Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 40(1): 245-252, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892573

RESUMO

AIM: It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis. PATIENTS AND METHODS: Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database. RESULTS: All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001). CONCLUSION: This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.


Assuntos
Grupo com Ancestrais do Continente Asiático , Vírus da Hepatite B/genética , Neoplasias Hepáticas/genética , Proteínas de Fusão Oncogênica/genética , Separase/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Separase/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
2.
J Clin Transl Hepatol ; 7(3): 221-225, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608213

RESUMO

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 µg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

3.
Antivir Ther ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566575

RESUMO

BACKGROUND: This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status. METHODS: Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression. RESULTS: 281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not (P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m2, HCV GT1, platelet count <100×109/l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100×109/l (multivariate Cox regression, P<0.05). CONCLUSIONS: Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.

4.
Virol J ; 16(1): 47, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992019

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is one of the leading causes of liver cancer, creating enormous economic and social burdens. The Chinese government recommends routine screening of inpatients for HCV before invasive procedures to prevent iatric infections. However, the diagnosis and treatment rates for HCV remain low. The aim of this study was to use available routine screening data to understand the HCV screening of inpatients in different regions of China. METHODS: Inpatient information and HCV screening results were collected from January 2016 to December 2016 at eight tertiary hospitals in different regions of China to compare the HCV-positivity of hospitalized patients among different regions and age groups. RESULTS: The HCV screening rate of inpatients was more than 50%. A total of 467,008 inpatients were enrolled in the study (51.20% were male), and the HCV antibody (anti-HCV) -positive rate was 0.88% (95% confidence interval [CI], 0.85-0.91%) among the total population. This rate was significantly higher among all males compared with all females (0.91% vs 0.85%). Moreover, the HCV antibody-positive rate increased with age and was highest for the 60-64-year age group. Notably, 90.14% (3722/4129) of the anti-HCV seropositive patients were 40 years of age or older. HCV screening for people over 40 years old is recommended. CONCLUSIONS: This study highlights the key role of routine examination for HCV infection in hospitalized patients. Full use of inpatient screening results to manage HCV antibody-positive patients and a screening strategy targeting inpatients 40 years and older were found to be low-cost and effective, which will help to find the missing millions of yet unaware patients and also accelerate the elimination of HCV in China.


Assuntos
Hepatite C/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Hepatite B/imunologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Hospitalização/estatística & dados numéricos , Hospitais , Humanos , Lactente , Recém-Nascido , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
5.
Health Qual Life Outcomes ; 16(1): 124, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29903024

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is one of the most common liver infections, with a decrement in HRQoL of HCV patients. This study aims to assess Health-related quality of life (HRQoL) in Chinese patients with chronic HCV infection, and to identify significant predictors of the HRQoL in these patients of China. METHODS: In this cross-sectional observational study, treatment-naïve Han ethnic adults with chronic HCV infection were enrolled. Adopting European Quality of Life scale (EQ-5D) and EuroQOL visual analogue scale (EQ-VAS) were used to qualify HRQoL. Results were reported in descriptive analyses to describe sociodemographic and clinical characteristics. Multiple linear regression analysis was applied to investigate the associations of these variables with HRQoL. Binary logistic regression analysis was performed to identify associations of these variables with HRQoL by dimensions of EQ-5D. RESULTS: Nine hundred ninety-seven patients were enrolled in the study [median age 46.0 (37.0, 56.0) years; male 54.8%]. Mean EQ-5D index and EQ-VAS score were 0.780 ± 0.083 and 77.2 ± 14.8. Multiple Linear regression analysis showed that income (< 2000 RMB, ß = - 0.134; 2000-4999 RMB, ß = - 0.085), moderate or severe symptoms of discomfort (more than one symptoms, ß = - 0.090), disease profile (cirrhosis, ß = - 0.114), hyperlipidemia (ß = - 0.065) and depression (ß = - 0.065) were independently associated with EQ-5D index. Residence (the west, ß = 0.087), income (< 2000 RMB, ß = - 0.129; 2000-4999 RMB, ß = - 0.052), moderate or severe symptoms of discomfort (more than one symptoms, ß = - 0.091), disease profile and depression (ß = - 0.316) were the influencing factors on EQ-VAS. Binary logistic regression indicated that disease profile and clinical depression were the major influencing factors on all five dimensions of EQ-5D. CONCLUSIONS: In this cross-sectional assessment of HCV patients in China, we indicated HRQoL of Chinese HCV patients. Significant negative associations between HRQoL and sociodemographic and clinical factors such as moderate or severe symptoms of discomfort, disease profile and depression emerged. We have to focus on optimally managing care of HCV patients and improving their HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01293279. Date of registration: February 10, 2011.


