An exciting new journal called "Clinical Liver Disease"-(CLD) has recently been launched, you can view the February issue here. This journal is an official digital educational resource from the American Association for the Study of Liver Diseases.
This March articles from the journal have been released for open access. The article topics are listed below. Visitors are able to view videos, full data, and download files in either HTML or PDF formats.
The first article has been posted on the blog below
Stevan A. Gonzalez and Gary L. DavisArticle first published online: 6 MAR 2012 | DOI: 10.1002/cld.3
Additional Articles
A brief history of the treatment of viral hepatitis C (pages 6–11)
Doris B. Strader and Leonard B. Seeff
Article first published online: 6 MAR 2012 | DOI: 10.1002/cld.1
Watch the interview with the authors
Watch the video presentation of this article
The new standard of HCV therapy: Treatment in therapy-naive patients (pages 12–15)
Saurabh Agrawal and Paul Y. Kwo
Article first published online: 6 MAR 2012 | DOI: 10.1002/cld.7
Watch the interview with the authors
The new standard of HCV therapy: Retreatment in experienced patients (pages 16–19)
Naveen Gara and Marc G. Ghany
Article first published online: 6 MAR 2012 | DOI: 10.1002/cld.4
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Watch the video presentation of this article
The long-term horizon: Patients who will remain untreated in the era of triple therapy (pages 20–23)
Andrew Aronsohn and Donald Jensen
Article first published online: 6 MAR 2012 | DOI: 10.1002/cld.5
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The horizon: New targets and new agents (pages 24–27)
Alison B. Jazwinski and Andrew J. Muir
Article first published online: 6 MAR 2012 | DOI: 10.1002/cld.2
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Introduction To The New Journal
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It is with great enthusiasm that I welcome you to an exciting new educational product. It is called Clinical Liver Disease, and it is an official digital educational resource from the American Association for the Study of Liver Diseases.Clinical Liver Disease is an online educational journal that takes advantage of new technology to provide online information on the rapidly changing field of hepatology. This topic-focused resource selects a clinically relevant area within hepatology with new and emerging knowledge and presents it to you in written, audio, and video formats. All contributions to Clinical Liver Disease will be commissioned from thought leaders in hepatology. We will offer continuing medical education and board exam style questions and answers.More than anything else, our goal is to provide you with cutting-edge information related to the care of the patient with liver disease—whenever you want it and in whatever format you prefer. With Clinical Liver Disease, you can learn from some of the leading authorities in hepatology. Anytime. Anywhere.Whether you are a doctor, advanced practice nurse, student, fellow, resident, or any other health care professional interested in advances in liver disease, Clinical Liver Disease is designed for you. We are pleased that we can make Clinical Liver Disease free to the user because of financial support provided to the publication in the form of educational grants.So, let me be the first to welcome you to Clinical Liver Disease. We want to hear from you about the content and format and about topics and authors of interest to you. We invite you to comment on controversies and challenging new information. Most of all, with Clinical Liver Disease, we hope to provide you the opportunity to never stop learning.
Volume 1, Issue 1, pages 2–5, February 2012
Demographics of hepatitis C virus today
Gary L. Davis M.D.2
Article first published online: 6 MAR 2012
DOI: 10.1002/cld.3
Copyright © 2012 the American Association for the Study of Liver Diseases
Watch the interview with the authors
Watch the video presentation of this article
It is currently estimated that 3 to 4 million individuals in the United States and up to 170 million individuals worldwide are chronically infected with hepatitis C virus (HCV).1–3 HCV remains the most common chronic blood-borne infection in the United States and accounts for up to two-thirds of newly diagnosed cases of chronic liver disease.3, 4 Because HCV is primarily transmitted through parenteral routes, populations known to have a particularly increased risk of exposure to HCV include recipients of blood transfusions before 1992 or coagulation factors before 1987, hemophiliacs, hemodialysis patients, individuals infected with human immunodeficiency virus (HIV), and injection drug users.5 Consequently, these groups are included in the current recommendations for identifying individuals who would benefit from screening5, 6 (Table 1). Although these recommendations have been in place for more than a decade, it remains questionable whether this strategy has been effective in identifying individuals with chronic HCV infections, most of whom were born between 1945 and 1964.3 An additional consideration is that certain populations with the greatest prevalence of HCV, such as injection drug users, incarcerated individuals, and the homeless, may not have access to health care or may not be included in population-based surveillance programs; as a result, the true prevalence of HCV may be underestimated.1 Injection drug use remains the most frequent means of HCV transmission in the United States; the seroprevalence of the antibody to HCV may rise to more than 70% with 3 to 5 years of habitual exposure7, 8 (Fig. 1). Efforts to implement prevention and treatment strategies in this population may become increasingly important for controlling new HCV infections.
Figure 1. Risk factors for exposure occurring within 6 months of the presentation of an acute HCV infection (identified in 2075 individuals included in a national surveillance program conducted by the Centers for Disease Control and Prevention from 1994 to 2006).
*The HCV-positive sex partner category includes both known and suspected HCV positivity.
**The aggregate risk category indicates circumstances in which the individual acknowledged an exposure risk but would not specify the category.
Adapted with permission from Archives of Internal Medicine.7
Injection drug users or individuals with a history of injection drug use
Individuals infected with HIV
Individuals with hemophilia
Recipients of clotting factors or other blood products before 1987
Hemodialysis patients
Individuals with elevated liver enzyme levels
Recipients of solid organ transplants before 1992
Recipients of blood transfusions before 1992
Children born to HCV- positive mothers
Individuals with any known potential exposure via HCV-positive blood donors, organ donors, or occupational exposures
Sexual partners of HCV-infected individuals
This table was adapted with permission from Hepatology
5 and MMWR Recommendations and Reports.6
HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus.
The importance of effective screening strategies is highlighted by the recent availability of increasingly effective antiviral therapy.9, 10 The achievement of long-term viral clearance after a course of antiviral therapy, which is defined as a sustained virological response, is durable and demonstrates that the eradication of HCV is possible with successful treatment.11, 12 In addition, the successful treatment of an HCV infection can have a major impact on the natural history of HCV-associated chronic liver disease because the achievement of a sustained virological response may result in a substantial decrease in the risk of hepatocellular carcinoma (HCC) and liver-related mortality.13–17 Although an important step in minimizing the overall burden associated with HCV infections is the identification of individuals with chronic HCV who may be candidates for antiviral therapy, emerging data suggest that the majority of individuals with chronic HCV have not been diagnosed and remain untreated (Fig. 2). As many as 75% of those with chronic HCV in the United States are unaware that they are infected.18 In addition, only a small proportion of those diagnosed with chronic HCV undergo antiviral therapy.19–22 Barriers to treatment may include a failure to identify the infection, a lack of awareness of the seriousness of the infection, limited access to adequate health care or insurance, a fear of treatment side effects, and misperceptions about the effectiveness of treatment.23 Outlining a national strategy for the prevention and control of HCV, a recent report by the Institute of Medicine emphasized these findings and stressed the importance of increased awareness, recognition, and management of chronic HCV.18
Figure 2. Estimated proportions of individuals with chronic HCV in the United States who have been diagnosed with HCV and have then undergone antiviral therapy.18–22
Up to 85% of adults acutely exposed to HCV progress to a chronic infection; at least 20% of these individuals may progress to advanced liver disease over a 20- to 30-year period.24 Factors associated with an increased risk of disease progression include the duration of the HCV infection, heavy alcohol intake, advanced age, obesity, fatty liver disease, male sex, and HIV coinfection with low CD4 cell counts.25 Chronic liver disease associated with HCV is a major health care burden in the United States and globally and results in significant morbidity and mortality. Currently, more than 12,000 deaths occur annually in the United States as a result of HCV-related liver disease,26 and the number of deaths attributable to HCV may be greater than 360,000 per year on a global scale.27 As individuals with HCV continue to age and their duration of chronic infection increases, the prevalence of advanced hepatic fibrosis, end-stage liver disease, and HCC is also increasing. Indeed, the prevalence of cirrhosis and decompensation has doubled over the last decade, and the prevalence of HCC has increased 20-fold.28 Although HCV remains the leading indication for liver transplantation in the United States, the proportion of cases attributable to HCV appears to have plateaued, perhaps because of the aging of these individuals. However, the proportion of transplants related to HCC is rapidly increasing, and most of these cases are due to HCV29–31 (Fig. 3).
