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1.
J Viral Hepat ; 30(9): 746-755, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37415492

RESUMO

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Humanos , Masculino , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/complicações , Estudos de Coortes , Medição de Risco , Resposta Viral Sustentada , Cirrose Hepática/complicações , Hepatite C/tratamento farmacológico
2.
J Viral Hepat ; 30(6): 544-550, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36872452

RESUMO

Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75-5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31-3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22-0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors-diabetes, cirrhosis and BMI-were associated with PD/PKM.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Doença de Parkinson Secundária , Doença de Parkinson , Humanos , Antivirais/uso terapêutico , Estudos de Coortes , Doença de Parkinson/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Hepacivirus , Resposta Viral Sustentada , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/complicações , Doença de Parkinson Secundária/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico
3.
J Infect Dis ; 226(5): 896-900, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-35039863

RESUMO

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Atenção à Saúde , Hepatite B/complicações , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia
4.
J Viral Hepat ; 29(3): 189-195, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34905259

RESUMO

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with 'definite' indications for antiviral therapy remained untreated.


Assuntos
Hepatite B Crônica , Alanina Transaminase , Antivirais/uso terapêutico , Estudos de Coortes , DNA Viral , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Estados Unidos
5.
J Clin Gastroenterol ; 56(3): 273-279, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33780209

RESUMO

BACKGROUND: Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS: Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS: Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS: From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Prevalência
6.
Clin Infect Dis ; 73(5): 891-894, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-33561187

RESUMO

Using electronic health records, we found that hepatitis C virus (HCV) reporting on death certificates of 2901 HCV-infected decedents from 4 US healthcare organizations during 2011-2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the US HCV mortality burden.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Causas de Morte , Hepacivirus , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia
7.
Clin Epidemiol ; 12: 1261-1267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204167

RESUMO

BACKGROUND: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients. METHODS: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis. RESULTS: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively). CONCLUSION: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

8.
Open Forum Infect Dis ; 6(7): ofz286, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31341929

RESUMO

BACKGROUND: Trends in the epidemiology of chronic hepatitis B (CHB) among routine clinical care patients in the United States are not well documented. We used data from the Chronic Hepatitis Cohort Study to investigate changes in prevalence and newly recorded cases of CHB from 2006 to 2015. METHODS: Annual percentage changes (APCs) were estimated using join point Poisson regression. Analyses were adjusted by study site; when an interaction with the trend was observed, APCs were estimated by subgroups. Differences in rates based on race, age, and sex were calculated with rate ratios. RESULTS: We identified 5492 patients with CHB within select health systems with total populations that ranged from 1.9 to 2.4 million persons. From 2006 to 2014, the prevalence of diagnosed CHB increased from 181.3 to 253.0 per 100 000 persons in the health system population; from 2014 to 2015, it declined to 237.0 per 100 000 persons. APC was +3.7%/y through 131 December 2014 (P < .001) and -15.0%/y (P < .001) thereafter. The rate of newly reported cases of CHB did not change significantly across the study period (APC, -1.1%/y; P = .07). The rates of newly reported cases were 20.5 times higher among patients in the Asian American/American Indian/Pacific Islander (ASINPI) category, compared with white patients, and 2.8 times higher among African American patients. The ratio of male to female patients was roughly 3:2. CONCLUSIONS: The prevalence of diagnosed CHB in this US patient population increased from 2006 to 2014, after which it decreased significantly. Rates declined most rapidly among patients ≤40 or 61-70 years old, as well as among ASINPI patients. The rate of newly reported cases remained steady over the study period.

9.
Clin Infect Dis ; 68(6): 956-963, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30060032

RESUMO

BACKGROUND: According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). METHODS: We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. RESULTS: Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P < .001). CHB patients died at an average age of 59.8 years-14 years younger than the general U.S. population-and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851-1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81-16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. CONCLUSIONS: Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB.


Assuntos
Hepatite B Crônica/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Seguimentos , Vírus da Hepatite B , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
10.
Dig Dis Sci ; 62(11): 3221-3234, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28965221

RESUMO

BACKGROUND: Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. AIM: Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. METHODS: Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. RESULTS: Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87). CONCLUSION: This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR.


