RESUMO
BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.
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Antivirais , Disparidades em Assistência à Saúde , Hepatite B Crônica , Humanos , Feminino , Masculino , Antivirais/uso terapêutico , Estudos Transversais , Pessoa de Meia-Idade , Estudos Retrospectivos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/etnologia , Adulto , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Fatores Sexuais , Etnicidade/estatística & dados numéricos , Saúde GlobalRESUMO
BACKGROUND: A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. METHODS: We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/-) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). RESULTS: We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03-5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). CONCLUSION: Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Hepatite B Crônica/tratamento farmacológico , Estudos Retrospectivos , DNA Viral/uso terapêutico , Vírus da Hepatite B , Cirrose Hepática/complicações , Antivirais/uso terapêutico , Antígenos E da Hepatite B/uso terapêuticoRESUMO
BACKGROUND: Chronic hepatitis B (CHB) can progress to cirrhosis, but there are limited noninvasive tools available to estimate cirrhosis risk, including in patients receiving antiviral therapy. This study developed and validated a simple model to assess risk in CHB patients. METHODS: The derivation cohort included 3000 CHB patients from 6 centers in the United States, with 52.60% receiving antiviral therapy. External validation was performed for 4552 CHB individuals from similar cohorts in Taiwan, with 21.27% receiving therapy. Cox proportional hazards regression analyses were used to screen predictors and develop the risk score for cirrhosis. Areas under receiver operating characteristic curves (AUROCs) were calculated for predictive value. RESULTS: Sex, age, diabetes, antiviral treatment status/duration, hepatitis B e-antigen, and baseline alanine aminotransferase/aspartate aminotransferase levels were significantly associated with increased cirrhosis risk. A 13-point risk score was developed based on these predictors. The AUROCs for predicting cirrhosis risk were 0.82 at 3 years, 0.85 at 5 years, and 0.89 at 10 years in the derivation cohort, and 0.82, 0.79, and 0.77 in the validation cohort, respectively. CONCLUSIONS: We developed and validated a simple cirrhosis prediction model with an independent external cohort that can be applied to both treatment-naive and treatment-experienced CHB patients in diverse settings and locations.
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Hepatite B Crônica/epidemiologia , Cirrose Hepática/epidemiologia , Adulto , Idoso , Antivirais/uso terapêutico , Povo Asiático , Progressão da Doença , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients. METHODS: In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups. RESULTS: Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio [HR], 0.19 [95% confidence interval {CI}, .12-.33], Pâ <â .001 and HR, 0.21 [95% CI, .09-.51], Pâ =â .001, respectively) in antiviral-treated patients but not in untreated patients. CONCLUSIONS: FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.
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Carcinoma Hepatocelular , Fígado Gorduroso , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Fígado Gorduroso/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases. RESULTS: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77). DISCUSSION: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Tenofovir/uso terapêutico , Adulto , Carcinoma Hepatocelular/etiologia , China , Estudos de Coortes , Progressão da Doença , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Hong Kong , Humanos , Cooperação Internacional , Japão , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Taiwan , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort. METHODS: Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score. RESULTS: A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001). CONCLUSIONS: The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.
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Antivirais/efeitos adversos , Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Projetos de Pesquisa , Administração Oral , Adulto , Antivirais/administração & dosagem , Ásia/etnologia , Povo Asiático , Estudos de Coortes , DNA Viral/genética , Confiabilidade dos Dados , Feminino , Hepatite B Crônica/etnologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Distribuição Aleatória , Medição de RiscoRESUMO
BACKGROUND: Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial. METHODS: The retrospective cohort study of 1224 Asian chronic hepatitis B (CHB) patients greater than 18 years without baseline osteopenia/osteoporosis seen at four US centers from 2008 to 2016. Patients were categorized into three groups-treatment-naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until the development of osteopenia/osteoporosis or end of the study. RESULTS: Of the 1224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs 16.3% for TDF and 17.6% for ETV; P < 0.001). The 8-year cumulative incidence rate of osteopenia/osteoporosis was 13.17% for TDF, 15.09% for ETV, and 10.17% for untreated patients, with no statistically significant difference among the three groups ( P = 0.218). On multivariate Cox regression controlling for demographics, osteoporosis risk factors, albumin, and hepatitis B virus (HBV) DNA levels, neither TDF (adjusted hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.34 and 1.59) nor ETV (adjusted HR = 0.98; 95% CI: 0.51 and 1.90) were associated with increased osteopenia/osteoporosis risk compared with untreated patients. CONCLUSIONS: Our retrospective study suggests that there is no significant increase in the incidence of osteopenia/osteoporosis for patients with CHB treated with TDF or ETV during a median follow-up of about 4 to 5 years. However, further study with longer follow-up is needed as an anti-HBV therapy, which is often lifelong or long-term and the development of osteopenia/osteoporosis can be a slow process.
