Friday, February 24, 2017

The Liver Loving Diet - A Must Read For People With HCV Or Liver Disease

The Liver Loving Diet

My admiration runs deep for a small group of bloggers who spend hours in front of a computer helping those suffering with HCV. What they accomplish is astounding, why do they do it?

So that no one with this disease ever feels alone.

HCV is a progressive liver disease that can be cured, although cirrhosis is usually irreversible and can potentially lead to life threating complications.

Karen Hoyt understands this only to well, she is devoted to offering support and accurate information to people coping with the effects of liver disease. Karen writes from a patients' perspective about living with and treating hepatitis C, cirrhosis, liver cancer and liver failure on her blog, "Your Best Friends Guide To Hepatitis C."

This compassionate author, HCV advocate, and survivor, once again is doing what she does best, keeping us informed and full of hope. Karen has recently announced her new book, "The Liver Loving Diet" is available to enjoy, a book that will help you learn to eat well during all phases of liver disease. For the cost of a few cups of liver friendly coffee - this book can be yours.

Purchase is now available through PayPal, click here to learn more.

From Karen

Low Sodium, Healthy Protein Plan
After my diagnosis with Hepatitis C and liver failure, I got busy putting together a low sodium, healthy protein plan for eating.

Here at Your Best Friends Guide, you all have blown me away with requests for an easy menu plan. I love the emails pouring in from you all sitting in hospitals, grocery stores, and at home. You’ve begged for recipes. Well, it’s taken some time (2 years), but I heard you and here it is!

Drumroll please….

The Liver Loving Diet Book is a big picture peek at liver disease that helps you understand how valuable it is to eat well during treatments, cures, setbacks, cancer, and transplant. My diet played a huge role in keeping me alive and active. Now I’m handing all that power to you in one tidy package – tied up with love and priced at $4.99. I worked extra hard to give you a simple book with over 300 pages of personal stories and recipes.

Visit Karen on Facebook or follow her on Twitter

Thursday, February 23, 2017

Hepatitis C virus infection and risk of thyroid cancer: A systematic review and meta-analysis

Systematic review

Hepatitis C virus infection and risk of thyroid cancer: A systematic review and meta-analysis
Peng Wanga, 1, Zhaohai Jingb, 1, Changjiang Liua, Meihua Xua, Pei Wanga, Xiao Wanga,
Yulei Yina, Ying Cuia, Dunlin Renc, Xiaopang Raoa, ,

Received 8 August 2016, Accepted 21 January 2017, Available online 20 February 2017
http://dx.doi.org/10.1016/j.ajg.2017.01.003

Abstract
Purpose
Several epidemiological studies investigated the relationship between hepatitis C virus (HCV) infection and risk of thyroid cancer, but the results were not consistent. A systematic review and meta-analysis was conducted to assess the impact of HCV infection on thyroid cancer risk.

Methods
The literature was searched up to March 15, 2016 for case-control or cohort studies on the association between HCV infection and thyroid cancer risk. The summary relative risks (RR) and 95% confidence intervals (CI) were calculated.

Results
Five studies (two case-control studies and three cohort studies) were included in the meta-analysis, with a total of 751,551 participants and 367 cases of thyroid cancer. Meta-analysis of those 5 studies found that there was no statistically significant association between HCV infection and thyroid cancer risk (summary RR = 2.09, 95%CI 0.78–5.64, p = 0.145; I2 = 81.2%). However, HCV infection was significantly associated with increased risk of thyroid cancer (summary RR = 2.86, 95%CI 1.63–5.03, p = 0.003; I2 = 24.9%) after adjusting the heterogeneity.

Conclusion
There is a possible association between HCV infection and increased risk of thyroid cancer, and more cohort studies are needed to validate the possible association.

Abbreviations
RR, relative risk;
CI, confidence interval;
NOS, Newcastle Ottawa scale;
HCV, hepatitis C virus

With hep C franchises languishing, Merck’s MK-3682 goes from blockbuster to bomb

With hep C franchises languishing, Merck’s MK-3682 goes from blockbuster to bomb
by John Carroll

A little less than three years after acquiring the hepatitis C drug MK-3682 (uprifosbuvir) in its $3.85 billion buyout of Idenix, Merck’s prospects in the field have cooled dramatically, and its once great hopes for the drug have been reduced to nearly nothing.

