CHILDHOOD OBESITY LINKED TO INCREASED RISK OF HEPATOCELLULAR CARCINOMA IN ADULTHOOD

Barcelona, Spain, 19 April 2012 /PRNewswire/ — Childhood obesity is a widespread global epidemic and in parallel with non-alcoholic fatty liver disease (NAFLD)2 is now the leading cause of liver disease among children. New data presented today at the International Liver CongressTM 2012 furthers this concern by showing that childhood obesity is positively linked with developing hepatocellular carcinoma (HCC) the most common form of liver cancer in adulthood. 4

The Danish study monitored birth weight and BMI at school age of 165,540 men and 160,883 women born between 1930 and 1989. The study authors calculated and compared the risk of developing HCC from the 252 participants that had developed HCC at follow-up. At age 7 the risk of developing HCC increased by 1.12 per unit of increase in BMI; however, at age 13 this risk increased to 1.25. Therefore, as units of BMI increased into adulthood, so did the risk of developing HCC. This was consistently similar across the sexes and ages.

EASL Scientific Committee Member Dr. Frank Lammert commented: “Childhood obesity not only leads to the development of many adverse metabolic conditions, such as Type 2 Diabetes and heart disease, but also fatty liver disease, which may subsequently result in liver cancer. The importance of maintaining a healthy childhood BMI cannot be underestimated. These alarming study results point to a potential correlation between childhood obesity and development of liver cancer in adulthood.”

Other factors in the development of liver cancer include alcoholic conditions, infection by hepatitis B and C and other liver diseases.5 Results did not change when participants with these co-morbidities were removed from the study, indicating that childhood obesity was the major factor in the development of HCC. Only around 10-20% of liver cancers can be removed completely with surgery and if this is not successful the disease is usually fatal within 3-6 months.3 Therefore prevention is the best protection against the development of liver cancer.

This study was funded by and carried out as part of the FLIP (Fatty Liver Inhibition of Progression) consortia, built around practising clinical hepatologists, basic scientists and two industrial partners who focus on research into the underlying mechanisms and management of patients with NAFLD. The aim of the FLIP project is to understand and prevent the progression of NAFLD into more severe conditions, such as cirrhosis and hepatocellular carcinoma. The project is supported by the European Commission through the Seventh Framework Programme for Research and Development and has been running since January 1st 2010.


Notes to Editors

About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL 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.

EASL’s main focus on education and research is delivered through numerous events and initiatives, including:

  • The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
  • Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
  • Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
  • Journal of Hepatology published monthly
  • Participation in a number of policy initiatives at European level
  • iLiver iPhone app: a free medical app developed by EASL, with content fully authored, validated and accredited by 42 independent liver specialists

About The International Liver CongressTM 2012
The International Liver CongresTM 2012, the 47th annual meeting of the European Association for the study of the Liver, is being held at the Centre Convencions Internacional (CCIB) in Barcelona from April 18 – 22, 2012. The congress annually attracts over 8,300 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com
Travis Taylor: Onsite tel: +44-7894-386-422
Vicky O'Conner: Onsite tel: +44-7894-386-428

References

1. WHO 2012, http://www.who.int/dietphysicalactivity/childhood/en/

2. Angulo P, Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31

3. Hepatocellular carcinoma, ADAM Medical Encyclopedia 2011

4. Berentzen TL et al (2012) Childhood body size and the risk of hepatocellular carcinoma. Abstract presented at the International Liver CongresTM 2012.

5. El-Serag HB, Hepatocellular Carcinoma. N Engl J Med 2011;365:1118-1127

GUT MICROBIOTA TRANSPLANTATION MAY PREVENT DEVELOPMENT OF DIABETES AND FATTY LIVER DISEASE

Barcelona, Spain, 19 April 2012 /PRNewswire/ — Exciting new data presented today at the International Liver CongressTM 2012 shows the gut microbiota’s causal role in the development of diabetes and non-alcoholic fatty liver disease (NAFLD), independent of obesity1. Though an early stage animal model, the French study highlights the possibility of preventing diabetes and NAFLD with gut microbiota transplantation – the engrafting of new microbiota, usually through administering faecal material from a healthy donor into the colon of a diseased recipient.2

In the 16 week study, two groups of germ free mice received gut microbiota transplants; one set from donor mice displaying symptoms of insulin resistance and liver steatosis (responders), the other from normal mice (non responders). The donor mice were selected due to their response to being fed a high fat diet.

