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1.
World J Gastroenterol ; 27(9): 782-793, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33727770

RESUMO

Coronavirus disease 2019 (COVID-19) has become a global pandemic and garnered international attention. The causative pathogen of COVID-19 is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel, highly contagious coronavirus. Numerous studies have reported that liver injury is quite common in patients with COVID-19. Hepatitis B has a worldwide distribution as well as in China. At present, hepatitis B virus (HBV) remains a leading cause of cirrhosis, liver failure, and hepatocellular carcinoma. Because both viruses challenge liver physiology, it raises questions as to how coinfection with HBV and SARS-CoV-2 affect disease progression and mortality. Is there an increased risk of COVID-19 in patients with HBV infection? In this review, we summarize the current reports of SARS-CoV-2 and HBV coinfection and elaborate the interaction of the two diseases. The emphasis was placed on evaluating the impact of HBV infection on disease severity and clinical outcomes in patients with COVID-19 and discussing the potential mechanism behind this effect.


Assuntos
/fisiopatologia , Coinfecção/fisiopatologia , Hepatite B Crônica/fisiopatologia , /diagnóstico , /mortalidade , Coinfecção/diagnóstico , Coinfecção/imunologia , Coinfecção/mortalidade , Progressão da Doença , Saúde Global , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/imunologia , Hepatite B Crônica/mortalidade , Humanos , Prognóstico , Índice de Gravidade de Doença
2.
Aliment Pharmacol Ther ; 52(2): 382-389, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432816

RESUMO

BACKGROUND: Chronic hepatitis B infection is an important contributor to mortality in the United States, yet impact of available and effective oral antivirals on mortality among infected individuals is unknown. AIMS: To compare risks and predictors of mortality in a recent time period between those with chronic, prior and no hepatitis B infection. METHODS: This is a population-based cohort study of National Health and Nutrition Examination Surveys participants between 1999 and 2014 linked to National Death Index data. Adults aged 20 years or older with hepatitis B serologic testing were included. Outcomes of all-cause and liver-related mortality were evaluated using Cox regression. RESULTS: Of 39 206 participants, 192 (0.5%) had chronic and 2694 (6.9%) had prior hepatitis B infection. The all-cause age/sex-standardised mortality rates for chronic, prior and uninfected were 21.4, 15.1 and 11.8 per 1000 person-years respectively. Liver-related mortality occurred at respective rates of 4.1, 0.3 and 0.1 per 1000 person-years. In multivariable analyses, those with chronic infection had 1.9-fold (95% CI 1.1-3.3) increased hazard of all-cause mortality and 13.3-fold (95% CI 3.9-45.5) increased hazard of liver-related mortality compared to uninfected. Predictors of all-cause mortality among chronic infection included heavy alcohol use (HR 18.3, 95% CI 3.3-100.6) and higher alanine aminotransferase (HR 1.02, 95% CI 1.00-1.03). CONCLUSIONS: Mortality among adults living with chronic hepatitis B infection still exceeds that of uninfected despite availability of improved therapeutics. Identification of chronic infection, initiation of treatment among eligible and modulation of co-factors for disease progression are needed to improve survival.


Assuntos
Hepatite B Crônica/mortalidade , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/mortalidade , Estudos de Coortes , Feminino , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
3.
Zhonghua Gan Zang Bing Za Zhi ; 28(4): 310-318, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32403883

RESUMO

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Hepatite B Crônica/complicações , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/virologia , Feminino , Vírus da Hepatite B , Hepatite B Crônica/mortalidade , Humanos , Masculino , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
4.
Sci Rep ; 10(1): 2753, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066795

RESUMO

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/diagnóstico , Vírus da Hepatite E/patogenicidade , Hepatite E/diagnóstico , Doença Aguda , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/patologia , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Idoso , Bilirrubina/sangue , Biomarcadores/sangue , Coinfecção , Creatinina/sangue , Feminino , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/mortalidade , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Hepatite E/mortalidade , Hepatite E/patologia , Hepatite E/virologia , Vírus da Hepatite E/crescimento & desenvolvimento , Humanos , Testes de Função Hepática , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida
5.
J Gastroenterol Hepatol ; 35(9): 1610-1618, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32032974

