Saturday, November 18, 2017

Clinical improvement after successful antiviral DAA therapy for hepatitis C

Follow-up of sustained virologic responders with hepatitis C and advanced liver disease after interferon/ribavirin - free treatment
Karin Kozbial 1 , Stephan Moser 2 , Ramona Al - Zoairy 3 , Remy Schwarzer 4 , Christian Datz 5 , Rudolf Stauber 6 , Hermann Laferl 7 , Michael Strasser 8 , S andra Beinhardt 1 , Albert Friedrich Stättermayer 1 , Michael Gschwantler 2 , H einz Zoller 3 , Andreas Maieron 4 ,9 , Ivo Graziadei 10 , Michael Trauner 1 , P etra Steindl - Munda 1 , Harald Hofer 1, 11 , P eter Ferenci

doi: 10.1111/liv.13629

Link To Article: https://jumpshare.com/v/HPTaAyMtTjxr5Wd8brk1
*Article downloaded and shared by Henry E. Chang‏ today on Twitter.

Key points
SVR is durable irrespective of the interferon - free DAA regimen used. 
Survival was excellent for patients with F3 and Child - Pugh A cirrhosis. 
Decompensation before or at baseline was significantly associated with decompensation and with death during follow-up . 
Despite successful therapy a risk of hepatocellular carcinoma remains among patients with cirrhosis, necessitating a regular follow-up

Vosevi & Mavyret: The Impact of New Options for DAA-Experienced Patients With HCV

Updated
Latest ClinicalThought commentaries from Clinical Care Options (CCO).

Over at Clinical Care Options, using an easy to follow patient case scenario experts discuss treatment options with newly approved drugs: Mavyret (glecaprevir/pibrentasvir) GLE/PIB and Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) SOF/VEL/VOX.

11/16/2017
The Impact of New Options for DAA-Experienced Patients With HCV
Jordan J. Feld MD, MPH - 11/16/2017
With the approvals of SOF/VEL/VOX and GLE/PIB, what is the new management approach for DAA-experienced patients with HCV infection?

In this viral hepatitis case series, we highlight common patient case scenarios and the critical decision making that informs selection of optimal patient management strategies. This commentary features a woman with cirrhosis who is seeking retreatment after failure of first-line direct-acting antiviral (DAA) therapy. The impact of the recent approvals of sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) and glecaprevir (GLE)/pibrentasvir (PIB) on treatment for this class of patient is discussed.

Case Details
A 59-year-old white woman with compensated cirrhosis (elastography 24 kPa) and genotype 1a HCV infection was previously treated with SOF/ledipasvir (LDV) for 12 weeks, but she experienced a relapse at posttreatment Week 6. She reports strict adherence to her previous regimen and is seeking advice on retreatment options.
Continue reading @ CCO

11/15/2017
How Recent Drug Approvals Have Affected First-line HCV Treatment
Nancy Reau MD, FAASLD, AGAF - 11/15/2017
What parameters now qualify a patient infected with HCV for shortened first-line therapy?

In this viral hepatitis case series, we highlight common patient case scenarios and the critical decision making that informs selection of optimal patient management strategies. This commentary features a treatment-naive, noncirrhotic patient who is infected with HCV and ready to begin therapy. The candidacy of this patient for 8-week vs 12-week therapy is discussed, with a focus on the latest treatment options and guidelines.

Case Details
A 56-year-old white man newly diagnosed with genotype 1a HCV infection presents for initiation of treatment. His baseline HCV RNA is 8,500,000 IU/mL and he has F2 fibrosis. He expresses a desire to take as short a course of HCV treatment as possible.
Continue reading @ CCO

*Free registration is required

Friday, November 17, 2017

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without SVR after interferon-based therapy

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy: Prioritize who needs urgent direct-acting antiviral agents
Huang, Chao-Min PhDa; Hu, Tsung-Hui MD, PhDb; Chang, Kuo-Chin MDb; Tseng, Po-Lin MDb; Lu, Sheng-Nan MD, PhDb; Chen, Chien-Hung MD, PhDb; Wang, Jing-Houng MD, PhDb; Lee, Chuan-Mo MD, PhDb; Tsai, Ming-Chao MDb; Lin, Ming-Tsung MDb; Yen, Yi-Hao MDb; Hung, Chao-Hung MD, PhDb; Cho, Chung-Lung PhDa; Wu, Cheng-Kun MDb,* Section Editor(s): Gao., Chun

Medicine: November 2017 - Volume 96 - Issue 46 - p e8696
doi: 10.1097/MD.0000000000008696
Research Article: Observational Study

View Full Text Article
Online
Article as PDF (513 KB)

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).

A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.

HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.

The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.
http://journals.lww.com/md-journal/Fulltext/2017/11170/Dynamic_noninvasive_markers_predict_hepatocellular.70.aspx

Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review

Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review
Hosnieh Fathi, Andrew Clark, Nathan R. Hill and Geoffrey Dusheiko

BMC Infectious Diseases BMC series – open, inclusive and trusted 201717:722 https://doi.org/10.1186/s12879-017-2820-z©

View Full Text Article Online

Received: 24 May 2017
Accepted: 6 November 2017
Published: 16 November 2017

Abstract
Background
Six distinct genetic variants (genotypes 1 − 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development.

Methods
According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016).

Results
Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses.

Conclusions
On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.

Keywords
Hepatitis C virus Genotype 3 Direct-acting antiviral Cirrhosis Co-infection Systematic literature review
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2820-z

For Patients
HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
This version of the guidance has been updated to reflect several important developments, including the recent approvals of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. Updated recommendations reflecting these approvals are provided throughout the guidance

New Treatment-Naïve & Treatment-Experienced
The following pages include guidance for management of treatment-naive patients.
The following pages include guidance for management of treatment-experienced patients.
Stay current with all guideline updates, "click here."