The germ free group that received microbiota from symptomatic mice (responder receivers - RR) showed higher levels of fat concentration in the liver as well as being insulin resistant. The germ free group that received microbiota from healthy mice (non-responder-receivers – NRR) maintained normal glucose levels and sensitivity to insulin.

EASL Scientific Committee Member Dr Frank Lammert said: “The factors leading to Non-Alcoholic Fatty Liver Disease (NAFLD) are poorly understood, but it is known that NAFLD and Type 2 diabetes are characterised, respectively, by liver inflammation and metabolic disorders like insulin resistance.”

“This study shows that different microbiota cause different metabolic responses in animals. By implanting microbiota from healthy mice, the study authors prevented the development of liver inflammation and insulin resistance, both indications of liver disease and diabetes. Thus, gut microbiota transplants could have a therapeutic role in the development of these diseases.”

The RR mice also showed lower levels of microorganisms than usually found in the healthy gut. Lachnospiraceae was identified as the species most important in developing fatty liver and insulin resistance.

At present, the intestinal microbiota is considered to constitute a “microbial organ”: one that has pivotal roles in the body’s metabolism as well as immune function. Therefore transplantation aims to restore gut functionality and re-establish a certain state of intestinal flora.


Notes to Editors

About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL 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.

EASL’s main focus on education and research is delivered through numerous events and initiatives, including:

  • The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
  • Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
  • Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
  • Journal of Hepatology published monthly
  • Participation in a number of policy initiatives at European level
  • iLiver iPhone app: a free medical app developed by EASL, with content fully authored, validated and accredited by 42 independent liver specialists

About The International Liver CongressTM 2012
The International Liver CongressTM 2012, the 47th annual meeting of the European Association for the study of the Liver, is being held at the Centre Convencions Internacional (CCIB) in Barcelona from April 18 – 22, 2012. The congress annually attracts over 8,300 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com
Travis Taylor: Onsite tel: +44 7894 386 422
Vicky O'Conner: Offsite tel: +44 7894 386 428

References

1. Le Roy T et al. Gut microbiota transplantation demonstrates its causal role in the development of type 2 diabetes and fatty liver. Abstract presented at the International Liver CongressTM 2012

2. Khoruts A and Sadowsky MJ, Therapeutic transplantation of the distal gut microbiota. Mucosal Immunology 2011;4:4-7.

Chronic Hepatic Diseases Generate High Costs to Europe

Separate Study Links Acute-on-Chronic Liver Failure to High Short-Term Mortality

Barcelona, Spain, 19 April 2012 /PRNewswire/ — Two studies presented at the International Liver CongressTM 2012 show the true impact that liver disease has across Europe. One highlights the financial cost of liver disease to the community and the second highlights the high mortality rates associated with cirrhosis.

A naturalistic, multicenter, retrospective, Cost of Illness study (COME) was developed to assess costs occurring in 1,088 patients over six months. Patients enrolled had liver diseases including hepatitis C, cirrhosis, hepatitis B, hepatic carcinoma and other hepatic diseases (cholestasis, NASH etc.). The study found that liver disease cost the EU on average at least €644.77 per patient per month1. Hospitalisations account for 50.6% of the overall mean direct costs per month, with treatment accounting for 41.2% of costs1. In addition, patients and family caregivers lost an average of 1.15 days per patient per month of productivity, an important indirect cost.

EASL Vice Secretary Professor Markus Peck-Radosavljeic commented: “These results demonstrate the real life costs involved in the treatment and ongoing management of patients with liver disease. Liver disease is an increasing problem and having concrete information on the financial impact can help us plan our treatment strategies more effectively and more importantly, might engage health authorities more to invest into preventive action like reducing harmful alcohol consumption and fight obesity.”

The study concludes that although treatment costs account for just over 40% of direct costs, the use of efficient treatments is necessary to reduce worsening of patients’ health, direct and indirect costs.

