commercially acquired tattoos as a potentially important source of hepatitis c infection robert w....

Commercially Acquired TattoosAs a Potentially Important Source

of Hepatitis C Infection

Robert W. Haley, M.D.University of Texas Southwestern Medical Center

R. Paul Fischer, M.D.Presbyterian Hospitals and Dallas Spine Group

Dallas, Texas

Journal Reference

• Haley RW, Fischer RP

• Commercial tattooing as a potentially important source of hepatitis C infection: clinical epidemiology of 626 consecutive patients unaware of their hepatitis C serologic status

• Medicine

• 2001; 80: 134-151.

Objective

• To assess the relative importance of all known risk factors for HCV infection

• To measure risk factors by a physician’s standardized interview in an office practice

• To identify risk factors accounting for acquisition of all cases of HCV infection

Setting and Subjects• A private orthopedic clinic specializing in

treatment of patients referred for spinal problems (10% workers comp)

• Patients referred from TX, OK, AR and LA

• 626 consecutive patients visiting the clinic during 18 months in 1991-1992

• An internist interviewed all subjects for risk factors at the end of a routine history and physical examination

• Informed consent and confidentiality assured

Physician’s Risk Factor Interview

• Interview followed a 25-item questionnaire.

• Risk factors included all found in literature review of epidemiologic studies of HCV, HBV and HIV.

• Before IDU questions, repeated confidentiality assurance and emphasized need for candor.

• Tattoos directly observed, measured and described (size, artistic quality, colors).

• Recorded risk factors before HCV serology results known.

Serologic Testing

• Tested 629 serum samples for HCV, HBV and HIV.

• Screened all sera for HCV Ab with both first generation EIA-1 (Roche) and second generation EIA-2 (Abbott).

• Confirmed all EIA-1 or EIA-2 positives by second generation 4-antigen RIBA-2 (Chiron).– Reactive: 2 or more bands scored as > 1+

– Indeterminate: only 1 band scored as > 1+

– Non-reactive: all bands either ± or 0

Serologic Testing for HIV Ab

• EIA screening by HIVAB HIV-1/HIV-2 (rDNA, Abbott Laboratories)

• Positives confirmed by western blot testing using the NovapathTM HIV-1 test kit (Bio-Rad)

Statistical Methods• Adjusted prevalence odds ratios obtained from

logistic regression by exponentiating LR coeff.

• Population attributable risk percentage (PARP, adjusted etiologic fraction, EF) calculated for each of r risk factors (EFr) in a multivariate

model (Bruzzi et al. Am J Epidemiol 1985; 122: 904)

• Summary EF (% of all cases attributed to joint effects of all model risk factors) by same method

• Note: sum of EFr‘s not equal the summary EF.

Statistical Methods

• Estimated population prevalence rates by direct standardization to the age, sex, race, occupation distribution of the 1990 U.S. population.

• U.S. population data obtained from 1990 census.

• Occupation data from the 1990 U.S. civilian work force, U.S. Census Bureau

• Used the inverse sampling probability estimates (Nj/nj) to weight the observations in each category.

Sample Characteristics

Number of subjects 626Age (mean) 42Gender (% male) 57Race (% white) 74

(% black) 14Median income $20,000Education (% college) 27Home, (% Dallas area) 41

(% Texas) 51

Results: Seroprevalence (%) Sample Population Dallas Co.