Of Interest
September 29,2017
Merck Discontinues MK-3682B and MK-3682C Development Programs
Merck announced its strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection

Potential impact of coffee consumption on chronic liver disease, liver cancer and cirrhosis

Perspective
Moderate coffee intake reduces risk for liver cancer, cirrhosis, fibrosis
November 16, 2017
In a roundtable format, experts gathered to discuss the latest research on coffee and liver disease, which indicate that drinking approximately three to five cups per day is associated with a reduced risk for hepatocellular carcinoma, cirrhosis and fibrosis.
Read more @ Healio

Report suggests association between coffee and up to 70 percent reduced risk of liver disease
New report on coffee and liver health discusses potential impact of coffee consumption on chronic liver disease, liver cancer and cirrhosis

Institute for Scientific Information on Coffee
17th November 2017 - A new roundtable report from the Institute for Scientific Information on Coffee (ISIC) on 'Looking after the liver: coffee, caffeine and lifestyle factors' highlights the potential role of coffee consumption in reducing the risk of liver diseases such as liver cancer and cirrhosis.

Roundtable delegates including academics, media medics and representatives from national liver associations from across seven European countries, met to discuss the most recent research into coffee and liver health, and the potential mechanisms behind a suggested reduced risk of liver disease.

The roundtable, held at the Royal Society of Medicine in London, was chaired by Professor Graeme Alexander (University College London and senior advisor to the British Liver Trust) who also presented on the prevalence of liver disease in Europe and the role of lifestyle. Dr. Carlo La Vecchia (Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano) discussed the latest research on coffee and liver health and potential mechanisms. Group discussion focussed on how best to disseminate the latest findings and challenges for both liver associations and healthcare professionals.

Liver disease is a significant concern across Europe, where chronic liver disease is the fifth most common cause of death1 and approximately 29 million people in the European Union suffer from a chronic liver condition2.

Key research findings highlighted in the report include:
  • Meta-analyses have suggested that coffee consumption versus no coffee consumption is associated with up to a 40% risk reduction of liver cancer, although this appears to be a dose-dependent relationship3-5.
  • Research from the US6 and Italy7,8 suggests that coffee consumption is consistently associated with a reduced risk of cirrhosis, with a potential risk reduction of 25-70%.
  • Research suggests an inverse association between coffee consumption and risk of chronic liver disease, with an average risk reduction of 25-30% in low coffee consumers, and up to 65% in high coffee consumers9.*.
During the roundtable, Professor Alexander suggested that it is likely that liver cancer develops from an existing liver disease, and proposed that the association between coffee consumption and a reduced risk of liver cancer may in fact link back to an effect of coffee drinking on liver disease.

One of the main issues discussed at the roundtable was the diagnosis of liver disease, and the fact that a majority of sufferers are unaware of their condition. Even though the liver is a vital organ, the perception in some European countries is that liver health is not considered as high a priority as other conditions, such as heart disease.

Professor Graeme Alexander, senior advisor to the British Liver Trust, commented: "Liver disease is on the rise across Europe and it is important that we understand how coffee, one of the most popular drinks in the world, and diet affects the disease. Research suggests that coffee may reduce the risk of liver diseases and it is important patients have access to dietary information and advice from health care professionals in a manner that is easy for them to understand and act upon."

Judi Rhys, Chief Executive, British Liver Trust said: "Liver disease is a silent killer as often there are no symptoms until it's too late. Coffee is something that is easily accessible to everyone and regularly drinking it - filtered, instant or espresso - may make a difference in preventing and, in some cases, slowing down the progression of liver disease- it is an easy lifestyle choice to make."

To read the report, titled 'Looking after the Liver: Lifestyle, Coffee and Caffeine' click here.

Readers interested in finding out more about coffee and health can visit: http://www.coffeeandhealth.org

* Definitions of low and high coffee consumption from the studies within the meta-analysis vary and tend to be study specific dependent on levels of coffee consumed by participants.
* Moderate coffee consumption can be defined as 3-5 cups per day, based on the European Food Safety Authority's review of caffeine safety.
* To read a full overview of coffee and liver function, click here.

Roundtable delegates
  • Professor Graeme Alexander University College London and senior advisor to the British Liver Trust, United Kingdom.
  • Dr. Carlo La Vecchia, Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy.
  • HIlje Logtenberg-van der Grient, Physician Educator, Scientific Committee ELPA/Dutch Liver Patient Association, The Netherlands.
  • Andreas Röhrenbacher, Steering Committee Member, Die Hepatitis Hilfe Osterreich, Plattform Gesunde Leber (HHO), Austria.
  • Raquel Peck, CEO, World Hepatitis Alliance, United Kingdom.
  • Dr David Semela, Council Member, Swiss Association for the Study of the Liver, Switzerland.
  • Dr Trisha Macnair, Speciality Doctor/Medical Journalist, NHS, United Kingdom.
  • Dr Ellie Cannon, NHS GP, Abbey Medical Centre, London, United Kingdom.
  • Dr JW Langer, medical doctor, author, lecturer and medical journalist, Denmark.
  • Dr Luca Miele, MD, PhD, Consultant Internist and Hepatologist, University Hospital Policlinico A. Gemelli Foundation, Italy.
  • Dr Beatrice Alfonso PhD, Fondazione Italiana Fegato, ONLUS- Italian Liver Foundation, Italy.
  • Gerardo Reyna, Federación Nacional de Enfermos y Trasplantados Hepáticos, Spain.
References
1. European Association for the Study of the Liver (2013) 'The burden of Liver Disease in Europe: A Review of Available Epidemiological Data' Available at: http://www.easl.eu/medias/EASLimg/Discover/EU/54ae845caec619f_file.pdf
2. Eurostat (2007) 'Europe in Figures: Eurostat yearbook 2006-07' Available at: http://www.nefmi.gov.hu/letolt/eu/ks_cd_06_001_en.pdf
3. Bravi F. et al. (2007) Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatol, 46:430-435.
4. Larsson S.C. et al. (2007) Coffee consumption and liver cancer: a meta-analysis. Gastroenterol, 132:1740-1745.
5. Bravi F. et al. (2013) Coffee reduces risk for hepatocellular carcinoma: An updated meta-analysis. Clin Gastro and Hepatol, 11:1413-1421.
6. Klatsky A.L. et al. (1993) Coffee, tea, and mortality. Ann Epidemiol. 3(4):375-81.
7. Corrao G. et al. (1994) The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption - A case-control study. Europ J Epidemiol, 10 (6): 657-664.
8. Gallus S. et al. (2002) Does coffee protect against liver cirrhosis? Ann Epidemiol, 12(3):202-5.
9. Bravi F. et al. (2016) Coffee and the risk of hepatocellular carcinoma and chronic liver disease: a systematic review and meta-analysis of prospective studies. Eur J Cancer Prev, 26(5):368-377.
10. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2015) Scientific Opinion on the safety of caffeine. EFSA Journal, 13(5):4102.
https://www.eurekalert.org/pub_releases/2017-11/k-rsa111517.php

