Friday, September 8, 2017

TGIF HCV Rewind - Coming to grips with an emerging epidemic of viral hepatitis

TGIF - HCV Rewind
Greetings, here is a quick rewind of news and research you may have missed over the last five days.

Listen
Silent killer: Coming to grips with an emerging epidemic of viral hepatitis
8th September, 2017
Infectious diseases expert and epidemiologist Dr Ben Cowie explains why viral hepatitis is fast becoming a hidden epidemic with significant public health consequences. Most people with chronic hepatitis types B and C aren't even aware they have the diseases as they show no obvious symptoms or signs, yet they risk severe illness or liver damage. So how is the global health community targeting hepatitis, and how to  grow awareness in a largely unsuspecting public? Presented by Dr Andi Horvath.
Listen here, or read the transcript.

Hep Fall 2017 - Special Issue
America’s opioid and hepatitis C crises
Topics
America’s opioid and hepatitis C crises
Meet Lynn Taylor, MD, a primary care physician fighting for cures on the front lines of America’s opioid and hepatitis C crises.
Getting Better
Health officials say opioid and heroin addiction—along with the resulting overdoses and HCV transmission—is rising at an alarming rate.
Begin here

Recommended Reading
Early intervention, testing keys to addressing hepatitis C problem, says CDC scientist
The problem with hepatitis C infections in the U.S. has several fronts: new patients from injection drug users caught up in the opioid crisis, a large population in prison that may not be getting tested and treated and a large number of Baby Boomers, many of whom don’t know they are infected, said a senior scientist with the Centers for Disease Control and Prevention.

Global health experts are today are calling for the removal of restrictions preventing people who use drugs from accessing new hepatitis C cures. So long as these restrictions exist, the goal of disease elimination will remain out of reach, they say.

Healio
Updates In Hepatology
Injection drug users with HCV lack awareness of DAA efficacy
September 8, 2017
Most people who inject drugs were not aware of currently available, highly effective hepatitis C treatments, according results of a national survey in Scotland presented at the International Symposium on Hepatitis Care in Substance Users.

In The News
Canada Pot Stocks Rally as Ontario Plans to Open 150 Stores
By Jen Skerritt, Aoyon Ashraf , and Doug Alexander
Canadian marijuana producers rose on Friday after Ontario said it will open as many as 150 government-run pot stores and allow online purchases as the country gears up for legalized recreational sales next July.

Drinks industry distorts alcohol cancer risk
The World Health Organization says drinking alcohol is a well-established risk factor for a range of cancers, including tumours of the mouth, liver, breast and colon and bowel. And the risk of cancer rises with levels of alcohol consumed.

The end still is not in sight for San Diego County’s deadly hepatitis A outbreak.

In Switzerland, about every tenth adult suffers from morbid obesity. Such corpulence can not only lead to diabetes or cardiovascular disease, but also to fat accumulation in the liver. Worldwide, about 25 to 30 percent of all adults and increasingly children are affected by such steatosis - becoming the most frequent liver disease in recent years. Some patients suffer from inflammation that could lead to a scarred shrinkage of the liver (cirrhosis) or even cancer.

Gail Connor Roche
Publish Date: Friday, September 08, 2017
Men with chronic hepatitis C (HCV) infection or individuals who have had a blood transfusion experience faster progression of the liver-attacking virus, researchers in Canada say. The team—led by Aysegul Erman, a PhD candidate at the University of Toronto—also reported that longer duration and genotype 1 infection are associated with slower HCV progression.

Updated Informational Websites
News-Medical.Net
Last Updated: Sep 8, 2017

In The Journals 
Case series of 5 patients with quantifiable viral loads at the end of treatment who subsequently achieved sustained virologic response (SVR) 
Owing to the limitations of this small case series of 5 patients, definitive conclusions regarding the clinical usefulness of end-of-treatment viral loads cannot be made. Although further studies are needed to determine the significance of quantifiable viremia at the end of treatment, the results of this case series demonstrate that this phenomenon does not always imply therapeutic failure.

HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment
Digestive and Liver Disease
September 2017 Volume 49, Issue 9, Pages 1022–1028

Risk for hepatocellular carcinoma after HCV antiviral therapy with DAAs: case closed?
Several studies of patients treated with interferon -based therapy nicely documented that the risk for hepatocellular carcinoma (HCC) was markedly lower in patients who achieved SVR compared to those without SVR. 5-7 As a result, it was naturally assumed that with higher cure rates with DAAs, cancer rates would start to decline. It was therefore surprising and unsettling in 2016 to see a series of reports of unexpectedly high rates of ‘early’ HCC recurrence after ‘curative’ therapy as well as higher than expected rates of de novo HCC in patients who achieved SVR with DAAs.