N prev. (%) prev. (%)* Population†

HCV 43 6.91.0‡ 2.8 --

HIV 1 0.20.2 0.1 0.40.1

*Standardized to the age, sex, race, occupation distribution of 1990 U.S. population†1989 random sample household HIV serosurvey

‡Prevalence rate SE

Risk Factor Prevalence (%)Prevalence

N rate (%)

IDU 40 6*Tattoo 113 18HC worker 121 19Heavy drinker 118 1910 sex partners 127 20Transfusion 122 19

*Prevalence of IDU in 1989 Dallas Co. pop was 4.00.8

Prevalence Relative Risk for HCV

Risk Factor N HCV+ % RR p

No IDU 585 28 5 1.0IDU 40 15 38 7.8 <.0001

None 585 28 5 1.0<1 year 21 4 19 4.01-2 yrs 6 3 50 10.43-10 yrs 9 6 67 13.9 trend>10 yrs 4 2 50 10.4 <.0001


Risk Factor N HCV+ % RR p

No tattoo 513 18 4 1.0Tattoo 113 25 22 6.3 <.0001

At home/pvt. 46 6 13 3.7 .002Jail/prison 6 1 17 4.8 .2Commercialtattoo parlor 52 17 33 9.3 <.0001

Prevalence Relative Risk for HCVTattoo feature N HCV+ % RR p

Technical qualityLow 35 5 14 4.1Medium 24 5 21 5.9 trendHigh 51 14 28 7.8 <.0001

Surface area (cm2)1-4 80 14 18 5.05-14 19 6 32 9.015-20 6 2 33 9.5 trend>20 7 3 43 12.2 <.0001

Prevalence Relative Risk for HCVTattoo feature N HCV+ % RR p

No. tattooings1 75 15 20 5.72 17 3 18 5.0 trend3 21 7 33 9.5 <.0001

No. of tattoos1 50 11 22 6.32 27 3 11 3.23 14 5 36 10.5 trend4 19 5 26 7.5 <.0001


Tattoo colors N HCV+ % RR

White 6 3 50 2.4Yellow 18 7 39 2.0Orange 9 3 33 1.6Red 44 13 30 1.7Black 100 22 22 1.0

Prevalence Relative Risk for HCVHC workersby gender/job N HCV+ % RR p

Never a HC worker 505 30 6 1.0Women/PC or lab 47 1 2 0.4 .2Men/PC or lab 10 1 10 1.7 .5Women/ancillary 33 1 3 0.5 .4Men/ancillary 31 10 32 5.8 <.0001

*Patient care or lab: nurses, aides, orderlies, ward clerks, other Ancillary: housekeeping, maintenance, dietary


Alcohol N HCV+ % RR p

No beer 456 23 5 1.0Beer 170 20 12 2.3 .003

No wine 588 41 7 1.0Wine 38 2 5 0.8 .8

No liquor 570 40 7 1.0Liquor 56 3 5 0.8 .8


Alcohol N HCV+ % RR p

No beer 456 23 5 1.0Beer 170 20 12 2.3 .003

6-packs/mo.

None 456 23 5 1.0<3 52 4 8 1.53-10 97 11 11 2.2 trend11-60 21 5 24 4.7 <.0001


Transfusions N HCV+ % RR p

No 504 38 8 1.0Yes 122 5 4 0.5 .2

No. unitsNone 504 38 8 1.01-2 85 5 6 0.8 trend>2 37 0 0 0.0 .08


Sexual partnersn peak year N HCV+ % RR p

<10 497 27 5 1.0 10 or more 127 16 13 2.3 .004


Other risk factors RR (95% CI)

Acupuncture* 0.0Electrolysis* 0.0Bone graft* 2.1 (1.0-4.5)Obesity Trend p=.4Blue collar occup. 1.9 (1.0-3.5)Middle income 2.5 (1.4-4.6)

*33 patients reported acupuncture, 10 electrolysis, 53 bone graft.


