Showing posts with label Nonalcoholic Steatohepatitis (NASH). Show all posts
Showing posts with label Nonalcoholic Steatohepatitis (NASH). Show all posts

Thursday, November 29, 2018

HighTide Receives Fast Track Designation for new drug to treat NASH

[Rockville, Maryland, Nov. 27, 2018] — HighTide Therapeutics Inc., a clinical-stage biopharmaceutical company, announced that the U.S. FDA has granted Fast Track Designation to its investigational new drug, HTD1801, for the treatment of patients with nonalcoholic steatohepatitis (NASH).

Liping Liu, PhD, Chief Executive Officer of HighTide, commented, “NASH represents a rapidly developing field with potential therapeutic options in the pipeline, yet none have made it to the market. At the recent AASLD Liver Meeting, experts in the field generally agreed that modest clinical responses to date are likely to be improved by thoughtful combination approaches. HTD1801, a multifunctional oral therapeutic, was designed to address the complex nature of NASH, especially for patients with comorbid diabetes and/or dyslipidemia. We are pleased by the FDA’s decision and look forward to bringing this much needed solution to millions of patients suffering from this disease.”

“This represents another step forward in our development of HTD1801 for the treatment of liver diseases with no currently approved therapies. We are proceeding with parallel clinical development of HTD1801 for NASH as well as primary sclerosing cholangitis (PSC) for which HTD1801 already received Orphan Drug Designation and Fast Track Designation,” said Janice Soreth, M.D., Chief Strategy and Regulatory Officer of HighTide, former Associate Commissioner for Special Medical Programs at the FDA.

FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An investigational drug that receives Fast Track Designation is eligible for more frequent communications between the FDA and the company relating to the development plan and clinical trial design, and may be eligible for priority review if certain criteria are met.

HighTide completed a first in human study of HTD1801 in healthy volunteers. A multi-center Phase 2 trial in adult patients with NASH is scheduled to enroll soon in the United States. A multi-center Phase 2 trial in adult patients with PSC is currently ongoing in the United States.

About HighTide Therapeutics and HTD1801
HighTide Therapeutics Inc., founded in 2011, is dedicated to the discovery and development of innovative therapeutics for people suffering from chronic liver diseases, gastrointestinal diseases and metabolic disorders with large and unsatisfied market needs.

HTD1801 is a new molecular entity being developed for the treatment of PSC and NASH.

About Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH), a form of nonalcoholic fatty liver disease (NAFLD), is a chronic, complex liver disease characterized by hepatitis – inflammation of the liver – and liver cell damage, which can lead to fibrosis of the liver. NASH can lead to cirrhosis and liver cancer. Prevalence of NASH is on the rise and it may soon surpass hepatitis C as a cause for liver transplant. Currently, there are no approved therapies for NASH.

Friday, November 9, 2018

Gilead Presents Data From Nonalcoholic Steatohepatitis (NASH) Development Program for Advanced Fibrosis at The Liver Meeting® 2018

Meeting Coverage @ Healio
Nov 27, 2018
SAN FRANCISCO — In this exclusive video perspective from The Liver Meeting 2018, Rob Myers, MD, senior director of the liver diseases therapeutic area at Gilead…

View all updates on this blog (LINK), recommended coverage elsewhere (LINK). 

Gilead Press Release
November 09, 2018
Gilead Presents Data From Nonalcoholic Steatohepatitis (NASH) Development Program for Advanced Fibrosis at The Liver Meeting® 2018

-- Phase 2 Data Presented on Investigational FXR Agonist GS-9674 in NASH --
-- Enrollment Complete in Phase 2 ATLAS Combination Trial of Three Investigational Therapies Targeting Distinct Mechanisms of the Disease --

SAN FRANCISCO--(BUSINESS WIRE)--Nov. 9, 2018-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from the company’s clinical development program for advanced fibrosis due to nonalcoholic steatohepatitis (NASH). Data presented support the ongoing development of the company’s investigational compounds, evaluate the utility of noninvasive tests for the identification of patients with advanced fibrosis, and demonstrate the significant burden of disease in affected patients. The data presented across 24 abstracts are being shared at The Liver Meeting® 2018 in San Francisco this week.

Data from a Phase 2 randomized, placebo-controlled trial of the investigational, selective, non-steroidal farnesoid X receptor (FXR) agonist GS-9674 will be presented. In this study, 140 NASH patients were treated with GS-9674 100 mg, GS-9674 30 mg or placebo orally once daily for 24 weeks. A decline of at least 30 percent in hepatic fat measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was observed in 38.9 percent of patients treated with GS-9674 100 mg (p=0.011 vs placebo), 14 percent treated with GS-9674 30 mg (p=0.87), and 12.5 percent with placebo. Improvements in liver biochemistry tests (serum GGT) and markers of reduced bile acid synthesis (serum C4 and bile acids) were observed in the 30 mg and 100 mg arms of GS-9674-treated patients.

GS-9674 was generally well tolerated; moderate to severe pruritus, or itching, occurred in 14 percent of patients in the GS-9674 100 mg arm compared to four percent in the GS-9674 30 mg and placebo arms. Changes in lipid profile and glycemic parameters did not differ between GS-9674 and placebo-treated patients. The most common adverse events in patients treated with GS-9674 were pruritus, upper respiratory tract infection, headache and fatigue. Treatment was discontinued due to adverse events in one patient treated with GS-9674 100 mg (two percent), five patients treated with GS-9674 30 mg (nine percent), and two patients with placebo (seven percent).

A separate Phase 2 study (ATLAS) is investigating treatment with GS-9674, the investigational apoptosis signal-regulating kinase 1 (ASK-1) inhibitor selonsertib, and the investigational acetyl-CoA carboxylase (ACC) inhibitor GS-0976 alone or in combination, in patients with advanced fibrosis due to NASH. This randomized, double-blind 52-week study will assess improvement in fibrosis without worsening of NASH, adverse events and laboratory abnormalities in approximately 350 patients.

“We believe our development program is well positioned to address the unmet need for effective therapies for people living with advanced fibrosis due to NASH. We are pleased to share that the Phase 2 ATLAS combination trial of experimental GS-9674, selonsertib, and GS-0976 has completed enrollment ahead of schedule,” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead Sciences. “We also continue to support the liver community in the study of noninvasive tests to help overcome the risks and limitations of liver biopsies in the diagnosis of advanced fibrosis due to NASH.”

Noninvasive Tests
In a late-breaker session, Gilead will present an analysis of baseline data from its Phase 3 STELLAR trials of selonsertib suggesting that the use of currently available noninvasive tests (NITs) can accurately identify patients with advanced fibrosis (F3-F4) due to NASH and potentially reduce the need for liver biopsy. The use of the Fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test and liver stiffness measurement by FibroScan® (FS) each demonstrated good sensitivity and specificity for the discrimination of advanced fibrosis due to NASH when compared to liver biopsy. When used sequentially, FIB-4 followed by FS or the ELF test accurately identified advanced fibrosis in 76-81 percent of patients while reducing the frequency of indeterminate results to as low as 13 percent.