Hepatocellular carcinoma: Resection vs. transplantation
Liver transplantation is the gold standard for treating early hepatocellular cancers. Because of the lack of donors, this option is, however, available to a limited degree only. Curative liver resection is an alternative in this setting. Markus B. Schoenberg, Julian N. Bucher, and coauthors investigated whether liver resection (LR) can yield results that are comparable to those of liver transplantation (LT) (Dtsch Arztebl Int 2017; 114: 519-26).

Blog Updates
Diagnosed with Hepatitis B? Preventing Transmission to Others. Learning the HBV Basics Transmission – Part III
Please be sure to talk to your doctor if you are unsure, and don’t forget to get copies of those labs. Check out transmission part I and part II if you are looking for a little more transmission information.

Flu Season
Recommended Reading
Read all past and current Seasonal Flu Vaccine articles posted on this blog.

CDC guidance for the 2017-2018 influenza season has been published.

Prepare for A Really Intense Flu Season, Say the Experts
Sam Benson Smith
Experts predict that this is going to be one of the most intense flu seasons in recent memory, according to NBC. Australia has a particularly severe flu season, then the U.S. will as well. Well, Australia had a particularly severe flu season.....

5 Things You Should Know About the Upcoming Flu Season
SEPTEMBER 11, 2017
Flu season is approaching soon, and it is a great time for pharmacists to educate patients on the importance of the annual influenza vaccine. Influenza can cause serious illness and death, especially among older adults, very young children, pregnant women, and individuals with certain chronic medical conditions. Below, please find 5 things you should know about the upcoming flu season

Harvard Women's Health Watch
Flu vaccine less effective in obese individuals
Research we're watching
Not only is obesity a risk factor for flu complications, but it might actually make the flu vaccine less effective, says a study published online June 6, 2017, by the International Journal of Obesity. Scientists at the University of North Carolina at Chapel Hill found that the flu shot provides less protection in people who are obese.

The study compared flu rates in 1,022 people during two recent flu seasons. All participants were vaccinated against the flu. The researchers looked at immune response to the vaccine and also tracked who went on to get the virus. They found that nearly 10% of obese participants got the flu, compared with 5% of their healthy-weight counterparts. This is bad news, because individuals with a body mass index of 40 or higher are also more prone to flu complications.

It's not totally clear why obesity reduces the effectiveness of the flu vaccine, but the researchers suggested that the differences might indicate that certain immune cells, called T cells, don't work as well in obese individuals.

Health Capsule
Flu Vaccine Skin Patch Tested
To help increase these numbers, scientists are trying to develop easier ways to give the flu vaccine. A new study shows that a special skin patch may work as well as a shot with a hypodermic needle. The patch is about the size of a dime and has 100 tiny needles that contain flu vaccine. The needles are just long enough to pierce skin. Once inside skin, they dissolve within minutes.

Enjoy the upcoming weekend, thanks for stopping by.
Tina
Posted by at No comments:
File Under , , , , ,

Drinks industry distorts alcohol cancer risk

Drinks industry distorts alcohol cancer risk
Last Updated: 2017-09-07

By Kate Kelland
LONDON (Reuters) - The alcohol industry uses denial, distortion and distraction to mislead people about the risks of developing cancer from drinking, often employing similar tactics to those of the tobacco industry, a study said on Thursday.

Drinks industry organizations often present the relationship between alcohol and cancer as highly complex, implying there is no clear evidence of a consistent link, said the study led by scientists at the London School of Hygiene and Tropical Medicine (LSHTM) and Sweden's Karolinska Institute. The article was published online September 7 in Drug and Alcohol Review.

Other strategies include denying any relationship exists, or saying inaccurately that there is no risk with moderate drinking, the study found. The industry also seeks to mention a wide range of other real and potential cancer risk factors in an effort to present alcohol as just one of many, it added.

Responding to the study, the Distilled Spirits Council, a U.S. alcohol trade association, said it was "a highly selective" review authored by researchers with "anti-alcohol biases."

"The Council does not recommend that people drink alcohol for potential health benefits," it said in a statement. "Drinking in moderation may pose health risks for some people, and some individuals should not drink at all."

The International Alliance for Responsible Drinking, which represents large brewers and distillers including Anheuser-Busch InBev and Diageo, said it disagreed with the study's conclusions. "We . . . stand by the information that we publish on drinking and health," it said.

RISING RISK
The World Health Organization says drinking alcohol is a well-established risk factor for a range of cancers, including tumours of the mouth, liver, breast and colon and bowel. And the risk of cancer rises with levels of alcohol consumed.

The research team behind Thursday's study analyzed the information relating to cancer on the websites and documents of nearly 30 alcohol industry organizations around the world between September 2016 and December 2016.

"The weight of scientific evidence is clear - drinking alcohol increases the risk of some of the most common forms of cancer," said Mark Petticrew, a professor of public Health at the LSHTM who co-led the study.

"It has been argued that greater public awareness, particularly of the risk of breast cancer, poses a significant threat to the alcohol industry. Our analysis suggests that the major global alcohol producers may attempt to mitigate this by disseminating misleading information."