Other risk factors RR (95% CI)

Truck driver 3.5 (1.8-6.8)HS dropout 2.3 (0.7-8.4)College dropout 1.5 (0.4-5.9)Black man 5.0 (1.9-12.8)White man 2.8 (1.2-6.4)Born in U.S. 3.5 (0.5-24.8)

Multiple Logistic Regression Analysis

Risk factors AOR* (95% CI) p

IDU >1 year 23.0 (7.5-70.6) <.0001 Male ancill. HCW 9.6 (3.8-24.3) <.0001Commercial tattoo 6.5 (2.9-14.8) <.0001>3 six-packs/mo. 4.0 (1.8-8.7) .0004

*Adjusted odds ratio

Fate of Other Risk Factors in Stepwise Logistic Regression Analysis

Truck Driver-----X2 to enter at----

Independent RFs X2 This step Next step

IDU >1 year 79.7 13.7 10.3 Male ancill. HCW 47.6 10.3 5.5Commercial tattoo 20.3 5.5 3.6>3 six-packs/mo. 13.6 3.6 2.4


Sexual Promiscuity*-----X2 to enter at----



*>10 sexual partners at peak sexual age


Tattoo Quality*-----X2 to enter at----



*Same effect for tattoo size, color and 3 tattooings

% of HCV Cases Attributable to Each Risk Factor (PARP, EF)

Independent RFs %

Tattoo 41Heavy beer drinking 23Injection-drug use 17Male ancillary HCW 8

All 4 risk factors 91*

*EF’s do not sum to overall EF because risk factors are not mutually exclusive.

Tattooing

Relative risk

0 1 2 3 4 5 6 7 8 27

Haley and FischerKaldor et al.Ko et al. '92

Holsen et al.Mele et al.

Balasekaran et al.Kelen et al.

Thomas et al. '94 womenThomas et al. '94 men

Thomas et al. '95Weinstock et al.

Silverman et al.Alter et al. '99

Osmand et al. womenEsteban et al.

Sun et al.Conry-Cantilena et al.

Injection-drug use

Relative risk

0 5 10 15 20 25 30 60 80

Excluded

Excluded

ExcludedExcluded

Excluded

Excluded

Alcohol

Relative risk0 5 10 15 20 25









Healthcare worker

Relative risk0 1 2 3 4 5 6 7 8 9 10

Alcohol Inhibits the Cellular Immune Response to HCV

• In cross-over experiments in mice immunized with HCV core protein, chronic alcohol ingestion inhibited T-helper (Th) cell, cytotoxic lymphocyte responses and cytokine secretion, and altered normal proliferating Th1 cell subtype to Th0 subtype.

• Corrected by removing the mice from alcohol but progressed in those continued on alcohol.

• Alcohol suppresses cellular immune steps between sensitization and response (impaired clearance).

From Geissler et al. Hepatology 1997; 26: 764-770.

Clinical Evidence for Alcohol Effects on HCV Persistence

• Heavy alcohol consumption increases HCV viral load in patients with chronic HCV infection.

• Continued alcohol consumption during anti-viral therapy for HCV reduces the likelihood of sustained clearing of the virus.

Pessione et al. Hepatology 1998;27:1717-22.

Schiff. Hepatology 1997; 26 (Suppl): 39S-42S.

Transfusion

Relative risk0 1 2 3 4 5 6 7 8 9 10









Sexual promiscuity

Relative risk0 1 2 3 4 5 6 7

Excluded

ExcludedExcluded

NIH/American Red Cross Study*• HCV serology on 954,316 blood donors, 4,166 EIA+

• All EIA+ invited to participate, only 481 (12%) did.

• Subjects knew their RIBA status before volunteering.

• Case-control study done in 248 RIBA+ vs 131 RIBA-.

• RIBA- group had higher rate of college educated and repeat blood donors.

• Interpretation: voluntary self-selection at a 12% rate attracted concerned RIBA+ subjects with more risk factors and altruistic RIBA- subjects with fewer risk factors. This may explain unusual associations. *Conry-Cantilena et al. NEJM 1996;334:1691

Incomplete Disclosure of Stigmatized Behaviors such as IDU

• Common problem in survey research

• The more uncomfortable, the more likely to answer with socially desirable responses.

• It has been suggested that incomplete disclosure could inflate the association between HCV and other risk factors such as sexual promiscuity or tattooing.

