Newcastle Disease Virus Isolation and Its Prevalence in Uganda Poultry Farms

The present research work was carried out to isolate and identify Newcastle disease virus (NDV) by using haemagglutination inhibition (HI) test and HA-HI virus isolation, embryonated eggs (EE) and chicken embryo fibroblasts (CEF). A total of 95 clinical (blood, tracheal and cloacal swabs) and post-mortem (brain, lung, colon and spleen) samples were collected from chickens of field outbreaks of suspected Newcastle disease virus (NDV). The HI and HA-HI were employed to detect NDV in tissue homogenates of all the clinical and post-mortem samples as well as laboratory samples (AF and ICF). Among the four different types of post-mortem samples, virus isolation rate was found to be low in body organs. In CEF cell culture system, the rate of virus isolation from all the aforesaid samples was found to be at 100% with the exception of serum samples;while in tracheal and cloacal swabs, it was at 90%;while in serum, it was at 10%, in all clinical cases. The isolation rate of NDV was higher in CEF culture system (66.7%) compared to that of avian embryos (33.3%). Samples were inoculated and the allantoic fluid (AF) of the dead embryos and the infected culture fluid (ICF) of the CEF were harvested at 24 to 96 hours of the post-infection, respectively, which revealed that the virulent strain of NDV is highly prevalent in the region. The prevalence of NDV was established at 1.1%, 2.1% and 4.2% using HA-HI, EE, and CEF methods. Rapid detection and identification of the virus are crucial for the effective control of the disease as conventional diagnostic methods such as virus isolation on embryonated eggs followed by serological identification in haemagglutination-inhibition test are laborious and time-consuming. The speed of the diagnosis can be considerably increased by using methods based on molecular biology, e.g. reverse transcription—polymerase chain reaction. However, the genetic variability of APMV-1 isolates should be considered carefully as the potential cause for false negative results of genetic-based laboratory tests.

Hepatitis C virus infection and insulin resistance

Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.

Cancer and Infectious Causes

Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.

Hepatocellular Carcinoma: Known and Emerging Risk Factors

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.

Hepatitis delta virus:Making the point from virus isolation up to 2014

Chronic infection with hepatitis delta virus(HDV) has lately regained clinical importance because of the recent evidence of increasing prevalence in several European countries,due to immigration from highly endemic areas. HDV requires the mandatory presence ofhepatitis B virus(HBV) for propagation to hepatocytes. It is transmitted by the same routes of HBV and it can be acquired either by co-infection(simultaneous transmission of the two viruses) or super-infection(acquisition of HDV by an already chronic carrier of HBV). As a consequence,every HBV carrier is potentially at risk for HDV superinfection. Since the clinical course of superinfection can be severe,early diagnosis of HDV infection is necessary.

Exploring the Effects of Gap-Penalties in Sequence-Alignment Approach to Polymorphic Virus Detection

Antiviral software systems (AVSs) have problems in identifying polymorphic variants of viruses without explicit signatures for such variants. Alignment-based techniques from bioinformatics may provide a novel way to generate signatures from consensuses found in polymorphic variant code. We demonstrate how multiple sequence alignment supplemented with gap penalties leads to viral code signatures that generalize successfully to previously known polymorphic variants of JS. Cassandra virus and previously unknown polymorphic variants of W32.CTX/W32.Cholera and W32.Kitti viruses. The implications are that future smart AVSs may be able to generate effective signatures automatically from actual viral code by varying gap penalties to cover for both known and unknown polymorphic variants.

COVID-19 Coronavirus: Is Infection along with <i>Mycoplasma</i>or Other Bacteria Linked to Progression to a Lethal Outcome?