Efficacy/prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma

Annals of HematologyDecember 2017, Volume 96, Issue 12, pp 2057–2061 |

Efficacy and prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma
Yutaka Tsutsumi, Chie Nakayama, Koki Kamada, Ryo Kikuchi, Daiki Kudo, Shinichi Ito, Satomi Matsuoka, Souichi Shiratori, Yoshiya Yamamoto, Hirohito Naruse, Takanori Teshima

Full Text

Discussion
It was recently reported that performing antiviral therapy against HCV in the treatment of HCV-positive lymphoma has had positive effects including improvement of the lymphoma, and that antiviral therapy including interferon against low-grade lymphoma may be able to improve the prognosis when performed following chemotherapy for low-grade lymphoma [9, 10]. In our report, since HCV is often stained in tissue samples, and since cases where there is a drop in HCV viral RNA are less likely to recur [7], it is suggested that HCV is directly or indirectly associated with the occurrence and progression of lymphoma. However, the main causes of the transition to lymphoma are still unclear. Furthermore, it has been reported that improvements can be obtained with antiviral therapy alone (e.g., in cases of splenic marginal zone lymphoma), and it is expected that the use of antiviral therapy against HCV-positive lymphoma yields an improved prognosis [11, 12, 13].

On the other hand, studies of whether treatment of HCV with antiviral drugs after treatment for diffuse large-cell lymphoma contributes to the prognosis are being conducted either retrospectively or through a combination of retrospective and prospective methods [14, 15]. It has been reported that the 5-year OS and PFS can both be improved [14, 15]. Also, a report by Michot et al. pointed out the possibility of including cases where diffuse large B cell lymphoma is thought to have transformed from splenic marginal zone lymphoma [14], but in this case, cases that have transformed from splenic marginal zone lymphoma are not included. In Europe and the USA, there are many cases where splenic marginal zone lymphoma is associated with HCV. These cases are highly responsive to HCV antiviral therapy, suggesting the possibility of an improved prognosis. On the other hand, in a report by Michot et al., there were cases in which SVR could not be obtained in the antiviral therapy group, while in a report by Hosry et al., there were many cirrhosis cases among the analysis subjects, and it is thought that these factors may have acted on OS and PFS in a negative direction [14, 15]. In our analysis, genotype 2 was more common in the DAA group, while genotype 1 was more common in the control 1 group, and the difference in genotype may also have affected the outcome of treatment. It is thought that this affected the OS and PFS analysis of this report and earlier reports [14, 15].

Since DAA was used after obtaining confirmation of chronic HCV-positive hepatitis by liver biopsy in the cases analyzed here, DAA therapy was performed about 6 weeks after treatment with anticancer drugs. However, there are no clear guidelines on the appropriate timing for DAA treatment, such as whether antiviral therapy should be performed after or during lymphoma treatment, or before anticancer treatment of the lymphoma. A recent report investigated the interactions of DAA administered simultaneously with various anticancer drugs in cancer cases complicated by HCV infection. In this report, although blood toxicity and gastrointestinal toxicity were found, the change brought about by DAA therapy was only 10%, and the SVR was also 95%, and it was reported that it may be possible to use DAA therapy simultaneously with anticancer treatment [16, 17]. On the other hand, in this analysis, there were no problems arising from the continued use of DAA therapy, or complications requiring a change of medication regime, but this could be because there were no cases where DAA therapy was performed at the same time as the anticancer treatment.

In this study, we are conducting a prospective examination of five cases, and so far, 2 years has elapsed since the start of treatment, but in all five cases, the patients have survived without any recurrence, and it seems that following chemotherapy with antiviral therapy may contribute to the prognosis in cases of HCV-positive diffuse large-cell lymphoma. Furthermore, although analysis has only been performed in a few cases, it seems that HCV-RNA-positive cases may have a poorer prognosis than non-HCV-infected diffuse large-cell lymphoma cases, and although there are signs that the prognosis is improved for DAA treatment cases, it may be recommended that DAA treatment is performed after remission in HCV-RNA-positive diffuse large-cell lymphoma. However, since we have only examined a few cases for a short period of time, we are hopeful that the usefulness of antiHCV therapy will be demonstrated more clearly by a prospective study involving a larger number of people.

The Impact of Hepatitis B Virus Infection and Vaccination on the Development of Non-hodgkin Lymphoma

Perspective > Journal of Viral Hepatitis

The Impact of Hepatitis B Virus Infection and Vaccination on the Development of Non-hodgkin Lymphoma

This study investigated the association of HBV infection and risk of non-Hodgkin's lymphoma. Might HBV vaccination reduce the risk in certain populations?

The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing

BMC Infectious Diseases
The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing
Joseph D. Tucker, Kathrine Meyers, John Best, Karyn Kaplan, Razia Pendse, Kevin A. Fenton, Isabelle Andrieux-Meyer, Carmen Figueroa, Pedro Goicochea, Charles Gore, Azumi Ishizaki, Giten Khwairakpam, Veronica Miller, Antons Mozalevskis, Michael Ninburg, Ponsiano Ocama, Rosanna Peeling, Nick Walsh, Massimo G. Colombo and Philippa Easterbrook
Published: 1 November 2017


Map of countries with contributions to the hepatitis testing innovation contest

Abstract
Background
Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines.

Methods
This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines.

Results
The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7).

