Shingles Vaccine Video, New Name for C. diff, Flu B Rising, and More — A Pre-Valentines Day ID Link-o-Rama

NEJM Journal Watch

HIV and ID Observations
An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.

Shingles Vaccine Video, New Name for C. diff, Flu B Rising, and More — A Pre-Valentines Day ID Link-o-Rama

Paul E. Sax, MD

Highlights

The ACIP issued its official recommendations for herpes zoster (shingles) immunization.

Preferred: the new recombinant zoster vaccine, abbreviated RZV, for people 50 and older. They do not recommend it (yet) for immunocompromised individuals — stay tuned. Does the recommendation include our stable, on-therapy HIV patients, who in increasing numbers are over 50? I say yes.

In this terrible flu season, should we be choosing one type of flu vaccine over another?

In the absence of head-to-head trials, it’s difficult to make an official endorsement. But as this interesting piece notes, there are differences between the available vaccines, differences that may lead to different rates of protection. Credit to Helen Branswell, a local journalist who has done superb reporting on the flu this year.

FDA approves bictegravir/FTC/TAF for initial and switch HIV therapy.

Now come two inevitable questions: 1) When will my patient’s insurance/ADAP/etc. cover it? 2) Who came up with that brand name? Biktarvy, jeepers.

Elsulfavirine, an investigational NNRTI, is also approved for HIV therapy.

OK, ok, so it’s approved in Russia, not here. Here’s a clinical trial comparing it to efavirenz from last year’s CROI.

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Mortality Benefit of Successful Anti-HCV DAA Therapy in Patients Without Advanced Liver Disease

NEJM Journal Watch
February 9, 2018
Mortality Benefit of Successful Anti-HCV DAA Therapy in Patients Without Advanced Liver Disease 
Atif Zaman, MD, MPH reviewing Backus LI et al. Hepatology 2018 Jan 29.

Compelling evidence supports elimination of insurers' restrictions on providing direct-acting antiviral therapy to these patients.

Although direct-acting antiviral (DAA) regimens are effective in eradicating hepatitis C virus (HCV), their effect on long-term survival is unclear. Early studies in the interferon-based treatment era noted improved survival among HCV patients with advanced fibrosis, but studies in those with milder fibrosis are lacking.

In an observational cohort analysis, researchers assessed mortality in over 40,000 patients of Veterans Affairs facilities who received all-oral DAA therapy for genotype 1, 2, or 3 HCV infection and did not have advanced liver disease (FIB-4 score ≤3.25 and no evidence of overt compensated or decompensated cirrhosis or hepatocellular carcinoma).

In patients who achieved sustained virologic response (SVR; rate, 97%), the mortality rate (1.2 deaths/100 patient-years) was significantly lower compared with nonresponders (2.8) and some 60,000 untreated patients (3.8). In subgroup analyses by FIB-4 score, responders with a FIB-4 score <1.45 had mortality reductions of 46% and 67% compared with nonresponders and untreated patients, respectively, and those with a FIB-4 score of 1.45 to <3.25 had mortality reductions of 63% and 71% compared with those respective groups. In multivariate analysis, SVR was independently associated with reduced risk for death.

Comment
This is the most direct and compelling evidence showing that DAA treatment in HCV-infected patients who have early fibrosis/nonadvanced liver disease improves overall survival. Strengths of this study include a large sample size, a well-defined population, and the fact that all patients were offered HCV treatment. These results should be enough evidence to lift restrictions imposed by public and private payers who base treatment candidacy on degree of liver fibrosis.

Citation(s):
Backus LI et al. Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease. Hepatology 2018 Jan 29; [e-pub]. (https://doi.org/10.1002/hep.29811)

Source - https://www.jwatch.org/na46054/2018/02/09/mortality-benefit-successful-anti-hcv-daa-therapy-patients

Medicaid Skimps on Hepatitis C Treatment in Many States

Medicaid Skimps on Hepatitis C Treatment in Many States
by Liz Highleyman
Contributing Writer, MedPage Today
"Hepatitis C: The State of Medicaid Access," issued by the National Viral Hepatitis Roundtable (NVHR) and the Center for Health Law and Policy Innovation (CHLPI) at Harvard Law School, evaluated hepatitis C treatment policies in all 50 states, the District of Columbia, and Puerto Rico.

The report shows that 12 states cover treatment only for people with advanced liver fibrosis, 20 states require at least 6 months of abstinence from drug or alcohol use, and nine require treatment to be prescribed by a liver disease specialist, NVHR executive director Ryan Clary reported at the American Association for the Study of Liver Diseases (AASLD) annual Liver Meeting in October.

Hepatitis C kills more Americans each year than all other infectious diseases combined, yet more than half of U.S. Medicaid programs continue to impose discriminatory and medically unfounded restrictions on hepatitis C cures," Clary told MedPage Today. "

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Hepatitis C drugs not being accessed by thousands of Australians with the disease

Hepatitis C drugs not being accessed by thousands of Australians with the disease

By Lexi Metherell

The trend means the Government is at risk of missing its target to eradicate hepatitis C and of spending far more than necessary on the treatments.

Hepatitis Australia said fewer than half as many people were accessing the direct acting antivirals as they were immediately after they were first listed on the Pharmaceutical Benefits Scheme (PBS) in March 2016.

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Eight-year survival in chronic HBV patients under long-term entecavir or tenofovir therapy is similar to the general population

The Journal of Hepatology
Eight-year survival in chronic HBV patients under long-term entecavir or tenofovir therapy is similar to the general population

George V. Papatheodoridis, Vana Sypsa, George Dalekos, Cihan Yurdaydin, Florian Van Boemmel, Maria Buti, John Goulis, Jose Luis Calleja, Heng Chi, Spilios Manolakopoulos, Alessandro Loglio, Spyros Siakavellas, Nikolaos Gatselis, Onur Keskın, Maria Lehretz, Savvoula Savvidou, Juan de la Revilla, Bettina E. Hansen, Anastasia Kourikou, Ioannis Vlachogiannakos, Kostantinos Galanis, Ramazan Idilman, Massimo Colombo, Rafael Esteban, Harry L.A. Janssen, Thomas Berg, Pietro Lampertico

Full-Text

Full-text article downloaded and shared by @HenryEChang via Twitter

Highlights

•Chronic hepatitis B patients under entecavir/tenofovir have excellent 8-year survival.
•Mortality of non-cirrhotics seems to be lower than that of the general population.
•Mortality of cirrhotics is similar to that of the general population.
•Hepatocellular carcinoma is the main factor affecting their mortality.

Abstract
Background/Aims
The effects of long-term antiviral therapy on survival have not been adequately assessed in chronic hepatitis B (CHB). In this 10-center, ongoing cohort study, we evaluated the probability of survival and factors affecting survival in Caucasian CHB patients treated with long-term entecavir/tenofovir therapy.

Methods
We included 1951 adult Caucasians with CHB with or without compensated cirrhosis and no hepatocellular carcinoma (HCC) at baseline who received entecavir/tenofovir for ≥12 months (median: 6 years). Kaplan-Meier estimates of cumulative survival over time were obtained. Standardized mortality ratios (SMR) were calculated by comparing death rates with the Human Mortality Databases.

Results
The 1-, 5- and 8-year cumulative probabilities were 99.7%, 95.9% and 94.1% for overall survival, 99.9%, 98.3% and 97.4% for liver related survival and 99.9%, 97.8% and 95.8% for transplantation free liver related survival. Overall mortality was independently associated with older age and HCC development, liver related mortality with HCC development only and transplantation free liver related mortality with HCC development and lower platelets at baseline. Baseline cirrhosis was not independently associated with any type of mortality. Compared to general population, mortality was not significantly different in all CHB patients (SMR: 0.82), while it was lower in patients without HCC regardless of baseline cirrhosis (SMR: 0.58) and higher in patients who developed HCC (SMR: 3.09).

Conclusion
Caucasian patients with CHB and compensated liver disease treated with long-term entecavir/tenofovir therapy have excellent overall and liver related 8-year survival, which is similar to that of the general population. HCC is the main factor affecting their overall mortality and the only factor affecting their liver related mortality.

Lay summary
Caucasian chronic hepatitis B patients with or without compensated cirrhosis treated with long-term entecavir or tenofovir therapy have an excellent overall 8-year survival which is similar to that of the general population.

Hepatocellular carcinoma is the main factor affecting their overall mortality and the only factor affecting liver related mortality in this setting.

https://jumpshare.com/v/2SEtriThRc5FnmTJYk1W

Salk researchers discover how liver responds so quickly to food

Salk researchers discover how liver responds so quickly to food

LA JOLLA--(February 9, 2018) Minutes after you eat a meal, as nutrients rush into your bloodstream, your body makes massive shifts in how it breaks down and stores fats and sugars. Within half an hour, your liver has made a complete switch, going from burning fat for energy to storing as much glucose, or sugar, as possible. But the speed at which this happens has flummoxed scientists--it's too short a time span for the liver's cells to activate genes and produce the RNA blueprints needed to assemble new proteins to guide metabolism.

Now, Salk researchers have uncovered how the liver can have such a speedy response to food; liver cells store up pre-RNA molecules involved in glucose and fat metabolism.

"The switch from fasting to feeding is a very quick switch and our physiology has to adapt to it in the right time frame," says  Satchidananda Panda, a professor in the Salk Institute's Regulatory Biology Laboratory and lead author of the paper, published February 6, 2018 in Cell Metabolism. "Now we know how our body quickly handles that extra rush of sugar."

It was known that a RNA-binding protein called NONO was implicated in regulating daily ("circadian") rhythms in the body. But Panda, along with first author Giorgia Benegiamo, a former graduate student in the Panda lab, and their collaborators wondered whether NONO had a specific role in the liver. They analyzed levels of NONO in response to feeding and fasting in mice. After the animals ate, speckled clumps of NONO suddenly appeared in their liver cells, newly attached to RNA molecules. Within half an hour, the levels of corresponding proteins--those encoded by the NONO-bound RNA--increased.

"After mice eat, it looks as if NONO brings all these RNAs together and processes them so they can be used to make proteins," says Panda.

When mice lacked NONO, it took more than three hours for levels of the same proteins, involved in processing glucose, to increase. During that time lag, blood glucose levels shot up to unhealthy levels. Since blood glucose levels are also heightened in diabetes, the researchers think that the mice without NONO may act as a model to study some forms of the disease.

"Understanding how glucose storage and fat burning are regulated at the molecular level will be important for the development of new therapies against obesity and diabetes," says Benegiamo.

Questions still remain about how exactly NONO is triggered to attach to the pre-RNA molecules after a meal. And Panda is hoping to assemble a more complete list of all the pre-RNAs that NONO binds to--in both the liver and other parts of the body. NONO has been found at high levels in the brain and muscle cells, so the researchers are planning studies to see whether is reacts similarly in those organs to food. 

https://www.salk.edu/news-release/salk-researchers-discover-liver-responds-quickly-food/

JOURNAL
Cell Metabolism
TITLE
The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding
AUTHORS
Giorgia Benegiamo, Ludovic S. Mure, Galina Erikson, Hiep D. Le, Ermanno Moriggi, Steven A. Brown and Satchidananda Panda

HCV infection and liver cirrhosis - Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort

World J Gastroenterol. Feb 21, 2018; 24(7): 852-861
Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.852

Retrospective Study

Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort

Niels Steinebrunner, Kerstin Stein, Catharina Sandig, Thomas Bruckner, Wolfgang Stremmel, Anita Pathil

Therapeutic regimens for patients with chronic hepatitis C virus (HCV) infection have substantially improved over the last few years. However real-life data in patients with cirrhosis are still limited, and predictors of functional benefit of direct-acting antivirals are not well defined. We analysed data from patients with HCV infection and liver cirrhosis to evaluate predictors of functional benefit for identifying patients profiting most from antiviral therapy beyond HCV eradication.

View full text article online

Abstract
AIM
To define predictors of functional benefit of direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) infection and liver cirrhosis.

METHODS
We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated (76%) and decompensated (24%) liver cirrhosis at two tertiary centres in Germany. Patients were included with treatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.

RESULTS
Viral clearance was achieved in 88% (175/199) of patients. Sustained virological response (SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90% (n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57% (n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87% (n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67% (n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37% (65/179) of patients, no change of MELD score in 41% (74/179) of patients, and an aggravation was observed in 22% (40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.

CONCLUSION
Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.

Full Text

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Herbal assault: liver toxicity of herbal and dietary supplements

DOI: https://doi.org/10.1016/S2468-1253(18)30011-6

Editorial
Herbal assault: liver toxicity of herbal and dietary supplements
The Lancet Gastroenterology & Hepatology
Published: March 2018

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The worldwide market for herbal and dietary supplements is booming. Even actress Gwyneth Paltrow's lifestyle company Goop has got in on the action, pedalling quirkily named supplements like “Balls in the air” and “The mother load”, targeted at those working at an “intense pace” and expectant mothers, respectively. These supplements promise to revitalise, replenish, and reinvigorate, in part via proprietary blends of herbal extracts. But the health benefits of such products are largely unsubstantiated by scientific data, and they are increasingly associated with harmful side-effects, including liver toxicity.

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