A Fighter by Nature – Tatjana Reic and the Viral Hepatitis Story

A Fighter by Nature – Tatjana Reic and the Viral Hepatitis Story

The experts in the European Liver Patients Association (ELPA) Hep-CORE advisory group provide a window on the broad range of hepatitis activities and perspectives in Europe today. Hep-CORE PI Jeffrey Lazarus has been interviewing some of them about how they came to work with viral hepatitis, how the field has been changing, and what new research is called for.

Jeffrey V. Lazarus 26 Sep 2016

The ninth interview in the series is with Tatjana Reic, President of the European Liver Patients Association (ELPA).

How did you initially get involved with viral hepatitis?

Today when I look back it seems like it must have been somehow written in the stars – me and the viral hepatitis story.

36 years ago, at the age of 20 in the middle of the summer of 1980, I was hospitalized with a diagnosis of Acute Hepatitis B (HBV). At that time in my medical record, besides positive so-called Australian antigen, the clinicians also had written “NON A NON B.” I didn’t know what that meant. The doctors also did not pay a lot of attention to non A non B. After 35 days spent in the hospital I simply continued with my life; as a reconvalescent I was not the best model of patient. However, per the doctor’s instructions I regularly checked my liver enzymes for the next 5-6 years and then practically forgot about my illness.

So at the age of 34 I got married and pregnant – the most exciting period in my life – I was going to become a mother, oh how great that feeling was! Although by that time it was 1994 – and there was war in Croatia. Because of my history of hepatitis B, I was referred for a blood test on viral hepatitis during my pregnancy. And that’s how I became aware of my diagnosis: Chronic Hepatitis C (cHCV). The illness was unknown to me at the time so I tried to find out more about it but found little help even from close family members who were medical professionals.

My daughter was born anti-HCV positive, PCR undetectable. Although I was advised by my treating physician that her antibodies should be eliminated in 6-12 months it did not happen. Instead it took 4 years and gave me sleepless nights for the first 4 years of her life. I thought, “Oh my God, what have I done to the most precious person in my life, I transmitted her a deadly threat disease”.

In the meantime, I lost my job and started my first treatment with interferon monotherapy – injections 3 times per week for 52 weeks. That was really tough. At that time the was war coming to the end and I was looking for a job as doctor of veterinary medicine. But with a small child, at the age of almost 40 and with a chronic (stigmatized) disease, it was practically impossible. On top of this I was still going through multiple strenuous treatments. Deep depression overtook me.

However, since I am a fighter by nature I decided to do take things into my own hands, so I completed my degree as a Master of Science. In 2000 my life started to completely change. I established the first Croatian hepatitis patient group, joined the European Liver Patients Association (ELPA) in 2005, became ELPA Vice-President in 2007 and since 2011 have been the ELPA President.

I was a patient highly motivated to fight for my life, integrity, dignity, dissent job and the future of my children

Finally, in 2010, when WHO endorsed World Hepatitis Day as only the fourth disease-specific official day, coincidentally appointing it to the day of my birthday – July 28, I began to truly realize my mission and my passion on this Earth – to contribute in the global fight for hepatitis patients’ rights and the right to not be neglected any more.

So my short answer to your question is – I was a patient highly motivated to fight for my life, integrity, dignity, decent job and the future of my children.
How has the viral hepatitis field, especially HCV, been changing?

I can easily speak about that topic from my own experience as I failed 6 very, very tough interferon treatments: 4 out of 6 treatments were with “old” non-pegylated IFN and 1 was a 72-week PEG/RIBA treatment. In total I have spent 5-6 years of my life on IFN treatment. This is the equivalent of 292 weeks, or 2,044 days – after all that the treatments still failed.

Going through treatment with DAAs was like chewing gum compared with IFN treatments.

Later, luckily, I spent 12 more weeks dedicated to my 7th treatment, this time with direct-acting antivirals (DAAs), and today I am cured. Going through treatment with DAAs was like chewing gum compared with IFN treatments.

But I have no regrets. I am sure that the interferon helped postpone the progression of liver fibrosis and kept my liver damage at a comparatively mild level for all those decades, about 22 years after being diagnosed and 35 years since I initially contracted the virus, helping me survive.

Besides my own experience it is evident that viral hepatitis, in particular the field of HCV, has significantly changed.

We have seen revolutionary achievements in the field of treatment. The dreams of every patient who went under IFN treatments finally came true – drugs that can cure almost 100% of patients with almost no side-effects during 4 times shorter duration of treatment. That’s real perfectavir.

Additionally, global awareness of viral hepatitis in general is much higher since the WHO endorsement of World Hepatitis Day.

