Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 72 Records) |
Query Trace: Holmberg SD[original query] |
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Mortality among patients with chronic hepatitis B infection: The Chronic Hepatitis Cohort Study (CHeCS)
Bixler D , Zhong Y , Ly KN , Moorman AC , Spradling PR , Teshale EH , Rupp LB , Gordon SC , Boscarino JA , Schmidt MA , Daida YG , Holmberg SD . Clin Infect Dis 2019 68 (6) 956-963 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. |
Low uptake of direct-acting antiviral therapy among hepatitis C patients with advanced liver disease and access to care, 2014-2017
Spradling PR , Xing J , Rupp LB , Moorman AC , Gordon SC , Lu M , Teshale EH , Boscarino JA , Schmidt MA , Daida YG , Holmberg SD . J Clin Gastroenterol 2020 55 (1) 77-83 GOALS: To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs). BACKGROUND: There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings. STUDY: We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs. RESULTS: Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in >/=12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers. CONCLUSIONS: During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited. |
Trends in diagnosed chronic hepatitis B in a US health system population, 2006-2015
Lu M , Zhou Y , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Boscarino JA , Daida YG , Schmidt MA , Li J , Rupp LB , Trudeau S , Gordon SC . Open Forum Infect Dis 2019 6 (7) ofz286 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. |
Hepatocellular carcinoma surveillance in a cohort of chronic hepatitis C virus-infected patients with cirrhosis
Abara WE , Spradling P , Zhong Y , Moorman A , Teshale EH , Rupp L , Gordon SC , Schmidt M , Boscarino JA , Daida YG , Holmberg SD . J Gastrointest Cancer 2019 51 (2) 461-468 BACKGROUND: Six-monthly hepatocellular carcinoma (HCC) screening in cirrhotic patients has been recommended since 2011. HCC prognosis is associated with diagnosis at an early stage. We examined the prevalence and correlates of 6-monthly HCC surveillance in a cohort of HCV-infected cirrhotic patients. METHODS: Data were obtained from the medical records of patients receiving care from four hospitals between January 2011 and December 2016. Frequencies and logistic regression were conducted. RESULTS: Of 2,933 HCV-infected cirrhotic patients, most were >/= 60 years old (68.5%), male (62.2%), White (65.8%), and had compensated cirrhosis (74.2%). The median follow-up period was 3.5 years. Among these patients, 10.9% were consistently screened 6 monthly and 21.4% were never screened. Patients with a longer history of cirrhosis (AOR = 0.86, 95% CI = 0.80-0.93) were less likely to be screened 6 monthly while decompensated cirrhotic patients (AOR = 1.39, 95% CI = 1.06-1.81) and cirrhotic patients between 18 and 44 years (AOR = 2.01, 95% CI = 1.07-3.74) were more likely to be screened 6 monthly compared to compensated cirrhotic patients and patients 60 years and older respectively. There were no significant differences by race, gender, or insurance type. CONCLUSION: The prevalence of consistent HCC surveillance remains low despite formalized recommendations. One in five patients was never surveilled. Patients with a longer history of cirrhosis were less likely to be surveilled consistently despite their greater HCC risk. Improving providers' knowledge about current HCC surveillance guidelines, educating patients about the benefits of consistent HCC surveillance, and systemic interventions like clinical reminders and standing HCC surveillance protocols can improve guideline-concordant surveillance in clinical practice. |
Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes
Li J , Gordon SC , Rupp LB , Zhang T , Trudeau S , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Boscarino JA , Schmidt MA , Daida YG , Lu M . Aliment Pharmacol Ther 2019 49 (5) 599-608 BACKGROUND: The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied. AIM: We investigated whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). METHODS: We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event. RESULTS: Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end-stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate. CONCLUSION: Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes. |
Sustained virological response does not improve long-term glycemic control in patients with type 2 diabetes and chronic hepatitis C