“There is a major need for accurate and readily available tests to diagnose patients with advanced fibrosis due to NASH, a disease which affects many aspects of patients’ lives,” said Zobair Younossi, MD, MPH, FACP, FACG, AGAF, FAASLD, lead study author and Chairman and Professor, Department of Medicine, Inova Fairfax Hospital. “These findings from the STELLAR program indicate that currently available noninvasive tools, when used alone or sequentially, can identify these patients with advanced fibrosis due to NASH rather accurately, providing a potentially simple option for physicians to use in clinical practice.

Burden of Disease
Baseline data from patients enrolled in the STELLAR Phase 3 program presented in a poster session at The Liver Meeting® 2018 demonstrate the significant burden of disease among people with advanced fibrosis due to NASH. In 1,660 patients enrolled in the STELLAR trials, patient-reported outcome measures (PROs) were assessed prior to treatment initiation and compared with population norms. The data demonstrate that physical health-related PRO scores of NASH patients were significantly lower than population norms. In addition, patients with cirrhosis had lower PRO scores than those with bridging fibrosis in areas including bodily pain, social functioning, and all but one domain of the disease-specific Chronic Liver Disease Questionnaire (CLDQ) for nonalcoholic fatty liver disease (NAFLD) and NASH.

In another analysis of patients enrolled in the STELLAR Phase 3 study presented during a poster session, elevated values of the ELF test and NAFLD fibrosis score were associated with impairment in PROs, especially physical health-related scores and the scores captured by the disease-specific CLDQ-NAFLD/NASH. These data extend prior observations that noninvasive fibrosis markers may predict fibrosis stage and adverse clinical outcomes, and now, impairments in health-related quality of life, in patients with NASH.

GS-9674, selonsertib and GS-0976 are investigational compounds and are not approved by the U.S. Food & Drug Administration (FDA) or any other regulatory authority. Their safety and efficacy have not been established.

About Gilead’s Clinical Programs in NASH
NASH is a chronic and progressive liver disease characterized by fat accumulation and inflammation in the liver, which can lead to scarring, or fibrosis, that impairs liver function. Individuals with advanced fibrosis, defined as bridging fibrosis (F3) or cirrhosis (F4), are at a significantly higher risk of liver-related mortality.

Gilead is advancing multiple novel investigational compounds for the treatment of advanced fibrosis due to NASH, evaluating single-agent and combination therapy approaches against the core pathways associated with NASH – hepatocyte lipotoxicity, inflammation and fibrosis. Investigational compounds in development include the ASK1 inhibitor selonsertib, the selective, non-steroidal FXR agonist GS-9674 and the ACC inhibitor GS-0976. The STELLAR Phase 3 trial program evaluating selonsertib among NASH patients with bridging fibrosis (F3) or cirrhosis (F4) is ongoing. GS-9674 and GS-0976 are currently in Phase 2 studies in NASH.
http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2376502

The Liver Meeting: Gilead making gains in NASH, PSC programs
New data from two mid-stage studies of Gilead Sciences Inc.'s farnesoid X receptor agonist (FXR) reported during the American Association for the Study of Liver Diseases meeting showcased the company's ongoing efforts to establish new strengths beyond viral hepatitis C, where time and competition have eroded its dominance. Though still active on the next frontier of the hepatitis battle, HBV, most of the company's liver disease pipeline today is focused on nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), and primary biliary cirrhosis (PBC).

Thursday, November 8, 2018

Liver Meeting® 2018 - Conatus Pharmaceuticals Announces Presentations and Posters

Liver Meeting® - Conatus Pharmaceuticals Announces Presentations and Posters

SAN DIEGO, Nov. 08, 2018 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ: CNAT) announced today the schedule of upcoming oral presentations and posters addressing clinical and preclinical results with the company’s pan-caspase inhibitor emricasan, or addressing preclinical results with the company’s pan-caspase inhibitor IDN-7314, at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco November 9-13, 2018.

Poster #1226, “Multicenter, double-blind, randomized trial of emricasan in subjects post liver transplantation (LT) with recurrent hepatitis C virus (HCV) and liver fibrosis or cirrhosis despite achieving sustained virologic response (SVR),” will be displayed by Catherine Frenette, M.D., (Scripps Clinic, La Jolla, CA) in the Liver Transplantation: Viral Hepatitis section on Saturday, November 10, from 2:00 p.m. to 7:30 p.m. PT, in the Moscone Center Poster Hall – Hall C.

Presentation #251A, highlighting selected content from poster #1226, will be delivered by K. Rajinder Reddy, M.D., (University of Pennsylvania Medical Center, Philadelphia, PA) in the Parallel 37: Liver Transplantation: Alcohol and Hepatitis C session on Monday, November 12, at 3:15 p.m. PT, in the Moscone Center Room 153/155.

Presentation #25, “Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis,” will be delivered by Kai M. Schneider (Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany) in the Presidential Plenary Session on Translational Science and Genomics on Tuesday, November 13, 9:00 a.m. PT., in the Moscone Center General Session – Hall D.

Poster #1344, “Molecular mechanisms underlying the effects of emricasan in portal hypertension and chronic liver disease: the hepato-sinusoidal cross-talk matters,” will be displayed by Jordi Gracia-Sancho, Ph.D., (Idibaps Biomedical Research Institute, Ciberehd, Barcelona, Spain; Hepatology, Inselspital, Bern, Switzerland; and Barcelona Liver Services) in the Portal Hypertension and Other Complications of Cirrhosis: Experimental section on Saturday, November 10, from 2:00 p.m. to 7:30 p.m. PT, in the Moscone Center Poster Hall – Hall C.

“With three ongoing ENCORE Phase 2b clinical trials evaluating emricasan in patients with nonalcoholic steatohepatitis (NASH), all with top-line results expected over the next nine months, we are encouraged by the preclinical and clinical data being featured at the AASLD meeting demonstrating the activity and effects of pan-caspase inhibitors,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. “We thank our principal investigators and our scientific collaborators for their continued efforts to better understand and apply the multiple mechanistic effects of caspase inhibitors on liver structure and function, driving their disease-modifying potential. We are pleased with the opportunity to share their latest findings at the AASLD meeting, and we look forward to sharing results from the ENCORE trials.”
www.conatuspharma.com.

Monday, November 5, 2018

Liver Meeting® 2018- Exalenz to Present Positive Clinical Data for Breath ID® in NASH cirrhosis patients

Exalenz to Present Positive Clinical Data for the Breath ID® 13C-Methacetin Breath Test System at the Liver Meeting® 2018

MODI’IN, Israel and MANASQUAN, N.J., Nov. 05, 2018 (GLOBE NEWSWIRE) -- Exalenz Bioscience Ltd. (TASE: EXEN), a leader in developing and marketing non-invasive medical devices for diagnosing and monitoring a range of gastrointestinal and liver diseases, today announced that the Company will present positive data from a Phase 2 trial, conducted by Galectin Therapeutics in NASH cirrhosis patients (ie the NASH-CX trial), utilizing its BreathID® 13C-Methacetin Breath Test (MBT) System in patients with compensated non-alcoholic steatohepatitis (NASH).

The poster presentation is titled “The Noninvasive Point of Care MBT Accurately Predicts Decompensation Events Better Than MELD in Compensated (MELD <15) Nash Cirrhotics” (#1337) will be presented at the Liver Meeting® 2018 on November 10 at 2:00 PM PT / 5:00 PM ET. The Liver Meeting, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), is being held November 9 - 13, 2018 in San Francisco. The lead author is Naga Chalasani, MD, Associate Dean for Clinical Research and a Professor of Medicine at the Indiana University School of Medicine.