Most patients with COVID-19 disease caused by the SARS-CoV-2 virus recover from this infection, but a significant fraction progress to a fatal outcome. As with some other RNA viruses, co-infection or activation of latent bacterial infections along with pre-existing health conditions in COVID-19 disease may be important in determining a fatal disease course. Mycoplasma spp. (M. pneumonaie, M. fermentans, etc.) have been routinely found as co-infections in a wide number of clinical conditions, and in some cases this has progressed to a fatal disease. Although preliminary, Mycoplasma pneumoniae has been identified in COVID-19 disease, and the severity of some signs and symptoms in progressive COVID-19 patients could be due, in part, to Mycoplasma or other bacterial infections. Moreover, the presence of pathogenic Mycoplasma species or other pathogenic bacteria in COVID-19 disease may confer a perfect storm of cytokine and hemodynamic dysfunction, autoimmune activation, mitochondrial dysfunction and other complications that together cannot be easily corrected in patients with pre-existing health conditions. The positive responses of only some COVID-19 patients to antibiotic and anti-malaria therapy could have been the result of suppression of Mycoplasma species and other bacterial co-infections in subsets of patients. Thus it may be useful to use molecular tests to determine the presence of pathogenic Mycoplasma species and other pathogenic bacteria that are commonly found in atypical pneumonia in all hospitalized COVID-19 patients, and when positive results are obtained, these patients should treated accordingly in order to improve clinical responses and patient outcomes.

鸭瘟病毒弱毒株在免疫雏鸭体内的分布和排毒规律

鸭瘟病毒(DPV)弱毒Cha株经皮下、口服和滴鼻3种途径免疫1日龄雏鸭,应用聚合酶链反应(PCR)检测了病毒在体内分布和排毒规律。Cha株免疫雏鸭后,对血液、心、肝、脾、肺、肾、十二指肠、直肠、法氏囊、胸腺、胰腺、延脑、大脑、小脑、舌、肌肉、骨髓、粪便和食道共19种组织PCR检测结果如下(1)皮下接种雏鸭后4h,即可在心、肝、脾、肾、法氏囊、胸腺、胰腺、延脑、大脑和小脑共10种组织中检出DPV的DNA;8h后,所有采取的组织器官均可检测到DPV的DNA。(2)口服接种雏鸭后4h,可在舌和食道中检测到DPV的DNA;8h后,可在心、肝、脾、肾、胸腺、胰腺、延脑、大脑、小脑、舌、食道和血液共12种组织器官中检出DPV的DNA。(3)滴鼻接种雏鸭后4h,未能在各种组织中检出DPV的DNA;8h后,可在心、肝、脾、肾、胸腺、延脑、大脑、小脑、舌、食道和血液共11种组织中检测到DPV的DNA。(4)在3种免疫途径中,检出时间最早和检出率最高的组织器官为肝脏、脑(大脑、小脑和延脑);3种途径免疫的鸭,从免疫后12h至21d均能从所有采集的组织中检测出DPVDNA。

Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null.

Gene editing for corneal disease management

Gene editing has recently emerged as a promising technology to engineer genetic modifications precisely in the genome to achieve long-term relief from corneal disorders.Recent advances in the molecular biology leading to the development of clustered regularly interspaced short palindromic repeats(CRISPRs) and CRISPR-associated systems,zinc finger nucleases and transcription activator like effector nucleases have ushered in a new era for high throughput in vitro and in vivo genome engineering.Genome editing can be successfully used to decipher complex molecular mechanisms underlying disease pathophysiology,develop innovative next generation gene therapy,stem cell-based regenerative therapy,and personalized medicine for corneal and other ocular diseases.In this review we describe latest developments in the field of genome editing,current challenges,and future prospects for the development of personalized genebased medicine for corneal diseases.The gene editing approach is expected to revolutionize current diagnostic and treatment practices for curing blindness.

Significance of tumor-infiltrating immunocytes for predicting prognosis of hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR)= 66.007, 95% confidence interval (CI): 8.361-521.105;P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.

Persistent delayed auditory memory and executive function deficits 5 years after West Nile Virus Encephalitis: A neuropsychological and neuroimaging single case study