Continue reading...

Of Interest
MK-3682 + grazoprevir + elbasvir or MK-3682 + grazoprevir + MK-8408 There are two triplet therapies and at least one doublet regimen in development by Merck (Kenilworth, NJ) that include MK-3682 (a novel NS5b nucleotide polymerase inhibitor) with or without grazoprevir and with either elbasvir or MK-8408 (a novel NS5A inhibitor). MK-3682 was tested in 300 mg and 450 mg doses in the CREST 1 (for genotypes 1 and 2) and CREST 2 (for genotype 3) studies. The CREST 1 study showed mITT SVR24 of 91–100% for genotypes 1 (n = 93 with 46 GT1a and 47 GT1b) with either elbasvir or MK-8408 at both doses for MK-3682. However, only the MK-3682 (450 mg)/grazoprevir/MK-8408 regimen showed efficacy >90% in genotype 2 patients (n = 61). For genotype 3 patients, both the 300 mg and 450 mg doses of MK-3682 showed SVR24 rates >90% (n = 86).....

Links On This Blog
Show posts with label MK3(MK-3682/grazoprevir/ruzasvir1)

Egypt Targets Spain, Belgium, Italy, Netherlands and the UK hepatitis C patients for medical tourism

Egypt targets hepatitis C patients for medical tourism

In mid 2016, Prime Pharma, a private Egyptian pharmaceutical company, launched Tour n’ Cure to revive therapeutic tourism in Egypt. The first target is hepatitis C patients from around the world. Countries targeted are Spain, Belgium, Italy, Netherlands and the UK.

Continue reading...

Chronic Hepatitis C Virus Infection and the Risk for Diabetes

Chronic Hepatitis C Virus Infection and the Risk for Diabetes
Does chronic hepatitis C infection increase diabetes risk?
February 23, 2017

Abstract
Background

The association between hepatitis C virus (HCV) infection and the occurrence of type II diabetes remains controversial. Prospective studies are needed to assess its causal temporality.

Methods
A cohort of 21 559 adults enrolled from seven townships in Taiwan during 1991–1992 and followed till the end of 2010. Incident diabetes over a study time period from 2000 to 2010 was ascertained through computerized linkage with the National Health Insurance database and the National Death Certification profiles. Cox's proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Antibodies against HCV (anti-HCV) were tested for all participants, and serum HCV RNA levels were measured for anti-HCV seropositives.

Results
During 180 244 person-years of follow-up, there were 1917 incident diabetes cases recorded. The cumulative risk for diabetes was 10.9% for anti-HCV seronegatives and 16.7% for anti-HCV seropositives respectively. The HR for diabetes of anti-HCV seropositivity was 1.53 (95% CI: 1.29–1.81) compared with anti-HCV seronegatives after adjustment for risk predictors. The adjusted HRs were 1.63 (1.31–2.02) for anti-HCV seropositives with positive HCV RNA compared to anti-HCV seronegatives (P<.001).

Conclusion
Chronic HCV infection was associated with an increased risk for diabetes after adjustment for other risk predictors.

Discussion Only
Medscape - Full Text Article
Liver International
In this study, our data suggested that HCV infection brought significant increasing risk for the occurrence of diabetes after controlling several risk factors. Whereas the findings from NHANES were inconsistent, and their most recent report did not demonstrate an association of HCV infection with diabetes or with insulin resistance. NHANES is a large survey that consists of interviews, health examinations and laboratory data collected from a stratified, multistage probability cluster sample to obtain a nationally representative sample of the noninstitutionalized civilian US population. The first investigation using the NHANES data that evaluated the relationship between HCV infection and diabetes used the survey collected in the cycles of 1988–1994.[12] The investigators found that among individuals who were 40 years of age or older, those with HCV infection had an increased likelihood of having diabetes with the odds ratio of 3.8 (95% CI: 1.8–7.8) after controlling risk factors.[12] However, during the later study cycles (1999–2004 and 2005–2008), a statistically significant association was not found.[10] In the NHANES survey, the prevalence of obesity, insulin resistance and diabetes increased steadily over the same time period.[25] Thus, it is possible that estimates of the relationship between HCV infection and diabetes became attenuated in the presence of this epidemic of obesity and increased numbers of metabolic factors in recent decades. More recently, investigators using NHANES data have found that chronic hepatitis C patients, defined as anti-HCV seropositives with positive HCV RNA levels, had a two-fold risk for insulin resistance or diabetes,[9] suggesting that serum HCV RNA testing which enables the differentiation of past HCV infection with spontaneous clearance of HCV RNA (undetectable HCV RNA) and chronic HCV infection (detectable HCV RNA) might be important.