“Results of this study indicate that the MBT has the potential to predict liver decompensation in patients with compensated NASH cirrhosis, which may enable earlier intervention and improved management of these patients,” said Raffi Werner, Chief Executive Officer of Exalenz Bioscience. “We believe that these results add to the growing body of data supporting the MBT as an important alternative to more invasive detection methods and support our strategy to advance this innovative test to the market, potentially launching the product in 2020.”

About MBT
MBT is a simple, noninvasive Point of Care breath-based test in which a patient drinks a half glass of a tasteless solution that is metabolized exclusively in the liver. The patient’s exhaled breath is automatically collected and assayed with the BreathID® system to measure the amount of a specific breakdown product of the solution, which reflects the rate of liver metabolism.

In addition to evaluating MBT to monitor NASH patients, it is also being developed to detect CSPH in the advanced NASH patient population, as well as in monitoring patients with confirmed diagnoses of acute liver failure (ALF). The ability to monitor patients with a simple, noninvasive test has the potential to radically improve the management and outcomes of patients with an array of liver diseases.

About NASH
More than 8 million people in the United States and Europe are living with advanced non-alcoholic steatohepatitis (NASH), the most severe form of non-alcoholic fatty liver disease (NAFLD) and a major risk factor for liver transplant and the development of primary liver cancer. The incidence of NAFLD is expected to increase more than 21% by 2030, with a concomitant increase of more than 63% in the incidence of NASH in the same period.

Liver Meeting® 2018 - Intercept's NASH clinical development program

Intercept Announces New OCA Data to be Presented at The Liver Meeting® 2018

NEW YORK, Nov. 05, 2018 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced that multiple obeticholic acid (OCA) abstracts will be presented at The Liver Meeting® 2018, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place November 9-13 in San Francisco, California.

“At this year’s Liver Meeting, we look forward to sharing new data from our innovative clinical programs, which further our understanding of treatment approaches aimed at impacting the lives of patients with progressive non-viral liver diseases,” said Christian Weyer, M.D., M.A.S., Intercept's Executive Vice President, Research & Development. “As we approach the read-out from the interim analysis of our Phase 3 REGENERATE trial in the first half of 2019, we are excited to present abstracts that highlight the depth and breadth of our NASH clinical development program.”

Select presentations at The Liver Meeting include:

Oral Presentation:
Sunday, November 11, 2018 – 11:30 a.m. PT
“Obeticholic Acid Was Safe and Well Tolerated in Patients with NASH and Compensated Cirrhosis: A Secondary Analysis of the CONTROL Study” (Abstract #0071)
Dina Halegoua-DeMarzio, Paul Thuluvath, Manal F. Abdelmalek, Courtney Van Biene, Reshma Shringarpure, Leigh MacConell

Poster Presentations:
Sunday, November 11, 2018 – 8 a.m. – 5:30 p.m. PT
“CONTROL: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Investigating the Effects of Obeticholic Acid and Atorvastatin Treatment on Lipoprotein Metabolism in Patients with Nonalcoholic Steatohepatitis” (Abstract #1672)
Paul J. Pockros, Michael Fuchs, Bradley Freilich, Eugene Schiff, Anita Kohli, Eric J. Lawitz, Paul A. Hellstern, David E. Cohen, Janet Owens-Grillo, Courtney Van Biene, Reshma Shringarpure, Leigh MacConell, David Shapiro

“Efficacy and Safety of Obeticholic Acid in Patients with Nonalcoholic Steatohepatitis and Significant Fibrosis Using Endpoint Definitions and Populations Accepted for Registrational Studies” (Abstract #1673)
Brent A. Neuschwander-Tetri, Kris V. Kowdley, Arun J. Sanyal, Manal F. Abdelmalek, Norah Terrault, Arthur J. McCullough, Peter Wang, Reshma Shringarpure, Leigh MacConell, David A. Shapiro, Rohit Loomba

“Safety, Pharmacokinetics and Pharmacodynamics of Obeticholic Acid in Subjects with Compensated Cirrhosis due to NASH” (Abstract #1709)
Naim Alkhouri, Jeffrey Edwards, Fred Poordad, Eric Lawitz, Lois Lee, Sharon Karan, Jason Campagna, Leigh MacConell

“Beyond Sirius Red: Collagen Isoforms for Quantitative Histological Analysis of Liver Fibrosis in Preclinical Models of Diet-induced and Biopsy-confirmed Nonalcoholic Steatohepatitis” (Abstract #1760)
Thea Johansen, Denise Oró, Sanne S. Veidal, Michael Feigh, Henrik H. Hansen, Niels Vrang, Mark Young, Jacob Jelsing, Jonathan D. Roth

Monday, November 12, 2018 – 8 a.m. – 5:30 p.m. PT
“Hepatic Safety Overview of Obeticholic Acid for the Treatment of Patients with Primary Biliary Cholangitis” (Abstract #1931)
Paul J. Pockros, Mitchell L. Shiffman, Christopher Bowlus, Arun J. Sanyal, Frederik Nevens, Richard Pencek, David Shapiro, Amrik Shah, Leigh MacConell

“PBC Patient Care Pathway” (Abstract #1886)
Gideon M. Hirschfield, Marco Carbone, Helena Cortez-Pinto, Guilherme Macedo, Victor de Lédinghen, Olivier Chazouilleres, Femi Adekunle

“Characterization of Primary Biliary Cholangitis (PBC) in Canadian Patients” (Abstract #1916)
Eric Yoshida, Robert Bailey, Magdy Elkhashab, Dusanka Grbic, Nir Hilzenrat, Euiseok Kim, Gerald Minuk, Meaghan O'Brien, Kevork Peltekian, Marco Puglia, Alnoor Ramji, Mark Swain, Edward Tam, Cynthia Tsien, Catherine Vincent, Vlad Popovic, Jamie Twiselton, Belinda Yap

A full list of sessions at The Liver Meeting is available on the AASLD website at: www.aasld.org/events-professional-development/liver-meeting.

Thursday, October 25, 2018

Cirius Therapeutics Reports On Phase 2b Trial in NASH Patients with Fibrosis

Cirius Therapeutics Reports Positive Data for MSDC-0602K in Interim Analysis of Phase 2b Clinical Trial in NASH Patients with Fibrosis

- Interim analysis showed statistically significant reductions in liver enzymes, including ALT and AST, measured from baseline at six months

- In two highest dose groups, at least 50% of patients with high baseline ALT or AST improved to normal range at six months

- Statistically significant reductions in HbA1c and other measures of glycemic control and insulin resistance were observed

- Overall adverse event rate was similar across placebo and all doses of MSDC-0602K

- Largest Phase2b clinical trial including paired biopsies conducted in NASH; biopsy data after 12 months of treatment expected to be reported in the second half of 2019

SAN DIEGO and KALAMAZOO, Mich., Oct. 25, 2018 /PRNewswire/ -- Cirius Therapeutics today announced positive results from an interim analysis of exploratory endpoints from its ongoing, fully enrolled Phase 2b clinical trial (the EMMINENCE trial) evaluating MSDC-0602K in 402 patients diagnosed with non-alcoholic steatohepatitis (NASH) with fibrosis. The interim analysis, which was conducted in the first 328 patients to reach their six-month follow-up visit, showed that patients treated with MSDC-0602K had significant improvements from baseline in measures of liver function and insulin resistance at six months. MSDC-0602K, a second-generation insulin sensitizer, is designed to selectively modulate the mitochondrial pyruvate carrier (MPC), which at the cellular level mediates the effects of overnutrition, a major cause of NASH and other metabolic disorders.

