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Hepatitis C: A Bitter Harvest
EDITORIAL
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"A self-limited epidemic of injection drug use over several decades amplified the transmission of hepatitis C, we are now seeing the delayed, bitter harvest of chronic liver disease"
note from Jules Levin: about 30% of HIV-infected individuals are coinfected with HCV (about 300,000 coinfected persons in the USA). The proportion is much higher among the undereducated, poor and underserved patient groups (as is the case in HCV monoinfection), and these are the ones most likely accessing their health care and services through the Ryan White Care Act. It is imperative to address their HCV-related healthcare needs immediately.)
Jules L. Dienstag, MD
From Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114.
Annals of Internal Medicine
16 May 2006 | Volume 144 Issue 10 | Pages 770-771
".....approximately 4 million persons-had serum antibodies to HCV (anti-HCV), serologic evidence of past or current infection. Approximately 3 million persons had detectable levels of serum HCV RNA.... Because fewer than 1 million of these infected persons have come to clinical attention, we have encountered only the proverbial tip of the iceberg..... despite a dramatic 80% reduction in the annual incidence of new, acute HCV infections in the 1990s (7, 8), the prevalence of HCV infection in the United States remained constant..... U.S. citizens who have had HCV infection for 20 years or more will continue to increase; this "wave" is expected to crest in 2015 and then dissipate as members of the cohort die of causes unrelated to HCV infection.... What accounts for this curious distribution of HCV infection? Almost half of the anti-HCV-positive group between 20 and 59 years of age reported a history of injection drug use, generally in the remote past: The cohort of persons with HCV infection who are now 40 to 59 years of age acquired their infections primarily through injection drug use that began in the 1960s and peaked in the 1980s. Most of these anti-HCV-positive individuals are part of the "baby-boomer" generation, which came of age in the 1960s and 1970s during a time of widespread experimentation with substances of abuse.... most of the surveyed population with detectable anti-HCV had engaged in "risky" behavior "at some point in their lives"... Many had probably experimented with injection drugs transiently during adolescence and early adulthood.... many had suppressed long-forgotten flirtations with such risky behaviors; this "selective amnesia" was documented among volunteer blood donors with HCV infection. This cohort has lived with unrecognized HCV infection for several decades; however, as they age, they are more likely to seek regular medical care and apply for life insurance, unearthing their HCV infection....."
article text
We know a lot about chronic infection with hepatitis C virus (HCV): It affects 170 million people worldwide, accounts for approximately 40% of all cases of chronic liver disease, can be associated with hepatic decompensation and hepatocellular carcinoma, and is the most common indication for liver transplantation (1). Although we have learned so much about this disease during the past 3 decades, we continue to be surprised by new insights and revelations.
In this issue, 2 articles on HCV infection reinforce the far-reaching nature of this disease. In a thought-provoking article, McGuire and colleagues (2) describe the frequent occurrence of glomerulonephritis in patients with HCV-associated cirrhosis who undergo liver transplantation. Although we tend to attribute renal compromise in such patients to tubular injury, this report adds to evidence (3, 4) that glomerular lesions are unappreciated, suggesting that we should evaluate renal injury more thoroughly before and after liver transplantation.
In the other article, Armstrong and colleagues at the Centers for Disease Control and Prevention (5) focus attention on another inadequately recognized dimension of HCV infection by presenting an updated analysis of the prevalence and acquisition of HCV. This article, which is based on data collected between 1999 and 2002 as part of the National Health and Nutrition Examination Survey (NHANES), provides a valuable perspective on how human behaviors have contributed to the scourge that hepatitis C has become.
A previous NHANES analysis conducted between 1988 and 1994 (6) showed that 1.8% of the U.S. population- approximately 4 million persons-had serum antibodies to HCV (anti-HCV), serologic evidence of past or current infection. Approximately 3 million persons had detectable levels of serum HCV RNA, virologic evidence of ongoing infection. This substantial prevalence of infection translates into an enormous burden of chronic liver disease and its future consequences. Because fewer than 1 million of these infected persons have come to clinical attention, we have encountered only the proverbial tip of the iceberg.
In the 1999-2002 NHANES, 1.6% of the U.S. population was anti-HCV-positive and 1.3% was HCV RNA-positive, which means that the earlier decade's levels of 4 million ever infected and 3 million still infected have not changed (5). Therefore, despite a dramatic 80% reduction in the annual incidence of new, acute HCV infections in the 1990s (7, 8), the prevalence of HCV infection in the United States remained constant. The recent survey showed that age-stratified peak prevalence had shifted from persons between 30 and 39 years of age to those between 40 and 49 years of age. This secular trend reflects the aging of the same cohort with HCV infection that was identified during the 1988-1994 survey (the generation born between 1945 and 1964). Therefore, in the absence of a high incidence of new infections in the 1990s, a reservoir of infections acquired 2 to 3 decades ago has sustained the prevalence of HCV infections. This trend follows earlier predictions that the number of U.S. citizens who have had HCV infection for 20 years or more will continue to increase; this "wave" is expected to crest in 2015 and then dissipate as members of the cohort die of causes unrelated to HCV infection (7).
What accounts for this curious distribution of HCV infection? Armstrong and colleagues marshal convincing evidence to support the role of injection drug use as the paramount risk factor for HCV infection. Almost half of the anti-HCV-positive group between 20 and 59 years of age reported a history of injection drug use, generally in the remote past; among the 89 adults who reported ever having used injection drugs, almost 60% were anti-HCV-positive. Furthermore, the investigators' multiple logistic regression analysis showed that injection drug use increased the risk for HCV exposure by a factor of almost 150 (based on an adjusted relative odds ratio). This dwarfs by far the odds ratio for any other risk factor, including high-risk sexual behavior.
The cohort of persons with HCV infection who are now 40 to 59 years of age acquired their infections primarily through injection drug use that began in the 1960s (7, 9) and peaked in the 1980s (7). Most of these anti-HCV-positive individuals are part of the "baby-boomer" generation, which came of age in the 1960s and 1970s during a time of widespread experimentation with substances of abuse. As Armstrong and colleagues emphasize, most of the surveyed population with detectable anti-HCV had engaged in "risky" behavior "at some point in their lives" (5). Many had probably experimented with injection drugs transiently during adolescence and early adulthood. Potentially, many had suppressed long-forgotten flirtations with such risky behaviors; this "selective amnesia" was documented among volunteer blood donors with HCV infection (10). This cohort has lived with unrecognized HCV infection for several decades; however, as they age, they are more likely to seek regular medical care and apply for life insurance, unearthing their HCV infection.
In this updated NHANES, other risk factors for HCV infection were also identified, including sexual promiscuity (20 or more lifetime sexual partners) and, among anti-HCV-positive persons 60 years of age and older, a history of blood transfusion before 1992 (the year in which highly sensitive donor-blood screening for HCV infection was fully implemented). After adjustment for other variables, however, blood transfusion was not associated significantly with serologic evidence of HCV infection. This observation is consistent with the negligible contribution to the prevalence of hepatitis C of reported transfusion-associated cases (among which, ironically, HCV was first recognized and ultimately identified) even before screening measures were adopted to eliminate HCV from the blood supply (11). The dramatic reduction in new cases of HCV infection reported in the United States during the 1990s paralleled the decline in acute cases among injection drug users (8, 11) that, in turn, seems to have resulted from the drug-using community's efforts to modify its behaviors to prevent the transmission of HIV/AIDS.
Armstrong and colleagues identify an independent (albeit weak) association between HCV infection and promiscuous sexual activity that seems to suggest that HCV is a sexually transmitted disease. Although sexual transmission can occur under unusual circumstances, dissecting the contribution of sexual activity in the setting of underlying, confounding injection drug use is difficult. Instead, sexual transmission of HCV is the exception rather than the rule-just as hepatitis A virus, which can be transmitted under extraordinary conditions by blood-product infusion (12), behaves as an enterically spread, not bloodborne, agent. This study also showed that anti-HCV was not increased among men who have sex with men, a very telling observation that also weighs heavily against efficient sexual transmission of HCV infection. In other studies of men who have sex with men, the risk for HCV infection was very low compared with that for hepatitis B virus and HIV infections, which are efficiently transmitted by sexual contact (13-15). Furthermore, the risk for HCV infection did not correlate with the intensity or duration of sexual exposure. Similarly, in studies of the monogamous sexual partners of persons with HCV infection, sexual transmission of HCV was absent or negligible, and risk factors other than sexual exposure accounted for most instances of HCV infection in both partners (16-18).
Ultimately, the new data build on those reported previously to paint a vivid portrait of hepatitis C in the United States. A self-limited epidemic of injection drug use over several decades amplified the transmission of hepatitis C, and we are now seeing the delayed, bitter harvest of chronic liver disease. Between the declining frequency of new infections and the exciting advances in antiviral therapy (1), we can look forward to a time in the near future when this legacy of epidemic injection drug use-the hepatic (and less recognized renal) consequences of HCV infection-will be behind us.
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