Petticrew's team identified three main industry strategies: Denying any link with cancer, or selective omission of the relationship; distortion by mentioning some risk of cancer, but misrepresenting or obfuscating its size; and distraction by seeking to draw focus away from the risks of alcohol and towards other cancer risks.

One of the most significant findings was that industry materials omitted or misrepresented evidence on breast and bowel cancer, both of which are linked to drinking. When breast cancer was mentioned, 21 of the organizations studied gave no, or misleading, information about it, the study said.

Ian Gilmore, chair of the Alcohol Health Alliance UK, said the study "clearly shows the alcohol industry misleading the public."

"With only 1 in 10 people aware of the link between alcohol and cancer, people have both a need and a right to clear information about the health risks of drinking alcohol."

Petticrew said the study's findings, published in the journal Drug and Alcohol Review on Thursday, were important partly because the alcohol industry is often involved in spreading health information to people around the world.

SOURCE: http://bit.ly/2wMhNCx
Drug Alcohol Rev 2017.
Posted by at No comments:
File Under ,

Small case series of 5 patients - Viral load at the end of HCV treatment may not always imply therapeutic failure

Correspondence
The American Journal of Gastroenterology -

Case series of 5 patients with quantifiable viral loads at the end of treatment who subsequently achieved sustained virologic response (SVR)

Owing to the limitations of this small case series of 5 patients, definitive conclusions regarding the clinical usefulness of end-of-treatment viral loads cannot be made. Although further studies are needed to determine the significance of quantifiable viremia at the end of treatment, the results of this case series demonstrate that this phenomenon does not always imply therapeutic failure.

Download PDF
View Online

Detectable Viremia at the End of Treatment With Direct-Acting Antivirals Can Be Associated With Subsequent Clinical Cure in Patients With Chronic Hepatitis C: A Case Series
Lindsey M. Childs-Kean University of Florida College of Pharmacy, Department of Infectious Diseases, Gainesville, Florida Joseph Hong Antimicrobial Stewardship Program, Bay Pines VA Healthcare System, Bay Pines, Florida

DOI: http://dx.doi.org/10.1053/j.gastro.2017.06.062

We report a case series of 5 patients with quantifiable viral loads at the end of treatment who subsequently achieved sustained virologic response (SVR) with recommended hepatitis C virus (HCV) direct-acting antiviral (DAA) regimens.

All 5 patients had HCV genotype 1a, were male, and none were coinfected with human immunodeficiency virus.

Their ages ranged from 56 to 67 years. All patients had a baseline viral load between 2,000,000 and 7,000,000 IU/mL (Table 1).

Three of the patients received 8 weeks of ledipasvir/sofosbuvir (LDV/SOF), one received 12 weeks of LDV/SOF, and one received 12 weeks of paritaprevir/ritonavir/ombitasvir/dasabuvir with ribavirin (PrOD+RBV). One patient who received 8 weeks of LDV/SOF and the patient who received PrOD+RBV were African American. One of the patients who received LDV/SOF had possible cirrhosis based on his elevated Fibrosis-4 scores; none of the other patients who received LDV/SOF seemed to have cirrhosis. The patient who received PrOD+RBV had compensated cirrhosis. All of the patients who received LDV/SOF were treatment naïve; the patient who received PrOD+RBV had previously received pegylated interferon monotherapy. Two patients receiving LDV/SOF received concomitant omeprazole therapy and were advised to take it at the same time as LDV/SOF. All patients reported complete adherence to the DAA regimen and tolerated treatment well. Viral loads were measured using the Abbott M2000 RealTime System (Abbott Laboratories, Lake Bluff, IL), which has a lower limit of quantification of 12 IU/mL, lower than that in published phase III trials.1, 2, 3
Table 1 Virologic Trends During and After HCV Treatment
       
Patients Units Baseline Week 2 Week 4 Week 6 Week 8 Week 10 Week 12 SVR4 SVR12
1IU/mL2,200,224—35018170——23ND
Log_HCV6.34—2.542.261.85——1.36ND
2IU/mL2,557,795—496321——<12ND
Log_HCV6.41—1.691.801.33——<1.08ND
3IU/mL3,852,020—100—51—13NDND
Log_HCV6.59—2—1.71—1.12NDND
4IU/mL5,799,6601564486286107——<12ND
Log_HCV6.763.192.692.462.03——<1.08ND
5IU/mL6467,86930087804412485625<12ND
Log_HCV6.813.482.892.642.391.751.40<1.08ND

 HCV, hepatitis C virus; ND, not detected; SVR, sustained virologic response.