Finally, the most recent report from NHANES, using data from the 1999 through 2010 surveys failed to find an association between HCV infection and diabetes.[11] However, they did find a positive relationship between insulin resistance and elevated liver enzymes.[11] The elevated serum liver enzyme levels may be as result of either HCV infection or other conditions such as metabolic syndrome or steatohepatitis. It is difficult to disentangle the association of these factors and diabetes by cross-sectional study design in which participants were tested for their serum levels of liver enzymes and diabetes at the same time. Compared with the participants in NHANES, the participants in our study had lower educational levels, lower BMI and a lower percentage of cigarette smoking and alcohol drinking habits than the participants in NHANES. In other words, our study population seemed to have relatively fewer metabolic risk factors for diabetes. The major risk factor for HCV infection was illicit drug use in NHANES, whereas iatrogenic factors were the main transmission route for HCV infection in our population.[17,26] Thus, differences in the findings from our study from those in the NHANES study might be caused by differences in the characteristics of the study populations as well as in the study design.

Comparing to anti-HCV seronegatives, the adjusted HR was 1.39 for anti-HCV seropositives with seronegative HCV RNA, and 1.63 for anti-HCV seropositives with seropositive HCV RNA respectively. It showed a trend effect on the risk of diabetes for patients who had replication of HCV. Whereas, among anti-HCV seropositives, the risk of diabetes was only increased slightly when comparing to HCV RNA seronegatives and RNA seropositives, suggesting that the lipid profiles may be altered once individuals infected by HCV. However, the mechanisms still need to be further evaluated. Our study suggested that HCV infection has a major public health impact, not only for hepatic diseases but also for extrahepatic diseases.

Our cohort is recognized as a natural history cohort because most of the participants did not have the experience of antiviral treatment as a result of its high cost and adverse effects. Until October 2003, only patients with abnormal ALT levels (>82 U/L) and moderate fibrosis proven by liver biopsy could be reimbursed for treatment by the National Health Insurance. However, there are still huge gaps of self-awareness, referral and linking to care.[27] Although it is an important clue to compare the patients with or without antiviral treatment for further clarification of the associations between HCV infection and diabetes in the future.

In addition, we identified diabetes cases through a computerized data linkage with the National Health Insurance database, which provided coverage for 96% of the total population for Taiwan (23 million) in 2000, 98% in 2005 and 99.6% in 2009.[22] A limitation of our study is that we enrolled the participants and collected the questionnaires and blood samples during 1991–1992, whereas the index date for the linkage with the National Health Insurance database for the study described in this study was January 1, 2000 when the claims data were released. Life style and biochemical markers in the REVEAL-HCV enrolees might have changed over the period 1991–1992 to 2000. In particular, there might have been new infection with HCV during the 10 years of follow-up. However, establishing the incidence of HCV is very difficult because most infections are initially asymptomatic. In Taiwan the incidence of transfusion-associated hepatitis decreased as a result of the effectiveness of a series of donor screening intervention.[28] Also the presence of such cases would result in an underestimate of the effects of HCV on the incidence of diabetes. In this study, we defined the patients with diabetes with the stringent criteria: patients with at least one hospital admission code with diabetes diagnosis or with three or more outpatient visits code for diabetes,[21,22] which made the findings conservatively.

During the long-term follow-up, BMI may change when individuals change their life style, it is important to consider the follow-up changes on anthropometrical parameters. In our study, the anti-HCV seropositives were asked and invited for regular health examinations every 6–12 months. We obtained BMI data during their follow-up, and it showed similar results in the four models of multivariate analyses. The stratification analysis showed that chronic HCV infection may increase the risk for diabetes by comparing anti-HCV seronegatives. The changes in BMI during follow-up of each person were highly correlated (r=.84, P<.0001), and the correlation was even higher after grouping by <23 and ≥23 (r=.98, P<.0001). Another limitation of our study is that we did not measure blood glucose in our study. Thus, data of blood glucose are not available. However, serum level of triglycerides is highly correlated with blood glucose. We included triglyceride levels as an alternative marker for glucose levels in the analyses.

