Our study demonstrated that the THIN database contains a reliably diagnosed cohort of HCV-infected patients. THIN's HCV diagnostic codes had a positive predictive value exceeding 85%, suggesting that the majority of patients coded as having HCV infection indeed have the disease. Moreover, THIN contains information on important confounding variables in HCV epidemiologic studies such as alcohol and socioeconomic status, although additional data are needed to determine the validity of these variables.19
Thus, THIN could be used to conduct studies of HCV epidemiology.
However, our study identified important limitations in utilizing THIN for HCV epidemiologic research. First, 22% of randomly-selected viral hepatitis NOS patients had HCV infection. Manual review of these patients' electronic records enabled us to identify the cause for hepatitis in 76%. This review revealed an additional HCV diagnostic code (“hepatitis C status”) that, when reported as positive in the free text comments, improved our ability to identify HCV-infected patients. Thus, using manual review, only 7% of viral hepatitis NOS patients actually had HCV infection. Knowledge of this misclassification rate can be used in future THIN HCV studies when designing inclusion criteria, determining the potential efficiency of implementing surveys to identify additional HCV patients, and interpreting results.
Second, the THIN database misclassified the date of incident HCV diagnosis in approximately 40% of HCV-infected patients. This misclassification may be because HCV infection is a chronic disease that may be present for years prior to diagnosis. Moreover, GPs may not always accurately enter into the electronic record diagnoses that occurred prior to registration with the practice or prior to implementation of the electronic record. We examined the database's free text comments to identify additional information on the date of incident HCV diagnosis, but GPs did not record this date in that field. It should be noted that in most cases, incident HCV diagnoses recorded in the database may be months or years removed from the actual date of HCV infection.
Another limitation of the THIN database for HCV epidemiologic research was the lack of data on HCV antibody, RNA, and genotype. Hepatic aminotransferase results, which are markers of liver inflammation, were also not available for all HCV-infected patients. The absence of such data limits the ability to identify spontaneous HCV clearance, determine chronic infection, examine data on HCV genotypes, and evaluate hepatotoxicity of medications. This information could be obtained through GP surveys.
Very few HCV patients had prescriptions for anti-HCV medications recorded in the THIN database. Among the randomly-selected sample of HCV-infected patients whose GP's were surveyed, receipt of interferon-based treatment was recorded in the THIN database in only one patient among the six reported by their GP to have received such therapy. In the UK, liver specialists typically prescribe antiviral therapy for chronic HCV patients, and this information might not be recorded in GP's electronic records. This limits the usefulness of THIN for pharmacoepidemiologic studies in which knowledge of exposure to anti-HCV therapy is important.
This study provided a unique opportunity to compare the prevalence of HCV infection in THIN with that previously reported in the UK. The estimated prevalence of HCV infection in England and Wales has ranged from 0.1% to 1%.18,20,21
We observed the prevalence of HCV infection in THIN to be 0.03%, which is considerably lower than these estimates. This finding is due in part to the misclassification of HCV infection as viral hepatitis NOS described above. However, this is counterbalanced by the knowledge that 14% of patients with an HCV code did not have documented HCV infection. Differences between our results and that of prior studies could be related to differences in the methods of ascertaining HCV prevalence. In prior studies, prevalence of HCV was assessed by antibody testing of sera from residual specimens submitted to laboratories for routine diagnostic examination. Furthermore, since HCV infection is often asymptomatic, there are likely many patients in THIN who have not yet been diagnosed. Finally, the characteristics of THIN patients could differ from other populations that have been studied, such as having a slightly higher socioeconomic status.
The cumulative incidence of hepatic decompensation in this study was comparable to that reported in prior cohort studies examining long-term outcomes of HCV infection. These studies reported incidences of hepatic decompensation ranging from 2% to 12%.4-8
The cumulative incidence of hepatic decompensation among the THIN HCV patients followed in this study fell within this range. Future studies should confirm further the validity of THIN's diagnostic codes for hepatic decompensation.
There are several potential limitations to our study. First, in any survey-based study, one must consider the potential for non-response bias. Our response rate was high, so this form of bias should have little impact on our results. Second, the questionnaire was administered to GPs in practices that are willing to participate in THIN research studies, and therefore results might not be generalizable to non-participating practices. Likewise, one must consider whether the patients randomly sampled for validation were representative of the full population. We observed that those sampled were similar to the full population in terms of Townsend scores, suggesting this to be the case (data not shown). Finally, we assumed that GP's responses to the questionnaire reflected the truth. It is possible that errors might have occurred in completing the questionnaire. However, we did request copies of the correspondences between the GPs and specialists related to the HCV diagnosis to ensure misclassification of the outcome was minimized.
In conclusion, THIN can be an important resource for studying HCV epidemiology. The positive predictive value of THIN's HCV diagnostic codes was high. Manual review of THIN's records can help identify the cause of hepatitis among viral hepatitis NOS patients. The lack of data on HCV-related laboratory results and medications are limitations that can potentially be overcome by obtaining supplemental information from GPs.