Tocomin SupraBioÒ Improves Liver Stiffness Measurement In Patients With Non-Alcoholic Fatty Liver Disease

PRESS RELEASE Edison, New Jersey, USA, November 4^th, 2013

Tocomin SupraBio^Ò Improves Liver Stiffness Measurement In Patients With Non-Alcoholic Fatty Liver Disease

November 4^th, 2013 – New Jersey, USA –At the recently concluded Asian Pacific Association for the Study of the Liver (APASL), a research team of medical doctors from the Philippines, led by Dr. Marilyn Arguillas shows that supplementation with Tocomin SupraBio^® patented and bio-enhanced full spectrum palm tocotrienol/tocopherol complex (manufactured by Carotech) at 100mg daily for 3 months significantly reduces liver stiffness in patients with non-alcoholic fatty liver disease (NAFLD).

Dr. Marilyn Arguillas used non-invasive Transient Elastography (FibroScan) to measure liver stiffness among NAFLD patients. Liver Stiffness Measurement (LSM) is routinely used to determine the hepatic fibrosis stage in NAFLD patients.

“The development of fibrosis marks the connection between fatty liver disease and end-stage liver disease,” Dr. Arguillas said in a newspaper interview.

The study involved 67 patients for three months. Patients were divided into two groups (treatment group and control group). Both groups were placed under Lifestyle Modification Advice Group (LMAG), which included nutritional counseling and advice on exercise. The Treatment group, however, was also placed on 100mg of mixed tocotrienol (containing Tocomin SupraBio^®) daily for 3 months.

After 3 months, 57% of all patients (n=38) showed decrease in their liver stiffness measurement, but 43% (n=29) did not improve. 79% of those who improved were from the Treatment group and 21% from LMAG alone. Out of the 29 patients who did not improve, 23 patients or 79% are from LMAG alone and only 6 patients or 21% from Treatment group.

The study shows that lifestyle modification and exercise together with supplementation of tocotrienol (Tocomin SupraBio^®) had a significant effect on the improvement of liver stiffness measure

NAFLD often coexists with metabolic syndrome especially type 2 diabetes and obesity. It is reported to be an independent risk factor for cardiovascular disease and affects approximately 30% of the population in Western countries. Recently, the University of Hong Kong reported that a staggering 40% of healthy Hong Kong population have non-alcoholic fatty liver disease, with majority of them not aware of the condition.

In an earlier animal study[1], Japanese researchers reported that simultaneous intake of tocotrienols with alpha-tocopherol synergistically inhibited lipid accumulation, inflammation and fibrosis in the liver, which further underscores the importance of tocotrienols and tocopherols in reducing the severity or risk of NAFLD.

“Human studies using Tocomin SupraBio^® have previously shown that tocotrienols improve liver conditions in NAFLD and end stage liver disease and that alpha-tocopherol works in a synergistic manner with tocotrienols in exerting these liver protective effects. We are pleased to learn of this latest study from the Philippines, which further supports hepatoprotective benefits of Tocomin SupraBio^®,” says WH Leong, Vice President of Carotech Inc.

“To date, there is no drug or therapeutic agent that could cure NAFLD. This study shows that supplementation of Tocomin SupraBio^® at 100mg daily coupled with life style modification for 3 months have significant benefits in reducing liver stiffness, hence minimizing risk of progressing to NASH, as well as other NAFLD-related diseases including obesity, diabetes, and cardiovascular disease (metabolic syndrome),” added WH Leong.

Sources: “The Effect of Vitamin E (Mixed Tocotrienol) on the Liver Stiffness measurement Measured by Transient Elastography (FibroScan) among NAFLD Patients”, presented at APASL Liver Week, Singapore, June 7^th, 2013.

About Carotech

Carotech, incorporated in 1990, is the first and largest producer of natural full spectrum tocotrienol/tocopherol complex (Tocomin^® & Tocomin SupraBio^®), natural mixed carotene complex (Caromin^®), phytosterol complex (Stelessterol™), red palm oil concentrate (Spectra™) in the world via its patented technology.

