ABSTRACT
BACKGROUND: Free flaps are widely used in maxillofacial reconstruction; however, this approach was not feasible in the current case. It was not possible because the free flap method requires microvascular anastomosis expertise, which is difficult, time-consuming and costly. CASE PRESENTATION: An 86-year-old woman suffered squamous cell carcinoma on the right side of her face, which resulted in a large soft-tissue defect. Here, we present a case of facial reconstruction from the inferior margin of the jaw to the top of the head. The size of the defect was 18.5 cm × 7.5 cm, which is rare for a patient of this age in the maxillofacial area. We used the supraclavicular artery island flap (SCAIFP) which measured 19.3 cm × 8.3 cm to repair the defect. After the operation, the flap survived without complications. Then, the patient was followed for 10 months and was satisfied with the aesthetic and functional results at the donor and recipient sites following the tumour resection. The tumour did not recur, and facial nerve function was preserved. CONCLUSION: Our results provide a new choice for the reconstruction of large defects of the head and face, and expand the potential applications of the SCAIFP.
Subject(s)
Carcinoma, Squamous Cell , Facial Neoplasms , Plastic Surgery Procedures , Aged, 80 and over , Carcinoma, Squamous Cell/surgery , Facial Neoplasms/surgery , Female , Free Tissue Flaps , Humans , Plastic Surgery Procedures/methods , Subclavian Artery , Treatment OutcomeABSTRACT
Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease. As a dengue non-endemic country, China has experienced several dengue outbreaks in recent years. However, dengue patients in China displayed distinct clinical characteristics compared to patients in endemic countries. To standardize the diagnosis and treatment of dengue fever, the experts of the Society of Infectious Diseases, Society of Tropical Medicine and Parasitology of Chinese Medical Association, and the Society of Emergency Medicine, China Association of Chinese Medicine have reached this guideline based on guidelines for diagnosis, treatment, prevention and control of dengue (World Health Organization, 2009); guidelines for diagnosis and treatment of dengue (National Health and Family Planning Commission of the People's Republic of China, 2014, Edition 2), health industry standard of the People's Republic of China "diagnosis for dengue fever (WS216-2018)" and systemic reports on dengue. The guideline includes 8 aspects: introduction, terminology, epidemiology and prevention, etiology and pathogenesis, clinical features, diagnosis, treatment and problems to be solved.
Subject(s)
Dengue/diagnosis , Dengue/drug therapy , Disease Outbreaks/prevention & control , Practice Guidelines as Topic , China , Humans , World Health OrganizationABSTRACT
Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion: In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens/drug effects , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Antiviral Agents/adverse effects , DNA, Viral , Female , Hepatitis B, Chronic/immunology , Humans , Injections , Interferon-alpha/adverse effects , Polyethylene Glycols , Recombinant Proteins , Treatment OutcomeABSTRACT
Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion: In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.
Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Sustained Virologic Response , Adult , Drug Therapy, Combination , Female , Genotype , Hepacivirus/drug effects , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Recombinant Proteins/therapeutic use , Treatment Outcome , Viral Load/drug effectsABSTRACT
Reports on the efficacy and safety of long-term entecavir treatment in chronic hepatitis B (CHB) predominantly genotype B or C are insufficient. This study presents the efficacy and safety of entecavir maleate in Chinese CHB patients. Patients were randomly assigned to receive 48-week treatment with either 0.5 mg/day entecavir (group A) or 0.5 mg/day entecavir maleate (group B), and then all patients received treatment with 0.5 mg/day entecavir maleate from week 49. Two hundred and seventy-five patients with CHB (HBeAg-positive: 218) were analysed, predominantly (98.5%) with genotype B or C. Baseline characteristics were balanced. For the HBeAg-positive CHB patients, the mean HBV DNA level decreased similarly (A: by 6.36 log10 IU/mL vs B: by 6.31 log10 IU/mL) between groups at week 144. The percentages of patients who achieved undetectable HBV DNA were similar (A: 70.59% vs B: 66.67%) between groups. Similar HBeAg loss rates (A: 43.53% vs B: 40.23%; P>.05) and HBeAg seroconversion rates (A: 21.52% vs B: 21.18%) were achieved. For the HBeAg-negative CHB patients, similar reductions in HBV DNA levels from baseline (A: by 6.13 log10 IU/mL vs B: by 5.65 log10 IU/mL) and percentages of patients who achieved undetectable HBV DNA (A: 100% vs B: 100%) were achieved. The overall incidence of adverse events was comparable between groups. In conclusions, 48-week administration of entecavir maleate and entecavir showed similar efficacy and safety in Chinese patients with CHB. Long-term entecavir maleate treatment was effective and safe in CHB patients.
