Our study demonstrates a highly significant increase in the burden of HCV on the health care system. For the primary outcomes of interest – liver-related hospitalizations, lengths of stay, and in-hospital mortality – we observed average annual increases ranging from 15% to 18%. In contrast, alcoholic cirrhosis-related hospitalizations, costs and inpatient deaths remained stable. These results suggest that the future burden of HCV will likely surpass previous expectations. Zou et al (10
) projected a doubling of the number of patients with HCV-related complications, including liver-related deaths, between 1998 and 2008. Between 1994 and 2004, fourfold increases in liver-related HCV hospitalizations, lengths of stay and inpatient deaths were observed, suggesting that published projections of HCV burden may be conservative. Our results are in keeping with hospitalization data in the United States, which showed three- to fourfold increases in these outcomes between 1994 and 2001 (22
). In this study, Grant et al (22
) also reported a 26% annual growth rate for HCV-related hospital charges, which was slightly lower than the 41% annual increase in costs that we observed. Based on the costs and annual growth rates observed in the CHR, we project that liver-related HCV hospitalizations will cost the Canadian health care system approximately $240 million in the year 2020.
Our results are consistent with natural history studies describing the impact of age, sex and HIV coinfection on the progression of chronic HCV (4
). The role of aging is highlighted by the disproportionate shares of hospitalizations among patients in their 40s and 50s, in whom average annual growth statistics ranging from 19% to 27% were observed. Because the prevalence of HCV is highest in this subgroup (26
), aging of these patients will exact an increasing toll on the health care system in coming years. As expected, men contributed to a majority of HCV-related hospitalizations due to their higher HCV prevalence (26
) and accelerated disease progression (4
). Surprisingly, however, we observed a disproportionate increase in the number of hospitalizations among women – a previously unreported finding that warrants confirmation in larger studies. A sex-dependent difference in under-reporting at the beginning of the interval (eg, less frequent testing in women due to their lower HCV prevalence) is a potential, but entirely speculative, explanation.
Finally, HIV/HCV coinfected patients experienced alarming annual growth rates, ranging from 30% to 40%, for liver-related and all-cause HCV hospitalizations. In an analysis of United States hospitalization data among HIV-infected patients, Gebo et al (27
) described a 29% reduction in overall hospitalizations, but a tripling of HCV-related hospitalizations between 1996 and 2000. Due to reductions in HIV-related mortality attributable to highly active antiretroviral therapy and prophylaxis of opportunistic pathogens, HCV has emerged as a major cause of morbidity and mortality in coinfected patients (28
). For example, in a nationwide population of HIV-infected patients in France (30
), deaths due to end-stage liver disease – the majority of which were due to HCV – occurred in 1.5% of patients in 1995, 6.6% in 1997, 14.3% in 2001 and 12.6% in 2003. We also found that HIV/HCV coinfected patients admitted for liver-related conditions were approximately 10 years younger than their HIV-negative counterparts, in keeping with the accelerated natural history of HCV in this subgroup (6
The increasing burden of chronic HCV that we have observed highlights the importance of primary prevention of HCV infections and initiating anti-HCV therapy in eligible patients. Currently available regimens consisting of peginterferon and ribavirin lead to viral eradication in approximately one-half of treated individuals (31
). Viral clearance has been associated with improved clinical outcomes, even in those who have already progressed to cirrhosis (33
). Unfortunately, due to its cost, contraindications, toxicities, the requirement for intensive monitoring and counselling that is typically available in only specialized centres, and the reluctance of patients to undergo treatment, the widespread uptake of anti-HCV therapy has been limited (36
). Of the roughly 200,000 prevalent cases in Canada, only an estimated 5000 are treated annually (2
). In a recent study from a Canadian hepatology centre (38
), only 29% of 1317 patients were considered eligible for therapy, and of these, only 38% (11% of the total) actually received treatment. Hopefully, the more widespread dissemination of antiviral therapy, including more effective and better-tolerated agents under development (39
), will be able to stem the coming tide of HCV-related morbidity and mortality, as suggested in modelling studies (11
Our study had several limitations. Most importantly, under-reporting of HCV diagnoses during the early years of the study may have led to an overestimation of the true increase in the burden of HCV. Several points argue against the significance of this limitation. First, we observed parallel increases in all-cause and liver-related HCV outcomes. Although under-reporting is conceivably more likely in patients admitted for nonhepatic conditions, it is much less likely that patients with liver-related admissions would not be tested for HCV or have the diagnosis recorded in their discharge abstract. Second, greater annual increases in liver-related HCV hospitalizations were observed among 40- to 59-year-olds than among older patients. There is no evidence to suggest an age-dependent effect on under-reporting of HCV. Finally, our sensitivity analysis supported the robustness of our findings. In every scenario, including the most extreme in which 75% of cases were under-reported in 1994, increases in liver-related HCV admissions remained significant. Our study was also limited by the inability to track individual patients over time. Thus, we cannot distinguish changes in overall hospitalization counts from the numbers of hospitalizations per patient. Finally, our data originates from a single, albeit large, Canadian health region. The generalizability of our findings to other regions (within Canada and elsewhere) requires confirmation.
Shortly following its discovery, HCV was described as “a sleeping giant” (40
); our data support previous findings that the giant has indeed awoken (22
). We observed highly significant increases in HCV-related hospitalizations, lengths of stay, hospital costs and in-hospital deaths that likely foreshadow an even greater burden on the health care system. To stem this tide, health care policy makers and physicians must focus on preventive initiatives and strategies to maximize the dissemination and most effective use of potentially curative therapies.