Showing posts with label HCV Baby Boomers. Show all posts
Showing posts with label HCV Baby Boomers. Show all posts

Thursday, February 22, 2018

Hepatitis C: The Bane of Baby Boomers, Though Treatable


Hepatitis C: The Bane of Baby Boomers, Though Treatable
FEBRUARY 21, 2018
Jeannette Y. Wick, RPh, MBA, FASCP

More than 3 million Americans have chronic hepatitis C virus (HCV), and physicians diagnose about 17,000 new cases annually. HCV is a silent disease, and most infected individuals are unaware that they are infected until they develop liver damage, cirrhosis, or liver cancer. Consequently, 12,000 Americans die from HCV complications each year.1,2,3 And people born between 1945 and 1965 are 5 times more likely to have hepatitis C than others.4 Although treatments have been available for many years, the consistent ability to cure HCV is recent.

Choosing the Treatment Regimen
Treatment goals include a persistent absence of HCV ribonucleic acid in serum 6 months or more after completing antiviral treatment, and preventing progression to serious complications.

Since 2013, oral regimens combining direct-acting antivirals from different classes (Table 1) have effectiveness exceeding 90%. These therapies have shorter durations and fewer adverse effects than older options.

Thursday, September 28, 2017

CDC - Mandating HCV Screening Increased Newly Diagnosed and Access to Care

Centers for Disease Control and Prevention
Morbidity and Mortality Weekly Report (MMWR)

Evaluation of the Impact of Mandating Health Care Providers to Offer Hepatitis C Virus Screening to All Persons Born During 1945–1965 — New York, 2014
Colleen A. Flanigan, MS1; Shu-Yin J. Leung, MA2; Kirsten A. Rowe, MS2; Wendy K. Levey, MA3; Andrea King, MPH4; Jamie N. Sommer, MS5; Johanne E. Morne, MS6; Howard A. Zucker, MD, JD7

Weekly / September 29, 2017 / 66(38);1023–1026

Implementation of the New York law mandating health care providers to offer HCV testing to persons born during 1945–1965 was associated with an increase in HCV testing, and an increase in the percentage of persons with newly diagnosed HCV infections who were linked to care. Marked increases in the number of HCV tests performed and rates of testing were observed immediately after enactment of the law and remained steady over a 12-month period. Smaller increases were noted in the number of persons who accessed care after receiving a positive HCV screening test result.

Summary

What is already known about this topic?

Persons born during 1945–1965 account for approximately 75% of all hepatitis C virus (HCV) infections in the United States and 73% of HCV-associated mortality. Most infected persons do not know their status. In January 2014, New York became the first state to enact an HCV testing law, which is expected to increase the number of persons who are aware of their HCV status.

What is added by this report?

One year after implementation of the 2014 New York HCV Testing Law, marked increases were observed in the number of HCV screening tests and rates of testing. Increases were observed almost immediately after enactment of the law and remained steady at levels substantially higher than those in the years preceding enactment of the law. Smaller increases were noted in the number of persons who accessed HCV care following a positive HCV screening test.

What are the implications for public health practice?

State-level HCV testing laws could increase the number of persons who know their HCV status and of HCV-infected persons who are linked to care. With the availability of new therapies that can stop disease progression and provide a cure in most persons, testing and linkage to care for infected persons is likely to reduce HCV-related morbidity and liver cancer-associated mortality.

Saturday, July 8, 2017

Looking at the Twin Epidemics of HCV

AGA Reading Room

Looking at the Twin Epidemics of HCV
by Pippa Wysong
Contributing Writer, MedPage Today

Younger cohorts at risk of HCV need more attention
They are a unique group of individuals in which most new infections are happening," he told MedPage Today. "Treating them is more complicated than simply giving them medical therapy." He was lead author of a recent large study in BMC Infectious Diseases that elucidated the characteristics of the twin epidemics.
When researchers look at the causes of mortality among this younger cohort, deaths are often related to acquisition-related causes such as injection drug use and drug overdose. Baby boomers, on the other hand, are more likely to present later with HCV and to die from chronic diseases and liver-related causes.
Continue reading....

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Wednesday, July 5, 2017

Healio Hepatology - Top HCV reports for June 2017 focus on guides, screening

Top HCV reports for June 2017 focus on guides, screening
July 5, 2017
In the direct-acting antiviral era, researchers and medical professionals are continuing their efforts to eliminate hepatitis C by defining the most instrumental guides for screening, treatment and management.

Healio.com/Hepatology presents some of the highlights in HCV research data and formal reports for June 2017. The reports include EASL’s response to a controversial review of DAA studies, recommendations for the elimination of HCV from Georgetown University, the utility of electronic screening for HCV among the baby boomer generation, and a survey that identified gaps in current HCV and hepatitis B testing guides in Europe.

The European Association for the Study of the Liver responded with serious concern to a systematic review published by the Cochrane Group Review....

Continue reading

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Sunday, March 12, 2017

Recent Hepatitis C Virus Testing Patterns Among Baby Boomers

Introduction
Approximately 3.5 million people are chronically infected with hepatitis C virus (HCV) in the U.S., 80% of whom are “baby boomers” (born between 1945 and 1965).1 Most infected individuals are not aware of their infections despite availability of treatments that may reduce their risk of HCV-related diseases, including chronic hepatitis, cirrhosis, and liver cancer.2 To curb the growing burden of these HCV-associated diseases, the U.S. Preventive Services Task Force (USPSTF) recommended one-time HCV testing for baby boomers in 2013.3 The authors previously noted low HCV testing prevalence among baby boomers in 2013, at baseline4; however, it is unknown whether HCV testing has changed following the USPSTF recommendation.

Methods
Data from the 2013 and 2015 National Health Interview Survey, including 23,967 baby boomers, were used. Self-reported HCV blood testing was the primary study outcome. Analyses were restricted to respondents with non-missing HCV testing data (n=21,827). Weighted prevalence of HCV testing (ever) was calculated by sociodemographic and lifestyle factors. Multivariable prevalence ratios (PRs) and 95% CIs of HCV testing according to the 2015 survey were estimated using predicted margins. Interaction terms between survey year and each covariate were included in additional models using 2013 and 2015 survey data to determine if changes in HCV testing varied across subgroups; none were statistically significant (data not shown). All statistical analyses were conducted in 2016 with SAS-callable SUDAAN, version 9.0.3.

Results
From 2013 to 2015, HCV testing prevalence among baby boomers slightly increased from 12.3% to 13.8% (p=0.013) (Table 1). Of the 76.2 million estimated baby boomers in 2015, only 10.5 million reported ever receiving HCV testing. Relative to privately insured adults, those with Medicare plus Medicaid (PR=1.83, 95% CI=1.32, 2.53), Medicaid only (PR=1.35, 95% CI=1.04, 1.76), or military insurance (PR=1.62, 95% CI=1.16, 2.26) had higher HCV testing prevalence. HCV testing was also greater in men versus women (PR=1.25, 95% CI=1.08, 1.44) and among people who had lived with someone with hepatitis versus those who did not (PR=2.44, 95% CI=2.01, 2.96). Individuals with less than or only a high school diploma had lower HCV testing than college graduates (PR=0.63, 95% CI=0.48, 0.82 and PR=0.58, 95% CI=0.48, 0.72, respectively).

Table 1Hepatitis C Testing Among Adults Born Between 1945 and 1965, NHIS 2013–2015 (n=21,827)a
CharacteristicUnadjusted prevalence2013 vs 2015, p-valueaPR (95% CI) among respondents in the 2015 surveyb
2013, % (95% CI)2015, % (95% CI)
Total12.3 (11.5, 13.1)13.8 (12.9, 14.7)0.013
Race/ethnicity
 Non-Hispanic white12.4 (11.5, 13.4)13.9 (12.9, 15.0)0.0371.00
 Hispanic11.5 (9.3, 14.0)11.3 (9.2, 13.9)0.9280.96 (0.71, 1.30)
 Non-Hispanic black12.6 (10.7, 14.7)14.5 (12.2, 17.3)0.2241.09 (0.87, 1.35)
 Non-Hispanic Asian10.1 (7.4, 13.7)13.9 (10.0, 18.9)0.1511.24 (0.84, 1.83)
 Non-Hispanic other19.5 (12.0, 29.9)25.4 (16.6, 36.9)0.3661.61 (1.01, 2.55)
Health insurance
 Private11.7 (10.6, 12.9)12.8 (11.7, 14.0)0.2001.00
 Medicaid16.5 (13.0, 20.8)18.5 (15.1, 22.6)0.4691.35 (1.04, 1.76)
 Medicaid+Medicare21.3 (16.0, 27.7)26.1 (19.9, 33.4)0.3181.83 (1.32, 2.53)
 Medicare9.5 (7.9, 11.4)12.5 (10.8, 14.4)0.0120.89 (0.74, 1.06)
 Military22.1 (17.6, 27.5)22.5 (16.9, 29.2)0.9281.62 (1.16, 2.26)
 Uninsured11.2 (9.2, 13.4)11.1 (8.6, 14.2)0.9560.96 (0.70, 1.31)
 Other17.1 (13.4, 21.5)17.9 (13.2, 23.8)0.8041.22 (0.86, 1.74)
Sex
 Female11.1 (10.1, 12.3)12.4 (11.3, 13.5)0.1101.00
 Male13.5 (12.3, 14.8)15.4 (14.0, 16.9)0.0601.25 (1.08, 1.44)
Education
 College graduate13.7 (12.2, 15.3)14.5 (12.9, 16.2)0.4631.00
 Some college15.2 (13.7, 16.8)16.5 (14.9, 18.4)0.2451.03 (0.86, 1.22)
 HS or GED8.9 (7.4, 10.6)11.0 (9.4, 12.8)0.0880.58 (0.48, 0.72)
 Less than HS diploma9.3 (7.7, 11.2)11.4 (9.4, 13.8)0.1490.63 (0.48, 0.82)
Marital status
 Married11.3 (10.3, 12.4)13.1 (12.1, 14.3)0.0151.00
 Not currently marriedc14.0 (12.7, 15.3)15.3 (13.7, 17.1)0.2261.09 (0.94, 1.28)
 Never married14.2 (12.1, 16.6)14.3 (12.1, 16.8)0.9730.93 (0.75, 1.16)
Born in U.S.
 Yes12.5 (11.6, 13.4)14.2 (13.2, 15.2)0.0111.00
 No11.3 (9.5, 13.3)12.0 (10.1, 14.3)0.5780.89 (0.67, 1.19)
Alcohol consumption
 0−1 drinks/day12.2 (11.4, 13.1)13.9 (13.0, 14.9)0.0071.00
 ≥2 drinks/day12.9 (10.7, 15.4)12.8 (10.0, 16.2)0.9731.23 (0.93, 1.61)
Lived with someone with hepatitis
 No9.5 (8.8, 10.3)11.2 (10.4, 12.1)0.0041.00
 Yes29.4 (24.4, 35.0)27.9 (23.3, 33.0)0.6882.44 (2.01, 2.96)

Note: Boldface indicates statistical significance (p<0.05).
aWeighted number receiving hepatitis C virus testing in 2013 was 9,144,299 and in 2015 was 10,511,639. Weighted number eligible for hepatitis C virus testing in 2013 was 74,506,656 and in 2015 was 76,178,472. Weighted numbers take into account the assigned sampling weights of respondents.
bIncludes 10,176 respondents from the 2015 survey only. Model is adjusted for race/ethnicity, health insurance, sex, education, marital status, alcohol consumption, and having lived with someone diagnosed with hepatitis.
cIncludes divorced, separated, and widowed. aPR, adjusted prevalence ratio; GED, General Educational Development test; HS, high school; NHIS, National Health Interview Survey.

Discussion
There was a small, albeit statistically significant, increase in HCV testing (from 12.3% to 13.8%) among baby boomers 2 years after the 2013 USPSTF recommendation for one-time HCV testing. Reasons for the overall slow uptake of testing may include barriers to preventive care; unapparent symptoms; lack of awareness of the need to be tested among patients, who may not be fully covered by insurers2; and lack of physician awareness of the USPSTF recommendations. The relatively higher prevalence of testing in military-insured individuals may reflect ongoing HCV testing in the Veterans Health Administration to reduce the disproportionately high burden of HCV-associated disease in this population.5, 6, 7

Greater HCV testing in those with dual Medicare and Medicaid and Medicaid-only insurance coverage may reflect more risk factors for HCV and associated diseases in this population.8 People with lower educational attainment and the uninsured had especially suboptimal HCV testing, despite having greater HCV burden, perhaps as a result of lower awareness about testing and barriers to accessing care.1 Limitations of this study include recall bias due to self-reported HCV testing and exclusion from the National Health Interview Survey of institutionalized baby boomers (e.g., incarcerated individuals and active-duty military) in whom HCV testing and infection may be more common.6, 7 The HCV testing estimates are substantially lower than those from recent studies among baby boomers,9, 10 where 90% of patients in a safety net clinic were tested, and in a New York community hospital where testing increased from 47% before to 88% after an intervention to improve HCV testing was put into place.9, 10 The lower proportion of HCV testing in the current study’s population could be a result of under-reporting of HCV testing, as well as differences between the current study population and these institutional-based studies.9,

Conclusions
Prevalence of HCV testing among baby boomers did not substantially increase and remains low 2 years after the USPSTF recommendation in 2013. Notably, only 10.5 million of 76.2 million baby boomers reported ever receiving HCV testing. These findings underscore the need for increased awareness for HCV testing among healthcare providers and baby boomers and other innovative strategies such as state-mandated HCV testing.
http://www.ajpmonline.org/article/S0749-3797(17)30092-2/fulltext

Monday, February 20, 2017

HCV Screening Shouldn't Just Focus on At-Risk Populations

HCV Screening Shouldn't Just Focus on At-Risk Populations
FEB 20, 2017 | CAITLYN FITZPATRICK
At the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle, Washington, researchers from MedStar Health Research Institute in Maryland presented new data on hepatitis C virus (HCV)-positive non-baby boomers.

It’s widely acknowledged that those individuals belonging to the baby boomer age group (those born between 1946 and 1964) are at higher risk of acquiring HCV infection. According to the Centers for Disease Control and Prevention (CDC), these individuals are five times more likely to be infected with HCV. However, other at-risk populations may not be getting adequately tested for the virus.

Monday, December 26, 2016

Hepatitis C - Screening for HCC in the Post-SVR12 Setting

2018 - Updates
Letter to the editor
Jan 2018

SVR Reduced HCC by 71%
from Jules: there never was any doubt that SVR would reduce or eliminate risk for HCC. In this study cirrhosis prior to treatment had a higher HCC risk then for those without cirrhosis, but that is to be expected and merely reinforces how crucial it is to treat HCV as early as possible...
Full Text

Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline.

Dec 2016
Healio
The following articles appeared in the December print edition of HCV NEXT, published online at Healio.






Monday, October 31, 2016

Dating after Hepatitis C: Hope on the horizon for the 1 in 30 boomers estimated to be infected

Dating after Hepatitis C: Hope on the horizon for the 1 in 30 boomers estimated to be infected

Baby boomers are 6 times more likely to be infected than other adults. We need to talk about testing and treatment

Recently I went on a first date — a stroll in a city park — that went rather well. We had so much in common, from a love of reading to a history of youthful troublemaking. If I wasn’t convinced already he was someone I could relate to, my new friend shared that he’d been cured of Hepatitis C.

I could hardly believe it. Instead of having to awkwardly explain my medical history, I’d met someone who shares it. It was a first. The only other time I’d met people who’d been cured of Hepatitis C, I was at an event at Johns Hopkins celebrating the first 1,000 successes of the new drugs. Some of my fellow drug program participants had gotten it from blood transfusions, some from vaccinations in the military. Some had no idea how.

Continue reading..

Tuesday, September 20, 2016

NVHR Webinar: Conveying the Urgency of Baby Boomer HCV Testing

National Viral Hepatitis Roundtable (NVHR)

NVHR Webinar: Conveying the Urgency of Baby Boomer HCV Testing
Published on Sep 20, 2016
This webinar, held on September 16, 2014, featured Dr. Cami Graham, Co-Director, Viral Hepatitis Center, Division of Infectious Diseases at Beth Israel Deaconess Medical Center on why and how to make the case for the importance and urgency of screening baby boomers (those born 1945-1965) for hepatitis C. We also shared information about how NVHR's educational program offers resources for implementing screening and linkage to care programs in your health care setting or community.

NVHR Website



The National Viral Hepatitis Roundtable is a broad coalition working to fight, and ultimately end, the hepatitis B and hepatitis C epidemics. We seek an aggressive response from policymakers, public health officials, medical and health care providers, the media, and the general public through our advocacy, education, and technical assistance. We believe an end to the hepatitis B and C epidemics is within our reach and can be achieved through addressing stigma and health disparities, removing barriers to prevention, care and treatment, and ensuring respect and compassion for all affected communities.

View All Videos
National Viral Hepatitis Roundtable (NVHR)


Sunday, April 3, 2016

New research says hep C epidemic not caused by 1960s sex and drug lifestyle

New research says hep C epidemic not caused by 1960s sex and drug lifestyle

Peak of hep C infection epidemic actually occurred in 1950, not 1965 as previously thought

By Karin Larsen, CBC News Posted: Apr 03, 2016 7:00 AM PT Last Updated: Apr 03, 2016 7:00 AM PT

A new study, worked on by B.C. researchers, says baby boomers living a sex and drug lifestyle in the 1960s aren't to blame for hepatitis C infections in their demographic.
In fact, the research suggests all baby boomers should be tested for the hep C virus because widespread hospital practices predating the 1950's likely led to many accidental transmissions.

The findings suggest an increase in medical procedures post World War II and inadequate hospital sterilization of reusable needles and syringes are the culprits.

Continue reading...


Friday, January 30, 2015

PODCAST: Baby Boomers Should Get Tested For Hep-C




Posted Friday, January 30th 2015 @ 9am

Houston's Morning News with Matt Patrick welcomes KTRH Medical expert Dr. Joe Galati, to discuss more about baby boomers who overall, need to be tested for Hep C. Some reports advise against it, but Dr. Galati defuses that by explaining why more baby-boomers have the Hepatitis C today, adding it's highly curable. Listen in for details.

Source 

Tuesday, January 27, 2015

Quest in broad deal with CDC for hepatitis analysis

Quest in broad deal with CDC for hepatitis analysis
Tuesday, January 27, 2015 2 p.m. CST

(Reuters) - Laboratory testing company Quest Diagnostics Inc said on Tuesday it had signed a $520,000 agreement with the Centers for Disease Control and Prevention to identify trends in screening, diagnosis and treatment of four strains of viral hepatitis.

Quest will provide the U.S. public health agency with analytics and access to Quest's national database of clinical testing hepatitis data, which includes information from more than 20 billion test results.

The agreement expands on Quest's previous efforts with the CDC on hepatitis C testing data for Baby Boomers, or individuals born between 1945 and 1965, one of the groups most exposed to the virus.

The government in 2012 recommended that Baby Boomers be screened for hepatitis C, which can cause death.

The expanded agreement aims to identify trends in screening for hepatitis A, B, C and E and will focus on data for hepatitis B and C in pregnant women to find possible gaps that the CDC could use to target screening and treatment.

The data have been modified to protect the identity of the patients.

"If you can get people diagnosed, then the next obvious stage is to get them into care," said Rick Pesano, medical director for infectious diseases at Quest.

Treatment for hepatitis C has changed dramatically since Gilead Sciences Inc introduced its Sovaldi drug in December of 2013 with few side effects. It has since introduced a second combination drug Harvoni and AbbVie Inc has launched a competitor that offers similar cure rates above 90 percent.

(Reporting by Caroline Humer; Editing by Richard Chang)
Source - Reuters

Friday, October 3, 2014

Be Hip To Hep: Dispelling old myths and discovering the hopes for those with hepatitis C

Be Hip To Hep: Dispelling old myths and discovering the hopes for those with hepatitis C

Good morning folks, over at DentistryIQ an insightful article about living with hepatitis C now available for your reading pleasure.

Dr. Muñoz, professor of English at Cosumnes River College writes from a patients perspective about living with HCV.

The article offers information about; diagnosis, transmission/sexual transmission, risk factors, blood tests, stigma - "In addition to work difficulties, my personal life disintegrated. I felt a sense of shame as I listened to a friend unwittingly joke how Pamela Anderson was repulsive. Not because of her famously exaggerated cup size, but rather (and solely) because she had the misfortune of contracting HCV." as well as treatment, and advice for persons living with the virus.

Be hip to hep

Dispelling old myths and discovering the hopes for those with hepatitis C

BY HEIDI EMMERLING MUÑOZ, PhD

"You have hepatitis C."

Those words turned my life upside down. I tell this story not to elicit sympathy but to illustrate what it means to live with hepatitis C (HCV): the physical as well as the emotional. Only now, because I am out of clinical hygiene and because there is a cure in sight, do I feel safe in telling my story.

I also tell this story to urge screening and to give hope to anyone living with HCV.
Continue reading....

Monday, August 4, 2014

Hepatitis C Could Become Rare Disease in 20 Years: Study

Hepatitis C Could Become Rare Disease in 20 Years: Study

Newer medications, better screening would fuel the trend, researcher says

By Amy Norton
HealthDay Reporter

MONDAY, Aug. 4, 2014 (HealthDay News) -- The once tough-to-treat liver infection hepatitis C could become a rare disease in the United States in the next two decades, a new study estimates.

Hepatitis C, a viral infection that harms the liver, is usually passed through infected blood. For most people, the infection becomes chronic and it can eventually lead to scarring of the liver (cirrhosis) or liver cancer.

U.S. health officials estimate that over 3 million Americans currently have chronic hepatitis C -- most of whom don't know it because the infection usually causes no symptoms.

But with recent treatment advances, hepatitis C could become rare by 2036, researchers report in the Aug. 5 issue of the Annals of Internal Medicine.

"Rare" refers to a disease that affects one in 1,500 people at most, said senior researcher Jagpreet Chhatwal, who conducted the study while at the University of Pittsburgh Graduate School of Public Health. Right now, around one in 100 Americans has chronic hepatitis C.

But that could quickly shift, since new drugs are changing the landscape of hepatitis C treatment, according to Chhatwal's team.

"We're in the middle of a very interesting time for hepatitis C patients," said Chhatwal, who is now an assistant professor at the University of Texas MD Anderson Cancer Center in Houston.

For decades, the only treatment for the disease involved the drug interferon -- which had to be injected and taken for up to a year. It also often caused fatigue and flu-like side effects. After all that, the cure rate was only 40 percent to 50 percent, according to the U.S. Food and Drug Administration.

But in just the past few years, new drugs have been approved and more are on the way, Chhatwal said.

One is Sovaldi (sofosbuvir), a pill the FDA approved last December. The treatment lasts just 12 weeks, with no need for interferon injections.

"There are highly effective drugs becoming available, with a shorter duration of treatment," Chhatwal said. "So, patients should be more amenable to taking them."

Besides the treatment advances, more hepatitis C cases could be caught. Since 2012, U.S. health officials have recommended that all "baby boomers" -- Americans born between 1945 and 1965 -- get a one-time blood test to screen for hepatitis C.

Baby boomers are targeted because they account for about 80 percent of chronic hepatitis C cases, Chhatwal said.

That's partly because of experimentation with injection drugs decades ago, and partly from exposure to contaminated blood before widespread screening of the blood supply in 1992.

For the new study, which was funded by the U.S. National Institutes of Health, Chhatwal's team used a computer model to estimate the future effects of both hepatitis C screening and new drug regimens.

The researchers predict that within the next 22 years, hepatitis C could become rare. What's more, nearly 79,000 cases of liver cancer, over 124,000 cases of cirrhosis and 126,500 deaths could be averted by 2050.

"Those are certainly reasonable predictions. I don't think they're overstating the situation at all," said Dr. Eugene Schiff, director of the Schiff Center for Liver Diseases at the University of Miami Miller School of Medicine.

Schiff, who was not involved in the study, explained that traditionally people with hepatitis C have not been automatically treated, because the drugs were so hard to take and not very effective.

"Now we're moving toward an era of 'test and treat,'" Schiff said. "Cure rates are approaching 100 percent with these new regimens, and they're very well-tolerated."

Treatment could also get even easier, Schiff noted. Gilead Sciences, maker of Sovaldi, has another pill in the pipeline. It combines Sovaldi and another drug, called ledipasvir, into a once-daily tablet that can be taken for as few as eight weeks.

The FDA is expected to make a decision on that drug in October, Schiff said.

The obstacle in all of this is money. Sovaldi costs $1,000 a day, or $84,000 for the typical 12-week course. Some insurers and state Medicaid programs are restricting coverage to certain patients, saying the drug's huge price tag could break the bank.

"As a clinician, the big hurdle right now is being able to get this medication to patients," Schiff said. But he added that payers' worries are understandable -- with an influx of people who'd been living with chronic hepatitis C now wanting treatment.

Costs should come down, Schiff noted, as competitors come onto the market.

Chhatwal's team also looked at what could happen if all Americans -- not just baby boomers -- got a one-time hepatitis C screening test. They say that would nearly double the number of cases detected in the next decade -- from 487,000 to almost 934,000.

What the study does not address, Chhatwal said, is costs. He said more research is needed to see whether the costs of screening and treatment could be offset by the reduction in liver disease and liver transplants.

More information

The U.S. Centers for Disease Control and Prevention has more on hepatitis C.

SOURCES: Jagpreet Chhatwal, Ph.D., assistant professor, health services research, University of Texas MD Anderson Cancer Center, Houston, Texas; Eugene Schiff, M.D., director, Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Fla.; Aug. 5, 2014 Annals of Internal Medicine

Last Updated: Aug 4, 2014

Friday, April 18, 2014

Previous Exposure to HCV Among Persons Born During 1945–1965

Previous Exposure to HCV Among Persons Born During 1945–1965

Prevalence and Predictors, United States, 1999-2008

Bryce D. Smith, PhD, Geoff A. Beckett, PA-C, MPH, Anthony Yartel, MPH, Deborah Holtzman, PhD, Nita Patel, DrPH, John W. Ward, MD
Am J Public Health. 2014;104(3):474-481.

Abstract and Introduction
Abstract

Objectives. We examined HCV exposure prevalence and predictors among persons in the United States born during 1945–1965.

Methods. With data from the 1999–2008 National Health and Nutrition Examination Survey, we calculated the proportion of persons born during 1945–1965 who tested positive for HCV antibody (anti-HCV) and analyzed the prevalence by sociodemographic and behavioral risk factors.

Results. Anti-HCV prevalence in the 1945–1965 birth cohort was 3.2% (95% confidence interval [CI] = 2.8%, 3.8%), substantially higher than among other adults (0.9%). Within the cohort, anti-HCV prevalence was higher among non-Hispanic Blacks (6.4%; 95% CI = 5.3%, 7.7%), persons with injection drug use histories (56.8%; 95% CI = 48.4%, 64.8%), and persons with elevated alanine aminotransferase levels (12.7%; 95% CI = 10.7%, 15.1%). Injection drug use (adjusted odds ratio = 98.4; 95% CI = 58.8, 164.5) was the strongest anti-HCV prevalence predictor. Among anti-HCV–positive persons, 57.8% reported having 2 or more alcoholic drinks daily.

Conclusions. With the high prevalence of HCV among persons born during 1945–1965, the increasing morbidity and mortality associated with HCV, and reductions in liver cancer and HCV-related mortality when HCV is eradicated, it is critically important to identify persons with HCV and link them to appropriate care.
Introduction

In the United States, the incidence of HCV infection rose dramatically through the 1970s and 1980s reaching more than 200 000 new infections per year through the mid- to late-1980s.[1] This high incidence resulted in a disproportionately high burden of HCV infection among Americans who were born between the mid-1940s and the mid-1960s, a birth cohort popularly referred to as the baby boom generation.[2] Alter et al. first documented the relatively high prevalence of HCV infection among this cohort in their analysis of1988–1994 National Health and Nutrition Examination Survey (NHANES) data, reporting that 65% of persons with HCV infection were aged 30 to 49 years during the survey period.[3] In an analysis of NHANES data from 1999 to 2002, a similarly high proportion of all persons with HCV antibody had been born from 1945 through 1964.[1] This cohort effect on the high prevalence of HCV infection in the baby boom generation has been attributed largely to exposures (principally injection drug use [IDU] and blood transfusion before 1992) that occurred many years before the survey periods.[1,3] However, a significant proportion of HCV-infected persons do not report any risk factors,[4–6] perhaps because of fear of being stigmatized,[7] or simply lack of recall or knowledge of exposures such as those that may occur in health care settings.[8,9]

A validated Markov model forecasting lifetime morbidity and mortality attributable to HCV infection projected that of 2.9 million persons with untreated HCV infection who did not have cirrhosis of the liver in 2005, 1 071 000 (36.8%) will die from complications of HCV.[10] In the United States, HCV-associated disease is the leading indication for liver transplantation and HCV infection is a leading cause of hepatocellular carcinoma.[11–14] Approximately 73.9% of HCV-associated mortality occurs among persons born from1945 to 1965.[15]

In 1998, the Centers for Disease Control and Prevention recommended[16] that persons with certain risk factors (e.g., any history of IDU) or medical conditions (e.g., persistently elevated alanine aminotransferase [ALT] levels) be tested for HCV infection. Despite these recommendations, testing practices over the past decade have had limited success in identification of HCV infection in the United States as estimates of the proportion of persons who are unaware of their infection range from 40% to 85%.[17–20] Contributing to the limited success of the recommendations is the difficulty in obtaining risk behavior history that occurred in the distant past, the primarily asymptomatic nature of the infection, and a less than optimal level of physician knowledge regarding the natural history and prevalence of infection, the current recommendations for testing, and interpretation of test results.[21–24]

In 2011, the prospects for successful medical treatment of HCV infection were significantly improved with the US Food and Drug Administration licensure of 2 direct-acting antiviral medications, both in the protease inhibitor class. In clinical trials, the rates of sustained viral response—equivalent to a "virological cure"—increased from 44% with use of the current standard regimen, to 75% when a direct-acting antiviral medication was added to that regimen in treatment of persons infected with HCV genotype 1, the genotype that is most common in the United States.[25] Since this article was accepted for publication, the US Food and Drug Administration has approved new HCV medications[26,27] that have further increased cure rates to as high as 90% in clinical trials.

Persons who achieve a sustained viral response after treatment experience significantly less liver-related morbidity (including hepatocellular carcinoma),[28] less liver-related mortality,[29] and reductions in all-cause mortality.[30] However, the potential population benefits from these improvements in treatment effectiveness will be limited unless there are concurrent increases in the rate of identification and treatment of HCV-infected persons.[31]

Because of the limited effectiveness of risk based testing strategies to date and the high prevalence of HCV infection and projected disease burden, the Centers for Disease Control and Prevention recently issued the Recommendations for the Identification and Initial Care of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965[32] with the goal of identifying persons with HCV infection who are undiagnosed. The recommendation was subsequently made by the US Preventive Services Task Force.[33] The purpose of the current study was to determine the proportion of persons in the birth cohort who were positive for antibody to HCV (anti-HCV), and to examine the sociodemographic and behavioral risk factors associated with anti-HCV prevalence.

Methods
We analyzed NHANES data collected from 1999 to 2008. NHANES is an annual nationally representative multistage, stratified probability cluster survey of the US civilian, noninstitutionalized population. Information on the survey design and implementation, including institutional review board approval and consent, is detailed in the survey documentation.[34,35]
Anti-HCV testing is administered to NHANES participants aged 6 years or older. We restricted our analysis to adult participants born from 1945 to 1965 who were interviewed and provided serum samples for anti-HCV testing. Birth year was estimated by subtracting participant age at time of survey from estimated year in which participant was surveyed. Because NHANES does not release data on participant birth year or the actual year in which a participant was interviewed or examined, we estimated the earliest survey year for each participant according to the variable, "six month time period when the examination was performed: November 1 through April 30, May 1 through October 31." As an example, for the 1999–2000 survey cycle, participants examined from November 1 to April 30 were assigned an earliest survey year of 1999 and those examined from May 1 through October 30 were assigned to the 2000 survey year. We excluded participants without specimens for testing and those with indeterminate anti-HCV results from the final analytic sample.

Outcome Variable
The outcome measure was anti-HCV prevalence as determined by serologic testing. We chose anti-HCV status as an endpoint because HCV RNA testing was not performed for the 2003–2004 NHANES cycle, and we determined that combining data from all 10 years (1999–2008) was necessary to achieve sufficient subdomain sample sizes for improved precision and reliability of point estimates.

Specimens were tested for antibodies to HCV by repeated enzyme-linked immunosorbent assay (ELISA version 3.0, Ortho Diagnostic Systems Inc, Raritan, NJ). Reactive specimens were confirmed by recombinant immunoblot assay (RIBA version 3.0, Chiron Corporation, Emeryville, CA). Participants who tested positive by both ELISA and RIBA were categorized as anti-HCV–positive.

Independent Variables
We examined the following independent variables as potential predictors or confounders of anti-HCV prevalence within the birth cohort: race/ethnicity, gender, country of birth, veteran status, marital status, educational attainment, family income, health insurance status, daily alcohol consumption within the past 12 months, age at first sexual intercourse, number of lifetime sexual partners, lifetime IDU (cocaine, heroin, and methamphetamine), history of blood transfusion before 1992, and ALT level.[1,3] We categorized race/ethnicity as non-Hispanic White, non-Hispanic Black, Mexican American, and other. We categorized educational attainment as completed less than high school and completed high school or more; marital status as married or living with partner, divorced or separated or widowed, and never married; and family income as greater than 2 times federal poverty threshold, 1 to 2 times federal poverty threshold, and less than the federal poverty threshold. We defined elevated ALT as 40 or more international units per liter. For independent variables with 10% or more of observations with missing values, we created an "unknown" category to include those missing values as valid for analysis. Accordingly, we categorized alcohol consumption as 0 or 1, 2 or more, and unknown number of drinks per day within the past year; age at first sexual intercourse as 17 years or younger, 18 years or older, and unknown; number of lifetime sexual partners as 0 to 9, 10 to 19, 20 or more, and unknown; lifetime drug use as never, non–injection drug use, IDU, and unknown.
NHANES questions related to sexual behavior and history of IDU are restricted to adult participants younger than 60 years. Thus, all analyses involving these variables in the current study were similarly restricted.

Statistical Analysis
We generated proportions and 95% confidence intervals (CIs) to describe the characteristics of the 1945–1965 birth cohort. We also produced estimates of anti-HCV prevalence in the birth cohort and by subgroups. We specified linear contrasts of estimates to test for statistical differences in characteristics between anti-HCV–positive participants and all participants, and to test for differences in anti-HCV prevalence between subgroups. We assessed statistical reliability of estimated proportions by evaluating relative standard errors (< 30%) and by ensuring that subdomains met NHANES minimum sample size requirements. We generated unadjusted odds ratios from univariate logistic regression models. We defined statistical significance as P value less than .05.

We developed a multivariate logistic regression model to identify independent risk factors associated with anti-HCV positivity within the birth cohort after we controlled for covariates. We specified an estimated full model by including all independent variables with a P value of less than .1 from the univariate analyses. Using a backward elimination procedure, we removed variables with the lowest observed partial F-statistic at a predetermined P value of less than .1. We simultaneously tested for 2-way interaction effects between race and IDU or gender and IDU, by using multiple partial F-tests. We assessed multicollinearity among covariates by review of diagnostic statistics including variance inflation factors (> 2.5), condition indices (> 15), and variance proportions (> 0.5; SAS version 9.3, SAS Institute, Cary, NC). In deciding whether to exclude a covariate because of collinearity, we also considered the relative importance of the covariate, its relationship with key variables such as IDU, and its contribution to the overall model fit.

We used the Hosmer–Lemeshow goodness-of-fit test to evaluate the overall fit of the final model. Except as otherwise specified, we analyzed all data with SAS-callable SUDAAN to account for the complex survey design (version 10.0.1, Research Triangle Institute, Research Triangle Park, NC). We rescaled sample weights after combining data across multiple survey years. We estimated variance and standard errors by using the Taylor series (linearization) method

Results
We identified a total of 8167 participants estimated to be born from 1945 to 1965 who were both interviewed and examined. After we excluded participants without specimens (n = 411) and those with indeterminate anti-HCV results (n = 33), the final analytic sample for the birth cohort was 7723 (95% of those examined). Table 1 shows the demographic, behavioral, and clinical characteristics of the birth cohort population and those in the cohort who were anti-HCV–positive. Relative to the total birth cohort population, a greater proportion of anti-HCV–positive participants were male, non-Hispanic Black, had a family income below the poverty threshold, and had no health insurance coverage. Among anti-HCV–positive participants, 41.9% reported a history of IDU, 16.2% received a blood transfusion before 1992, 57.8% consumed 2 or more alcoholic drinks per day, and 51.3% had elevated ALT levels. Combined, persons with a history of IDU or blood transfusion accounted for 51.7% of anti-HCV–positive participants; 48.3% reported no known exposure risks.

Prevalence of Anti-HCV in the Birth Cohort
Prevalence estimates for the birth cohort and subgroups are presented in Table 2. The overall prevalence of anti-HCV in the birth cohort was estimated at 3.2% (95% CI = 2.8%, 3.8%) or approximately 2.8 million (2.4 million to 3.2 million) persons with anti-HCV. Anti-HCV prevalence was higher among men (4.3%; 95% CI = 3.6%, 5.2%), non-Hispanic Blacks (6.4%; 95% CI = 5.3%, 7.7%), and persons with a family income below the poverty threshold (7.8%; 95% CI = 6.3%, 10.0%), respectively, compared with women, non-Hispanic Whites, and persons with a family income of more than 2 times the poverty threshold.

Table 2.  Characteristics and Risk Factors Associated With HCV Antibody Prevalence Among Adults Born From 1945 to 1965: National Health and Nutrition Examination Survey, 1999–2008
CharacteristicParticipants Tested, No.Prevalence of Anti-HCVUnadjusted Odds Ratios
% (95% CI)P a Unadjusted OR (95% CI)P
Overall77233.2 (2.8, 3.8)
Gender
   Female (Ref)39112.2 (1.7, 2.9)1.0
   Male38124.3 (3.6, 5.2)< .0012.0 (1.4, 2.8)< .001
Race/ethnicity
   Non-Hispanic White (Ref)36482.9 (2.3, 3.6)1.0
   Non-Hispanic Black17006.4 (5.3, 7.7)< .0012.3 (1.7, 3.0)< .001
   Mexican American15643.3 (2.4, 4.4).511.1 (0.8, 1.6).5
Marital status
   Married or living with partner (Ref)51702.7 (2.2, 3.4)1.0
   Divorced, separated, or widowed16404.3 (3.3, 5.5).241.6 (1.1, 2.3).02
   Never married7475.7 (4.0 8.0).0042.2 (1.4, 3.3)< .001
Country of birth
   United States58363.6 (3.1, 4.2)< .0013.3 (1.9, 5.6)< .001
   Other (Ref)18841.1 (0.7, 1.8)1.0
Education level
   £ high school38384.8 (4.0, 5.9)< .0012.3 (1.7, 3.1)< .001
   > high school (Ref)38792.2 (1.8, 2.7)1.0
Family income to poverty threshold
   > 2 times (Ref)44642.1 (1.7, 2.7)1.0
   1–2 times15245.6 (4.2, 7.5)< .0012.8 (1.9, 4.1)< .001
   Below11837.8 (6.3, 9.6)< .0013.9 (2.9, 5.3)< .001
Health insurance coverage
   Yes (Ref)59192.7 (2.3, 3.1)1.0
   No17576.2 (4.8, 8.0)< .0012.4 (1.8, 3.3)< .001
Served in the US armed forces
   No (Ref)67653.0 (2.5, 3.5)1.0
   Yes9555.1 (3.7, 6.9).011.7 (1.2, 2.5).004
Average no. of alcoholic drinks/d, last y
   0–1 (Ref)24921.2 (0.8, 1.8)1.0
   ‡ 232724.3 (3.6, 5.3)< .0013.7 (2.3, 5.9)< .001
   Unknown19594.2 (3.3, 5.2)< .0013.6 (2.3, 5.6)< .001
Age at first sexual intercourse (up to 59b y; n = 7210), y
   £ 1732585.0 (4.3, 5.9)< .0013.7 (2.5, 5.5)< .001
   ‡ 18 (Ref)28711.4 (1.0, 2.1)1.0
   Unknown10813.5 (2.5, 5.0).0042.5 (1.5, 4.4)< .001
No. of lifetime sexual partners (up to 59b y; n = 7210)
   0–9 (Ref)45071.4 (1.0, 2.0)1.0
   10–199163.9 (2.6, 5.7).0012.9 (1.8, 4.6)< .001
   ‡ 2011339.9 (8.2, 11.9)< .0017.8 (5.2, 11.8)< .001
   Unknown6544.5 (3.1, 6.5).0013.3 (1.9, 5.7)< .001
Lifetime drug use (up to 59b y; n = 7210)
   Never (Ref)51011.2 (0.9, 1.6)1.0
   Non-IDU12803.7 (2.8, 4.8)< .0013.1 (2.1, 4.5)< .001
   IDU18756.8 (48.4, 64.8)< .001107.0 (69.3, 165.1)< .001
   Unknown6424.7 (3.3, 6.8)< .0014.0 (2.5, 6.6)< .001
Blood transfusion before 1992
   No (Ref)70302.9 (2.5, 3.5)1.0
   Yes5816.7 (4.8, 9.4).0022.4 (1.6, 3.5)< .001
Serum alanine aminotransferase level, U/L
   < 40 (Ref)65991.8 (1.5, 2.2)1.0
   ‡ 40105612.7 (10.7, 15.1)< .0018.0 (6.0, 10.5)< .001
Note. Anti-HCV = HCV antibody; CI = confidence interval; IDU = injection drug use; OR = odds ratio.

aObtained by specifying linear contrasts of proportions among the levels of the subgroups.


bNational Health and Nutrition Examination Survey data collection on certain risk factors was limited to participants aged 20–59 years at time of survey; accordingly the 2005–2006 and 2007–2008 National Health and Nutrition Examination Survey cycles do not contain data risk factor for participants born in 1945–1946 and 1945–1948, respectively.

Among participants reporting a history of IDU, 56.8% (95% CI = 48.4%, 64.8%) were anti-HCV–positive compared with 1.2% (95% CI = 0.9%, 1.6%) for those who had never used any illicit drugs. Persons who received a blood transfusion before 1992 had a higher prevalence of anti-HCV (6.7%; 95%CI = 4.8%, 9.4%) than did those without this history (2.9%; 95% CI = 2.5%, 3.5%). Among persons with elevated ALT levels, 12.7% (95% CI = 10.7%, 15.1%) were anti-HCV–positive relative to 1.8% (95% CI = 1.5%, 2.2%) for those with normal ALT levels.

Factors Associated With Anti-HCV Prevalence Within the Birth Cohort
Unadjusted odds ratios (ORs) and 95% CIs for characteristics associated with anti-HCV prevalence are displayed in Table 2. Men, non-Hispanic Blacks, and persons with a family income below the poverty threshold, respectively, were more likely to be anti-HCV–positive compared with women, non-Hispanic Whites, and persons with family income of more than 2 times the poverty level. Injection drug use was the strongest predictor of anti-HCV prevalence among the birth cohort. Other characteristics significantly associated with anti-HCV prevalence were elevated ALT level, consumption of 2 or more alcoholic drinks per day, sexual intercourse before age 18 years, 20 or more lifetime sexual partners, and blood transfusion before 1992.

After we controlled for covariates in a multivariate logistic regression model (Table 3), IDU (adjusted OR = 98.4; 95% CI = 58.8, 164.5) remained the strongest predictor of anti-HCV prevalence. We also identified the following variables as significant risk factors for anti-HCV prevalence in the multivariate model: elevated ALT level (9.0; 95% CI = 6.0, 13.7), a family income below the poverty threshold (4.7; 95% CI = 3.0, 7.4), US-born (3.2; 95% CI = 1.7, 6.1), non-Hispanic Black race (2.3; 95% CI = 1.7, 3.2), and blood transfusion before 1992 (2.3; 95% CI = 1.3, 4.0). We removed number of sexual partners and age at first sexual intercourse from the multivariate model because of collinear relationships with IDU. No interaction terms were significant.

Discussion
These findings highlight the relatively high prevalence of anti-HCV (3.2%) among persons in the 1945–1965 birth cohort compared with the prevalence among adults aged 20 to 70 years during the 1999–2008 survey period, but born before 1945 or after 1965 (0.9%; unpublished Centers for Disease Control and Prevention data); persons in the birth cohort were 4 times more likely to be anti-HCV–positive than adults outside the cohort. Our finding that history of IDU, blood transfusion, elevated ALT, Black race, and poverty were associated with HCV infection within the birth cohort is consistent with previous findings based on the general US adult population.[1,3] However, IDU and blood transfusions before 1992, the most common exposure risks reported by persons infected with HCV, account for only 52% of infections and the remaining 48% report no known exposure risk and may not be identified through risk-based testing approaches. Testing for HCV infection on the basis of the birth cohort presents an opportunity to identify a significant proportion of cases that may otherwise go undetected in a subpopulation that accounts for approximately 75% of the burden of HCV infection in the adult US population.[5] The 1945–1965 birth cohort has the highest incidence of HCV-related liver disease and death, which is projected to increase sharply over the next 2 decades.[10,36,37]

Most persons in the birth cohort are likely to have been infected for 20 to 40 years or more, and multiple models have indicated that there will be dramatic increases in the numbers of HCV-infected persons with significant liver disease over the next 10 to 20 years[31,38] without effective public health interventions. Even with declining prevalence in the overall US population, HCV disease burden is expected to increase significantly because of the aging of the infected population.[10,36] Identification of HCV-infected persons and planning for care and therapy now, however, will improve efforts for long-term care and management of the infected population.[39] Although treatment response is better among persons younger than 40 years than those aged 40 years or older, persons older than 65 years have been shown to respond as well to therapy as those between the ages of 40 and 65 years, a fact that will become increasingly important as the birth cohort ages into retirement.[40]

For HCV-infected persons for whom antiviral treatment is indicated,[41] there have been recent medical advances that significantly improve the efficacy of therapy. Unfortunately, HCV treatment rates are low.[42] We found that almost one third of anti-HCV–positive persons in this cohort report being uninsured, a problem that certainly contributes to low treatment rates and difficulty accessing care. Expansion of coverage for medical care could increase access to care and treatment.
Even for those infected persons who do not receive antiviral medication, because of treatment contraindications or for other reasons, interventions are available that may limit disease progression and decrease HCV transmission to other persons. Reducing alcohol use can prevent exacerbation of liver disease. In our analysis, however, we found that nearly 58% of anti-HCV–positive persons in the birth cohort reported drinking 2 or more alcoholic drinks per day on average. Alcohol use is associated with development and progression of fibrosis and significant increase in liver-related and overallmortality.[41,43,44] Among HCV-infected persons, history of and current moderate alcohol use (approximately 2 drinks/day or less) have been found to be associated with a 2-fold increase in all-cause mortality and 7-fold increase for those who report drinking 2 or 3 drinks per day.[43] The prevalence of alcohol use among anti-HCV–positive birth cohort members suggests that use of Screening and Brief Interventions for Referral for Treatment of the Reduction of Alcohol Use as recommended by the US Preventive Services Task Force may be beneficial.[45] It has furthermore been suggested that, among heavy drinkers, knowledge of HCV-positive status and brief counseling received from health care providers upon diagnosis may be important factors in the reduction of alcohol use.[46,47]

Limitations
There are limitations in this study. First, NHANES samples include only the US civilian, noninstitutionalized population. A large number of high-risk persons who are incarcerated, institutionalized, or homeless are excluded; thus, these analyses are likely to result in an underestimate of anti-HCV prevalence. Second, behavioral risk-factor data were limited to participants aged 60 years or younger. As a consequence, for the 2005–2006 NHANES cycle, no risk-factor information was available for participants born during 1945–1946 (who would have been aged 60–61 years during the 2005–2006 cycle). Likewise, there were no risk factor data for participants born during 1945– 1948 in the 2007–2008 cycle. Third, nearly all risk-factor data used in this analysis were self-reported. Participants may overreport or underreport behaviors in response to questions such as IDU or number of lifetime sexual partners, which might bias our results. Fourth, participant birth year was approximated from estimated year of interview and age at survey.
Finally, we did not examine differences by sociodemographic and risk characteristics between persons who knew and those who did not know their HCV-infection status (positive or negative) before testing because prior knowledge of HCV-infection status is not assessed for NHANES participants. However, among participants who test positive for anti-HCV or those with an indeterminate test result for anti-HCV plus a positive HCV-RNA, NHANES conducts a separate follow-up survey to ascertain knowledge of HCV infection status before receiving notification of results from NHANES. Although analyses[31,48] of the follow-up survey data have suggested differences— by age, access to health care, knowledge of risk factors—between HCV-positive persons who were aware of their status versus those who were unaware, those findings are by themselves limited by small sample sizes, low survey response rates, and their lack of generalizability to all persons, HCV-positive or -negative.

Conclusions
This study provides additional evidence of the high prevalence of anti-HCV among persons in the 1945–1965 birth cohort consistent with earlier studies of infection prevalence. Considerable racial and socioeconomic disparities by anti-HCV positivity status also are apparent within the cohort. High rates of alcohol use reported by anti-HCV–positive respondents suggest the importance of diagnosing infection and providing effective interventions to decrease alcohol consumption and slow the progression of liver disease. In light of the high prevalence of HCV infection among persons born during 1945–1965, the increasing morbidity and mortality associated with HCV infection, and reductions in liver cancer and HCV-related mortality when HCV infection is eliminated, it is critically important to identify those persons living with hepatitis C and link them to appropriate care and treatment.

References

Friday, January 17, 2014

Treatment of Chronic Hepatitis C Virus Infection: Some Remaining Obstacles in the United States


Treatment of Chronic Hepatitis C Virus Infection: Some Remaining Obstacles in the United States

Liver International
Accepted Articles, Accepted manuscript online: 13 JAN 2014

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Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Review Article

Gloria Searson1, Ellen S. Engelson2,  Damaris Carriero1,3, Donald P. Kotler1,2,*
DOI: 10.1111/liv.12467

This article is protected by copyright. All rights reserved.

Publication History
Accepted manuscript online: 13 JAN 2014 01:05AM EST
Manuscript Accepted: 6 JAN 2014
Manuscript Revised: 25 DEC 2013
Manuscript Received: 27 JUN 2013

Keywords: effectiveness research;  health disparities;  substance abuse; alcoholism;  chronic liver disease

Abstract
Hepatitis C infection is an important problem in inner city neighborhoods, which suffer from multiple health disparities. Important factors in this population include alcoholism and substance abuse, mental illness, and homelessness, which may be combined with mistrust, poor health literacy, limited access to health care, and outright discrimination. Systemic barriers to effective care include a lack of capacity to provide comprehensive care, insufficient insurance coverage, poor coordination among caregivers and between caregivers and hospitals, as well as third party payers. These barriers affect real world treatment effectiveness as opposed to treatment efficacy, the latter reflecting the world of clinical trials. The components of effectiveness include efficacious medications, appropriate diagnosis and evaluation, recommendation for therapy, access to therapy, acceptance of the diagnosis and its implications by the patient and adherence to the recommended therapy. Very little attention has been given to assisting the patient to accept the diagnosis and adhere to therapy, i.e., care coordination. For this reason, care coordination is an area in which greater availability could lead to greater acceptance/adherence and greater treatment effectiveness

These are exciting times in the field of Hepatitis C virus (HCV) infection. After many years of ominous predictions, the outlook fo r HCV-infected patients has im proved substantially with the introduction of direct acting agents (1, 2). However, it is too soon to declare victory. It has even been said that we are only ‘at the end of the beginning’ of the struggle (3). There are several remaining obstacles. The purpose of this paper is to enumerate and discuss some of the remaining barriers to effective HCV treatment in the United States, predominantly from an inner city perspective.

The medical and economic burdens of HCV have been increasing for the past 3 decades (4, 5), and will continue to rise for the next 15 years. The burden of managing HCV-infected patients will fall increasingly on public institutions, i.e., inner city hospitals, clinics and community health centers, and the costs will shift progressively to public payers, such as Medicaid and Medicare (5). Official estimates of disease prevalence in the United States range from around 4 million (6) to as high at 7 million (7 ). The largest subgroup, comprising almost 80%, was born between 1945 and 1965 (8). Other cohorts of HCV-infected individuals exist, including immigrants, patients with sexually transmitted HCV infection, plus other routes of transmission, including nosocomial. A majority are unaware of their HCV serostatus (9).

There are multiple obstacles to access of effective antiviral therapy in all countries, with variations within and between them for different subgroups of patients. The barriers can be classified as virologic, host, and systemic. Virologic factors will not be considered here. Host factors may be modifiable or non-modifiable. In addition to age, sex and HIV co-infection, genetic factors exist, such as the IL28B polym orphism, which partially explain the observed racial variation in treatment re sponse (15). While hepatitis C has its highest prevalence in a cohort defined by birth year, it is an especially important problem in African-American communities. The authors’ institutions treat residents of Harlem and surrounding neighborhoods in New York City, which have high prevalence rates for HCV infection and other co-morbidities (10). Similar conditions exist in many inner-city environments in the US.

It is not appropriate to discuss HCV infection in African-Americans without noting the presence of health disparities in general. In a recent publication, Williams and colleagues noted that overall death rates in African-Americans are 30% higher than in Caucasians (11), with higher death rates for 10 of the 15 leading causes of death, though not for liver cirrhosis. Health disparities also exist in HCV infection, in terms of higher prevalence (6) and poorer response to therapy (12). Despite these facts, African-Americans have long been under-represented in clinical trials (13). To identify and reduce such disparity, the FDA Safety and Innovation Act, recently passed by Congress, requires the FDA to report annually on the inclusion of subjects by age, sex, race, and ethnicity in clinical trials supporting applications of new drugs and medical devices (14).

Important host factors that are potentially modifiable include substance abuse, mental illness, and homelessness. A co-morbidity that ha s received very little attention is alcoholism. Alcohol accelerates hepatic fibrosis in mono- and co-infected patients with HCV infection (16, 17). A prospective, case-control study published in 1999, of chronic viral hepatitis, alcoholism, and the development of chronic liver disease at Harlem Hospital Center (18) showed that the combination of HCV infection and heavy alcohol intake, but not HCV infection or alcoholism alone, significantly promoted the development of chronic liver disease. The cohort was followed for four years and death rates were numerically higher in the HCV plus alcohol group. The authors called for greater attention to the management of alcoholism to mitigate the development of chronic liver disease, even in the absence of effective anti-HCV therapy at the time. In a review of HCV-infected patients followed over a 15-year period in clinics in Scotland, the fraction of cirrhosis attributable to heavy alcohol intake was estimated at 36%, and at 61% for heavy drinkers (19). Importantly, since active alcoholism is an absolute contraindication to anti- HCV therapy, the subgroup at most risk of disease progression often is excluded from treatment. Recent studies from Switzerland and France have demonstrated reasonable rates of sustained viral response in alcohol-dependent patients (20,21). Poorer responses to anti-HCV therapy in the US VA system were felt to be related more to poorer treatment adherence than a direct effect of alcohol intake (22). Maintaining adherence to treatment may be as important or even a more important goal than enforcing abstinence. A study to test this hypothesis would be one comparing the effects of abstinence and harm reduction. However, while determining the relative importance of HCV and of alcohol intake, including amount, drinking pattern, and chronicity, in liver disease progression is of interest, the ultimate goal of therapy should be to cure both conditions. Other host factors may affect treatment adherence, however. Simoni and colleagues analyzed 13 studies in HIV infection that used electronic drug monitoring. Demographic variables such as sex, age, economic status, education level, plus depression and substance abuse, did not fully explain a lower level of adherence observed in African-American subjects (23). The authors cited evidence that mistrust , poor health literacy, in equalities in access to health care, as well as outright discrimination might be responsible for the differences. Patient mistrust acts synergistically with nihilism and stigmatization to confound attempts at therapy. Patients whose clinical problems are related to socially unacceptably behaviors may be especially prone to feeling stigmatized, while caregivers may unconsciously express bias. Cultural competence, which involves developing attitudes, behaviors, and policies that enable effective work in cross-cultural situations, are routine medical education and core competency initiatives, but have not overcome the prevailing host barriers.

The host barriers to effective treatment may become institutionalized so that caregivers do not aggressively promote and patients do not aggressively seek proven therapies. These biases may be resistant to change.

A substantial proportion of patients currently presenting for HCV testing are aware of their HCV status or of the presence of liver disease (G. Searson, personal observations). In many cases, patients had been told by a health care provider one, two, or three decades ago that they were going to be OK or that their liver tests were relatively normal and not to worry, and now are being told that they have a serious disease. It is especially difficult for the medical establishment to engage patients who exist outside the formal health care system. The Affordable Care Act may be helpful in expanding coverage to some people, but it will not aid people who harbor a fundamental mistrust in the health care system. Community-based organizations may be helpful in this situation; fostering trust by helping people to feel at ease through non-judgmental treatment; creating an environment where people may be more truthful about personal matters: self-worth, future prospects, or even existential concerns.

Systemic barriers to effective care are multiple and diverse. Perhaps the most important is the lack of capacity of our system to provide comprehensive care to our patients. Mental health issues especially often are unrecognized, overlooked, or undertreated. In HIV infection, Ryan White funding allowed the development of a comprehensive care model, with resources devoted to social work needs, including food and shelter, as well as mental health needs. Such support is not available for HCV-infected patients.

Lack of insurance, or insufficient insurance coverage, is common among HCV-infected patients (24). Poor coordination between caregivers and hospitals and between caregivers and third party payers may lead to unanticipated treatment interruptions. Few institutions have a centralized system for toxicity management, relying on standard emergency services. However, a visit to an Emergency Department or a hospital admission is likely to lead to treatment interruption for a patient irrespective of the presenting complaint. Few hospitals have direct- acting anti-HCV agents on formulary and the patient is “supposed to” bring his/her outpatient medications to the hospital, which may not occur in the face of an emergency.

There are two ways to evaluate treatment success: efficacy and effectiveness. Most discussions are centered on the notion of treatment efficacy, which can be defined as the number cured/number treated, and which reflects the world of clinical trials. Inclusion and exclusion criteria minimize the host factors interfering with therapy while the study design and pharmaceutical support minimize the systemic obstacles to therapy. A more accurate measure of treatment success from a public health standpoint is treatment effectiveness, which can be defined as the number cured/number infected. Its importance is seen in the example of alcoholism.

As discussed above , alcoholism increases the risk for developing chronic liver disease, but is a contraindication for therapy, including inclusion in clinical trials. For this reason, alcoholism does not affect measured treatment efficacy though it markedly reduces treatment effectiveness, as might be measured by the prevention of chronic liver disease. Measured rates of effectiveness for pegylated interferon and ribavirin averaged 3.5% in clinical experience (25, 26), while the effectiveness in the registration trials ranged from 12-17%, and efficacy in the same trials aver aged around 45% (discussed in 25).

Recent and emerging advances in therapy will allow the role of new regimens on treatment effectiveness to be determined, especially the application of interferon-free regimens. Treatment efficacy for genotype 1, treatment-naïve patients in clinical trials averaged 40-50%, using pegylated interferon and ribavirin (27), compared to around 75% in trials also using a directing agent (1). However, real world results in an inner city population in New York City showed an efficacy of 14% in genotype 1 patient s. In addition, a recent presentation showed an SVR rate of 43% using a direct acting agent in a similar patient group (28). Treatment effectiveness, including cost effectiveness will require closing the gap between clinical trials and real world results. Depending on the specific community, net effectiveness also may require improvements in the prevention of risk behaviors, which may lead to reinfection after SVR (29). Furthermore, improvements in efficacy are irrelevant for a patient who remains unengaged with the formal health care system.

One can divide treatment effectiveness into several components (30). Effective therapy includes the availability of efficacious medications as well as a system to evaluate patients appropriately, recommend therapy, provide access to therapy, as well as patient compliance with the evaluation and recommendations as well as adherence to therapy. Developing efficacious medications is the task of the pharmaceutical industry, while making diagnoses and treatment recommendations plus providing access to therapy are tasks for the health care system. Accepting the diagnosis and adhering to therapy is the job of the patient and patient advocates. While great effort has gone into developing efficacious therapies and an increasing amount of attention is being given to screening, diagnosis, and evaluation, less attention has been placed on treatment access and very little attention has been given to assisting the patient to accept the diagnosis and adhere to therapy, i.e., care coordination. For this reason, care coordination is an area in which greater availability, supported by a currently nonexistent funding source, could lead to greater acceptance/adherence, and greater treatment effectiveness. The elements of care coordination, which include individual counseling, education, behavioral modification, and other support, are the same for the management of many diseases.

In summary, if we can overcome the obstacles to care delineated above, then treatment effectiveness will equal efficacy.

 http://onlinelibrary.wiley.com/doi/10.1111/liv.12467/pdf

References