There are few data on the impact of end of treatment viremia on achieving SVR with DAAs. Sidharthan et al4 assessed the impact of viremia at the end of treatment in predicting SVR. Six patients were identified with quantifiable viremia at end of treatment, five who received 6 weeks of LDV/SOF + GS-9669 and one who received 6 weeks of LDV/SOF + GS-9451. All 6 patients achieved SVR.4 In the ION-2 trial (Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection); 1 patient receiving 12 weeks of LDV/SOF had a viral load of 42 IU/mL at the end of treatment. Subsequent viral loads at weeks 4, 12, and 24 weeks after treatment were undetectable.5 To our knowledge, there are no additional published accounts describing the impact of quantifiable viral loads at the end of treatment in patients who have received recommended DAA regimens.

Sidharthan et al4 offered theories as to the mechanisms of ongoing viral clearance after completion of HCV treatment, namely, the ability of the patient’s innate immune system to eradicate the remaining residual virus after completing therapy. Another theory involves the detection of residual noninfectious viral particles by the HCV assay. A viral kinetic study by McGivern et al6 discovered the production of defective virions in the presence of DAAs, detectable by in vitro assays but incapable of assembly and release as infectious virus.

The patients in our case series were managed before updated treatment duration recommendations for 8-week LDV/SOF regimens based on subgroup analyses. Backus et al7 evaluated the real-world efficacy of LDV/SOF in treatment-naïve veterans with HCV genotype 1 infections. Independent factors reducing the likelihood of achieving SVR in patients receiving 8 weeks of treatment included those with quantifiable viral loads at week 4 and African Americans. The impact of race is consistent with findings from a study by Su et al,8 which evaluated the association between race and treatment failure rates in those receiving either an 8-week or 12-week treatment course of LDV/SOF monotherapy. Although 1 patient in this case series involved an African American man who achieved SVR after 8 weeks of LDV/SOF, the authors do not currently advocate this practice given the currently available literature. Similarly, 2 patients had quantifiable viremia at week 4 of treatment and, thus, should be given a treatment extension to 12 weeks. However, our case series may provide some assurance of SVR if a patient chooses to self-discontinue treatment after only 8 weeks of LDV/SOF.

Owing to the limitations of this small case series of 5 patients, definitive conclusions regarding the clinical usefulness of end-of-treatment viral loads cannot be made. Although further studies are needed to determine the significance of quantifiable viremia at the end of treatment, the results of this case series demonstrate that this phenomenon does not always imply therapeutic failure.

The American Journal of Gastroenterology -  
Posted by at No comments:
File Under , ,

Thursday, September 7, 2017

Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis

Recommended Reading
April 2017 - Statins May Benefit Cirrhotic Patients with Hepatitis B or C Infections

Alimentary Pharmacology & Therapeutics  Volume 46, Issue 7
October 2017  Pages 673–680
Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis. A nationwide case-cohort study
C. Bang, T. Benfield, F. Bendtsen
First published: 7 September 2017
DOI: 10.1111/apt.14243

Full Text Article
View Online

Summary
Background
Reports have indicated that the use of statins may ameliorate the course of cirrhosis.

Aim
To determine the relationship between use of statins and mortality rate in patients with cirrhosis.

Methods
We did a retrospective case-cohort analysis based on data from the Danish registers from the period 1995 through 2014. Index date was time of diagnosis of cirrhosis (ICD-10: K703) and cohort entry depended on whether the patient was statin user or not. We used propensity score matching with a statin:non-statin ratio of 1:2. We included the exposure to statins (ATC classification C10AA) from the index date until death or end of follow-up based on prescription claims. Use of statins based on at least two statin claims as well as the longitudinal pattern over time of statin claims was tested against mortality. The main outcome was mortality rate.

Results
A total of 24 748 patients with alcoholic cirrhosis were identified and 5417 were eligible for matching. The mean age was 56 (SD 10) years and 36% were females. The prevalence of use of statins was 15%. We included 744 in the matched cohort. Mortality rates were 88 (95% CI 73-105) per 1000 years for patients using statin and 127 (95% CI 114-141) for non-statin patients with a HR of 0.57 (95% CI 0.45-0.71). A more regular pattern of statin claims was related to a lower risk of death.

Conclusions
Our results showed an association between regular use of statins and reduced mortality in patients with alcoholic cirrhosis.

Posted by at No comments:
File Under , ,

Watch Opioid Nation -- An American Epidemic

One hour in-depth program on opioids in Detroit

Opioid Nation -- An American Epidemic

https://www.clickondetroit.com/opioids-epidemic/watch-at-10-pm-opioid-nation-an-american-epidemic

Devin Scillian looks at how we got this point in the opioid epidemic.