RESUMO

BACKGROUND AND AIMS: Improvement in Model for End-Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)-related cirrhosis. We aimed to identify factors associated with transplant-free survival and on-treatment MELD score improvement. METHODS: We identified patients with CHB-related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant-free survival at month 6. The secondary endpoints at month 6 were transplant-free survival with > 5-point improvement in MELD score and transplant-free survival with MELD score < 15. RESULTS: Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant-free survival at month 6. Proportion of transplant-free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant-free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant-free survival, 276 (45.6%) achieved > 5-point improvement in MELD score; 183 (30.2%) had 1-point to 5-point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant-free survival had a MELD score < 15 at month 6. CONCLUSION: On top of lower MELD score, patients with CHB-related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant-free survival after 6 months of antiviral treatment.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/mortalidade , Projetos de Pesquisa , Tenofovir/uso terapêutico , Fatores Etários , Idoso , Alanina Transaminase/sangue , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/mortalidade , Falência Hepática/etiologia , Falência Hepática/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Albumina Sérica , Taxa de Sobrevida , Resultado do Tratamento
6.
J Infect Dis ; 221(4): 589-597, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31574141

RESUMO

BACKGROUND: To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis. METHODS: This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death. RESULTS: A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039). CONCLUSIONS: Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis.


Assuntos
Antígenos de Neoplasias/sangue , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/mortalidade , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/etiologia , Glicoproteínas de Membrana/sangue , Adulto , Idoso , Antivirais/uso terapêutico , Biomarcadores Tumorais/sangue , Feminino , Glicosilação , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Risco
7.
Hepatology ; 71(2): 539-548, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31309589

RESUMO

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) and nonalcoholic fatty liver disease are increasingly observed together in clinical practice, and development of nonalcoholic steatohepatitis (NASH) represents another leading cause of liver-related morbidity and mortality. Our aims were to determine whether biopsy-proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk factors. APPROACH AND RESULTS: CHB patients attending two tertiary centers in North America and Europe over 13 years with available clinical and biopsy data were included. Patients were categorized as no-NASH or probable/definite NASH based on standardized histological assessment. Clinical events (death, decompensation, transplant, and hepatoma) were evaluated, and Kaplan-Meier survival estimates and Cox proportional hazards regression were used to analyze the incidence of events. There were 1,089 CHB patients, classified as no-NASH (n = 904, 83%) or NASH (n = 185, 17%), with 52 (6%) versus 27 (15%) experiencing outcome events during follow-up, respectively. In the multivariable analysis adjusting for age, sex, hepatitis B e antigen serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was significantly associated with clinical outcomes (hazard ratio [95% confidence interval], 4.8 [2.6-9.0], P < 0.01) when compared to absence of NASH and AF (reference). NASH and AF were associated with a greater risk of outcomes compared to AF (P = 0.01) or NASH alone (P < 0.01). Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, were independently associated with clinical outcomes (P < 0.05) in place of NASH. NASH was significantly associated with increased risk of hepatocellular carcinoma and death (P < 0.01) but not decompensation (P = 0.33). CONCLUSIONS: In our large combined tertiary center cohort, patients with concomitant NASH and CHB had more AF and shorter time to development of liver-related outcomes or death compared to patients with CHB alone. Among patients with AF, superimposed NASH predicted poorer clinical outcomes.


Assuntos
Hepatite B Crônica/complicações , Hepatite B Crônica/mortalidade , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
9.
Sci Rep ; 9(1): 19417, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857656

RESUMO

The coexistence of HBsAg and anti-HBs has been reported in some chronic hepatitis B patients; however, the long-term outcomes of this serological profile have not been elucidated. We aimed to evaluate the long-term outcomes of HBsAg/anti-HBs double-positive chronic hepatitis B patients. Chronic hepatitis B patients who underwent baseline abdominal ultrasonography and follow-up (HBsAg/anti-HBs assessment and abdominal ultrasonography) at our healthcare center were included. The "coexistence group" included patients positive for both HBsAg and anti-HBs and the "control group" included patients positive for only HBsAg during follow-up. The outcomes were hepatocellular carcinoma (HCC) incidence, HBsAg seroclearance and overall mortality. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Of the 2,341 eligible patients, 166 (7.1%) were in the coexistence group. The total follow-up duration was 5.4 years. The coexistence group had a 3.08-fold higher risk of HCC than the control group [hazard ratio (HR) 3.08, 95% confidence interval(CI) 1.26-7.55, P = 0.014] in multivariate analysis. The coexistence group had more HBsAg seroclearance than the control group (HR 1.43, 95% CI 1.01-2.03, P = 0.046). However, overall mortality did not significantly differ between the 2 groups. The coexistence group is heterogeneous and includes subjects with unfavorable outcomes (incidence of HCC) and favorable outcomes (more HBsAg seroclearance).