Carotech is the only GMP-Certified tocotrienol producer in the world. Its laboratory is accredited with ISO/ISE 17025 accreditation.

Tocomin SupraBio^® is a patented (US Patent No. 6,596,306) self emulsifying palm tocotrienol complex that ensures optimal tocotrienols oral absorption.

Carotech manufactures these products under the tradenames: Tocomin^®, Tocomin SupraBio^®, Caromin^®, Stelessterol™ and Spectra™.

Carotech’s branded ingredients are 100% Non-GMO, Kosher and Halal certified.

Websites: www.carotech.net and www.tocotrienol.org

Contacts:

Mr. WH Leong, Vice President, Carotech, Australia Tel : +61 (03) 9801 3881 E-mail: info@caro-bf.com

Dr. Sharon Ling, Carotech, Europe Tel : +44 (0) 1296 623 214 Email : sling@caro-bf.com

Mr. Bryan See, Carotech Inc, USA Tel : +1 (732) 906 1901 Email: klsee@caro-bf.com

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[1] Yachi R, et al., 2013. Effects of tocotrienol on tumor necrosis factor-alpha/D-galactosamine-induced steatohepatitis in rats. J. Clin. Biochem. Nutr., 52(2), pp. 146-153.

Source Carotech INC.

Also See: The Effect of Vitamin E (Mixed Tocotrienol) on the Liver Stiffness Measurement Measured by Transient Elastography (FibroScan) among NAFLD Patients

The Effect of Vitamin E (Mixed Tocotrienol) on the Liver Stiffness Measurement Measured by Transient Elastography (FibroScan) among NAFLD Patients

Abstract

Speaker: Eduward E.J. Thendiono

Author: Eduward Jansen Thendiono, Marylin Arguillas

Affiliation: Internal Medicine, Davao Doctors Hospital, Davao City, Philippines

Session: Distinguished Posters - NAFLD

Date: Friday - June 07, 2013 13:30-14:00

Location: Exhibition Hall

Subtopic: Clinical

Topic: NAFLD

Introduction: Vitamin E has been shown to slow down progression or cause regression of fibrosis stage among NAFLD patients. Transient Elastography (FibroScan) is a non-invasive tool that has been used to determine the stage of fibrosis among NAFLD patients and may be used for treatment monitoring.

Methods: NAFLD patients diagnosed by ultrasound who met the inclusion criteria were enrolled in the study. Liver Stiffness Measurement (LSM) was measured by FibroScan at base line and at the end of 3 months. A change in the LSM was the primary objective. Chi Square analysis was used to measure the change of LSM pre and post treatment. P value less than 0.05 was considered significant.

Patients were assigned to either the Life style Modification Advice Group (LMAG)—with nutritional counseling and advise to exercise—or the Treatment Group (Vitamin E as Mixed Tocotrienol 100 mg daily for 3 months plus lifestyle modification advise).

Result: Fifty-seven percent (38/67) of patients enrolled in both arms of the study improved --with decrease in their LSM measurements -- but 43% (29 of 67) did not.

Of those who improved 79% (30 / 38) were from the Treatment Group (Vitamin E) and 21% (8 / 38) were from the LMAG.

Twenty -nine (29) patients did not improve: 79% (23/29) from LMAG and only 6/29 (21%) from the Treatment Group. Chi-square analysis showed that treatment with Vitamin E had a significant effect (p= < 0.05) on improvement of LSM.

Conclusion: Vitamin E (mixed Tocotrienol) 100 mg daily for 3 months could decrease the LSM among NAFLD patients.

