Acute HCV infection is entirely asymptomatic in 60 –70% of those infected. Jaundice is present in only about 20% of those with acute infection, and nonspecific symptoms occur in 10 –20%. Eighty-five percent or more of those with acute HCV infection will progress to chronic HCV infection. Approximately 70% of those with chronic infection will have chronic hepatitis and about 20% of those will develop cirrhosis. Those with cirrhosis have a 1-4% per year risk of developing hepatocellular carcinoma. It is estimated that over 3.9 million Americans (1.8% of the population) have been infected with HCV, making it the most common chronic blood borne infection in this country. There is no vaccine currently available.

HCV occurs among persons of all ages, races, and genders. The highest incidence of acute infection is among those aged 20 –39, with males predominating. African Americans and whites have similar rates, and the rate for Hispanics is slightly higher. The highest prevalence rates are found in males aged 30 – 49, with African Americans having a higher prevalence than whites.

HCV is transmitted by direct exposure to infected blood or blood products. Before July 1992, there was a significant risk of post-transfusion hepatitis C. Due to screening of the blood supply, HCV is now rarely transmitted by blood transfusion. Previously, clotting factors and immunoglobulins in the U.S. were known to transmit HCV. In 1987, effective techniques for inactivation of virus in clotting factors were introduced. After 1994, inactivation for immunoglobulin products in the U.S. was implemented.

The predominant risk factor for HCV transmission is injecting drug use, accounting for approximately 60% of HCV transmission in the U.S. today. Other risk factors include: Chronic hemodialysis patients, infants born to HCV-positive mothers, history of multiple sex partners, and health care worker exposure to blood. Other exposures showing independent association with HCV infection include intranasal cocaine use and history of tattooing or body piercing, but there is little data to define the extent of increased risk, if any. For at least 10% of those infected with HCV, no obvious risk factor can be identified.

Sexual transmission of HCV is an inefficient mode of transmission. Although an association exists between sexual exposure to an HCV-positive partner, the risk of infection via sexual contact in a long-term monogamous relationship with an infected partner is extremely low, approaching that of the general population. Transmission to non-sexual household contacts of HCV-positive individuals is also rare.

The diagnostic approach for detection of HCV infection varies depending upon the clinical presentation of the patient and the patient’s risk profile. The CDC has provided a diagnostic algorithm for HCV infection testing in asymptomatic persons. The initial screening test is an enzyme immunoassay (EIA). This must be confirmed by either a recombinant immunoblot assay (RIBA) or a polymerase chain reaction (PCR) for HCV ribonucleic acid (RNA). Once HCV infection has been confirmed, a number of additional tests, such as serum alanine aminotransferase (ALT) enzyme and liver biopsy, may be employed to assess disease progression.

Two different regimens are approved for treatment of chronic hepatitis C in the U.S. These are monotherapy with alpha interferon and combination therapy with alpha interferon and ribavirin. Combination therapy is recommended for the majority of patients as it yields higher rates of sustained response than monotherapy. Treatment leads to normalization of ALT levels in 50 – 75% of patients, and to disappearance of detectable HCV RNA in 30 – 50%. A response is considered sustained if HCV RNA remains undetectable 6 months or more after cessation of therapy. Relapse after this point is rare. There is a sustained response in 35 – 45% of patients receiving combination therapy and in only 15 –20% of those receiving monotherapy. Therapy is not generally advised for those with normal ALT levels, decompensated cirrhosis, or solid-organ transplants. Specific contraindications to therapy for alpha interferon, such as active alcohol or other substance abuse, and contraindications to ribavirin are also reasons why therapy may not be initiated.

The CDC recommends vaccination against hepatitis A and B viruses and pneumococcus for patients with chronic hepatitis C. In addition, patients with HCV should be counseled on means to prevent transmission of the disease.

Although the reporting mechanism for positive hepatitis C test results has been voluntary, the ISDH annually receives thousands of such reports. An internal review of the 1998 ISDH data revealed an intriguing finding: 68% of individuals reported to be HCV-positive by the EIA screening test had no subsequent confirmatory testing reported to the ISDH. Likewise, for 1999, nearly 70 % of the approximately 4600 cases were unconfirmed according to reported data.

Since the CDC recommends that a positive EIA test be confirmed by means of either a RIBA or PCR test, a potentially high number of patients may not have received appropriate diagnostic testing. Assessing compliance of medical providers with the CDC recommendations, both for confirmatory testing and for medical follow-up in hepatitis C patients, became the primary objectives of this study. The main impetus for the project was to determine whether the findings from the internal review were true or simply a misleading by-product of the voluntary reporting rule. If patients were truly not tested appropriately, their follow-up for medical care might also have been compromised. Assessing compliance of medical providers with the CDC recommendations, both for confirmatory testing and for medical follow-up in hepatitis C patients, became the primary objectives of this study. Alternatively, if the misleading data proved to be largely the result of the voluntary reporting rule, ISDH could confirm the need for a mandatory reporting rule to obtain meaningful data.

