic cysts had almost disappeared during the 6-month fo-llow-up period after surgery.CONCLUSION Early EUS-guided aspiration and lavage combined with late ERCP catheter drainage may be effective methods for intervention in infected ANCs.

Research Progress of Atrial Fibrillation Detection Technology

Atrial fibrillation (AF) is the most common chronic arrhythmia in clinical practice, which can cause high disability and mortality with the progress of the disease. Many studies at home and abroad have shown that the incidence of atrial fibrillation gradually increases with age. Clinically, the onset of most AF patients is insidious, which is difficult to capture by routine electrocardiogram, and there is some difficulty in the diagnosis. In order to make the early diagnosis of atrial fibrillation more efficient and accurate, this paper reviews the current status and research progress of detection technology for atrial fibrillation at home and abroad, in order to provide a scientific basis for the early diagnosis of atrial fibrillation.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity:Insights from national inpatient sample 2020

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(COVID-19)hospitalizations with varied obesity levels is scarce.Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.AIM To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.METHODS COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease-10 CM codes in the 2020 National Inpatient Sample database.Overweight and Obesity Classes Ⅰ,Ⅱ,and Ⅲ(body mass index 30-40)were compared.Major adverse cardiac and cerebrovascular events(MACCE)(all-cause mortality,acute myocardial infarction,cardiac arrest,and stroke)were compared between groups.Multivariable regression analyses adjusted for sociodemographic,hospitalization features,and comorbidities.RESULTS Our analysis comprised 13260 hospitalizations,7.3% of which were overweight,24.3% Class Ⅰ,24.1% Class Ⅱ,and 44.3% Class Ⅲ.Class Ⅲ obesity includes younger patients,blacks,females,diabetics,and hypertensive patients.On multivariable logistic analysis,Class Ⅲ obese patients had higher risks of MACCE,inpatient mortality,and respiratory failure than Class Ⅰ obese patients.Class Ⅱ obesity showed increased risks of MACCE,inpatient mortality,and respiratory failure than Class I,but not significantly.All obesity classes had non-significant risks of MACCE,inpatient mortality,and respiratory failure compared to the overweight group.CONCLUSION Class Ⅲ obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class Ⅰ.Using the overweight group as the reference,unfavorable outcomes were not significantly different.Morbid obesity had a greater risk of MACCE regardless of the referent group(overweight or Class Ⅰ obese)compared to overweight NAFLD patients admitted with COVID-19.

Effects of ethanol and sex on propionate metabolism evaluated via a faster ^(13)C-propionate breath test in rats

BACKGROUND Alcoholism is regarded as a risk factor for vitamin B_(12)(VB_(12))deficiency.Because V B_(12) serves as a coenzyme of methylmalonyl-CoA mutase,a key enzyme in propionate metabolism,the ^(13)C-propionate breath test(PBT)has been studied as a non-invasive diagnostic modality for VB_(12) deficiency.However,the conventional PBT requires 2 h,which is inconvenient in clinical practice.We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice.AIM To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats(ERs).METHODS ERs were obtained by replacing standard drinking water(for control rats,CRs)with 16%ethanol solution in descendants of F344/DuCrj rats.Faster PBT was performed by administering ^(13)C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach;exhaled gas was collected in a bag to measure its ^(13)CO_(2)/12CO_(2) isotope ratio via infrared isotope spectrometry.Serum VB_(12) and alanine transaminase(ALT)levels were measured via chemiluminescence immunoassay and the lactate dehydrogenaseultraviolet method,respectively.We evaluated statistical differences in mean body weight,change in ^(13)CO_(2)(Δ^(13)CO_(2)‰),peakΔ^(13)CO_(2)‰,and serum VB_(12) and ALT,between males and females and between ERs and CRs using the t-test and Mann-Whitney U test for normally and non-normally distributed variables,respectively.RESULTS Males weighed significantly more than females(P<0.001);CRs weighed significantly more than ERs(P<0.008).Δ^(13)CO_(2) reached a peak(C_(max))at 20 min and 30 min in females and males,respectively,decreasing after 20-30 min without rebound in all groups.Males had significantly higher C_(max) andΔ^(13)CO_(2) at 15-45 min than females(P<0.05;for all pairs).Propionate metabolism was enhanced in male ERs relative to male CRs,whereas metabolism did not differ markedly between ERs and CRs for females.Males had higher serum VB_(12) levels than females,without prominent differences between the ER and CR groups.Male CRs had notably higher ALT levels than male ERs.Thus,chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition.CONCLUSION Faster PBT shows that 16%ethanol consumption promotes propionate metabolism without inducing liver injury.This PBT may be used clinically to evaluate gut flora status.