Li J , Gordon SC , Rupp LB , Zhang T , Trudeau S , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Boscarino JA , Schmidt MA , Daida YG , Lu M . Liver Int 2018 39 (6) 1027-1032 BACKGROUND: Sustained virological response (SVR) to treatment for chronic hepatitis C (HCV) may improve short-term glucose control among patients with type 2 diabetes (T2D), but the long-term impact remains largely unknown. We used data from the Chronic Hepatitis Cohort Study to investigate the impact of SVR on long-term trends in HbA1c in patients with T2D. METHODS: "Index date" was defined as the date of treatment initiation (treated patients) or HCV diagnosis (untreated patients). To address treatment selection bias, we used a propensity score approach. We used a piecewise, linear-spline, mixed-effects model to evaluate changes in HbA1c over a five-year period. RESULTS: Our sample included 384 HCV patients with T2D (192 untreated, 192 treated, with SVR or treatment failure [TF]). After adjusting for BMI, HbA1c was stable among untreated and TF patients. In SVR patients, Hb1Ac trajectories evolved in three phases: 1) index through 6 months post-index, average HbA1c decreased significantly from 7.7-5.4% per 90 days (p<0.001); 2) 6-30 months post-index, HbA1c rebounded at a rate of 1.5% every 90 days (p=0.003); and 3) from 30 months onward, HbA1c stabilized at an average level of 7.9 (p-value =0.34). Results from an analysis restricted to patients receiving direct-acting antivirals were consistent with the main findings. CONCLUSION: Successful HCV treatment among patients with T2D significantly reduces HbA1 shortly after treatment, but these decreases are not sustained long-term. Less than three years after SVR, HbA1c rebounds to levels similar to untreated/TF patients, and higher than recommended for type 2 diabetic maintenance. This article is protected by copyright. All rights reserved. |
Long-term liver disease, treatment, and mortality outcomes among 17,000 persons diagnosed with chronic hepatitis C virus infection: Current Chronic Hepatitis Cohort Study status and review of findings
Moorman AC , Rupp LB , Gordon SC , Zhong Y , Xing J , Lu M , Boscarino JA , Schmidt MA , Daida YG , Teshale EH , Spradling PR , Holmberg SD . Infect Dis Clin North Am 2018 32 (2) 253-268 Chronic Hepatitis Cohort Study (CHeCS) publications using data from "real-world" patients with hepatitis C virus (HCV) have described demographic disparities in access to care; rates of advanced liver disease, morbidity, and mortality (2.5%-3.5% per year during 2006-10, although only 19% of all CHeCS decedents, and just 30% of those with deaths attributed to liver disease, had HCV listed on death certificate); substantial comorbidities, such as diabetes, advanced liver fibrosis (29% prevalence), renal disease, and depression, and partial reversal of all these with successful antiviral therapy; patient risk behaviors; and use of noninvasive markers to assess liver disease. |
The predictive value of International Classification of Disease codes for chronic hepatitis C virus infection surveillance: The utility and limitations of electronic health records
Abara WE , Moorman AC , Zhong Y , Collier MG , Rupp LB , Gordon SC , Boscarino JA , Schmidt MA , Trinacty CM , Holmberg SD . Popul Health Manag 2018 21 (2) 110-115 Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and underreporting. With increasing use of electronic health records (EHRs), the authors evaluated the predictive value of using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify chronic HCV cases from EHR data. Longitudinal EHR data from 4 health care systems during 2006-2012 were evaluated. Using chart abstraction and review to confirm chronic HCV cases ("gold standard" definition), the authors calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2 case definitions: (1) >/=2 ICD-9 codes separated by >/= 6 months and (2) >/=1 positive HCV RNA (ribonucleic acid) test. Among 2,718,995 patients, 20,779 (0.8%) with ICD-9 codes indicating a likely diagnosis of chronic HCV infection were identified; 13,595 (65.4%) of these were randomly selected for review. Case definition 1 (>/= 2 ICD-9 codes separated by >/= 6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (>/= 1 positive HCV RNA test) had 74.1% sensitivity, 97.4% PPV, 99.9% specificity, and 99.9% NPV. The predictive values of these alternate EHR-derived ICD-9 code-based case definitions suggest that these measures may be useful in capturing the burden of diagnosed chronic HCV infections. Their use can augment current chronic HCV case surveillance efforts; however, their accuracy may vary by length of observation and completeness of EHR data. |
Impact of sustained virological response on risk of type 2 diabetes among hepatitis C patients in the US
Li J , Zhang T , Gordon SC , Rupp LB , Trudeau S , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Boscarino JA , Schmidt MA , Daida YG , Lu M . J Viral Hepat 2018 25 (8) 952-958 Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts risk of subsequent type 2 diabetes mellitus. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated incidence of type 2 diabetes mellitus from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virological response [SVR] or treatment failure) and baseline risk factors on development of type 2 diabetes mellitus, considering any possible risk factor-by-SVR interactions and death as a competing risk. Among 5,127 patients with an average follow-up of 3.7 years, type 2 diabetes mellitus incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR]= 0.79; 95%CI 0.65-0.96). Risk of type 2 diabetes mellitus was higher among African American and Asian American patients than white patients (aHR=1.82 and 1.75, respectively; p<0.05), and among Hispanic patients than non-Hispanics (aHR=1.86). Patients with BMI >/=30 and 25-30 (aHR=3.62 and 1.72, respectively; p<0.05) demonstrated higher risk than those with BMI <25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR=1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for development of type 2 diabetes mellitus than patients with treatment failure. This article is protected by copyright. All rights reserved. |