Assuntos
Hepatite C Crônica/psicologia , Qualidade de Vida , Adulto , China , Estudos Transversais , Depressão/complicações , Feminino , Hepatite C Crônica/classificação , Hepatite C Crônica/complicações , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Dor/complicações , Análise de Regressão , Índice de Gravidade de Doença , Inquéritos e Questionários , Escala Visual Analógica
6.
Hepatol Int ; 12(2): 126-132, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29637511

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a significant medical burden in China, affecting more than 10 million persons. In clinical trials and real-world settings, treatment with ledipasvir/sofosbuvir in patients with genotype 1 HCV infection resulted in high sustained virologic response rates. Ledipasvir/sofosbuvir may provide a highly effective, short-duration, single-tablet regimen for Chinese patients with HCV infection. METHODS: Chinese patients with genotype 1 HCV infection who were HCV treatment naive or treatment experienced, without cirrhosis or with compensated cirrhosis, were treated with open-label ledipasvir/sofosbuvir for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after completing treatment (SVR12). For treatment-naive patients, SVR12 was compared to a historical rate of 57%. The primary safety endpoint was adverse events leading to permanent discontinuation of study drug; serious adverse events were also evaluated. The presence of resistance-associated substitutions (RASs) was evaluated by viral sequencing. RESULTS: All 206 enrolled patients achieved SVR12 (100%; 95% CI 98-100%), including 106 treatment-naive patients (100%; 95% CI 97-100%), which was superior to a historical SVR rate of 57% (p < 0.001). All patients with baseline NS5A and NS5B RASs (14 and 1% of patients, respectively) achieved SVR12. The most common adverse events were viral upper respiratory tract infection (17%), upper respiratory tract infection (14%), and cough (6%). There were no discontinuations due to adverse events; and no treatment-related serious adverse events were reported. CONCLUSION: Ledipasvir/sofosbuvir is a well tolerated and highly effective treatment for Chinese patients with genotype 1 HCV, regardless of prior treatment experience, cirrhosis status, or the presence of pretreatment RASs.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Esquema de Medicação , Farmacorresistência Viral , Feminino , Fluorenos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , RNA Viral/efeitos dos fármacos , Comprimidos , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversos , Adulto Jovem
7.
J Clin Transl Hepatol ; 6(1): 25-34, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29577029

RESUMO

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusions: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

8.
J Gastroenterol Hepatol ; 33(6): 1168-1176, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29380415

RESUMO

BACKGROUND AND AIM: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6. METHODS: Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12). RESULTS: Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment-unrelated adverse events. CONCLUSIONS: Sofosbuvir-based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Adulto Jovem
9.
J Gastroenterol Hepatol ; 33(7): 1389-1396, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29266382