Assuntos
Carcinoma Hepatocelular/virologia , Técnicas de Apoio para a Decisão , Hepatite C Crônica/complicações , Neoplasias Hepáticas/virologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Plaquetas , Carcinoma Hepatocelular/diagnóstico , Ensaios Enzimáticos Clínicos , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos , Adulto Jovem
11.
Clin Epidemiol ; 9: 369-376, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28744162

RESUMO

Viral hepatitis-induced cirrhosis can progress to decompensated cirrhosis. Clinical decompensation represents a milestone event for the patient with cirrhosis, yet there remains uncertainty regarding precisely how to define this important phenomenon. With the development of broader treatment options for cirrhotic hepatitis patients, efficient identification of liver status before evolving to decompensated cirrhosis could be life-saving, but research on the topic has been limited by inconsistencies across studies, populations, and case-confirmation methods. We sought to determine whether diagnosis/procedure codes drawn from electronic health records (EHRs) could be used to identify patients with decompensated cirrhosis. In our first step, chart review was used to determine liver status (compensated cirrhosis, decompensated cirrhosis, non-cirrhotic) in patients from the Chronic Hepatitis Cohort Study. Next, a hybrid approach between Least Absolute Shrinkage and Selection Operator regression and Classification Regression Trees models was used to optimize EHR-based identification of decompensated cirrhosis, based on 41 diagnosis and procedure codes. These models were validated using tenfold cross-validation; method accuracy was evaluated by positive predictive values (PPVs) and area under receiver operating characteristic (AUROC) curves. Among 296 patients (23 with hepatitis B, 268 with hepatitis C, and 5 co-infected) with a 2:1 ratio of biopsy-confirmed cirrhosis to noncirrhosis, chart review identified 127 cases of decompensated cirrhosis (Kappa=0.88). The algorithm of five liver-related conditions-liver transplant, hepatocellular carcinoma, esophageal varices complications/procedures, ascites, and cirrhosis-yielded a PPV of 85% and an AUROC of 92%. A hierarchical subset of three conditions (hepatocellular carcinoma, ascites, and esophageal varices) demonstrated a PPV of 81% and an AUROC of 86%. Given the excellent predictive ability of our model, this EHR-based automated algorithm may be used to successfully identify patients with decompensated cirrhosis. This algorithm may contribute to timely identification and treatment of viral hepatitis patients who have progressed to decompensated cirrhosis.

12.
Clin Infect Dis ; 63(9): 1205-1208, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27486115

RESUMO

Among 2338 chronic hepatitis B patients followed during 2006-2013 in the Chronic Hepatitis Cohort Study, 78% had ≥1 alanine aminotransferase and 37% had ≥1 hepatitis B virus DNA level assessed annually. Among cirrhotic patients, 46% never had hepatic imaging. Patients in this cohort were insufficiently monitored for disease activity and hepatocellular carcinoma.


Assuntos
Atenção à Saúde , Hepatite B Crônica/terapia , Adolescente , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Continuidade da Assistência ao Paciente , Feminino , Seguimentos , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/fisiopatologia , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
13.
Dig Dis Sci ; 61(7): 2087-93, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27216163

RESUMO

BACKGROUND: Guidelines for the treatment of HCV-infected persons were updated in August 2015 with new recommendations for patients with renal impairment. Treatment is imperative for patients with severe, renal-associated extrahepatic manifestations of HCV infection. AIMS: We sought to describe the prevalence of these conditions among current HCV-infected patients in a population-based prospective, observational cohort study at four large US health systems. METHODS: Data from cohort patients with chronic HCV infection during 2012 were analyzed for the period from 2006 to 2013. We determined the prevalence of mild to moderately impaired renal function defined as having the most recent estimated glomerular filtration rate [eGFR] ≤ 80 ml/min/1.73 m(2), with severe impairment defined as eGFR < 30 ml/min/1.73 m(2), based on the treatment guidelines. Prevalence of extrahepatic conditions was ascertained using ICD9-codes. RESULTS: Among 5772 persons, the prevalence of eGFR ≤ 80 was 33 % and eGFR < 30 was 2 %, including among patients with hepatic fibrosis. Diagnosed extrahepatic renal manifestations were rare: vasculitis- 0.2 %, nephrotic syndrome- 0.3 %, and cryoglobulinemia- 0.9 %. CONCLUSIONS: While the prevalence of severe renal impairment and diagnosed extrahepatic manifestations was low, mild-to-moderate renal impairment was common in HCV patients, including those with advanced liver fibrosis for whom the need for treatment is urgent.


Assuntos
Hepatite C Crônica/complicações , Insuficiência Renal/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
14.
J Viral Hepat ; 23(9): 718-29, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27028626

RESUMO

Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV) reduces risk of hepatocellular carcinoma (HCC), but there is little information regarding how treatment failure (TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study (CHeCS-an observational study based in four large US health systems, with up to 7 years of follow-up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582 (43%) of these achieved sustained virological response (SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50-2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all-cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48, CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause mortality (aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93 for TF patients).