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Tempo , Resultado do Tratamento
10.
Medicine (Baltimore) ; 98(52): e18527, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876748

RESUMO

This study aim was to evaluate whether plasma D-dimer levels could serve as a novel prognostic biomarker for 1-month mortality in patients with HBV-related decompensated cirrhosis (HBV-DeCi).This was a retrospective study that enrolled 132 HBV-DeCi patients. Univariate and multivariate regression models were used to identify risk factors for mortality. The area under the receiver operating characteristic curve was calculated to estimate and compare the predictive values of different prognostic markers.In the present study, the plasma D-dimer levels were higher in the nonsurviving group than in the surviving group. Additionally, the D-dimer level was positively correlated with the model for end-stage liver disease (MELD) score. The results of multivariate analysis showed that both the MELD score and D-dimer level are independent predictors of 1-month mortality in HBV-DeCi patients (both P < .01).Plasma D-dimer can be considered a new additional prognostic marker for 1-month mortality in HBV-DeCi patients.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hepatite B Crônica/mortalidade , Cirrose Hepática/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
11.
Aliment Pharmacol Ther ; 50(9): 1037-1048, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31524304

RESUMO

BACKGROUND: Lamivudine and entecavir reduce hepatic events and death in chronic hepatitis B (CHB) patients with cirrhosis, but the impact of tenofovir disoproxil fumarate (TDF) is less well studied. AIM: To investigate the effectiveness of TDF therapy in CHB patients with cirrhosis. METHODS: We studied TDF-treated and untreated CHB patients with cirrhosis from three tertiary centres. TDF cohort included consecutive patients who received TDF for ≥12 months while the untreated cohort were historical controls receiving routine clinical care prior to the availability of anti-viral therapy. The primary outcome was 5-year cumulative probability of hepatocellular carcinoma (HCC) with secondary outcomes being hepatic decompensation and death or liver transplantation (LT). RESULTS: A total of 1088 (291 untreated and 797 TDF-treated) patients were included in the study. Five-year cumulative probabilities in untreated vs TDF-treated cohorts were 14.9% vs 9.8% for HCC (P = .07), 22.3% vs 5.9% for decompensation (P < .01) and 13.1% vs 1.1% for death or LT (P < .01) respectively. On multivariable Cox regression, TDF treatment was independently associated with reduced risks of HCC (adjusted hazard ratio [aHR] 0.46, P < .01), decompensating events (aHR 0.28, P = .01) and death or LT (aHR 0.06, P < .01). On sensitivity analyses, these risk reductions with TDF treatment were consistently demonstrated regardless of severity of liver disease and prior anti-viral treatment. TDF treatment led to sustained improvements in most validated prognostic scores for predicting HCC, decompensation and death. CONCLUSIONS: Compared to untreated patients, TDF treatment reduces the risks of HCC, hepatic decompensation and death in CHB patients with cirrhosis at 5 years.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/mortalidade , Cirrose Hepática/tratamento farmacológico , Falência Hepática/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Tenofovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Falência Hepática/etiologia , Falência Hepática/mortalidade , Falência Hepática/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
12.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414767

RESUMO

BACKGROUND: The C-reactive protein to albumin ratio (CAR) is a novel inflammation index that has recently been used as a marker for poor prognosis or mortality in various patient groups. This study aimed to evaluate the association between the CAR and 30-day mortality in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). METHODS: This was a retrospective cohort study of 113 patients who had been diagnosed with HBV-DeCi. Univariate and multivariate regression models were used to determine risk factors for mortality. RESULTS: The CAR was observed to be significantly higher in the non-surviving patients compared to the surviving patients. Moreover, the CAR was positively correlated with the model for end-stage liver disease (MELD) score and Child-Pugh score. In multivariate analysis, the CAR and the MELD score were independent prognostic factors for HBV-DeCi patients. CONCLUSIONS: A high CAR value at admission can serve as an independent predictor of 1-month mortality in patients with HBV-DeCi.


