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Cancer rates among patients with hepatitis C are significantly increased compared to those not infected Researchers suggest an extrahepatic manifestation of hepatitis C may be an increased risk of cancer

April 24, 2015, Vienna , Austria: Results announced today at The International Liver CongressTM 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer.

The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin’s lymphoma, renal and prostate cancers, as well as liver cancer.

A retrospective study at Kaiser Permanente, Southern California, USA, was conducted. The study authors recorded all cancer diagnoses in patients over 18 years of age with or without HCV during 2008-2012. Within the timeframe of the study 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non-HCV cohort.

In the HCV cohort there were 2,213 cancer diagnoses (1,524/100,000) during the 5-year period and 1,654 cancer diagnoses when liver cancer was excluded (1,139/100,000). In the non-HCV cohort there were 84,419 cancer diagnoses (605/100,000) during the same 5-year period and 83,795 (601/100,000) when liver cancer was excluded. When all cancers are considered the rate is 2.5 times higher in the HCV cohort; when liver cancers are excluded, the rate is still almost 2 times higher.

Lisa Nyberg, MD, MPH, Kaiser Permanente, Southern California, senior author of the study, explains: “The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers. These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer. However, the findings must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results.”

Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver, commented: “This data adds to the evidence bank linking hepatitis C with an increased risk of cancer, and highlights that there is still a long way to go in order to fully understand this complex and devastating disease.”

About The International Liver Congress™This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share

research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL (www.easl.eu)Since EASL’s foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

ContactFor more information, please contact the ILC Press Office at:• [email protected] or• +44 (0)20 3580 5444

Viral Hepatitis C: Clinical, Hall D Presentation time: 16:30 – 16:45 Presenter: Anders H. Nyberg (United States)Abstract O058: INCREASED CANCER RATES IN PATIENTS WITH CHRONIC HEPATITIS C: AN ANALYSIS OF THE CANCER REGISTRY IN A LARGE U.S. HEALTH MAINTENANCE ORGANIZATION

Novel therapeutic candidate targets key driver of hepatocellular carcinoma in genomically defined subset of patients Preclinical data demonstrate that BLU-554 is first potent and selective FGFR4 inhibitor

April 24, 2015, Vienna, Austria: Findings were presented today at The International Liver CongressTM 2015 on a novel therapeutic candidate for a genomically defined subset of hepatocellular carcinoma (HCC) patients with an aberrant fibroblast growth factor receptor 4 (FGFR4) pathway. BLU-554, a small molecule inhibitor of FGFR4, has been identified as a potential treatment option for up to 30% of HCC patients. In preclinical studies, the investigational drug was shown to be potent and ‘exquisitely selective’ for FGFR4 compared to other kinases targeting the FGFR family.

Overexpression of fibroblast growth factor 19 (FGF19), the ligand for FGFR4, can promote liver tumour formation (as observed in genetically-engineered mice), a process that can be blocked by

knocking out the FGFR4 gene. This suggests that FGFR4 inhibition might be an effective treatment strategy in HCC patients whose tumours have an active FGF19/FGFR4 signalling axis.

The study authors found that BLU-554 had significant anti-tumour activity in liver cancer models that are dependent on FGFR4 signalling pathway and was well tolerated at the highest dose level.

Klaus Hoeflich, PhD, Director of Biology at Blueprint Medicines, explains: “HCC is a disease with a high unmet need and no approved genomically targeted therapies. These findings support the investigation of BLU-554 in clinical studies of patients with hepatocellular carcinoma driven by aberrant FGFR4 signalling. By identifying patients most likely to respond to therapy based on the molecular profile of their cancer, we hope to make a meaningful difference for HCC patients.”

With limited treatment options available to patients with HCC, these findings provide a new avenue of hope; Phase I clinical trials with BLU-554 are planned to start in mid-2015.

“Most people are diagnosed with hepatocellular carcinoma once the cancer is at an advanced stage and the outlook is poor. Median survival from time of diagnosis is about six months. Finding new disease drivers and treatment options for patients with hepatocellular carcinoma is critical to make strides against this devastating disease” said Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver.

About The International Liver Congress™This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL (www.easl.eu)Since EASL’s foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.ContactFor more information, please contact the ILC Press Office at:• [email protected] or• +44 (0)20 3580 5444

Liver tumours: Clinical, Lehar 1 & 2Presentation time: 16:00 – 16:15Presenter: Klaus Hoeflich (United States)Abstract O048: FIRST SELECTIVE SMALL MOLECULE INHIBITOR OF FGFR4 FOR THE

TREATMENT OF HEPATOCELLULAR CARCINOMAS WITH AN ACTIVATED FGFR4 SIGNALING PATHWAY

Once-daily grazoprevir/elbasvir is effective and well-tolerated in patients infected with chronic hepatitis C virus Positive results from the Phase 3 C-EDGE TN study in treatment-naive patients

April 24, 2015, Vienna, Austria: Results presented today at The International Liver Congress™ 2015 show that a 12-week oral regimen of once-daily single tablet grazoprevir/elbasvir (GZR/EBR) is effective and well-tolerated in treatment-naive (TN) patients infected with chronic hepatitis C virus (HCV) genotypes (GT)-1, -4 or -6, including those with compensated cirrhosis.

