The burden of hepatitis C in the United States

Date: Mon, 20 Jan 2003 03:43:07 EST
From: JuLev@aol.com
Subject: NATAP: Burden of Hepatitis C Virus in the USA

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According to the third National Health and Nutrition Examination Survey
(NHANES), 3.9 million of the U.S. civilian population have been infected with
hepatitis C virus (Hepatitis C Virus), of whom 2.7 million (74%) have chronic infection.
Hepatitis C virus infection is most common among non-Caucasian men, ages 30
to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in
groups not represented in the NHANES sample, such as the homeless or
incarcerated, may be as high as 40%. The age-adjusted death rate for non-A,
non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons
per year between 1982 and 1999. In 1999, the first year hepatitis C was
reported separately, there were 3,759 deaths attributed to Hepatitis C Virus, although this
is likely an underestimate. There was a 5-fold increase in the annual number
of patients with Hepatitis C Virus who underwent liver transplantation between 1990 and
2000. Currently, more than one third of liver transplant candidates have Hepatitis C Virus..
Inpatient care of Hepatitis C Virus-related liver disease has also been increasing. In
1998, an estimated 140,000 discharges listed an Hepatitis C Virus-related diagnosis,
accounting for 2% of discharges from non-federal acute care hospitals in the
United States. The total direct health care cost associated with Hepatitis C Virus is
estimated to have exceeded $1 billion in 1998. Future projections predict a
4-fold increase between 1990 and 2015 in persons at risk of chronic liver
disease (i.e., those with infection for 20 years or longer), suggesting a
continued rise in the burden of Hepatitis C Virus in the United States in the foreseeable
future. (HEPATOLOGY 2002;36:S30-S34. W. Ray Kim).

Editorial note from Jules Levin: It's estimated by studies that 30% of
HIV-infected individuals have Hepatitis C Virus and 60-90% of individuals infected with HIV
by IVDU have Hepatitis C Virus. The total estimate for coinfected individuals in the USA is
300,000. The estimate for NYC is 60,000 to 85,000.

A cost-of-illness study conducted by the American Gastroenterological
Association estimated that there were 317,000 outpatient visits for the
treatment of hepatitis C in the United States in 1998.18 The cost for
outpatient physician services was projected to be $24 million. During the
same year, $530 million was spent for the antiviral treatment of Hepatitis C Virus.

In July 2000, the United States Surgeon General declared that hepatitis C
represents a "silent epidemic." Indeed, hepatitis C is the most common
chronic bloodborne infection in the United States, affecting almost 3 million
Americans. This review focuses attention on the disease burden associated
with hepatitis C virus (Hepatitis C Virus) infection. The term, "disease burden,"
encompasses several aspects of the impact of a disease on the health of a
population, ranging from the frequency of the disease, as measured by
incidence and prevalence, to its effect on (1) longevity, such as mortality
rate and years of life lost because of premature death; (2) morbidity,
including impairment in health status and quality of life as well as the need
for health care; and (3) finance, including direct health care expenditures
and indirect costs related to lost income from premature death or disability..

 

Future research needs
    
There is an ongoing, critical need for up-to-date and accurate information on
the prevalence, incidence, health care costs, mortality, and morbidity of
hepatitis Câ?"related illnesses in the United States. In formulating health
care policies to prioritize health interventions and research and to allocate
resources accordingly, accurate information about the current and future
burden of disease is essential. Chronic Hepatitis C Virus infection is common, affecting
nearly 2% of the general population and a much higher percentage of people
under special circumstances, such as the homeless and incarcerated. Although
the incidence of Hepatitis C Virus infection appears to have decreased, national statistics
indicate that morbidity, mortality, and health care utilization associated
with consequences of long-standing infection with hepatitis C have increased
since the early 1990s.