The subjects included in this interim analysis had significant liver disease, as established by liver biopsy, with an average non-alcoholic fatty liver disease (NAFLD) activity score at baseline of 5.3. Almost sixty percent of these subjects had a baseline fibrosis score of 2 or 3 and approximately fifty percent also had a diagnosis of Type 2 diabetes at baseline. Overall, baseline characteristics were well-balanced across treatment groups.

Key findings from the interim analysis include improvements in liver enzymes, with placebo-corrected reductions at 6 months of 14.3 U/L (p<0.001) and 7.9 U/L (p=0.012) in ALT and AST, respectively, in the 125mg cohort, and 10.6 U/L (p=0.004) and 4.0 (NS) in ALT and AST, respectively, in the 250mg cohort. Placebo-corrected reductions, relative to baseline, were 25% and 18% in ALT and AST, respectively, in the 125mg cohort, and 19% and 9% in ALT and AST, respectively, in the 250mg cohort. Importantly, normalization of hepatic enzymes was observed across all three dose levels of MSDC-0602K. 


Percentage of patients with high baseline values who returned to normal range
Placebo
62.5mg
125mg
250mg
ALT
15%
29%
60%
56%
AST
20%
36%
50%
52%
*ALT normal range defined as 6-34 U/L and 6-43 U/L for women and men, respectively; AST normal range defined as 9-34 U/L and 11-36 U/L for women and men, respectively) 

"We believe these interim results around improved measures of liver function and glycemic control, together with the preliminary adverse event profile, support MSDC-0602K's potential to be used in the treatment of NASH with fibrosis, including for those patients with Type 2 diabetes, a group which represents approximately 50% of patients with NASH," said Cirius' chief medical officer Howard Dittrich, M.D. "These results support the view that therapies directed toward the MPC have the potential to achieve insulin sensitizing pharmacology with an improved profile over first generation insulin sensitizers. We look forward to presenting full data to the scientific community." 

In addition to the improvement in ALT and AST, observations included significant improvement at six months in fasting glucose, HbA1c, insulin levels and HOMA-IR at the 125mg and 250mg dose levels.  Significant improvement in HbA1c was also observed in subjects with a diagnosis of Type 2 diabetes in the 125mg and 250mg cohorts.  

In this interim analysis, the overall rate of treatment emergent adverse events was similar across placebo and all MSDC-0602K cohorts. There was a higher rate of treatment emergent adverse events reported in the 250mg dose compared to placebo in the musculoskeletal and connective tissue disorders category. Within this category, arthralgia and back pain were the most frequently reported individual adverse events across the pooled 328 subjects. A modest dose-dependent increase in body weight was seen in MSDC-0602K treated subjects, a finding seen with insulin and with other therapies that seek to improve insulin resistance. The rate of peripheral edema observed at six months was similar to that observed at baseline and was comparable across placebo and all MSDC-0602K cohorts. 

"The interim results from the EMMINENCE trial, the largest Phase 2b clinical trial to include paired biopsies ever conducted in NASH, are compelling," said Stephen Harrison, M.D., the principal investigator in the EMMINENCE trial. "The improvements in hepatic enzymes observed to date are impressive, especially when combined with the meaningful improvements in glycemic control." 

About the EMMINENCE Trial
The EMMINENCE trial is a 12-month, randomized, double-blind, placebo-controlled trial evaluating three oral dose levels of MSDC-0602K. Endpoints of the clinical trial include hepatic histological changes measured by biopsy after 12 months of treatment, changes in liver and metabolic function measured by the liver enzymes ALT and AST, markers of liver fibrosis, glycemic control and safety and tolerability. Not all of these endpoints were examined in this interim analysis; rather, in addition to the safety variables of incidence of treatment-emergent adverse events and  peripheral edema grades, changes from baseline relative to placebo for a number of endpoints, including liver functions tests such as ALT and AST, among others, biomarkers and indirect measures of apoptosis and fibrosis, circulating inflammatory markers and markers of bone metabolism, serum triglycerides and fasting cholesterol, markers of insulin sensitivity, and blood pressure, were examined in an exploratory manner. 

About Cirius Therapeutics
Cirius is a clinical-stage pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and metabolic diseases. Our lead product candidate, MSDC- 0602K, is a novel small molecule being developed as a once-daily oral therapy to treat NASH with fibrosis. MSDC-0602K is designed to selectively modulate the MPC, which mediates at the cellular level the effects of overnutrition, a major cause of NASH and other metabolic disorders. We are conducting a Phase 2b clinical trial of MSDC-0602K, which we have fully enrolled with 402 patients diagnosed with NASH with fibrosis. We expect to report final data from this clinical trial in the second half of 2019.

Tuesday, October 2, 2018

The Liver Meeting®2018 - GENFIT: New data to be presented ahead of key results expected in 2018 and 2019

GENFIT: New data to be presented at 2018 AASLD meeting, ahead of key results expected in 2018 and 2019

KOL event to be held ahead of expected data release with elafibranor in PBC by end of 2018 (Phase 2) and in NASH end of 2019 (Phase 3)

Confirmation of the diagnostic performance of NIS4 algorithm in identifying NASH patients eligible to therapeutic intervention

Elafibranor’s potential as cornerstone drug in combination therapies for NASH confirmed with new data

New data indicating elafibranor’s potential in treating hepatic cancer (HCC)

Bioinformatics approaches based on deep learning methods paving the way for automatization of histological NASH diagnosis

Lille (France), Cambridge (Massachusetts, United States), October 2, 2018 – GENFIT (Euronext: GNFT – ISIN: FR0004163111), is a biopharmaceutical company focused on discovering and developing drug candidates and diagnostic solutions targeting liver diseases, in particular those of metabolic origin, and hepatobiliary diseases today announces its participation in The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 9-13, 2018. Abstracts are available on the meeting’s website. The Liver Meeting® is one of the most important congresses organized for the medical and scientific community specializing in hepatology worldwide. It brings together more than 10,000 scientists, gastroenterologists and hepatologists.

Update on NASH landscape
The 2018 edition of AASLD comes after the recent publication of a number of early-stage clinical study results, and importantly ahead of 2019, expected to bring significant catalysts in the NASH space. To date, only three programs globally have finalized the enrollment of their Phase 3 cohorts in NASH (Subpart H), paving the way for first late stage data readouts in 2019. GENFIT’s elafibranor is one of the aforementioned programs having the potential to be part of a first set of marketing approvals to offer clinicians the first therapeutic solutions for treating NASH (other molecules may follow only a few years later). It is also ideally positioned to potentially cover the widest spectrum of NASH patients, based on compelling Phase 2 data (Ratziu et al., Gastroenterology, 2016) that have shown elafibranor’s potential to combine:
Efficacy on “NASH resolution without worsening of fibrosis” (26% vs 5%; p-value 0,02), the biopsy-based regulatory endpoint for market approval that addresses the underlying cause of disease progression;
Beneficial cardiovascular profile (LDL, TG, HDL, insulin resistance), known to be crucial for NASH patients;
Clean safety and tolerability, essential for a chronic and silent condition like NASH.