Subject(s)
Antiviral Agents/therapeutic use , Genotype , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Maleates , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/chemistry , Biomarkers , DNA, Viral , Drug Compounding , Drug Resistance, Viral , Female , Guanine/administration & dosage , Guanine/adverse effects , Guanine/chemistry , Guanine/therapeutic use , Hepatitis B, Chronic/diagnosis , Humans , Male , Maleates/chemistry , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Treatment Outcome , Viral Load , Young AdultABSTRACT
Studies regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) in patients with chronic hepatitis B receiving first-line nucleos(t)ide analogues is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with entecavir. This was a retrospective cohort study consisting of 139 Chinese patients enrolled in a multicenter clinical trial treated with entecavir or entecavir maleate for up to 240 weeks. Anti-HBc evaluation was conducted for all the available samples using a newly developed double-sandwich anti-HBc immunoassay. At week 240, 35 (25.2%) patients achieved a serological response (HBeAg seroconversion) and these patients at week 240 had significantly higher levels of anti-HBc (P<.01). We defined 4.65 log10 IU·mL-1 , with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict seroconversion. Patients with baseline anti-HBc ≥4.65 log10 IU·mL-1 had 28.0% (26/93) and 35.5% (33/93) chance of seroconversion at weeks 144 and 240, respectively. The baseline anti-HBc level was the strongest predictor for seroconversion at week 144 (OR: 5.78, 95% confidence interval [CI]: 2.05-16.34, P=.001). The baseline anti-HBc level was a strong predictor for seroconversion at week 240 (OR: 5.36, 95% CI: 2.17-13.25, P<.001). Hence, baseline anti-HBc titre is a useful predictor of long-term entecavir therapy efficacy in HBeAg-positive CHB patients, which could be used to optimize antiviral therapy.
Subject(s)
Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B Antibodies/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/immunology , Adult , China , Female , Guanine/therapeutic use , Humans , Male , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
Tenofovir disoproxil fumarate (TDF) has demonstrated long-term efficacy and a high barrier to resistance in multiple chronic hepatitis B (CHB) populations outside of China. This study aimed to evaluate the efficacy and safety of TDF compared with adefovir dipivoxil (ADV) in Chinese patients with CHB during 48 weeks of treatment (ClinicalTrial.gov number, NCT01300234). A Phase 3, multicentred, randomized, double-blind, controlled trial compared the efficacy and safety of TDF with ADV in Chinese patients with CHB. The primary endpoint was the proportion of patients with HBV DNA <400 copies/mL in each treatment group at Week 48, using an unpooled Z-test for superiority. Secondary endpoints included viral suppression, serologic response, histological improvement, normalization of alanine aminotransferase (ALT) levels and the emergence of resistance mutations. A total of 509 patients, 202 hepatitis B e antigen (HBeAg)-positive and 307 HBeAg-negative, with HBV DNA ≥10(5) copies/mL received either TDF 300 mg od or ADV 10 mg od. At Week 48, TDF demonstrated superior viral suppression compared with ADV in both HBeAg-positive (76.7% vs 18.2%, P < 0.0001) and HBeAg-negative (96.8% vs 71.2%, P < 0.0001) patients. The majority of patients in both treatment arms achieved ALT normalization (>85%). No resistance to TDF was observed. The frequency of adverse events was comparable between treatment arms (TDF 3.9% vs ADV 4.8%). In this double-blind, randomized, clinical trial, TDF demonstrated superiority over ADV with respect to viral suppression in Chinese patients with CHB at 48 weeks of treatment and without the development of resistance.
Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Organophosphonates/therapeutic use , Adenine/adverse effects , Adenine/therapeutic use , Adolescent , Adult , Aged , Antiviral Agents/adverse effects , Asian People , China , DNA, Viral/blood , Double-Blind Method , Drug Resistance, Viral , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Male , Middle Aged , Organophosphonates/adverse effects , Tenofovir , Treatment Outcome , Viral Load , Young AdultABSTRACT
Enterobacter amnigenus (EA76) and Klebsiella pneumoniae (KP76) isolates with multidrug-resistant (MDR) patterns were identified from the same patient in the neurosurgery department of our hospital. An outbreak of MDR K. pneumoniae had also occurred in this department. To characterize the resistance mechanism and molecular epidemiology of these isolates, sequential experiments including antimicrobial susceptibility testing, polymerase chain reaction (PCR), plasmid analysis, pulsed field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. EA76 and KP76 were resistant to all of the antibiotics tested, except colistin and tigecycline. blaKPC-2, blaTEM-1, blaSHV-12, blaCTX-M-3, blaCTX-M-14, and rmtB genes were identified in both isolates, with blaKPC-2, blaTEM-1, blaCTX-M-14, and rmtB being co-carried on one plasmid in each isolate. Further analysis showed different restriction patterns between the two KPC-carrying plasmids. Of the 11 carbapenem-resistant isolates found in the outbreak, all were resistant to all of the ß-lactams tested, with 63.64% (7/11) also exhibiting resistance to aminoglycosides and 72.73% (8/11) exhibiting resistance to quinolones. PCR analysis and molecular typing of the 11 K. pneumoniae strains revealed that the seven aminoglycoside-resistant isolates shared the same antibiotic-resistant gene pattern and identical or one-band-difference PFGE profiles relative to KP76. In addition, all of the eight aminoglycoside-resistant isolates, including KP76, belonged to the national epidemic clone ST11. The overall results indicate the emergence of E. amnigenus and outbreak of ST11 K. pneumoniae, with both co-harboring blaKPC and rmtB genes on a single plasmid in our neurosurgery wards.
Subject(s)
Enterobacter/genetics , Genes, Bacterial , Klebsiella pneumoniae/genetics , Methyltransferases/genetics , Plasmids/isolation & purification , beta-Lactamases/genetics , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Cluster Analysis , Drug Resistance, Multiple, Bacterial , Electrophoresis, Gel, Pulsed-Field , Enterobacter/drug effects , Enterobacter/isolation & purification , Enterobacteriaceae Infections/microbiology , Female , Genotype , Humans , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Male , Middle Aged , Multilocus Sequence Typing , Polymerase Chain ReactionABSTRACT
BACKGROUND: Previous studies suggested that a finite course of peginterferon alfa-2a may offer an alternative rescue therapy for patients with lamivudine resistance. However, because of the limitation of study design and small sample size, it is difficult to make definitive conclusion. AIM: To explore the role of peginterferon alfa-2a, in the rescue treatment of HBeAg-positive chronic hepatitis B patients with lamivudine resistance. METHODS: In this randomised study, chronic hepatitis B patients with lamivudine resistance were treated with peginterferon alfa-2a for 48 weeks (n=155) or adefovir for 72 weeks (n=80). All enrolled patients were treated with lamivudine for the first 12weeks. RESULTS: At 6 months posttreatment, 14.6% (18/123) of peginterferon alfa-2a-treated patients achieved HBeAg seroconversion, in contrast to 3.8% (3/80) of adefovir-treated patients after 72 weeks continuous therapy (P=0.01). For peginterferon alfa-2a-treated patients, the rate of HBeAg seroconversion at week 72 was significantly higher in patients who had HBsAg decline >0.5 Log(10) IU/mL from baseline at week 24, compared with patients with HBsAg decline ≤0.5 Log(10) IU/mL from baseline at week 24 (25.5% vs. 7.7%, P=0.01). After 72 weeks continuous adefovir treatment, 22.5% of patients achieved HBV DNA <80 IU/mL, compared with 10.6% in peginterferon alfa-2a-treated patients at 6months off-treatment (P=0.02). CONCLUSIONS: Overall, the response to peginterferon alfa-2a among patients with lamivudine resistance was suboptimal. HBeAg seroconversion rate at week 72 by 48 weeks peginterferon alfa-2a treatment was higher than continuous adefovir therapy. Monitoring HBsAg levels can help to predict response to peginterferon alfa-2a.
Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/therapeutic use , Drug Resistance, Viral/drug effects , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Lamivudine/therapeutic use , Organophosphonates/therapeutic use , Polyethylene Glycols/therapeutic use , Adenine/therapeutic use , Adolescent , Adult , Aged , China , Drug Therapy, Combination , Female , Humans , Interferon alpha-2 , Male , Middle Aged , Recombinant Proteins , Time Factors , Treatment Outcome , Young AdultABSTRACT
Chinese herbs are widely used in the treatment of chronic viral hepatitis B. The effectiveness of 2 months' treatment with Astragali compound (AC), containing Radix Astragali and adjuvant components, was studied for the treatment of chronic viral hepatitis in 116 patients; 92 patients were given other drugs in regular clinical use for viral hepatitis (controls). The clinical efficacy of AC was significantly better in AC-treated patients than in controls. Negative seroconversions of hepatitis B virus (HBV) antigen e and HBV DNA were also significantly higher in AC-treated patients than in controls. Of eight duck viral hepatitis B models infected with duck hepatitis B virus (DHBV) and treated with AC, three showed negative seroconversion of DHBV DNA and serum DHBV DNA levels significantly decreased after AC administration compared with the controls; DHBV DNA was negative in biopsied liver tissue by in situ hybridization and immunohistochemistry in two ducks treated with AC. Pathological changes were milder in AC-treated ducks than in controls. These results indicate that AC may promote recovery from viral hepatitis and inhibit HBV replication.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Hepatitis B, Chronic/drug therapy , Hepatitis, Viral, Animal/drug therapy , Animals , DNA, Viral/blood , Disease Models, Animal , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/pharmacology , Hepatitis B Virus, Duck/drug effects , Hepatitis B, Chronic/blood , Hepatitis, Viral, Animal/blood , Humans , Treatment OutcomeABSTRACT
The objective of this study was to determine the predictive value of the model for end-stage liver disease (MELD) scoring system in patients with acute-on-chronic hepatitis B liver failure (ACLF-HBV), and to establish a new model for predicting the prognosis of ACLF-HBV. A total of 204 adult patients with ACLF-HBV were retrospectively recruited between July 1, 2002 and December 31, 2004. The MELD scores were calculated according to the widely accepted formula. The 3-month mortality was calculated. The validity of the MELD model was determined by means of the concordance (c) statistic. Clinical data and biochemical values were included in the multivariate logistic regression analysis based on which the regression model for predicting prognosis was established. The receiver-operating characteristic curves were drawn for the MELD scoring system and the new regression model and the areas under the curves (AUC) were compared by the z-test. The 3-month mortality rate was 57.8%. The mean MELD score for the patients who died was significantly greater than those who survived beyond 3 months (28.7 vs 22.4, P = 0.003). The concordance (c) statistic (equivalent to the AUC) for the MELD scoring system predicting 3-month mortality was 0.709 (SE = 0.036, P < 0.001, 95% confidence interval 0.638-0.780). The independent factors predicting prognosis were hepatorenal syndrome (P < 0.001), liver cirrhosis (P = 0.009), HBeAg (P = 0.013), albumin (P = 0.028) and prothrombin activity (P = 0.011) as identified in multivariate logistic regression analysis. The regression model that was constructed by the logistic regression analysis produced a greater prognostic value (c = 0.891) than the MELD scoring system (z = 4.333, P < 0.001). The MELD scoring system is a promising and useful predictor for 3-month mortality of ACLF-HBV patients. Hepatorenal syndrome, liver cirrhosis, HBeAg, albumin and prothrombin activity are independent factors affecting the 3-month mortality. The newly established logistic regression model appears to be superior to the MELD scoring system in predicting 3-month mortality in patients with ACLF-HBV.
