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In June 2022, the World Health Organization released the"Global health sector strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022—2030". It sets more specific and large-scale goals for eliminating the major infectious diseases, which are still threatening human health. In combination with our clinical practice, present document highlights the advances and challenges in the process of implementing the suggested strategies and ways to achieve the stated goal of eliminating the viral hepatitis in China.
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Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.
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ObjectiveTo investigate missed detection in the screening for hepatitis C virus (HCV) infection in a general hospital in 2015-2018. MethodsA retrospective analysis was performed for the data of 3659 patients who attended People’s Hospital, Peking University, from 2015 to 2018 and underwent the detection of anti-HCV and HCV RNA. Architect I2000 by Abbott and Vitros 3600 by Johnson and Johnson were used to measure anti-HCV, and the Roche Cobas AmpliPrep/Cobas Taqman 96 automatic virus quantification system was used to measure HCV RNA. The specimens were collected from the patients with positive HCV RNA and negative anti-HCV, and Sanger sequencing was used to determine HCV genotype. The patients were followed up to observe the status of HCV infection and clinical conditions. The signal-to-cut-off (S/CO) ratio was used to express the results of anti-HCV detection. GraphPad Prism 5.0 was used to plot the distribution map of the S/CO ratio of anti-HCV. ResultsOf all 3659 patients, 6 (0.16%) had negative anti-HCV based on at least one reagent and positive HCV RNA, with a mean level of (6.40±1.86)log10 IU/ml. Among these 6 patients, 5 (83%) had acute leukemia and 1 had respiratory disease; among these patients, 1 had good prognosis, 3 had poor prognosis, and 2 died. ConclusionWhen antibody is used as the primary screening method for HCV infection, the rate of missed detection reaches 0.16%, and most of these patients have poor prognosis. HCV RNA detection should be performed for patients with immunodeficiency to avoid missed detection.
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Objective To evaluate the prevalence and risk factors of metabolic syndrome among hepatitis C patients in Chinese Han population .Methods This was a multicenter ,cross-sectional study . A total of 997 Chinese Han patients with hepatitis C virus (HCV) infection were enrolled .Demographic data ,anthropometric data and clinical parameters related to metabolic syndrome were collected .Statistical analysis was performed by t-test (normal distribution) or Mann-Whitney U two-sample test (non-normal distribution) and χ test .Binary logistic regression analyses were used to determine the parameters significantly related to metabolic syndrome .Results Among the 997 patients ,170 (17 .1%) patients were diagnosed with metabolic syndrome .Binary logistic regression showed that genotype 2 (OR＝1 .594 ;95% CI :1 .045－2 .431 , P＝ 0 .030) ,older age (OR＝ 1 .040 ;95% CI :1 .022 －1 .058 , P＜ 0 .01) , overweight (OR＝3 .876 ;95% CI :2 .593－5 .792 ,P＜0 .01) ,fatty liver history (OR＝2 .106 ;95% CI : 1 .384－3 .204 ,P＝0 .001) ,homeostasis model assessment insulin (HOMA-IR) (OR＝1 .263 ;95% CI :1 .118－1 .427 , P＜0 .01) ,fasting insulin (OR＝0 .949 ;95% CI :0 .915 －0 .985 , P＝0 .006) ,lower serum albumin level (OR＝0 .957 ;95% CI :0 .915 －1 .000 , P＝0 .049) and higher γ-GT level (OR＝1 .004 ;95% CI :1 .000 －1 .008 , P＝ 0 .0041 ) were all significantly associated with the presence of metabolic syndrome .Conclusions Hepatitis C patients with genotype 2 ,older age ,overweight ,fatty liver history ,higher HOMA-IR ,lower fasting insulin level ,lower serum albumin level or higher γ-GT level should be screened for metabolic syndrome .
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Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.
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Objective To investigate the level of serum free fatty acid (FFA )after improving the life style in patients with coronary heart disease complicated metabolic syndrome and the effect of therapeutic life style on traditional risk factors of coronary artery disease.Methods A total of 395 patients with coronary heart disease complicated metabolic syndrome were recruited.Pa-tients were divided into intervention group (group A,conventional drug therapy+ intensive life style intervention,n=97)and non-intervention group (group B,conventional drug therapy,n=38)according to the scores of life style.Serum free fatty acid (FFA) was determined by ELASA.The scores of life style was obtained bylife style questionnaire.Results (1)The serum FFA of pa-tients with coronary heart disease complicated metabolic syndrome were positively related to waist circumference and waist-high-ra-tio.(2)Waist circumference,BMI and FFA of group A were significantly lower than those in group B after therapeutic life style in-tervention(P <0.05).(3)Compared with the baseline,the constitution index and FFA in group A were significantly lower after 6-months therapeutic life style intervention(P <0.05).Conclusion Therapeutic life style can reduce the level of FFA and constitution index of the patients with coronary heart disease complicated metabolic syndrome.