In a previous study, anti-HCV seropositives had increased mortality from diabetes (106.1 per 100 000 person-years) than anti-HCV seronegatives (60.8 per 100 000 person-years).[5] These results are consistent with the results from a database study of deaths in patients with diagnosed chronic hepatitis C infection which showed a 1.77 times increased risk of death from diabetes compared to the general population in the USA.[29] Although the evidence from these two studies of mortality provided an indication of a relationship between HCV and diabetes, it could not determine whether the infection increased the risk for the incidence of diabetes or worsened the prognosis for those with diabetes. The current longitudinal study has estimated the incidence of diabetes in those with and without anti-HCV seropositivity. Although data on steatosis in our study were lacking, we stratified by surrogate measures for steatosis including BMI, ALT and triglycerides.

In conclusion, our data suggested that HCV infection has increased risk for the occurrence of diabetes after controlling other risk factors. Chronic hepatitis C patients may benefit from antiviral treatment to decrease their risks for diabetes. More affordable prices of the effective drugs are required to increase the accessibility for the patients in need.
Continue to Full Text Article

Wednesday, February 22, 2017

Ontario Becomes First Province To List EPCLUSA™ On Public Drug Plan To Treat All Six Genotypes Of Chronic Hepatitis C Infection

Feb. 22, 2017
Ontario Becomes First Province To List EPCLUSA™ On Public Drug Plan To Treat All Six Genotypes Of Chronic Hepatitis C Infection

-- Ontario Also Broadens Access for Patients
with Less Advanced Disease with Co-Factors --

MISSISSAUGA, ON, Feb. 22, 2017 /CNW/ - Gilead Sciences Canada, Inc. (Gilead Canada) today announced, effective February 28th, 2017, Ontario will provide public access to EPCLUSA™ (sofosbuvir/velpatasvir) tablets, the first once-daily, pan-genotypic single tablet regimen for the treatment of adults with genotype 1-6 chronic hepatitis C virus (HCV) infection. This listing will support patients to access curative therapy, and will advance Canada's efforts to achieving its World Health Organization commitment to eliminate hepatitis C by 2030.

EPCLUSA, one tablet taken daily for 12 weeks, is for use in adult patients without cirrhosis or with compensated cirrhosis, and in combination with ribavirin (RBV) for those with decompensated cirrhosis. It is also the first single tablet regimen approved for the treatment of patients with genotypes 2 and 3, without the need for RBV.

The approval of EPCLUSA was supported by data from four international Phase 3 studies, ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4. Of the 1,035 patients with compensated disease treated with EPCLUSA for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 per cent) achieved SVR12 (sustained virologic response 12 weeks after the end of treatment). In ASTRAL-4, patients with decompensated cirrhosis receiving EPCLUSA with RBV for 12 weeks achieved a high SVR12 rate (94 per cent) compared to those who received EPCLUSA for 12 weeks or 24 weeks without RBV (83 per cent and 86 per cent, respectively). The most common adverse events in the four ASTRAL studies were headache, fatigue and nausea, and were comparable in incidence to the placebo group included in ASTRAL-1.

The Ontario listing follows the completion of a recent agreement between the pan-Canadian Pharmaceutical Alliance (pCPA) with member provincial, territorial and federal drug plans to fund this innovative therapy for patients. In addition, aligned with the pCPA agreement, Ontario will expand access to include patients with less advanced disease (fibrosis scores of F0 or F1) if they have been diagnosed with certain co-existing factors. All HCV patients with fibrosis scores of F2 or higher also remain eligible for reimbursement.