Based on preliminary results from 316 GZR/EBR recipients in the immediate treatment arm, 299 patients (95%) achieved a sustained virologic response at 12 weeks (SVR12).

“These initial results show that once-daily grazoprevir/elbasvir offers significant advantages over older treatments, demonstrating the ideal combination of high efficacy with good tolerability and convenience in treatment-naive patients infected with chronic HCV,” said Rajender Reddy, MD, FAASLD Professor of Medicine, Professor of Medicine in Surgery, Director of Hepatology, Medical Director of Liver Transplantation, University of Pennsylvania, USA.

Serious adverse events (AEs) occurred in 9 (3%) and 3 (3%) patients in the active (immediate treatment) and placebo (deferred treatment) arms, respectively.

“Newer antiviral regimens such as the combination of grazoprevir/elbasvir offer much hope to people living with hepatitis C. They have shown great efficacy and tolerability for the treatment of this chronic infection,” said Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver.

C-EDGE TN is an international, randomised, blinded, placebo-controlled, parallel-group trial of an oral fixed-dosed combination of GZR 100 mg/EBR 50 mg once-daily in TN patients infected with HCV GT-1, -4 or -6, including cirrhotic and non-cirrhotic patients.

About The International Liver Congress™This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the

50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.



General Session 2, Hall DPresentation time: 08:30 – 08:45 Presenter: Stefan Zeuzem (Germany)Abstract G07: THE PHASE 3 EDGE TREATMENT-NAÏVE (TN) STUDY OF A 12-WEEK ORAL REGIMEN OF GRAZOPREVIR (GZR, MK-5172)/ELBASVIR (EBR, MK-8742) IN PATIENTS WITH CHRONIC HCV GENOTYPE (GT) 1, 4, OR 6 INFECTION

Non-alcoholic steatohepatitis associated with a 50% higher chance of death compared with non-alcoholic fatty liver disease Large population-based cohort provides important new insights into mortality and cardiovascular disease over the non-alcoholic fatty liver disease spectrum

April 24, 2015, Vienna, Austria: Results from a large population-based cohort of almost a million people in the UK found that the chances of dying from non-alcoholic steatohepatitis (NASH), over a 14-year period, was approximately 50% higher than for those with non-alcoholic fatty liver disease (NAFLD).

Reported today at The International Liver CongressTM 2015, the large study analysed the overall burden of cardiovascular disease and all-cause mortality across the spectrum of NAFLD. The four stages of NAFLD are steatosis (or simple fatty liver), non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis.

Data from over 900,000 patients in England was obtained from a local computerised hospital activity analysis register. Data was processed to identify patients with NAFLD, NASH and

NAFLD cirrhosis throughout the study period. Cardiovascular comorbidities were coded and their prevalence were analysed over 14 years.

During the 14-year study period, 2,701 patients were diagnosed with NAFLD-spectrum conditions: 1,294 with NAFLD, 122 with NASH and 1,285 with cirrhosis. All-cause mortality was higher in people with NASH than NAFLD (22.1% vs 14.5%) and in those with cirrhosis than NAFLD (53.1% vs 14.5%). Congestive cardiac failure was less prevalent in NAFLD than NASH and cirrhosis.

Dr Jake Mann, University of Cambridge, UK, concluded: “Non-alcoholic fatty liver disease is recognised as a risk factor for cardiovascular disease. Our results suggest that non-alcoholic steatohepatitis conveys an even greater risk. This study provides important new insights into mortality and burden of cardiovascular disease in patients across the non-alcoholic fatty liver disease spectrum.”

Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver, commented: “In non-alcoholic fatty liver disease, fat builds up in the liver which can cause inflammation and, eventually, lead to permanent scarring. Non-alcoholic fatty liver disease has four stages and these findings clearly link the severity of the disease with the increased risk of cardiovascular disease and death. It is therefore imperative that we identify people in the early stages of non-alcoholic fatty liver disease so they can be treated through diet and lifestyle interventions before their condition becomes potentially deadly.”