Subject(s)
Hepatitis B, Chronic/complications , Liver Failure/diagnosis , Models, Statistical , Severity of Illness Index , Adult , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival AnalysisABSTRACT
SETTING: The prognosis of tuberculous meningitis (TBM) is linked to early diagnosis and prescription of adequate treatment. OBJECTIVE: To evaluate the efficacy of the rpoB nested polymerase chain reaction (PCR) and sequencing assay to detect and identify Mycobacterium tuberculosis complex (MTC) strains and strains resistant to rifampicin (RMP) in cerebrospinal fluid specimens (CSF) from patients with highly suspected TBM. DESIGN: Retrospective blinded hospital-based study. RESULTS: rpoB nested PCR and sequencing assay detected MTC in 31/36 CSF specimens from 16 patients with clinically suspected TBM. All of the control CSF specimens from 25 patients with non-TBM showed negative results. One of the 16 patients had a mutation at codon C526G as compared to the rpoB sequences in GenBank. This corresponds to a diagnostic sensitivity of 86% (95%CI 71-95) and a specificity of 100% (95%CI 86-100). CONCLUSION: Our results suggest that rpoB nested PCR and sequencing assay can detect MTC and simultaneously determine its RMP susceptibility in CSF from patients with highly suspected TBM.
Subject(s)
Drug Resistance, Bacterial/genetics , Polymerase Chain Reaction/methods , Tuberculosis, Meningeal/diagnosis , Tuberculosis, Meningeal/genetics , Adolescent , Adult , Aged , Antitubercular Agents/pharmacology , Bacterial Proteins/cerebrospinal fluid , Bacterial Proteins/genetics , Cerebrospinal Fluid/microbiology , DNA, Bacterial/cerebrospinal fluid , DNA, Bacterial/genetics , DNA-Directed RNA Polymerases , Drug Resistance, Bacterial/drug effects , Early Diagnosis , Female , Humans , Male , Middle Aged , Mutation , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Retrospective Studies , Rifampin/pharmacology , Sensitivity and Specificity , Single-Blind Method , Tuberculosis, Meningeal/cerebrospinal fluid , Tuberculosis, Meningeal/drug therapy , Tuberculosis, Meningeal/microbiology , Young AdultABSTRACT
The aims of this study were to investigate the viral differences among lamivudine-resistant hepatitis B virus (HBV) genotypes B and C in vivo. Fifty-three patients carrying lamivudine-resistant HBV were enrolled in this study. HBV genotypes, Levels of alanine aminotransferase (ALT), HBV DNA levels were monitored during therapy. The polymerase and precore/core promoter genes were amplified by polymerase chain reaction and their products were sequenced directly. Among 53 patients resistant HBV genotypes B and C accounted for 41.50% and 58.50%, respectively. The occurrence of reverse transcriptase rt204I mutants was lower in genotype B (36.36%) than that in genotype C (87.10%), whereas rt204V mutants was higher in genotype B (63.64%) than that in genotype C (12.90%). The occurrence of precore mutation (nt1896A) was higher in genotype B (77.27%) than that in genotype C (32.26%). Serum HBV DNA levels after emergence of lamivudine resistance were higher in genotype C (7.71 +/- 0.80 Log copies/mL) compared with genotype B (6.97 +/- 0.77 Log copies/mL). Multivariate analysis identified pretreatment HBV DNA levels, HBeAg status and HBV genotype as independent factors associated with a shorter time to lamivudine resistance(P = 0.035, P = 0.006 and P = 0.001, respectively). Multivariate analysis showed that HBV genotype (P = 0.004) and pretreatment ALT levels (P = 0.01) was independently associated with YMDD mutational patterns. The results showed that the YMDD mutational patterns, precore mutation and serum HBV DNA levels differ between lamivudine-resistant HBV genotypes B and C in vivo. It is valuable for treatment of lamivudine-resistant HBV in clinic.