At the end it is important to stress that with recent 69th World Health Assembly’s adoption of first-ever Global Health Sector Strategy (GHSS) on Viral Hepatitis in Geneva has generated strong political will. The GHSS states a goal to eliminate hepatitis B and C by 2030 and includes prevention and treatment targets to reduce annual deaths by 65% and increase treatment by 80%. It was unanimously adopted by 194 Member States in a historic commitment, signaling the greatest global policy development in the field of viral hepatitis ever.

What areas of viral hepatitis research do you think are still being neglected?

Let’s not fool ourselves – in the past decade a lot has been done in the viral hepatitis field, but a lot more is still on our TO DO list.
In the research area – a treatment to cure cHBV,
In the research area – a vaccine to prevent HCV
Diagnosis and screening – case finding of the undiagnosed HCV population; which is the majority of cases
Secure global access to the best care and treatment options for all patients
Development of national strategies for viral hepatitis
Implementation of national strategies, especially in terms of prevention


Previous interviews in the Hep-CORE advisory group 2016 series:
Let’s not forget ‘prevention as prevention’ ; interview with Eberhard Schatz
The task now is identifying people who don’t know they’re infected and connecting them to care ; interview with Luis Mendão
Without a vaccine, eliminating HCV will be a huge challenge ; interview with Antons Mozalevskis
The same debates, 25 years later ; interview with Marie Jauffret-Roustide
Outside the biomedical box of hepatitis C research ; interview with Magdalena Harris
Changing to a holistic approach towards hepatitis policy ; interview with Achim Kautz
Patient associations: a key catalyst for hepatitis advocacy and impact ; interview with Charles Gore
A clinician’s career in viral hepatitis: a powerful history and optimistic future ; interview with Mojca Maticic

Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications

Eradication of HCV infection in patients With cirrhosis reduces risk of liver and non-liver complications
In this prospective study patients with cirrhosis treated with interferon-based therapy or interferon-free regimens who achieved sustained virologic response (SVR) reduced; overall mortality and risk of death from liver-related and non–liver-related causes.......

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

In addition 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. A link to the above mentioned article was tweeted by Mr. Chang this morning.

Abstract

Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications

Abstract
Background & Aims
We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis.

Methods
We collected data from 1323 patients included in the prospective ANRS CirVir cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then direct antiviral agents) and underwent ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR.

Results
After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved an SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (HCC; hazard ratio [HR] compared to patients without an SVR=0.29; 95% CI, 0.19–0.43; P< .001) and hepatic decompensation (HR=0.26; 95% CI, 0.17–0.39; P<.001). Patients with SVRs also had a lower risk of cardiovascular events (HR=0.42; 95% CI, 0.25–0.69; P=.001) and bacterial infections (HR=0.44; 95% CI, 0.29–0.68; P<.001). Metabolic features were associated with higher risk of HCC in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR=0.27 compared to patients without SVR; 95% CI, 0.18–0.42; P<.001) and death from liver-related and non–liver-related causes. Similar results were obtained in a propensity score-matched population.

Conclusions
We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non–liver-related causes. A longer follow-up is required to accurately describe and assess specific risk factors for complications in this population.

A Review of Daclatasvir Drug-Drug Interactions

Review article
A Review of Daclatasvir Drug-Drug Interactions.
Garimella T, et al. Adv Ther. 2016

Adv Ther. 2016 Sep 23. [Epub ahead of print]

Download - Full text review article

Abstract
The treatment of hepatitis C virus (HCV) infection has been revolutionized in recent years by the development of direct-acting antiviral regimens that do not contain peginterferon (pegIFN) and/or ribavirin (RBV). While direct-acting antiviral-based regimens have been shown to be greatly superior to pegIFN/RBV-based regimens in terms of efficacy and safety, they have a greater susceptibility to drug–drug interactions (DDIs).

Daclatasvir (DCV)—the benchmark pangenotypic nonstructural protein 5A inhibitor—has been shown to be efficacious and generally well tolerated in partnership with other HCV direct-acting antivirals, including sofosbuvir, asunaprevir (ASV), and ASV plus beclabuvir. DCV may be the object of a DDI via the induction or inhibition of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) by the concomitant medication, or the precipitant of a DDI via DCV-based induction/inhibition of CYP 3A4 or inhibition of P-gp, organic anion transporting polypeptide 1B1/B3, and/or breast cancer resistance protein.

This article presents an overview of the drug interaction studies conducted during the clinical development of DCV, the findings of these studies that led to the guidance on concomitant medication use and dosage along with any required DCV dose modifications, and the use of the known metabolic pathway of DCV to guide concomitant dosing where direct drug–drug studies have not been conducted. The robust characterization of the DCV clinical pharmacology program has demonstrated that DCV has few or no clinically relevant DDIs with medications with which it is likely to be co-administered, and the majority of DDIs that do occur can be predicted and easily managed.

Funding: Bristol-Myers Squibb.

