Risk Factors for Hepatocellular Carcinoma in a Cohort Infected With Hepatitis B or C

Scott R Walter; Hla-Hla Thein; Heather F Gidding; Janaki Amin; Matthew G Law; Jacob George; Gregory J Dore


J Gastroenterol Hepatol. 2011;26(12):1757-1764. 

In This Article

Abstract and Introduction


Background and Aim: The incidence of hepatocellular carcinoma (HCC) has increased in Australia in recent decades, a large and growing proportion of which occurs among a population chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). However, risk factors for HCC among these high-risk groups require further characterization.
Methods: We conducted a population-based cohort study using HBV and HCV cases notified to the New South Wales Health Department between 2000 and 2007. These were linked to cause of death data, HIV/AIDS notifications, and hospital records. Proportional hazards regression was used to identify significant risk factors for developing HCC.
Results: A total of 242 and 339 HCC cases were linked to HBV (n = 43 892) and HCV (n = 83 817) notifications, respectively. For both HBV and HCV groups, being male and increasing age were significantly associated with risk of HCC. Increasing comorbidity score indicated high risk, while living outside urban areas was associated with lower risk. Hazard ratios for males were two to three times those of females. For both HBV and HCV groups, cirrhosis, alcoholic liver disease, and the interaction between the two were associated with significantly and considerably elevated risk.
Conclusion: This large population-based study confirms known risk factors for HCC. The association with older age highlights the potential impact of HBV and HCV screening of at-risk groups and early clinical assessment. Additional research is required to evaluate the impact of improving antiviral therapy on HCC risk.


Hepatocellular carcinoma (HCC) is one of the leading causes of cancer incidence and mortality worldwide.[1–3] Although less common in Australia than other regions, there has been a marked increase in HCC incidence in recent decades.[4–6] Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the main risk factor for HCC,[7,8] with over 80% of cases worldwide developing in the presence of these infections.[9] The increasing prevalence of chronic viral hepatitis in Australia has been identified as a key driver behind the rising incidence of HCC.[10,11] Other known HCC risk factors include cirrhosis, alcoholic liver disease (ALD), aflatoxin B1,[12] hemochromatosis,[8] HIV,[13] diabetes,[14–16] and HBV/HCV co-infection.[17–20] Increasing age, being male,[21] and certain ethnicities[22] have also been identified as risks, along with lifestyle factors, such as high alcohol intake and smoking. The prevalence of risk factors can vary considerably between geographical regions.[21]

Many published studies have examined risk factors for HCC in various regions of the world,[8,21,23–26] some of which have looked at risk within HBV- or HCV-infected groups.[23–25] However, there are very few studies of HCC risks in the Australian context,[10] and none which quantify risk among HBV- or HCV-infected people at a population level. To this end, we conducted a population-based, retrospective cohort study to identify and quantify risk factors for HCC among an already high-risk group of HBV or HCV infected individuals in New South Wales (NSW), Australia's most populous state.


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