  • Dr. McGeorge delves into the role doctors played in this crisis and how their job has changed when it comes to prescribing medication. He will also have the checklist you can follow in your own life to help protect yourself or a loved from from abusing opioids.
  • Kimberly Gill has a candid conversation about how this addiction does not discriminate.
  • Defender Karen Drew gains special access to border patrol agents and discovers what lengths people are going to in order to smuggle these drugs into the country.
  • Defender Kevin Dietz learns from a former dealer what parents should know to protect their children from addiction.
  • Steve Garagiola takes us inside a local drug court trying to fix the drug problem and not just put people in jail
    • Posted by at No comments:
    File Under ,

    Wednesday, September 6, 2017

    HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment

    Digestive and Liver Disease 
    September 2017 Volume 49, Issue 9, Pages 1022–1028

    HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study
    Antonio Massimo Ippolito, Michele Milella, Vincenzo Messina, Fabio Conti, Raffaele Cozzolongo, Filomena Morisco, Giuseppina Brancaccio, Michele Barone, Teresa Santantonio, Chiara Masetti, Paolo Tundo, Antonina Smedile, Vito Carretta, Pietro Gatti, Antonio Patrizio Termite, Maria Rosa Valvano, Giuseppe Bruno, Claudia Fabrizio, Pietro Andreone, Marianna Zappimbulso, Giovanni Battista Gaeta, Nicola Napoli, Luca Fontanella, Gianfranco Lauletta, Giuseppe Cuccorese, Antonio Metrangolo, Ruggiero Francavilla, Emanuela Ciracì, Salvatore Rizzo, Angelo Andriulli

    DOI: http://dx.doi.org/10.1016/j.dld.2017.03.025

    Full Text Download
    PDF (373 KB)

    Abstract
    Background
    Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D’Amico might provide new insights on timing for antiviral therapy.

    Methods
    We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n = 575) or cirrhosis (n = 2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines.

    Results
    The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients.

    Conclusion
    Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3–5) who are at greatest risk and have the most to gain from therapy. The present study conducted by a network of 25 Italian centers involved in the management of patients with HCV-related liver disease, has reviewed the efficacy and safety of DAA treatment in patients with compensated cirrhosis, particularly those with previous decompensation. Our investigation examined a cohort of patients with previously decompensated cirrhosis (n = 279) and reported an unexpectedly high rate of SVR12 (95.7%), comparable with that of patients with less advanced liver damage.

    Discussion Only
    Full Text Article Available Online
    Information on the therapeutic response of patients with CPT class C cirrhosis to DAAs is fragmentary, as safety concerns regarding DAA use has limited their enrollment in registered trials [[4], [5], [6]]. Data are numerically more consistent for CPT class B, but the characteristics of patients in this subgroup are very heterogeneous. Indeed, CPT class C patients with decompensated cirrhosis (ascites, bleeding, encephalopathy, jaundice) may be reclassified into class B following successful treatment of the event. In addition, CPT class B can include both patients with a past decompensated event and minimal alteration in biochemical parameters (INR, bilirubin, albumin) and patients who have never decompensated but have larger changes in hepatic indices. There is a confusing relationship between CPT class and impairment of liver function. CPT classification considers five variables, of which two are clinical events consequent to portal hypertension (ascites and encephalopathy) and three are laboratory tests likely reflecting impaired liver function. Although the laboratory parameters are only marginally affected by therapeutic interventions, ascites and encephalopathy may resolve following treatment but recur during follow-up. This variability means an individual patient may be classified differently over time, with a likely transition from one class to another one during CPT staging. In contrast, the D’Amico staging system [8][8] only considers the status of cirrhosis in relation to portal hypertension, the most important consequence of liver fibrosis and a harbinger of episodes of decompensation. Adoption of this system means a patient with cirrhosis and ascites remains in the same stage even after successful treatment of the event. In our investigation, SVR rates ranged from 96.5% in the absence of portal hypertension, to 95.1% in the presence of varices (stage 2), 100% and 95.7% in the event of past decompensation (stages 3 and 4, respectively), and 93.6% in patients with multiple events (stage 5). Our findings suggest the use of DAAs for previously decompensated (stages 3–5) patients urgently needing for a cure of their HCV infection could be expanded.

    As there are no head-to-head randomized controlled trials comparing DAA regimes, and our data were sufficient to conduct supplemental analyses, we undertook indirect treatment comparisons of the efficacy of the different DAA schedules. The analysis provided comparable SVR rates for all regimens: 95.4% for sofosbuvir/simeprevir ± ribavirin, 97.4% for sofosbuvir/ledipasvir ± ribavirin, and 96.4% for dasabuvir/ombitasvir/paritaprevir/ritonavir ± ribavirin. For countries with budget constraints, our results would allow therapeutic choice to be governed only by the cost of the drug(s).

    In general, patients with cirrhosis who received treatment with the new DAAs whether or not in registered trials [10][10] had lower rates of SVR compared to patients in the present cohort. A likely explanation may be the exclusion from our analysis of patients treated with sofosbuvir/ribavirin, a regimen considered of limited efficacy for GT1 and GT4 patients with cirrhosis. A further reason could be the meticulous checking for potential drug interactions between the DAAs and other agents co-administered to the patient [13][13].

    Benefit from therapy in this fragile population should not obscure the safety issue. Weker et al. have recently documented the frequency of hepatic decompensation during the course of DAA treatment for hepatitis C [17][17]. Gray et al. have also reported a 6% rate of on-treatment mortality in patients who were in CPT class B at baseline, and of 21% in those in CPT class C [18][18]. This high frequency of serious adverse events has been reported with virtually all oral regimens [19][19]. However, the alternative view that these events may be unrelated and coincidental to therapy, representing progression of the disease despite antiviral therapy, has been discussed [20][20]. The safety profile in our real-world cohort was excellent: adverse events occurred in a few patients but the majority of events were mild to moderate and aggravated by ribavirin co-administration. It should be remembered that a consistent proportion of our patients with cirrhosis received off-label therapy with simeprevir-containing schedules and a dasabuvir/ombitasvir/paritaprevir/ritonavir combination, regimens that are not recommended in CPT B and C cirrhosis [15][15]. Despite this, only three life-threatening events were seen in the 27 patients in these classes.

    A favorable outcome following DAA administration has been consistently documented in previous studies [[1], [2], [10]]: in general, improvements in CPT classes and/or MELD scores have been noted in about one third of treated patients, and are usually thought to reflect better liver function. However, these two staging systems do not only reflect hepatic synthetic function, as two portal hypertension adverse events are included in the CPT classification, and creatinine value in the MELD scoring. Our data in previously decompensated patients revealed improvements in two liver synthetic indices, in platelets counts, and in creatinine values.

    In conclusion, the main finding after treating 2612 HCV-infected patients with advanced fibrosis or cirrhosis in a real-world setting is that the treatment is safe and efficacious even for patients with previously decompensated disease. With the recommendation to check for drug interactions between DAAs and other co-administered agents, this subgroup of patients may benefit the most from DAA treatment: following a positive therapeutic outcome, parameters of liver synthetic capability are improved and the number of hepatic decompensation events is reduced.
    http://www.dldjournalonline.com/article/S1590-8658(17)30805-8/fulltext
    Posted by at No comments:
    File Under ,

    Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study

    Nutrients
    Effect of Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study
    Ludovico Abenavoli 1,*, Marta Greco 1, Natasa Milic 2, Francesca Accattato 1, Daniela Foti 1, Elio Gulletta 1 and Francesco Luzza 1 1 Department of Health Sciences, University “Magna Græcia”, 88100 Catanzaro, Italy 2 Department of Pharmacy, University of Novi Sad, 21000 Novi Sad, Serbia * Received: 3 July 2017 / Accepted: 8 August 2017 / Published: 12 August 2017

    Abstract:
    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, characterized by liver fatty acid accumulation and fibrosis, not due to excessive alcohol consumption. Notably, nutritional habits have been reported to be implicated in the onset and severity of the hepatic damage, while the Mediterranean diet has shown beneficial effects on NAFLD. Free radicals and oxidative stress were suggested to be involved in the pathogenesis and progression of NAFLD, and several data highlighted the efficacy of antioxidant supplementation in its treatment. The aim of this study was to compare the effects of the Mediterranean diet, with or without an antioxidant complex supplement, in overweight patients suffering from NAFLD. In this prospective study, fifty Caucasian overweight patients were randomized into three groups (Groups A–C). A personalized moderately hypocaloric Mediterranean diet was prescribed to all patients included in the A and B groups. In addition to the diet, Group B was administered antioxidant supplementation daily and for the period of six months. Group C did not have any type of treatment. The study proved that the Mediterranean diet alone or in association with the antioxidant complex improved anthropometric parameters, lipid profile and reduced hepatic fat accumulation and liver stiffness. However, Group B patients, in which the diet was associated with antioxidant intake, showed not only a significant improvement in insulin sensitivity, but also a more consistent reduction of anthropometric parameters when compared with Group A patients. Taken together, these results support the benefit of antioxidant supplementation in overweight patients with NAFLD.

    Discussion Only
    Full Text Available Online
    Despite the rapidly growing recognition of NAFLD over the last few decades, the treatment of this condition remains debated [39,40]. In the clinical management of NAFLD patients, a dietary change and increased physical exercise are essential to reduce body weight, in order to improve metabolic parameters and normalize the biochemical blood profile, as well as transaminase levels [24]. The “ideal” treatment for NAFLD should reduce the liver damage and its progression by reducing anthropometric parameters, by improving insulin resistance and impairment in glucose and lipid metabolism and by reducing the cytokine-mediated pathophysiological link between adipose tissue and liver [41]. The traditional Mediterranean diet is a dietary pattern that was associated with favorable health impact, in particular on cardiovascular diseases, cancer and in the treatment of metabolic syndromes [42]. Carotenoids, fibers and folic acid, which are basic components of this diet, can play a pivotal role in preventing or slowing down the oxidative stress process. In addition, vegetables, which are the staple foods included in the Mediterranean diet, are the main source of phytosterols, known as natural cholesterol-lowering agents, reducing cardiovascular risk [43,44].
    Several pharmaceutical agents are currently being evaluated for the treatment of NAFLD, and NASH in particular. However, no single therapy has been approved so far [23,45]. On this basis, the beneficial effects of complementary medicine, and particularly of herbal extracts, on NAFLD patients have received increasing attention in the last few years. The use of this approach has many advantages, including worldwide availability, minimal reported side effects and wide application due to low treatment costs [46].