General Session 2, Hall DPresentation time: 10:15 – 10:30Presenter: Jake P. Mann (United Kingdom)

Abstract G12: THE BURDEN OF CARDIOVASCULAR DISEASE AND MORTALITY ACROSS A SPECTRUM OF NON-ALCOHOLIC FATTY LIVER DISEASE: A 14-YEAR FOLLOW-UP POPULATION STUDY OF 929,465 INDIVIDUALS

Ledipasvir-sofosbuvir combination proves highly effective in subset of patients with chronic hepatitis C Simple, ribavirin- and interferon-free, all-oral regimen provides new treatment option for people with hepatitis C, genotypes 4 and 5

April 24, 2015, Vienna, Austria: A new study presented today at The International Liver Congress™ 2015 has demonstrated that ledipasvir (LDV) in combination with sofosbuvir (SOF) achieves sustained virologic response rates 12 weeks after treatment (SVR12; primary endpoint), of 93% and 95% in patients chronically infected with hepatitis C virus (HCV) genotypes 4 or 5, respectively.

In the study, LDV/SOF was administered in a once-daily, fixed-dose combination tablet for 12 weeks to treatment-naive and treatment-experienced patients with or without cirrhosis. A total of 85 patients were enrolled in the study: 44 patients had GT-4 and 41 patients had GT5 chronic HCV infection. SVR12 rates were similar across all patient types.

HCV GT-4 is estimated to account for 8% to 13% and GT-5 for about 1% of all chronic HCV infections globally. Clinical studies evaluating the treatment outcome with new direct-acting antiviral agents in GT-4 and especially GT-5 HCV infection have been limited, to date.




Viral Hepatitis C: Clinical, Hall DPresentation time: 16:00 – 16:15Presenter: Armand Abergel (France)Abstract O056: LEDIPASVIR/SOFOSBUVIR TREATMENT RESULTS IN HIGH SVR RATES IN PATIENTS WITH CHRONIC GENOTYPE 4 AND 5 HCV INFECTION

Investigational anti-diabetic compound may offer potential for management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis Remogliflozin etabonate shown to reverse insulin resistance and provide anti-oxidant activity

April 23, 2015, Vienna, Austria: Data presented today at The International Liver Congress™ 2015 demonstrates that remogliflozin etabonate, an investigational drug in type 2 diabetes, is a potential treatment option for the management of patients with non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD).

In clinical studies, remogliflozin etabonate was shown to significantly improve insulin sensitivity and beta cell function, as well as reduce body weight and levels of alanine aminotransferase (ALT). In pre-clinical studies, remogliflozin etabonate significantly reduces fat accumulation in the liver and causes a marked reduction in the levels of circulating markers of oxidative stress. Unlike other drugs of its class (SGLT2 inhibitors), remogliflozin etabonate has intrinsic anti-oxidant activity, which may reverse the steatohepatitis and oxidative stress associated with the maintenance and progression of NASH.

The clinical study consisted of 336 treatment-naive subjects with type 2 diabetes and an HbA1c between 7.0% and 9.5%. Subjects were equally randomised to each of the remogliflozin etabonate treatments (50, 100, 250, 500 or 1000 mg twice daily), matching placebo or 30 mg pioglitazone (once daily). At Week 12, remogliflozin etabonate improved insulin sensitivity by 6-33% and beta cell function by 23-43%. Patients receiving remogliflozin etabonate also had significant weight loss (1.4-3.6 kg vs placebo). Importantly, post-hoc analysis of changes in ALT indicated that remogliflozin etabonate-treated subjects with elevated ALT showed statistically significant (p < 0.049) reductions of 32-42% at Week 12 as compared to placebo. “In multiple trials to date, remogliflozin etabonate has been shown to be a safe and potent anti-diabetic

compound. In addition to its ability to reverse insulin resistance and cause weight loss, it also uniquely offers intrinsic anti-oxidant activity, which may prove useful in the treatment of patients with NAFLD and NASH,” said William Wilkison, Ph.D., COO, Islet Sciences, Inc. “NAFLD and NASH are both closely associated with diabetes and obesity, and together are now considered the number one cause of liver disease in Western countries. Consequently there is an urgent need for effective treatment options for these diseases. We know that NASH is due, in part, to insulin resistance and oxidative stress resulting from steatosis. Given the mode of action of remogliflozin etabonate, it could potentially offer benefits when treating patients with both NASH and NAFLD,” said Professor Markus Peck, Secretary General, European Association for the Study of the Liver. About The International Liver Congress™ This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria. About EASL (www.easl.eu) Since EASL’s foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy. Contact For more information, please contact the ILC Press Office at: • [email protected] or • +44 (0)20 3580 5444

Genomic analyses point to the potential of personalised care for liver cancer patients Use of exome sequencing helps determine which hepatocellular carcinoma patients could benefit from targeted anticancer treatments

April 23, 2015, Vienna, Austria: A new study presented today at The International Liver Congress™ 2015 shows that by using genomic analyses to understand how and when carcinogenic mutations occur in patients with hepatocellular carcinoma (HCC), it is possible to identify specific molecular profiles. It is hoped that these molecular profiles will help identify which patients would benefit from specific anticancer treatments.