Ahead of next year’s data readout in NASH with elafibranor, GENFIT is expected to make several announcements over the next few months in the field of PBC, NASH and fibrosis:
Elafibranor Phase 2 data readout in PBC by year end 2018;
Launch of a Phase 2 proof of concept study of nitazoxanide in NASH fibrosis;
Enrollment of the first pediatric NASH patient: elafibranor is the first and only molecule to be evaluated in pediatric NASH after having shown safety and efficacy in a Phase 2 trial on adult NASH patients;
Regulatory and commercial development milestones of the In Vitro Diagnostic test aimed at identifying NASH patients to be considered for treatment.

Events during AASLD
Prior to the new Phase 2 clinical data for elafibranor in PBC by year end 2018, GENFIT will hold a NASH/PBC KOL Meeting during AASLD, providing financial analysts and institutional investors a unique opportunity to understand how medical and scientific opinion leaders approach the challenges posed by these diseases and how they evaluate the potential of diagnostic and therapeutic solutions currently under development.

GENFIT will continue to engage with key stakeholders in order to move forward with the set up of its first Market Access Advisory Board that will be held in January next year. Early payer research already points to the strong differentiation of elafibranor.

Following the success of the 1st International NASH Day, GENFIT will host the first steering committee aimed at preparing the 2019 edition. It will be organized together with learned societies and patients associations who are expected to play an increasingly important leadership role. Feedback from the satisfaction survey run over the summer will help further increase the scale of the next edition.

From November 10 to 12, GENFIT will be present at the “Moscone North and South Convention Center” exhibition hall, allowing all scientific and medical staff attending the event to keep informed on the ongoing R&D programs. The institutional booth #635 and The NASH Education Program booth #244 will welcome meeting attendees.

New data presented during the Liver Meeting:
NASH Diagnostic: oral presentation, Sunday, November 11

The NIS-4 algorithm – non-invasive score combining circulating levels of miR-34a, Alpha2-macroglobulin, YKL-40 and HBA1c – is confirmed as a powerful NASH diagnostic tool to identify patients with active NASH (NAS>=4) and significant fibrosis (F>=2) irrespective of patient sex, age, obesity or type of diabetes.

“NIS4 for the detection of active NASH (NAS>=4) and significant fibrosis (F>=2) in 714 patients at risk of NASH: diagnostic metrics are not affected by age, sex, presence of type 2 diabetes or obesity”, R. Hanf et al. (Abstract 142)
Treatment with elafibranor: “Poster of distinction” and poster, Friday, November 9

New anti-NASH treatment combinations, using elafibranor – “first-in-class” PPAR alpha and delta receptor agonist – as backbone, were studied in in vitro and in vivo NASH models, associating it with an acetyl-CoA carboxylase inhibitor. A complementary and synergistic action was observed on fatty acid catabolism accompanied by resolution of liver steatosis. In addition, elafibranor counteracted the ACC inhibitor-induced hypertrigliceridemia.

“Elafibranor synergizes with ACC inhibitors to enhance fatty acid catabolism and reduce steatosis in the liver of a NASH model”, V. Legry et al. (Abstract 732)

As NASH is projected to become the most common risk factor for HCC, this in vivo study has shown that preneoplastic lesion development was prevented to a significant extent upon elafibranor treatment in rodent model. In addition, elafibranor directly reduced tumor cell proliferation.

“Elafibranor administration prevents liver tumor development in mouse models of NASH”, P. Parroche et al. (Abstract 737)
NASH diagnosis through deep learning: Poster, Saturday, November 10

The study has shown that scoring systems based on deep-learning methods showed similar results as with human evaluation which could facilitate the analysis of preclinical and, in the future, clinical NASH patients’ biopsies. GENFIT’s technology could also assist experts in better interpreting certain specific regions of cells in histological samples that are difficult to interpret.

“A rapid and reproducible quantification of ballooning and inflammation using a deep-learning approach and comparison with manual scoring”, E. Perspicace et al. (Abstract 1298)

About elafibranor
Elafibranor is GENFIT’s lead pipeline product. Elafibranor is an oral once-daily treatment, and a first-in-class drug acting via dual peroxisome proliferator-activated alpha/delta pathways developed to treat, in particular, nonalcoholic steatohepatitis (NASH) and Primary Biliary Cholangitis (PBC). Elafibranor is believed to address multiple facets of NASH, including inflammation, insulin sensitivity, lipid/metabolic profile, and liver markers. Elafibranor also presents a particularly interesting profile to potentially treat PBC, a rare liver disease.

About NASH
“NASH”, or nonalcoholic steatohepatitis, is a liver disease characterized by an accumulation of fat (lipid droplets), along with inflammation and degeneration of hepatocytes. The disease is associated with long term risk of progression to cirrhosis, a state where liver function is diminished, leading to liver insufficiency, and also progression to liver cancer.

About PBC
“PBC”, or Primary Biliary Cholangitis, is a chronic disease in which bile ducts in the liver are gradually destroyed. The damage to bile ducts can inhibit the liver’s ability to rid the body of toxins, and can lead to scarring of liver tissue known as cirrhosis.

About GENFIT
GENFIT is a biopharmaceutical company focused on discovering and developing drug candidates and diagnostic solutions targeting liver diseases, in particular those of metabolic origin, and hepatobiliary diseases. GENFIT’s concentrates its R&D efforts in areas of high unmet medical needs corresponding to a lack of approved treatments. GENFIT’s lead proprietary compound, elafibranor, is a drug candidate currently being evaluated in one of the most advanced Phase 3 studies worldwide (“RESOLVE-IT”) in nonalcoholic steatohepatitis (NASH), considered by regulatory authorities as a medical emergency because it is silent, with potentially severe consequences, and with a prevalence on the rise. It is also evaluated in a Phase 2 study in Primary Biliary Cholangitis (PBC), a rare liver disease. As part of its comprehensive approach to clinical management of NASH patients, GENFIT is conducting an ambitious discovery and development program aimed at providing patients and physicians with a blood-based test for the diagnosis of NASH, i.e. non-invasive and easy-to-access. With facilities in Lille and Paris, France, and Cambridge, MA (USA), the Company has approximately 130 employees. GENFIT is a public company listed in compartment B of Euronext’s regulated market in Paris (Euronext: GNFT – ISIN: FR0004163111). www.genfit.com

http://www.genfit.com/wp-content/uploads/2018/10/2018.10.02-AASLD-2018-PR-EN-.pdf

Monday, June 18, 2018

Hepatitis C Weekend Video: NASH What Is It?


Weekend Video
Welcome, this weekend we start with a few articles on a "silent" but potentially serious condition called nonalcoholic fatty liver disease (NAFLD), followed by a new seven part video series on nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD.

What Is NAFLD? 
Non-alcoholic fatty liver disease (NAFLD) is the build up of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, if more than 5% – 10% percent of the liver’s weight is fat, then it is called a fatty liver (steatosis), learn more, here

While the burden of liver disease from HCV decreases - lowering the number of patients waiting or undergoing liver transplant - the waitlist for nonalcoholic steatohepatitis (NASH) has increased. In addition, NASH is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates.