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Falha de Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
15.
Clin Infect Dis ; 62(3): 289-297, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26417034

RESUMO

BACKGROUND: A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. METHODS: This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. RESULTS: Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. CONCLUSIONS: The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/mortalidade , Falência Hepática/epidemiologia , Adulto , Idoso , Biópsia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
16.
Am J Gastroenterol ; 110(8): 1169-77; quiz 1178, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26215529

RESUMO

OBJECTIVES: The severity of liver disease in the hepatitis C virus (HCV)-infected population in the United States remains uncertain. We estimated the prevalence of cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters including liver biopsy, diagnosis/procedure codes, and a biomarker. METHODS: Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received health services during 2006-2010 were included. Cirrhosis was identified through liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic decompensation, and Fibrosis-4 (FIB-4) scores ≥5.88. Demographic and clinical characteristics associated with cirrhosis were identified through multivariable logistic modeling. RESULTS: Among 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%) patients, whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%) patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only 356 (54%) had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender, Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes, history of antiviral therapy, and history of alcohol abuse were independently associated with higher odds of cirrhosis (all, P<0.05). Conversely, private health insurance coverage, black race, and HCV genotype 2 were associated with lower odds of cirrhosis. CONCLUSIONS: A high proportion of patients with biopsy-confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD-9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis in cohort studies. Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.


Assuntos
Infecções por HIV/epidemiologia , Hepatite C Crônica/epidemiologia , Cirrose Hepática/epidemiologia , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Idoso , Alcoolismo/epidemiologia , Antirretrovirais/uso terapêutico , Asiático/estatística & dados numéricos , Biópsia , Coinfecção , Diabetes Mellitus/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Seguro Saúde , Classificação Internacional de Doenças , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Estados Unidos/epidemiologia
17.
Hepatology ; 61(5): 1479-84, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25131217

RESUMO

UNLABELLED: To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis-defined by liver biopsy or mean FIB-4 score >5.88-and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for "late diagnosis" with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. CONCLUSION: Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality.


Assuntos
Diagnóstico Tardio , Hepatite C Crônica/diagnóstico , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Clin Gastroenterol Hepatol ; 12(5): 885-93, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24107395

RESUMO

BACKGROUND & AIMS: Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers. METHODS: We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence. RESULTS: Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL. CONCLUSIONS: In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bioestatística , Carcinoma Hepatocelular/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Incidência , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
19.
Clin Infect Dis ; 57(2): 240-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23592832

RESUMO

BACKGROUND: Liver biopsy remains critical for staging liver disease in hepatitis C virus (HCV)-infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis sought to validate APRI (aspartate aminotransferase [AST]-to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase [ALT], AST, and platelets plus patient age) to stage liver disease. METHODS: Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0-F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale. RESULTS: We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3-F4) from mild-to-moderate fibrosis (F0-F2) were 0.80 (95% confidence interval [CI], .78-.82) for APRI and 0.83 (95% CI, .81-.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher. CONCLUSIONS: In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.


Assuntos
Biomarcadores/sangue , Técnicas de Laboratório Clínico/métodos , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biópsia , Feminino , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/patologia , Pessoa de Meia-Idade , Contagem de Plaquetas , Soro/química , Índice de Gravidade de Doença , Estados Unidos , Adulto Jovem
20.
Clin Infect Dis ; 56(1): 40-50, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22990852

RESUMO

BACKGROUND: The Chronic Hepatitis Cohort Study (CHeCS), a dynamic prospective, longitudinal, observational cohort study, was created to assess the clinical impact of chronic viral hepatitis in the United States. This report describes the cohort selection process, baseline demographics, and insurance, biopsy, hospitalization, and mortality rates. METHODS: Electronic health records of >1.6 million adult patients seen from January 2006 through December 2010 at 4 integrated healthcare systems in Detroit, Michigan; Danville, Pennsylvania; Portland, Oregon; and Honolulu, Hawaii were collected and analyzed. RESULTS: Of 2202 patients with chronic hepatitis B virus (HBV) infection, 50% were aged 44-63 years, 57% male, 58% Asian/Pacific Islander, and 13% black; and 5.1% had Medicaid, 16.5% Medicare, and 76.3% private insurance. During 2001-2010, 22.3% had a liver biopsy and 37.9% were hospitalized. For the 8810 patients with chronic hepatitis C virus (HCV) infection, 75% were aged 44-63 years, 60% male, 23% black; and 12% had Medicaid, 23% Medicare, and 62% private insurance. During 2001-2010, 38.4% had a liver biopsy and 44.3% were hospitalized. Among persons in care, 9% of persons with HBV and 14% of persons with HCV infection, mainly those born during 1945-1964, died during the 2006-2010 five-year period. CONCLUSIONS: Baseline demographic, hospitalization, and mortality data from CHeCS highlight the substantial US health burden from chronic viral hepatitis, particularly among persons born during 1945-1964.


Assuntos
Hepatite B Crônica/mortalidade , Hepatite C Crônica/mortalidade , Adulto , Idoso , Registros Eletrônicos de Saúde , Feminino , Havaí/epidemiologia , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Oregon/epidemiologia , Pennsylvania/epidemiologia , Estudos Retrospectivos
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