Saturday, February 4, 2017

Weekend Reading - Natural History And Conditions Related To HCV

Greetings to all, welcome to this edition of Weekend Reading. Thanks to Henry E. Chang, a quick overview of HCV and related conditions is the focus on the blog today. The good doctor often tweets PDF full text HCV articles on twitter, follow him here.

The Stats
Today, approximately 2.7 million Americans are infected with hepatitis C, with an estimated 130–200 million people worldwide. Of persons infected with hepatitis C, 15-25 percent will recover (spontaneous clearance) and 75-85 percent will become chronically infected.

A Review of the Natural History of Chronic Hepatitis C Infection
The natural history of hepatitis C remains controversial. Among HCV-infected individuals progression to advanced liver disease generally requires decades but is influenced by several host factors. For instance studies have shown factors such as; (age, sex, race, genetics), viral characteristics (genotype), behavioral (smoking, alcohol), metabolic factors (insulin resistance, obesity), and co-infection (Hepatitis B and HIV) may impact the degree of fibrosis and progression to cirrhosis as well as the potential for development of liver cancer. These factors are discussed in a review of the natural history of hepatitis C, published in the 2014 issue of  North American Journal Of  Medicine And Science.

Does Alcohol  Influence Spontaneous Clearance?
The effects of alcohol on spontaneous clearance of acute hepatitis C virus infection in females versus males; Results indicate that abstaining from drinking alcohol may increase the likelihood of spontaneous clearance among women.

Although, chronic infection can be cured about 90% of the time with FDA approved treatments, host factors still determine disease progression in people without viral eradication. As an example, persons with HCV-related cirrhosis, who consume light-to-moderate alcohol, compared to people who do not drink - increase the risk for liver cancer.

But can host factors influence mortality risk in people who successfully clear the virus with HCV therapy?
In an article reviewing a study published in the Journal of Hepatology (2016), Michael Carter writes about the mortality rates among people with HCV who achieve SVR. Again, host factors/health risk behaviors were an important factor for mortality. He writes; Most of the excess mortality was due to drug use or liver cancer. Several modifiable characteristics were associated with subsequent mortality risk, including drug use and heavy alcohol consumption. People without these risk factors – approximately a third of the study population – had survival that matched that of the general population. Here is the article; People with HCV attaining SVR continue to have increased mortality risk but this is due to alcohol and drug use.

Disease Progression
Researchers often reference a unique cohort of HCV patients when describing the natural history of hepatitis C. Never has there been a more perfect natural history study, in that - the known dates of infection were clear and precise. This for the most part is difficult to achieve since the time of acute HCV infection is often impossible to establish.

The somewhat famous and tragic cohort include 704 Irish women (1977-1978) and 917 German women (1978-1979) who were exposed to hepatitis C from contaminated Anti-D immunoglobulin, all from a single source. Researchers have studied the aging population of women at 17, 20, 25 and 35 years after infection.

In the German cohort previous studies suggest low rates of liver disease progression at 20 and 25 years after infection, showing only 0.5% end-stage liver cirrhosis at 25 years after infection, according to an article published in Hepatology 2014;58:49–57.

In the article investigators extended the study to 35 years after infection comprising of 718 patients of the original anti-D cohort.

Mortality at 35 Years After Infection
Figure 4 summarizes the overall mortality of the German HCV cohort at 35 years after infection in relation to the HCV infection status.

In total, 30 patients (4.2%) of the actual study cohort died since 1979. In the group of HCV RNA-negative patients, 10 (3.0%) died, among them 2 who were classified as inoculated patients without hepatitis, 7 with spontaneous recovery from HCV infection, and 1 with SVR after treatment who died of a malignant disease other than HCC.

In the group of HCV RNA-positive patients, 20 (5.3%) died, among them 9 (1.3%) who succumbed to definite HCV-related end-stage liver complications, such as esophageal variceal bleeding or hepatic coma. The remaining 11 HCV RNA-positive patients (1.5%) died from additional non-liver-related causes, such as cardiac failure, nonliver malignancy, apoplectic insult, or accident.

Click on image to enlarge

Conclusion: The present study provides further evidence for a mild, but significant, disease progression at 35 years after infection in the German HCV (1b)-contaminated anti-D cohort. Patients with self-limited HCV infection or SVR after antiviral treatment were protected from progressive liver disease and showed the best clinical long-term outcome.
Review the article; Evaluation of liver disease progression in the German HCV (1b)-contaminated anti-D cohort at 35 years after infection.

Of Interest
New study launched to discover how “super” immune system can prevent hepatitis C
Scientists from Trinity College Dublin are seeking volunteers who were exposed to anti-D contaminated with hepatitis C virus (HCV) between 1977 and 1979 as they attempt to discover why some people are naturally protected from HCV infection, while others are not.

Extrahepatic Manifestations
Review this series of great articles on the extrahepatic manifestations of HCV.
Published in Journal of Advanced Research
Volume 8, Issue 2, March 2017, Pages 85–87

Index Of Articles
HCV - Fatty liver disease and genotype 3
In this post a collection of journal articles and videos reviewing HCV and fatty liver disease is offered; with a focus on individuals afflicted with both conditions. In addition given the development of steatosis (abnormal levels of fat in your liver) is higher in people with HCV and genotype 3, links are provided to current therapies in this difficult to cure genotype. Finishing off with several tips to help keep your liver healthy.

An Overview Of Hepatitis C Medications
Treatment Options in Hepatitis C — The Current State of the Art
By Stefan Zeuzem published in the January 2017 issue of Deutsches Ärzteblatt International
This review is based on relevant publications retrieved by a selective literature search, and particularly on studies and reviews concerning the course and treatment of hepatitis C.
Begin here...

Clinical Care Options
How Data From the 2016 Boston Hepatology Meeting Will Influence Future HCV Patient Management
Mark S. Sulkowski MD - 1/31/2017
I am really enjoying treating patients with HCV infection in this era of highly effective direct-acting antivirals (DAAs). Think about it: Our patients present with life-threatening, chronic infections, and we cure more than 95% of them with few adverse events. Other than insurance challenges, what’s not to love?
Despite the relatively easy road to cure with modern therapy in most of my HCV-infected patients, I can think of 2 recent patients who presented challenges: a patient with relapse and resistance associated substitutions (RASs) after treatment with a DAA and a patient with genotype 3 HCV infection and severely reduced renal function...
*Free registration required to view article

Achieving A Cure
Liver- and Non-Liver Related Critical Events Down in HCV and Cirrhosis
For patients with hepatitis C virus (HCV) infection and biopsy-proven cirrhosis, sustained viral response (SVR) is associated with a reduction in critical events, both liver and non-liver related, according to research recently published in Gastroenterology.

Helpful Links

HCV Advocate
Clinical Trials Reference Guide
Users can search for a hepatitis C clinical trial by category (genotype), or learn how to evaluate a clinical trial and become familiar with commonly used terms. HCV Advocate offers an easy to navigate HCV Medications Blog as well, organized by HCV genotype.

2017-HCV Genotypes/Treatment
Offered on this page of the blog is research updates with a focus on treating HCV according to genotype using FDA approved and investigational medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities. 

Hopefully, this small summary will leave you with a better understanding of the natural history of  hepatitis C, conditions outside the liver (Extrahepatic Manifestations) and medications used to treat the virus.   

May you all enjoy the rest of your weekend.

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