Research Articles:

The Effects of Physical Exercise on Fatty Liver Disease
For people with HCV (without fatty liver disease) research shows weight reduction leads to a decrease in steatosis and liver enzymes, and also to an improvement in fibrosis, despite persistence of the virus. Previous research also indicates HCV patients who participated in a diet and exercise program lowered their grade of steatosis and remarkably their fibrosis score, according to a study published in Nutrition 2013. Whether you have fatty liver disease, HCV or both read; The Effects of Physical Exercise on Fatty Liver Disease, published in Gene Expression 2018, to learn more about the effects of exercise on NAFLD and NASH.

2016
NAFLD & Type 2 Diabetes 
Published in World J Gastroenterology 2016
"NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time."
Also noted in the article, prevalence of Nonalcoholic Steatohepatitis (NASH) in people who are obese and have type 2 diabetes may be as high as 40%, whereas it is less than 5% in people without type 2 diabetes.
Read the article, here.

2018
NAFLD Is a Growing Problem
NAFLD is the most common form of liver disease in Western countries.[4] Men are affected more than women.[5] Persons with a "high body mass index in late adolescence" are at risk for advanced liver disease and hepatocellular carcinoma (HCC)..

The term "NAFLD" describes both hepatic steatosis with hepatocyte fat accumulation in a liver lacking inflammation, whereas NASH is associated with fat accumulation, hepatic inflammation, and hepatocyte injury with or without fibrosis or cirrhosis..

Not every patient with NAFLD is obese. Seven percent of lean patients have NAFLD,[18] especially in the presence of metabolic syndrome.[19] Lean patients with fatty liver also are observed among those with polycystic ovary syndrome.[20] Compared with lean patients, obese patients with NAFLD are more likely to have greater fibrosis and a worse clinical prognosis.[21] Nonobese patients with NAFLD have a lower prevalence of hypertension, diabetes mellitus, metabolic syndrome, and steatohepatitis than obese patients[22] but remain at risk for development of advanced liver disease[23] and associated metabolic abnormalities and cardiovascular disease.[22] 
Continue reading @ Medscape
Free registration may be required. 

2017
The International Liver Congress 2017
NASH: It's Fibrosis, Not Fat, that Matters
Analysis sheds new light on what drives disease progression
AMSTERDAM -- It isn't fat but rather fibrosis that drives disease progression in people with advanced non-alcoholic steatohepatitis (NASH), a researcher said here
Continue reading....
Free registration may be required. 

2017
HCV & Steatosis
Given the development of steatosis is well-known in people with HCV, the following articles may be of interest to you, lets start with an article published in Clinical Liver Disease 2017; Metabolic Manifestations of Hepatitis C Virus
Out of excessive consumption, steatosis should be classified into 2 types according to hepatitis C virus (HCV) genotypes: metabolic steatosis, which is associated with features of metabolic syndrome and insulin resistance in patients infected with nongenotype 3, and viral steatosis, which is correlated with viral load and hyperlipemia in patients infected with genotype 3.
Download the article, here

2016
Published in the 2016 issue of International Journal of Molecular Sciences; NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations, researchers investigated factors associated with NAFLD/NASH in chronic HCV, and the role of “viral steatosis” associated with HCV genotype 3 infection. 

2018
Of Interest
HCV Treatment Genotype 3
The International Liver Congress, 2018
Treatment for hepatitis C genotype 3 infection can be completed in 8 weeks in people without cirrhosis, three real-world studies presented at the conference confirmed. 

2018
Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR 
According to data published March 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals. 
Core tip: This is the first prospective study to assess the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals. The study’s findings that fatty liver is present in 47.5% of these patients and that some steatotic patients have clinically significant fibrosis despite normal liver enzymes should raise awareness of the post-sustained virological response (SVR) prevalence of fatty liver and the importance of post-SVR assessment of steatosis and fibrosis and long-term follow up with these patients.
Full-text, here

2018
NASH Leading Cause of Liver Transplant in Women
"NASH is currently the second leading cause for LT waitlist registration/liver transplantation overall, and in females, the leading cause. Given the rate of increase, NASH will likely rise to become the leading indication for LT in males as well" according to a June 2018 study published in The American Journal of Gastroenterology.

Videos
7 sequences about NASH
On June 12, 2018, the 1st International NASH Day was launched by The NASH Education Program, along with their seven part educational program to help patients understand this serious liver disease. Listen to expert interviews, learn about symptoms, non-invasive tests used to measure liver inflammation and fibrosis, and hear from patients struggling with the disease.

NASH What Is It?
The video is the first part of a WEBTV of 7 sequences about NASH
Published June 12, 2018
Speakers: Pr Stephen Harrison, Pr Sven Francque
In this first TV show you will understand – thanks to a worldwide overview – how little-known NASH is and why this situation has to be changed. Liver experts will go over non-alcoholic steatohepatitis (NASH) details, its mechanisms, consequences, symptoms and stigmas. These will also be highlighted by a patient testimony at the end of the video footage.

Part One



SUBTITLES ARE AVAILABLE IN 6 LANGUAGES, using settings of the video (Gear Icon at the bottom right of the video): English - Spanish - French - Italian - German - Portugese

Full Playlist:
PART 1 NASH What Is It?  
https://www.youtube.com/watch?v=ND3AV...
In this first TV show you will understand – thanks to a worldwide overview – how little-known NASH is and why this situation has to be changed. Liver experts will go over non-alcoholic steatohepatitis (NASH) details, its mechanisms, consequences, symptoms and stigmas. These will also be highlighted by a patient testimony at the end of the video footage.

PART 2 NASH How Common Is It?
https://www.youtube.com/watch?v=luYVh...
In this second TV show, you will understand how widespread NASH is, with prevalence figures and future projections exposed. During the interviews, livers experts will bring up information on NASH frequency, genetic predispositions, how children are now subject to this preventable disease, and which populations are most commonly affected.

PART 3 NASH: Who is at risk?  
https://www.youtube.com/watch?v=nAjMR...
In this third TV show, you will discover that NASH is much more than just a liver disease and that it is related to metabolic disorders – such as diabetes and obesity – and closely linked to modern lifestyles: unhealthy diets and lack of physicial activity. The diverse speaker panel will explain why some people are more at risk than others and how much exercise can help, if sufficient and sustained. Lastly, the video will follow patients associations in their mobilizations against NASH.

PART 4 NASH: Getting Diagnosed 
https://www.youtube.com/watch?v=x_nwF...
In this fourth TV show, you will discover how much of challenge NASH diagnosis is – mainly because NASH is a silent disease (no symptoms) which makes it difficult to diagnose – and how current procedures can be a bottleneck in the patient journey. Liver experts will explain the current invasive and non-invasive diagnostic techniques used when NASH is suspected, as well as latest research in novel diagnostic tools and what the future holds in terms of diagnosis.

PART 5 NASH: Disease evolution and consequences  
https://www.youtube.com/watch?v=Sl9Fu...
In this fifth TV show, you will learn more about the consequences of non-alcoholic steatohepatitis in the liver, but also in the rest of the body, with associated conditions. A French sports journalist will share his testimony as a NASH patient that overcame a liver transplant and a kidney as the last resort to survive, and a representative from The Liver Forum will explain how experts work to research the best patient clinical management solutions. In the end, you will know more about the consequences on health, the consequences on the economy, stigmas, lessons learned and the dire need for awareness.