Biochemical indicators and the Peradeniya Organophosphate Poisoning scale in prediction and prognosis of organophosphorus poisoning:An observational prospective study

Objective:To study the value of some biochemical indicators and Peradeniya Organophosphate Poisoning scale in prediction and prognosis of organophosphorus poisoning.Methods:This was a hospital-based prospective,observational study.Various biochemical tests viz.complete blood count,random blood sugar,liver and renal function tests,creatine phosphokinase,and electrolytes were performed.Patients were assessed based on the Peradeniya Organophosphate Poisoning scale.All the patients were followed till the end point like recovery/death.Results:Out of the 100 patients,72%were males and 28%were females.The majority of the patients were farmers and 21 to 30 years of age.Suicidal was the most common manner(92,92%).Based on the Peradeniya Organophosphate Poisoning scale,47%were mild,34%moderate,and 19%severe.Serum creatinine,creatine phosphokinase,serum glutamic-oxaloacetic transaminase,serum glutamic pyruvic transaminase,and alkaline phosphatase levels showed a significant correlation with severity.Conclusions:Some biochemical indicators such as creatine phosphokinase,alkaline phosphatase can be used as prognostic markers of organophosphorus poisoning.The Peradeniya Organophosphate Poisoning scale can be used for assessing severity of the poisoning.

Diagnosis and treatment of post-cholecystectomy diarrhoea

The incidence of cholecystitis is relatively high in developed countries and may usually be attributed to gallstones,the treatment for which involves complete surgical removal of the gallbladder(cholecystectomy).Bile acids produced following cholecystectomy continue to flow into the duodenum but are poorly absorbed by the colon.Excessive bile acids in the colon stimulate mucosal secretion of water and electrolytes leading,in severe cases,to diarrhoea.Bile acid diarrhoea(BAD)is difficult to diagnose,requiring a comprehensive medical history and physical examination in combination with laboratory evaluation.The current work reviews the diagnosis and treatment of BAD following chole-cystectomy.

Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome with dilated cardiomyopathy: A case report

BACKGROUND Polyneuropathy,organomegaly,endocrinopathy,M-protein,skin changes(POEMS)syndrome is a rare paraneoplastic syndrome that encompass multiple systems.The most common clinical symptoms of POEMS syndrome are pro-gressive sensorimotor polyneuropathy,organ enlargement,endocrine disorders,darkening skin,a monoclonal plasma cell proliferative disorder,and lymph node hyperplasia.The organomegaly consists of hepatosplenomegaly and/or lym-phadenopathy;cases of cardiomyopathy are rare.Diagnoses are often delayed because of the atypical nature of the syndrome,exposing patients to possibly severe disability.Therefore,identifying atypical symptoms can improve the prognosis and quality of life among POEMS syndrome patients.lenalidomide and dexamethasone.CONCLUSION When patients with cardiomyopathy have systemic manifestations such as numb limbs and darkening skin,the POEMS syndrome is the most possible diagnosis.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.

Spread of human immunodeficiency virus 1 among men who have sex with men is emerging as a genuine social concern and affecting the general populace- case reports from Eastern India

Human immunodeficiency virus(HIV) infection among men who have sex with men(MSM) has increased to a drastic proportion throughout India in the last couple of years due to a lack of productive identification and management framework. In apprehension of social disgrace these men attempt to live a normal hetero conjugal life and, in the process, act as a bridge in spreading the virus to their women partners. In this case report we have highlighted two cases which clearly distinguished the adequacy of HIV treatment among MSM when they are diagnosed during early or late phases of infection. An intensive and ample counseling to comprehend the psychology and sexual behavior of these men was found to be critically important in both the cases. Our study, which is actually the first of its kind, recorded and documented evidence of HIV infected MSM from Eastern India and renders a ray of hope among this marginally isolated group to comprehend the challenges and health risks faced by the MSM population. It also provides a format for the medical practitioners here in managing and treating related cases.

Prevalence of linked angina and gastroesophageal reflux disease in general practice

