Should Patients with Abnormal Liver Function Tests in Primary Care be Tested for Chronic Viral Hepatitis

David T Arnold; Louise M Bentham; Ruth P Jacob; Richard J Lilford; Alan J Girling

Disclosures

BMC Fam Pract 

In This Article

Results

Patients

One thousand, three hundred and forty-four patients consented to the study. Fifty-four were excluded because they did not match the entry criteria in the protocol, along with a further 54 where data on at least one viral hepatitis test was missing (Figure 1). This left 1,236 patients for this study. One hundred and five of these patients were from Lambeth and 1,131 were from Birmingham. The median interval between index and repeat testing was 31 days (inter-quartile range 19–52 days).

Figure 1.

Flow diagram of exclusions and inclusions in the study.

Chronic Viral Hepatitis Cases

Thirteen of the 1,236 patients where the test result was available had chronic viral hepatitis - nine cases of hepatitis B and four cases of hepatitis C. This gives an estimate of 1.1% (95% CI: 0.6%-1.8%) for the prevalence rate in a primary care population with abnormal LFTs; only slightly more than the baseline prevalence in the general population (0.7%). The demographic breakdown of patients with and without viral hepatitis is shown in Table 2.

The breakdown LFT results in the infected cases is given in Table 3. In 10 of these 13 cases, more than one analyte was abnormal. In eight cases the ALT was abnormal and was notably raised in six of those (above twice the upper limit of normal). In one case (perhaps detected by serendipity) only protein levels were abnormal and all the enzyme tests (ALT, AST, GGT and ALP) were normal. Eleven of the 13 patients with chronic viral hepatitis had an abnormality on the repeat LFT. There were two other cases where there were missing data among the repeat LFT panels. Of the 1,113 patients with no viral hepatitis who underwent a complete LFT panel, 169 (15%) reverted to normal.

The country of origin was recorded in 1,208 of the 1,236 study cases, and of these, 170 people were born in a country with an intermediate or high prevalence of viral hepatitis (based on WHO definitions of prevalence[23–25]) and 1,038 were from low-risk countries. The high-risk group contained 11 of the 13 cases (85%) of viral hepatitis. None of the 13 cases admitted to use of intravenous drugs at any time.

As expected from the literature, ALT or AST levels when abnormal tended to be more extreme for cases with viral hepatitis than for cases that did not have this disease (Table 4).

Diagnostic Performance

The sensitivity and positive predictive value of each detection strategy are given in Table 5. It can be seen that the recommended strategy (A), of repeating the LFT and then doing a viral test if an abnormality persists, is highly sensitive. However, the predictive value is low (1.15%). Strategy D, simply carrying out a viral test if the patient originates from a high or intermediate risk country, detects 85% of cases and has a much higher predictive value of 6.47% than the strategy of repeating the LFT test. The strategy of ordering an LFT if the ALT is raised (B), is neither particularly sensitive (67%), nor does it have a high predictive value (1.91%). The more selective strategy of testing if the index ALT was over twice the upper limit of normal (C) has a higher predictive value, but is less sensitive. The best features of C and D are combined in the hybrid strategy F which achieves high sensitivity (92%) and worthwhile predictive value (5.12%).

Costs and Cost Minimisation Analysis

The cost of the laboratory tests and the practice costs are given in Table 6. The average cost per case detected and the incremental costs of detecting each additional case are shown in Table 7. Strategy E (viral test if patient born in an intermediate/high-risk country and ALT is greater than twice the upper limit of normal) provides the lowest cost per case detected. This strategy was therefore designated as the base case for the calculation of the ICERs. Strategy A, the intuitive and widely advocated practice of repeating LFTs, turns out to be the most expensive per case detected. It is dominated by strategy G, where all patients have a viral test. Similarly strategy B (viral test if the index ALT is abnormal) is dominated by strategy D (perform viral test if patient was born in an intermediate or high risk country). Strategy C (viral test if the ALT is greater than two times the upper limit of normal) can be eliminated by an extended dominance principle. If strategy C is preferred to E, this can only be because the extra cases detected by C are deemed worth the extra cost. However, strategy D finds yet more cases than C at lower incremental cost. Therefore either E or D are preferable to C. The cost-effectiveness of the remaining admissible strategies can be visualised from Figure 2. The dotted lines join strategies that cannot be eliminated by dominance principles. The absence of any explicit penalty for missing cases of viral hepatitis in this analysis implies that the costs of E, D and F are under-estimated with respect to G. However, F must be regarded as highly competitive with G - it picks up almost as many cases and has very high efficiency in terms of cost per case detected.

Figure 2.

Cost per detected case for seven testing strategies. The number of detected cases per patient is estimated as (Sensitivity of strategy) × 1.05% where the latter figure is the viral hepatitis prevalence observed in the complete sample of 1,236 patients. The number used differs slightly from the actual number of cases detected per patient in table 5 because of variation in the prevalence of the condition across the samples in which each strategy was tested. The current approach achieves a more consistent comparison of strategies within our data-set; for example, it ensures that the estimate of detected cases per patient for a strategy with 100% sensitivity will always be at least as great as that of any other strategy.

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