Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Differential expression and significance of 5-hydroxymethylcytosine modification in hepatitis B virus carriers and patients with liver cirrhosis and liver cancer

BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)-positive carrier status and liver cancer has been extensively studied.However,the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown.The epigenetic modification of DNA hydroxymethylation is critical in tumor development.Further,5-hydroxymethylcytosine(5hmC)is an important base for DNA demethylation and epigenetic regulation.It is also involved in the assembly of chromosomes and the regulation of gene expression.However,the mechanism of action of 5hmC in HBsAgpositive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated.AIM To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma(HCC)progression from cirrhosis.METHODS Forty HBsAg-positive carriers,forty patients with liver cirrhosis,and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants.Free DNA was extracted using a cf-DNA kit.cfDNA was extracted by 5hmC DNA sequencing for principal component analysis,the expression profiles of the three groups of samples were detected,and the differentially expressed genes(DEGs)modified by hydroxymethylation were screened.Bioinformatic analysis was used to enrich DEGs,such as in biological pathways.RESULTS A total of 16455 hydroxymethylated genes were identified.Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients,of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers.Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes,of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis.These genes may have potential loci that are undiscovered or unelucidated,which contribute to the development and progression of liver cancer.Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion.The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2.CONCLUSION The occurrence and development of liver cancer involves multiple genes and pathways,which may be potential targets for preventing hepatitis B carriers from developing liver cancer.

Clinical significance of serum oxidative stress and serum uric acid levels before surgery for hepatitis B-related liver cancer

BACKGROUND The incidence and mortality of liver cancer are among the highest of all malignant tumors in China.The high recurrence rate after conventional hepatectomy is worrying.There is a lack of effective prognostic indicators for liver cancer.AIM To explore the clinical significance of preoperative serum oxidative stress and serum uric acid(UA)levels in hepatitis B-related liver cancer.METHODS The medical records of 110 hepatitis B-related liver cancer patients who under-went hepatectomy in Gansu Provincial Hospital were retrospectively analyzed.Recurrence in patients within 3 years after surgery was determined.The logistic regression model and Pearson or Spearman correlation were used to analyze the correlation between oxidative stress level and UA,and the recurrence of hepatitis B-related liver cancer.RESULTS Compared with the non-recurrence group,the levels of superoxide dismutase(SOD)and glutathione(GSH)in the recurrence group were lower and the levels of malondialdehyde(MDA)and UA were higher(all P<0.05).UA,SOD,MDA,and GSH were risk factors for postoperative recurrence in hepatitis B-related liver cancer patients(P<0.05).UA was positively correlated with MDA(r=0.395,P<0.001)and negatively correlated with GSH(r=-0.204,P=0.032).The area under the receiver operating characteristic curve(AUC)of SOD,MDA,GSH,and UA in predicting the prognosis was 0.276,0.910,0.199,and 0.784,respectively(all P<0.001).CONCLUSION The preoperative serum SOD,GSH,MDA,and UA levels had significant predictive effects on postoperative recurrence of hepatitis B-related liver cancer.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.

Barcelona Clinic Liver Cancer Classification and Treatment of Hepatocellular Carcinoma in a Côte d’Ivoire University Hospital

