Aa
HCV Mortality Rates pt 2
The study by Neal et al is among several recent studies in which population-based data were used to analyze mortality in HCV-infected individuals. In 2006, Amin et al reported a large, carefully conducted study about the impact of hepatitis C in the population at large in Australia (Lancet 2006;368:938–945). Linking data from their viral hepatitis registry with the National Death Index, they found a total of 78,468 individuals with hepatitis C diagnosis, of whom 4194 died during a 13-year study period. The incidence of liver-related death was 0.14% per year for those with hepatitis C alone and 0.29% for those with co-infection between hepatitis B and C. The SMR for liver-related death for HCV infection was 16.8. Importantly, among those with HCV infection, the incidence of death (0.27% per year) and SMR (19.3) from drug-related causes were actually higher than those from liver-related causes, a trend more pronounced in women and younger age (<40 years) groups.
In the United States, although gastroenterologists and hepatologists have long been aware that end-stage liver disease and HCC are important causes of death in patients with HCV infection, reliable population-based data about the mortality impact of HCV are sparse. For example, although up to 4 million Americans are infected with HCV, it has been estimated that only a small proportion of those infected, approximately 10,000, are estimated to die of sequelae of HCV infection. This translates to a mortality risk of approximately 0.3% per year on average. If an average person with HCV infection lives 30–40 years after the onset of infection, the lifetime risk of liver-related mortality may be about 10%. This indicates that 90% of our patients with HCV infection will die of a “natural” cause. Moreover, as Neal et al demonstrate, a substantial proportion of those who died of liver-related causes also had excessive alcohol consumption, further reducing the significance of HCV as an important cause of liver-related mortality. If these estimates are extrapolated to the US statistics, one would surmise that the mortality risk in Americans infected with HCV is not too different from that reported by Amin et al (0.14% per year).
The debate about the natural history of HCV infection and its significance on mortality seems to have lost favor recently. On the one hand, if the infection can be cured without a risk to the patient and at a low cost to the health care system, it may not be relevant how likely a given patient is going to develop serious liver disease with associated morbidity and mortality; treating everyone with the infection would be the best strategy. On the other hand, if therapy is associated with many adverse events and a high cost, attempts to direct treatment to patients who are most likely to experience poor outcome from HCV infection would make more sense. At the dawn of a new era of specific antiviral agents against HCV, we hope that the former scenario may materialize in the near future. However, as of 2008, we submit that it is still relevant for clinicians to make the best judgment as to whom to treat and whom to monitor while withholding therapy.
There are limitations to the data by Neal et al and other papers such as that of Amin et al. First, the incidence of late consequences of HCV infection increases with the duration of infection (Lancet 1997;349:825–832). As many American (and likely European and Australian) patients with HCV infection may be in their 3rd or 4th decade of infection, the incidence of liver-related death among HCV-infected individuals may accelerate in the future. Second, most of these studies are based on death certificates for determination of the cause of death. At least in the United States, death certificates are often incomplete and data based on death certificates tend to underestimate the true burden of the disease in question. Thus, not all deaths from HCV infection are attributed to the same, resulting in a falsely low estimate of the burden. Last, epidemiology data based on disease registry, by definition, exclude individuals whose HCV infection has not been diagnosed. Further, the proportion of undiagnosed HCV is likely much lower in subjects with evidence of liver disease than those without. This leads to an overestimation of the mortality risk because the denominator population (everyone with HCV) is underestimated. These different biases introduce inaccuracies in the estimation of mortality risk attributable to HCV infection.
Given these considerations, what are we to make of these data? First, it remains pertinent that the clinician exercise the best judgment to estimate the future risk of an individual patient. As noted, not all patients with chronic hepatitis C have premature mortality from the infection and, in fact, the majority of patients with HCV are likely to live their natural life span. Therefore, efforts to estimate the risk of progression to serious liver disease continue to be of importance. In this sense, measures to gauge the progression of fibrosis, such as a liver biopsy or noninvasive measures of liver stiffness continue to be important. As we await more effective pharmaceutical agents to become available, hopefully in the near future, watchful waiting may be a very good strategy in those patients with minimal to mild liver disease and low likelihood of response to current therapy. Second, in the opposite situation, where antiviral therapy is likely highly to be successful and well tolerated, estimating the future risk of morbidity and mortality becomes less critical. Examples may include patients with genotype 2 and those with genotype 3 with low viral load in whom it may be possible to shorten the therapy to 12–16 weeks. Finally, both Neal et al and Amin et al highlight the importance of comorbid conditions prevalent in patients with HCV infection, such as drug addiction and alcohol abuse. Management of these patients is a challenging problem for clinicians and a multidisciplinary approach is necessary to address not only their liver disease but also co-existent psychosocial conditions, including depression and chemical addiction.