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Liver stiffness more predictive of decompensation than biopsy results in HIV/HCV coinfection

Provided by Healio

July 9, 2013

Liver stiffness measurement is similarly predictive of overall mortality and more predictive of decompensation than liver biopsy results among patients with HIV/HCV coinfection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated 297 patients coinfected with HCV and HIV who underwent liver biopsy (LB) and liver stiffness measurement (LSM) within 12 months of one another. The midway point between the procedures was considered the baseline date for analysis. Ninety-three percent of participants were receiving therapy with antiretrovirals at baseline, with undetectable plasma HIV RNA levels in 79% of cases and a median CD4 cell count of 514 cells/mcL.

Among evaluable participants after 26 cases were lost to follow-up, overall mortality across the cohort was 1.56 deaths per 100 person-years. Increased risk for death was associated with elevated LSM values (adjusted HR=1.28; 95% CI, 1.12-1.46 per 5 kPa increase) and fibrosis stage at baseline as indicated by LB (aHR=1.56; 95% CI, 1.02-2.4). Liver decompensation occurred at a rate of 1.59 cases per 100 person-years, with LSM (aHR=1.37; 95% CI, 1.21-1.54) and fibrosis stage at baseline (aHR=1.67; 95% CI, 1.15-2.43) as predictive factors.

Integrated discrimination improvement (IDI) analysis indicated that models incorporating LMS values performed 3.9% better in predicting mortality than models incorporating LB, but was not statistically significant (P=.072). For the prediction of liver decompensation, LMS-based models performed 8.4% better than LB-based models (P=.045).

“LSM-based prediction achieves a similar yield [to] LB-based models to predict overall mortality in HIV/HCV coinfected patients, and the former could better predict liver decompensations,” the researchers concluded. “LSM may replace LB as [a] prognostic tool in this setting.”

For more information:

Macías J. TUAB0104: Prediction of Survival and Decompensations of Cirrhosis Among HIV/HCV Coinfected Patients: A Comparison of Liver Stiffness Versus Liver Biopsy. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Non-invasive tests for fibrosis and liver stiffness predict 5-year survival of patients chronically infected with hepatitis B virus

Alimentary Pharmacology & Therapeutics

Volume 37, Issue 10, pages 979–988, May 2013

V. de Lédinghen^1,2,*, J. Vergniol¹, C. Barthe¹, J. Foucher^1,3, F. Chermak¹, B. Le Bail^2,4, W. Merrouche¹, P.-H. Bernard³

Article first published online: 5 APR 2013

DOI: 10.1111/apt.12307

© 2013 Blackwell Publishing Ltd

Abstract

Summary

Background

Liver stiffness and non-invasive tests predict overall survival in chronic hepatitis C. However, in patients chronically infected with hepatitis B virus (HBV), only the association between liver stiffness and the risk of hepatocellular carcinoma has been published.

Aim

To evaluate the 5-year prognostic value of liver stiffness, non-invasive tests of liver fibrosis, and liver biopsy, to predict overall survival in chronic hepatitis B.

Methods

In a consecutive cohort, we prospectively assessed fibrosis, with liver stiffness, FibroTest, APRI, FIB-4 and liver biopsy (if indicated). We examined death and liver transplantation during a 5-year follow-up, and factors associated with overall survival.

Results

A total of 600 patients (men 64%, mean age 42 years, inactive carriers 36%) with chronic hepatitis B were included. At 5 years, 25 patients were dead (13 liver-related deaths) and four patients had liver transplantation. Overall survival was 94.1% and survival without liver-related death 96.3%. No liver-related death was observed in inactive carriers. Survival was significantly decreased in patients diagnosed with severe fibrosis, whatever the non-invasive method used (P < 0.0001), or liver biopsy (P = 0.02). Patients' prognosis decreased as liver stiffness and FibroTest increased. In multivariate analysis, FibroTest and liver stiffness had the highest hazard ratio with survival. The association persisted after adjustment on age, necro-inflammatory histological activity presumed by ActiTest and treatment.

Conclusions

Liver stiffness measurement or FibroTest can predict survival in chronic HBV infection. Thus, these tools may help physicians to early assess prognosis and discuss specific treatments, such as liver transplantation.