Figure 3. Number of liver transplants performed in the United States for chronic HCV and HCC on a yearly basis from 1992 to 2010 (based on data from the Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients).32
It has been projected that the overall prevalence of HCV in the United States will decline over the next 2 decades; however, the health care and social burden associated with advancing HCV-related liver disease will continue to rise.33, 34 Predictive modeling has estimated that by 2030, the proportion of individuals with chronic HCV who have cirrhosis will approach 50% (Fig. 4). Likewise, the prevalence of clinical decompensation and HCV-associated HCC is expected to increase during this time period. In addition, the annual number of liver-related deaths attributed to chronic HCV could more than double in the years leading up to 2030.33 Ultimately, this trend will have an economic impact as well. The estimated economic burden of HCV in the United States in 1997 was $5.5 billion.35 This amount is expected to nearly double to just under $10 billion per year over the next decade.36
Figure 4. Projected prevalence of cirrhosis in individuals with chronic HCV in the United States through 2030 (based on predictive modeling data).33
Antiviral therapy should decrease the prevalence of cirrhosis and liver-related deaths associated with HCV. The impact of therapy should become more pronounced as the efficacy of treatment improves. The treatment of half of HCV-infected persons today could result in overall decreases of 30% to 40% in liver failure, HCC, and liver-related mortality over the next decade.33 These findings highlight the importance of the early detection and selection of treatment candidates. An improved understanding of the demographics of HCV infection may lead to more effective screening strategies, which could possibly include both a targeted approach and the casting of a wider net based on age groups at the greatest risk for past exposure.37 Ultimately, the control of new HCV infections will require continued efforts to educate and increase awareness in populations at the greatest risk, including those exposed to injection drug use.
References
- 1 , , , , . Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int 2011;31:1090–1101.
Direct Link: - 2 . Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011;17:107–115.
Direct Link: - 3 , , , , , . The prevalence of hepatitis C virus infection in the United States, (1999 through 2002). Ann Intern Med 2006;144:705–714.
- 4 , , , , , , et al. The epidemiology of newly diagnosed chronic liver disease in gastroenterology practices in the United States: results from population-based surveillance. Am J Gastroenterol 2008;103:2727–2736.
Direct Link: - 5 , , , ; for American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009;49:1335–1374.
Direct Link: - 6 Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47:1–39.
- 7 , , , . Incidence and transmission patterns of acute hepatitis C in the United States, 1982–2006. Arch Intern Med 2011;171:242–248.
- 8 , , , , , , et al. Seroprevalence of hepatitis C virus and hepatitis B virus among San Francisco injection drug users, (1998 to 2000). Hepatology 2007;46:666–671.
Direct Link: - 9 , , , , , , et al.; for ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011;364:2405–2416.
- 10 , , , , , , et al.; for SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011;364:1195–1206.
- 11 , , , , , , et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology 2008;135:821–829.
- 12 , , , , , , et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 1997;127:875–881.
- 13 , , , , , , et al. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol 2010;8:192–199.
- 14 , , , , , , et al.; for Italian Association of the Study of the Liver Disease (AISF). Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology 2007;45:579–587.
Direct Link: - 15 , , , , , , et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 2008;149:399–403.
- 16 , , , , , , et al. Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol 2009;104:1147–1158.
- 17 , , , , , , et al. Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol 2007;46:206–212.
- 18 Colvin HM, Mitchell AE, eds. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: National Academies Press; 2010.
- 19 , , , . Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology 2009;50:1750–1755.
Direct Link: - 20 , , , . Management of patients with hepatitis C in a community population: diagnosis, discussions, and decisions to treat. Ann Fam Med 2004;2:116–124.
- 21 , , . Barriers to the treatment of hepatitis C. Patient, provider, and system factors. J Gen Intern Med 2005;20:754–758.
- 22 , , , , , , et al. Clinical pathways for patients with newly diagnosed hepatitis C—what actually happens. J Viral Hepat 2006;13:264–271.
Direct Link: - 23 , , , . Identification and management of hepatitis C patients in primary care clinics. Am J Gastroenterol 2003;98:639–644.
Direct Link: - 24 . Natural history of chronic hepatitis C. Hepatology 2002;36(suppl 1):S35-S46.
Direct Link: - 25 , , , , , , et al. Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol 2006;44(suppl):S19-S24.
- 26 Centers for Disease Control and Prevention. Disease burden from viral hepatitis A, B, and C in the United States. http://www.cdc.gov/hepatitis/hcv/StatisticsHCV.htm. Accessed January 2012.
- 27 , , , , . The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529–538.
- 28 , , , , , , et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology 2011;140:1182–1188.
- 29 , , . Indications for liver transplantation. Gastroenterology 2008;134:1764–1776.
- 30 , . Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557–2576.
- 31 , , . Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from (1975 to 2005). J Clin Oncol 2009;27:1485–1491.
- 32 Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov. Accessed January 2012.
- 33 , , , , . Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 2010;138:513–521.
- 34 , , , , , , et al. Applying a system approach to forecast the total hepatitis C virus-infected population size: model validation using US data. Liver Int 2011;31(suppl 2):4–17.
Direct Link: - 35 , , , . Costs of hepatitis C. Arch Intern Med 2001;161:2231–2237.
- 36 , , , . Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health 2000;90:1562–1569.
- 37 , , , , , , et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med 2012;156:263–270.