Hepatitis B virus infection and hepatitis C virus treatment in a large cohort of hepatitis C-infected patients in the United States
Moorman AC , Xing J , Rupp LB , Gordon SC , Spradling PR , Boscarino JA , Schmidt MA , Daida YG , Teshale EH , Holmberg SD . Gastroenterology 2018 154 (3) 754-758 The rare emergence of hepatitis B virus (HBV) reactivation among hepatitis C virus (HCV)-infected patients receiving direct-acting antiviral (DAA) therapy raises questions about how many HCV-infected patients have active, past, or latent/occult HBV co-infection, and their DAA treatment experience1–3 We sought to characterize these factors, including possible post-DAA reactivation, among HCV patients in the Chronic Hepatitis Cohort Study (CHeCS), a “dynamic” observational study conducted at 4 large integrated U.S. health care systems. Study methods have been described elsewhere.4 |
A point system to forecast hepatocellular carcinoma risk before and after treatment among persons with chronic hepatitis C
Xing J , Spradling PR , Moorman AC , Holmberg SD , Teshale EH , Rupp LB , Gordon SC , Lu M , Boscarino JA , Schmidt MA , Trinacty CM , Xu F . Dig Dis Sci 2017 62 (11) 3221-3234 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. |
Comparison of ICD-9 codes for depression and alcohol misuse to survey instruments suggests these codes should be used with caution
Boscarino JA , Moorman AC , Rupp LB , Zhou Y , Lu M , Teshale EH , Gordon SC , Spradling PR , Schmidt MA , Trinacty CM , Zhong Y , Holmberg SD , Holtzman D . Dig Dis Sci 2017 62 (10) 2704-2712 BACKGROUND: Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern. AIMS: To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments. METHODS: Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments. RESULTS: Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3-23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%). CONCLUSIONS: ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients. |
Race, Age, and Geography Impact Hepatitis C Genotype Distribution in the United States.
Gordon SC , Trudeau S , Li J , Zhou Y , Rupp LB , Holmberg SD , Moorman AC , Spradling PR , Teshale E , Boscarino JA , Daida YG , Schmidt MA , Lu M . J Clin Gastroenterol 2017 53 (1) 40-50 GOALS: To determine the impact of geography and patient characteristics on hepatitis C virus (HCV) genotype and subtype distribution in a large sample of patients under routine clinical care BACKGROUND:: HCV genotype impacts disease course and response to treatment. Although several studies have reported genotype distribution within specific US populations, there are no comprehensive descriptions in large, geographically diverse cohorts. STUDY: Using data from the Chronic Hepatitis Cohort Study, we present the distribution of HCV genotypes (GT) and subtypes (ST) among a racially diverse cohort of over 8000 HCV-infected patients from four large US health systems. RESULTS: Genotype distribution varied significantly by geographic and demographic factors. In age-adjusted analyses, African American patients had significantly higher prevalence of GT1 (85%) than other racial categories, largely driven by a markedly higher proportion of GT1 subtype b ( approximately 34%) than in Asian/other (24%) and white (21%) patients. GT3 represented an increasing proportion of infections as birth decade progressed, from 4% in patients born before 1946 to 18% of those born after 1976. Within the cohort of "living/uncured" patients, highly elevated alanine aminotransferase (>2 times the upper limit of normal) was significantly more common in GT3 patients, whereas Fibrosis-4 Index scores indicative of cirrhosis were most common in the combined group of GT4&6 patients. CONCLUSION: Distribution of HCV genotypes and subtypes in the United States is more variable than suggested by previous national-level estimates and single-center studies. "Real-world" prevalence data may improve targeting of prevention, screening, and treatment efforts for hepatitis C. |
Changing trends in complications of chronic hepatitis C