In a separate study the EASL-CLIF consortium report that 28 day mortality for Acute-on-Chronic liver failure (ACLF) is 35.5% . The consortium set out to address questions around ACLF, a poorly defined syndrome characterized by acute deterioration of cirrhosis, representing a main cause of hospitalisation and death. At present, no diagnostic criteria and information on prevalence, pathogenesis or prognosis are available. The consortium aimed to develop a new score (CLIF-SOFA, derived from the existing sequential organ failure assessment score) to assess the severity and number of organ failures.

1,379 patients, admitted to 29 hospitals due to complications of cirrhosis, were enrolled in this observational prospective European CANONIC study. Data presented at The International Liver Congress™2012 reports on results of the first 920 cases.

Four grades of ACLF were identified:

  • ACLF-1: renal failure or a nonrenal organ failure associated with creatinine 1.5-2 mg/dL and/or grade I-II encephalopathy
  • ACLF-2: 2 organ failures
  • ACLF-3: 3 organ failures
  • ACLF-4: 4-6 organ failures

The overall prevalence of ACLFwas 22.6% with twenty-eight-day mortality of ACLF patients at 35.3% compared (but as high as 85.7% in ACLF-4 patients) to only 4.1% in patients without ACLF. ACLFoften developed in patients with previously compensated (21%) or recently decompensated (< 3 months, 18%) cirrhosis and was significantly associated with bacterial infections and active alcoholism, but not gastrointestinal hemorrhage. Hepatitis, TIPS, paracentesis without albumin and surgery were infrequent precipitating events. In about 20% of cases no precipitating event was identified. ACLF was associated with an inflammatory reaction (both in infected and not infected patients) as estimated by increased WBC and plasma C-reactive protein levels.


Notes to Editors

About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL 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.

EASL’s main focus on education and research is delivered through numerous events and initiatives, including:

  • The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
  • Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
  • Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
  • Journal of Hepatology published monthly
  • Participation in a number of policy initiatives at European level
  • iLiver iPhone app: a free medical app developed by EASL, with content fully authored, validated and accredited by 42 independent liver specialists

About The International Liver CongressTM 2012
The International Liver CongressTM 2012, the 47th annual meeting of the European Association for the study of the Liver, is being held at the Centre Convencions Internacional (CCIB) in Barcelona from April 18 – 22, 2012. The congress annually attracts over 8,300 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com
Travis Taylor: Onsite tel: +44 7894 386 422
Vicky O'Conner: Offsite tel: +44 7894 386 428

References

1. Fagiuoli S, et al, Societal burden in patients with Chronic Hepatic Diseases: the COME study results. Abstract presented at the International Liver CongressTM 2012.

2. Moreau R, et al, DIAGNOSIS, PREVALENCE, AND PROGNOSIS OF ACUTE-ON-CHRONIC LIVER FAILURE (ACLF): RESULTS OF THE EASL-CHRONIC LIVER FAILURE (CLIF) CONSORTIUM CANONIC STUDY. Abstract presented at the International Liver CongressTM 2012.

NEW DATA SUGGESTS INTERFERON-FREE THERAPY AROUND THE CORNER FOR HCV PATIENTS

Further data shows PegIFN-λ’s comparable efficacy but better safety profile than PegIFN-α

Barcelona, Spain, 19 April 2012 /PRNewswire/ — New data presented at the International Liver Congress™ 2012 shows consolidation of the interferon-free (IFN) revolution in HCV treatment. The much anticipated data from a number of clinical trials 1,2,3,4,5,6 confirm that combinations of antivirals offer the hope of shorter, more effective treatment with fewer side effects.

The following new studies cover the treatment of HCV patients with genotypes (GT) 1, 2 or 3, who were administered ribavirin (RBV) - without IFN - and either one or two other drugs: direct-acting antivirals HCV nucleotide analogues, HCV protease inhibitors, non-nucleoside RNA polymerase inhibitors – or host-targeting antivirals cyclophilin A inhibitor.

PROTON & ELECTRON

  • Lawitz E, et al ‘PSI-7977 PROTON and ELECTRON: 100% concordance of SVR4 with SVR24 in HCV GT1, GT2, & GT3’ and the related abstract Gane EJ, et al ‘ELECTRON: once daily PSI-7977 plus RBV in HCV GT1/2/3’.
  • In Lawitz E, et al, 100% of HCV GT2 or 3 patients (10) achieved SVR4 after treatment with PSI-7977 and RBV. In Gane EJ, et al, of nine HCV GT1 prior null-responders treated with PSI-7977 and RBV for 12 weeks, 7 had undetectable levels of HCV RNA by week 2.

