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Pre-EASL Notes from Jules
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from Jules Levin, NATAP: Here are 4 official EASL press releases on studies to be presented at EASL 2016 starting Thursday April 14 to the 17th.
In the shadow of terrorist unrest in Europe thousands gather at EASL in Barcelona where the very latest in research will be presented including data for new DAAs. We will see significant improvements in HCV therapy in the near future with new DAA regimens including 2nd generation drugs that are more potent and effective and are showing 98-99% SVR rates in studies and are pangenotypic. Abbvie, Gilead, Merck and J&J are developing these new potent regimens that contain 2nd generation HCV drugs, and many of which contain 3 drugs instead of the 2 drugs in the currently available therapy regimens. The new Abbvie regimen has 2 drugs, 2nd generation NS5A & protease: ABT530+ ABT493. Gilead has 2 new regimens coming first in July with Sofosbuvir/Velpatasvir, and in the future Sofosvuvir/Velpatasvir + GS-9857, a 2nd generation protease. Merck is developing a 3-drug 2nd generation regimen that includes their current protease grazoprevir+ a new 2nd generation NS5A MK-8408 and a nucleotide like sofosbuvir named MK-3682. J&J is developing a new 3-drug regimen that includes AL-335 a new nucleotide like sofosbuvir, plus a new 2nd generation NS5A ACH-3102 and also including their protease simeprevir, and they also have another new nucleotide polymerase inhibitor, JNJ-54257099. These new therapies will provide even greater strides forward in treatment.
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High rate of cancer recurrence in Hepatitis C patients despite successful virus eradication by direct-acting antiviral therapy
April 13, 2016
Scientists call for close monitoring of Hepatitis C virus patients prescribed direct-acting antivirals, particularly for those with a history of liver cancer
April 13, 2016, Barcelona, Spain: Data from a new study show that patients with Hepatitis C virus (HCV) taking direct-acting antiviral treatments (DAAs), who have previously fought off hepatocellular carcinoma (HCC), the most common form of liver cancer,1 had a 'high rate' of re-developing their illness. The large retrospective cohort study, presented today at The International Liver CongressTM in Barcelona, Spain found 29% of patients who had a history of HCC re-developed the condition during or after taking DAAs.
According to the World Health Organization, liver cancer accounts for 662,000 deaths and is the third leading cause of cancer-related death, exceeded only by cancer of the lung and stomach.2 Approximately 75% to 80% of cases of HCC occur in Asia, however, there is considerable variation within continents.2 The overwhelming majority of HCC cases occur in patients with chronic liver disease, where approximately 80% to 90% have cirrhosis (scarring of liver tissue), and most of the remainder have moderate to advanced fibrosis (an accumulation of scar tissue in the liver).2
"Even in a relatively short observation period, we have shown that high recurrence rates of hepatocellular carcinoma can occur in Hepatitis C patients taking direct-acting antivirals," said Dr Federica Buonfiglioli, DIMEC, University of Bologna, Italy and study author. "Even though further investigation is needed, we believe our findings justify close monitoring for all cirrhotic patients on such treatments."
In the Italian study, medical records of 344 HIV-negative patients with HCV related cirrhosis, who did not have active HCC, were analysed. All patients had received treatment with one of the following DAA combinations: sofosbuvir and simeprevir (34%), 3D combination* (22%), sofosbuvir and ribavirin (17%), sofosbuvir and daclatasvir (16%) and sofosbuvir and ledipasvir (10%). Occurrences of HCC were assessed by comparing baseline enhanced-ultrasonography and MRI/CT-scans with those taken during the six month post treatment follow-up.
Sustained virologic response was achieved in 89% of patients at 12 weeks post treatment. At 24 weeks post treatment, active HCC was detected in 7.6% of all patients (n=26) without a history of HCC - deemed to be a 'standard rate' by the study authors. However, in the 59 patients who had a previous history of HCC, a 'high rate' of 29% (n=17) redeveloped the condition.
"These initial findings provide important insight to how Hepatitis C management strategies could be developed to detect HCC early in patients who are most at risk," said Professor Laurent Castera, EASL Secretary General. "These findings deserve further investigation given their clinical significance."