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<p><b>OBJECTIVE</b>To perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).</p><p><b>METHODS</b>A total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks. Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment, while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment. Serum hepatitis C virus RNA levels at baseline,treatment weeks 4, 12 and 24, end of treatment, and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.</p><p><b>RESULTS</b>The overall sustained virological response (SVR) rate was 85.1%. In all, 91.0% of patients achieved cEVR and were assigned to group A, which had an SVR rate of 90.8%. There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4% vs. 25.0%, P more than 0.05). The positive PV of rapid virological response (RVR), cEVR and delayed virological response (DVR) for SVR was 93.4%, 90.8% and 77.8% respectively, and the negative PV of RVR, EVR and DVR for SVR was 28.0%, 93.3% and 100% respectively. Overall, 66.9% of the patients experienced adverse events (AEs), but only 1.9% of patients experienced sevcre AEs.</p><p><b>CONCLUSION</b>The majority of Chinese RHC treatmentna(i)ve patients (91.0%) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.</p>
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Humans , Antiviral Agents , Asian People , Drug Therapy, Combination , Hepatitis C, Chronic , RibavirinABSTRACT
Both long term follow up and real world research on chronic hepatitis B have accumulated data on nucleos (t) ide analogues in anti-HBV treatment,which shows that resistance mutation turns out to be the major obstacle in achieving response.Identification of genotypic resistance at early stage is key to improve strategy.Deep-sequencing will be helpful to predict resistance earlier.Direct acting autiviral agents on hepatitic C virus tell us resistance at the very beginning,however,more data is still needed to elucidate how to use resistance monitoring of anti-HCV treatment.
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Persistent infection of hepatitis C virus (HCV) remains as a worldwide threat to public health,which involves a complex interaction between virus- and host related factors.HCV is classified as six genotypes and many subtypes according to the sequence heterogenecity.HCV genotype should be determined prior to treatment initiation since it plays a key role in selection of therapeutic regimen for chronic hepatitis C.Development of the antiviral treatment with protease inhibitor in combination with pegylated IFN-α and ribavirin requires the accurate determination of subtypes,e.g. 1a and 1b,as well.Genotyping methods based onsequenceanalysis, reversehybridizationorreal-timePCRhavebeendevelopedand evaluated.Some issues,however,should be settled to standardize the utility and result interpretation of these methods.More recently,host genotypes of IL28B have been found to be closely associated with HCV spontaneous clearance and the response to antiviral therapy.Moreover,polymorphisms in inosine triphosphate pyrophosphatase gene affect ribavirin-induced anemia.Therefore, host genotyping will be beneficial in predicting the outcome of chronic hepatitis C and monitoring the drug-induced adverse events.
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Objective To determine the distribution of HCV genotypes in patients with chronic hepatitis C,study the distribution of genotype in different gender and the relationship between genotypes and serum HCV-RNA levels.Methods Two hundred and six cases of HCV RNA positive patients(all with relevant clinical data) receiving pegylated interferon therapy were collected from May to December 2010.HCV RNA was detected in 206 hepatitis C patients from 40 hospitals in China by Roche Cobas AmpliPrep/Cobas TaqMan HBV test,and genotype was determined by Abbott RealTime HCV G enotype Ⅱ .The distribution of genotypes in the gender was analyzed by chi-square test analysis.The relationship between genotypes and serum HCV RNA levels was detected by single factor analysis and two independent sample t test analysis.Results There were seven different subtypes of HCV in 206 samples,including genotype 1,7 cases(3.4% ,7/206); genotype 1a,2 cases(1.0%,2/206); genotype 1b,123 cases (59.7 %,123/206); genotype 2,32 cases(15.5 %,32/206); genotype 3,27 cases(13.1%,27/206); genotype 6,6 cases(2.9% ,6/206) ;genotype 1/6,5 cases(2.4% ,5/206) ;genotype 2/4,1 cases(0.5%,1/206).There was no significant difference between HCV genotype and gender in 132 cases with genotype 1 and 65 cases with non-genotype 1(genotype 2,3,6) (x2 = 0.000,P ＞ 0.05).There was significant association between quantity of HCV RNA and genotype in 188 patients with HCV(F = 3.371,P＜ 0.01).The 197 patients with HCV single genotype were divided into five groups in terms of region(East,South,West,North and Center).There was no significant difference between HCV genotype 1 and non-genotype 1 in the five groups(x2 = 5.840,P ＞ 0.05).Conclusions It is suggested that HCV 1 b is the most prevalent type in China,followed by HCV 2.There is no significant difference between HCV genotype and gender.The levels of HCV RNA with genotype 1b are significantly higher than those with genotype 3.The levels of HCV RNA with genotype 2 are significantly higher than those with genotype 3.The levels of HCV RNA with genotype 6 are significantly higher than those with genotype 3.
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Objective To evaluate the performance of a DNA microarray method for detecting HBV antiviral drug-resistant mutations. Methods Two hundred and twenty four serum samples from patients with CHB were tested in parallel by DNA microarray and direct sequencing for the mutations within the HBV reverse transcriptase (rt) region, which included rtL180, rtA181, rtM204 and rtN236. Samples with discrepant results were retested by clonal sequencing. Results Complete concordance between DNA microarray and direct sequencing results was observed in 214 out of 224 samples (95. 5% ). The presence of mixed viral populations in the other 10 samples detected by DNA microarray but not by direct sequencing was confirmed by clonal analysis. The DNA microarray could detect minor viral populations which constituted 5.0%-15. 0% of the total viral load. Conclusion DNA microarray is highly consistent with direct sequencing in detecting HBV mutations conferring drug resistance and more sensitive in detecting mixed mutant and wild-type sequences than direct sequencing, which makes it a useful tool for early detection of drug resistance early.
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Hepatitis C virus (HCV) is a common blood-borne pathogen that relies heavily on laboratory assays for the confirmation of infection. Anti-HCV testing is the earliest and classical method which is easy to perform but has a long window period (7 - 8 weeks with the third-generation method) compared to the nucleic acid test (NAT). NAT provides direct evidence for the presence of HCV and quantitative HCV RNA testing has been applied to monitor the antiviral response to treatment. In some developed countries NAT is also used for blood screening. Cost-effectiveness and standardization are the major challenges for NAT. In recent years HCV core antigen assay and the combination antigen-antibody assay have been introduced in some clinical laboratories and proved to be premising in the early diagnosis of HCV, whereas they still remain less sensitive than NAT and require methodological improvement. Finally, HCV genotyping assays based on sequencing or reverse hybridization can provide important prognostic information related to therapeutic response, however, it is rarely used in China due to the high cost.
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Objective To investigate the level of human cytomegalovirus(HCMV)specific CD8+ T lymphoeytes in peripheral blood and the immune reaponae of HCMV reactivation after kidney transplantation.Methods Thirty-eight HCMV seropesitive HLA-A*0201 kidney transplant recipients(9 with HCMV infection and 29 without HCMV infection)and 54 healthy individuals were enrolled.The levels of total HCMV specific CD8+ T cells were measured using HLA-A2 pentamer folded with HCMV-peptide NLVPMVATV.The levels of IFN-γ secreting CD8+ T cells were measured by intracelluhr IEN-γ staining pulsed with the same peptide.Results The median levels of pentamer stained CD8+ T cells were 1.19%(0-19.42%),1.20%(0-18.40%)and 3.2%(0.51%-18.90%)in healthy group,negative HCMV group and positive HCMV group(H=5.34,P＞0.05),respectively.The median levels of IFN-γ secreting CD8+ T cells were 0.72%(0-0.70%),0.47%(0-5.61%)and 0.67%(0.07%-4.00%),respectively(H=0.58,P＞0.05).However,the mean proportions of IFN-γ secreting pentamer stained T cells relative to total HCMV specifc CIL were(60.18±19.16)%,(39.19±17.22)% and(20.02±13.26)%,respectively.There were significant differences among the groups(P＜0.01).Condusiorm There was no significant difference of levels of HCMV specific CD8+ T lymphocytes in peripheral blood between the kidney transplant recipients and healthy individuals.However,the proportion of HCMV-specific IFN-γ producing CD8+ T cells in pentamer stained cells was reduced in the kidney transplant recipients especially in those with active HCMV infection,which may contribute to the inability to control HCMV reactivation.
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The procedures for the calculation and measurement and calibration of output dose of the Siemens primus E accelerator with IAEA regulation are introduced to probe an accurate,rapid and effective method.The parameter value of measurement is determined according to IAEA regulations and absorbed dose calculation formal is briefed to the form that the reading of instrument multiplies exposure calibration coefficient Nx and Air temperature,pressure and humidity effects Ktp and cumulative correction factor Cf the precision of accelerator conform to the standard of QA&QC by the measurement and calibration of the Hospital Primus E accelerator in output dose.The methods of measurement and calibration can be used for the determination of output dose in precise radiotherapy of digital medical linear accelerator and clinical treatment.
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The choline acetyltransferase (CHAT) and the molecular forms of acetyl-cholinesterase (ACHE) activites in various brain regions of 20-day-old hypothyroid and hyper-thyroid rats were measured. The results provided the following information: 1) CHAT and ACHE activities were directly interrelated with thyroid hormones. 2) In both hypothyroid and hyperthyroid rats the nonextractable ACHE activity was distinctly decreased in every brain region, suggesting that both conditions were affected in the critical period of cholinergic synaptic development. 3) The ratio of membrane-bound ACHE to soluble ACHE decreased;it showed that thyroid hormone deficiency might distrub development and maturation of cholinergic neurons. 4) In most regions of the central nervous system,the CHAT seemed to be more affected than ACHE by thyroid hormones.