Novel population‐based study finding higher than reported hepatocellular carcinoma incidence suggests an updated approach is needed

Abstract

Hepatocellular carcinoma (HCC) incidence is rising rapidly in many developed countries. Primary epidemiological data have invariably been derived from cancer registries that are heterogeneous in data quality and registration methodology; many registries have not adopted current clinical diagnostic criteria for HCC and still rely on histology for classification. We performed the first population-based study in Australia using current diagnostic criteria, hypothesizing that HCC incidence may be higher than reported. Incident cases of HCC (defined by American Association for the Study of Liver Diseases diagnostic criteria or histology) were prospectively identified over a 12-month period (2012)(2013)) from the population of Melbourne, Australia. Cases were captured from multiple sources: admissions to any of Melbourne's seven tertiary hospitals; attendances at outpatients; and radiology, pathology, and pharmacy services. Our cohort was compared to the Victorian Cancer Registry (VCR) cohort (mandatory notified cases) for the same population and period, and incidence rates were compared for both cohorts. There were 272 incident cases (79% male; median age: 65 years) identified. Cirrhosis was present in 83% of patients, with hepatitis C virus infection (41%), alcohol (39%), and hepatitis B virus infection (22%) the commonest etiologies present. Agestandardized HCC incidence (per 100,000, Australian Standard Population) was 10.3 (95% confidence interval [CI]: 9.0-11.7) for males and 2.3 (95% CI: 1.8 to 3.0) for females. The VCR reported significantly lower rates of HCC: 5.3 (95% CI: 4.4 to 6.4) and 1.0 (95% CI: 0.7 to 1.5) per 100,000 males and females respectively (P < 0.0001). Conclusions: HCC incidence in Melbourne is 2-fold higher than reported by cancer registry data owing to under-reporting of clinical diagnoses. Adoption of current diagnostic criteria and additional capture sources will improve registry completeness. Chronic viral hepatitis and alcohol remain leading causes of cirrhosis and HCC. (HEPATOLOGY 2016;63:1205-1212 SEE EDITORIAL ON PAGE 1078 P rimary liver cancer (PLC) has become the second leading cause of cancer mortality worldwide and is also the fifth-most common cancer. (1) Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, mostly arises in the setting of cirrhosis, with the most common etiologies being chronic viral hepatitis B and C, alcohol, and nonalcoholic fatty liver disease.

The underreporting of hepatocellular carcinoma to the cancer register and a log‐linear model to estimate a more correct incidence

“…Our findings are in line with a recent Australian study estimating the HCC incidence in Melbourne to be 2‐fold higher than reported by CR data, but there are some important differences. Misclassification was a major explanation in the Australian study, only HCC cases with histological verification were classified as HCC (138 in 1 year), the HCCs diagnosed by noninvasive methods and reported to the CR were classified as LCa UNS (123/162 LCa UNS), but about 25% of HCCs were not reported at all.…”

Impact of viral hepatitis aetiology on survival outcomes in hepatocellular carcinoma: A large multicentre cohort study

“…Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are both major risk factors for HCC, with an associated 5‐100 fold increased risk of HCC in patients with chronic HBV infection, and a 15‐20 fold increased risk for HCV infection . While previous studies reported that both viral infections account for an estimated 19% of HCC cases in developed countries, a recent prospective epidemiological study from our group indicates that as many as 41% of cases are associated with HCV and 22% of cases are due to HBV infection …”

Surveillance improves survival of patients with hepatocellular carcinoma: a prospective population‐based study

“…We recently reported the first Australian population‐based study of incident HCC 14 . We found that age‐standardised incidence rates of HCC in Melbourne were twice as high as reported by the Victorian Cancer Registry: 10.3 cases (95% confidence interval [CI], 9.0–11.7) per 100 000 men and 2.3 cases (95% CI, 1.8–3.0) per 100 000 women.…”