Context/Objectives: Hepatocellular carcinoma occurs mainly and increasingly in developing countries, where the prognosis is particularly poor. The Barcelona Clinic Liver Cancer classification is used to guide the treatment of hepatocellular carcinoma. The aim of this retrospective study was to describe the Barcelona Clinic Liver Cancer classification and the treatment of hepatocellular carcinoma in a University Hospital in Côte d’Ivoire. Methods: Patients with hepatocellular carcinoma hospitalized in the hepato-gastroenterology unit of the University Hospital of Yopougon from 01 January 2012 to 30 June 2017 were included. The diagnosis of hepatocellular carcinoma was based on the presence of hepatic nodules on the abdominal ultrasound scan, typical images with the helical scanner associated or not with an increase of the α-fetoprotein higher than 200 ng/ml or with histology. Demographic, clinical, biological and radiological data were determined at the time of diagnosis. Patients were classified according to the Barcelona Clinic Liver Cancer classification. Their treatment was specified. Results: There were 258 patients whose median age was 48.1 years. Viral hepatitis B virus was the primary cause of hepatocellular carcinoma in 64.7% of cases. The severity of the underlying cirrhosis was Child-Pugh A in 12.1%, B in 63.6% and C in 24.3% of cases. The median size of the tumor was 63 mm. The α-fetoprotein level was higher than 200 mg/ml in 56.03% of cases. The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) system was ≥2 in 82.9%. The Barcelona Clinic Liver Cancer classification was A in 1.3%, B in 0%, C in 55.2% and D in 43.5% of patients. There was no transplantation or hepatic resection. Very few patients (1.9%) received radio-frequency curative therapy. The treatment was predominantly symptomatic in 97.8% of patients. During hospitalization 43.7% of patients died. Conclusion: Hepatocellular carcinoma occurs on a liver with severe cirrhosis at a late stage. This does not allow cure treatment and explains a high mortality rate during hospitalization. Hepatitis B virus is the main risk factor and immunization at birth will reduce the incidence of this cancer in Africa.

Negative impact of hepatitis B surface seroclearance on prognosis of hepatitis B-related primary liver cancer

AIM To assess the impact of hepatitis B surface(HBs Ag) seroclearance on survival outcomes in hepatitis B-related primary liver cancer.METHODS Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBs Ag(-) and HBc Ab(+) liver cancer were included in the HBs Ag seroclearance(SC) group. HBs Ag(+) liver cancer patients strictly matched for liver cancer stage(AJCC staging system, 8 th edition), Child-Pugh score, and first diagnosis/treatment method(surgery, ablation and TACE) were assigned to the HBsA g non-seroclearance(NSC) group. Then, clinical, pathological and survival data in both groups were assessed.RESULTS The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age(P < 0.001) and platelet count(P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma(ICC) and combined HCC-CC(CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups(4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group(P = 0.019), with 1-,3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2%vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage Ⅰ disease in the SC group was lower than that of the NSC group(P = 0.029).CONCLUSION Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.

Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by the hepatitis B virus(HBV).Since laboratory animal models susceptible to HBV infection are limited,woodchucks experimentally infected with WHV,a hepatitis virus closely related to HBV,are increasingly used to enhance our understanding of virus-host interactions,immune response,and liver disease progression.A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established,which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans.HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size,morphology,and molecular gene signature to those of HBV-infected patients.Accordingly,woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC.In addition,drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs,alone or in combination with other compounds,minimizes the risk of liver disease progression to HCC.More recently,woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute,self-limited and chronic infections.Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae,including the onset of HCC.Therefore,woodchucks with chronic WHV infection constitute a well-characterized,fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities,which are based on chemo,gene,and immune therapy,for the prevention and treatment of HCC in patients for which current treatment options are dismal.

EXPERIMENTAL PRIMARY LIVER CANCER IN TREE SHREWS EXPOSED TO HUMAN HEPATITIS B VIRUS AND AFLATOXIN B_(1)

On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.

Clinical and Paraclinical Profiling of Patients with Viral Hepatitis B and C Attending Saint Camille Hospital in Ouagadougou (HOSCO)