Using exome sequencing – a technique for sequencing all the protein-coding genes in a genome – the study identified relationships between environmental exposures, such as tobacco smoke and alcohol use, and mutational patterns in HCC. It also determined the landscape of driver genes and pathways altered in different clinical stages and aetiological backgrounds. Out of eight mutational signatures identified in the study, two new mutational signatures for HCC were found.

Professor Jessica Zucman-Rossi, director of the INSERM/university Paris Descartes “Functional Genomics of Solid Tumors” laboratory explained: “Mutational signatures help with understanding the biological history of a cancer and can enable differentiation between ongoing mutational processes and historical ones. This helps identify potential new targets for anticancer therapies.”

In the study, most patients had at least one damaging alteration which could potentially be treated with either an FDA-approved drug (28% of patients) or an investigational drug (86% of patients) which has been studied in Phase I to Phase III clinical trials.

“Hepatocarcinogenesis is a multi-step process in which pre-cancerous lesions can ultimately transform into liver cancer. Genomic analyses, such as exome sequencing, allow us to better understand the mutational processes involved in the development of cancers. This detailed knowledge then helps us to unravel the mutagenic processes and to optimise personalised patient care,” said Professor Markus Peck, Secretary General, European Association for the Study of the Liver.

The study authors hope that the use of exome sequencing will lead to the identification of potential new targets for anticancer therapy and create optimised personalised patient care.




Combination therapy offers new hope for difficult-to-treat patients with chronic hepatitis C Preliminary results from the SOLAR 2 trial show that ledipasvir/sofosbuvir in combination with ribavirin is safe and effective in patients with decompensated liver disease or who have undergone liver transplantation

April 23, 2015, Vienna, Austria: Results presented today at The International Liver Congress™ 2015 show that the use of the fixed-dose combination of ledipasvir/sofosbuvir (LDV/SOF) in combination with ribavirin (RBV) was well tolerated and demonstrated high sustained virologic response rates 12 weeks post treatment (SVR12) in patients with chronic hepatitis C virus (HCV) infection who have decompensated liver disease (cirrhosis) or have undergone liver transplantation.

SOLAR 2 data are presented for 328 HCV genotype-1 or -4 treatment-naive or treatment-experienced patients with decompensated liver disease or recurrent HCV following a liver transplant. More than 75 percent of patients in the study were treatment-experienced.

The participants were randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV. Ten patients were excluded from the analysis because of transplantation (n=7) or because they were pre-transplantation, but not decompensated (n=3); an additional 27 of these patients have not yet reached post-treatment week 12. The number and proportion of genotype 1 patients with available data achieving SVR12 are summarized in the table below:

Of the 32 genotype 4 patients, 27 (84%) achieved SVR12. Additionally, among patients with cirrhosis and decompensated cirrhosis before and after liver transplantation, virologic response was associated with improvements in Model for End-Stage Liver Disease (MELD) and CPT scores.

“Current treatment options are limited for HCV patients with decompensated liver disease or in those where the virus persists even after having a liver transplant,” said Professor Michael Manns, Professor and Chairman, Department of Gastroenterology, Hepatology and

Endocrinology,Hannover Medical School, Germany. “We are therefore pleased that the combination of LDV/SOF+RBV has proved to be so effective, and consider this a significant step forward in the management of these difficult-to-treat patients,” he added.

“As we constantly seek to improve the lives of people with chronic HCV, results from trials such as SOLAR 2 give hope to those with an advanced form of the disease such as cirrhosis and disease persisting even after a liver transplant,” said Professor Markus Peck, Secretary General, European Association for the Study of the Liver.In the study, the most common adverse events were fatigue, anaemia, nausea and headache. Sixty-nine patients (21 percent) experienced serious adverse events (SAEs). Nine patients had SAEs considered to be related treatment-related: anaemia (five), fall, diarrhoea, vomiting and hyperbilirubemia. Six patients have discontinued treatment.




New survey shows that half of people with hepatitis suffer from discrimination Findings reveal the extent to which stigma and discrimination affect those living with viral hepatitis

April 23, 2015, Vienna, Austria: As many as half of people infected with viral hepatitis have suffered discrimination and one-quarter admit that family members have avoided physical

contact with them after finding out they had the infection. A shocking patient survey presented at The International Liver CongressTM 2015 has shown the devastating impact the infection has on their daily lives.

Research conducted with the Ministry of Health in Brazil questioned 1,217 people infected with hepatitis B or C in Europe and America using an online survey tool. The aim of the research was to find out, from those infected, when and with what intensity stigma and discrimination affect their quality of life.