Conclusion
The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed.

Wednesday, November 15, 2017

Blog Updates Around The Web: Does an SVR to Therapy for HCV-associated Cirrhosis Reduce Portal Pressure?

Viral Hepatitis Updates
With Thanksgiving just around the corner, and Christmas on the way, it's a busy time of the year, hopefully you'll save some time online with this quick summary of blog and journal updates. 
______________________________
AGA Journals BLOG
Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology. She has worked as an editor at biomedical research journals and as a science writer for 15 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.

Does an SVR to Therapy for HCV-associated Cirrhosis Reduce Portal Pressure?
A sustained virologic response (SVR) to all-oral therapy in patients with hepatitis C virus (HCV)-associated cirrhosis significantly reduces the hepatic venous pressure gradient (HVPG), researchers report in the November issue of Gastroenterology. Nevertheless, almost 80% of patients maintain significant portal hypertension and have a continued risk of decompensation.
Continue reading...
_________________________________________
Clinical Care Options CCO
Mission Statement - To optimize clinicians’ competence with the goal of improving patient care through the development of educational solutions that address the explosion of new medical information and the overwhelming task of its assimilation by clinicians, with easy-to-use, innovative, interactive educational and decision support models that can be used at the point of care and provide the latest evidence-based information whenever, wherever, and however it is needed.

Hepatology Meeting Shed Light on the Clinical Benefits of HCV DAAs
Jordan J. Feld, MD, MPH - 11/14/2017 Clinical Thought 
For the first time in several years, we did not see the presentation of dramatic data from phase III trials of emerging investigational HCV therapies at the American Association for the Study of Liver Diseases (AASLD) meeting. What we learned is that we likely now have the full complement of direct-acting antivirals (DAAs) and—unfortunately—that some relatively promising regimens that were in clinical development are unlikely to come to clinical use.

What did emerge at the meeting were several studies that provided critical evidence that treatment with DAAs leads to important clinical benefits for patients with HCV infection. Although these types of studies can feel like something of a foregone conclusion, they are actually critical for payers, policymakers, and clinicians to be confident that contemporary HCV therapies are associated with the intended benefits.

*Free registration required
_________________________________________
On Twitter
The Cochrane Review Conclusion for Hepatitis C DAA Therapies Is Wrong

*Article shared by Henry E. Chang‏ today on Twitter.



Full Text Articles
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

On The Blog
_________________________________________
HepCBC
HepCBC is a non-profit organization run by and for people infected and affected by hepatitis C. Our mission is to provide education, prevention and support to those living with HCV.

Read today's news or check out the latest issue of: Weekly Bull
_________________________________________
CATIE Blog
The CATIE Blog is a unique opportunity for individuals to express a wide latitude of opinion on a range of issues. The views expressed in the blog are solely those of the authors and do not necessarily reflect the policies or opinions of CATIE nor the views of its funders

Eliminating viral hepatitis is possible: Four lessons from the World Hepatitis Summit
By Melisa Dickie
As deaths from many communicable diseases continue to decline globally, deaths caused by viral hepatitis have now surpassed all other chronic infectious diseases, including HIV/AIDS, malaria and tuberculosis. Yet it is one of the few global health threats with easy solutions. Highly effective vaccines exist for hepatitis A and B. We now have a cure for hepatitis C. With these tools at our disposal, why aren’t we seeing an impact on the epidemic?
Continue reading....
_________________________________________
National Viral Hepatitis Roundtable
The National Viral Hepatitis Roundtable is a broad coalition working to fight, and ultimately end, the hepatitis B and hepatitis C epidemics. We seek an aggressive response from policymakers, public health officials, medical and health care providers, the media, and the general public through our advocacy, education, and technical assistance.

Why We Need a Movement for Racial Justice and Health Equity in Order to Eliminate Hepatitis B and Hepatitis C
by the National Viral Hepatitis Roundtable’s Steering Committee
Recently, some people have questioned why the National Viral Hepatitis Roundtable’s staff and members of its Steering Committee have made statements in words and action standing up for racial justice. We hope this statement provides additional context for why speaking out about the need for racial justice and health equity is critical to the hepatitis B and hepatitis C response.

NVHR Welcomes New Hepatitis B Vaccine
NVHR today welcomed the U.S. Food and Drug Administration’s (FDA) approval of HEPLISAV-B for prevention of hepatitis B virus infection in adults ages 18 and older.
_________________________________________
Médecins Sans Frontières/ Doctors Without Borders (MSF)
Médecins Sans Frontières (MSF) is an international, independent, medical humanitarian organisation. We offer assistance to people based on need, irrespective of race, religion, gender or political affiliation. Our actions are guided by medical ethics and the principles of neutrality and impartiality.

Fighting Hepatitis in Cambodia: Medical Week

"The best part of Medical Week was the opportunity to meet MSF colleagues from all over the world, most of whom had more experience than I have and who had lots of advice for me, such as..."
Continue reading....
_________________________________________
POZ
POZ is an award-winning print and online brand for people living with and affected by HIV/AIDS. Offering unparalleled editorial excellence since 1994, POZ magazine and POZ.com are identified by our readers as their most trusted sources of information about the disease.

Finding Folks Who Have HIV or Hep C in an Opioid-Ravaged Region
West Virginia has been hit hard by the opioid epidemic, so it is important to identify people living with HIV and hepatitis C virus (HCV), which can be spread by injection drug use. A four-year $1.375 million grant aims to do exactly that. Funding goes to the West Virginia University (WVU) School of Medicine’s Department of Emergency Medicine and arrives from Frontlines of Communities in the United States (FOCUS), an initiative of pharma giant Gilead Sciences.
Continue reading....
_________________________________________
HEPATITISC.NET
At HepatitisC.net we empower patients and caregivers to take control of Hepatitis C by providing a platform to learn, educate, and connect with peers and healthcare professionals.