Focused studies on the incidence and prevalence of Hepatitis C Virus infection and liver
disease in specific populations at risk are needed. While population surveys
provide an accurate estimate of the prevalence of Hepatitis C Virus infection, a
significant gap exists between the sero-epidemiologic data and burden of
Hepatitis C Virus-related liver disease at the population level. This is in part because of
the long period between Hepatitis C Virus infection and clinically significant liver
disease, as well as our incomplete understanding of the natural history of
Hepatitis C Virus infection at the population level. Most investigations about the extent
and natural history of liver disease associated with hepatitis C have been
conducted at academic tertiary centers based on patients referred with
established disease. By contrast, the majority of the projected 3 million
Americans infected with Hepatitis C Virus have not been diagnosed, and their liver disease
status remains unknown. Studies about liver disease in people with Hepatitis C Virus
infection in the population at large are necessary to fill this gap in our
knowledge. Moreover, systematic epidemiologic studies focused on patients not
represented in population-based surveys (e.g., homeless and incarcerated) are
needed.

Finally, continuing studies of hepatitis C in patients with other
comorbidities are needed. A significant proportion of Hepatitis C Virus-infected patients
have a number of comorbid conditions, including poly-substance abuse (e.g.,
alcohol) and mental disorders (e.g., depression and anxiety disorders). It is
uncertain the extent to which the morbidity present in people infected with
Hepatitis C Virus is purely attributable to Hepatitis C Virus infection. Determining the extent of the
contribution of extraneous comorbidity is important, because in people with
comorbid conditions, antiviral therapy alone is unlikely to be successful in
improving the health of the individual. Comprehensive yet cost-effective
strategies to incorporate treatment for hepatitis C in the management of
patients with substance use remain to be defined.

Prevalence and Incidence of Hepatitis C Virus

Disease frequency may be measured either by the pool of existing cases or by
the occurrence of new cases. The former (prevalence) describes the proportion
of the population that has the disease in question at a specific point in
time, whereas the latter (incidence) describes the frequency of occurrence of
new cases during a defined time period.

Prevalence

The most widely quoted data on the prevalence of Hepatitis C Virus in the United States are
derived from the third National Health and Nutrition Examination Survey
(NHANES), a national survey of a representative sample of
noninstitutionalized civilian Americans conducted between 1988 and 1994. Of
21,000 people tested for Hepatitis C Virus, 380 (1.8%) carried antibodies against the
virus, of whom 280 (74%) had detectable viral RNA in their serum. Projecting
these numbers to the U.S. population indicates that 3.9 million Americans
(95% CI: 3.1 to 4.8 million) have been infected with Hepatitis C Virus, of whom 2.7 million
(95% CI: 2.4 to 3.0 million) have on-going chronic infection.

Data from the NHANES survey showed that there was significant demographic
variation in the Hepatitis C Virus prevalence. It was most common in persons 30 to 49 years
of age; non-Hispanic whites had the lowest prevalence (1.5%) and non-Hispanic
blacks had the highest prevalence (3.2%).

Men were 20% more likely to have hepatitis C than women.

Although these data may be representative of demographic variability in the
general population, socioeconomic characteristics may also influence the
prevalence of Hepatitis C Virus infection. In surveys of emergency medical technicians
undertaken in various parts of the country, the seroprevalence of Hepatitis C Virus was
found to range between 1.3% and 3.2%, comparable to that of the NHANES
sample.2 On the other hand, a survey conducted at a Veterans Affairs
outpatient clinic showed that 18% of those screened (n = 1,032) had antibody
to hepatitis C virus,3 while in another Veterans Affairs study conducted
among homeless veterans (n = 829) the prevalence was 40%.4 A cross-sectional
survey of prison inmates in California showed that 39% of men (n = 6,536) and
54% of women (n = 977) were positive for Hepatitis C Virus at the time of entry.5 These are
undoubtedly high prevalence rates, but they are comparable to reports from
other parts of the world.