The survey revealed that nearly half (49.6%) of those infected have suffered some kind of discrimination. Of the 94.1% who told their family they had the infection, a quarter (24.6%) said that relatives started to avoid physical contact. Furthermore, of the 73.7% who told friends about their condition, nearly half (46.9%) said they suffered discrimination and 23.8% said they were no longer invited to social events.

“Few studies have evaluated the circumstances and the degree to which stigma and discrimination are present for those living with viral hepatitis. This is one of the first studies that listens to the voice of the patient in order to find out from them the context and intensity of stigma and discrimination that they experience and how it affects their quality of life,” said Carlos Varaldo, president of Grupo Otimismo ‘Support Group for People Who Live with Hepatitis’.

Of the 57.4% of those infected with viral hepatitis who told their partner about their condition, 33.3% said it affected their relationship and nearly half (42.7%) said it had an impact on their sex life.

Stigma and discrimination was also found to heavily impact the workplace. Of the 46.1% who told work colleagues, 10.1% lost their jobs. Self-image was affected in 55.8% of the cases and 41.4% said they felt ashamed of their condition.

The survey indicates that 70% of health professionals looked after sufferers properly; however, 24.6% of those health professionals have maintained a certain distance from the patient and 6.9% denied care to people infected with hepatitis, the survey revealed.

“This shocking survey highlights the true toll viral hepatitis can have on people’s lives. Not only are these people dealing with the illness, it is very evident that viral hepatitis infection still has a major stigma attached to it across all areas of people’s lives, including their family life and even the workplace,” said Marcelo C. M. Naveira – Viral Hepatitis Coordination, Secretariat for Disease Surveillance Ministry of Health of Brazil.

“The stigma and discrimination faced by people living with hepatitis is all too often based on misunderstandings about the virus and its transmission. Not only is this damaging to people diagnosed with the disease, but it may also discourage others from getting tested and accessing treatment and support. There is a pressing need to educate the general public about hepatitis to erode this stigma and break down barriers to timely testing, treatment and care for those who need it,” said Professor Markus Peck, Secretary General, European Association for the Study of the Liver.




Diabetes drug shows promise in the treatment of non-alcoholic steatohepatitis In a randomised controlled trial, liraglutide met the primary endpoint of histological clearance of non-alcoholic steatohepatitis, and a reduction in progression of fibrosis

April 23, 2015, Vienna, Austria: A drug approved to treat type 2 diabetes could prove to be a powerful new treatment option for non-alcoholic steatohepatitis (NASH), according to research presented today at The International Liver CongressTM 2015. Results from a randomised controlled trial showed liraglutide met the primary endpoint of histological clearance of NASH, and a reduction in the progression of fibrosis. The research was supported by the Wellcome Trust and the NIHR.

In the Liraglutide Efficacy and Action in NASH (LEAN) trial, overweight patients with biopsy-confirmed NASH were randomised (1:1) to receive a 48-week treatment with once-daily, subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). The primary outcome was improvement in liver histology, defined as ‘resolution of definite NASH’ and no worsening in fibrosis from baseline to end-of-treatment.

Of the 52 randomised patients, 45 underwent end-of-treatment liver biopsies. The primary endpoint was met, and 9 (39%) of 23 patients on liraglutide had resolution of definite NASH with no worsening of fibrosis compared to 2 (9%) of the 22 patients on placebo. Only 2 (9%) patients

on liraglutide had worsening of fibrosis compared to 8 (36%) on placebo. Moreover, liraglutide was shown to reduce weight, BMI and fasting glucose compared to placebo. There were no drug-related serious adverse events in patients on liraglutide.

Dr Matthew Armstrong, LEAN co-investigator, NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, commented: “Although NASH is the most common cause of chronic liver disease, there are still no licensed drugs to treat it. Results from the LEAN trial are a major breakthrough and point towards a potential treatment option for this disease. A Phase 3 trial is now needed to confirm the potential of this class of medication, known as human glucagon-like peptide-1 analogues, as a valid therapeutic option for patients with NASH.”

Professor Philip Newsome, LEAN Chief Investigator, NIHR Birmingham Liver Biomedical Research Unit, University of Birmingham, added: “Clearance of NASH in this study was very encouraging and means we are a step closer to new treatments for patients suffering with non-alcoholic fatty liver disease.”

“NASH occurs when the liver becomes inflamed due to the accumulation of fat. Over time, persistent inflammation can lead to the formation of fibrous scar tissue in the liver and around its blood vessels, which can eventually cause cirrhosis. In Europe, the prevalence of NASH is approximately 5% so we welcome the ongoing research and development in this area to help the millions of people affected by this disease,” said Professor Markus Peck, Secretary General, European Association for the Study of the Liver.

Notes to editors

The study research was supported by the Wellcome Trust and the National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit.

About the National Institute for Health ResearchThe National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (www.nihr.ac.uk).