There are presently no in-depth published neuropsychological studies of West Nile Virus (WNV) encephalitis patients that have been well-correlated with high resolution structural MRI. In this study a middleaged male who developed West Nile Virus encephalitis five years previously was examined three times over a two year period. We examined him with the Wechsler Adult Intelligence Scales—Fourth Edition and the Wechsler Memory Scale—Fourth Edition (WAIS-IV/WMS-IV) and Advanced Clinical Solutions battery supplemented by tests of attention, executive, motor and sensory functions. Neuroradiological imaging revealed hypodensities within the left hippocampus in the axial and coronal planes with T2-FLAIR MRI. The man was previously high functioning and although he had prior history of well-controlled epilepsy it seems unlikely that the epilepsy could fully account for the neuropathological changes. The patient had previously completed a demanding six year double science degree program before he became ill with WNV and he had been a successful manager and director of a research company. Delayed auditory memory scores were at least two standard deviation units below age expected levels and semantic fluency and Booklet Category Tests of executive function were also in the impaired range. Moreover the illness onset profile of muscle weakness, extreme fatigue, memory complaints as well as inability to carry out research projects involving planning on the job were highly consistent with WNV encephalitis. If the memory and executive function deficits had been premorbid manifestations of epilepsy it is unlikely he would have attained the levels he did educationally and occupationally. This left hippocampal lesion is characteristic of other encephalitic viral infections such as herpes simplex virus. To our knowledge this is the first lateralized WNV encephalitis medial temporal lobe patient in the published literature.

Establishment of transgenic mouse harboring hepatitis B virus (adr subtype) genomes

INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).

Hepatocellular carcinoma occurrence in DAA-treated hepatitis C virus patients:Correlated or incidental? A brief review

Hepatitis C virus(HCV) chronic infection induces liver fibrosis and cirrhosis but is also responsible for a significant portion of hepatocellular carcinoma(HCC) occurrence. Since it was recognized as a causative factor of chronic hepatitis,there have been multiple efforts towards viral eradication,leading to the first-generation HCV treatment that was based on interferon(IFN)-α and its analogs,mainly PEGylated interferon-α(PEG IFNα). Sustained virological response(SVR),defined as the absence of detectable RNA of HCV in blood serum for at least 24 wk after discontinuing the treatment,was accepted as a marker of viral clearance and was achieved in approximately one-half of patients treated with PEG IFNα regimens. Further research on the molecular biology of HCV gave rise to a new generation of drugs,the so-called direct antiviral agents(DAAs). DAA regimens,as implied by their name,interfere with the HCV genome or its products and have high SVR rates,over 90%,after just 12 wk of per os treatment. Although there are no questions about their efficacy or their universality,as they lack the contraindication for advanced liver disease that marks PEG IFNα,some reports of undesired oncologic outcomes after DAA treatment raised suspicions about possible interference of this treatment in HCC development. The purpose of the present review is to investigate the validity of these concerns based on recent clinical studies,summarize the mechanisms of action of DAAs and survey the updated data on HCV-induced liver carcinogenesis.

Studies of non-metallic organic disinfectants on inactivation of avian influenza viruses

Six different kinds of non-metallic or organic disinfectants were obtained in this research study including “Neutral Electrolyzed Water”, “M22” organic disinfectant solution, Superoxy Food Wash disinfectant, Hydrogen Peroxide, Clorox Germicidal Bleach and Clidox-S. The effectiveness of these disinfectants was studied against various subtypes of avian influenza virus (AIV). The virus-disinfectant mixtures were prepared in serial dilutions of each disinfectant with a constant virus titer and incubated at ambient temperature in different time intervals for virus inactivation. The virus inactivation results were determined by virus recovery in embryonating chicken eggs. Among the six different kinds of nonmetallic disinfectants obtained for this research project, Neutral Electrolyzed Water, “M22” solution, Clorox Germicidal Bleach and Clidox-S were effectively inactivated AIV with appropriate working dilutions and reaction times. Superoxy Food Wash disinfectant and Hydrogen Peroxide were found having limited effect on virus inactivation with extended exposure times of more than 2 hours. These research findings provide scientific data to poultry industry with guidelines to select and use non-metallic organic disinfectants for poultry flock sanitation and disinfection to effectively prevent and control of avian influenza outbreaks.

Vitamin D deficiency and hepatitis viruses-associated liver diseases:a literature review

The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses(HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response(SVR) to interferon(IFN) plus ribavirin(RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBVand HCV-related chronic liver diseases. Furthermore,current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.

High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay

Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors(HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference(HT-RNAi) screens has led to the identification of several key factors involved in the viral lifecycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested(such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase Ⅲα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HTRNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.