Lu M , Li J , Rupp LB , Zhou Y , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Boscarino JA , Daida YG , Schmidt MA , Trudeau S , Gordon SC . Liver Int 2017 38 (2) 239-247 BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV)-related complications have increased over the past decade. METHODS: We used join-point regression modeling to investigate trends in these complications from 2006-2015, and the impact of demographics on these trends. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we identified points at which the trend significantly changed, and estimated the annual percent change (APC) in rates of cirrhosis, decompensated cirrhosis, and all-cause mortality, adjusted by race, sex, and age. RESULTS: Among 11,167 adults with chronic HCV infection, prevalence of cirrhosis increased from 20.8% to 27.6% from 2006 to 2015 with adjusted annual percentage change (aAPC) of 1.2 (p<0.01). Although incidence of all-cause mortality increased from 1.8% in 2006 to 2.9% in 2015, a join-point was identified at 2010, with aAPCs of 9.6 before (2006<2010; p<0.01) and -5.2 after (2010≤2015; p<0.01), indicating a decrease in mortality from 2010 and onward. Likewise, although overall prevalence of decompensated cirrhosis increased from 9.3% in 2006 to 10.4% in 2015, this increase was confined to patients 60 or older (aAPC=1.5; p=0.023). Asian American and Black/ African American patients demonstrated significantly higher rates of cirrhosis than White patients, while older patients and men demonstrated higher rates of cirrhosis and mortality. CONCLUSIONS: Although cirrhosis and mortality among HCV-infected patients in the US have increased in the past decade, the mortality has decreased in recent years. |
Uptake of and factors associated with direct-acting antiviral therapy among patients in the Chronic Hepatitis Cohort Study, 2014 to 2015
Spradling PR , Xing J , Rupp LB , Moorman AC , Gordon SC , Lu M , Teshale EH , Boscarino JA , Schmidt MA , Daida YG , Holmberg SD . J Clin Gastroenterol 2017 52 (7) 641-647 BACKGROUND: Limited information is available describing the uptake of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection among patients in general US health care settings. We determined the proportion of HCV-infected patients in the Chronic Hepatitis Cohort Study prescribed DAAs in 2014, who initiated treatment and identified characteristics associated with treatment initiation. METHODS: Uptake was defined as the proportion of HCV-infected patients with at least 1 clinical encounter in 2013 who were prescribed a DAA regimen during 2014 and initiated the regimen by August 2015. Using multivariable analysis, we examined demographic and clinical characteristics associated with receipt of DAAs. RESULTS: The cohort comprised 9508 patients; 544 (5.7%) started a DAA regimen. Higher annual income [adjusted odds ratios (aOR) 2.3 for income>$50K vs. <$30K], higher Fibrosis-4 score (aORs, 2.1, 2.0, and 1.4 for Fibrosis-4, >5.88, 3.25 to 5.88, 2.0 to 3.25, respectively, vs. <2.0), genotype 2 infection (aOR 2.2 vs. genotype 1), pre-2014 treatment failure (aOR 2.0 vs. treatment-naive), and human immunodeficiency virus (HIV) coinfection (aOR 1.8 vs. HCV monoinfection) were associated with DAA initiation. Black race/ethnicity (aOR 0.7 vs. whites) and Medicaid coverage (aOR 0.5 vs. private insurance) were associated with noninitiation. Sex, age, comorbidity, previous liver transplant, and duration of follow-up were not associated with receipt of DAAs. CONCLUSIONS: Among patients in these general US health care settings, uptake of DAA therapy was low in 2014, and especially so among minority and Medicaid patients. Systemic efforts to improve access to DAAs for all patients are essential to reduce morbidity and mortality from HCV infection. |
Hepatitis C virus infection among reproductive-aged women and children in the United States, 2006 to 2014
Ly KN , Jiles RB , Teshale EH , Foster MA , Pesano RL , Holmberg SD . Ann Intern Med 2017 166 (11) 775-782 Background: In the United States, hepatitis C virus (HCV) infection has increased among young persons who inject drugs, but the extent of this epidemic among reproductive-aged women and their children is unknown. Objective: To estimate numbers and describe characteristics of reproductive-aged women with HCV infection and of their offspring. Design: Analysis of the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014. Setting: United States. Participants: 171 801 women (aged 15 to 44 years) and 1859 children (aged 2 and 13 years) with HCV infection reported to the NNDSS; 2.1 million reproductive-aged women and 56 684 children who had HCV testing by Quest Diagnostics. Measurements: NNDSS HCV case reports and Quest laboratory data regarding unique reproductive-aged women and children who were tested for HCV infection. Results: The number of reproductive-aged women with acute and past or present HCV infection in the NNDSS doubled, from 15 550 in 2006 to 31 039 in 2014. Of 581 255 pregnant women tested by Quest from 2011 to 2014, 4232 (0.73% [95% CI, 0.71% to 0.75%]) had HCV infection. Of children tested by Quest, 0.76% (CI, 0.69% to 0.83%) had HCV infection, but the percentage was 3.2-fold higher among children aged 2 to 3 years (1.62% [CI, 1.34% to 1.96%]) than those aged 12 to 13 years (0.50% [CI, 0.41% to 0.62%]). Applying the Quest HCV infection rate to annual live births from 2011 to 2014 resulted in an estimated average of 29 000 women (CI, 27 400 to 30 900 women) with HCV infection, who gave birth to 1700 infants (CI, 1200 to 2200 infants) with the infection each year. Limitations: Only a fraction of HCV infections is detected and reported to the NNDSS. Quest data are potentially biased, because women who are asymptomatic, do not access health care, or have unreported risks may be less likely to be tested for HCV infection. Conclusion: These data suggest a recent increase in HCV infection among reproductive-aged women and may inform deliberations regarding a role for routine HCV screening during pregnancy. Primary Funding Source: Centers for Disease Control and Prevention. |
