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.

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.

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.

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.

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.

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.

Gene modulation associated with inhibition of liver regeneration in hepatitis B virus X transgenic mice

AIM： To analyze the modulation of gene expression profile associated with inhibition of liver regeneration in hepatitis B X （HBx）-expressing transgenic mice. METHODS： Microarray technology was performed on liver tissue obtained from 4 control （LacZ） and 4 transgenic mice （HBx-LacZ）, 48 h after partial hepatectomy. The significance of the normalized logratios was assessed for each gene, using robust t-tests under an empirical Bayes approach. Microarray hybridization data was verified on selected genes by quantitative PCR. RESULTS： The comparison of gene expression patterns showed a consistent modulation of the expression of 26 genes, most of which are implicated in liver regeneration. Up-regulated genes included DNA repair proteins （Rad-52, MSH6） and transmembrane proteins （syndecan 4, tetraspanin）, while down-regulated genes were connected to the regulation of transcription （histone deacetylase, Zfp90, MyoDl） and were involved in the cholesterol metabolic pathway and isoprenoidbiosynthesis （farnesyl diphosphate synthase, Cyp7b1, geranylgeranyl diphosphate synthase, SAA3）. CONCLUSION： Our results provide a novel insight into the biological activities of HBx, implicated in the inhibition of liver regeneration,

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.

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.

Hepatitis B virus X protein promotes proliferation and upregulates TGF-β1 and CTGF in human hepatic stellate cell line,LX-2

BACKGROUND:Chronic hepatitis B virus(HBV)infection is a major cause of liver fibrosis,but the mechanisms underlying HBV-related fibrogenesis are still unknown. Although the roles of HBV X protein(HBx)remain poorly understood,it is thought to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to determine the role of HBx in liver fibrogenesis by studying the effect of HBx on the proliferation and expression of fibrosis-related molecules in the human hepatic stellate cell line,LX-2. METHODS:We established an in vitro co-culture system with LX-2 cells and a stable QSG7701-HBx cell line which had been transfected with the HBx gene. 3 H-TdR incorporation and flow cytometry were used to determine the effects of HBx on the proliferation of LX-2 cells. α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),transforming growth factor-βreceptor Ⅱ(TGF-βRⅡ),and connective tissue growth factor (CTGF)in LX-2 cells were analyzed by Western blotting.In addition,the expression levels of collagen typeⅠ(ColⅠ) from the co-cultured media were measured by ELISA. RESULTS: 3 H-TdR incorporation increased significantly in LX-2 cells co-cultured with QSG7701-HBx cells compared to those cultured with QSG7701-pcDNA3 and QSG7701 (non-tumorigenic human liver cell line).Cell cycle results revealed that HBx accelerated the progression of G1 to S in LX-2 cells.The expressions ofα-SMA,TGF-β1,TGF-βR Ⅱ,CTGF and ColⅠwere significantly increased in the co- cultures of LX-2 cells with stable QSG7701-HBx cells. CONCLUSION:These results suggest that HBx may facilitate liver fibrosis by promoting hepatic stellate cell proliferation and upregulating the expression of fibrosis- related molecules.

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.

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.

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.

Correlation analysis of TCM syndrome types with T lymphocytes and biochemical indices in patients with HBV-related primary liver cancer

Objective:To investigate the correlation between T lymphocytes and biochemical indices in patients with Primary liver cancer(PLC)associated with hepatitis B virus(HBV)and TCM syndrome differentiation.Methods:263 HBV-related PLC patients who were admitted to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2018 to December 2019 were retrospectively collected.There were 127 cases of liver depression and spleen deficiency syndrome(48.3%),48 cases of spleen deficiency and dampness syndrome(18.3%),31 cases of liver and gallbladder dampness and heat syndrome(11.8%),35 cases of liver and blood stasis syndrome(13.3%),and 22 cases of liver and kidney Yin deficiency syndrome(8.4%).The general data,T cell subsets,oncology and virology indicators,oncology characteristics,biochemical indicators and other data were counted.Epidata and Excel were used to collect and summarize the data,and SPSS26.0 software was used for statistical analysis.Results:There was no significant difference in gender and age distribution among the five syndrome types(χ^(2)=5.462,F=1.979,ALL P>0.05).The differences among T lymphocyte count(χ^(2)=57.785,P<0.001),CD4(+)T cell count(χ^(2)=47.103,P<0.001)and CD8(+)T lymphocyte count(F=12.760,P<0.001)were statistically significant.The T lymphocyte count,CD4(+)T lymphocyte count and CD8(+)T lymphocyte explicit count in patients with liver and kidney Yin deficiency syndrome were significantly lower than those in the other four syndrome types.AFP(χ^(2)=89.986,P<0.001),CEA(χ^(2)=95.501,P<0.001),CA199(χ^(2)=30.044,P<0.001)of the five syndrome types increased successively from the syndrome of liver depression and spleen deficiency to the syndrome of liver and kidney Yin deficiency,and the difference was statistically significant.There were statistically significant differences in the inner diameter of main portal vein,portal vein cancer thrombin and extrahepatic metastasis among the five syndrome types(ALL P<0.001).The main symptoms of portal vein cancer thrombin and extrahepatic metastasis were liver-gallbladder dampness-heat syndrome and liver-blood stasis syndrome.The differences among PLT(χ^(2)=39.234,P<0.001),Alb(χ^(2)=75.171,P<0.001),TBil(χ^(2)=51.140,P<0.001),AST(χ^(2)=55.881,P<0.001),PT(χ^(2)=21.515,P<0.001)were statistically significant.PLT and Alb decreased successively from the syndrome of liver depression and spleen deficiency to the syndrome of liver and kidney Yin deficiency.PLT and Alb of the syndrome of liver depression and spleen deficiency were significantly higher than those of the other four groups,and TBil and AST of the syndrome of liver and gallbladder dampness and heat were significantly higher than those of the other four groups.PT of liver and kidney Yin deficiency was significantly higher than that of the other four groups.The lymphocyte count,CD4(+) lymphocyte count and CD8(+) lymphocyte count were negatively correlated with AFP,PT and TBil(ALL P<0.05),and positively correlated with PLT(P<0.05).T lymphocyte count was positively correlated with AIb(P<0.05).Conclusion:This study found that patients with liver depression and spleen deficiency syndrome have better cellular immune function,liver function and prognosis.Patients with liver and kidney Yin deficiency have lower cellular immunity,worse liver function,and worse prognosis.Portal vein carcinoma embolus and extrahepatic metastasis were mainly characterized by dampness and heat of liver and gallbladder and blood stasis of liver.Patients with lower lymphocyte counts have poorer blood clotting,worse the liver reserve,and the higher the risk of further cancer.