The present study aims to describe the clinical and paraclinical profile of patients infected by viral hepatitis B and C and follow-up. The clinical and paraclinical data used in this description are from patients infected by viral hepatitis B and C of the HOSCO Hepato-Gastroenterological Department from May 15, 2021 to July 23, 2021. The informed consent was provided to each patient included in this study. “Univariate analyses were evaluated using Pearson’s Chi2 test” using R software version 4.0.2. During the study period, we identified 149 patients with viral hepatitis B and/or C who met our inclusion criteria. The sex ratio was 0.83 at the rate of 68 men for 81 women with the average age at 37.17 years ± 12.21 years. The most represented age group was 30 - 44 years (49.7%). The most incriminated risk factors were medical care by injection (62.58%), excision (31.90%), blood transfusion (4.29%) and scarification (1.23%). HBV infection was the majority with a frequency of 95.97%. The HBV viral load was measured in 91.95% of patients, 77.18% of whom had a detectable DNA viral load ≤ 2000 IU/mL. The clinical and biological course was good in patients after therapeutic initiation. HBV-HCV-HIV co-infection was 0.67%. Abdominal ultrasound was normal in 87.92% of patients. Fibrosis was minimal and moderate in 58.39% and 19.46% of patients. Among patients, 52.35% were on Tenofovir therapy, 2.68% on Sofosbuvir/Velpatasvir, 0.67% on ARVs and 44.29% did not require treatment. Viral hepatitis B and C are common, and both affect sex. Thus, new screening strategies need to be implemented to improve the diagnosis of hepatitis B and C. Effective strategies against viral hepatitis B and C must be developed, subsequently.

Direct antiviral agents in hepatitis C virus related liver disease:Don’t count the chickens before they’re hatched

Since molecules with direct-acting antiviral(DAA)became available,the landscape of the treatment of hepatitis C virus(HCV)infection has completely changed.The new drugs are extremely effective in eradicating infection,and treatment is very well tolerated with a duration of 8-12 wk.This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages,identifying some clinically relevant hot topics.First,do the rates of virological response remain as high when patients with more advanced cirrhosis are considered?Large studies have shown slightly lower but still satisfactory rates of response in these patients.Nevertheless,modified schedules with an extended treatment duration and use of ribavirin may be necessary.Second,does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer?Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis.In contrast,the risk of recurrence seems to be unaffected by viral clearance;however,DAA treatment improves survival because of the reduced risk of progression of liver disease.Third,can HCV treatment also have favorable effects on major comorbidities?HCV eradication is associated with a reduced incidence of diabetes,an improvement in glycemic control and a decreased risk of cardiovascular events;nevertheless,a risk of hypoglycemia during DAA treatment has been reported.Finally,is it safe to treat patients with HCV/hepatitis B virus(HBV)coinfection?In this setting,HCV is usually the main driver of viral activity,while HBV replication is suppressed.Because various studies have described HBV reactivation after HCV clearance,a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.

Survey of hepatitis B virus infection for liver cancer screening in China:A population-based,cross-sectional study

Background:Hepatitis B virus(HBV)infection is the primary cause of hepatocellular carcinoma(HCC)in China.The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen(HBsAg).However,current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking.We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China.Methods:Questionnaires including information of sex,age,ethnicity,marital status,educational level,source of drinking water,as well as smoking and alcohol consumption history and serum samples were collected from females aged 45-64 years and males aged 35-64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023.Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg.Results:A total of 603,082 individuals were enrolled,and serum samples were collected for analysis from January 1,2015 to December 31,2023.The prevalence of HBsAg positive in the study population was 5.23%(31,528/603,082).The prevalence of HBsAg positive was greater in males than in females(5.60%[17,660/315,183]vs 4.82%[13,868/287,899],χ^(2)=187.52,P<0.0001).The elderly participants exhibited a greater prevalence of HBV infection than younger participants(χ^(2)=41.73,P<0.0001).Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females.Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier.Conclusions:The current prevalence of HBV infection remains above 5%in populations eligible for HCC screening in China.Further efforts should be made to increase the accessibility of HCC screening among individuals with HBV infection.

