Monday, March 4, 2019

Hepatitis C among intravenous drug users in upper middle-income countries.

Estimating the prevalence of hepatitis C among intravenous drug users in upper middle income countries: A systematic review and meta-analysis
Víctor Granados-García , Yvonne N. Flores, Lizbeth I. Díaz-Trejo, Lucia Méndez-Sánchez, Stephanie Liu, Guillermo Salinas-Escudero, Filiberto Toledano-Toledano, Jorge Salmerón

Published: February 26, 2019

Abstract
Aim
This systematic review and meta-analysis characterizes the prevalence of hepatitis C virus (HCV) infection among intravenous drug users (IDUs) in upper middle-income countries.

Methods
Five databases were searched from 1990–2016 for studies that took place in countries with a GDP per capita of $7,000 to $13,000 USD. The data extraction was performed based on information regarding prevalence, sample size, age of participants, duration of intravenous drug use (IDU), recruitment location, dates of data collection, study design, sampling scheme, type of tests used in identifying antibody reactivity to HCV, and the use of confirmatory tests. The synthesis was performed with a random effects model. The Cochrane statistical Q-test was used to evaluate the statistical heterogeneity of the results.

Results
The 33 studies included in the analysis correspond to a sample of seven countries and 23,342 observations. The point prevalence value estimates and confidence intervals of the random effects model were 0.729 and 0.644–0.800, respectively for all seven countries, and were greatest for China (0.633; 0.522–0.732) as compared to Brazil (0.396; 0.249–0.564). Prevalence for Montenegro (0.416; 0.237–0.621) and Malaysia (0.475; 0.177–0.792) appear to be intermediate. Mexico (0.960) and Mauritania (0.973) had only one study with the largest prevalence. A clear association was not observed between age or duration of IDU and prevalence of HCV, but the data from some groups may indicate a possible relationship. The measures of heterogeneity (Q and I2) suggest a high level of heterogeneity in studies conducted at the country level and by groups of countries.

Conclusions
In this systematic review and meta-analysis, we found that the pooled prevalence of HCV was high (0.729) among a group of seven upper middle income countries. However, there was significant variation in the prevalence of HCV observed in China (0.633) and Brazil (0.396). 

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NIH study of brain energy patterns provides new insights into alcohol effects

NIH scientists present a new method for combining measures of brain activity (left) and glucose consumption (right) to study regional specialization and to better understand the effects of alcohol on the human brain.
Dr. Ehsan Shokri Kojori, NIAAA

NIH study of brain energy patterns provides new insights into alcohol effects
Assessing the patterns of energy use and neuronal activity simultaneously in the human brain improves our understanding of how alcohol affects the brain, according to new research by scientists at the National Institutes of Health. The new approach for characterizing brain energetic patterns could also be useful for studying other neuropsychiatric diseases. A report of the findings is now online in Nature Communications.

“The brain uses a lot of energy compared to other body organs, and the association between brain activity and energy utilization is an important marker of brain health,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of NIH, which funded the study. “This study introduces a new way of characterizing how brain activity is related to its consumption of glucose, which could be very useful in understanding how the brain uses energy in health and disease.”

The research was led by Dr. Ehsan Shokri-Kojori and Dr. Nora D. Volkow of the NIAAA Laboratory of Neuroimaging. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH. In previous studies they and their colleagues have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, which is assessed through changes in blood oxygenation.

“The findings from this study highlight the relevance of energetics for ensuring normal brain function and reveal how it is disrupted by excessive alcohol consumption,” says Dr. Volkow.

In their new study, the researchers combined human brain imaging techniques for measuring glucose metabolism and neuronal activity to derive new measures, which they termed power and cost.

“We measured power by observing to what extent brain regions are active and use energy,” explained Dr. Shokri-Kojori. “We measured cost of brain regions by observing to what extent their energy use exceeds their underlying activity.”

In a group of healthy volunteers, the researchers showed that different brain regions that serve distinct functions have notably different power and different cost. They then investigated the effects of alcohol on these new measures by assessing a group of people that included light drinkers and heavy drinkers and found that both acute and chronic exposure to alcohol affected power and cost of brain regions.

“In heavy drinkers, we saw less regional power for example in the thalamus, the sensory gateway, and frontal cortex of the brain, which is important for decision making,” said Dr. Shokri-Kojori. “These decreases in power were interpreted to reflect toxic effects of long-term exposure to alcohol on the brain cells.”