Assuntos
Proteína C-Reativa/análise , Hepatite B Crônica/complicações , Cirrose Hepática/complicações , Albumina Sérica/análise , Adulto , Idoso , Feminino , Hepatite B Crônica/mortalidade , Humanos , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
13.
Immunol Lett ; 213: 39-45, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376415

RESUMO

T cell exhaustion is involved in the pathogenesis of chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). B lymphocyte-induced maturation protein 1 (BLIMP-1), encoded by the PRDM1 gene, plays a crucial role in T cell exhaustion. This study investigated PRDM1 rs1010273 and rs2185379 polymorphisms in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 liver cirrhosis and 113 HCC), 70 spontaneous HBV infection resolvers and 196 healthy controls. The results showed that the rs1010273 and rs2185379 polymorphisms had no significant differences between patients with chronic HBV infection and healthy controls or between patients with different clinical diseases. However, PRDM1 rs1010273 polymorphism was shown to be significantly associated with the overall survival of patients with HBV-related HCC. The 1-, 3-, and 5-year survival rates of HCC patients were 70.5%, 34.6%, and 11.5%, respectively, in genotype GG carriers and 91.4%, 51.4% and 31.4%, respectively, in genotypes AA + GA carriers (p =  0.008). Multivariate analysis showed that PRDM1 rs1010273 polymorphism was an independent factor associated with the overall survival of patients with HCC (odds ratio, 0.529; 95% confidence interval, 0.126-0.862; p =  0.002). These results provide novel evidence for a role of PRDM1 rs1010273 in the pathogenesis of HBV-related HCC. Additional studies are needed to replicate and extend the findings of this study and to elucidate the underlying mechanisms.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B/imunologia , Hepatite B Crônica , Neoplasias Hepáticas , Polimorfismo Genético , Fator 1 de Ligação ao Domínio I Regulador Positivo , Adulto , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Intervalo Livre de Doença , Feminino , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Hepatite B Crônica/mortalidade , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/imunologia , Taxa de Sobrevida
14.
PLoS One ; 14(8): e0221958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469875

RESUMO

BACKGROUND & AIMS: To evaluate virological breakthrough (VBT) and the risk of hepatocellular carcinoma (HCC) in HBeAg-positive chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment. METHODS: A retrospective cohort study was conducted in a tertiary referral hospital and a total of 228 HBeAg-positive CHB patients treated with ETV for more than 48 weeks were enrolled. Clinical outcome measures included HBeAg seroclearance, maintained virological response and the development of HCC. RESULTS: During a median follow-up period of 197 weeks, VBT developed in 26 (11.4%) patients (VBT group), and the other 202 patients without VBT (non-VBT group). The overall cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group were 23.1% and 23.8%, 27.1% and 37.9%, 27.1% and 55.1%, 27.1% and 74.1%, 27.1% and 76.7% from week 48 to 240, respectively(p = 0.013). The cumulative probability of maintained virological responses from week 48 to 240 were 7.69% and 21.78%, 7.69% in the VBT groups and 36.85%, 7.69% and 51.68%, 7.69% and 64.97%, 7.69% and 72.1% in the non-VBT groups, respectively (p<0.001). In the multivariate analysis, age (p<0.001) and virological response at week 24 (p = 0.005) were independently associated with VBT. Cox regression analysis showed that cirrhosis had carried the highest risk for HCC (HR = 4.99, CI = 1.14-21.81, p = 0.033). Subgroup survival analysis by Kaplan-Meier method showed that patients with VBT had higher incidence of developing HCC than without VBT in cirrhotic patients (50% (95%CI = 1-99%) vs 9% (95% CI = 1-9%); p = 0.048). CONCLUSIONS: VBT was associated with adverse clinical outcomes, including a low probability of HBeAg seroclearance, failure to achieve maintained virological responses, and a risk of developing HCC. Patients, particularly with cirrhosis, who had experienced VBT during ETV treatment, more likely developed HCC.


Assuntos
Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Hepatite B Crônica/mortalidade , Hepatite B Crônica/virologia , Carga Viral , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Feminino , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/análogos & derivados , Guanina/uso terapêutico , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
15.
Clin Liver Dis ; 23(3): 401-416, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31266616

RESUMO

Hepatitis B virus (HBV) infection is the most common chronic viral infection worldwide and remains a significant global health problem. Chronic HBV infection can progress to cirrhosis, liver failure, and hepatocellular carcinoma. Outcome of chronic HBV infections depends on the host, virus, and environmental factors. Although effective prophylactic vaccines and antiviral therapies exist, curative treatment is not yet available. Intense research into a cure for HBV is ongoing and proposed definitions of cure and endpoints for clinical trials evaluating "curative" therapy are discussed.