AIM: To evaluate the association between gastroesophageal re? ux diseases (GERD) and coronary heart diseases. METHODS: One thousand nine hundred and seventy consecutive patients who attended our hospital were enrolled. All of the patients who first attend our hospital were asked to respond to the F-scale questionnaire regardless of their chief complaints. All patients had a careful history taken, and resting echocardiography (ECG) was performed by physicians if the diagnostic necessity arose. Patients with ECG signs of coronary artery ischemia were defined as STsegment depression based on the Minnesota code. RESULTS: Among 712 patients (36%) with GERD, ECG was performed in 171 (24%), and ischemic changes were detected in eight (5%). Four (50%) of these patients with abnormal findings upon ECG had no chest symptoms such as chest pain, chest oppression, or palpitations. These patients (0.6%; 4/712) were thought to have non-GERD heartburn, which may be related to ischemic heart disease. Of 281 patients who underwent ECG and did not have GERD symptoms, 20 (7%) had abnormal findings upon ECG. In patients with GERD symptoms and ECG signs of coronary artery ischemia, the prevalence of linked angina was considered to be 0.4% (8/1970 patients).CONCLUSION: The present study suggested that ischemic heart disease might be found although a patient was referred to the hospital with a complaint of GERD symptoms. Physicians have to be concerned about missing clinically important coronary artery disease while evaluating patients for GERD symptoms.

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease(MAFLD).AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index(APRI),fibrosis-4 index(FIB-4),body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes score(BARD),and nonalcoholic fatty liver disease fibrosis score(NFS)in patients with MAFLD.METHODS Consecutive patients with histologically confirmed MAFLD were included.The discrimination ability of different non-invasive scores was compared.RESULTS A total of 417 patients were included;156(37.4%)of them had advanced fibrosis(Metavir≥F3).The area under receiver operating characteristic curve of FIB-4,NFS,APRI,and BARD for predicting advanced fibrosis was 0.736,0.724,0.671,and 0.609,respectively.The area under receiver operating characteristic curve of FIB-4 and NFS was similar(P=0.523),while the difference between FIB-4 and APRI(P=0.001)and FIB-4 and BARD(P<0.001)was statistically significant.The best thresholds of FIB-4,NFS,APRI,and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05,-2.1,0.42,and 2.A subgroup analysis showed that FIB-4,APRI,and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group.CONCLUSION APRI and BARD scores do not perform well in MAFLD.The FIB-4 and NFS could be more useful,but a new threshold is needed.Novel non-invasive scoring systems for fibrosis are required for MAFLD.

Diagnosis of follicular lymphoma of the gastrointestinaltract:A better initial diagnostic workup

Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis.

Fine needle aspiration diagnosis of isolated pancreatic tuberculosis: A case report

Tuberculosis(TB) involving the pancreas are uncommon, especially when present in immunocompetent hosts. Pancreatic TB is more frequently associated with miliary TB or widely disseminated disease. Pancreatic TB may present as cystic or solid pancreatic masses, pancreatic abscess or acute or chronic pancreatitis. Majority of the cases are diagnosed after surgical exploration for presumed pancreatic malignancy and preoperative diagnosis is quite difficult. However, improvement in imaging techniques and the resulting imageguided interventions gradually can obviate the need for more invasive diagnostic surgical procedures and expedite the planning of therapy. Herein, we report a rare case of isolated pancreatic TB which presented with pancreatic mass lesion in an immunocompetent host. Diagnosis was made by contrast enhanced computed tomography and guided fine needle aspiration of the pancreatic mass which revealed acid-fast bacillion Ziehl-Neelsen stain. The case was treated successfully with antituberculous drugs. Pancreatic tuberculosis should be considered in the differential diagnosis of a pancreatic mass when the patient is young, residing in the endemic zone of tuberculosis. Every attempt should be made to diagnose the cases to prevent unnecessary operation.

Current status and agenda in the diagnosis of nonalcoholic steatohepatitis in Japan

Nonalcoholic fatty liver disease(NAFLD),a manifestation of metabolic syndrome,includes a wide range of clinical entities from simple fatty liver,a benign condition,to nonalcoholic steatohepatitis(NASH),a condition which can progress to cirrhosis,hepatocellular carcinoma and hepatic failure.The diagnosis of NASH requires no history of previous or current significant alcohol cons umption and no evidence of other chronic liver dis eases.Ethanol intake levels of 20 g daily(or 140 g weekly) are endorsed as the acceptable threshold to define no nalcoholic patients.Liver biopsy is the current gold stan d ard for the diagnosis of NASH and provides progn o stic information.Histopathological diagnosis of NASH is based on the following 3 features:(1) hepatic macrovesicular steatosis;(2) lobular inflammation;and(3) ballooning degeneration of hepatocytes.It is impractical to biopsy every patient with suspected NAFLD.Although highly accurate and affordable noninvasive screening tools can differentiate NASH from NAFLD,no imaging studies or laboratory tests are able to precisely diagnose NASH.There is no universal agreement regarding the indications for liver biopsy in NAFLD patients.In Japan,liver biopsies are considered in patients with sus pected NAFLD based on several criteria including low platel et counts,elevated fibrosis markers,increasing age and other deciding parameters.Further studies are needed to establish a suitable scoring system that can distinguish steatohepatitis from simple steatosis.