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Antivirais/efeitos adversos , Povo Asiático , Doenças Ósseas Metabólicas/induzido quimicamente , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Osteoporose/induzido quimicamente , Adulto , Doenças Ósseas Metabólicas/etnologia , Feminino , Seguimentos , Guanina/efeitos adversos , Guanina/análogos & derivados , Hepatite B Crônica/etnologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/etnologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tenofovir/efeitos adversos , Resultado do Tratamento , Estados UnidosRESUMO
For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2â×âupper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels.We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2â×âULN vs <2â×âULN) and subgrouped by treatment status. Kaplan-Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores.A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10-0.58; Pâ=â0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALTâ<â2â×âULN: 314.46 versus 0 per 100,000 person-years, Pâ=â0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)â≥â2000âIU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALTâ<â2â×âULN and ≥2â×âULN, respectively.After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALTâ<â2â×âULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14-15) in patients with mildly elevated HBV DNAâ≥â2000âIU/mL regardless of ALT levels.
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Antivirais/uso terapêutico , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Transaminases/sangue , Adulto , Distribuição por Idade , Estudos de Coortes , Feminino , Humanos , Incidência , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por SexoRESUMO
GOALS: This study aims to compare the eligibility and treatment rates of patients evaluated by gastroenterology [gastrointestinal (GI)] specialists for chronic hepatitis B (CHB) and patients followed by their primary care physicians (PCPs) only. BACKGROUND: Guidelines have been devised to direct the care of patients with CHB but data on the application of these guidelines, especially in primary care settings, has been limited to date. STUDY: Consecutive CHB patients were enrolled retrospectively from several community clinics in the San Francisco Bay Area: 2 GI referral clinics, 3 primary care clinics, and a multispecialty medical center. Patients were classified as group 1 if they saw a gastroenterologist for CHB within 6 months of presentation or as group 2 if they only saw PCPs. Eligibility according to AASLD 2009 and US Panel 2008 guidelines was determined using clinical and laboratory data available within 6 months of presentation. RESULTS: Patients in group 2 had lower eligibility rates according to both US Panel 2008 (32% vs. 51%, P < 0.001) and AASLD 2009 (8% vs. 24%, P < 0.001) guidelines. GI specialists treated US Panel-eligible patients more readily than PCPs (45% vs. 25%, P < 0.001), and treatment rates in AASLD-eligible patients suggested a similar trend (68% vs. 50%, P = 0.080). CONCLUSIONS: GI specialists were more likely than PCPs to see patients who were treatment eligible, and also more likely to initiate antiviral therapy. However, there are still a considerable number of patients from both settings who did not receive treatment despite being eligible.
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Antivirais/uso terapêutico , Serviços de Saúde Comunitária , Definição da Elegibilidade , Gastroenterologia , Disparidades em Assistência à Saúde , Hepatite B Crônica/tratamento farmacológico , Padrões de Prática Médica , Atenção Primária à Saúde , Adulto , Serviços de Saúde Comunitária/normas , Definição da Elegibilidade/normas , Feminino , Gastroenterologia/normas , Fidelidade a Diretrizes , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde/normas , Hepatite B Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Valor Preditivo dos Testes , Atenção Primária à Saúde/normas , Encaminhamento e Consulta , Estudos Retrospectivos , São FranciscoRESUMO
BACKGROUND AND AIMS: Data on usage of antiviral therapy and application of chronic hepatitis B (CHB) management guidelines in different settings are limited. Our goal is to evaluate the proportion of treatment-eligible patients by 6-month follow-up and treatment rate among eligible patients by 12-month follow-up in diverse settings. METHODS: In this retrospective cohort study, 1,976 treatment-naïve CHB patients were categorized as primary care physician (PCP) group if seen by community PCP (n = 329), gastroenterology (GI) group if seen by community gastroenterologists (n = 1,268), and hepatology group if seen by university hepatologists (n = 379). Treatment eligibility was based on the US Panel 2008 and American Association for the Study of Liver Diseases (AASLD) 2009 guidelines. RESULTS: All groups had similar age, gender, and ethnic distribution. GI and hepatology groups had similar treatment eligibility rates by US Panel (53-54 %) and AASLD guidelines (24-25 %). However, treatment rate was significantly higher in hepatology compared to GI group by the US Panel guideline (59 vs. 45 %, P = 0.001). PCP group had the lowest eligibility and treatment rates by both guidelines. Common reasons for non-treatment were perceived "normal" alanine aminotransferase, desire for further observation, and patient refusal. Male gender, age >50, and subspecialty care predicted treatment initiation in treatment-eligible patients. CONCLUSIONS: Less than half of treatment-eligible patients at primary care clinics received treatment. Community gastroenterology and university liver clinics treated about one-half to two-thirds of eligible patients. Patient and provider education should highlight treatment benefits and the new alanine aminotransferase upper limit of normal.