RESUMO

BACKGROUND AND AIM: The aim of this study is to investigate the impact of hepatitis B virus (HBV) S gene integration on serum hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B with long-term nucleos(t)ide analogue (NUC) therapy. METHODS: Chronic hepatitis B patients who performed liver biopsy at baseline and treated with long-term NUC therapy were recruited. The integration of HBV S gene in baseline liver biopsy specimen was detected by Alu polymerase chain reaction method. Serum HBsAg levels were measured at baseline and the second year and the fourth year after NUC therapy by Roche reagent, respectively. Serum HBsAg levels between HBV S gene integrated group and nonintegrated group were compared and analyzed. RESULTS: Seventy patients were eligible for this study. Among them, 11 (15.7%) were found to have HBV S gene integration in their baseline liver biopsy specimens. Similar significant decrease of HBsAg levels was found in both integrated and nonintegrated groups (2.63 vs 2.65 log IU/mL, P = 0.478) after the first 2 years of NUC therapy. Thereafter, the decrease of HBsAg level from 2 to 4 years after therapy was largely unchanged in integrated group as compared with that of nonintegrated group (0.1 vs 2.53 log IU/mL, P = 0.002), with statistical difference. CONCLUSIONS: Serum HBsAg could be originated from the expression of the integrated HBV S gene in patients with S gene integration, which implicated the limitations when regarding HBsAg as a surrogate biomarker of covalently closed circular DNA activity and as an indicator of safe NUC discontinuation.


Assuntos
Antivirais/administração & dosagem , Genes Virais , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Integração Viral/genética , Adulto , Estudos de Coortes , DNA Circular/genética , DNA Viral/genética , Feminino , Hepatite B Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
J Gastroenterol Hepatol ; 32(1): 244-252, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27289083

RESUMO

BACKGROUND AND AIM: In China, chronic hepatitis C virus (HCV) infection represents a considerable healthcare burden. Although interferon-based therapy has been the standard-of-care for many years, few long-term, real-life studies have assessed interferon-based treatment in China. The objective of CCgenos follow-up study was to analyze long-term treatment patterns and outcomes in a cohort of treatment-naïve, Han ethnic, patients with chronic HCV infection. METHODS: Patients who had participated in the CCgenos cross-sectional study were invited to enter this 5-year follow up. Clinical information and centralized HCV-RNA measures were collected at scheduled study visits every 6 months for untreated patients and every 3 months for treated patients. RESULTS: Among 512 patients enrolled, 334 (65.2%) received interferon-based treatment and 178 (34.8%) remained untreated over a median of 4.1 (1.2-4.3) years. A total of 82.8% (424/512) of patients had an IL28B CC genotype (GT); 60.7% (311/512) had HCV GT1b infection, including 121 (38.9%) untreated. Most patients with baseline cirrhosis were untreated (26/46, 56.5%). Among patients who completed treatment and 24 weeks of post-treatment follow up, the duration of interferon-based therapy was frequently longer than recommended (52.9% [92/174] of GT1b-infected were treated for > 1 year). Rates of sustained virologic response (SVR24) were 71.1% (226/318) overall; 62.4% (111/178) among patients with HCV GT1b infection; and 42.9% (15/35) among patients with cirrhosis. CONCLUSIONS: There remains a high unmet need for effective HCV treatment in China, evidenced by a high proportion of patients remaining untreated by the current standard-of-care and relatively low SVR24 rates for patients with both GT1b infection and cirrhosis.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Fatores de Tempo , Resultado do Tratamento
12.
World J Gastroenterol ; 21(46): 13087-94, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26673249

RESUMO

AIM: To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM). METHODS: This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups. RESULTS: Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five-year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group. CONCLUSION: Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Adulto , Antivirais/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , China/epidemiologia , Esquema de Medicação , Farmacorresistência Viral , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/mortalidade , Humanos , Incidência , Lamivudina/efeitos adversos , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto Jovem
13.
J Gastroenterol Hepatol ; 30(6): 1049-56, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25611567