About The International Liver Congress™This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the

50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.



Pooled analysis confirms vitamin E as a treatment for non-alcoholic steatohepatitis Study found that vitamin E is a safe and effective treatment for both adults and children

April 23, 2015, Vienna, Austria: Results revealed today at The International Liver Congress™ 2015 show that vitamin E (d-alpha-tocopherol) is an effective treatment for non-alcoholic steatohepatitis (NASH). NASH occurs when the liver becomes inflamed due to the accumulation of fat. Over time, persistent inflammation can lead to the formation of fibrous scar tissue in the liver and around its blood vessels, which can eventually cause cirrhosis.

A pooled analysis of data from two randomised trials comparing vitamin E versus placebo, and the placebo group from another trial comparing vitamin E use versus non-use, demonstrates that the efficacy of vitamin E is comparable to other treatments for NASH, including pioglitazone, metformin and obeticholic acid. In addition, treatment with vitamin E is associated with significant improvements in both NASH histology (45% vs 22% in those not treated with vitamin E) and resolution of disease (38% vs 20% in those not treated with vitamin E). There was no increase in cardiovascular events and no adverse lipid profiles were observed with vitamin E treatment.

A total of 347 patients (155 treated with vitamin E, 192 not treated with vitamin E) were included in the analysis which compared data from three clinical trials that investigated the efficacy and safety of vitamin E as a treatment for NASH: the PIVENS, TONIC and FLINT trials. Histologic improvement was defined as ≥ 2 point improvement in NAS with no worsening of fibrosis, and NASH resolution measured effectiveness.

The study supports the use of vitamin E as a treatment for NASH.




Daclatasvir-sofosbuvir combination is highly effective and well tolerated in patients with hepatitis C and HIV co-infection Results from ALLY-2 confirm drug was well tolerated and effective across genotypes 1-4

April 23, 2015, Vienna, Austria: Phase III results revealed today at The International Liver Congress™ 2015 show that once-daily treatment with daclatasvir (DCV) plus sofosbuvir (SOF) resulted in an overall 97% sustained virologic response (SVR) at 12 weeks post-treatment in patients with hepatitis C virus (HCV) and HIV co-infection, including cirrhotic patients.

HIV co-infection more than triples the risk of hepatitis C-related liver disease, liver failure and liver-related death. Co-infection can also complicate the management of HIV infection.

In the ALLY-2 randomised, open-label study, the combination of DCV+SOF was well tolerated and effective across the four different genotypes. Importantly, due to their limited pharmacokinetic interactions with other agents, DCV+SOF was able to work effectively across a broad range of concomitant combination antiretroviral therapy (cART) regimens without compromising HIV virologic control (98% of patients were on cART).

The study included treatment-naive (n = 151) and treatment-experienced (n = 52) adults co-infected with HIV and HCV. Treatment-naive patients were randomised 2:1 to receive 12 or 8 weeks of SOF 400 mg + DCV 60 mg (dose adjusted for cART); experienced patients received DCV+SOF for 12 weeks. The primary endpoint was SVR at post-treatment week 12 in treatment-naive genotype-1 patients who received 12 weeks of DCV+SOF.

A total of 98% of patients completed the study treatment. In genotype-1 patients, SVR was achieved by 96% of treatment-naive and 98% of experienced patients after 12 weeks of DCV+SOF. These positive results were also seen in genotype-2, -3 and -4 patients, with SVR at post-treatment week 12 reaching 100% (13/13), 100% (10/10) and 100% (3/3), respectively. Eight weeks of treatment appeared less effective with an SVR at 12 weeks post treatment of 76% in genotype-1 patients.

There were no treatment-related serious adverse events (AEs) and none of the patients stopped treatment due to AEs.

The results show that 12 weeks of DCV-SOF is a highly effective and well-tolerated treatment regimen for HCV in patients with HIV co-infection, including cirrhotic patients.




Herbal remedy derived from milk thistle demonstrates efficacy in non-alcoholic steatohepatitis Silymarin results in resolution of non-alcoholic steatohepatitis and improvement in fibrosis

April 23, 2015, Vienna, Austria: Results from a double-blind, placebo-controlled study of silymarin, which is derived from the milk thistle plant, have shown that this herbal remedy may be a useful treatment option for non-alcoholic steatohepatitis (NASH).

An interim analysis of the study, revealed today at The International Liver Congress™ 2015, shows a significantly higher percentage of patients experienced NASH resolution and improvement in fibrosis after 48 weeks of treatment with silymarin compared to placebo.

NASH occurs when the liver becomes inflamed due to the accumulation of fat. Over time, persistent inflammation can lead to the formation of fibrous scar tissue in the liver and around its blood vessels, which can eventually cause cirrhosis.