Incidence

Hepatitis C virus is a reportable infectious disease in the United States,
and the Centers for Disease Control and Prevention has put mechanisms in
place to capture incident cases of Hepatitis C Virus infection. These include passive
surveillance programs such as the National Notifiable Disease Surveillance
System and hepatitis-specific active surveillance programs such as the
Sentinel Counties Study of Acute Viral Hepatitis. Despite these efforts, the
incidence of new Hepatitis C Virus infection is very difficult to estimate accurately. This
is because many patients with acute Hepatitis C Virus infection are asymptomatic and thus
do not present themselves for diagnosis. Under-reporting by health care
providers of diagnosed cases is also thought to be common. Furthermore,
individuals at high risk of infection may not have ready access to health
care, decreasing the likelihood of timely diagnosis of newly acquired Hepatitis C Virus
infection. Because of these limitations, enumerating reported cases of acute
hepatitis C significantly underestimates the true incidence of hepatitis C
infection.7
Given these caveats, the Centers for Disease Control and Prevention has
undertaken mathematical modeling studies to estimate the past incidence of
Hepatitis C Virus. The model indicated that the annual incidence of acute Hepatitis C Virus infection in
the United States decreased from an average of approximately 230,000 new
cases per year in the 1980s to 38,000 cases per year in the 1990s.8 The
number of persons with transfusion-associated Hepatitis C Virus infection decreased
significantly following the introduction in 1985 of guidelines for selecting
safer blood donors. It declined further with the institution of screening of
blood donors for antibody to hepatitis C virus beginning in 1989 with the
first generation test and the second-generation assay introduced in July
1992. In addition, safer needle-using practices among injection drug users
facilitated by human immunodeficiency virus prevention programs are also
thought to have decreased the incidence of Hepatitis C Virus infection.8
It may be expected that the reduction in incident cases will eventually lead
to a decrease in the prevalence of Hepatitis C Virus infection. Indeed, a report based on
blood donors from 5 U.S. blood centers indicates that the prevalence of Hepatitis C Virus
infection may already be on a decline. Between 1992 and 1996, during which
time 1.1 million first-time blood donors were tested, the prevalence of Hepatitis C Virus
infection over the course of this period decreased from 0.6% to 0.4% (P <
.01). Among the same blood donors, the prevalence of hepatitis B virus
infection over the study period remained unchanged at 0.2%. The anticipated
reduction in the prevalence has been corroborated by a report from the
Centers for Disease Control and Prevention which projected that, following a
peak in the mid-1990s at slightly above 2.0%, prevalence of Hepatitis C Virus infection
would gradually decrease to 1.0% by 2030.

 

Although the incidence of Hepatitis C Virus infection may be decreasing, the prevalence of
liver disease caused by Hepatitis C Virus is on the rise. This is because there is a
significant lag, often 20 years or longer, between the onset of infection and
clinical manifestation of liver disease. The Centers for Disease Control and
Prevention projects a 4-fold increase in the number of persons with
long-standing (20 years or longer) infection between 1990 and 2015.10
However, it is uncertain whether the projected decline in the Hepatitis C Virus prevalence
based on NHANES data (non-institutionalized civilians) will translate to a
similar decline in other population groups known to have very high
prevalences of Hepatitis C Virus infection, such as active injection drug users and prison
inmates.

Mortality From Hepatitis C Virus Infection

Mortality statistics in the United States are based on the "underlying cause
of death" listed on death certificates. Deaths attributable to viral
hepatitis result primarily from chronic liver disease and liver failure.
Consequently, viral hepatitis may not necessarily be listed as the underlying
cause of death. Therefore, it is likely that the death certificate
designation may underestimate the true incidence of deaths related to viral
hepatitis. Further, until 1999, when the International Classification of
Disease version 10 (ICD-10) began to be used to classify causes of death,
hepatitis C was not given an independent code, making it difficult to
estimate the total number of deaths attributable to Hepatitis C Virus infection.

In 1982, 814 deaths were attributed to viral hepatitis, which increased
6-fold by 1999 to 4,853 deaths.11 There was a corresponding increase in the
age-adjusted death rate from 0.4 to 1.8 deaths per 100,000 persons per year.
Based on data from 1999, the first year hepatitis C was reported separately,
the majority (77%; n = 3,759) of these deaths were caused by Hepatitis C Virus infection..
Comparing the deaths in the non-Hepatitis C Virus portion of the 1999 data with all viral
hepatitis deaths in the early 1980s suggests that the increase in deaths
since the late 1980s may be entirely because of hepatitis C.