RESUMO

BACKGROUND AND AIM: The hepatitis C virus (HCV) may promote pancreatic ß-cell apoptosis-like cell death through a caspase 3-dependent pathway, initiating the onset of type 2 diabetes mellitus (T2DM); however, the risk factors for development of T2DM and other abnormal glycometabolic factors in HCV patients of the Chinese Han ethnicity have been poorly explored. METHODS: A total of 947 patients Chinese Han patients with confirmed HCV infection were enrolled in a multicenter study in order to examine the genetic and physiological parameters associated with the onset of abnormal glycometabolic conditions, including T2DM and prediabetes. RESULTS: HCV genotype 1b and host interleukin-28B CC genotype were most commonly observed. A total of 145 (15.3%) patients were diagnosed with T2DM and prediabetes. Elevated age, waist circumference, smoking duration, and systolic and diastolic blood pressure were shown to increase risks for abnormal glycometabolism. Liver dysfunction was shown to have positive correlations with abnormal glycometabolism in HCV patients. Genome-wide association studies indicated that certain genetic encoding inosine triphosphatase polymorphs (rs6051702) were associated with elevated risks for abnormal glycometabolism. Coupled with previous research data, it is likely that abnormal glycometabolism may be a useful predictor of risk for poor response to antiviral therapies and treatment-induced complications, such as anemia, in treatment naïve patients. CONCLUSIONS: Abnormal glycometabolism and other such complications of HCV and HCV treatment may share critical metabolic and genetic pathways, providing potentially novel targets for future antiviral therapies for treatment resistant HCV genotypes.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etiologia , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/genética , Hepatite C/virologia , Humanos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/genética , Prevalência
14.
J Gastroenterol Hepatol ; 30(4): 748-55, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25352300

RESUMO

BACKGROUND AND AIM: Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE). METHODS: Adult patients without antiviral therapy within 6 months before screening with hepatitis B virus (HBV)-DNA ≥ 10(5) copies/mL, alanine aminotransferase 1.3-10 times upper limit of normal and compensated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were randomized into three groups with 1:1:1 ratio. Patients in OPTIMIZE group started with lamivudine 100 mg q.d., and ADV 10 mg q.d. was added to suboptimal responders (HBV-DNA > 1000 copies/mL at week 24) from week 30 to week 104, whereas patients with early virological response (HBV-DNA ≤ 1000 copies/mL at week 24) continued MONO until week 104. For all the patients receiving MONO, ADV would be added if virological breakthrough was confirmed. RESULTS: At week 104, more patients in COMBO and OPTIMIZE groups achieved HBV-DNA < 300 copies/mL (53.3% [64/120] and 48.3% [58/120]), with less lamivudine resistance (0.8% and 6.7%) compared with MONO group (HBV-DNA < 300 copies/mL 34.8% [41/118], lamivudine resistance 58.5%). Patients under MONO with early virological response showed superior efficacy at week 104 (HBV-DNA < 300 copies/mL 73.1% [38/52], HBeAg seroconversion 40.4% [21/52]). All regimens were well tolerated. CONCLUSION: Combination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HBeAg-positive CHB patients. In lamivudine-treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development.


Assuntos
Antivirais/administração & dosagem , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Adenina/administração & dosagem , Adenina/análogos & derivados , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
J Clin Gastroenterol ; 49(4): 323-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25014234

RESUMO

OBJECTIVE: To investigate the relationship between relapse and the levels of the residual amount of HBV DNA in serum at cessation in chronic hepatitis B patients meeting 2008 Asian Pacific Association for the Study of the Liver (APASL) nucleos(t)ide analogs (NAs) cessation criteria. METHODS: A total of 72 chronic hepatitis B patients who took NAs and had reached 2008 APASL cessation criteria entered the study. Patients were followed up for 6 months or longer after antiviral therapy was stopped. Serum HBV DNA level at cessation was detected by a highly sensitive polymerase chain reaction assay with detection limitation of 2 IU/mL. RESULTS: Of all the 72 patients, 42 patients (65.3%) relapsed after NA cessation. The detectable rate of the trace amount of HBV DNA at cessation was 41.7% by highly sensitive polymerase chain reaction reagents. The detectable rate of patients with consolidation treatment duration of <18 months was higher than that with consolidation duration of ≥18 months (47.5% vs. 15.4%, P=0.034), and the detectable rate of patients with HBeAg seroconversion within 6 months of treatment was lower than that of ≥6 months (25.0% vs. 61.5%, P=0.036). The residual amount of HBV DNA and detectable rate at cessation showed significant differences between relapsed and nonrelapsed patients (130.4±420.90 vs 44.6±155.16 IU/mL, P=0.004; 55.3% vs. 16.0%, P=0.001). The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840. CONCLUSIONS: Residual amount of HBV DNA in serum at NA cessation is associated with HBV relapse. The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840.