Elimination: What Does It Look Like?
By Daryl Luster—November 14, 2017
Elimination. There’s a kind of ominous ring this word, but this is what we hear a lot in the world of viral hepatitis, including HBV and HCV. The meaning here is meant to describe a global effort to eliminate hep C as a health threat. With estimates of worldwide infection ranging wildly, suffice to say it is well over 100 million people now living with hep C. Some peg it at around 150-170 million, and no matter which is accurate it is a huge number.
_________________________________________
Hepatitis B Foundation
The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide. Our commitment includes funding focused research, promoting disease awareness, supporting immunization and treatment initiatives, and serving as the primary source of information for patients and their families, the medical and scientific community, and the general public.

Diagnosing Hepatitis Delta in the U.S.
November 15, 2017 hepbtalk
Hepatitis D, or hepatitis delta, is the most severe form of viral hepatitis known to humans. The hepatitis D virus infects the liver and is dependent on the hepatitis B virus to reproduce. This means that people who are already infected with hepatitis B are at risk of contracting hepatitis D as well.
_________________________________________
MD Magazine
MD Magazine is a comprehensive clinical news and information portal that provides physicians with up-to-date specialty and disease-specific resources designed to help them provide better care to patients.

Aspirin Could Reduce HBV Patients' Liver Cancer Risk
Patients with chronic hepatitis B virus (HBV) who take an aspirin a day may reduce their risk of hepatocellular carcinoma (HCC), the most common form of adult liver cancer, a new study suggests.
_________________________________________
Medscape
Medscape is the leading online global destination for physicians and healthcare professionals worldwide, offering the latest medical news and expert perspectives; essential point-of-care drug and disease information; and relevant professional education and CME.

Preventing Perinatal Transmission of Hepatitis B
November 14, 2017
 Dr William Balistreri surveys the latest guidelines and studies aiming to improve maternal and neonatal outcomes.
_________________________________________
Kaiser Family Foundation
Kaiser Health News (KHN) is a nonprofit news service committed to in-depth coverage of health care policy and politics. And we report on how the health care system — hospitals, doctors, nurses, insurers, governments, consumers — works.

Vaccine Shortage Complicates Efforts To Quell Hepatitis A Outbreaks
By Stephanie O'Neill
San Diego County, battling a deadly outbreak of hepatitis A, is postponing an outreach campaign to provide the second of two inoculations against the contagious liver disease until a national shortage of the vaccine is resolved, the county’s chief public health officer said. “Our goal is to get that vaccine in as many arms as possible for that first dose,” said Dr. Wilma Wooten, who is leading the fight against an epidemic that has ravaged unsanitary homeless encampments in San Diego County for the past year, sickening 544 people and killing 20 of them as of Nov. 6.
Continue reading.......
_________________________________________
Harvard Health Blog
Harvard Health Publishing is the media and publishing division of the Harvard Medical School of Harvard University, under the direction of Dr. Gregory Curfman, Editor in Chief. The goal of our publications is to bring people around the world the most current health information that is authoritative, trustworthy, and accessible, drawing on the expertise of the 10,000+ faculty physicians at Harvard Medical School.

Seasonal Influenza
What’s new with the flu shot?
Posted November 13, 2017, 10:30 am
Dominic Wu, MD, Contributing Editor
Should you get the influenza (flu) vaccine this year? The short, quick answer (barring any medical reasons you shouldn’t, such as severe allergies), is yes! But recent research raises another important question: When should you get the shot?
_________________________________________
Healio
Healio.com features the industry’s best news reporting, dynamic multimedia, question-and-answer columns, CME and other educational activities in a variety of formats, quick reference content, blogs, peer-reviewed journals and a full line of popular book titles.

Welcome to the New World Order A Competitive HCV Drug Marketplace
November/December print edition of HCV NEXT, available online at Healio.
_________________________________________
MPR
Monthly Prescribing Reference (MPR) is a multispecialty drug information resource for healthcare professionals offering concise prescribing information, point-of-care tools, as well as news and features on hot topics in pharmacotherapy.

Labeling for Several HCV Drugs Updated With New Drug Interactions
Specifically, the prescribing information for Viekira Pak (ombitasvir, paritaprevir, ritonavir, with dasabuvir; AbbVie), Viekira XR (dasabuvir, ombitasvir, paritaprevir, ritonavir; AbbVie), Technivie (ombitasvir, paritaprevir, ritonavir; AbbVie), Sovaldi (sofosbuvir; Gilead), Harvoni (ledipasvir, sofosbuvir; Gilead), Epclusa (sofosbuvir, velpatasvir; Gilead), Vosevi (sofosbuvir, velpatasvir, voxilaprevir; Gilead), Olysio (simeprevir; Janssen), Daklinza (daclatasvir; Bristol-Myers Squibb), and Zepatier (elbasvir, grazoprevir; Merck) has been updated to include information pertaining to changes in International Normalized Ratio (INR) values in patients receiving warfarin. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment.
Read more..... 
_________________________________________

Journal Updates
_________________________________________
PLOS ONE
The world’s first multidisciplinary Open Access journal, PLOS ONE accepts scientifically rigorous research, regardless of novelty. PLOS ONE’s broad scope provides a platform to publish primary research, including interdisciplinary and replication studies as well as negative results. The journal’s publication criteria are based on high ethical standards and the rigor of the methodology and conclusions reported.

Evolution of acute hepatitis C virus infection in a large European city: Trends and new patterns
The aims of this study were to describe the evolution of acute hepatitis C virus (HCV) infections since 2004 and to determine its associated factors. Acute HCV infections diagnosed in Barcelona from 2004 to 2015 were included. Incidence ratios (IR) were then estimated for sex and age groups. Cases were grouped between 2004–2005, 2006–2011 and 2012–2015, and their incidence rate ratios (IRR) were calculated. In addition, risk factors for acute HCV infection were identified using multinomial logistic regression for complete, available and multiple imputed data. 204 new HCV cases were identified. Two peaks of higher IR of acute HCV infection in 2005 and 2013 were observed. Men and those aged 35–54 had higher IR. IRR for men was 2.9 times greater than in women (95% confidence intervals (CI): 1.8 ‒ 4.7). Factors related to the period 2012–2015 (versus 2006–2011) were: a) sexual risk factor for transmission versus nosocomial (relative-risk ratio (RRR): 13.0; 95% CI: 2.3 ‒ 72.1), b) higher educated versus lower (RRR: 5.4; 95% CI: 1.6 ‒ 18.7), and c) HIV co-infected versus not HIV-infected (RRR: 53.1; 95% CI: 5.7 ‒ 492.6). This is one of the few studies showing IR and RRRs of acute HCV infections and the first focused on a large city in Spain. Sexual risk for transmission between men, higher educational level and HIV co-infection are important factors for understanding current HCV epidemic. There has been a partial shift in the pattern of the risk factor for transmission from nosocomial to sexual.
Continue to full text article........

Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.
Stroffolini T, et al. PLoS One. 2017
Abstract
BACKGROUND: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation.

OBJECTIVE: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis.
DESIGN: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis.
RESULTS: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex.
CONCLUSIONS: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.
_________________________________________
The Lancet
The Lancet began as an independent, international weekly general medical journal founded in 1823 by Thomas Wakley. Since its first issue (October 5, 1823), the journal has strived to make science widely available so that medicine can serve, and transform society, and positively impact the lives of people.

Eliminating viral hepatitis: time to match visions with action

_________________________________________
Of Interest
AMI Podcast - November 13, 2017 episode
2017 World Hepatitis Summit

Hepatitis C in Canada

Dr. Jordan Feld from the Toronto Centre for Liver Disease discuss what it will take for hepatitis C to be cured in Canada.

Of all infectious disease in Canada the one disease that causes most years of life lost is hepatitis C. 
Listen here......

Podcast: What it will take for hepatitis C to be cured in Canada

AMI Podcast
November 13, 2017 episode
2017 World Hepatitis Summit

Hepatitis C in Canada 
Dr. Jordan Feld from the Toronto Centre for Liver Disease discuss what it will take for hepatitis C to be cured in Canada.

Of all infectious disease in Canada the one disease that causes most years of life lost is hepatitis C. 

Listen here......

Listen: With Stricter Guidelines, Do You Have High Blood Pressure Now?

November 14, 201712:56 PM ET
Heard on All Things Considered
You may not have had high blood pressure Sunday, but you may have it today. Even if your blood pressure hasn't changed a smidge. What's up?

The rules shifted Monday. It used to be that we encouraged people to adopt healthy behavior to keep their blood pressure down but didn't label someone as having hypertension until systolic blood pressure (the top number) exceeded 140 millimeters of mercury and/or the diastolic blood pressure (the bottom number) exceeded 90 mm Hg. Lots of people watch those numbers closely.

Now the American College of Cardiology and the American Heart Association have updated blood pressure guidelines that move the goal post for many people.
Continue reading......

NIH blood pressure study supports important part of new AHA/ACC hypertension guidelines
Today the AHA and the ACC issued the first comprehensive new high blood pressure guidelines in more than a decade that indicate high blood pressure should be treated earlier with lifestyle changes and in some patients with medication – at 130/80 mm Hg rather than 140/90. An important component of these guidelines was informed by the results of the Systolic Blood Pressure Intervention Trial (SPRINT), a clinical study sponsored in part by the NHLBI and designed to determine the best way to treat blood pressure in adults with hypertension, 50 years or older, who are at high risk for heart disease.

SPRINT, which began in the fall of 2009, included more than 9,300 participants, recruited from about 100 medical centers and clinical practices throughout the United States. It remains the largest study of its kind to date to examine how maintaining systolic blood pressure at a lower than previously recommended level would impact cardiovascular and kidney diseases.
http://hepatitiscnewdrugs.blogspot.com/2017/11/nih-blood-pressure-study-supports.html

Tuesday, November 14, 2017

Current and emerging pharmacological therapy for non-alcoholic fatty liver disease

Editorial
World J Gastroenterol. Nov 14, 2017; 23(42): 7495-7504
Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7495

Full Text Article Available Online
https://www.wjgnet.com/1007-9327/full/v23/i42/7495.htm

Current and emerging pharmacological therapy for non-alcoholic fatty liver disease
The main treatment of patients with non-alcoholic fatty liver disease (NAFLD) is life style modification including weight reduction and dietary regimen. Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis (NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an anti-oxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.

Core tip: Non-alcoholic fatty liver disease (NAFLD) is an increasing liver disease worldwide. However, most of patients are treated with life style modification including weight loss and dietary regimen. Pharmacologic therapy may be indicated in a group of patients with non-alcoholic steatohepatitis. Here in, the current and emerging medications for treatment of NAFLD was reviewed briefly with regard of their beneficial effects on histological outcomes.

Full Text: https://www.wjgnet.com/1007-9327/full/v23/i42/7495.htm

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences

Alimentary Pharmacology & Therapeutics
The negative impact of HBV/HCV coinfection on cirrhosis and its consequences


Full Text Article 
Alimentary Pharmacology & Therapeutics

Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series.

Dr Pol and colleagues from France compared the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study.

Of the 20,936 included patients, 95 had HBV/HCV coinfection, and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis.

F3-F4 fibrosis was more frequent in coinfected patients than in HBV-, but similar in HCV-monoinfected patients. Decompensated cirrhosis was more frequent in coinfected patients than in HBV- or HCV- monoinfected patients.

Past excessive alcohol use was more frequent in coinfected patients than in HBV, but similar in HCV monoinfected patients.

The researchers found that coinfected patients had a higher proportion with arterial hypertension than HBV- or HCV-monoinfected patients.

The research team confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients, and the association between decompensated cirrhosis and coinfection in HBV infected or HCV infected patients.

Dr Pol's team concludes, "HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients."

"HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients."