For more information on the expanded access criteria: http://www.health.gov.on.ca/en/pro/programs/drugs/formulary42/summary_edition42_20170228.pdf

"We now have the ability to cure the majority of patients with chronic HCV with a simple, safe and effective 12-week treatment, regardless of genotype or patient history," said Dr. Curtis Cooper, Associate Professor of Medicine, University of Ottawa, and Director, The Ottawa Hospital and Regional Hepatitis Program. "Broader access to EPCLUSA, particularly at the earlier stage of the disease, means that we can move more quickly to help patients achieve a cure and improve their quality of life, while saving valuable funds associated with the significant long-term burden of illness and costs to the healthcare system."

In Ontario, the Public Health Agency of Canada estimates that more than 102,000 people are living with chronic HCV. In Canada, it is estimated that 250,000 Canadians are living with chronic HCV, with thousands of new cases diagnosed each year. There are six genotypes of hepatitis C. Genotype 1 infection is the most prevalent genotype in Canada representing 64.1 per cent of infected individuals. Genotypes 2 and 3 account for approximately 14.1 per cent and 20.2 per cent of infections in Canada, whereas genotypes 4, 5, and 6 are less prevalent in Canada (0.3 per cent).

"Canada, and other countries, have committed to eliminating hepatitis C by 2030, and to accomplish this goal we need to significantly increase treatment rates," said Dr. Morris Sherman, Chairperson, Canadian Liver Foundation and hepatologist at Toronto General Hospital. "Treatment regimens are getting shorter, simpler and more widely effective across genotypes meaning that treatment is now easier for both patients and physicians to manage.

"Currently, an estimated 44 per cent still remain undiagnosed, so increasing treatment rates also means improving screening and diagnosis, which is why the Canadian Liver Foundation recommends that all Canadians born between 1945-1975 receive a one-time test for hepatitis C," added Dr. Sherman. "Treatment should be an option for everyone, but the cost of treatment has been an obstacle. We're glad to see that the pCPA and the provinces are taking steps to make these treatments accessible regardless of where someone lives or their ability to pay."

"Gilead Canada is pleased that the pCPA and the Ontario Ministry of Health and Long-Term Care are recognizing the innovation and clinical value of EPCLUSA for the treatment of all genotypes of hepatitis C in a single tablet regimen," said Kennet Brysting, General Manager, Gilead Canada. "Broader treatment access for patients will potentially have a profound impact on disease elimination efforts in Canada, and supporting such efforts is a key priority for our company. We will continue to work closely with all jurisdictions to bring this simple and cost-effective curative treatment to all eligible patients, regardless of their genotype or stage of fibrosis."

Related
ZEPATIER®
Feb. 22, 2017
Ontario and British Columbia expand treatment access to chronic hepatitis C (CHC) patients
Effective February 28, Ontario will become the first province to reimburse ZEPATIER®  (elbasvir/grazoprevir), a simple one pill, once daily, 12 week no ribavirin regimen for most patients, and will be followed by British Columbia on March 21

  • In addition to patients with liver fibrosis stage F2+, patients with liver fibrosis stage F0 and F1 with poor prognostic factors, who had no public access to a potential cure under existing public plans, are now eligible for treatment
  • Patients with CHC genotypes 1 and 4, with chronic kidney disease (CKD) and intraveinous drug users - representing the highest number of new cases1 - will have access to treatment

  • KIRKLAND, QC, Feb. 22, 2017 /CNW Telbec/ - An estimated 185,000 people in Ontario and
    British Columbia have hepatitis C, a chronic liver disease that, if left untreated, can lead to cirrhosis, liver cancer and liver transplants.2 Merck Canada Inc. today announced that the Government of Ontario and of British Columbia are strengthening their commitment in the global fight against hepatitis C by becoming the first provinces to reimburse ZEPATIER® (elbasvir/grazoprevir). Zepatier is indicated in the treatment of chronic hepatitis C genotypes 1, 3 or 4 infections in adults patients.3 The product monograph with detailed product indication is available online by clicking here.
    "We're pleased to have worked with the pan-Canadian Pharmaceutical Alliance (pCPA) and participating jurisdictions to provide access to Zepatier to patients who need it, including those at higher risk," says Chirfi Guindo, President and Managing Director, Merck Canada Inc. "Hepatitis C is a curable disease, and today's announcement brings us one step closer to eradicating the virus in Canada."

