**IL 10-98-013**

In Reply Refer To: 11

**June 11, 1998**

**UNDER SECRETARY FOR HEALTH'S INFORMATION LETTER**

**HEPATITIS C: STANDARDS FOR PROVIDER EVALUATION AND TESTING**

1\. **Background:** Hepatitis C virus (HCV) infection was first
recognized in the 1970's, when the majority of transfusion-associated
infections were found to be unrelated to hepatitis A and B, the two
hepatitis viruses recognized at the time. This transmissible disease was
then simply called "non-A, non-B" hepatitis. Sequencing of the HCV
genome was accomplished in 1989, and the term hepatitis C was
subsequently applied to infection with this single strand ribonucleic
acid (RNA) virus. The genome of HCV is highly heterogeneous and, thus,
the virus has the capacity to escape the immune surveillance of the
host; this circumstance leads to a high rate of chronic infection and
lack of immunity to reinfection. Reliable and accurate (second
generation) tests to detect antibody to HCV were not available until
1992, at which time an effective screening of donated blood for HCV
antibody was initiated.

2\. HCV infection is now recognized as a serious national problem.
Nearly 4 million Americans are believed to be infected, and
approximately 30,000 new infections occur annually. Only about 25 to 30
percent of these infections will be diagnosed. HCV is now known to be
responsible for 8,000 to 10,000 deaths annually, and this number is
expected to triple in the next 10 to 20 years.

3\. Hepatitis C has particular import for the Department of Veterans
Affairs (VA) because of its prevalence in VA's service population. For
example, a 6-week inpatient survey at the VA Medical Center, Washington,
DC, revealed a prevalence of 20 percent antibody positivity. A similar
investigation at the VA Medical Center San Francisco, CA, found 10
percent of inpatients to be antibody positive. Veterans Health
Administration (VHA) Transplant Program data reveal that 52 percent of
all VA liver transplant patients have hepatitis C. An electronic survey
of 125 VA medical centers conducted by the Infectious Disease Program
Office from February through December of 1997, identified 14,958 VA
patients who tested positive for hepatitis C antibody. Clearly, HCV
infection is becoming a leading cause of cirrhosis, liver failure, and
hepatocellular carcinoma. The incidence and prevalence rates are higher
among nonwhite racial and ethnic groups.

4\. HCV is transmitted primarily by the parenteral route. Sources of
infection include transfusion of blood or blood products prior to 1992,
injection drug use, nasal cocaine, needlestick accidents, and, possibly,
tattooing. Sexual transmission is possible, and while the risk is low in
a mutually monogamous relationship, persons having multiple sexual
partners are at higher risk of infection.

5\. After infection, 90 percent of HCV infected patients will develop
viral antibodies within 3 months. The disease becomes chronic in 85
percent of those infected, although one-third will have normal
aminotransferase levels. The rate of progression is variable, and
chronic HCV infection leads to cirrhosis in at least 20 percent of
infected persons within 20 years; 1 to 5 percent of those infected will
develop hepatocellular carcinoma.

6\. At present, treatment for HCV infection is limited, consisting
primarily of administration of interferon alpha, with or without the
addition of ribavirin. The treatment benefits some patients and appears
to alter the natural progression of the disease, although evidence is
lacking that it will translate into improvements in quality of life or
reduction in the risk of hepatic failure. Current regimens include the
use of 6 or 12-month courses of interferon alpha, with or without
ribavirin. The recent National Institutes of Health Consensus Statement
on Hepatitis C concluded that liver biopsy should be performed prior to
initiating treatment. If little liver damage is apparent, therapy need
not be initiated; treatment is probably appropriate for those with
significant histologic abnormalities. However, data presented at this
Consensus Conference indicated that significant uncertainty remains
regarding indications for treatment. Treatment options and a listing of
VA protocols will be the subject of a separate Information Letter.

7\. A number of serologic tests are available for diagnosis and
evaluation of HCV infection. Enzyme immunoassays (EIA) are "first line"
tests, and are relatively inexpensive. They contain HCV antigens and
detect the presence of antibodies to those antigens. Recombinant
immunoblot assays (RIBA) contain antigens in an immunoblot format, and
are used as supplemental or confirmatory tests. Viral RNA can be
detected by reverse-transcription polymerase chain reaction (PCR)
testing. Quantitative HCV RNA testing uses target amplification PCR or
signal amplification (branched deoxyribonucleic acid (DNA)) techniques.

8\. The EIA tests have sensitivities in the range of 92 to 95 percent.
Specificities depend on the risk stratification pre-testing. That is, in
blood donors with no risk factors, 25 to 60 percent of positive EIA are
also positive by PCR for viral RNA. About 75 percent of low risk donors
with positive EIA and RIBA will be positive by PCR. Positive EIA tests
should be confirmed by RIBA. If that is also positive the patient has,
or has had, HCV infection. In high-risk patients who are EIA positive,
particularly if there is evidence of liver disease, supplemental testing
with RIBA or HCV RNA analysis is probably unnecessary. Quantitative RNA
tests may be useful in the selection and monitoring of patients
undergoing treatment.

9\. All patients will be evaluated with respect to risk factors for
hepatitis C, and this assessment documented in the patient's chart.
Based upon those risk factors, antibody testing should be utilized as
elaborated on in the algorithm found in Attachment A.

S/Kenneth W. Kizer, M.D., M.P.H.

Under Secretary for Health

Attachment

**DISTRIBUTION:** CO: E-mailed 6/11/98

FLD: VISN, MA, DO, OC, OCRO, and 200 -- FAX 6/11/98

EX: Boxes 104,88,63,60,54,52,47,and 44 -- FAX 6/11/98

**ATTACHMENT A**

**HEPATITIS C VIRUS ANTIBODY SCREEENING**

**FOR THE VETERAN POPULATION**

HISTORY OF POSITIVE TEST FOR

HEPATITIS C VIRUS ANTIBODY

YES NO

PRESENCE OR HISTORY OF ANY OF THE FOLLOWING:

1.  Transfusion of blood or blood products prior to 1992

2.  Injection illicit drug use - past or present -- any number of
    injections -- skin or intravenous site

3.  Unequivocal blood exposure on or through skin or mucous membrane --
    medical worker, combat casualty care, needlestick injury

4.  Multiple sexual partners -- past or present

5.  Hemodialysis

6.  Tattoo or repeated body piercing

7.  Intranasal cocaine use -- past or present

8.  Unexplained liver disease

9.  Unexplained abnormal ALT value

10. Intemperate alcohol use

> YES NO
>
> Low priority for HCV antibody screening; not

Recommend: recommended unless at patient's request

1\. Counseling for risk behavior

2.  Screening HCV antibody (e.g. EIA)

3.  Measure ALT if not yet done

HCV antibody positive HCV antibody negative

Perform confirmatory test (e.g., RIBA)

if low-risk patient or normal ALT

Test positive Test negative

> Patient unlikely to have true positive HCV antibody. Repeat testing
>
> based on individual risk

Individual patient care decisions

regarding counseling, further testing

and potential treatment options are

necessary. These should be based upon

current literature or performed within

approved research protocols