Continue to full text - http://onlinelibrary.wiley.com/doi/10.1111/apt.14352/full
  • First published:
  • DOI: 10.1111/apt.14352

  • FDA warns of ‘deadly risks’ of the herb kratom, citing 36 deaths

    FDA warns of ‘deadly risks’ of the herb kratom, citing 36 deaths

    Nonalcoholic fatty liver disease increases risk of liver, colorectal, and breast cancers

    Public Release: 13-Nov-2017
    Nonalcoholic fatty liver disease increases risk of liver, colorectal, and breast cancers
    NAFLD is not only linked to hepatocellular carcinoma, but also to cancers outside the liver, report investigators in the Journal of Hepatology

    Amsterdam, November 14, 2017 - Nonalcoholic fatty liver disease (NAFLD) is one of the more common chronic liver diseases worldwide. It is associated with metabolic syndrome (i.e. insulin resistance and diabetes) and predisposes to cardiovascular disease. In a new study published in the Journal of Hepatology, researchers identified links not only between NAFLD and hepatocellular carcinoma (HCC), which have been well established, but also to cancers outside the liver, including colorectal and breast cancer.

    "NAFLD is a very important multisystem disease to which much attention should be paid," explained lead author Gi-Ae Kim, of the Health Screening and Promotion Center, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea. "Despite its strong relationship with HCC development, little attention has been paid to the association of NAFLD with the development of other extrahepatic cancers. Our study presents statistical evidence that NAFLD is associated with extrahepatic cancers. We hope this study will raise awareness of the increased cancer potential that NAFLD might have."

    This retrospective study evaluated the records of almost 26,000 Korean individuals who underwent health checkups from September 2004 through December 2005, who had no cancer diagnosis within one year of the checkup, and were followed for an average of 7.5 years.

    Data revealed that 8,721 (33.6%) of individuals in the study were diagnosed with NAFLD, and cancer incidence in that group was 32% higher than in the non-NAFLD group. Once the data were adjusted for demographic and metabolic factors, significant risks for specific cancers became evident. Specifically, patients with NAFLD were 16.73 times more likely to develop HCC, twice as likely to develop colorectal cancer (men), and almost twice as likely to develop breast cancer (women).

    High scores on two measurements of liver fibrosis, the NAFLD fibrosis score (NFS) and the FIB-4 score, were also associated with a higher risk for all cancers, and especially HCC. A high NFS score indicated an 87% increase in risk and high FIB-4 score a 74% increase in risk. These scores serve as a predictor of cancers and of HCC in particular.

    Principal investigator Han Chu Lee, MD, of the Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, noted, "Our results suggest that patients with NAFLD require multidisciplinary evaluation with particular attention to the development of cancers. Further studies are needed to specify which high-risk groups among patients with NAFLD carry a greater risk of developing specific cancers, including HCC, colorectal cancer, and breast cancer and that we should pay more attention to the cancer potential of NAFLD in clinical practice."

    In an accompanying editorial, Peter Jepsen, PhD, of the Department of Hepatology and Gastroenterology and Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark, and co-authors add perspective. "NAFLD is likely to become the most prevalent liver disease in many countries, yet clinicians are struggling to determine exactly why they should care about NAFLD. Is it merely a bystander--a manifestation of the metabolic syndrome resulting in cardiovascular disease--or is it a liver disease in its own right?"

    Dr. Jepsen concludes that despite a number of open issues, the Korean cohort study by Kim et al provides relevant and valid information on the association between NAFLD and cancer risk, and definite evidence on its strong association with HCC.

    'Mini liver tumors' created in a dish for the first time

    Public Release: 13-Nov-2017
    'Mini liver tumors' created in a dish for the first time

    Wellcome Trust
    Scientists have created mini biological models of human primary liver cancers, known as organoids, in the lab for the first time. In a paper published today in Nature Medicine, the tiny laboratory models of tumours were used to identify a new drug that could potentially treat certain types of liver cancer.

    Primary liver cancer is the second most lethal cancer worldwide. To better understand the biology of the disease and develop potential treatments, researchers need models that can grow in the lab and accurately reflect how the tumours behave in patients. Previously, cultures of cells had been used but these are hard to maintain and fail to recreate the 3D structure and tissue architecture of human tumours.

    The researchers created the mini tumours (up to 0.5mm) - termed tumouroids - to mimic the three most common forms of primary liver cancer. The tumour cells were surgically removed from eight patients and grown in a solution containing specific nutrients and substances which prevent healthy cells out-competing the tumour cells. The team, from the Wellcome/Cancer Research UK Gurdon Institute in Cambridge, used the tumouroids to test the efficacy of 29 different drugs, including those currently used in treatment and drugs in development. One compound, a type of protein inhibitor, was found to inhibit the activation of a protein called ERK in two of the three types of tumouroids, a crucial step in the development of liver cancer.

    The researchers then tested this compound in vivo, transplanting two types of tumouroids into mice and treating them with the drug. A marked reduction in tumour growth was seen in mice treated with the drug, identifying a potential novel treatment for some types of primary liver cancer.

    The tumouroids were able to preserve tissue structure as well as the gene expression patterns of the original human tumours from which they were derived. The individual subtypes of three different types of liver cancer, as well as the different tumour tissues which they came from, were all still distinguishable even after they had been grown in a dish for a long time. As the tumouroids retain the biological features of their parent tumour, they could play an important role in developing personalised medicine for patients.

    The creation of biologically accurate models of tumours will also reduce the number of animals needed in certain experiments. Animal studies will still be required to validate findings, but the tumouroids will allow scientists to explore key questions about the biology of liver cancer in cultures rather than mice.

    Lead researcher Dr Meritxell Huch, a Wellcome Sir Henry Dale Fellow from the Gurdon Institute, said: "We had previously created organoids from healthy liver tissue, but the creation of liver tumouroids is a big step forward for cancer research. They will allow us to understand much more about the biology of liver cancer and, with further work, could be used to test drugs for individual patients to create personalised treatment plans."

    Dr Andrew Chisholm, Head of Cellular and Developmental Sciences at Wellcome said: "This work shows the power of organoid cultures to model human cancers. It is impressive to see just how well the organoids are able to mimic the biology of different liver tumour types, giving researchers a new way of investigating this disease. These models are vital for the next generation of cancer research, and should allow scientists to minimise the numbers of animals used in research."