    For the first time special populations, including hepatitis C patients with fibrosis stage F0 and F1 who are co-infected with human immunodeficiency virus (HIV) or hepatitis B virus or who have chronic kidney disease (CKD), will be eligible for treatment as of February 28th under the Ontario Drug Benefit Program (ODB), and as of March 21st under B.C.'s PharmaCare program.

    "The publicly funded availability of Zepatier in Canada for hepatitis C treatment represents a major milestone in the access to care for patients; not only those patients with advanced liver damage or cirrhosis have access to treatment but now those who may progress to more serious liver damage in the future can be cured. The dedication of Merck to addressing clinical studies in targeted and specific populations in need such as those with cirrhosis, advanced kidney disease and those who inject drugs, allow all treaters to use this treatment regimen to cure their patients safely," said Dr. Sergio Borgia, Medical Director and Corporate Division Head of the Infectious Disease Program at William Osler Health System.

    These provincial public funding announcements follow the World Health Organization's (WHO) adoption of  the first global health strategy on viral hepatitis, which includes a goal of 30% reduction in new cases of hepatitis B and C by 2020 and a 10% reduction in mortality, as well as increased access to treatment for hepatitis B and C.4 In June 2016, the Government of Canada announced its commitment in the global fight against viral hepatitis with the adoption of the Global Strategy on Viral Hepatitis. It has for objective to eliminate hepatitis B and C by 2030.5

    Feb. 22, 2017
    More patients to benefit from hepatitis C treatments
    Thousands of British Columbians living with hepatitis C will have better access to treatment as a result of successful negotiations brokered by the pan-Canadian Pharmaceutical Alliance (pCPA).
    “This agreement changes the landscape for hepatitis C patients living in B.C.,” said Health Minister Terry Lake. “Not only are there four new treatment options for what is now a curable virus, but the savings that were negotiated will allow us to cover treatment options for all hepatitis C patients – rather than just those in more advanced stages of the disease.”
    British Columbia and Ontario co-led the negotiations with the drug manufacturers on behalf of the pCPA. The alliance helps provinces and territories leverage their collective buying power and negotiate better prices for new drugs.....

    Daklinza (daclatasvir) – new
    Epclusa (sofosbuvir/velpatasvir) – new
    Harvoni (ledipasvir/sofosbuvir)
    Sovaldi (sofosbuvir)
    Sunvepra (asunaprevir) – new
    Zepatier (elbasvir/grazoprevir) – new

    Continue Reading...

    Deal reduces price of life-saving hepatitis C drugs for Canadians

    More patients to benefit from hepatitis C treatments
    Thousands of British Columbians living with hepatitis C will have better access to treatment as a result of successful negotiations brokered by the pan-Canadian Pharmaceutical Alliance (pCPA).
    “This agreement changes the landscape for hepatitis C patients living in B.C.,” said Health Minister Terry Lake. “Not only are there four new treatment options for what is now a curable virus, but the savings that were negotiated will allow us to cover treatment options for all hepatitis C patients – rather than just those in more advanced stages of the disease.”
    British Columbia and Ontario co-led the negotiations with the drug manufacturers on behalf of the pCPA. The alliance helps provinces and territories leverage their collective buying power and negotiate better prices for new drugs.

    The collaborative effort resulted in a significant cost savings to drug plans for participating provinces and territories. The agreement also allows access to treatment for all eligible patients in a fiscally sustainable manner. Prices and terms for this negotiation are confidential.
    The list cost to the health system for hepatitis C treatment has ranged from $45,000 to over $100,000 per patient, depending on the drug and disease progression.
    Agreements with the pCPA were reached with Gilead Sciences Canada, Merck Canada, and Bristol-Myers Squibb Canada to provide several hepatitis C drugs at an improved cost:
    • Daklinza (daclatasvir) – new
    • Epclusa (sofosbuvir/velpatasvir) – new
    • Harvoni (ledipasvir/sofosbuvir)
    • Sovaldi (sofosbuvir)
    • Sunvepra (asunaprevir) – new
    • Zepatier (elbasvir/grazoprevir) – new
    PharmaCare is expanding the criteria in March 2017 to provide coverage to more patients living with hepatitis C. Physicians can apply for coverage of the new drugs on behalf of their patients on or around March 21, 2017. Starting in 2018-19, PharmaCare will provide coverage for any British Columbian living with chronic hepatitis C, regardless of the type or severity of their disease.
    Up to 75,000 British Columbians are estimated to be living with hepatitis C. Approximately 24% of those exposed to the virus are able to clear it on their own. However, when left untreated, it can cause serious complications such as liver failure and liver cancer. The new modern hepatitis C therapies are highly effective, with the ability to clear the virus at rates over 95%.
    If untreated, hepatitis C virus infection can be a life-threatening communicable disease. Risk and harm reduction practices are strongly encouraged for those who may be at higher risk for re-acquiring the virus after successful treatment, including people who inject drugs, men who have sex with men, and commercial sex workers.
    Hepatitis C is the most-frequent cause of premature death among reportable infectious diseases in North America, and has become the most-frequent cause of premature death among people living with both hepatitis C and HIV.