Source

Advanced probe reliably measured LSM in nonobese NAFLD patients

Wong VWS. Am J Gastroenterol. 2012;doi:10.1038/ajg.2012.331.

October 16, 2012

A new, larger transient elastography probe measured liver stiffness effectively in patients with nonalcoholic fatty liver disease, but its accuracy and reliability were reduced among obese patients in a recent study.

Researchers used M and new XL probes to perform liver stiffness measurement (LSM) on 193 patients with nonalcoholic fatty liver disease (NAFLD) in France and Hong Kong. The XL probe is larger, uses a lower ultrasound frequency than the M probe and is intended to improve measurement success among obese patients. Biopsy was performed within 24 hours after LSM, and liver histology served as reference standard to determine LSM accuracy.

Overall accuracy was similar between probes, and measurements correlated well (r2=0.9025, P<.001), but the XL probe often indicated lower LSM measurements (80% of patients). AUROC analysis produced the following values according to fibrosis staging:

• F2 or higher: 0.83 for M probe; 0.80 for XL
• F3 or higher: 0.87 for M; 0.85 for XL
• F4: 0.89 for M; 0.91 for XL

Investigators established an ideal cutoff of 7.2 kPa for F3 disease or higher, with a sensitivity and specificity of 78%, a PPV of 60% and NPV of 89%.

The XL probe obtained 10 valid acquisitions (95% of cases compared with 81%, P<.001)and a success rate greater than 60% (90% of cases compared with 74%, P<.001)more frequently than the M probe. Failure occurred in 10% of patients with the M probe vs. 2% with the XL (P=.002).

Success rate differences were more pronounced among obese patients, with 10 valid acquisitions obtained in 93% of patients compared with 60% using the M probe (P<.001).

Discordance of two or more stages between histology and XL probe results occurred in 9% of patients. Investigators observed an independent association between discordance and a BMI greater than 35 kg/m2 (aOR=9.09; 95% CI, 1.10-75.43).

“XL probe achieved successful and reliable LSM in the majority of NAFLD patients … but obesity is associated with less accurate and reliable measurements,” the researchers wrote. “With high negative predictive value, the technique can be used to exclude advanced fibrosis and cirrhosis reliably in routine clinical practice.”

Disclosure: See the study for a full list of relevant disclosures.

Source

Noninvasive Tests for Fibrosis and Liver Stiffness Predict 5-Year Outcomes of Patients With Chronic Hepatitis C

Gastroenterology
Volume 140, Issue 7 , Pages 1970-1979.e3, June 2011.

Julien Vergniol, Juliette Foucher, Eric Terrebonne, Pierre–Henri Bernard, Brigitte le Bail, Wassil Merrouche, Patrice Couzigou, Victor de Ledinghen

Received 28 November 2010; accepted 18 February 2011. published online 03 March

Abstract

Background & Aims

Liver stiffness can be measured noninvasively to assess liver fibrosis in patients with chronic hepatitis C. In patients with chronic liver diseases, level of fibrosis predicts liver-related complications and survival. We evaluated the abilities of liver stiffness, results from noninvasive tests for fibrosis, and liver biopsy analyses to predict overall survival or survival without liver-related death with a 5-year period.

Methods
In a consecutive cohort of 1457 patients with chronic hepatitis C, we assessed fibrosis and, on the same day, liver stiffness, performed noninvasive tests of fibrosis (FibroTest, the aspartate aminotransferase to platelet ratio index, FIB-4), and analyzed liver biopsy samples. We analyzed data on death, liver-related death, and liver transplantation collected during a 5-year follow-up period.

Results
At 5 years, 77 patients had died (39 liver-related deaths) and 16 patients had undergone liver transplantation. Overall survival was 91.7% and survival without liver-related death was 94.4%. Survival was significantly decreased among patients diagnosed with severe fibrosis, regardless of the noninvasive method of analysis. All methods were able to predict shorter survival times in this large population; liver stiffness and results of FibroTest had higher predictive values. Patient outcomes worsened as liver stiffness and FibroTest values increased. Prognostic values of stiffness (P < .0001) and FibroTest results (P < .0001) remained after they were adjusted for treatment response, patient age, and estimates of necroinflammatory grade.