* 3D combination consists of ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir, and the nonnucleoside polymerase inhibitor dasabuvir and ribavirin
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Increase in coffee consumption could provide a protective effect in non-alcoholic fatty liver disease
April 13, 2016
A daily dose of coffee could improve several key markers of non-alcoholic fatty liver disease by reducing permeability of the gut
April 13, 2016, Barcelona, Spain: Adding coffee to the diet of people with non-alcoholic fatty liver disease (NAFLD) could help reverse the condition, according to a new study conducted in mice presented at The International Liver CongressTM 2016 in Barcelona, Spain.
The study found that a daily dose of coffee (equivalent to six cups of espresso coffee for a 70kg person) improved several key markers of NAFLD in mice that were fed a high fat diet. These mice also gained less weight than others fed the same diet without the dose of caffeine.
The scientists also showed how coffee protects against NAFLD by raising levels of a protein called Zonulin (ZO)-1, which lessens the permeability of the gut.1 Experts believe that increased gut permeability contributes to liver injury and worsens NAFLD.2 People suffering from NAFLD can develop scaring of the liver, also known as fibrosis, which can progress to a potentially life-threatening condition known as cirrhosis.3
"Previous studies have confirmed how coffee can reverse the damage of NAFLD but this is the first to demonstrate that it can influence the permeability of the intestine," said Vincenzo Lembo, at the University of Napoli, Italy and study author. "The results also show that coffee can reverse NAFLD-related problems such as ballooning degeneration, a form of liver cell degeneration."
Researchers analysed three different groups of mice over a 12 week period. Group one received a standard diet, group two had a high fat diet and group three was given a high fat diet plus a decaffeinated coffee solution.
Coffee supplementation to a high fat diet significantly reversed levels of cholesterol (p<0.001), alanine aminotransferase (an enzyme which levels increase in the blood when the liver is damaged) (p<0.05), amount of fat in the liver cells (steatosis) (p<0.001) and ballooning degeneration (p<0.05). The combination of coffee and a high fat diet also reduced weight gain over time (p=0.028) in the mice. The study results suggest that coffee supplementation could cause variations in the intestinal tight junctions, which regulate the permeability of the intestine.4
"Italy is famous for its coffee and this Italian study has reinforced our knowledge on the link between it and non-alcoholic fatty liver disease," said Professor Laurent Castera, EASL Secretary General. "Although not suggesting that we should consume greater levels of coffee, the study offers insights that can help future research into and understanding of the therapeutic role coffee can play in combating NAFLD."
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Differing perspectives on antiviral treatment efficacy in patients co-infected with HIV and HCV
April 13, 2016
Approximately 2.3 million people worldwide are co-infected with HIV and HCV1
April 13, 2016, Barcelona, Spain: Two separate studies presented today at The International Liver Congress™ 2016 in Barcelona, Spain have offered alternative conclusions regarding the efficacy of direct-acting antivirals (DAAs) among patients co-infected with HIV and Hepatitis C virus (HCV).
GEHEP-SEIMC and HEPAVIR study group data:
In this prospective, multi-cohort study from Spain, researchers have shown that HIV negatively impacts rates of response to DAA medications in people co-infected with HCV. Patients with HIV and HCV co-infection had an 11% lower rate of achieving SVR12 (or the eradication of HCV from the body at 12 weeks) with interferon-based DAAs compared to patients with only HCV. Those co-infected patients taking interferon-free DAAs had a 6% lower rate of achieving SVR12 compared to patients with only HCV.
"Our study demonstrates the impact of HIV co-infection on the effectiveness of DAA-based treatment," said Dr Karin Neukam from the Unit of Infectious Diseases and Microbiology, University Hospital of Valme, Seville, Spain and lead author of the study. "We must keep a close eye on co-infected patients to ensure that they receive the treatment they need."
The study was conducted in 1,276 patients from 33 hospitals throughout Spain. The primary efficacy outcome was the achievement of SVR at 12 weeks and the primary safety outcome was the discontinuation of therapy due to adverse events.
US Veterans Health Administration study data:
By contrast, data from a US real-world retrospective study of 408 patients predominantly of genotype 1 (GT1=79%) HCV infection found SVR rates in excess of 88% at 12 weeks post treatment with combinations of simeprevir and sofosbuvir, ledipasvir and sofosbuvir, or ombitsavir, paritaprevir, ritonavir and dasabuvir. In this study, a logistic regression analysis controlling for patient demographics, disease severity and other co-morbidities led the study authors to conclude that a statistically significant impact of HIV co-infection on achieving SVR12 could not be found.