Assuntos
DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Suspensão de Tratamento/estatística & dados numéricos , Adulto , Antivirais/uso terapêutico , Feminino , Seguimentos , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nucleotídeos/uso terapêutico , Projetos Piloto , Reação em Cadeia da Polimerase , Recidiva
16.
J Gastroenterol Hepatol ; 29(3): 545-53, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24090188

RESUMO

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management. METHODS: In this cross-sectional observational study, treatment-naïve Han ethnic adults with recently confirmed chronic HCV infection were enrolled at 28 hospitals across China. HCV genotype and host interleukin 28B (IL28B) genotypes were determined and compared with patient demographic parameters and medical status. RESULTS: Among the 997 HCV-positive patients analyzed, 56.8% were infected with HCV genotype 1b, followed in prevalence by genotypes 2, 3, and 6, with substantial regional variation. Overall, 84.1% of patients were IL28B genotype CC (rs12979860), with little regional variation. Cirrhosis was reported in 10.1% of patients and was significantly associated with hepatitis B virus coinfection, low HCV viral load, low serum alanine aminotransferase, high serum aspartate aminotransferase, diabetes, and high pickled food consumption. Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6. CONCLUSIONS: Most HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hepacivirus/genética , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Adulto , China/epidemiologia , China/etnologia , Coinfecção , Estudos Transversais , Feminino , Genótipo , Hepatite B , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/transmissão , Humanos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
18.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 19(7): 412-5, 2007 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-17631709

RESUMO

OBJECTIVE: To compare the clinical value in predicting the prognosis of chronic severe hepatitis between the Child-Turcotte-Pugh (CTP) score and the model for end-stage liver disease (MELD) score. METHODS: Fifty-five cases with chronic severe hepatitis were scored by CTP and MELD score systems based on their biochemical and coagulation parameters, and related signs within 24 hours after their admission. The termination date of observation was the 90th day after their admission. The actual survival time were recorded. The comparison scores of CTP/MELD were conducted respectively and compared between the survival group and death group, among different clinical stages of chronic severe hepatitis. The correlation of CTP/MELD score with the clinical stages was analyzed respectively. The survival time, mortality and survival rate were compared respectively among the groups classified by CTP/MELD score according to Kaplan-Meier (K-M) survival curve. RESULTS: The CTP score and the MELD score in death group were higher than those in survival group (both P<0.01). The CTP and MELD scores in the advanced stage group were also higher than those in the early and middle stage (both P<0.01). The correlation of the MELD score with the stage was higher (r(s) =0.689,P<0.01) than that of the CTP score (r(s)=0.428, P<0.01). The survival time of patients with CTP<12 scores, was longer than with CTP>or=12 scores, and their survival rate was also higher(both P<0.01). When the MELD score lowered, survival time was longer, and survival rate was higher. The survival time, mortality and survival rate showed significant difference among the groups classified by MELD score (or=40 points, all P<0.01). CONCLUSION: The parameters employed in MELD score system are more OBJECTIVE: and easy to achieve, the score range for patients classification is wider and more practical, and the correlation with the clinical stage is higher than CTP score system, suggesting the MELD score system is better in predicting the prognosis of patients with chronic severe hepatitis than the CTP score system.


Assuntos
Hepatite Crônica/diagnóstico , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Feminino , Hepatite Crônica/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA