Hepatitis C Patients Taxing Medical System: hospitalizations increasing for HCV

[Guest guest]

Hepatitis C Patients Taxing Medical System: hospitalizations

increasing for HCV mono and coinfected

Forbes.com

FRIDAY, Dec. 30 (HealthDay News) -- The use of health-care resources

by hepatitis C patients in the United States has been increasing by

25 percent to 30 percent a year, says a Duke University study in the

December issue of Hepatology.

About 3 million people in the United States have chronic hepatitis C

virus (HCV), and many of them contracted it in the 1970s, before

testing and safe needle-sharing practices became widespread. Health

experts have been predicting an increasing impact on the health

system as these people grow older.

The Duke researchers analyzed HCV patient hospitalization trends from

1994 to 2001, HCV-related doctors' visits from 1996 to 2002, and

prescription drug data for HCV patients from 1998 to 2000.

The study found that HCV-related hospitalizations, hospital days,

total charges and deaths increased by more than 20 percent per year.

That's three times higher than all-cause hospitalizations. The

largest increases were seen in patients in their 40s and 50s, who

spent more time in a hospital, incurred greater costs, and died more

often than HCV patients in other age groups.

The study also found that doctor office visits by HCV patients

increased by 36 percent a year, and spending on HCV drug therapy rose

from $78 per $100,000 of new prescriptions in 1998 to $259 per

$100,000 in 2000.

" The study documents accelerating use of health-care resources by

patients with HCV, indicating that the future burden of HCV infection

will match and may exceed analysts' forecasts, " the study authors

wrote.

HCV & Coinfection-Expected Increased Hospitalizations Rates:

complications expected to quadruple - (12/08/05)

Â

Hospitalizations increased for liver-related complications from 8% to

13% and for chronic HCV from 1% to 5% in this period: 1996-2000; 4-

fold increase - (12/08/05)

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HCV & Coinfection-Expected Increased Hospitalizations Rates:

complications expected to quadruple

HCV has aptly been described as a sleeping giant: Our findings

corroborate existing concerns over the aging of patients with HCV. As

the patients continue to age and the disease burden progresses,

suboptimal decisions regarding HCV treatments will bring increasing

opportunity costs for the health care system and society.

“Trends in health care resource use for hepatitis C virus infection

in the United Statesâ€

Hepatology

Dec 2005 Volume 42, Issue 6, Pages 1406-1413

C. Grant 1,

6Department of Medicine, Duke University Medical Center, Durham, NC

“…..HCV infection represents a substantial health care burden….

future HCV-related complications will presumably increase and present

further economic and other stresses on the health care system…..

However, increasing rates of patients with disease progression are

anticipated to raise the proportion of patients with cirrhosis from

25% in 2010 to 38% in 2040…..

….The primary outcomes of interest - hospitalizations, charges,

hospital days, and physician visits - showed average annual increases

in the range of 25% to 35%, indicating that the future burden of HCV

infection will match and may exceed analysts' forecasts….

…From 1990 to 2015, the number of persons with long-standing

complications is expected to at least quadruple…

….office visits by HCV patients increased at an average annual rate

of 36%....

….Nearly 3 times as many HIV patients were hospitalized for liver-

related reasons in 2001 than in 1994. Co-infected patients

constituted 44.9% of HIV liver-related hospitalizations in 2001, up

from just 9.1% in 1994…..

….From 1994 through 2001, HCV-related hospitalizations, hospital

days, total charges, and deaths increased at average annual rates

exceeding 20%, more than 3-fold higher than rates for all-cause

hospitalizations…..

….Patients in their 40s and 50s also spent more time in the

hospital, incurred greater costs, and died more frequently than

patients in other age groups….

….Compared with hospital days for any reason, HCV liver causes for

all ages accounted for almost 4 times as many hospital days in 2001

as in 1994 (371 vs. 98 per 100,000)….

….Racial/ethnic minorities constituted roughly half of HCV-related

hospitalizations but less than 20% of physician visits….

….Vertical transmission rates drive the trends among children and

adolescents, with active carriers born to mothers with HCV infection

with 1% to 5% likelihood……data indicate that pediatric HCV trends

merit further attention (HIV increases HCV MTCT rates)… Trends

among pediatric HCV patients are relatively more volatile and less

informative than for older patients…

HIV-HCV Co-infection.

(I extracted & put here the coinfection data since its so compelling.

See other detailed results & Discussion below)

Patients with HIV-HCV co-infection were another important subgroup in

the analysis. Because highly active antiretroviral therapy was

introduced to many of these patients during the study period, we

examined co-infection statistics for evidence of change. As shown in

Table 5, increases in liver-related hospitalizations were

approximately proportional to those of patients infected only with

HCV. As a fraction of all HCV liver-related hospitalizations,

hospitalization frequencies for co-infected patients were

consistently between 2% and 3%. Both within and across age groups,

hospitalizations among co-infected patients kept pace with rates of

increase for mono-infected patients.

For the aggregate HIV population, however, HCV liver complications

caused many more hospitalizations. Nearly 3 times as many HIV

patients were hospitalized for liver-related reasons in 2001 than in

1994. Co-infected patients constituted 44.9% of HIV liver-related

hospitalizations in 2001, up from just 9.1% in 1994. As a fraction of

all HIV hospitalizations (not specifically liver-related), co-

infected patients constituted 7.5 times as many hospitalizations in

2001 as in 1994, rising from 0.4% to 3.1%. The overall magnitude of

the HIV burden remains much larger than that of HCV. Over the 8-year

study period, HIV hospitalizations occurred at a frequency 3.4 times

that of HCV liver-related hospitalizations. Between 1994 and 2001,

total inpatient charges for HIV hospitalizations were 2.9 times

higher than for HCV liver-related hospitalizations.

ABSTRACT

Chronic hepatitis C virus (HCV) infection affects approximately 3

million people in the United States ( Edlin's study presented at

AASLD Nov 2005 finds 5 million with HCV & 4 million with chronic HCV

due to including homeless, incarcerated & other populations not

reported in previous NHAHNES data) and places tremendous demands on

the health care system.

As many observers have predicted, the disease burden continues to

grow as the infected population ages.

In this study, we analyzed inpatient data from the Healthcare Cost

and Utilization Project, outpatient data from the National Ambulatory

Medical Care Survey, and drug data from the Verispan Source

Prescription Audit.

We examined recent growth in the use of health care resources among

HCV patients by age group and found average annual increases of 25%

to 30% for hospitalizations, charges, hospital days, and physician

visits. Corresponding time-trend coefficients were positive (P

< .001). From 1994 to 2001, the HCV burden increased among patients

aged 40 to 60 years, reflecting the natural history of disease

progression.

In sensitivity analysis, HCV outcome growth rates remained

significant, unless more than 3 out of 4 cases were initially

underreported.

Also, patients co-infected with HIV and HCV in 2001 constituted 7.5

times as many hospitalizations and incurred 2.9 times the charges in

1994, relative to all HIV hospitalizations and charges.

Our findings highlight the urgency concerning HCV outcomes. In

conclusion, as patients continue to age and disease burden

progresses, suboptimal decisions regarding HCV treatments will bring

increasing opportunity costs for the health care system and society.

Article Text

As many observers have predicted, the treatment burden of hepatitis C

virus (HCV) continues to grow as the population of patients with HCV

grows older. With approximately 27,000 hospitalizations and $500

million in hospital charges recently attributed to the disease in the

United States,[1] HCV infection represents a substantial health care

burden. Because of the long, asymptomatic disease course,[2] many

patients with HCV infection are not diagnosed until the disease has

progressed to some degree of liver damage. Available treatments are

expensive, are associated with debilitating and sometimes dangerous

side effects, and are effective in only approximately half of

patients with genotype 1 HCV infection, the most common in the United

States. The incidence of HCV infection has fallen sharply because of

increased awareness of HIV and safer practices for injection drug use.

[3-7] However, existing and undiagnosed cases represent a latent

threat to public health. As the population of patients with HCV

infection ages, future HCV-related complications will presumably

increase and present further economic and other stresses on the

health care system.

Seroprevalence data have allowed researchers to estimate the

potential magnitude of HCV infection and thus the possible

complications. In the sample population of the Third National Health

and Nutrition Examination Survey, HCV antibodies and HCV RNA were

observed with respective frequencies of 1.8% and 1.4% among surveyed

individuals.[8][9] From these figures, it is estimated that 3 million

Americans are chronically infected with HCV. Incidence-based models

provide estimates of similar magnitude.[8] Because many of the

infections occurred in the 1970s, a wave of complications during the

1990s was predicted as the duration of infections reached critical

thresholds. Given the relatively low incidence of new infections, the

total number of infected patients will eventually diminish because of

deaths in the existing cohort. However, increasing rates of patients

with disease progression are anticipated to raise the proportion of

patients with cirrhosis from 25% in 2010 to 38% in 2040.[10]

Because of the potentially significant impact of HCV on public health

and the health care system overall, updated expectations concerning

HCV trajectories with quantitative observations from the recent past

would be of great value. Therefore, we analyzed hospitalization,

outpatient, and prescription data over 8 years (1994 through 2001) to

better understand how HCV outcomes are evolving. Our objective was to

provide longitudinal statistics concerning health care resource use

by patients with HCV, with a particular focus on the relative

distribution of HCV-related complications across age groups. We

intended the analysis to inform important policy perspectives

regarding treatment for patients with HCV in the near future.

Materials and Methods

Inpatient Trends.

We examined hospitalization trends using the Nationwide Inpatient

Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP).

[11] The NIS approximates a 20% stratified sample of community

hospitals in the United States and samples hospitals according to

relevant characteristics (e.g., urban vs. rural, county vs. private)

to produce a truly representative sample. After extrapolation to the

national level, the NIS represents approximately 35 million

hospitalizations per year and contains clinical, demographic, and

economic variables.

Each NIS observation contains up to 15 ICD-9-CM diagnoses. If a

patient had a primary or secondary diagnosis of HCV infection (ICD-9-

CM codes 070.41, 070.44, 070.51, or 070.54), we defined the

hospitalization as HCV-related. To better discern hospitalizations

likely associated with HCV-related complications, we also identified

liver-related hospitalizations. Based on criteria set forth by Kim et

al.[1] we considered a hospitalization to be liver-related if (1) the

principal diagnosis was HCV- or alcohol-related liver disease; (2)

there was any diagnosis of cirrhosis, portal hypertension, other

sequelae of liver disease, hepatic encephalopathy, ascites,

hepatorenal syndrome, hepatocellular carcinoma, or combined

hepatocellular carcinoma and cholangiocarcinoma; or (3) the patient

underwent liver transplantation.

For all HCV-related hospitalizations and for liver-related HCV

hospitalizations, we examined admittance frequencies, total hospital

days, liver transplantations, nationwide charges, and deaths for the

years 1994 through 2001. We constructed statistics for female

patients with HCV, patients co-infected with HCV and HIV (ICD-9-CM

codes 042.00 and 079.53), and 10-year age groups to better understand

demographic changes in the burden of HCV infection. Annual magnitudes

and annual group-specific shares for outcome variables provide

insight concerning the HCV patient life cycle. To adjust for overall

hospital population changes, we computed all statistics both in raw

terms and relative to all hospitalizations. We adjusted for inflation

using the US Consumer Price Index for Medical Care.

To assess the rate of change in outcomes, we used Poisson regressions

for annual count data, treating each 10-year age group as the

individual level of observation, observed in each of the 8 years from

1994 to 2001. For patients diagnosed with HCV, we ran separate

regressions for the following dependent variables: hospitalization

frequencies, liver-related hospitalization frequencies, total

hospital days, and deaths. The regressor for each of these

regressions was a simple time-trend variable for the years 1994 to

2001, the coefficient of which was used to assess the significance of

the rates of change in outcomes over the period.

Outpatient Trends.

In addition to hospitalization trends, we examined changes in

ambulatory care for patients with HCV and spending on prescription

drugs for HCV. Physician visits were tracked for the years 1996

through 2002 using the National Ambulatory Medical Care Survey

(NAMCS).[12] Based on randomly sampled visits during week-long

reporting periods, NAMCS contains information reported by office-

based physicians engaged in direct patient care. If HCV was indicated

in any of the 3 diagnostic fields, we categorized the office visit as

HCV-related. Stratified by 10-year age groups, the NAMCS data

displayed fairly unstable numbers of HCV-related office visits. As a

result, we focused on 3-year moving averages to smooth out year-to-

year volatility in the data.

Drug Trends.

Aggregate annual spending on prescriptions for interferon-ribavirin

combination therapy (ribavirin-interferon alfa-2b) from 1998 through

2000 was taken from the Verispan Source Prescription Audit,[13] which

provides total national prescription payments collected from more

than 35,000 retail pharmacies in the United States. Although

interferon monotherapy was also used to treat HCV during these years,

we have no way of identifying which prescriptions were intended to

treat cancer or other conditions. Combination therapy, however, is

only prescribed for HCV. Our interferon-ribavirin statistics describe

the aggregate volume of prescription demand and do not contain

patient-level data.

Analysis of Underreporting.

Because HCV antibody testing was introduced in 1991, it is unlikely

that the dissemination of testing into practice was complete by 1994.

The observed outcome frequencies probably understate the actual

numbers of HCV outcomes by greater proportions during earlier years

of our study period. To the extent that the rate of HCV testing and

reporting increased over time, the growth rates observed in our data

may overstate the increase in health care resource use for HCV.

Therefore, we conducted a sensitivity analysis to consider the

potential impact of underreporting.

As a baseline scenario, we hypothesized that 50% of cases were

underreported in 1994 and that underreporting fell each year by some

fixed amount, so that 0% of cases were underreported in 2001. For

comparison purposes, we allowed the initial underreporting rate to

vary between 25% and 75%. For each scenario, we maintained the

assumption that underreporting fell each year by an amount resulting

in 0% underreporting in 2001.

For purposes of comparison, we calculated hospitalization statistics

for alcohol-induced cirrhosis of the liver (ICD-9-CM code 571.2).

This condition was not as likely as HCV to be misclassified in the

early years of the study period. Differences in statistics for HCV

and alcohol-induced cirrhosis likely reflect both underreporting

effects and differences in underlying disease burden.

Results

Tables 1 and 2 provide demographic profiles for hospitalizations and

physician visits for the first and last years of each data set.

Racial/ethnic distributions were stable, except for a moderate

increase in the share of hospitalizations among Hispanic patients.

However, the racial/ethnic profile for hospitalizations differed

markedly from the profile for physician visits. Racial/ethnic

minorities constituted roughly half of HCV-related hospitalizations

but less than 20% of physician visits. Similar changes were seen with

respect to patient sex.

Hospitalizations.

From 1994 through 2001, HCV-related hospitalizations, hospital days,

total charges, and deaths increased at average annual rates exceeding

20%, more than 3-fold higher than rates for all-cause

hospitalizations. Supplementary Table 1 reports annual frequencies by

year for these variables. Table 3 reports year-over-year growth rates

in these statistics, averaged over the 8 years. The growth patterns

were most striking for patients in their 40s and 50s. Because these

groups' shares of hospitalizations rose so much, other age groups saw

their shares decline. Patients in their 40s and 50s also spent more

time in the hospital, incurred greater costs, and died more

frequently than patients in other age groups. From 1994 to 2001,

patients aged 40 to 49 saw their share of liver-related hospital days

increase from 32.3% to 37.6%. Similarly, the share of liver-related

hospital days among patients aged 50 to 59 rose from 17% to 30.1%.

Compared with hospital days for any reason, HCV liver causes for all

ages accounted for almost 4 times as many hospital days in 2001 as in

1994 (371 vs. 98 per 100,000).

In the Poisson regressions of the rates of change in outcomes, the

frequencies and lengths of stay increased significantly for all HCV-

related hospitalizations and for liver-related HCV hospitalizations,

relative to all-cause hospitalizations (P < .001 for all

comparisons). We also conducted sensitivity analyses of our

assumptions regarding underreporting of HCV infection in earlier

years of the study period (Fig. 1). In the baseline scenario - in

which 50% of actual cases were underreported in 1994 - the average

annual increase in HCV liver-related hospitalizations was 11.1%. The

increase in hospitalizations that we observed in the HCUP data would

be entirely attributable to underreporting only if more than 77% of

cases in 1994 were not reported.

Except among adolescents, the observed growth in HCV liver-related

hospital days was entirely extensive. That is, more hospital days

resulted from more frequent hospitalizations, as opposed to longer

lengths of stay. For HCV liver-related hospitalizations, average

length of stay declined to 6.9 days in 2001 from 8.5 in 1994.

However, adolescents experienced both extensive and intensive growth.

Average length of stay for HCV liver-related hospitalizations

increased by 2.1 days, and the number of liver-related

hospitalizations more than doubled (244 vs. 111).

Increasing hospitalizations and hospital days coincided with higher

expenditures for HCV. For every $100,000 in nationwide charges from

all hospitalizations, liver-related HCV hospitalizations resulted in

$427 in charges in 2001, compared with only $145 in 1994. Once again,

patients in the 40s and 50s age groups accounted for a large majority

of the increase. Higher spending for HCV resulted both from more

hospital days and higher charges per hospitalization, with 37% more

charges per HCV liver-related hospital day in 2001 than in 1994.

Table 4 shows trends in HCV-related hospitalizations among women.

Women aged 30 to 59 years accounted for much less than 50% of HCV

hospitalizations; however, younger women and women older than 60 were

hospitalized with HCV liver diagnoses more frequently than men. This

phenomenon among women in their 20s disappeared after correcting for

the spurious diagnosis of HCV in women whose primary reason for

diagnosis was pregnancy related (ICD-9-CM codes 641-677).

Physician Visits.

Outpatient data corroborate the upward trend in HCV burden. In the 9

years of NAMCS data, office visits by HCV patients increased at an

average annual rate of 36%. Between 1996 and 2002, the 3-year moving

average rose by approximately 1 million annual office visits, from

449,800 in 1996 to 1.49 million in 2002 (Supplementary Table 1).

Three-year averages were pulled up by spikes in 2002 office visits

among patients aged 40 to 59. We did not pursue further subgroup

analysis because of small and unstable numbers of women, children,

and HIV-HCV-co-infected patients in the HCV outpatient population.

Prescription Drugs.

The Verispan Source Prescription Audit data[13] revealed the entry of

the new ribavirin-interferon combination drug treatments for HCV. A

total of $352.5 million was spent on 372,000 prescriptions for

ribavirin plus interferon between 1998 and 2001, with no

prescriptions observed before 1998. For every $100,000 in new

prescriptions, spending for ribavirin-interferon rose from $78 in

1998 to $259 in 2000. Meanwhile, $297.9 million was spent on 578,000

prescriptions for interferon monotherapy between 1993 and 2000.

Spending for interferon monotherapy increased every year before 1998

(when combination therapy entered the market) and decreased every

year thereafter.

Discussion

This study documents accelerating growth in the use of health care

resources by patients with HCV. The primary outcomes of interest -

hospitalizations, charges, hospital days, and physician visits -

showed average annual increases in the range of 25% to 35%,

indicating that the future burden of HCV infection will match and may

exceed analysts' forecasts. From 1990 to 2015, the number of persons

with long-standing complications is expected to at least quadruple.

[14] In the 8 years from 1994 through 2001, we found 3-fold to 4-fold

increases. By 2015, long-standing infections may lead to even greater

numbers of complications than have been predicted.

Our findings corroborate existing concerns over the aging of patients

with HCV. Shatin et al.[15] estimated that the prevalence rate for

chronic HCV infection is highest for the group aged 45 to 54 years

(277 per 100,000). We found that the role of aging was highlighted by

disproportionately high outcome shares attributable to patients aged

40 to 60 years, among whom average annual growth statistics above 30%

and even 40% were common. As others have noted,[10][16] worsening

health for patients with HCV advancing into middle and late middle

age exacts increasing costs.

The possibility of underreporting in the mid-1990s poses a major

limitation to this study. Real increases in HCV outcomes were almost

certainly less than the observed increases because of underreporting.

However, some limit to this distortion is evident from the age group

variability. HCV liver-related hospitalizations occurred with nearly

the same frequencies for the 40s age group and the 60s age group in

1994. We have little reason to expect that underreporting would be

far greater for 40-year-olds than for 60-year-olds in 1994. Given

that hospitalizations increased 4 times as much for the former group

than for the latter, our overall findings are unlikely to be driven

entirely by underreporting.

Nevertheless, our sensitivity analysis quantified the extent to which

hypothetical underreporting mitigated the rise in hospitalizations.

In every scenario, significant rises in hospitalizations were robust

despite possible underreporting effects. Even if 50% of HCV liver-

related hospitalizations were underreported in 1994, we found an

increase in hospitalizations greater than 200% between 1994 and 2001.

An initial underreporting rate exceeding 77% is necessary to

completely nullify the increase in hospitalizations.

We found that growth rates were much lower for alcohol-induced

cirrhosis than the corresponding growth rates for HCV, which may

result in part from more underreporting of HCV in the early years of

the study period. From 1994 to 2001, growth in liver-related HCV

hospitalizations exceeded growth in alcohol-induced cirrhosis by a

factor of 14. For growth in liver transplantations, total charges,

and in-hospital death, HCV exceeded alcohol-induced cirrhosis by

factors of 3.3, 5.7, and 56, respectively.

Differences in hospitalization rates between men and women provide

additional insight into disease progression. Because infections are

approximately twice as common among men than among women,[15] finding

more frequent liver-related HCV hospitalizations among men was not

surprising. However, our analysis revealed interesting sex-based

variation in hospitalization rates according to age group, with women

in their 60s being hospitalized for HCV liver-related reasons more

frequently. The age group phenomenon may result in part from gender

differences in the progression of HCV. In general, complications are

more progressive in men than women, causing gender variations in

times between peaks in infections and hospitalization shares. The

rise in relative shares for women after age 60 may be a cumulative

result of slower progression in women. Many of these late-life

hospitalizations involve serious complications, including death,

which are relatively more likely to have occurred before age 60 for

men than for women.

Vertical transmission rates drive the trends among children and

adolescents, with active carriers born to mothers with HCV infection

with 1% to 5% likelihood.[17] Current guidelines do not involve HCV

screening for newborns, leading to uninformative data concerning

changes in childhood infection rates. This may help explain why

hospitalization rates remained flat for children younger than 10

years, whereas simultaneously a 15% average annual increase occurred

in HCV hospitalizations among adolescents. These patterns may reflect

in part new infections during adolescence, but initial HCV

presentation in vertically infected children likely accounts for part

of the increase. Have vertical infections really remained flat? What

are the implications for future changes in HCV outcomes among

adolescents? Because newborns are not routinely screened for HCV,

answers based on observational hospital data are not clear, but the

data indicate that pediatric HCV trends merit further attention. A

better understanding of these trends requires a thorough model of

vertical transmission and childhood progression. For the near future,

forecasts of HCV among adolescents will exhibit high variance.

Transfusion-induced cases became extremely rare after 1992, but their

frequency in prior years is uncertain. HCV prevalence in adolescents

in 2005 is therefore uncertain.

HIV-HCV-co-infected patients are another important subgroup deserving

further attention, because these patients are being hospitalized for

HCV liver-related reasons with increasing frequency. Because of

recent changes in treatments for HIV, HCV has taken on a larger role

as a competing risk for co-infected patients. Mixed evidence

concerning interactions between HIV therapies and HCV outcomes has

complicated treatment decisions in the presence of competing risks

for co-infected patients.[18] These interactions provide important

topics for future research.

Our analysis has some limitations. We must emphasize that the trends

found in this study reflect sample-based estimates, rather than

comprehensive counts of actual events. In addition, we were unable to

track individual patients over time and thus were unable to

distinguish between changes in the numbers of hospitalizations per

patient from overall hospitalization counts. Also, although HCUP uses

rigorous sampling procedures to best represent hospitals throughout

the United States, certain sectors are not included, such as the

Veterans Affairs system. The data allow for casual observation of

related trends; however, because we could not link patient identities

between the prescription and HCUP data, we were unable to develop

impact estimates. In addition, the prescription figures likely

understate the use and costs of drugs for patients with HCV, because

the standard of care now includes pegylated interferon.

HCV has aptly been described as a sleeping giant.[8] Our analysis

provides descriptive statistics portraying the recent extent and pace

of this giant's awakening. Hospitalization statistics indicate

increasing takeoff in the use of health care resources by patients

with HCV. Combined with predictions of seroprevalence-based models,

our age group analysis provides reason to believe that resource use

will continue to accelerate in the near future. For hospitalization

frequencies, length of stay, charges, and deaths, we find that rates

of increase are highest for patients in their 50s. The 40s age group

involved the highest magnitudes of these variables, however,

indicating an even greater growth potential as middle-aged

individuals continue to age. Trends among pediatric HCV patients are

relatively more volatile and less informative than for older

patients. As a result, the burden of HCV is harder to forecast over

the lifetimes of patients younger than 30. To refine our

understanding of the HCV outlook, future efforts to quantify

pediatric incidence and progression are also needed.

In conclusion, how to best care for the population of HCV-infected

patients is an increasingly important topic. For patients who have

already developed cirrhosis, combination therapy has improved

outcomes, and by 2010, additional benefits may be realized for

patients without cirrhosis.[16] Our findings highlight the urgency

concerning HCV outcomes. Across the United States, health care

providers are using tremendous amounts of resources for HCV care. As

the patients continue to age and the disease burden progresses,

suboptimal decisions regarding HCV treatments will bring increasing

opportunity costs for the health care system and society.

Hospitalizations increased for liver-related complications from 8% to

13% and for chronic HCV in HIV-Coinfection from 1% to 5% in this

period: 1996-2000; 4-fold increase

“…..Treatment complications of HAART, including diabetes and

cardiovascular, and cerebrovascular complications, have increased

during this period, but they still comprise a relatively small

proportion of the total number of HIV hospitalizations in these

states…..â€

“….The strongest time period effects were for chronic HCV;

between 1996 and 1998, hospitalization proportions increased by a

factor of 2.25, and they increased by a factor of 3.97 between 1996

and 2000…..†see table below. I think its clear that these

numbers can only increase after 2000, when studies are conducted, and

keep increasing, until we have a better policy to address the problem

of hepatitis C coinfection. On a different note, although during thie

time period of this study, 1996-2000, we did not see significant

increases yet for heart disease and diabetes, I submit we will. In

future years diseases associated with aging in the general population

like diabetes, heart disease & perhaps brain-associated diseases &

cognitive impairment, will increase disproportionately among people

with HIV. We need to be prepared to follow these trends & to

clinically address these potential developments. Jules Levin

“Hospitalizations for Metabolic Conditions, Opportunistic

Infections, and Injection Drug Use Among HIV Patients: Trends Between

1996 and 2000 in 12 Statesâ€

JAIDS Journal of Acquired Immune Deficiency Syndromes: Volume 40(5)

15 December 2005 pp 609-616

Gebo, A MD, MPH*; Fleishman, A PhD†; , D

MD, MHS*

>From the *Department of Medicine, s Hopkins University School of

Medicine, Baltimore, MD; and †Agency for Healthcare Research and

Quality, Rockville, MD.

Highly active antiretroviral therapy (HAART) has been shown to reduce

morbidity and mortality associated with HIV-1 infection in the United

States. Previous studies have shown that HAART reduces

hospitalization rates by as much as 24% to 43%. With decreased

mortality, other chronic diseases that are common to HIV-infected

patients, such as viral hepatitis, and complications of HAART, such

as diabetes, liver-related conditions, ischemic heart disease, and

cerebrovascular disease, may now have more opportunity to become

clinically apparent.

A previous study, using data from 9 large urban clinic indicated that

hospitalization rates decreased between 1995 and 1997 in all HIV-

infected patients but then reached a plateau and may have even begun

to increase between 1997 and 1998. Further analysis of these data

showed that this increase was attributable to admissions related to

hepatitis C virus (HCV) and liver disease.12 Other studies also

suggest that liver failure may be related to increases in overall

hospitalizations between 1998 and 2000 in HIV-infected individuals as

well as to increasing mortality. A recent study in Europe indicated a

decrease in hospitalization rates between 1995 and 2003 but an

increased risk of hospitalization in those with HCV-HIV coinfection

in 2001.

Studies have shown increases in hospitalizations attributable to

complications of cardiovascular and cerebrovascular disease, possibly

linked to effects of HAART and HIV infection itself. A recent study

of admissions to Veterans Affairs (VA) facilities found that rates of

admissions for cardiovascular or cerebrovascular disease among

persons with HIV remained relatively constant between 1993 and

2001.28 Confirmation of these results among patients outside the VA

system would be valuable.

If HIV-positive patients are being hospitalized for more life-

threatening conditions, including cardiac and cerebrovascular

disease, in-hospital mortality may in fact be increasing. Early

studies showed mortality in HIV patients to be lower in the era of

HAART, but little is known about inpatient mortality in the first

several years after the introduction of HAART.

This study uses data from several states in the United States to

examine the extent to which liver-related conditions, ischemic heart

disease, cerebrovascular disease, and several other conditions each

account for an increasing proportion of HIV-related hospitalizations

in 1996, 1998, and 2000. As points of comparison, we also examined

hospitalizations for opportunistic infections, complications of

intravenous drug use (which may be rising, given changes in the

demographics of people with HIV infection), and diabetes (a

consequence of treatment of HIV infection). In addition, we examined

associations between each of these conditions and in-hospital

mortality during these years.

ABSTRACT

Background: Rapid changes in HIV epidemiology and highly active

antiretroviral therapy (HAART) may have resulted in recent changes in

patterns of inpatient utilization.

Objective: To examine trends in inpatient diagnoses and mortality in

HIV patients.

Main Outcome Measures: Number of hospital admissions, inpatient

mortality.

Design/Setting/Patients: Serial cross-sectional analyses of HIV

patients hospitalized in 1996, 1998, and 2000, using hospital

discharge data from the Healthcare Costs and Utilization Project for

12 states. Each hospitalization was classified as an opportunistic

illness, complication of injection drug use (IDU), liver-related

complication, ischemic heart disease, cerebrovascular disease, non-

Pneumocystis carinii pneumonia (PCP), diabetes, or chronic hepatitis

C virus (HCV).

This study used data from 12 of the 27 states participating in the

HCUP as of 2000: California, Colorado, Florida, Iowa, Illinois,

Kansas, land, New Jersey, New York, Pennsylvania, South Carolina,

and Washington. For each state, we analyzed data from 1996, 1998, and

2000. Several of the states in the SID were excluded because they

began participating in the HCUP relatively recently and did not

provide data for a sufficient time period. States with relatively

high HIV prevalence were selected; Iowa, Kansas, and South Carolina

were included as relatively low-prevalence comparison states. Sites

were also chosen to facilitate comparison with prior analyses of HIV-

related hospitalizations using HCUP data

Results: We evaluated 316,963 admissions that occurred between 1996

and 2000, with an overall mortality of 7%. Hospitalizations for

opportunistic infections significantly decreased from 40% to 27% of

all HIV-related admissions. The overall proportion of IDU

complications remained relatively stable (6%) each year.

Hospitalizations increased for liver-related complications from 8% to

13% and for chronic HCV from 1% to 5% in this period. The number of

hospitalizations for cerebrovascular disease and for ischemic heart

disease was relatively negligible in all years. Overall, inpatient

mortality decreased between 1996 and 2000. Relatively higher

mortality was observed among African Americans, Hispanics, those with

Medicaid, those with Medicare, and the uninsured, however.

Opportunistic infections and liver-related complications were

associated with greater inpatient mortality.

Conclusion: Results do not show a significant recent rise in HIV-

related inpatient utilization. Admissions to treat opportunistic

infections have declined precipitously, consistent with the effects

of HAART. Although not dramatic, liver-related disease is an

increasing cause of hospitalization in HIV+ patients.

Table 2. Number of HIV Hospitalizations Stratified by Diagnosis and

Year

DISCUSSION

Across multiple states, the total number of HIV-related inpatient

hospitalizations decreased significantly between 1996 and 1998 and

then plateaued between 1998 and 2000. These results extend prior

analyses of HCUP data, which were based on 7 of the 12 states in the

current analysis. Admission diagnoses changed significantly over this

period, with a dramatic drop in hospitalizations for opportunistic

illnesses. Hospitalizations for liver-related complications increased

slightly in absolute numbers and as a proportion of all HIV-related

hospitalizations. Hospitalizations for chronic HCV and for conditions

related to diabetes also showed a notable rise. In contrast,

hospitalizations for complications of cerebrovascular and ischemic

heart disease remained relatively infrequent, consistent with prior

findings from the VA.28,

In this study, we chose to separate chronic HCV from acute liver-

related conditions. Of 31,865 hospitalizations with a liver-related

diagnosis, only 9% (n = 2865) also had a code for chronic HCV. Of

8792 hospitalizations with a chronic HCV code, 33% also had an acute

liver-related condition. Inpatient coding of chronic HCV without a

concomitant liver condition often reflects chronic HCV infection but

not an acute liver diagnosis. In addition, some insurers increase

reimbursement for cocoding of HIV and HCV; therefore, there is

financial incentive to hospital coders to code HCV even if there is

no evidence of acute liver disease. A recent analysis of

hospitalizations between 1995 and 2000 demonstrated this cocoding

phenomenon. As seen in the mortality analysis, the associations of

chronic HCV and liver disease are in opposite directions, suggesting

that coding of chronic HCV may in fact be a method to increase

reimbursement and may not reflect an acute liver-related condition.

Because one of the most common causes of bloodstream infections and

their sequelae is complications of IDU, we thought it appropriate to

classify these diagnoses as complications of injection drugs.

Although we did not have access to concomitant clinical information

to assess whether patients with IDU diagnoses were or were not

actively using drugs at the time of admission, approximately 33% of

hospitalizations with an IDU diagnosis had a concomitant substance

use/dependence code, indicating probable cooccurrence of these

conditions. In contrast, less than 2.5% of IDU-related admissions had

a concomitant diagnosis of end-stage renal disease, another condition

predisposing patients to bacteremias, abscesses, and osteomyelitis.

Overall inpatient mortality decreased over time. Certain conditions

increased the odds of in-hospital mortality, however, including

cerebrovascular disease, opportunistic illness, liver-related

complications, pneumonia, and ischemic heart disease. These results

emphasize the need for continued monitoring and management of these

conditions.

Female gender was strongly positively associated with

hospitalizations to treat complications of diabetes and pneumonia,

whereas men were more likely to be hospitalized with cardiovascular

complications, liver-related complications, opportunistic illnesses,

and complications of IDU. Women were significantly less likely to die

in the hospital than men. This is consistent with female gender being

associated with diseases with relatively lower mortality, including

treatment of gynecologic conditions.

Data from several hospitals obtained during the HAART era

demonstrated higher hospitalization rates for women than for men.

National data obtained at the beginning of the HAART era also showed

a similar gender differential. In those studies, the unit of analysis

was the individual patient, whereas hospitalization was the unit of

analysis in the current study. Most patients with HIV are men, and

the lower proportion of hospitalizations for women in this study may

reflect the relative numbers of men and women infected with HIV.

Previous studies have demonstrated higher overall hospitalization

rates for HIV-positive nonwhites than for whites. As with gender, the

current findings for racial/ethnic differences based on

hospitalizations as the unit of analysis are not directly comparable

to analysis based on patients as the unit of analysis. For HIV-

related hospitalizations, however, racial/ethnic differences depend,

in part, on specific conditions; for some conditions, such as liver-

related complications and IDU-related complications, hospitalization

rates for African Americans were lower than for whites.

Previous data demonstrating racial/ethnic disparities in access to

HAART would lead to the expectation that the admission rate for

opportunistic illnesses for African Americans would exceed that of

whites. In this context, the nonsignificant difference between whites

and African Americans in hospitalizations for opportunistic illnesses

was unexpected. This finding could be attributable to less advanced

disease in those of minority ethnicity; however, we were unable to

adjust for CD4 cell count, because our data set did not provide

clinical information. Future studies need to evaluate the relation

between race and hospitalizations for opportunistic illnesses.

Hospitalizations for specific diagnoses were consistent with

epidemiologic data on prevalence of these conditions.

Hospitalizations for diabetes, pneumonia, and cerebrovascular

complications were more likely to involve African Americans than

whites. In contrast, hospitalizations for complications of IDU,

ischemic heart disease, and chronic HCV were less frequent among

African Americans, Hispanics, and Native Americans.

Older age was associated with a higher proportion of hospitalizations

for each diagnostic category, with the exception of opportunistic

illness, as well as greater in-hospital mortality. Diseases

associated with increasing age, such as diabetes and cardiovascular

and cerebrovascular disease, are becoming more prevalent in the HIV

population. The trend of a higher proportion of hospitalizations

involving HIV patients older than 50 years of age in more recent

years (10% in 1996 vs. 15% in 2000) may presage increases in the

number of hospitalizations attributable to diseases associated with

increasing age.

Hospitalizations covered by private insurance decreased

proportionately more than those covered by Medicaid (45% vs. 31%),

but hospitalizations for persons covered by Medicare increased

between 1998 and 2000. These results could have significant cost

implications for publicly funded programs if the number of HIV

patients qualifying for Medicare continues to increase.

Hospitalizations for patients with Medicaid and Medicare coverage had

lower in-hospital mortality than hospitalizations for those with

private insurance. It is possible that patients with private coverage

were more integrated into a system of outpatient care and that they

were hospitalized only for more serious conditions compared with

those with public coverage. The difference between self-pay (ie,

uninsured) and private insurance was not significant for in-hospital

mortality.

This study has some limitations. First, the same patient could have

been admitted multiple times and would therefore be counted more than

once in the analysis. Unfortunately, the database did not include

unique patient identifiers that would enable linking multiple

hospitalizations for the same patient. Ignoring such clustering could

result in standard errors that were too low. In most cases, however,

the z tests of the significance of the coefficients reported in

Tables 3 and 4 were 3.0 or higher, suggesting that increasing the

standard error by as much as 50% would not alter most conclusions (4

coefficients with significant z values below 3.0 are marked with

asterisks in Table 3). Moreover, from the standpoint of examining

aggregate trends in inpatient resource utilization, the aggregate

temporal, demographic, and clinical differences do provide important

utilization information, even if they include multiple

hospitalizations for the same individual.

Another limitation concerns the accuracy of coding. We identified HIV-

related hospitalizations by the presence of specific ICD-9 codes as

primary or secondary diagnoses. It is possible that some HIV-related

hospitalizations were not assigned ICD-9 codes reflecting HIV

infection. In addition, we were unable to assess 30-day postdischarge

mortality. Also, because we did not have clinical data, we were

unable to adjust for severity of illness, which may have resulted in

an underestimate of inpatient mortality rates. Finally, the results

do not provide direct information on changes in the prevalence of the

diagnostic categories over time. There may be an increase in the

prevalence of certain conditions that are being treated successfully

on an outpatient basis; such conditions would not appear in the HCUP

data.

In conclusion, admission diagnoses for HIV-related hospitalizations

changed significantly between 1996 and 2000. Consistent with the

introduction of HAART, there was a concomitant decrease in

opportunistic illnesses, suggesting that HIV patients are benefiting

from HAART. Treatment complications of HAART, including diabetes and

cardiovascular, and cerebrovascular complications, have increased

during this period, but they still comprise a relatively small

proportion of the total number of HIV hospitalizations in these

states.

RESULTS

Number of Hospitalizations

Of the 316,963 HIV-related hospitalizations for adult patients in 12

states, 128,754 occurred in 1996, 96,811 took place in 1998, and

91,398 occurred in 2000. Consistent with the introduction of HAART in

1996, hospitalizations declined 25% between 1996 and 1998 but dropped

only 6% between 1998 and 2000. Overall, HIV-related hospitalizations

decreased 29% from 1996 to 2000. In a negative binomial regression,

estimated incidence rate ratios were 0.77 (95% confidence interval

[CI]: 0.60-0.98; P = 0.03) for 1998 versus 1996 and 0.69 (95% CI:

0.54-0.88; P = 0.003) for 2000 versus 1996 (results not tabulated).