The Best Way to Handle Incomplete Disclosure Is To Prevent It.

• Ensure confidentiality (and convince the subject).

• Place sensitive questions late after rapport developed.

• Preface sensitive questions with reassuring statements that lessen interviewer disapprobation.

• Obtaining information in a physician’s office as part of a medical examination is more accurate than field interviews.

Can Socially Desirable Responding Inflate Associations with Other Risk Factors?

• Latkin et al. (Addiction 1993;88:517) measured Social Desirability Responding Tendency (SDRT) in a large population of IDU with known HIV serostatus.

• SDRT scores were inversely associated with reported prevalence of stigmatized behaviors (needle-sharing).

• But SDRT scores did not differ by HIV serostatus.

• Thus, since a confounder must be associated with both the risk factor and the outcome, SDRT cannot confound other risk factor associations.

To be a confounder, a variable (C) must be associated with both the risk

factor (A) and the outcome (B).

A B

C

Conclusions• Repetitive IDU appears to be the most potent cause

of chronic HCV infection.

• HCV appears to be transmitted by commercial tattooing in Texas as in other countries. Undisclosed IDU does not account for this effect.

• Working in a hospital appears to pose no excess risk of chronic HCV infection except possibly in male ancillary employees before OSHA regulations.

• Heavy beer drinking may encourage persistence of HCV by suppressing immune response, or it may be a proxy for unmeasured blood exposures (e.g., brawling)

Conclusions• If all four of these risk factors are causal,

commercial tattooing may have produced more chronic HCV infections than IDU in Texas.

• Even though transfusing HCV-contaminated blood can cause HCV infection, its contribution to the current high population prevalence of HCV infection in Texas is probably negligible.

• Our finding adds weight to the strong argument against sexual transmission of HCV.

Conclusions• In the 1980s and 1990s, tattooing dramatically

increased in popularity.

• By 1993, 16% of Texas high school students had tattoos, and 33% of the non-tattooed were considering getting one (J Sch Nurs 1994;10:26).

• Although 30% of states have laws regulating tattooing, only Texas has appropriated funding for regular inspections of tattoo parlors.

• Consumers getting tattoos assume tattooists are regulated and inspected, but no one is checking!

Advice on Tattooing

•If you have a tattoo, get an HCV test.

•If you are considering a tattoo, either don’t or get it done in a tattoo parlor that has been state-licensed and inspected in Texas.

Disagreement over Role of Tattooing

• Seven Sentinel County Surveillance Study performs prospective surveillance of cases of acute hepatitis.

• Commonly finds IDU, transfusions and promiscuous sexual activity in incubation period.

• Rarely finds a tattooing experience in the incubation period.

• Concluded that tattooing is not an important cause of HCV seropositivity.

Adjusted Odds Ratios* for History of Acute Hepatitis and HCV Seropositivity

Hx of acute Seropositive

hepatitis for anti-HCVHistory of IDU 5.9 (2.5-13.8) 7.2 (3.1-16.5)Commercial tattoo 1.2 (0.5-3.3) 6.5 (2.9-14.4)

*Addition risk factors adjusted for in the logistic regression model include: having worked in a hospital, number of sexual partners in peak year, and amount of alcohol consumed. Numbers are adjusted odds ratio with 95% confidence interval.

Hypothesized Explanation

• HCV acute hepatitis is relatively rare and results from large intravenous doses of HCV virus from IDU and transfusions.

• Tattooing transfers relatively small intradermal innocula of HCV virus and causes chronic HCV infection without acute hepatitis.

Conclusion

• If this theory is true, surveillance of acute hepatitis cases may be systematically overlooking major modes of transmission of HCV infection that do not cause acute hepatitis.

• CDC has recently added a new surveillance component to study risk factors in chronic occult HCV infection.

commercially acquired tattoos as a potentially important source of hepatitis c infection robert w....

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