In the United States, although gastroenterologists and hepatologists have long been aware that end-stage liver disease and HCC are important causes of death in patients with HCV infection, reliable population-based data about the mortality impact of HCV are sparse. For example, although up to 4 million Americans are infected with HCV, it has been estimated that only a small proportion of those infected, approximately 10,000, are estimated to die of sequelae of HCV infection. This translates to a mortality risk of approximately 0.3% per year on average. If an average person with HCV infection lives 30–40 years after the onset of infection, the lifetime risk of liver-related mortality may be about 10%. This indicates that 90% of our patients with HCV infection will die of a “natural” cause. Moreover, as Neal et al demonstrate, a substantial proportion of those who died of liver-related causes also had excessive alcohol consumption, further reducing the significance of HCV as an important cause of liver-related mortality. If these estimates are extrapolated to the US statistics, one would surmise that the mortality risk in Americans infected with HCV is not too different from that reported by Amin et al (0.14% per year).
The debate about the natural history of HCV infection and its significance on mortality seems to have lost favor recently. On the one hand, if the infection can be cured without a risk to the patient and at a low cost to the health care system, it may not be relevant how likely a given patient is going to develop serious liver disease with associated morbidity and mortality; treating everyone with the infection would be the best strategy. On the other hand, if therapy is associated with many adverse events and a high cost, attempts to direct treatment to patients who are most likely to experience poor outcome from HCV infection would make more sense. At the dawn of a new era of specific antiviral agents against HCV, we hope that the former scenario may materialize in the near future. However, as of 2008, we submit that it is still relevant for clinicians to make the best judgment as to whom to treat and whom to monitor while withholding therapy.
There are limitations to the data by Neal et al and other papers such as that of Amin et al. First, the incidence of late consequences of HCV infection increases with the duration of infection (Lancet 1997;349:825–832). As many American (and likely European and Australian) patients with HCV infection may be in their 3rd or 4th decade of infection, the incidence of liver-related death among HCV-infected individuals may accelerate in the future. Second, most of these studies are based on death certificates for determination of the cause of death. At least in the United States, death certificates are often incomplete and data based on death certificates tend to underestimate the true burden of the disease in question. Thus, not all deaths from HCV infection are attributed to the same, resulting in a falsely low estimate of the burden. Last, epidemiology data based on disease registry, by definition, exclude individuals whose HCV infection has not been diagnosed. Further, the proportion of undiagnosed HCV is likely much lower in subjects with evidence of liver disease than those without. This leads to an overestimation of the mortality risk because the denominator population (everyone with HCV) is underestimated. These different biases introduce inaccuracies in the estimation of mortality risk attributable to HCV infection.
Given these considerations, what are we to make of these data? First, it remains pertinent that the clinician exercise the best judgment to estimate the future risk of an individual patient. As noted, not all patients with chronic hepatitis C have premature mortality from the infection and, in fact, the majority of patients with HCV are likely to live their natural life span. Therefore, efforts to estimate the risk of progression to serious liver disease continue to be of importance. In this sense, measures to gauge the progression of fibrosis, such as a liver biopsy or noninvasive measures of liver stiffness continue to be important. As we await more effective pharmaceutical agents to become available, hopefully in the near future, watchful waiting may be a very good strategy in those patients with minimal to mild liver disease and low likelihood of response to current therapy. Second, in the opposite situation, where antiviral therapy is likely highly to be successful and well tolerated, estimating the future risk of morbidity and mortality becomes less critical. Examples may include patients with genotype 2 and those with genotype 3 with low viral load in whom it may be possible to shorten the therapy to 12–16 weeks. Finally, both Neal et al and Amin et al highlight the importance of comorbid conditions prevalent in patients with HCV infection, such as drug addiction and alcohol abuse. Management of these patients is a challenging problem for clinicians and a multidisciplinary approach is necessary to address not only their liver disease but also co-existent psychosocial conditions, including depression and chemical addiction.
Dragonslayer, Marcia-- You are more than welcome for the info. Mortality is something everyone reflects on occasionally, and with a chronic disease perhaps a bit more than we should sometimes ;) This study seemed to be more thorough than some others I have read on this topic, including the two cited by the author of the article. I'm glad you found it useful.
virt- I don't think you have much too much to worry about. lol I've known slow fibrosers before but your numbers are the best I've ever seen !
virt- I don't think you have much too much to worry about. lol I've known slow fibrosers before but your numbers are the best I've ever seen !
Thanks for that insightful information.
Based on my known risk factors, I've been infected for 28 years and I'm stage 0, grade .25. So, hopefully I'm not going to take a downward spiral in the next 10 years or so, lol:
"If an average person with HCV infection lives 30–40 years after the onset of infection, ..."
V
Based on my known risk factors, I've been infected for 28 years and I'm stage 0, grade .25. So, hopefully I'm not going to take a downward spiral in the next 10 years or so, lol:
"If an average person with HCV infection lives 30–40 years after the onset of infection, ..."
V
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