Small rodent models of hepatitis B and C virus replication and pathogenesis

The narrow host range of infection supporting the long-term propagation of hepatitis B and C viruses is a major limitation that has prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease(CLD).With hepatitis B virus(HBV),this has been partially overcome by the discovery and characterization of HBV-like viruses in wild animals.With hepatitis C virus(HCV),related Flaviviruses have been used as surrogate systems for such studies.Independent work has developed various mouse strains for the transplantation of human hepatocytes,which are then susceptible to infection with HBV and HCV.Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication.Some HBV transgenic mouse models develop fulminant hepatitis,acute hepatitis,or CLD following adoptive transfer,while others spontaneously develop hepatocellular carcinoma(HCC),as in human infections.Among HCV transgenic mice,most develop no disease,but acute hepatitis has been observed in one model,while HCC appears in another.Other mouse models include the introduction of xenographs that replicate HBV or HCV.Although mice are not susceptible to these viruses,their ability to support virus replication and to develop liver disease characteristic of human infections,provides new opportunities to study pathogenesis and develop novel therapeutics.

叶下珠水提物对裸鼠人肝癌移植瘤HBx和VEGFR3表达的影响

目的探讨乙型肝炎病毒x基因(hepatitis B virux x gene,HBx)和血管内皮生长因子受体3(vascular endothelial growth factor receptor 3,VEGFR3)基因与乙型肝炎相关肝癌的相关性,以及叶下株水提物(aqueous extract of phyllanthus urinaria L,AEP)对HBx和VEGFR3蛋白表达的干预作用。方法将60只Balb/c-nu裸鼠随机分为10组。分别复制转染HBx、氯霉素乙酞转移酶(chloramphenicol acetyltransferase,CAT)和VEGFR3基因的HepG2肝癌细胞的裸鼠皮下移植瘤模型,用AEP进行干预,以生理盐水、环磷酰胺(cyclophosphamide,CTX)作为对照,共治疗6周。观察模型复制后不同时间各组裸鼠的移植瘤生长状况,采用酶联免疫吸附试验检测各组裸鼠血清甲胎蛋白(alpha fetal protein,AFP)水平,采用Western blot方法检测移植瘤组织中HBx和VEGFR3蛋白表达水平。结果肝癌移植瘤模型复制成功。各组裸鼠体质量均随着时间显著增长。实验结束时,接种HepG2-HBx细胞的各组中,AEP处理组肿瘤质量显著低于CTX处理组(P<0.05),其AFP水平显著高于NS处理组(P<0.05),其移植瘤组织中HBx表达水平显著低于NS组(P<0.05)。接种相同肝癌细胞的各组中,AEP处理组VEGFR3表达水平最低,但与CTX组VEGFR3表达水平比较,差异无统计学意义(P>0.05);AEP组和CTX组VEGFR3表达水平显著低于NS组(P<0.05)。对于相同的处理因素,接种HepG-HBx细胞和HepG-CAT细胞的裸鼠移植瘤组织中VEGFR3表达水平均显著低于接种HepG-VEGFR3细胞的裸鼠(P<0.01)。结论 AEP通过直接抑制HBx蛋白和VEGFR3蛋白表达,及通过抑制HBx蛋白表达而间接抑制VEGFR3蛋白表达,达到对肝癌移植瘤生长的抑制作用。