SOUND-C2

  • Zeuzem S, et al ‘SVR4 and SVR12 with an INTERFERON-FREE regimen of BI201335 and BI207127, +/- RIBAVIRIN, in treatment-naïve patients with chronic genotype-1 HCV infection: interim results of SOUND-C2’.
  • Treatment-naïve GT1 HCV patients treated with a regimen of BI201335, BI207127 and RBV achieved 60% SVR12 after 16 weeks of treatment and up to 70% SVR4 after treatment with a lower BI207127 dose (600mg BID) for 28 weeks.

VITAL-1

  • Pawlotsky J-M, et al ‘ALISPORIVIR plus RIBAVIRIN is highly effective as INTERFERON-FREE or INTERFERON-ADD-ON regimen in previously untreated HCV-GT2 or GT3 patients: SVR12 results from VITAL-1 phase 2b study’ and the related abstract Alberti A, et al ‘ALISPORIVIR (ALV) plus PEG-INTERFERON/RIBAVIRIN (PR) in HCV G1 treatment-experienced patients achieves primary endpoint with superior efficacy at treatment week 12 compared to retreatment with PR’.
  • In Pawlotsky J-M, et al, 88% of treatment-naïve HCV GT2 or 3 patients achieved SVR 12 after treatment with Alisporivir and RBV. In Alberti A, et al, 70% of null non-responders achieved cEVR when treated with Alisporivir, IFN and RBV.

AI444040

  • Sulkowski M, et al ‘Potent viral suppression with all-oral combination of DACLATASVIR (ns5a inhibitor) and GS-7977 (ns5b inhibitor), +/-RIBAVIRIN, in treatment-naïve patients with chronic HCV GT1, 2, or 3’
  • Treatment-naïve HCV GT1, 2, and 3 patients given an IFN- and RBV-free once-daily combination of DACLATASVIR and GS-7977 for 24 weeks achieved high rates of early virologic response (HCV RNA detectable at week 4 but undetectable at week 12 EVR) by mITT analysis: 97% EVR in GT1, 90% in GT2 and 3.

The combination of PegIFN-α and ribavirin (RBV) is the current standard of care for chronic HCV7, but is associated with a number of side effects – including flu-like symptoms, psychiatric manifestations, autoimmune reactions, and hematologic toxicities.8,9 Between 20-40% of patients require a dose reduction or temporary interruption in their PegIFN-α and ribavirin (RBV) treatment10 and in 10-14% of patients, side effects are so severe that treatment must be discontinued.8,9

However, studies have shown that achieving a virologic response in chronic HCV is much more dependent on the dose of IFN-α11/PegIFN-α12,13,14 than RBV15,16,17,11,18. As such, PegIFN-α free therapy is highly anticipated by healthcare professionals and patients alike.

EASL’s Secretary General Professor Mark Thursz commented on the exciting new data being showcased at the congress: “In the future, patients can look forward to all oral treatment regimens with high success rates and low side effects. Furthermore, there is a large cohort of patients with more advanced liver disease who will now be able to access treatment that was previously impossible due to the side effects of Interferon-alpha. Over the last five years we have seen an evolution in HCV treatment, with direct antivirals used in combination with Pegylated Interferon and Ribavirin. Interferon-free regimes truly represent a revolution in treatment.”

Separate data presented at the congress may provide a further option. New results from a phase IIb study show a different form of interferon pegylated Interferon-lambda (PegIFN-λ) – administered with RBV for 24 weeks in HCV GT2 & 3 patients gives comparable SVR24 (undetectable HCV RNA levels 24 weeks after treatment) to PegIFN-α-2a and RBV, but with fewer side effects (musculoskeletal and flu-like symptoms, hematologic toxicity) and dose modifications for PegIFN or RBV.

EASL’s Secretary General Professor Mark Thursz commented: “It remains possible that a number of patients will still need interferon based therapy for their HCV infection. Interferon-lambda, with a better side effect profile, looks like an excellent option in this group of patients, who are likely to have more advanced disease.”


Notes to Editors

About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL 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.