A secondary objective was characterizing the risk factors for HCV infection specific to Indiana. Educational and control interventions could best be designed for the state’s hepatitis C population if these risk factors could be assessed and appropriately addressed. Thus, the project objectives were as follows:

• Utilizing a representative sample of patients who had only a positive EIA reported to the state, assess the true percentage of these patients who had confirmatory diagnostic test(s) performed.
• Using the same representative sample of "unconfirmed" cases, assess the percentage of patients for whom appropriate follow-up medical care was initiated.
• Characterize the risk factor profile of hepatitis C patients within the state of Indiana by utilizing the selected sample.

During 1999, Indiana medical laboratories and providers reported 4,635 cases of hepatitis C to the ISDH. Of these, 1,472 (31.8%) cases were reported as confirmed by subsequent RIBA or PCR testing. The remaining submissions (68.2%) reported only results from the EIA test and indicated no confirmatory testing. To determine whether the reason for the high percentage of non-confirmed cases was a lack of adequate follow-up or a problem in the reporting process, a brief survey of medical providers was conducted on a random sample (n=363, or 11.5%) of the non-confirmed cases.

The survey questions were confined to one page, and check-boxes were provided for answers. The following information was requested: dates and results of any confirmatory testing, initiation of or contraindication for medical treatment, referrals to other physician specialists, history of ancillary vaccination (for hepatitis A, hepatitis B, and/or pneumococcus), history of risk factors for hepatitis C, and the initial provider’s medical specialty. An introductory cover letter from the ISDH was included to state the purpose of the survey and to provide assurance regarding patient confidentiality. Four providers from the confirmed group were asked to participate in a pretest and suggestions were incorporated into the final survey form.

Surveys were sent by facsimile to the provider listed in each patient’s ISDH record. Medical providers’ fax numbers were obtained either by calling the provider’s office or by using medically affiliated web sites. Respondents were asked to return the surveys by facsimile within two weeks of receipt. Two or more weeks later, surveys were re-faxed to non-responders, along with a new cover letter urging a timely response. All data collected on the survey were entered into a Microsoft Access database. To promote consistency in data-entry, one person from the group was designated to enter all survey data into the database. Subsequently, a different team member was designated to review the full data set to ensure that all cases had been coded, and to conduct a systematic accuracy verification on every fifth case (20%). The data were analyzed using the SAS system for Windows (version 6.12).

The random sample of cases chosen for survey was compared to the non-chosen cases to verify that the sample was representative. Cases chosen did not differ from the non-chosen unconfirmed population with respect to age at first EIA testing, gender, or percentage residing in Marion County. On the other hand, the percentage of whites in the sample did appear to be significantly lower than that in the non-sampled group. Although race appeared to be unevenly distributed between the two groups, 48% of the racial data were missing.

Of the 363 cases selected, 68 could not be surveyed because the necessary information was missing from the ISDH database or was erroneous. Providers for 229 of the remaining 295 cases were successfully contacted. Fifty-eight providers failed to respond and 20 indicated no knowledge of the cited patient, yielding 151 responses, or a rate of approximately 66%.

Survey respondents were most likely to be primary care physicians; their hepatitis C patients were most likely to be men living outside Marion County whose average age at EIA testing was 45 years. Non-respondents were similar to respondents in terms of age at EIA testing, gender, and race, but were significantly less likely to reside outside Marion County, and were initially tested (by EIA) by non-primary care physicians.

In regard to the first objective, assessing adequacy of testing (Table 1), 30.5% [95% CI (22.2% - 38.5%)] of provider responses indicated that a confirmatory test (either RIBA or PCR) had been performed (See Table 6.). Patients who either had not had a confirmatory test or whose testing status was unknown, but who had been referred to another physician for evaluation, were assumed to have been appropriately tested by the specialist to whom they had been referred. This group accounted for 35.1% [95% CI (27.5% - 43.3%)] of the responses. Testing status was unknown for an additional 23.8% [95% CI (17.3% - 31.4%)] of the patients. The remaining 10.6% [95% CI (6.2% - 16.6%)] definitively did not receive confirmatory testing.

For the second objective, regarding initiation of medical follow-up, the survey results show that of the appropriately tested patients, 96.9% (n=96, since 3 were missing) [95% CI (91.1% - 99.4%)] also received adequate treatment. Any of the following conditions was considered to be appropriate medical follow-up: 1) treatment was initiated, 2) treatment was recommended, although patient refused 3) patient was referred to another provider for further evaluation, and 4) treatment was not initiated due to an appropriate contraindication. While the group of patients who were identified by the testing physician as "lost to follow-up" does not indicate inappropriate care by the physician, this group constituted a significant segment of the sample at 16%. Table 2 shows the types of follow-up medical care reported by the providers who appropriately tested their patients.