The researchers also found a decrease in power during acute alcohol exposure in the visual regions, which was related to disruption of visual processing. At the same time, visual regions had the most significant decreases in cost of activity during alcohol intoxication, which is consistent with the reliance of these regions on alternative energy sources such as acetate, a byproduct of alcohol metabolism.

They conclude that despite widespread decreases in glucose metabolism in heavy drinkers compared to light drinkers, heavy drinking shifts the brain toward less efficient energetic states. Future studies are needed to investigate the mechanisms contributing to this relative inefficiency.

“Studying energetic signatures of brain regions in different neuropsychiatric diseases is an important future direction, as the measures of power and cost may provide new multimodal biomarkers for such disorders,” says Dr. Shokri-Kojori.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol use disorder. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at: https://www.niaaa.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference
Shokri-Kojori E, Tomasi D, Alipanahi B, Wiers CE, Wang GJ, Volkow ND (2019). Correspondence between cerebral glucose metabolism and BOLD reveals relative power and cost in human brain. Nat Commun. 10(1):690.

Sunday, March 3, 2019

HCV reinfection as a positive indication of high‐risk population treatment access

Recommended Reading
High response and re-infection rates among people who inject drugs treated for hepatitis C in a community needle and syringe programme
We show that it is feasible to recruit people who inject drugs(PWID) from a community-basedneedle and syringe programme (NSP) onto HCV treatment, and achieve over 80% SVR-12 andimpressive treatment adherence.

Commentary
HCV reinfection as a positive indication of high‐risk population treatment access
Gregory J Dore

First published: 25 February 2019
https://doi.org/10.1111/jvh.13092

Strategies to address HCV reinfection and limit its overall impact on HCV elimination are required, but the most important of these is ongoing engagement with high- risk individuals to enable detection of HCV reinfection and its retreatment without stigma and discrimination.

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Article shared via Twitter by Henry E. Chang‏.

First patient dosed in phase 2/3 trial of advanced HCC therapy

First patient dosed in phase 2/3 trial of advanced HCC therapy
March 3, 2019

Innovent Biologics announced first patient dosing in a phase 2/3 trial of Tyvyt with IBI305 for patients with advanced hepatocellular carcinoma taking place in China, according to a press release.

"HCC is the fourth most common cancer and the second leading cause of cancer related death in China,” Fan Jia, president of Zhongshan Hospital, said in the release. “The five-year survival rate is about 10%, and only 20-30% of patients have the opportunity for curative surgery. Current targeted therapies have only shown limited responses in HCC. Immune checkpoint inhibitors have brought new hope to patients with this life-threatening disease.”

Continue reading article...

Saturday, March 2, 2019

Discovery may lead to a blood test to detect early stages of NAFLD

Towards a blood test for early-stage liver disease
Researchers uncover a set of proteins that are enriched in pre-symptomatic non-alcoholic fatty liver disease

Heidelberg, 1 March 2019 – One in four people in Western and Asian societies develop a build-up of fat in the liver as a result of an unhealthy diet. This disease – referred to as non-alcoholic fatty liver disease (NAFLD) – causes no symptoms initially but can develop into end-stage liver cirrhosis with limited treatment options. A discovery, published today in Molecular Systems Biology, paves the way for a simple blood test to detect early stages of NAFLD, opening up the possibility of preventing the development of liver cirrhosis through lifestyle changes or pharmaceutical intervention.

The liver is an important organ, filtering toxic substances from the body and producing proteins required for digestion, blood clotting, and other important physiological functions.

“The liver is very resilient and capable of regenerating itself, which may be the reason why liver damages due to excessive fat deposition can go undetected for a long time,” says EMBO Member Matthias Mann of the University of Copenhagen, Denmark, and the Max Planck Institute of Biochemistry in Martinsried, Germany, who led the study. However, when damage accumulates liver function eventually starts to fail.

To date, the standard procedure for diagnosing NAFLD is liver biopsy – a cumbersome and costly procedure that can lead to complications. Non-invasive methods that reliably detect early stage NAFLD are therefore urgently required.

Mann and his colleagues investigated the plasma proteome – the entire set of proteins present in the blood plasma – of NAFLD patients. Using sophisticated mass spectrometry technologies, they uncovered a set of proteins that accumulate in the plasma of patients with non-symptomatic NAFLD.

In a first set of experiments, they determined that the blood proteome of patients in a late stage of the disease differed considerably from that of healthy controls. Many proteins that were altered in the patients’ blood proved to be associated with known aspects of the disease, such as thrombosis, vitamin A and D deficiency, or defects in glucose metabolism. These observations show the validity of the procedure to find new disease-related proteins.

In the next step, comparing the proteome of patients in early stage NAFLD with that of healthy individuals, the researchers found only minor differences. They did, however, succeed in identifying six proteins that were significantly associated with early stage NAFLD.

“One of the proteins we uncovered, termed PIGR, is of special interest,” says Mann. “Individuals with NAFLD who do not show any symptoms have increased levels of PIGR in their blood. And the concentration of the protein increases the further the disease progresses, making PIGR an interesting biomarker candidate for the inclusion in liver damage tests.”

While current blood tests only detect liver damage at a late stage in disease development, the present study is an important step towards developing new diagnostic tools to identify patients with NAFLD in a much earlier, pre-symptomatic phase.

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

Molecular Systems Biology
Lili Niu, Philipp E. Geyer, Nicolai J. Wewer Albrechtsen, Lise L. Gluud, Alberto Santos, Sophia Doll, Peter V. Treit, Jens J. Holst, Filip K. Knop, Tina Vilsbøll, Anders Junker, Stephan Sachs, Kerstin Stemmer, Timo D. Müller, Matthias H. Tschöp, Susanna M. Hofmann, Matthias Mann

DOI: 10.15252/msb.20188793
Read the paper: http://msb.embopress.org/cgi/doi/10.15252/msb.20188793

Current and future pharmacological therapies for managing cirrhosis and its complications

World J Gastroenterol. Feb 28, 2019; 25(8): 888-908
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.888

Current and future pharmacological therapies for managing cirrhosis and its complications
David Kockerling, Rooshi Nathwani, Roberta Forlano, Pinelopi Manousou, Benjamin H Mullish, Ameet Dhar 

Core tip: Pharmacological therapy is central to the management of cirrhosis and its complications. Whilst there has been recent debate about the safety of beta-blockade in patients with ascites, conversely there is growing interest in potential benefits relating to a reduction in gut bacterial translocation and hepatocellular carcinoma risk. In addition to its well-established role in treating hepatic encephalopathy, rifaximin may also have a key role in preventing secondary infections. In this review, we summarise these and other uncertainties, controversies and novel developments related to pharmacotherapy in the clinical management of chronic liver disease.

View full-text article online: 

Friday, March 1, 2019

Companies, states interested in Louisiana Netflix-style hepatitis C plan

Companies, states interested in Louisiana hepatitis C plan
By MELINDA DESLATTE Associated Press

BATON ROUGE, La.
Three drug companies are interested in Louisiana's plan to use a Netflix-style subscription model to buy access to hepatitis C drugs for Medicaid patients and prisoners, a treatment concept being watched by other states, the state health department announced Friday.

Health Secretary Rebekah Gee wants Louisiana to pay a fee to a drug manufacturer for unlimited access to its hepatitis C medication. The state will treat as many people as it can during the access period, rather than pay a per-patient treatment price
Continue reading:
https://www.ledger-enquirer.com/news/article226991064.html 
https://www.ledger-enquirer.com/news/article226991064.html
Read more here: https://www.ledger-enquirer.com/news/article226991064.html#storylink=cpy

Tuesday, February 26, 2019

Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification

Open Forum Infectious Diseases
Published: 22 February 2019 

Accepted Manuscript
Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification 
Charlotte Hedskog1, Bandita Parhy1, Silvia Chang1, Stefan Zeuzem2, Christophe Moreno3, Stephen D.Shafran4, Sergio M. Borgia5, Tarik Asselah6, Laurent Alric7, Armand Abergel8, Jyh-Jou Chen9, Jane Collier10,Dharmesh Kapoor11, Robert H. Hyland1, Peter Simmonds12, Hongmei Mo1, Evguenia S. Svarovskaia

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Abstract
Background
The hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. 

Methods
Full genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A and/or NS5B to HCV genotype (GT) 1 to 8 reference strains.

Results
14,653 patients with GT1 to 6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However for 19 patients, novel subtypes were identified with <85% homology compared to previously described subtypes. These novel subtypes had the following genotypes; 9 in GT2, 5 in GT4, 2 in GT6 and one each in GT1, GT3 and GT5. Despite presence of polymorphisms at resistance-associated substitutions (RAS) positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12. 

Conclusions
Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized. 

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