    However, literature data are often inconclusive on this topic, due to the high number of biases found in many trials and to the limited number of studies testing single herbal remedies [47].

    In the last two decades, several studies have emphasized the benefits in the NAFLD treatment of Silybum marianum, commonly called milk thistle (MT), a plant native to the Mediterranean area, which has been used for many centuries to treat liver diseases [48,49]. The active complex of MT is a lipophilic extract from the seeds of the plant, and it is composed by three flavonolignan isomers, silybin, silydianin and silychristin, collectively called silymarin.

    Studies of patients with NAFLD showed that silymarin treatment was associated with positive changes in insulin resistance and transaminase serum levels [50,51]. Loguercio et al., in a multicenter phase III double-blind clinical trial, showed that MT extracts, after 12 months, led to an improvement of insulin resistance, liver enzymes and liver histology, without any increase in body weight in NAFLD patients [52]. More recently, in a randomized clinical study, we have found out that Mediterranean diet, in association with silymarin and other antioxidants, is able to induce, after six months, significant changes in glucose and lipid metabolism [53].

    According to these data, in our cohort, we demonstrated an improvement of BMI, waist and hip circumference, TG, total cholesterol and LDL-C serum level in all patients who followed the Mediterranean diet for a period of six months (Group A and B). The diet also led to the decrease of intra-hepatic fat accumulation, evaluated by the FL index, and of liver stiffness, assessed by TE. However, in the overweight NAFLD Group B patients, who followed the Mediterranean diet in association with BIL antioxidant treatment, we reported the statistical reduction of the HOMA-IR and the TyG index, two surrogate indexes widely used to evaluate insulin resistance.

    The changes in glucose and lipid metabolism described in Group B can be explained also by the presence of chlorogenic acid, one component of the BIL complex. Chlorogenic acid is one of the most abundant polyphenols in the human diet. It is contained in coffee, fruits and vegetables and displays many biological properties, such as antidiabetic effects by stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes and by improving early fasting glucose and insulin responses [54]. The metabolic changes observed in our study can be explained by the synergic action of the Mediterranean diet in association with chlorogenic acid and silymarin.

    Another component of the BIL complex is protopine, an isoquinoline alkaloid present in Fumaria officinalis, with antioxidant and choleretic properties that inhibit the production of pro-inflammatory cytokines [55]. Our data suggest that protopine could be a potential candidate for NAFLD treatment.
    The increase in oxidative stress and free radical production observed in NAFLD lead not only to increased consumption of glutathione, the major intra-cellular antioxidant, but it also reduces the activity of s-adenosyl-l-methionine, the main biological methyl donor and a precursor of glutathione, essential for protecting antioxidant pathways [56]. Recent studies suggest that the reduction of glutathione levels, in combination with lower ATP availability due to mitochondrial deregulation, leads to an unbalance of reactive oxygen species production and to the subsequent progression of hepatic injury [57]. In this context, the administration of reduced glutathione and methionine can help to restore the oxidative balance.

    The BIL antioxidant complex treatment alone, not in association with physical activity and a calorie-controlled diet, is not effective in improving insulin resistance. However, our data confirm the possible therapeutic role of this antioxidant complex as a complementary approach to the treatment of overweight NAFLD patients and in particular in the management of insulin resistance in NAFLD-related pathologies.

    An important goal for modern hepatologists is to find effective non-invasive diagnostic approaches to NAFLD. In the last two decades, non-invasive diagnostic modalities for NAFLD have been investigated. On the basis of literature data, three non-invasive methods have been employed in the present study for the evaluation of NAFLD. In addition to the US examination, in particular, the FL index and TE have been used to assess respectively hepatic fat accumulation and liver stiffness. The FL index is an accurate and easy to employ predictor score to define steatosis presence that utilizes routine measurements in clinical practice such as a BMI, waist circumference, triglycerides and γGT [36]. In this way, the clinical use of the FL index is useful to identify patients with NAFLD to include in an outpatient lifestyle change program. The data on the reduction of hepatic fat accumulation were also confirmed by the reduction of the Hamaguchi score at the US examination in Groups A and B, compared to Group C.