EASL’s main focus on education and research is delivered through numerous events and initiatives, including:

  • The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
  • Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
  • Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
  • Journal of Hepatology published monthly
  • Participation in a number of policy initiatives at European level
  • iLiver iPhone app: a free medical app developed by EASL, with content fully authored, validated and accredited by 42 independent liver specialists

About The International Liver CongressTM 2012
The International Liver CongressTM 2012, the 47th annual meeting of the European Association for the study of the Liver, is being held at the Centre Convencions Internacional (CCIB) in Barcelona from April 18 – 22, 2012. The congress annually attracts over 8,300 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com
Travis Taylor: Onsite tel: +44 7894 386 422
Vicky O'Conner: Offsite tel: +44 7894 386 428

References

1. Lawitz E, et al, PSI-7977 PROTON and ELECTRON: 100% CONCORDANCE OF SVR4 WITH SVR24 IN HCV GT1, GT2, & GT3. Abstract presented at the International Liver CongresTM 2012.

2. Gane EJ, et al, ELECTRON: ONCE DAILY PSI-7977 PLUS RBV IN HCV GT1/2/3. Abstract presented at the International Liver CongressTM 2012.

3. Zeuzem S, et al, SVR4 and SVR12 WITH AN INTERFERON-FREE REGIMEN OF BI201335 AND BI207127, +/- RIBAVIRIN, IN TREATMENT-NAÏVE PATIENTS WITH CHRONIC GENOTYPE-1 HCV INFECTION: INTERIM RESULTS OF SOUND-C2. Abstract presented at the International Liver CongressTM 2012.

4. Pawlotsky J-M, et al, ALISPORIVIR PLUS RIBAVIRIN IS HIGHLY EFFECTIVE AS INTERFERON-FREE OR INTERFERON-ADD-ON REGIMEN IN PREVIOUSLY UNTREATED HCV-GT2 OR GT3 PATIENTS: SVR12 RESULTS FROM VITAL-1 PHASE 2B STUDY. Abstract presented at the International Liver CongressTM 2012.

5. Alberti A, et al, ALISPORIVIR (ALV) PLUS PEG-INTERFERON/RIBAVIRIN (PR) IN HCV G1 TREATMENT-EXPERIENCED PATIENTS ACHIEVES PRIMARY ENDPOINT WITH SUPERIOR EFFICACY AT TREATMENT WEEK 12 COMPARED TO RETREATMENT WITH PR. Abstract presented at the International Liver Congress™ 2012.

6. Sulkowski M, et al, POTENT VIRAL SUPPRESSION WITH ALL-ORAL COMBINATION OF DACLATASVIR (NS5A INHIBITOR) AND GS-7977 (NS5B INHIBITOR), +/-RIBAVIRIN, IN TREATMENT-NAÏVE PATIENTS WITH CHRONIC HCV GT1, 2, OR 3. Abstract presented at the International Liver Congress™ 2012.

7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 2011 vol. 55 245–264

8. Fried MW, et al, Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

9. Manns MP, et al, Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

10. Jang JY and Chung RT, Chronic Hepatitis C. Gut Liver. 2011 June; 5(2): 117–132.

11. McHutchison JG, et al, Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002 Oct;123(4):1061-9.

12. Heathcote EJ, et al, Re-treatment of chronic hepatitis C with consensus interferon. Hepatology. 1998 Apr;27(4):1136-43.

13. Lindsay KL, et al, A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology. 2001;34:395–403.

14. Reddy KR, et al, Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C. Hepatology. 2001;33:433–438.

15. Shiffman ML, et al, Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology. 2007;46:371–379.

16. Snoeck E, Wade JR, Duff F, Lamb M, Jorga K. Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. Br J Clin Pharmacol. 2006;62:699–709.

17. Shiffman ML, Ghany MG, Morgan TR, et al. Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C. Gastroenterology. 2007;132:103–112.

18. Hadziyannis SJ, Sette H, Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–355.

19. Zeuzem S, et al, PEGINTERFERON LAMBDA-1a (LAMBDA) COMPARED TO PEGINTERFERON ALFA-2A (ALFA) IN TREATMENT-NAÏVE PATIENTS WITH HCV GENOTYPES (G) 2 or 3: FIRST SVR24 RESULTS FROM EMERGE PHASE IIB. Abstract presented at the International Liver CongressTM 2012.