    Quick Facts:
    • Hepatitis C is a serious, communicable disease that is spread through direct contact with the blood of a person living with the virus. Symptoms may include fatigue, jaundice, abdominal pain and joint pain. In some people, it can cause liver damage (cirrhosis) or liver cancer.
    • Up to 75,000 people are estimated to be living with hepatitis C in British Columbia. However, many people with the virus have no symptoms. About one-quarter of people living with hepatitis C do not know they have it.
    • About one-quarter of people with hepatitis C do not need treatment, as their body fights off the infection.
    • Once someone is successfully treated and cured of hepatitis C infection, they are no longer able to pass the disease on to others.
    • Currently, there is no vaccine to prevent hepatitis C infection.
    • From March 2015 to December 2016, PharmaCare coverage was provided to about 3,800 people in B.C. for medication used to treat chronic hepatitis C.
    Learn More:
    For more information on the pan-Canadian Pharmaceutical Alliance:
    http://www.pmprovincesterritoires.ca/en/initiatives/358-pan-canadian-pharmaceutical-alliance
    For more information about B.C.’s PharmaCare program:
    http://www2.gov.bc.ca/gov/content/health/health-drug-coverage/pharmacare-for-bc-residents

    Deal reduces price of life-saving hepatitis C drugs for Canadians
    Kelly Grant - HEALTH REPORTER
    Tens of thousands of Canadian patients with mild versions of chronic hepatitis C could soon receive public funding for medications that cure the infection now that the provinces have sealed a deal with three pharmaceutical companies to reduce the cost of the ultra-expensive drugs.

    The pan-Canadian Pharmaceutical Alliance (pCPA), which negotiates prices on behalf of the provincial and territorial public drug programs, announced on Tuesday that it had reached an agreement with the makers of six breakthrough hepatitis C medications, including the best-known drugs in the class, Harvoni and Sovaldi.

    Shortly after the pCPA confirmed the deal, the British Columbia government declared that its PharmaCare program would begin covering the drugs for patients with chronic hepatitis C, regardless of the type or severity, beginning in 2018.

    HCV Genotype 1 No Longer a Treatment Bugbear

    AGA Reading Room

    HCV Genotype 1 No Longer a Treatment Bugbear
    by Pippa Wysong
    Contributing Writer, MedPage Today

    Hepatitis C (HCV) genotype 1 is now the HCV subtype most easily treated with direct-acting agents (DAAs), and cure rates approach 100%. Since genotype 1 infection is the most common subtype, affecting approximately 75% of HCV-infected patients worldwide, and was traditionally harder to treat, scientists directed efforts to develop DAAs effective against genotype 1. There are now multiple DAA regimens available for patients with genotype 1 HCV infection. Clinicians need to consider subtype (genotype 1a versus 1b), insurance factors, and patient factors such as the presence or absence of cirrhosis and the presence of resistant variants when deciding on which regimen to pick. In some situations, specific resistance testing should be done prior to initiating treatment in order to determine the efficacy of the chosen regimen.

    Treating patients with genotype 1 hepatitis C (HCV) can be rewarding because of a simple fact: modern direct-acting agents (DAAs) have a nearly 100 percent cure rate. Yet only four years ago, genotype 1 was considered the most difficult-to-treat type of HCV.
    Back then, interferon regimens were used, and cure rates for genotype 1 hovered around 50 percent, while genotypes 2 and 3 were considered better treatment successes stories.

    Continue reading..