    TE is a non-invasive tool for the evaluation of liver damage that demonstrated good accuracy in quantifying the levels of hepatic stiffness and to define fibrosis, in patients with liver diseases and in particular with NAFLD [37]. This technique is reliable, fast and reproducible, with a good intra- and inter-observer agreement, thus allowing for population-wide screening and disease follow-up.
    Finally, our study clearly shows that patients following a balanced diet and taking the antioxidant complex had a more significant attenuation of insulin resistance, hepatic fat accumulation and liver stiffness than patients following the diet alone. These results supported the effectiveness of the BIL complex to reduce liver fatty acid infiltration and its related damages, by positively influencing the mitochondrial function and by reducing oxidative stress.

    6. Conclusions
    Our study confirms that the Mediterranean diet can improve anthropometric parameters and lipid profile and can contribute to reducing hepatic fat accumulation and liver stiffness. Moreover, the association of this dietetic regimen with antioxidant supplementation can contribute to improving the insulin sensitivity parameters. These data support a possible role of antioxidant supplementation as a coadjuvant therapy in patients with NAFLD.
    Full Text Available Online

    Posted by at No comments:
    File Under , , ,

    People who use drugs require prioritization, not exclusion, in HCV elimination

    People who use drugs require prioritization, not exclusion, in HCV elimination

    Global health experts are today are calling for the removal of restrictions preventing people who use drugs from accessing new hepatitis C cures. So long as these restrictions exist, the goal of disease elimination will remain out of reach, they say.

    They are gathered in Oslo for the 5th International Symposium on Hepatitis Care in Substance Users, where new research continues to highlight not just the pivotal role treatment for people who use drugs plays in reducing hepatitis C transmission, but also how it can be rolled out to achieve best results.

    "The science is clear. We now need to focus on overcoming barriers to access, and harness latest research to implement programs that work," said President of the International Network of Hepatitis C in Substance Users (INHSU), Associate Professor Jason Grebely, the Kirby Institute, UNSW Australia.

    "To delay further is unethical and undermines public health," he added.

    Hepatitis C—which if left untreated can lead to cirrhosis and liver cancer—affects approximately 64-103 million people around the world, resulting in around 700 000 deaths per year. In countries such as the US and Australia, hepatitis C now kills more people than HIV. In the UK, the number of annual deaths due to hepatitis C has quadrupled since 1996.

    New, highly effective curative treatments have sparked hope of a world free of hepatitis C. The World Health Organisation (WHO) has set ambitious elimination targets of 90% diagnosed, 80% treated and a 65% reduction in hepatitis C-related mortality by 2030. In most high income countries, the vast majority (80%) of new infections are in people who inject drugs, but this group has faced widespread exclusion from the new therapies.

    Reasons given for this exclusion include the price of new medications, fears of poor adherence, fears of reinfection and concerns over efficacy. However, international research debunks these myths.

    The world's largest study of new hepatitis c curative therapies – the C-EDGE CO-STAR Clinical Trial – has now found that illicit drug use prior to and during hepatitis C therapy had no impact on the effectiveness of the therapy, and that reinfection is low, at 4%. The results also showed excellent treatment adherence. Cure rates were comparable to results in hepatitis C populations that exclude people who use drugs.

    Further, mathematical modelling suggests that even moderate levels of treatment uptake in people who use drugs could offer considerable prevention benefits.

    One study looking at settings in Scotland, Australia and Canada indicated a 3-5 fold increase in treatment uptake among people who inject drugs could halve hepatitis C prevalence in 15 years.

    Other studies modelled on people who inject drugs in the UK and France concluded realistic treatment scale-up could achieve 15-50% reduction in chronic hepatitis C prevalence in a decade.

    To add to the benefits, treating people who use drugs with moderate or mild hepatitis C with new therapies is cost-effective in most settings compared to delaying until cirrhosis.

    Several countries have introduced hepatitis C elimination programs, with Australia, France and Iceland offering unrestricted access. All eyes are now turned on Australia, where over 20 000 people (10% of the chronic HCV population) have initiated treatment in the first four months since subsidised treatment has become available.

    "Countries such as Australia and France have taken the lead in adopting evidence-based policies that will save lives. Now it's time for other countries, including the US and Norway, to follow their lead and allow all patients with chronic hepatitis C to be treated with the new drugs," said Professor Olav Dalgard, Chair of the INSHU 2016 Symposium.

    "We strongly recommend that all restrictions on access to new hepatitis C treatments based on drug or alcohol use or opioid substitution treatment be removed. There is no good ethical or health based evidence for such discriminations. Nor do the restrictions make clinical, public health or health economic sense," he said.

    "Providing treatment to people who inject drugs, integrated with harm reduction programs and linkage to care, is the key to hepatitis C program success. And our experience in Copenhagen shows this can work. Such efforts need to be initiated and scaled up globally," added Professor Jeffrey Lazarus, Centre for Health and Infectious Disease Research, Rigshospitalet, University of Copenhagen, Denmark, who is presenting at the Symposium.

    Posted by at No comments:
    File Under , , ,
    Subscribe to: Posts (Atom)