KeywordsConcomitant medications Daclatasvir Drug–drug interactions Hepatitis C virus Infectious diseases

Link To - Full text review article

UK patients who have liver transplants abroad get poorer management

UK patients who have liver transplants abroad get poorer management      
News Type: Clinical News
     
A small number of UK citizens are undergoing liver transplants abroad but their management is of a lower standard than in the UK.

These were the conclusions of researchers at Sheffield’s Royal Hallamshire Hospital, who sent questionnaires to all seven UK liver transplant units enquiring about liver patients receiving transplant abroad. Six of the seven centres responded.

A total of 12 patients were identified as having undergone liver transplantation overseas. The top destinations were India, China and Egypt.

Four units responded to questions regarding pre-transplant screening. One unit reported HBV and HCV screening not taking place. Four units responded to questions regarding post-transplant antimicrobial therapy. This revealed examples of patients inappropriately not receiving valganciclovir, co-trimoxazole, anti-fungal treatment and HBV immunoglobulins.

The researchers add that information transfer between overseas and UK based transplant teams is poor.

Reference
A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad. Winter BK, Odedra A, Green S. Travel Med Infect Dis. 2016 Sep 14 [Epub ahead of print]

Abstract
A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad.
Travel Med Infect Dis. 2016 Sep 14. pii: S1477-8939(16)30122-3. doi: 10.1016/j.tmaid.2016.09.004. [Epub ahead of print]

A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad.
Kerr Winter B1, Odedra A2, Green S2.

1Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, S10 2JF, England, UK. Electronic address: Ben.kerrwinter@gmail.com.
2Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, S10 2JF, England, UK.

Abstract
BACKGROUND:
Medical tourism, where patients travel abroad intentionally to access medical treatment, is a growing trend. Some of these patients travel to undergo organ transplantation. This study aims to quantify the number of UK patients who undergo liver transplantation abroad, assessing their motivations and management.

METHODS:
Questionnaires were sent to all seven UK liver transplant units enquiring about liver patients receiving transplant abroad. Included were questions on destination, motivation, and pre and post-transplant care.

RESULTS:
Responses were received from six of the seven transplant centres (86%). A total of 12 patients were identified as having undergone liver transplantation overseas. The top destinations were India, China and Egypt. Four units responded to questions regarding pre-transplant screening. One unit reported Hepatitis B and C screening not taking place. Four units responded to questions regarding post-transplant antimicrobial therapy. This revealed examples of patients inappropriately not receiving valganciclovir, co-trimoxazole, anti-fungal treatment and Hepatitis B immunoglobulins.

CONCLUSIONS:
UK patients are undergoing liver transplant abroad, albeit in small numbers. Pre and post-transplant management of these patients is of a lower standard than that provided to those undergoing transplantation in the UK. Information transfer between overseas and UK based transplant teams is poor.

Copyright © 2016. Published by Elsevier Ltd.

KEYWORDS:

Hepatology; Infectious diseases; Medical tourism; Transplantation
PMID: 27640117 DOI: 10.1016/j.tmaid.2016.09.004

Drugmakers racing each other on treatment for liver disease

Drugmakers racing each other on treatment for liver disease

By CAROLINE CHEN and JARED S. HOPKINS BLOOMBERG NEWS

Nonalcoholic steatohepatitis occurs when fat accumulates in the liver along with inflammation and damage, and as much as a quarter of the U.S. population may have a precursor condition called nonalcoholic fatty liver disease. The ailment develops slowly, and patients often don't show symptoms until their livers are heavily damaged. It's most common in people who are overweight or have diabetes, and doctors mainly prescribe diet changes and weight loss.

While doctors need to perform a biopsy to diagnose nonalcoholic steatohepatitis, between 6 and 15 million people in the U.S. alone are estimated to have the condition, and about 20 percent of them will go on to develop life-threatening cirrhosis. It will be the leading cause of liver transplants by 2020, according to Allergan. Drugs that treat it will likely command high prices, said Elizabeth Krutoholow, an analyst at Bloomberg Intelligence.

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We should aim to achieve complete elimination of hepatitis C

We should aim to achieve complete elimination of hepatitis C
Clinical Pharmacist
26 SEP 2016

Chair of the British Viral Hepatitis Group and Consultant in Infectious Diseases, North Manchester General Hospital

I read the letters from Charles Gore (Clinical Pharmacist 2016;8:232) and Anja St. Clair Jones (Clinical Pharmacist 2016;8:264) on the therapies and new services for hepatitis C with interest. The points made are valid and important.

The key issues highlighted by Gore were related to the fact that there are real restrictions placed on accessing the newer therapies for this infection that have not been imposed in other disease areas, with other medicines, in other patients. Resources are limited; however, denying individuals timely access to National Institute for Health and Care Excellence-approved, evidence-based, cost-effective therapies is, indeed, exceptional.