Hepatitis C: The Problem with Numbers, by Alan Franciscus, Editor-in-Chief

Originally Published July 15, 2015

A recently released journal article estimated that the real number of acute hepatitis C cases are much higher than the figures published by the Centers for Disease Control and Prevention (CDC).  This is not a revelation to those who work in HCV.  In this article, I will discuss the published numbers of acute and chronic HCV and what some experts believe is a better estimate of the number of acute, chronic and annual deaths caused by hepatitis C.

Acute
The CDC estimated that there were 29,700 acute cases of HCV in 2013 (range 23,500 to 101,400).  In the article, “Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System: A Case Series and Chart Review,” by S Onofrey, MPH et. al., published in the Annals of Internal Medicine, the authors challenged the way the CDC defined an acute case and compared the actual diagnosed cases to the number of diagnosed cases that fit the CDC definition. 

Note:  There are many problems with diagnosing acute HCV—there are no viral markers to distinguish acute vs. chronic.  Another issue is that most people acutely infected have no symptoms.

The current study took place in Massachusetts from 2001 to 2011.  There were 183 patients diagnosed with acute HCV, but only 149 cases were reported to the Massachusetts Department of Public Health.  Of these, 130 were classified as potential acute infection.  But only ONE met the national case definition that was reported to the CDC.  

This means that only 1% of acute HCV cases were ever reported to the CDC.  We know that there have been outbreaks of acute HCV around the country including recent outbreaks in regions in or near the Appalachia area. 

Chronic Hepatitis C
The CDC estimated that in 2013 there were 2.7 to 3.9 million people who were chronically infected with hepatitis C.  However, the NHANES survey doses not count certain populations such as prisoners, homeless, nursing home residents, people in mental institutions, nor active duty military—many of these populations have a very high incidence of hepatitis C.  If the populations that were excluded from the NHANES survey were to be included the number of people with chronic hepatitis C could reach 5 million Americans. 

Also if you include the surge of the new acute infections that would turn chronic this would also increase the total chronic infections.  It is all connected. 

HCV Deaths
The CDC estimated that there were 19,368 deaths caused by HCV in 2013.  There was also a footnote that read “Current information indicates these represent a fraction of deaths attributable in whole or in part to chronic hepatitis C.” 

Another article, “Mortality among Persons in Care with Hepatitis C Virus Infection—The Chronic Hepatitis Cohort Study (CHeCS), 2006–2010,” by R Mahajan and colleagues, was published in Clin Infect Disease 2014 Jun; 59(12)1792.  The study estimated the number of deaths caused by hepatitis C

In the study, 2,143,369 patients (MCOD group—all patients) seen between 2006 – 2010 at the CHeCS clinics were included in the analysis.  There were 11,703 (0.5%) HCV patients.  A total of 1,590 (14%) died and had HCV listed as the cause of death.  The majority were born between 1945 and 1965 (75%), white (50%), and male (68%).  The mean age was 59 yo. 

To illustrate why HCV is under reported on death certificates the following was mentioned in the study:

“Among the 1590 CHeCS members who died, only 306 (19%) had HCV infection listed as an underlying cause on their death certificate. Among people who died of liver cancer, only 32% had HCV listed as an underlying cause. Death certificates did not list HCV for most deaths regardless of whether the deaths were liver-related or not. Among CHeCS members who died, medical records (ICD-9 codes) noted liver disease in 63%, and FIB-4 scores indicated liver disease in 76%.”

The conclusion of the authors was that in 2010 listed deaths from hepatitis C only represent 1/5 of the 80,000 people with HCV who died that year—this figure includes 53,000 patients who had indications of chronic liver disease in their medical records. It’s important to remember that behind all these numbers are real people who have family, friends and loved ones.  As such they deserve to have medical care and treatment. And no one should die of hepatitis C!

http://hcvadvocate.org/news/newsLetter/2015/advocate0715_mid.html#1

Snapshots, by Alan Franciscus, Editor-in-Chief

Article:  Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials—ZM Younossi—et. al
   Source: Hepatology 2015 Jun;61(6):1798-808. doi: 10.1002/hep.27724. Epub 2015 Mar 18.

Results and Conclusions:  In the phase 3 clinical trials of ledipasvir and sofosbuvir with and without ribavirin patient report outcomes were measured.  There was a total of 1,952 patients in the study.  Patients were treated for 8, 12 or 24 weeks. In the groups that received ledipasvir and sofosbuvir (without ribavirin) who had early viral load suppression there was improved quality of life that was maximized by the end of treatment.  In the group that received ledipasvir/sofosbuvir and ribavirin their quality of life decreased regardless of treatment duration until the end of treatment. 

The Bottom Line:  Ribavirin during treatment reduced quality of life, but achieving a cure improved quality of life for all of the groups including the groups who received ribavirin.

 

Editorial Comments:  This is a no-brainer, but we need more of these studies to show that being cured improved quality of life and improved overall survival.  I hope that insurance companies are hearing this and loosen up the restrictions.

Article:  Antigenic cooperation among intrahost HCV variants organized into a complex network of cross-immunoreactivity—P Skums
  Source: Proc Natl Acad Sci USA. 2015 May 26;112(21):6653-8.doi:10.1073/pnas.1422942112. Epub 2015 May 4.

 

Results and Conclusions:
Most people who become acutely infected with hepatitis C become chronically infected – up to 85%.  The reason there is such a high rate of chronic infection is not completely understood, but there are many theories.  The current paper presented a mathematical model to show how the virus contributes to hepatitis C chronicity. 

What is interesting is that various proteins of the hepatitis C virus seem to act together to escape the human host—that is certain proteins of the virus work together to draw off parts of the immune system cells so that other parts of the hepatitis C virus can survive and persist in the body and infect liver cells. This enables the hepatitis C virus to act as a network of parts to establish a chronic infection.   

The Bottom Line:  As with any discovery in science these findings need to be replicated.  If the exact mechanism can be understood an effective protective vaccine could be developed. 

Editorial Comment:  Isn’t science interesting?  The hepatitis C virus is a wily little bugger and endlessly fascinating.  The key would be to understand why this strategy works for some and not others.   This could lead to the development of an effective vaccine.

 

Article: Differentiation of acute from chronic hepatitis C virus infection by nonstructural 5B deep sequencing: A population-level tool for incidence estimation—V. Montoya et. al
   Source:  Hepatology Volume 61, Issue 6, pages 1842–1850, June 2015

 

Results and Conclusions:  In the current study the authors examined the viral proteins from 13 acute and 54 chronic individuals by sequencing the NS5B region of the virus.  They were able to differentiate the viral diversity between the acute and chronic infection.  The viral diversity was significantly different between acute vs. chronic infection. 

 
Editorial Comment:  This and the last issue of the HCV Advocate have discussed the difficult task of trying to diagnose an acute infection of HCV.  If this study is replicated and IF the tool is made available at a reasonable cost it could be a game changer in the way we understand how many people are acutely infected with hepatitis C.

Source:  http://hcvadvocate.org/news/newsLetter/2015/advocate0815.html#3