PART 6 NASH: Patient care and clinical management 
https://www.youtube.com/watch?v=rWS-c...
In this sixth video, you will discover how much of a challenge patient management is, and especially, how to answer this burning question: “how can we care for patients in the absence of treatment?” – Today, on top of the lifestyle change (weight loss and exercise) ongoing research on therapeutic solutions paves the way for a better patient care. Moreover, you’ll discover how physicians are all working hand in hand to cover all the aspects of this multi-faceted disease. Finally, you will have the opportunity to hear the American Liver Foundation’s CEO’s perspectives on NASH.

PART 7 NASH: What perspectives?
https://www.youtube.com/watch?v=vDt5k...
In this seventh video, you will learn more about the next key challenges in the field of NASH, and about the crucial need for awareness and for public policy. Experts will give some forecast about NASH, ongoing research and the shed light on future management solutions You will get insights on the economic burden of NASH and the need for all stakeholders to be involved in NASH awareness. To conclude these seven sequences, there will be a special focus on how street art can help increase awareness and what we can hope for in the future.

Elsewhere
Non-alcoholic fatty liver disease: risks, prevention, and more
June 11, 2018
Lauren Phinney
Doctor Rohit Loomba appeared on KUSI News in San Diego to discuss Non-alcoholic fatty liver disease and how to prevent it. 
Watch his informative interview here.

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases
A recent publication from the American Association for the Study of Liver Diseases (AASLD) provides guidance for the evaluation and management of patients with NAFLD.
This guidance provides a data‐supported approach to the diagnostic, therapeutic, and preventive aspects of nonalcoholic fatty liver disease (NAFLD) care. A “Guidance” document is different from a “Guideline.” Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. 

On This Blog 

Maybe this weekend you might think about eating right or even start walking, two key elements for keeping your liver healthy. 
Tina

Wednesday, June 13, 2018

Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030

Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030
https://doi.org/10.1016/j.jhep.2018.05.036

Full-Text
View Online
Download PDF

Highlights
•Fatty liver disease is a growing cause of cirrhosis and liver cancer globally.
•Disease burden is expected to increase with the epidemics of obesity and diabetes.
•Modeling shows slow growth in total cases and greater increase in advanced cases.
•Mortality and advanced liver disease will more than double during 2016-2030.

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) with resulting nonalcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma (HCC) globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data.

Methods
A model was used to estimate NAFLD and NASH disease progression in 8 countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections.

Results
If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as result of urbanization and the lowest growth in Japan as result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as result of an aging/increasing population.

Conclusions
NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden.

Lay summary
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) can lead to advanced liver disease, and are occurring in increasing numbers in tandem with epidemics of obesity and diabetes. A mathematical model was built to understand how the disease burden associated with NAFLD and NASH will change over time. Results suggest increasing numbers of cases of advanced liver disease and liver-related mortality in the coming years.

Continue to article: View Online

Tuesday, June 12, 2018

NASH - Israeli company Galmed gets positive trial results for liver drug

Israeli company Galmed gets positive trial results for liver drug
Last Updated: 2018-06-12
By Reuters Staff
TEL AVIV (Reuters) - Galmed Pharmaceuticals said on Tuesday patients in a mid-stage trial for its treatment for non-alcoholic steatohepatitis (NASH), a fatty liver disease linked to obesity, showed a statistically significant reduction in liver fat. The results will allow Galmed to meet with regulators as soon as possible and discuss a pivotal Phase 3 study design, Galmed CEO Allen Baharaff said.

Press Release
Galmed's 600 mg Aramchol™ Achieved a Regulatory Approvable Endpoint Showing NASH Resolution Without Worsening of Fibrosis, in NASH Patients, in the Global Phase 2b ARREST 52-Week Study

Data Strongly Support Advancement of Aramchol™ 600mg to Phase 3

TEL AVIV, Israel, June 12, 2018 /PRNewswire/ --
Statistically significant reduction in liver fat was demonstrated by Magnetic Resonance Spectroscopy (MRS) in patients completing 52 weeks of treatment with Aramchol 400mg vs. placebo. Post hoc analysis of MRS responders, defined by a reduction of =5% absolute change from baseline, demonstrated a clinically and statistically significant effect of Aramchol 600mg vs. placebo.

Significantly more patients treated with Aramchol 600mg vs. placebo showed NASH resolution without worsening of fibrosis in the 52-week biopsy, a regulatory approvable endpoint.

A higher proportion of patients with at least one-point improvement in fibrosis score without worsening of NASH was demonstrated in Aramchol 600mg vs. placebo, in the 52-week biopsy, a regulatory approvable endpoint.

Statistically significant reductions in ALT and AST were demonstrated in Aramchol 400mg and 600mg vs. placebo.

Aramchol continues to show favorable safety and tolerability profile.

Monday, April 30, 2018

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Journal Of Hepatology
May 2018 Volume 68, Issue 5, Pages 1063–1075

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease
Thomas Jensen , Manal F. Abdelmalek, Shelby Sullivan, Kristen J. Nadeau, Melanie Green, Carlos Roncal, Takahiko Nakagawa, Masanari Kuwabara, Yuka Sato, Duk-Hee Kang, Dean R. Tolan, Laura G. Sanchez-Lozada, Hugo R. Rosen, Miguel A. Lanaspa, Anna Mae Diehl, Richard J. Johnson

Full-Text

TAKE-HOME MESSAGE
While we have known for many years that fructose and beverages sweetened with high fructose corn syrup can contribute to nonalcoholic fatty liver disease, this is an excellent review of the literature to date on this topic. In addition, it postulates the potential mechanisms that could be contributing to fructose's contribution to the development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. It also highlights the factors that can potentiate the effect that fructose has on the liver, including genetic mechanisms, the role of fructokinase, high-fat diets, and alcohol.

While certainly more research is needed, this review is beneficial when speaking to our patients and providing guidance on dietary changes that may improve their disease.

– Natasha VonRoenn, MD

Summary
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup [HFCS]) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

Monday, April 23, 2018

HCV, type 2 diabetes & fatty liver disease - Importance of diet and exercise

Importance of diet and exercise 

This Michigander is announcing winter might just be over. I am so done walking on my ugly, hated, overrated treadmill, looking forward to moving my morning routine outside.

If you too are feeling a bit of spring fever, or preparing for a lifestyle change, check out the links provided below and learn about the importance of diet and exercise for people with HCV, type 2 diabetes or fatty liver disease.

On The Radio
To get you started we begin with Dr Norman Swan, the host of Health Report, along with his guest Professor Mike Lean, lead author in a study investigating the impact of weight loss on type 2 diabetes, published in the Lancet 10 February 2018; Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The study found after a year, participants who lost weight (around 30 pounds) on a 800 calorie diet, no longer had type 2 diabetes. The diet may be too difficult or not recommended for some people, in the trial patients were followed closely, however, the outcome is amazing. The interview starts at 8:29, listen to the program, here, read the transcript below or visit Health Report.

Transcript
Norman Swan: There's good news, for once, from the west of Scotland where a trial in general practice of an extremely low calorie diet has reversed type 2 diabetes in a large percentage of participants. Mike Lean is Professor of Human Nutrition at the University of Glasgow and is on the line. Welcome to the Health Report.