Reply to "Younger age at cancer diagnosis may be driven by age structure of the HCV population"
Allison RD , Holmberg SD . J Hepatol 2016 64 (2) 517-518 We thank Dr. Shiels and co-authors for reading and commenting on our study.1,2 | | To summarize, we compared the age-adjusted incidence and mortality of 12,126 persons with chronic hepatitis C virus (HCV) infection in the Chronic Hepatitis Cohort Study (CHeCS) to Surveillance, Epidemiology and End Results Program (SEER) cancer registry data and to death certificate information from the Multiple Causes of Death (MCOD) database. We found that the incidence and mortality of many non-liver cancers were significantly higher in persons with HCV infection than in the comparison groups who approximate the US population. | | We also found that the mean age of cancer diagnosis and cancer-related death was younger for persons with HCV infection in the CHeCS. These latter analyses were not age-adjusted and the subject of the comments of Shiels et al. With regard to the younger age at cancer diagnosis among HCV-infected CHeCS patients, our Methods indicate we used the SEER13 database with exclusion of one of the 13 registries, the Alaska Natives registry. We did this to create a better comparison group for CHeCS: this “SEER12” more closely approximates the population of the other 49 states. In contrast, Shiels et al. compared our underlying population to SEER13. When we attempted to reproduce their analyses, but by comparing age of cancer diagnosis in CHeCS to SEER12, we found that the software developed to analyze data from SEER, called ‘SEER*STAT,’ (Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) version 8.2.1) appears to lack the required functionality. | | Specifically, age data can only be extracted from SEER13. There is no function to exclude a SEER registry (i.e. Alaska Natives) and then pull age data. We think this may be why Shiels et al. came to a different conclusion. | | Shiels et al. indicated a particular concern with the ≥64 year age group, the age group with the highest cancer incidence, and noted a smaller proportion of persons aged ≥64 in CHeCS (10%) versus SEER13 (19%). Using U.S. Census data corresponding to each SEER12 registry (i.e., SEER 13 excluding Alaska Natives) and for the US overall, by age group, we found the percentage of persons 64 years or older for SEER was 11.8% and for the entire U.S. population was 14.6%. We think that given the large numbers of patients involved, these close percentages may represent a statistically significant difference between CHeCS and either SEER or the US population. | | In considering the younger age of death among HCV-infected CHeCS cancer patients, it is helpful to remember that CHeCS patients have full ascertainment of their HCV infection, and analyses data from CHeCS and the MCOD show they die at a younger age compared with decedents without HCV infection.3,4 MCOD data –i.e., death certificates–only record 19% of patients who actually have HCV infection at the time of death.3 In sum, HCV-infected patients who develop cancer may indeed die at a younger age because of the contribution of both HCV infection and cancer to their morbidity and mortality. | | As a practical matter, we think that cancer screening-related guidelines should be based on all available data including ours. Given our age-adjusted findings of increased cancer-related incidence and mortality among persons with chronic HCV infection, we think that both general clinicians and specialists should be aware of these elevated risks and take preventive action, such as facilitating tobacco and alcohol cessation and curing HCV with recommended antiviral therapy. |
Long-term progression of viral load and serum markers of fibrosis among treated and untreated patients with chronic hepatitis B
Li J , Gordon SC , Rupp LB , Zhang T , Trudeau S , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Boscarino JA , Daida YG , Schmidt MA , Lu M . J Gastroenterol Hepatol 2016 32 (6) 1250-1257 BACKGROUND AND AIMS: Antiviral therapy for patients with hepatitis B (HBV) infection is generally deferred for "immune inactive" patients, although longitudinal changes in viral load and liver fibrosis remain understudied in this population. Likewise, in treated patients, the temporal relationship between changes in viral load and liver fibrosis is not well-characterized. Using data from the Chronic Hepatitis Cohort Study, we investigated viral load and the Fibrosis-4 index (FIB4, a serum-based marker of liver fibrosis) trajectories in both untreated and treated HBV patients. MATERIALS AND METHODS: We applied a bivariate, piecewise, linear spline, mixed-effects modeling approach to data from 766 HBV patients (342 untreated, 424 treated). Treatment selection bias was adjusted using propensity scores. Multiple sensitivity analyses were used to confirm results in untreated patients. RESULTS: Among all untreated patients, FIB4 began to increase by 0.9% per month (11% per year) (p < 0.05) at 28 months post-index date, suggesting fibrosis progression. Significant FIB4 progression was also observed within a subgroup analysis of "immune inactive" untreated patients. In treated patients, viral load declined 31.8% per month (p < 0.05) for the first 5 months after treatment initiation, and 1.4-1.7% per month (p < 0.05) thereafter. At 5 months after treatment initiation, FIB4 began to decline 0.5% per month (p < 0.05), stabilizing at 28 months. CONCLUSION: Among untreated HBV patients, FIB4 gradually increases over time, suggesting fibrosis progression, even in those patients designated as immune inactive. In treated patients, antiviral therapy results in a rapid decline in viral load followed by a delayed decline in markers of liver fibrosis. |
Distribution of disease phase, treatment prescription and severe liver disease among 1598 patients with chronic hepatitis B in the Chronic Hepatitis Cohort Study, 2006-2013
Spradling PR , Xing J , Rupp LB , Moorman AC , Gordon SC , Teshale ET , Lu M , Boscarino JA , Schmidt MA , Trinacty CM , Holmberg SD . Aliment Pharmacol Ther 2016 44 (10) 1080-1089 BACKGROUND: Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B (CHB) in US general healthcare settings. AIM: To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. METHODS: We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. RESULTS: Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen (HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus (HBV) DNA >2000 IU/mL. CONCLUSIONS: Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels. |
Frequency of and factors associated with receipt of liver-related specialty care among patients with hepatitis C in the Chronic Hepatitis Cohort Study
Foster MA , Xing J , Moorman AC , Boscarino J , Gordon SC , Lu M , Rupp L , Schmidt MA , Trinacty CM , Xu F , Holmberg SD , Spradling PR . Dig Dis Sci 2016 61 (12) 3469-3477 BACKGROUND: Linking persons with hepatitis C virus (HCV) to care and treatment is critical to reduction in disease burden; typically, this entailed referral to a specialist. However, data regarding the frequency and factors associated with referral among patients in healthcare organizations (HCOs) are lacking. METHODS: Among persons in four US HCOs with newly diagnosed HCV during 2006-2011, we determined the frequency of liver-related specialist care after diagnosis. We also identified sociodemographic and clinical characteristics associated with such care by multivariate analysis, adjusted for all variables. RESULTS: Among 3592 patients with newly diagnosed HCV, 57 % (range among sites 45-90 %) received specialist care; of these, 57 % received care within 90 days of diagnosis. Patient characteristics associated with receipt of specialist care included: affiliation with one of the study sites [adjusted odds ratio (aOR) 4.8 vs. the referent site); having Medicare plus private insurance (aOR 1.6 vs. Medicaid); and having elevated alanine aminotransferase (ALT) (aOR 1.6 vs. normal ALT) or lower platelet values (aOR 1.4 vs. normal platelet level). Specialist care within 90 days of diagnosis was associated with private insurance (aOR 1.5 vs. Medicaid), elevated ALT levels (aOR 1.3-2.3 vs. normal), and having ≥2 comorbid conditions (aOR 1.4 vs. no comorbid conditions). Compared to patients not referred, those referred were more likely to be treated (aOR 3.5). CONCLUSIONS: Receipt of specialist care among persons with newly diagnosed HCV varied among HCOs. Clinical evidence of liver disease and having private insurance were associated with prompt receipt of specialist care and HCV treatment. |
Infrequent clinical assessment of chronic hepatitis B patients in United States general healthcare settings
Spradling PR , Xing J , Rupp LB , Moorman AC , Gordon SC , Teshale ET , Lu M , Boscarino JA , Trinacty CM , Schmidt MA , Holmberg SD . Clin Infect Dis 2016 63 (9) 1205-1208 Among 2,338 chronic hepatitis B patients followed during 2006-2013 in the Chronic Hepatitis Cohort Study, 78% had ≥1 alanine aminotransferase and 37% had ≥1 HBV 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. |
Assessing the effect of potential reductions in non-hepatic mortality on the estimated cost-effectiveness of hepatitis C treatment in early stages of liver disease
Leidner AJ , Chesson HW , Spradling PR , Holmberg SD . Appl Health Econ Health Policy 2016 15 (1) 65-74 BACKGROUND: Most cost-effectiveness analyses of hepatitis C (HCV) therapy focus on the benefits of reducing liver-related morbidity and mortality. OBJECTIVES: Our objective was to assess how cost-effectiveness estimates of HCV therapy can vary depending on assumptions regarding the potential impact of HCV therapy on non-hepatic mortality. METHODS: We adapted a state-transition model to include potential effects of HCV therapy on non-hepatic mortality. We assumed successful treatment could reduce non-hepatic mortality by as little as 0 % to as much as 100 %. Incremental cost-effectiveness ratios were computed comparing immediate treatment versus delayed treatment and comparing immediate treatment versus non-treatment. RESULTS: Comparing immediate treatment versus delayed treatment, when we included a 44 % reduction in non-hepatic mortality following successful HCV treatment, the incremental cost per quality-adjusted life year (QALY) gained by HCV treatment fell by 76 % (from US$314,100 to US$76,900) for patients with no fibrosis and by 43 % (from US$62,500 to US$35,800) for patients with moderate fibrosis. Comparing immediate treatment versus non-treatment, assuming a 44 % reduction in non-hepatic mortality following successful HCV treatment, the incremental cost per QALY gained by HCV treatment fell by 64 % (from US$186,700 to US$67,300) for patients with no fibrosis and by 27 % (from US$35,000 to US$25,500) for patients with moderate fibrosis. CONCLUSION: Including reductions in non-hepatic mortality from HCV treatment can have substantial effects on the estimated cost-effectiveness of treatment. |
Prevalence of renal impairment and associated conditions among HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS)
Moorman AC , Tong X , Spradling PR , Rupp LB , Gordon SC , Lu M , Teshale EH , Boscarino JA , Trinacty CM , Schmidt MA , Xu F , Holmberg SD . Dig Dis Sci 2016 61 (7) 2087-93 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 m2, with severe impairment defined as eGFR < 30 ml/min/1.73 m2, 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. |
Higher all-cause hospitalization among patients with chronic hepatitis C: The Chronic Hepatitis Cohort Study (CHeCS), 2006-2013
Teshale EH , Xing J , Moorman A , Holmberg SD , Spradling PR , Gordon SC , Rupp LB , Lu M , Boscarino JA , Trinacity CM , Schmidt MA , Xu F . J Viral Hepat 2016 23 (10) 748-54 In the United States, hospitalization among patients with chronic hepatitis C virus (HCV) infection is high. The healthcare burden associated with hospitalization is not clearly known. We analysed data from the Chronic Hepatitis Cohort Study, an observational cohort of patients receiving care at four integrated healthcare systems, collected from 2006 to 2013 to determine all-cause hospitalization rates of patients with chronic HCV infection and the other health system patients. To compare the hospitalization rates, we selected two health system patients for each chronic HCV patient using their propensity score (PS). Propensity score matching was conducted by site, gender, race, age and household income to minimize differences attributable to these characteristics. We also compared primary reason for hospitalization between chronic HCV patients and the other health system patients. Overall, 10 131 patients with chronic HCV infection and 20 262 health system patients were selected from the 1 867 802 health system patients and were matched by PS. All-cause hospitalization rates were 27.4 (27.0-27.8) and 7.4 (7.2-7.5) per 100 persons-year (PY) for chronic HCV patients and for the other health system patients, respectively. Compared to health system patients, hospitalization rates were significantly higher by site, gender, age group, race and household income among chronic HCV patients (P < 0.001). Compared to health system patients, chronic HCV patients were more likely to be hospitalized from liver-related conditions (RR = 24.8, P < 0.001). Hence, patients with chronic HCV infection had approximately 3.7-fold higher all-cause hospitalization rate than other health system patients. These findings highlight the incremental costs and healthcare burden of patients with chronic HCV infection associated with hospitalization. |
Hepatitis C treatment failure is associated with increased risk of hepatocellular carcinoma
Lu M , Li J , Rupp LB , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Zhou Y , Boscarino JA , Schmidt MA , Lamerato LE , Trinacty C , Trudeau S , Gordon SC . J Viral Hepat 2016 23 (9) 718-29 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). |
Rising mortality associated with hepatitis C virus in the United States, 2003-2013
Ly KN , Hughes EM , Jiles RB , Holmberg SD . Clin Infect Dis 2016 62 (10) 1287-1288 In the United States, hepatitis C virus (HCV)-associated mortality is significant. From 2003-2013, this study found that the number of deaths associated with HCV significantly increased while other national notifiable infectious conditions decreased significantly. The increasing HCV-associated mortality trend underscores the urgency in finding, evaluating, and treating patients. |
Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection
Lu M , Li J , Zhang T , Rupp LB , Trudeau S , Holmberg SD , Moorman AC , Spradling PR , Teshale EH , Xu F , Boscarino JA , Schmidt MA , Vijayadeva V , Gordon SC . Clin Gastroenterol Hepatol 2016 14 (7) 1044-1055 e3 BACKGROUND & AIMS: Sustained viral response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on fibrosis-4 (FIB4) score, over a 10 year period. METHODS: We collected data from participants in the chronic hepatitis C cohort-part of an observational multicenter study of patients with hepatitis C at 4 large US health systems-from January 1, 2006 through December 31, 2013. We calculated patients' FIB4 and aminotransferase-to-platelet ratio index (APRI) scores over a 10 year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved an SVR. RESULTS: In propensity score-adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients with an SVR, FIB4 scores were initially higher than in patients without SVRs, but then decreased sharply, remaining significantly lower over the 10 year period than in untreated patients or patients with treatment failure (P<.001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P<.01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of FIB4 score. CONCLUSIONS: An SVR to HCV treatment appears to induce long-term regression of fibrosis, based on FIB4 or APRI scores collected over 10 years patients in a large study. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores. |
Hepatitis a infections among food handlers in the United States, 1993–2011
Sharapov UM , Kentenyants K , Groeger J , Roberts H , Holmberg SD , Collier MG . Public Health Rep 2016 131 (1) 26-29 We reviewed news reports of hepatitis A virus (HAV)-infected food handlers in the United States from 1993 to 2011 using the LexisNexis® search engine. Using U.S. news reports, we identified 192 HAV-infected food handlers who worked while infectious; of these HAV-infected individuals, 34 (18%) transmitted HAV to restaurant patrons. News reports of HAV-infected food handlers declined from 1993 to 2011. This analysis suggests that universal childhood vaccination contributed to the decrease in reports of HAV-infected food handlers, but mandatory vaccination of this group is unlikely to be cost-effective. |
All-cause mortality and progression risks to hepatic decompensation and hepatocellular carcinoma in patients infected with hepatitis C
Xu F , Moorman AC , Tong X , Gordon SC , Rupp LB , Lu M , Teshale EH , Spradling PR , Boscarino JA , Trinacty CM , Schmidt MA , Holmberg SD . Clin Infect Dis 2015 62 (3) 289-297 BACKGROUND: A key question in chronic hepatitis C (HCV) care is beginning treatment immediately versus delaying treatment. Risks of mortality and disease progression in "real-world" settings are important to assess the implications of delaying HCV treatment. METHODS: A cohort study in HCV patients identified from four 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 2,799 HCV mono-infected 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 progression risks to hepatic decompensation or hepatocellular carcinoma was 37.2% in F4 patients, 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. |
Limited access to new hepatitis C virus treatment under state Medicaid programs
Canary LA , Klevens RM , Holmberg SD . Ann Intern Med 2015 163 (3) 226-8 The burden of fatal liver disease is increasing in the estimated 3.2 million adults chronically infected with hepatitis C virus (HCV) in the United States (1–3). Sofosbuvir (Sovaldi, Gilead Sciences), which was approved by the U.S. Food and Drug Administration in December 2013, is a new oral HCV treatment that, when combined with other therapies, has a therapeutic efficacy (cure) greater than 90% across the 4 major HCV genotypes, limited adverse effects, and a shorter treatment window (usually 12 weeks) than its interferon-based predecessors (4). However, this drug currently retails at $84 000 per patient, forcing many payers to ration this lifesaving treatment. As such, Medicaid programs, which cover approximately 25% of patients with HCV infection who are hospitalized but have limited budgets, face the challenge of deciding who should receive new, costly treatments (4, 5). | To understand policies that might affect patient access to new HCV therapies, we obtained preferred drug lists and prior authorization criteria from state Medicaid fee-for-service program Web sites and, when these were unavailable, elicited feedback from Medicaid programs through direct communication. We compared the guidelines used by state Medicaid programs with those published by the Infectious Diseases Society of America (IDSA) and the American Association for the Study of Liver Diseases (AASLD) (www.hcvguidelines.org). On the basis of data collected from May through November 2014, Medicaid programs in 31 states had designated sofosbuvir a "nonpreferred" drug, the prescription of which requires that clinicians provide evidence of medical necessity as defined by state-specific laws. Seventeen states applied a "preferred" designation, and although demonstrated medical necessity is not necessarily required in these states, all but 2 required clinicians to seek "prior authorization" for sofosbuvir prescription (Table ). |
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