A total of 64 patients (silymarin = 30, placebo = 34) with biopsy-proven NASH had completed the study at the time of interim analysis. Silymarin has already demonstrated anti-oxidant, anti-inflammatory and anti-fibrotic properties, and these latest study results show that it may be a useful treatment for NASH.




Preliminary results show Civacir® prevents recurrence of hepatitis C in liver transplant patients Phase III data demonstrate prophylactic efficacy of Civacir® in patients who undergo antiviral therapy prior to transplantation

April 23, 2015, Vienna, Austria: New data from an ongoing Phase III trial revealed today at The International Liver CongressTM 2015 show that the use of hepatitis C immune globulin (HCIG, Civacir®) can effectively prevent hepatitis C virus (HCV) recurrence in patients following a liver transplant (LT). The data demonstrate that intravenous Civacir given both peri- and post-LT prevents HCV-reinfection in patients who also received antiviral therapy (AVT) before their transplant operation.

Civacir is a hepatitis C immune globulin (HCIG) produced from pooled plasma from hundreds of screened donors who have high antibody titers against HCV. In this trial, patients received AVT before their LT and those in the active treatment groups received 16 infusions of Civacir in the peri- and immediate post-LT period for 10 weeks. The control group received current standard of care (no treatment) post-LT.The preliminary results suggest that Civacir provides an effective alternative approach as compared to current standard of care to prevent HCV recurrence in post-LT patients. Civacir was well tolerated with no drug-related serious adverse events observed during the study.

Hepatitis C virus (HCV) remains the leading cause for liver transplantation (LT) and recurrent HCV disease is the most frequent cause of graft loss. Prevention of recurrence independent of genotype and severity of cirrhosis is highly desirable because it simplifies post-LT management.




All-oral, direct-acting antivirals show promise for hepatitis C and HIV co-infected, cirrhotic patients Latest results show sofosbuvir-based combinations are effective and well tolerated in difficult-to-treat patients

April 23, 2015, Vienna, Austria: A new study revealed today at The International Liver CongressTM 2015 shows that sofosbuvir (SOF)-based regimens are effective and well tolerated in hepatitis C and HIV co-infected, cirrhotic patients. Sustained virologic response at 4 weeks (SVR4) was observed in 98% of patients and in 95% at 12 weeks (SVR12).

The results are particularly encouraging as this patient group is considered difficult-to-treat and has a high mortality rate. The study included 142 patients of different hepatitis C virus (HCV) genotypes who were initiated onto SOF-based regimens.

Adverse events were reported in 42 patients (digestive 10%, anaemia 19%, asthenia 24%, others 48%). Treatment was stopped in 3 patients and dose-adjusted in 13.

These results show that direct-acting antivirals (DAAs) such as SOF-based regimens are effective and well tolerated in HIV-HCV co-infected, cirrhotic patients; however, it is important to note that surveillance for liver-related events should continue in these patients.


About EASL (www.easl.eu)Since EASL’s foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in

promoting research in liver disease, supporting wider education and promoting changes in European liver policy.


Many European countries ill-prepared to prevent and control the spread of viral hepatitis Comprehensive national strategies are urgently needed to manage the growing burden of disease

April 23, 2015, Vienna, Austria: Many countries in the World Health Organization (WHO) European Region are facing limitations in conducting chronic viral hepatitis disease surveillance, assessing the burden of disease and measuring the impact of interventions, according to results revealed today at The International Liver Congress™ 2015.

The study highlights that less than one-third (27%) of WHO European Member States have national strategies in place that contain a surveillance component. Furthermore, only 64% have a national surveillance system for chronic hepatitis B and 61% for chronic hepatitis C.

The study also reveals the main areas in which governments would like the WHO’s support:• Development of national plans for viral hepatitis prevention and control (39%)• Estimation of the national burden of viral hepatitis (34%)• Surveillance (23%)

The results were obtained by analysing the responses to surveillance-related questions in the WHO Global Hepatitis Policy Survey. In total, 44 out of 53 (83%) of the WHO European Member States responded to the survey.

The study demonstrates a clear need for better disease surveillance and improvements in the development of national strategies to help prevent and control the spread of viral hepatitis in the WHO European region.

About The International Liver Congress™This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe.

2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.



Global expansion of hepatitis vaccination and treatment is needed to make progress towards elimination of hepatitis B Expansion of existing interventions could prevent 13 million deaths due to hepatitis B

April 23, 2015, Vienna, Austria: Results revealed today at The International Liver Congress™ 2015 demonstrate current treatment and prevention programmes need to be scaled up in order to make elimination of hepatitis B virus (HBV) possible.

The study conducted by Imperial College Scientists, highlights that if existing interventions, such as infant hepatitis B vaccination and treatment programmes, were scaled up, the number of new chronic HBV infections could be reduced by 90% and mortality levels could be reduced by 65% by 2030. Globally, this would mean 13 million deaths could be prevented, including 6 million cancer cases.