"Our analysis showed that across the three treatments in our study, there was no statistically significant impact of HIV co-infection on the effectiveness of the DAAs," said Justin McGinnis from the University of Southern California, California, USA. "We know that these patients are at increased risk of liver disease progression from their HCV status, and these data suggest the co-infected patient group could benefit from treatment."
"These differing data confirm that the study of HCV treatment in HIV co-infected patients remains an interesting and valuable subject for study," said Professor Laurent Castera, EASL Secretary General. "More research is needed to come to a viable resolution so we can provide the best care for these co-infected patients."
About HCV and HIV coinfection
Between 130 and 150 million people globally have chronic Hepatitis C infection,2 with 15 million people in the World Health Organization's EU Region.3 A recent study demonstrated that worldwide, there are approximately 2.3 million people with HIV and HCV co-infection and 60% of these people with co-infection also are injecting drug users.1 Treatment with DAAs has become the gold standard of care for patients with HCV, with cure rates of nearly 100% demonstrated in clinical trials.4,5,6,7 Treatment of HIV and HCV co-infected patients requires healthcare professionals to be acutely aware of the complex drug interactions that can occur between DAAs and antiretroviral medications.
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Community-based treatment providers can help ease pressure on specialists in the battle against Hepatitis C
April 13, 2016
New research reveals the potential for community-based non-specialist providers to ease the growing pressure on specialist providers of Hepatitis C therapies
April 13, 2016, Barcelona, Spain: A new study, presented today, demonstrates treatment for Hepatitis C can be provided safely and effectively within a community-based and non-specialist setting. This illustrates the potential for alternative providers to ease pressure on currently overburdened specialists. The study, sponsored by the National Institutes of Health, was presented at The International Liver Congress™ 2016 in Barcelona, Spain.
Between 130 and 150 million people globally have chronic Hepatitis C virus (HCV) infection.1 It is estimated that 15 million people in the World Health Organization's EU Region are living with Hepatitis C, representing 2% of adults.2
"With such a large patient cohort, ensuring that patients can access safe, effective and appropriate treatment is essential," said Dr Sarah Kattakuzhy of the Institute of Human Virology at the University of Maryland, Baltimore, USA and lead author of the study. "Currently, the limited availability of experienced specialists restricts rapid expansion of Hepatitis C treatment, compromising the goal of global eradication. As such, care models which bypass this therapeutic bottleneck must be explored."
The multi-centre, open label, Phase 4 clinical trial assessed chronic HCV-infected patients at community health centres in the United States. Patients received non-randomised treatment from a specialist provider, primary care physician or nurse practitioner. According to study protocols, providers underwent uniform three hour training on the Infectious Disease Society of America (IDSA) - American Association for the Study of Liver Disease (AASLD) guidelines for HCV.
To ensure continuity, patients received the same standardised treatments with direct-acting antivirals (ledipasvir and sofosbuvir), with outcomes assessed via unquantifiable HCV RNA viral load 12 weeks after the completion of treatment (SVR12) and by a composite score of attendance.* Patients participating in the study were inclusive of challenging subpopulations; predominantly they were black (96%) and genotype 1a (72%), 24% were co-infected with HIV and HCV, 18% were treatment experienced and 20% had cirrhosis, or scarring of the liver.
The study found that of the 304 patients, 285 achieved SVR12 (93.8% per protocol; 88.2% intention-to-treat including patients who discontinued medication early), with no significant difference identified between providers for achieving this outcome. SVR12 was achieved by 92.1% of patients receiving care from specialists, 96.7% of patients receiving care from primary care physicians and 94.9% of patients receiving care from nurse practitioners.
"The data presented here is extremely welcome and shows great potential to escalate treatment options and protocols for Hepatitis C. We have the therapies, we now need to make sure we can effectively roll them out to patients," said Professor Tom Hemming Karlsen, EASL Vice-Secretary. "We know we have too few experienced specialists treating HCV and this is severely hampering our ability to eradicate this disease once and for all. This research has the potential to be a genuine game changer in the way we look at HCV treatment across the board, and could provide the opportunity to increase access to care and treatment to many regions of the world."
*Statistical analysis included chi-squared or Fisher's exact test and logistic regression using SAS, version 9.3.
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