Prevalence and virological profiles of hepatitis B infection in human immunodeficiency virus patients

AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm 3 and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients.METHODS: During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. Inclusion criteria: HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearsonχ 2 test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. RESULTS: Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm 3 (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm 3 . Plasma HIV-1 RNA load was elevated (≥ 5 log 10 copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2;P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2;P = 0.01;95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9;P = 0.04; 95% CI: 1.02-3.8). CONCLUSION: HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIVpositive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

瞄准：决定一座干扰素高山的功效哈并且为感染遗传型 2 的丙肝病毒(HCV ) 的日本病人的 ribavirin 联合治疗，多中心研究回顾地被分析。方法：总共，有 HCV 遗传型 2 的 173 个病人每天一个星期和 ribavirin 的 600-800 mg 为 24 wk 三次皮下地收到 interferon-alpha。结果：总的来说持续的 virological 反应(SVR ) ，在浆液的定义同样无法发现的 HCV RNA，在治疗的结束以后的 24 wk，在 84.4% 显著地高，(146/173 ) 由 intention-to-treat 分析。在 SVR 的有效差量有或没有 ribavirin (46.9% 对 92.9%) 的中止在病人之间被发现，但是没有差别有或没有 ribavirin 的剂量减小在那些之间被发现。在 SVR 的有效差量也与 16 或更与不到 16 wk 和病人在病人之间被发现 ribavirin 治疗(34.8% 对 92.0%) 的星期。结论：24-wk 干扰素和 ribavirin 治疗为有 HCV 遗传型 2 的日本病人是高度有效的。SVR 的重要预言者是 ribavirin 治疗的继续多达 16 个星期。

Fermented Ethnic Medicine (<i>Pueraria mirifica</i>) Designed by Lactobacillus Regulated Leukocyte Subsets via Activation of Complement Components

A plant fermentation was carried out by Lactobaccilli against the Rhizome from Pueraria milifica (f-PMF). This material was evidenced by safe in animal toxic study. The main aim of this study was to revise the traditional way of hot water extraction to fermentation so as to use up the original material and finding new activity. We tried to show the new activity through phytoestrogen and immune-competent cells from the host that administrated either of original remedy and the new fermented sample, plus activated water SRE. In mice, compromised host was prepared by cancer chemotherapeutic agent (Mitomycin-C). After administration of f-PMF to immno-suppressed animals, the effects by both samples were augmented by lymphocyte in number and functions, macrophage activities, anti-oxidative activity. However, the intense of effect was much more by fermented one but not by conventional one. The anti-oxidative assay was also carried out ex-vivo system by peritoneal macrophage that we proposed as suitable system for evaluating anti-oxidative assay. In our clinical study by 20 healthy volunteers, granulocyte and lymphocyte ratio was regulated as neutral in peripheral white blood cells, increasing one, two and three weeks after the administration of f-PMF. We have found the significant regulation of blood chemical factors that were important makers for the lifestyle-related diseases. The mechanism of augmentation by probing directory with immuno-electrophoretic method, generating new complement component, especially found by alternative pathway of complement. So we discussed the process concerning designed f-PMF molecule for activation of complement component and bound for the biological activity of each physical component. In a limited condition, fewer numbers of volunteers, the breast size was tending to increase along with the administration time. Including these evidences, we discussed the possibility of this traditional ethnic medicine, originally found and spread in the highland area in Thailand and Myanmar.

Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients

AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.

Prediction models for development of hepatocellular carcinoma in chronic hepatitis B patients

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in Asian-Pacific regions.Antiviral therapy reduces,but does not completely prevent,HCC development.Thus,there is a need for accurate risk prediction to assist prognostication and decisions on the need for antiviral therapy and HCC surveillance.A few risk scores have been developed to predict the occurrence of HCC in CHB patients.Initially,the scores were derived from untreated CHB patients.With the development and extensive clinical application of nucleos(t)ide analog(s)(NA),the number of risk scores based on treated CHB patients has increased gradually.The components included in risk scores may be categorized into host factors and hepatitis B virus factors.Hepatitis activities,hepatitis B virus factors,and even liver fibrosis or cirrhosis are relatively controlled by antiviral therapy.Therefore,variables that are more dynamic during antiviral therapy have since been included in risk scores.However,host factors are more difficult to modify.Most existing scores derived from Asian populations have been confirmed to be accurate in predicting HCC development in CHB patients from Asia,while these scores have not offered excellent predictability in Caucasian patients.These findings support that more relevant variables should be considered to provide individualized predictions that are easily applied to CHB patients of different ethnicities.CHB patients should receive different intensities of HCC surveillance according to their risk category.