Although universal infant vaccination programmes have proved successful in decreasing the number of new HBV infections, without further intervention the study estimates that the number of people infected with HBV will remain at the current level for the next 40 to 50 years, resulting in 20 million deaths by 2030.

The results were generated using a mathematical model of the worldwide HBV epidemic, which incorporated data on epidemiology, vaccination coverage, treatment, regional demography and the natural history of the virus. Predictions for incidence of new chronic infections, prevalence and HBV-related mortality were developed for interventions remaining at current levels. The

researchers then explored what scaling up of treatment and prevention would be needed to achieve control and elimination of HBV by 2030.

The study highlights the need to increase current levels of interventions, including the expansion of vaccination and treatment programmes, in order to significantly reduce the transmission of HBV and lower mortality.




Delaying treatment for hepatitis C puts patients’ lives at risk Analyses from the Veterans Administration healthcare system in the USA highlights dangers of delaying treatment to save costs

April 23, 2015, Vienna, Austria: Data revealed today at The International Liver Congress™ 2015 highlights the impact of delaying treatment for the hepatitis C virus (HCV). Researchers found that treatment delays have a serious detrimental effect on treatment efficacy, increasing the risk of morbidity and mortality among patients.

The study was conducted using retrospective patient data from the Veterans Administration in the USA to estimate the impact on risk of morbidity and death depending on whether treatment was initiated before or after a patient’s FIB4 levels became elevated. The FIB4 index is a simple formula used to predict liver damage (fibrosis) based on standard biochemical values and age.

Researchers found that delaying treatment until after a patient’s FIB4 level exceeds 3.25 has a clear detrimental effect on treatment effectiveness. Delaying therapy until after the patient’s FIB4 level exceeds 1.45 or 1.00 has a smaller detrimental effect on treatment effectiveness.

The study demonstrates that delaying HCV treatment in an attempt to save costs has a serious adverse impact on patients, with the most serious effect being the speeding up of time to death. Once HCV diagnosis has been confirmed the most suitable treatment should be initiated as soon as feasible balancing budgetary cash-flow issues against adverse impacts on patients.




All-oral, direct-acting antiviral treatment options for hepatitis C proven to be highly effective and well tolerated in patients with decompensated cirrhosis Interim report from the HCV-TARGET real world experience

April 23, 2015, Vienna, Austria: Interim data presented today at The International Liver CongressTM 2015 from the HCV-TARGET study show that all-oral, direct-acting antiviral therapy for hepatitis C (HCV) is well tolerated and highly effective in patients with

decompensated cirrhosis. Sustained virologic response (SVR) at 4 weeks was shown to be: sofosbuvir/ribavirin: 75%; sofosbuvir/simeprevir: 77%; sofosbuvir/simeprevir/ribavirin: 81%.

These results demonstrate that all-oral, direct-acting antiviral regimens are better tolerated and achieve higher rates of SVR in HCV patients with decompensated cirrhosis than older interferon-based therapy.

Importantly, markers of hepatic and synthetic liver function such as bilirubin and albumin values also improved during short-term follow-up. The analyses were restricted to patients with cirrhosis and a MELD score (scoring system to assess the severity of chronic liver disease) of ≥ 10 who had not undergone liver transplantation. Such well tolerated and highly efficacious therapy which can improve liver function presents an excellent option for many patients who do not have access to liver transplantation.

HCV-TARGET is an international research consortium of leading HCV investigators who have established a common research database and are conducting a longitudinal observational study to answer important questions about HCV therapy with direct-acting antiviral agents.




Novel immunotherapeutic, TG1050, shows early signs of potential for chronic hepatitis B cure

Study results show TG1050 achieves key clinical goals in mouse models

April 23, 2015, Vienna, Austria: A novel immunotherapeutic in early development for chronic hepatitis B (CHB), TG1050, has been shown to reach the clinical goals that are considered to be the hallmarks of a cure for CHB, according to results revealed today at The International Liver Congress™ 2015.

The hallmarks of a CHB cure are:• Elimination of HBsAg – the surface antigen of the hepatitis B virus, and• HBsAg seroconversion – which occurs when a specific antibody becomes detectable in the blood and the corresponding antigen becomes undetectable, in this case HBsAg

In the study, decrease of HBsAg and HBsAg seroconversion was achieved in 30% of TG1050-injected mice.

Earlier studies have proven that TG1050 is able to induce a robust, multi-specific and long-lasting immune response against the hepatitis B virus. These latest results, which show that TG1050 is able to decrease HBsAg and lead to anti-HBsAg seroconversion in HBV persistent mouse models, support the move to a first-in-man study and the start of clinical development.

About The International Liver Congress™This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26 2015, Vienna, Austria.



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