Assuntos
Antígenos E da Hepatite B/imunologia , Hepatite B/tratamento farmacológico , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Hepatite B/diagnóstico , Hepatite B/mortalidade , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/mortalidade , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Prevalência , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
16.
J Dig Dis ; 20(9): 467-475, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31231938

RESUMO

OBJECTIVE: Since July 1, 2011 antiviral therapy for hepatitis B virus infection has been listed as a reimbursable expense for medical insurance in Beijing. This study aimed to assess the impact of this program on liver-related death for patients with chronic hepatitis B (CHB). METHODS: Profiles of patients with CHB discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. Liver-related deaths in these patients occurring between January 2008 and December 2017 were retrieved by linking them to the death certification database. Liver-related mortality (number of deaths divided by the observed person-years) before and after this program was launched was calculated and compared. A Poisson regression was performed to assess the strength of association (risk ratio [RR]) between the reimbursement program and liver-related mortality. RESULTS: Information on 35 943 discharged patients (17 114 patients with non-cirrhotic and 18 829 with compensated cirrhotic CHB) was retrieved. Altogether 3 832 liver-related deaths during the 190 695 person-years were observed. After the reimbursement program was launched, liver-related mortality per 100 person-years dropped from 0.38% to 0.16% for patients with non-cirrhotic CHB, and from 4.03% to 3.39% for those with compensated cirrhosis. The program was associated with a lower risk of developing liver-related death for patients with non-cirrhotic CHB (RR 0.40, 95% confidence interval [CI] 0.30-0.52) and those with compensated cirrhosis (RR 0.84, 95% CI 0.78-0.89). CONCLUSION: Coverage of antiviral therapy by basic medical insurance reduced the risk of developing liver-related death for patients with non-cirrhotic and with compensated cirrhotic CHB.


Assuntos
Hepatite B Crônica/mortalidade , Reembolso de Seguro de Saúde/estatística & dados numéricos , Adulto , Distribuição por Idade , Antivirais/economia , Antivirais/uso terapêutico , Pequim/epidemiologia , Bases de Dados Factuais , Atestado de Óbito , Custos de Medicamentos/estatística & dados numéricos , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/economia , Humanos , Cirrose Hepática/economia , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por Sexo
17.
Gastroenterology ; 157(4): 1055-1066.e11, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31251928

RESUMO

BACKGROUND & AIMS: Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States. METHODS: We performed a population-based study using US Census and the National Center for Health Statistics mortality records from 2007 through 2017. We identified trends in age-standardized mortality using Joinpoint trend analysis with estimates of annual percent change. RESULTS: The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study, age-standardized mortality from hepatitis B virus-related extrahepatic complications increased by an average of 2.0% each year. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly. CONCLUSIONS: In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.


Assuntos
Causas de Morte/tendências , Hepatite B Crônica/mortalidade , Hepatite C Crônica/mortalidade , Hepatopatias Alcoólicas/mortalidade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Censos , Bases de Dados Factuais , Atestado de Óbito , Feminino , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Hepatopatias Alcoólicas/diagnóstico , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Prevalência , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
19.
BMC Gastroenterol ; 19(1): 74, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092203

RESUMO

BACKGROUND: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa. METHODS: Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality. RESULTS: Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26-276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23-173.48; p = 0.002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73-7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02-1.10; p = 0.007). CONCLUSIONS: Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients. TRIAL REGISTRATION: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/mortalidade , Tenofovir/uso terapêutico , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Etiópia/epidemiologia , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/fisiopatologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
20.
BMJ Open ; 9(4): e027696, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967410

RESUMO

OBJECTIVES: Chronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality. DESIGN: Population-based prospective cohort study. SETTING: China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008. PARTICIPANTS: 475 801 participants 30-79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Total and cause-specific mortality. RESULTS: A total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants. CONCLUSIONS: Among Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.


Assuntos
Hepatite B Crônica/epidemiologia , Hepatite B Crônica/mortalidade , Adulto , Hemorragia Cerebral/mortalidade , China/epidemiologia , Doenças do Sistema Digestório/mortalidade , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B , Hepatite B Crônica/imunologia , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Isquemia Miocárdica/mortalidade , Estudos Prospectivos , Fatores de Risco
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