As has been shown in prior analyses of HCUP data from 7 states,31

hospitalizations decreased proportionately more for men (33%) than

for women (18%) between 1996 and 2000. The proportionate decline in

hospitalizations was greatest for the 18- to 30-year-old group (56%).

In contrast, hospitalizations for patients older than 50 years of age

increased 8% during this interval. Hospitalizations decreased

proportionately more for whites (40%) and Hispanics (32%) than for

African Americans (20%). Hospitalizations covered by private

insurance decreased 45% between 1996 and 2000; those for Medicaid

patients dropped by 31%. Medicare hospitalizations decreased only 3%

between 1996 and 2000, however, and the number increased between 1998

and 2000.

Most HIV-related hospitalizations had none of the 8 diagnosis

categories (42.3%) or exactly 1 (48.5%) (results not shown). Two of

the diagnoses occurred together in 8.9% of the hospitalizations.

Thus, multiple indications for hospital admission were relatively

rare. In 1996 and 2000, the most common diagnosis was non-PCP. In

1996, the next most common diagnosis was Pneumocystis jiroveci

pneumonia; however, in 2000, consistent with the introduction of

HAART, this slipped to the eighth most common diagnosis. Other common

diagnoses in both years included hypovolemia, pancreatitis, opioid

dependence, and convulsions.

Table 2 reports the number of hospitalizations for each year by

diagnosis category. For each diagnosis category, the proportion of

hospitalizations differed significantly by year (P < 0.001 using a _2

test). Hospitalizations for opportunistic illnesses significantly

decreased from 51,050 in 1996 to 24,661 in 2000. Hospitalizations for

IDU complications also decreased in number from 6390 in 1996 to 5238

in 2000, but the overall proportion remained relatively stable. In

contrast, hospitalizations for liver-related complications increased

from 10,481 to 11,583, or from 8% to 13% of all HIV-related

hospitalizations. Hospitalizations for chronic HCV also rose from 1%

to 5% in this period. Hospitalizations for diabetes rose from 3% to

5% between 1996 and 2000. The numbers of hospitalizations for

cerebrovascular disease or for ischemic heart disease were relatively

negligible in all years. Hospitalizations for pneumonia dropped in

absolute numbers (13,230 to 12,461) but rose in proportion (10% to

14%), because the total number of hospitalizations declined even

faster.

Table 3 presents negative binomial regression results for each of the

8 diagnosis categories. The proportion of hospitalizations for

opportunistic illnesses decreased significantly between 1996 and 1998

and again between 1998 and 2000, controlling for state, age, gender,

and race/ethnicity. The proportion of hospitalizations for

cerebrovascular complications did not differ between 1996 and 1998

but was significantly higher in 2000 than in either previous year.

For all other diagnostic classes, the proportion increased

significantly in both periods; all differences between 1996 and 1998

were significant, as were the differences between 1998 and 2000. The

strongest time period effects were for chronic HCV; between 1996 and

1998, hospitalization proportions increased by a factor of 2.25, and

they increased by a factor of 3.97 between 1996 and 2000.

Women had lower hospitalization proportions for liver-related

complications, opportunistic illnesses, complications of IDU, and

ischemic heart disease compared with men, but women had relatively

higher proportions of hospitalization for pneumonia and diabetic

complications. Gender was not associated with hospitalizations for

cerebrovascular complications or chronic HCV.

Compared with patients aged 18 to 30 years, the proportions of

hospitalizations for patients in the 31- to 40-year-old and 41- to 50-

year-old age groups were significantly higher for all conditions

except opportunistic illnesses, for which they were significantly

lower. Hospitalizations for patients older than 50 years of age

showed a similar pattern to those of the middle-aged groups, with the

exception that they did not differ from the youngest group in

hospitalizations for IDU complications. The proportions of

hospitalizations for the oldest group were especially high for

ischemic heart disease and cerebrovascular complications.

Compared with hospitalizations for white patients, for African-

American patients, the proportions of hospitalization were

significantly higher for pneumonia, diabetes, and cerebrovascular

complications and were significantly lower for liver-related

diseases, chronic HCV, IDU complications, and ischemic heart disease.

Hospitalizations for Hispanic patients showed a pattern similar to

that for African Americans, with the exception of a higher proportion

of hospitalizations for opportunistic illnesses than whites.

Inpatient Mortality

Death occurred in 7% of all hospitalizations. Inpatient mortality

decreased across time, dropping from 8.5% of hospitalizations in 1996

to 6.3% in 1998 and 6.2% in 2000. Across all 3 years, the mortality

rate was highest for cerebrovascular disease (13.8%), followed by

opportunistic infections (10.1%), pneumonia (9.5%), liver-related

disease (8.8%), and ischemic heart disease (8.6%). Mortality rates

for other diagnoses were lower: 4.1% for IDU complications, 4.3% for

diabetes, and 5.8% for chronic HCV.

In multivariate logistic regression analysis, the adjusted odds of

inpatient death were 27% lower in 1998 than in 1996 and 30% lower in

2000 than in 1996. Consistent with the bivariate results, the odds of

death were more than twice as high when the hospitalization involved

cerebrovascular disease, and they were nearly twice as high for

opportunistic illnesses compared with hospitalizations that did not

involve any of the 8 diagnosis classes. In contrast, death was less

likely when the hospitalization involved complications of IDU or

diabetes. Women had lower odds of death than men. The likelihood of

death was higher for older patients. Medicare and Medicaid

hospitalizations had lower odds of inpatient mortality than those

covered by private insurance. Compared with hospitalizations for

white patients, those for African-American and Hispanic patients were

more likely to end in death.