Conclusions
Noninvasive tests for liver fibrosis (measurement of liver stiffness or FibroTest) can predict 5-year survival of patients with chronic hepatitis C. These tools might help physicians determine prognosis at earlier stages and discuss specific treatments, such as liver transplantation.

Keywords: Survival, Cirrhosis, FibroTest, FibroScan, Hepatitis C

Source

Noninvasive liver tests may predict hepatitis C patient survival

Public release date: 14-Jun-2011

Contact: Alissa J. Cruz
media@gastro.org
301-272-1602
American Gastroenterological Association

Non-invasive tests for liver fibrosis, such as liver stiffness measurement or the FibroTest, can predict survival of patients with chronic hepatitis C, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

"Liver stiffness measurement and/or the FibroTest could replace liver biopsy for the evaluation of hepatitis C, regardless of the stage of the disease," said Victor de Lédinghen, MD, PhD, of the Centre d' Investigation de la Fibrose Hépatique and lead author of this study. "Thus, these tools may help physicians assess prognosis early and discuss specific treatments."

Findings of this study are of major importance since liver stiffness, as a good predictive factor of survival, may help physicians evaluate the severity of liver disease earlier, decide with stronger arguments on a liver transplant or a portosystemic shunt (to bypass the liver), and evaluate more precisely the surgical risk of cirrhotic patients.

In chronic liver diseases, fibrosis assessment predicts liver-related complications and survival. In this study, doctors evaluated the five-year prognostic value of liver stiffness, non-invasive tests of liver fibrosis and liver biopsy to predict overall survival and survival without liver-related death in chronic hepatitis C.

A total of 1,457 patients with chronic hepatitis C were included. At five years, 77 patients died (39 liver-related deaths) and 16 patients had liver transplantation. Overall survival was 91.7 percent and survival without liver-related death was 94.4 percent. Survival was significantly decreased in patients diagnosed with severe fibrosis, no matter which non-invasive method was used.

All methods were able to predict shorter survival times; liver stiffness measurement and results of the FibroTest had higher predictive values. Doctors assessed fibrosis and — on the same day — liver stiffness, performed noninvasive tests of fibrosis (FibroTest, the aspartate aminotransferase to platelet ratio index, FIB-4), and analyzed liver biopsy samples.

"To our knowledge, this study is the first showing that liver stiffness has a prognostic value for overall survival and survival without liver-related death in patients with chronic hepatitis C virus infection," added Dr. Lédinghen. "The present study independently validated the prognostic value of the FibroTest and showed that liver stiffness and FibroTest can predict survival."

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For more information on hepatitis, please read the AGA brochure "Understanding Hepatitis" at www.gastro.org/patient-center/digestive-conditions/hepatitis.

About the AGA Institute
The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org.

About Gastroenterology
Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, Current Awareness in Biological Sciences, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit www.gastrojournal.org.

Source

Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study

Journal of Viral Hepatitis
Early View (Articles online in advance of print)

J. Fung, C.-L. Lai, D. K.-H. Wong, W.-K. Seto, I. Hung, M.-F. Yuen

Article first published online: 7 JAN 2011
DOI: 10.1111/j.1365-2893.2010.01428.x
© 2011 Blackwell Publishing Ltd

Author Information
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
*Correspondence: Prof Man-Fung Yuen, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. E-mail: mfyuen@hkucc.hku.hk

Abstract

Keywords:
chronic hepatitis B;fibroscan;liver stiffness;longitudinal;transient elastography