Mike Lean: Hello, how are you?

Norman Swan: Fine. You say in the paper that this is the first trial of its kind in type 2 diabetes, which is extraordinary.

Mike Lean: We've known about type 2 diabetes and thought of it as a distinct disease growing enormously in numbers and costing perhaps more than any other single disease for about 100 years, and it has been noted in a number of studies that some people if they lose enough weight will get rid of their diabetes. But no study has previously gone out to actually try and do that, to actually get as many people as possible to become non-diabetic, to get rid of their diabetes completely.

Norman Swan: So what did you do in this study?

Mike Lean: Well, this is not rocket science. What we did was we recruited people in primary care, in general practice, who were overweight, BMI over 27, so not enormously overweight but overweight, with type 2 diabetes. And we ask them to follow a formula diet, not a very low calorie but and 800-odd calorie diet for as long as it took, and it took quite a long time in some cases, to lose enough weight to become non-diabetic. And we aimed to get 15 kg weight loss because we knew from other observations that that was likely to do it. And of course not everybody managed, sadly, a lot of people found it really hard. A lot of people did manage. In the end we got about a quarter of our patients to lose that amount of weight. And those who lost 15 kg, almost 90% were no longer diabetic after a year, they were off all their medication, they were off all their diabetic medication and their antihypertensive medication, and they felt a lot better, their quality of life went up.

The remainder who didn't lose 15 kg, none of them got worse. Of those who lost over 10 kg, over half of them were non-diabetic. So you don't need to lose 15 kg but it's much better if you do. And I think what we've learnt from this is what we've regarded as a distinct disease, type 2 diabetes, is actually all part and parcel of obesity when you think about obesity as a disease process…

Norman Swan: We'll come back to the diet in a minute. And what was the recidivism rate, if you want to call it that, in terms of people gaining weight again and returning to diabetes?

Mike Lean: Yes, so that is of course…we've only published the one-year results and there's a lot more to find out. What we did find out was that the proportion of people with diabetes who wanted to have a go at this was very high. It was probably no great surprise because being diabetic is a penalty and it carries terrible medical risks as well as financial. The number within a year who put on any weight was really quite small, but we know very well from earlier studies that it's hard to maintain…the biggest problem is not losing the weight, it's actually maintaining it long term, and that's where our big research effort needs to go.

Norman Swan: So the diet itself…an 800 calorie diet is not something you try yourself at home because you can go into nutritional deficiency. This was a shakes and bars diet, wasn't it, it was a meal plan diet.

Mike Lean: That's correct, it was a formula diet which made sure it had all the vitamins and minerals, everything that was necessary, provided the patients actually followed this. And they didn't have to pay for it, they were given it for the study. And so they did that, so it was perfectly safe, there was no…

Norman Swan: That's my point, so it's one of these things you can buy in the chemist and it comes in various boxes, but we won't talk about the branding.

Mike Lean: The branding doesn't matter, all these things are pretty much the same. What matters is not what comes in the box or out of the packet, it's the support that is given with it, because people who go and get these type of diets from the chemist or from a supermarket generally do it for two or three or four weeks and then they peel off. If you are going to get rid of your diabetes you've got to stick in for probably 12 weeks if you do it full time. There are plenty of people who do it off and on for 12 weeks and need to carry on doing it off and on for a bit longer to lose their 10 or 15 kg. So there are different routes to getting there, you don't half to lose it all in one go but it works better if you do.

Norman Swan: What about complications, like if you lose weight fast when you are overweight you can get gallbladder disease…

Mike Lean: Ah, you're well informed!

Norman Swan: You can low blood sugar if you're on insulin, or diabetes complications. What sort of complications did people get?

Mike Lean: Well, the first thing was for this particular study we didn't include people who were already on insulin, partly because their likelihood of getting a remission is much lower. It had probably done damage to their pancreas by that stage. And what we did on day one was that we stopped all our anti-diabetes medication, so there's no risk of hypoglycaemia at all, and nobody had hypoglycaemia. And the same thing went for the blood pressure tablets, we stopped all their blood pressure tablets on day one because otherwise if you lose weight there is a risk of possible hypotension, and just to pick up your other point, there was one patient amongst the 150 who started, one who developed abdominal pains and we think that was probably by gallstones. That's a common complication of obesity, very common in people with diabetes anyway, and it can be made worse during weight loss.

Norman Swan: These are similar findings to bariatric surgery.

Mike Lean: Oddly the remission rate was actually a tiny bit better than bariatric surgery if you can lose 15 kg. If you lose 15 kg you will almost certainly get rid of your diabetes, whether or not it's done with surgery. There are of course many fewer hazards doing it without surgery. They produce very similar results, yes.

Norman Swan: Mike, thanks very much for joining us, a fascinating study.

Mike Lean: Thank you very much.

Norman Swan: Mike Lean is Professor of Human Nutrition at the University of Glasgow.

Fatty Liver Disease & Type 2 Diabetes 
"Given the increasing worldwide incidence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. Recent developments in the field have shown that NAFLD not only is a “liver disease” but also is the underlying cause of an increasing number of extrahepatic manifestations; thus, it should be treated as a multisystem disease. NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time."

Also noted in the article; The prevalence of Nonalcoholic Steatohepatitis (NASH), in people who are obese and have type 2 diabetes may be as high as 40%, whereas it is less than 5% in people without type 2 diabetes.
Read the article, here.

Presented at Liver Congress 2018
Alcoholic liver disease replaces hepatitis C infection as leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA
Two independent studies presented at the conference reported; that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.
Read the article, here.

Hepatitis C & Diabetes
Several studies have demonstrated the risk for development of diabetes is increased in people with chronic hepatitis C infection (HCV), for instance people with HCV have a 2.3 fold increased chance of having type 2 diabetes. According to a 2013 study published in Alimentary Pharmacology Therapeutics; Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.

HCV Treatment & Type 2 Diabetes
The good news is with today's high sustained viral response rates using direct antiviral medications to treat HCV, people who successfully reach SVR, or achieve a cure, lower their risk for the development of type 2 diabetes, the recent study was published in the Journal of Viral Hepatitis [published online February 25, 2018]. A quick overview of the study can be found online, here.

Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR
This particular study may be of interest to people with HCV, according to data published Mar 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals. Full-text, here....

Tips - Eating Right
Eating better tied to lower risk of liver disease
April 27, 2018
(Reuters Health) - People who make an effort to improve their diet may be more likely to have less fat in their livers and a lower risk of liver disease than individuals who stick to unhealthy eating habits, a U.S. study suggests.

The Liver Loving Diet
"The Liver Loving Diet" is a book that will help you learn to eat well during all phases of liver disease. Karen Hoyt, the author, also blogs about living with and treating hepatitis C, cirrhosis, liver cancer and liver failure.

Mediterranean diet reduces liver fat, risk for NAFLD
March 30, 2018
Improved diet quality based on the Mediterranean-style diet score and Alternative Healthy Eating Index score correlated with less liver fat accumulation and a reduced risk for new-onset nonalcoholic fatty liver, according to a recently published study.
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Bottom Line
Spring is a great time to start again, experts agree two key elements in the prevention and management of type 2 diabetes and fatty liver disease is weight loss and exercise. In the end, its all good for your liver!

See you soon,
Tina