92031例癌症患者HBV血清标志物特征分析

目的了解癌症患者乙型肝炎病毒(hepatitis B virus,HBV)的感染状态和感染特点。方法回顾性分析2017年7月26日至2023年9月18日于广西医科大学附属肿瘤医院确诊的92031例癌症患者的HBV血清标志物检测结果,以肝癌、非肝癌进行分组,比较未感染(全阴或Anti-HBs阳性)、感染(除外Anti-HBs任何一项阳性)、隐性感染(occult hepatitis B virus infection,OBI;HBsAg阴性、血清或肝组织HBV DNA阳性)的占比。结果92031例癌症患者的HBV总感染率为73.75%(67876/92031),其中肝癌患者的HBV总感染率为97.65%(8922/9137),非肝癌患者的HBV总感染率为71.12%(58954/82894),肝癌组的普通感染率和OBI率均显著高于非肝癌组(均P<0.001)。肝癌组HBV血清标志物中HBsAg、HBeAg、Anti-HBe、Anti-HBc的阳性率明显高于非肝癌组(均P<0.001),但Anti-HBs的阳性率低于非肝癌组(P<0.001)。肝癌组和非肝癌组分别有20种和27种血清标志物组合模式,其中14种模式构成比在两组间差异有统计学意义(均P<0.001);两组均有7种OBI血清组合模式,其中5种模式构成比在两组间的差异有统计学意义(均P<0.05)。结论癌症患者HBV感染状态和血清学组合模式复杂,区分肝癌与非肝癌进行HBV感染统计更利于癌症患者的HBV感染评估。

Qidong: a crucible for studies on liver cancer etiology and prevention

Qidong(Jiangsu, China) has been of interest to cancer epidemiologists and biologists because, until recently, it was an endemic area for liver cancer, having amongst the highest incidence rates in the world. The establishment of the Qidong Cancer Registry together with the Qidong Liver Cancer Institute in 1972 has charted the patterns of liver cancer incidence and mortality in a stable population throughout a period of enormous economic, social, and environmental changes as well as of improvements in health care delivery. Updated incidence trends in Qidong are described. Notably, the China age-standardized incidence rate for liver cancer has dropped by over 50% in the past several decades. Molecular epidemiologic and genomic deep sequencing studies have affirmed that infection with hepatitis B virus as well as dietary exposure to aflatoxins through contamination of dietary staples such as corn, and to microcystins–blue-green algal toxins found in ditch and pond water – were likely important etiologic factors that account for the high incidence of liver cancer in this region. Public health initiatives to facilitate universal vaccination of newborns against HBV and to improve drinking water sources in this rural area, as well as economic and social mandates serendipitously facilitating dietary diversity, have led to precipitous declines in exposures to these etiologic factors, concomitantly driving substantive declines in the liver cancer incidence seen now in Qidong. In this regard, Qidong serves as a template for the global impact that a package of intervention strategies may exert on cancer burden.

HBV infection decreases risk of liver metastasis in patients with colorectal cancer:A cohort study

AIM:To evaluate the effect of hepatitis B virus (HBV) infection on liver metastasis of colorectal cancer.METHODS:A total of 1298 colorectal cancer patients were recruited from January 2001 to March 2005 in this study.Enzyme-linked immunosorbent assay was used to test serum HBV markers for colorectal cancer.Patients were divided into study (infection) group and control (non-infection) group.Clinical features of patients in two groups were compared.RESULTS:Liver metastasis was found in 319 out of the 1298 colorectal cancer patients.The incidence of liver metastasis was significantly lower in study group than in control group (14.2% vs 28.2%,P < 0.01).HBV infection significantly decreased the risk of liver metastasis [hazard ratio (HR):0.50,95% confidence interval (95% CI):0.38-0.66],but the incidence of extrahepatic metastasis was significantly higher in study group than in control group (31.9% vs 17.0%,P < 0.01).The HR was the lowest in chronic hepatitis B group (HR:0.29,95% CI:0.12-0.72).The number of liver metastatic lesions was significantly less in study group than in control group with a higher surgical resection rate.However,no significant difference was found in survival rate between the two groups (P=0.95).CONCLUSION:HBV infection decreases the risk of liver metastasis in patients with colorectal cancer and elevates the surgical resection rate of liver metastatic lesions.

Medical training fails to prepare providers to care for patients with chronic hepatitis B infection

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.

Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area

AIM To determine the role of screening and surveillance of hepatocellular carcinoma(HCC) in treatment-na?ve chronic hepatitis B(CHB) patients. METHODS We recruited 2293 CHB patients(both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography(AUS) and serum alpha-fetoprotein(AFP) assay every 6 mo. The diagnosis,staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score < 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis.RESULTS Among 2293 treatment-na?ve CHB patients,seven cases had HCC at initial screening,giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis,all of which were Child-Pugh class A. With a median follow-up time of 42(range,3-48) mo,10 additional cases were diagnosed with HCC,resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage(Stage 0,A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation,with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis,increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 mg/L at diagnosis were observed in only 7/17 patients,most with a tumor size > 5 cm. For HCC screening and surveillance,AUS had a sensitivity and specificity of 94% and 82%,respectively,whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 mg/L were 41% and 98%,respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION Implementation of active screening and surveillance using AUS to detect early-stage HCC in na?ve CHB patients aged ≥ 40 years in an endemic area is of benefit.

乙型肝炎相关性肝癌患者T淋巴细胞、白介素-28B及高尔基体蛋白73的表达及临床意义

目的:分析乙型肝炎相关性肝癌患者T淋巴细胞、白介素-28B (IL-28B)及高尔基体蛋白73 (GP73)的表达及临床意义。方法:选取2018年10月—2021年10月商丘市第一人民医院收治的119例乙型肝炎相关性肝癌患者作为观察组,选取同期体检的112例健康人群作为对照组。比较两组研究对象血清IL-28B、GP73及T淋巴细胞水平,分析IL-28B、GP73、T淋巴细胞与病理特征及预后的关系。结果:观察组血清IL-28B、GP73及CD8^(+)表达水平均高于对照组,CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均低于对照组,差异有统计学意义(t=148.380、13.155、9.827、9.939、16.367、11.453,P<0.05)。不同年龄、性别、肿瘤直径的乙型肝炎病毒(HBV)相关性肝癌患者血清中IL-28B、GP73水平比较,差异无统计学意义(P>0.05)。有淋巴结转移、TNM分期Ⅲ~Ⅳ期、低分化、有血管浸润者血清中IL-28B、GP73水平高于无淋巴结转移、TNM分期Ⅰ~Ⅱ期、中/高分化、无血管浸润者,差异有统计学意义(P<0.05)。HBV相关性肝癌患者血清中CD3^(+)、CD4^(+)、CD8^(+)在不同年龄、性别、肿瘤直径中比较,差异无统计学意义(P>0.05),CD3^(+)、CD4^(+)、CD8^(+)水平在不同淋巴结转移情况、TNM分期、分化程度及血管浸润中比较,差异无统计学意义(P>0.05)。死亡者血清GP73、IL-28B水平均高于生存者,CD4^(+)/CD8^(+)指标低于生存者,差异有统计学意义(t=16.629、2.082、9.267,P<0.05)。结论:乙型肝炎相关性肝癌患者血清IL-28B、GP73及CD8^(+)表达水平明显升高,CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)指标下降,IL-28B、GP73及CD4^(+)/CD8^(+)水平与相关病理特征、预后具有密切的联系。