To estimate the degree of under-reporting of Hepatitis C Virus infection as the underlying
cause of death in the mortality data, the number of in-hospital deaths from
liver disease related to hepatitis C was abstracted from the Healthcare
Utilization Project database. In 1998 there were an estimated 4,500
in-hospital deaths in the United States from liver disease related to Hepatitis C Virus
infection.

Morbidity and health care Cost from Hepatitis C Virus
Morbidity and health care cost from Hepatitis C Virus infection    TOP
Because chronic hepatitis C has a prolonged natural history, and only a
relative minority of those affected require on-going medical care for their
hepatitis, it is difficult to estimate the magnitude of morbidity at the
population level. Patients with advanced stages of liver disease may present
with portal hypertension and hepatic decompensation, as manifested by
ascites, hepatic encephalopathy, or gastrointestinal bleeding. These
complications generally necessitate inpatient care that may include liver
transplantation. Thus, data on patients referred for and undergoing
orthotopic liver transplantation for end-stage liver disease or
hepatocellular carcinoma reflect the most severe degree of morbidity
associated with hepatitis C.

There was a 5-fold increase in the number of orthotopic liver transplantation
recipients with hepatitis C. The proportion of recipients with Hepatitis C Virus infection
increased from 12% to 37%. There was a similar increase in the number and
proportion of liver transplant candidates with hepatitis C registered on the
waiting list.

The United Network for Organ Sharing reports that as of 2001, there were
9,783 patients with hepatitis C awaiting a cadaveric liver transplantation.

The frequency of inpatient care of Hepatitis C Virus-related liver disease has been
estimated based on data derived from the Nationwide Inpatient Sample of the
Healthcare Utilization Project. This database represents a 20% stratified
sample from all non-federal, acute-care hospitals, which account for
approximately 95% of all hospitalizations in the nation. Because liver
disease from hepatitis C may not be the main reason for all hospitalizations
with a hepatitis C diagnosis, hospitalizations were divided into 3 groups.
These included hospitalizations in which liver disease from hepatitis C was
the primary reason for hospitalization, those in which liver disease from
hepatitis C was a secondary reason, and those in which neither hepatitis C
nor liver disease was a primary reason for the hospitalization.

During the 1990s there was a several-fold increase in the total number of
hospitalizations in which Hepatitis C Virus was listed in the discharge diagnosis. In 1998,
an estimated 140,000 discharges listed an Hepatitis C Virus diagnosis, accounting for
approximately 2% of all discharges in the database. Because of the
uncertainty of ascertainment of Hepatitis C Virus in the early 1990s, hospitalizations for
other chronic hepatitis (non-A, non-B) were also captured.

Some of the increase over time was because of the lack of ascertainment of
Hepatitis C Virus infection in the early 1990s, because there was a partially corresponding
decrease in the non-A, non-B hepatitis hospitalizations during the same
period. Figure 3 also shows the total charges associated with these
hospitalizations (1998 U.S. dollars). Hospitalizations were weighted
differently according to the hospitalization category, including 80% of
charges for primary hospitalizations for hepatitis C, 50% for secondary
hospitalizations, and 20% of the remainder. The estimated total hospital
charges for 1998 were in excess of $1 billion.

Population-based data on the morbidity in individuals with hepatitis C not
requiring hospitalization care are not available at the present time. Health
status and quality of life have largely been measured in patients seen at
referral centers or participating in randomized trials. These studies have
uniformly shown a significant decrement in the subjective health and quality
of life in patients with hepatitis C, although the effect of frequently
co-existing morbidities such as chemical dependence or depression is
difficult to assess separately. Although persons aware of the diagnosis of
chronic hepatitis C scored lower on quality-of-life scales than did
uninfected persons, it is uncertain how much of this decrement is because of
the Hepatitis C Virus infection itself or to the awareness of this condition.

A cost-of-illness study conducted by the American Gastroenterological
Association estimated that there were 317,000 outpatient visits for the
treatment of hepatitis C in the United States in 1998. The cost for
outpatient physician services was projected to be $24 million. During the
same year, $530 million was spent for the antiviral treatment of Hepatitis C Virus.



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