Summary.  For patients with chronic hepatitis B (CHB) infection, changes in liver stiffness measurement (LSM) over time are not known. We examined changes longitudinally in a cohort of patients. Four hundred and twenty-six patients with CHB underwent transient elastography. Patients were followed regularly, and repeat elastography was performed at 3 years. Hepatitis serology, viral load and routine liver biochemistry were monitored. Of the 426 patients, 38 (9%) were hepatitis B e-antigen (HBeAg)-positive, 293 (69%) were HBeAg-negative and 95 (22%) were patients with prior hepatitis B surface antigen (HBsAg) seroclearance. A total of 110 patients received oral antiviral therapy. There was a significant decline of LSMs at the follow-up measurement compared to baseline (6.1 vs 7.8 kPa respectively, P = 0.002) in treated patients who had elevated alanine aminotransferase (ALT) at baseline and subsequent normalization after 3 years (normal ALT limit being 30 U/L for males and 19 U/L for females). In nontreated patients, only the patients with persistently normal ALT at both time points had significantly lower LSMs at the follow-up measurement compared to baseline: 4.9 vs 5.3 kPa, respectively, in patients who remained positive for HBsAg (P = 0.005) and 5.1 vs 5.4 kPa, respectively, in patients who had HBsAg seroclearance (P = 0.026). In patients who remained positive for HBsAg, independent factors associated with a significant decline in LSM of ≥1 kPa included antiviral therapy (P = 0.011) and the ALT levels at the follow-up time point (P = 0.024). Thus, in patients with CHB, a significant decline in LSM after 3 years was observed in treated patients with ALT normalization and in untreated patients who had persistently normal ALT. Antiviral therapy and follow-up ALT levels were independent significant factors associated with a decline in LSM.

Source

LSM detects undiagnosed chronic liver disease

Published date :24-Dec-2010

MedWire News: Study findings show that liver stiffness measurement (LSM) can detect undiagnosed chronic liver disease in apparently healthy individuals, with the added benefit of a 100% positive predictive value for cirrhosis screening.

"So far, liver biopsy has been the gold standard for the assessment of fibrosis in patients with chronic liver disease," say Dominique Roulot (Avicenne Hospital, Bobigny, France) and co-authors.

"However, in cases of suspicion of non-alcoholic fatty liver disease (NAFLD), liver biopsy is difficult to recommend for apparently healthy patients with normal liver tests, because of its possible complications," they add.

A total of 1190 individuals from the general population, aged 45 years or older, attending for a medical check-up participated in the current study. All patients received LSM, in addition to laboratory tests and medical examinations. Those who scored over 8 kPa on the LSM were referred to a liver unit for further investigations.

Overall, 94 (8.5%) patients had a LSM >8 kPa, including nine patients with a LSM >13 kPa. The researchers note that although LSM values were normal in 4% of patients with perturbed liver tests, these tests came back as normal in 43% of patients with LSM >8 kPa.

NAFLD and alcoholic liver disease (ALD) were diagnosed as the likely causes of chronic liver disease in 52 and 20 patients, respectively. Hepatitis B and C were diagnosed in nine patients, and primary biliary cirrhosis in one patient.

Liver biopsy results confirmed that all of the nine patients with LSM >13 kPa had liver cirrhosis due to ALD or chronic hepatitis B/C. The remaining 18 biopsies showed liver fibrosis in all patients except one who presented with isolated steatosis.

Factors significantly associated with a LSM >8 kPa included being aged 57 years or older, having a body mass index ≥30 kg/m2, elevated waist circumference, diabetes, alanine aminotransferase ≥40 UI/l, and γ-glutamyltranspeptidase ≥45 UI/l.

The researchers say the findings suggest that "a relatively high percentage of liver diseases remain undiagnosed in apparently healthy individuals, and that LSM might contribute to referring these patients to hepatologists."

They conclude in the journal Gut: "If future studies determine that the superior positive predictive value of LSM can be achieved at an acceptable cost, compared with common screening methods, LSM might represent a first-line procedure for the mass screening of liver disease in the general population."

MedWire (http://www.medwire-news.md/) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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