HBV相关肝细胞癌患者PPP2R3A基因的表达与预后相关性分析

目的探讨蛋白磷酸酶2A调节亚基B″α(PPP2R3A)基因在HBV相关肝细胞癌患者中的表达水平以及与预后的关系。方法利用免疫组织化学方法检测PPP2R3A蛋白在82例乙肝相关性肝癌和21例良性肝病组织中的表达,采用RT-PCR方法检测mRNA水平。结果PPP2R3A在肝癌组织中的表达水平(95.12%)明显高于癌旁组织(43.9%)(P<0.05)。PPP2R3A蛋白的表达强度与肝癌患者的AFP值相关,具有统计学差异(P<0.05)。RT-PCR检测结果显示,肝癌组织中PPP2R3A mRNA中位表达水平为0.183(0.008~0.667),明显高于癌旁组织的0.098(0.004~0.583)(Z=6.839,P<0.05)。通过分析随访肝癌患者的生存期资料,结果发现PPP2R3A高表达组患者的总生存期(OS)的中位生存期为46.6个月,与低表达组的82.9个月比较差异有统计学意义(P<0.05)。PPP2R3A高表达组患者的RFS的中位生存期为18.3个月,低于低表达组的42.6个月(P<0.05)。PPP2R3A高表达组患者的PFS的中位生存期为15.9个月,低于低表达组的34.4个月(P<0.05)。PPP2R3A高表达组患者的DSS的中位生存期为70.5个月,低于低表达组的84.7个月(P<0.05)。结论PPP2R3A蛋白在HBV相关肝细胞癌组织及血清中呈高表达,且与肝癌的临床病理特征有相关性,PPP2R3A的高表达可能与肝癌的不良预后有关。

Hepatitis B among Inuit: A review with focus on Greenland Inuit

Hepatitis B virus(HBV) infection is a disease with a highly variable course. Chronic HBV infection may cause end-stage liver disease including cirrhosis and hepatocellular carcinoma, which is the 3rd most common cause of cancer related death due to the poor prognosis. The prevalence of HBV infection is low in many countries. Still, it remains important due to the potential consequences of the disease. HBV is endemic in the Arctic with serologic markers of chronic HBV infection in up to 29% of the population in some areas in Greenland. Interestingly, Inuit populations rarely show signs of liver disease despite the fact that around half of all Inuit has been exposed to HBV and around 8% of Inuit are chronically infected with HBV. These findings have been consistent in surveys conducted for more than four decades among Arctic Inuit. We thus review HBV infection in the Arctic with focus on Greenland Inuit and compared with Inuit in Canada, Alaska and Siberia. The aspects described include epidemiology and monitoring of the disease, as well as treatment and the risk of liver cancer.

HBV感染相关肝癌患者ICI治疗后HBV再激活及其与肝损伤事件的关系

目的探讨乙型肝炎病毒(HBV)感染相关肝癌患者免疫检查点抑制剂(ICI)治疗后HBV再激活及其与肝损伤事件的关系。方法选取东南大学附属中大医院2020年5月-2022年5月120例肝细胞癌患者,所有患者均接受ICI治疗。根据治疗前及治疗4个周期后患者HBV-DNA载量,将HBV-DNA绝对值超过10^(5)copies/ml或与基础值相比增加10倍以上者纳入再激活组,未达到上述标准者纳人非再激活组。分析HBV再激活的危险因素,对比两组肝损伤事件发生率,分析治疗后HBV-DNA载量与肝损伤程度的关系。结果120例HBV感染相关肝癌患者ICI治疗后,有19例(15.83%)出现HBV再激活;治疗前HBV-DNA载量≥10^(3) copies/ml是ICI治疗后HBV再激活的危险因素,接受抗病毒治疗是预防HBV再激活的保护因素(P<0.05);再激活组肝功能损伤发生率为36.84%高于非再激活组(P=0.016);两组严重肝功能损伤发生率比较差异无统计学意义(P=0.462);再激活组与非再激活组ICI治疗前肝功能指标水平差异无统计学意义;再激活组应用ICI治疗后肝功能指标谷草转氨酶(AST)、谷丙转氨酶(ALT)和总胆红素(TBIL)分别为(77.51±9.15)U/L、(73.44±8.27)U/L和(34.66±4.93)μmol/L高于未再激活组(P<0.05);Pearson相关性分析结果显示ICI治疗后HBVDNA复制水平与患者肝功能指标ALT、AST、TBIL水平呈正相关(r=0.623、0.548、0.517,P均<0.05)。结论ICI治疗在一定程度上增加了HBV感染相关肝癌患者HBV再激活的风险,HBV再激活可引发患者肝损伤事件的发生,加重患者肝损伤程度。