The survey also asked providers to list patients’ vaccination histories with respect to other hepatitis viruses (A and B) as well as pneumococcus. It was discovered that only about 10% of the studied patients were known to have received any of the vaccinations of interest. Approximately 2% of patients were reported as vaccinated against hepatitis A, nearly 4% against hepatitis B, and 5% against pneumococcus.

The final aim of the project was to characterize the risk factor profile of hepatitis C patients in Indiana. Risk factors reported by providers are detailed in Table 3. The most frequently reported factors were intravenous drug use (37.1%) and sexual contact (29.3%). Over one fourth (28.4%) of patients were said to have no known risk factors for hepatitis C.

Although the data suggest that the majority (65.6%) of patients were appropriately tested and/or referred for further evaluation, 10.6% remained who were not (as well as 23.8% whose testing status is not known). Some among the 10.6% (or 10.6% + 23.8%) may not actually have the disease, and many patients in need of medical intervention remain untreated.

Of the appropriately tested, 96.5% received adequate follow-up medical care. Physicians who provide appropriate confirmatory testing appear to provide adequate care as well, through either treatment or referral. The 3.5% of patients in this group who did not receive the approved care represent 2.3% of the total "unconfirmed" group.

Only a small minority of patients received any of the ancillary vaccinations recommended by the CDC. This low vaccination rate suggests the benefits of vaccination against other hepatitis viruses and pneumococcus have not been adequately stressed.

The reported prevalences of risk factors for hepatitis C patients in Indiana appear to differ from those reported nationally. For both groups, the most common factor is injecting drug use; but the study sample’s rate of 37.1% is much lower than the national figure of 60%. The risk factor reported as second in prevalence in the study is sexual contact (29.3%); the national figure falls below 20%. Nearly 29% of the sample patients were reported to evidence no known risk factors for hepatitis C; nationally, that figure is approximately 10%. One cause for these apparent differences may be that the factors were reported not by the patients, but by providers. Patients may more readily reveal the possibility of sexual contact as a risk factor than illegal drug use. Physicians who are unaware of the inefficiency of sexual transmission may then be less likely to probe for other risk factors, such as injecting drug use.

Several limitations exist in the present study. Limitations include the following:

• The sample size was not adequate to generalize the results of the study
• The random sample may contain racial bias. Race statistics from the non-studied group depict a make-up of 69.1% whites, while the sample group included only 61.0% whites. Since, however, race was reported for only 52% of the unconfirmed cases, the true difference in racial distributions may not be evident.
• Patient referral to another provider was assumed to have ensured the patient’s adequate medical management. The true nature and extent of consequent follow-up medical care has not been ascertained; further study is recommended.
• Time constraints and data insufficiency limited the number of providers that could be contacted initially and the number of providers that could be recontacted with a second fax.
• Many case records contained missing data fields, apparently because the reporting form submitted to the ISDH had not been properly completed. Automatic exclusion of records without a patient name or without a provider name reduced the number of patients eligible for study.
• Database errors impeded or delayed contact with providers, thereby further limiting the number of cases ultimately studied. It is presumed that some of the providers not contacted could not be located because of misspelled names and other errors.

The findings of this study indicate a need among Indiana physicians for further education concerning hepatitis C. Two small surveys of physician knowledge have indicated similar needs for hepatitis C education in other states. Anticipated alterations to Indiana’s reporting rule will require that the state’s physicians be notified by mail. That mailing should include a delineation of the CDC’s HCV testing and treatment algorithms as well as information about the advisability of hepatitis C, hepatitis B, and pneumococcal vaccination for all chronically ill patients. Once the mandatory reporting rule is implemented, it would be possible to generate a list of patients on a periodic basis, whose positive EIA remained unconfirmed by RIBA or PCR. As a means of continuing provider education, a letter reminding the provider of the CDC algorithm could be automatically generated.

Efforts to reduce the number of patients lost to follow-up are certainly warranted; the survey indicated that ~16% were lost to follow-up by the testing physician. Given the long-term impact of this disease, patient education interventions should be considered as well as implementation of more vigorous follow-up techniques in this unique population.

Lastly, the possible disparity between the national HCV risk factor profile and that for Indiana should be further evaluated. Until the risk factor profile for patients in Indiana is known, educational efforts aimed at specific audiences considered at higher risk for contracting HVC infection cannot be effectively created and implemented. One method, which has been utilized in other state(s) to obtain this risk factor data, is to automatically survey every nth patient (or provider) at the time the case report is received. With appropriate design, the assessment could be complete at the end of a full reporting year.

With mandatory reporting of all positive HVC tests, a well-maintained database, and an accurate assessment of Indiana’s risk factor profile, the ISDH will be well situated to provide strong leadership with HCV education and epidemiological information for the growing burden of chronic HCV in Indiana.

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