Assessment of the zinc turbidity test and the use of risk factors in detecting asymptomatic hepatitis C virus carriers: population based studyBMJ 1997; 314 doi: http://dx.doi.org/10.1136/bmj.314.7088.1169 (Published 19 April 1997) Cite this as: BMJ 1997;314:1169
- a Department of Public Health, Osaka University Medical School, 2-2, Yamadaoka, Suita-shi, Osaka 565, Japan
- Correspondence to: Dr Nakajima
- Accepted 27 November 1996
Early detection of carriers of hepatitis C virus, who are at risk of the long term sequelae of the infection, is necessary to provide comprehensive medical benefits such as education, follow up, and treatment.1 However, alanine aminotransferase concentration, even when measured several times, is a poor serum marker for detecting carriers because concentrations are often normal.2 Screening a healthy population by determining antibodies or hepatitis C virus RNA is not feasible. To target a population suspected of harbouring hepatitis C virus infection for further examination, we evaluated other biochemical tests as well as the use of risk factors for hepatitis C infection.
Subjects, methods, and results
Our 281 subjects, aged 30-82 (mean 55) years, (124 men) represented 43% of all residents who had health checkups in 1993 in a town with a high mortality from liver diseases. We assessed alanine aminotransferase (normal ≤35 IU/l), aspartate aminotransferase (≤40 IU/l), ɣ-glutamyl transpeptidase (≤50 IU/l), zinc turbidity (≤12.0 Kunkel), second generation antibody to hepatitis C virus (enzyme immunoassay; positive rate 27.0%), hepatitis B surface antigen (positive rate 1.8%), and risk factors for hepatitis C virus infection. Hepatitis C virus RNA was measured in 61 seropositive subjects. From four biochemical tests and eight risk factors, logistic regression (SAS–PC) was used to determine predictors for the infection.
As predictors of seropositivity, abnormal values in the zinc turbidity test (95% confidence interval 3.4 to 38); a history of jaundice of an unknown aetiology (1.8 to 11), blood transfusion (1.2 to 12), or acupuncture (0.9 to 4.0); and abnormal concentrations of alanine aminotransferase (0.6 to 7.6) were selected. Table 1) shows the predictability of seropositivity with different combinations of predictors. To simplify prediction, each predictor was assigned the same weight. The zinc turbidity test had higher sensitivity and specificity than alanine aminotransferase; together they had a higher positive predictive value than alanine aminotransferase alone. When the risk factors were considered, the specificities were substantially decreased. All 19 seropositive subjects with abnormal zinc turbidity had hepatitis C virus RNA (105-107copies/ml).
The difficulty in evaluating results of the zinc turbidity test has been the low specificity for liver diseases since the level reflects the overall fluctuations in several serum protein concentrations.3 We found that the zinc turbidity test was highly specific to positivity for antibodies to hepatitis C virus–possibly because its results, unlike other those of biochemical tests, are normal in fatty liver and alcoholic liver disease, which are often observed in healthy subjects undergoing routine physical examinations. Furthermore, several diseases which cause raised values on the zinc turbidity test, such as hepatitis B, connective tissue diseases, and myelomas,3 are less common than hepatitis C in healthy people in Japan. When the zinc turbidity test is used in other countries, the prevalence of diseases affecting its results, racial variations in the normal value, and reproducibility among laboratories should be considered.
In selected geographical areas, the zinc turbidity test helps detect carriers of hepatitis C virus who may have persistent liver damage despite having normal aminotransferase concentrations. These carriers should be given an opportunity for further clinical evaluation, even though their prognosis may differ from that of carriers with abnormal aminotransferase concentrations.4 Like the alanine aminotransferase concentration, the zinc turbidity test can fail to detect asymptomatic carriers. Because of the many false positive results, risk factors seem to be more useful as educational preventive tools than as ways to target high risk populations.