The coming wave of HCV-related liver disease: Dilemmas and challenges
Article Outline
Infections that target the liver appear to have targeted Egypt in a manner that has been likened to a curse [1]. The general population prevalence of hepatitis C virus (HCV) infection in Egypt is nearly an order of magnitude higher than in most other countries, with estimates ranging from 9% to over 20% [2], [3]. This modern epidemic has its roots in a debilitating disease that has afflicted Egypt since ancient times, schistosomiasis. It is now generally accepted that mass inoculation campaigns with parenteral antischistosomal therapy that continued until the early 1980s were the catalyst for widespread HCV transmission [2], [3], [4], [5]. Although the incidence of new infections in Egypt appears to have decreased in recent years, HCV has continued to be transmitted via iatrogenic exposures, blood transfusion, and other means [3], [4], [6], [7]. Thus, an enormous swath of the population has been left with chronic HCV infection and the impact of the HCV epidemic in Egypt, which is already substantial, will manifest itself for decades to come.
The actual course of Egypt's HCV epidemic is uncertain and will be influenced by a variety of ill-defined factors. These include past and future trends in incidence of infection, the natural history of infection within the affected population, and large-scale prevention or treatment efforts. In this issue of the Journal, Deuffic-Burban and colleagues report the results of a detailed modeling effort that projects the future course of HCV-related mortality in Egypt, based on the estimated incidence of HCV infection before 2000 [8]. The model used available HCV seroprevalence data and liver cancer mortality rates as benchmarks for fitting key model parameters such as the past incidence of HCV infection and rates of cirrhosis progression in Egypt. Despite the many uncertainties inherent in modeling efforts such as this, the authors' conclusion that HCV-related end-stage liver disease is likely to double in the next two decades seems well-founded.
Other countries also are facing a wave of increased HCV-related morbidity and mortality, which in some is already manifested by increasing rates of cirrhosis and liver cancer [9]. While the magnitude of Egypt's HCV problem is unique, the challenges and dilemmas to developing an appropriate response are shared by many countries. Challenges include defining the epidemiology of HCV infection and characterizing trends in disease burden that will determine the elements of a response plan; formulating a plan that addresses the prevention of new HCV infections while reducing the long-term sequelae among persons currently infected; and balancing the response to the HCV epidemic with initiatives aimed at other conditions. Since no country has unlimited resources, each faces a dilemma in assigning priorities between and within various health programs.
Prevention of infection remains the surest way to prevent HCV-related complications and has other benefits including reduced risks for transmission of hepatitis B virus and HIV. There are three major modes of HCV transmission that need to be addressed: unsafe practices related to healthcare delivery, unscreened blood transfusions, and injection of illicit drugs [9]. Efforts to address these issues face significant cultural and economic barriers. While Egypt is an extreme example, HCV transmission in many countries has been driven by unsafe injection practices and other infection control deficiencies [9]. Efforts to address this issue in many developing countries including Egypt are underway but the costs associated with the procurement and proper disposal of single use syringes and other disposable devices pose an obstacle. In addition, overuse of injections will likely remain widespread for reasons that include economic incentives for providers and patient beliefs that injections are the best form of treatment for many common conditions [10]. Transmission of HCV and other viruses from unscreened blood used for transfusions also remains a worldwide concern [9]. In developed countries, routine screening and testing procedures have virtually eliminated this risk. In developing world settings, transfusions have been relatively uncommon but as their use increases it is critical that volunteer-based blood donation systems that include screening for bloodborne viruses be implemented. However, the infrastructure needed to support such systems can be expensive to develop and maintain, and blood safety is not always recognized as a high priority. Finally, injection drug use is the primary mode of HCV transmission in developed countries [9], [11]. Efforts are needed to decrease the number of people who initiate injection drug use. Among those already injecting drugs, programs to reduce transmission and offer drug treatment are clear priorities. Such activities are hampered by the social stigma associated with drug use and by the substantial expenditures that would be required to provide universal access to drug treatment and harm reduction programs.
Preventing new infections will not impact the predicted wave of morbidity and mortality from persons already infected. Current strategies to reduce the long-term sequelae of chronic HCV infection include identifying infected persons by testing those at high risk and offering counseling, medical evaluation and treatment. Counseling and immunization can potentially modify or prevent the adverse effects of cofactors (for example, alcohol consumption or co-infections) on disease progression while treatment can eradicate the virus and eliminate or reduce liver inflammation and fibrosis [12]. Successful treatment, if widespread, also has the potential to help reduce the incidence of HCV infection by decreasing the reservoir of infected persons who can serve as a source for transmission. As with primary prevention, there also are challenges to implementing these strategies. Programs to screen and identify persons with HCV infection need to be supported and balanced by the ability to provide potentially beneficial services including medical management [11], [12]. Using the best available treatments (24–48 weeks of pegylated interferon plus ribavirin), virus elimination (sustained virologic response) can be achieved in 40–50% of treated persons infected with genotype 1 or 4 and in 75–85% of those infected with genotype 2 or 3 [12], [13], [14]. The cost of treatment represents a major barrier to its more widespread use, however. In Egypt, for example, the cost of 48 weeks of pegylated interferon plus ribavirin (about US $12,000) is far out of line with average annual per capita healthcare expenditures (about US $192) and less expensive treatments might gain legitimate appeal despite their decreased effectiveness [13].
Even under ideal conditions that eliminate cost issues, current treatments would likely be indicated for a relatively small proportion of all infected persons. Many HCV-infected persons have little or no evidence of active disease and might best be served by a wait-and-see approach, given that treatment is difficult to tolerate and involves potentially dangerous side effects [14]. Another fraction of HCV-infected patients has already entered the late stages of disease in which their limited options include palliative care or liver transplant, which is rare yet available to those with adequate resources even in some developing countries such as Egypt [15]. Among the remaining HCV-infected persons who might benefit most from current treatments, many would be considered poor candidates because of co-morbid conditions that contraindicate treatment [14]. Finally, for patients with genotypes that are less responsive to treatment, such as genotype 4 which predominates in Egypt and the Middle East, half of those who tolerate treatment would not clear their infection [13]. Thus, wide-scale application of current HCV treatments would likely have only a limited impact on disease burden. While this is a serious dilemma, it is not an excuse for inaction. The fact remains that there are many infected individuals in Egypt and other resource poor countries with HCV disease for whom treatment could be effective.
While better and more affordable treatments are eagerly anticipated, much can be accomplished in the interim. Affected countries must face the dilemmas at hand and give careful consideration to the array of available options for addressing and minimizing the coming wave of HCV-related liver disease. Performing studies and surveys that describe the prevalence and epidemiology of HCV among the general population and in select patient groups and establishing reliable cancer surveillance and cause of death statistics can provide the foundation for projecting the epidemic's future course. These evolving activities will be critical assets for the development and prioritization of sound and effective interventions and for their evaluation. In this way, countries might be well-positioned to take advantage of future advances in HCV prevention and treatment while balancing the many competing demands on their healthcare resources.
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PII: S0168-8278(05)00828-7
doi:10.1016/j.jhep.2005.12.007
© 2006 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