    Dr Vicky Robinson, Chief Executive of the NC3Rs which partially funded the work, said: "We are pleased to see that the funds from our annual 3Rs prize, sponsored by GlaxoSmithKline, have furthered Dr Huch's research. Each year the prize recognises exceptional science which furthers the 3Rs, and the work being conducted by Meri and her team is continuing to make progress in this area. This new breakthrough involving liver cancer organoids has the potential to reduce the number of animals required in the early stages of liver cancer research, and provide more biologically accurate models of human tumours."

    ###

    This work was funded by a National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) research prize, Wellcome and Cancer Research UK Cambridge Centre.

    The paper Human primary liver cancer-derived organoid cultures for disease modelling and drug screening is published in Nature Medicine http://dx.doi.org/10.1038/nm.4438 (URL will go live after embargo lifts)

    About the Wellcome/Cancer Research UK Gurdon Institute

    Named after its co-founder, Nobel Laureate Sir John Gurdon, the Gurdon Institute is a world-leading centre for research into the fundamental processes of biology and development, and how these go wrong in diseases such as cancer. More than 240 scientists work in the Institute's purpose-built laboratories on projects ranging from breast cancer and brain development to liver regeneration and leukaemia. Many have made pioneering contributions to the fields of basic cell biology, cellular reprogramming, epigenetics and DNA repair. Institute scientists use a range of model systems such as yeast, nematode worms, fruit flies, frogs, mammalian cells and organoids to study development and disease at the level of molecules, cells and tissues. Research conducted at the Institute has so far led to 11 spin-out companies (including Abcam, CellCentric, MISSION Therapeutics and Gen2 Neuroscience) and several candidate therapeutics have entered clinical trials. One of these, olaparib (Lynparza), has been approved in the UK, Europe and the USA for use against ovarian cancers. http://www.gurdon.cam.ac.uk

    About the NC3Rs
    The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is a leading independent scientific organisation dedicated to replacing, refining and reducing the use of animals in research and testing (the 3Rs). It supports the UK science base by driving and funding innovation and technological developments that minimise the need for animals in research and testing, and lead to improvements in welfare where animals continue to be used. It funds research, supports training and development, and stimulates changes in regulations and practice. Primarily funded by Government, the NC3Rs is also supported by the charitable and private sectors. It works with scientists in universities and industry in the UK and internationally. http://www.nc3rs.org.uk

    About Cancer Research UK Cambridge Centre
    The Cancer Research UK Cambridge Centre is a dynamic collaboration of over 600 academic researchers, clinicians, and scientists in the pharmaceutical and biotech industries, based in the Cambridge area. The Centre combines world-class science and technology with excellent patient care to pioneer new ways to prevent, detect, diagnose and treat cancer. By working together across different disciplines, the Centre is breaking down the barriers between the laboratory and the clinic, enabling patients to benefit from the latest innovations in cancer science faster. The formal partners of the Cancer Research UK Cambridge Centre are Cancer Research UK, the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust. http://www.crukcambridgecentre.org.uk

    About Wellcome
    Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. Wellcome.ac.uk

    A new strategy for prevention of liver cancer development

    Public Release: 
    A new strategy for prevention of liver cancer development
    A synthetic double-stranded RNA has potential for use as an anti-liver cancer vaccine

    University of California - San Diego
    Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective treatments or drugs. However, an unexpected finding made by a team of University of California San Diego School of Medicine researchers sheds light on the development of a new strategy for prevention of liver cancer.

    While studying the pathogenic mechanisms of liver cancer, the researchers discovered that a commonly used synthetic double-stranded RNA (dsRNA) strongly boosts a variety of anti-tumor innate immune functions. They suggest it may have the potential to be administered as a vaccine to prevent cancer in individuals at high-risk of developing liver cancer.

    "The liver has unique immune tolerance, which is why existing treatments, including immunotherapy, have little to no lasting effects on liver cancer," said Gen-Sheng Feng, PhD, professor of pathology and molecular biology at UC San Diego and senior author on the paper. "We were initially performing gene deletion to investigate how different types of cells communicate in the liver to promote or suppress cancer development when we found that this synthetic double-stranded RNA prevented liver cancer from initiating by harnessing the body's own innate immune system."

    In the findings, published online on November 14 in Cell Reports, researchers describe how dsRNA polyinosinic-polycytidylic acid (pIC) prevented primary liver cancer from occurring in mouse models when it was injected into the body cavity during the pre-cancer stage. Primary liver cancer is cancer that begins in the liver; metastatic liver cancer starts elsewhere in the body and spreads to the liver.

    The study showed that the formation of tumors -- or tumorigenesis -- was suppressed by reprogramming macrophages (specialized immune cells that destroy targeted cells) and activation of natural killer cells and dendritic cells that kill tumor cells directly or boost adaptive immunity.

    Mouse models with tumors induced either by chemical carcinogen or fatty liver diseases were injected with pIC at different stages. Tumor inhibition was successful in all models that received the dsRNA before tumor formation. The greatest decrease in tumor numbers and size was seen when pIC was administered at one month. At three months the impact was reduced but still significant. At five months, when tumors had already began to form, there was little inhibitory effect observed when comparing tumor numbers or sizes to control groups.

    Future studies will look at dosages and timing of pIC as a vaccine, said Feng. In addition, the researchers will evaluate the use of pIC in combination with other agents to stop tumor growth when cancer has already initiated.

    "The findings suggest that the drug may prevent liver cancer. We have more work to do, but we could make a real impact at a time when liver cancer rates are increasing," said Feng, also a researcher with UC San Diego Moores Cancer Center. "There is a large population living with chronic liver disease who are at high risk of developing cancer. If we can develop a vaccine that prevents tumor formation or a therapeutic combination that stops existing cancer from growing, we could reduce the rapid increase of liver cancer rates."

    Liver cancer in adults is among the leading causes of cancer mortality in the world, with more than 780,000 new cases and 740,000 deaths each year. More than 40,000 new cases are diagnosed and 29,000 deaths are reported in the United States annually.

    Co-authors include: Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M. Varki, Wenxian Fu, UC San Diego; Shuang-Jian Qiu, Fudan University; and Bing Ren, Ludwig Cancer Research Institute and UC San Diego.