    Genetic variant linked to risk of liver cancer after hep C eradication

    Related - Genome-wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection
    Download PDF.

    Genetic variant linked to risk of liver cancer after hep C eradication
    By Will Boggs MD
    NEW YORK (Reuters Health) – A single nucleotide polymorphism (SNP) in the tolloid-like 1 (TLL1) gene is associated with the development of hepatocellular carcinoma (HCC) after eradication of hepatitis C virus (HCV) infection, researchers from Japan report.

    “When we constructed different models for predicting HCC in patients with mild as opposed to advanced hepatic fibrosis by combining this TLL1 variant with other distinct risk factors, these proposed models including TLL1 variant could be useful for predicting the occurrence of HCC after achieving sustained virological response (SVR) in the clinical practice,” Dr. Yasuhito Tanaka from Nagoya City University Graduate School of Medical Sciences told Reuters Health by email.

    Even after SVR, as many as 2% of patients develop HCC within three years and as many as 8.8% develop HCC within five years, Dr. Tanaka and colleagues write in Gastroenterology, online February 3.

    Continue reading...

    Of Interest
    Liver Cancer After Treatment For Hepatitis C
    ​Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase?

    Tuesday, February 21, 2017

    Novel emerging treatments for hepatitis C infection: a fast-moving pipeline

    . 2017 Feb; 10(2): 277–282.
    Published online 2017 Jan 25. doi:  10.1177/1756283X16683875

    This update reviews some upcoming therapies for the treatment of chronic hepatitis C
    See table 1 below for; Direct-acting combination antiviral therapies expected to be approved in 2017

    Of Interest
    January 18, 2017 - Hepatitis C Treatment: What to Expect in 2017

    Novel emerging treatments for hepatitis C infection: a fast-moving pipeline
    Ara A. Kardashian and Paul J. Pockros

    Abstract
    Advances in the treatment of chronic hepatitis C has been one of the pinnacles of medical science in the last 25 years. The age of direct-acting antivirals (DAAs) has led to cure rates >95% with shorter duration and low toxicity regimens, thus changing the landscape of the era of pegylated interferon and ribavirin (RBV). However, there remain some challenges with these therapies as there are multiple regimens available with a fair amount of sophistication required to administer them. Treatment continues to require knowledge of prior treatment status, viral genotype and fibrosis assessment, thus affording an opportunity for improvement in future regimens. This update reviews some upcoming therapies for the treatment of chronic hepatitis C.
    Keywords: direct-acting antivirals, emerging treatments, hepatitis C

    Introduction
    Direct-acting antivirals (DAAs) target viral proteins of the hepatitis C virus (HCV) which are critical for viral replication, resulting in the four classes of antivirals currently approved: nonstructural protein 3 (NS3) protease inhibitors (PI), NS5A inhibitors, NS5b nucleot(s)ide polymerase inhibitors and NS5b non-nucleot(s)ide polymerase inhibitors. It is unlikely that drugs will be developed outside of these classes, other than recent efforts with microRNA-122. Instead, we will see improvements upon the current drugs with second generation compounds. There remain unmet needs for treatment in some patients such as those who have failed NS5A regimens, those who have developed resistance-associated substitutions (RASs) and those who have pre-existing RASs that confer resistance. Other opportunities for improvement include pangenotypic regimens, eliminating the need for ribavirin (RBV), reducing duration of therapy, and reducing the cost of therapy. This review will address novel therapies currently in late phase studies.

    Current treatment options
    Currently, treatment options are organized by genotype, presence or absence of cirrhosis, and treatment experience. The following is a brief overview of available regimens and their indications, not an indepth review.

    Treatment-naïve patients
    For genotype 1, treatment options include daily fixed-dose combinations of elbasvir/grazoprevir, ledipasvir/sofosbuvir, paritaprevir/ritonavir/ombitasvir with dasabuvir and RBV, sofosbuvir/velpatasvir, as well as simeprevir plus sofosbuvir, and daclatasvir plus sofosbuvir. Variations in the regimen are based on genotype (1a versus 1b), presence or absence of compensated cirrhosis, and presence of pretreatment RASs. Currently, only one regimen requires pretreatment determination of the presence of NS5A RASs (elbasvir/grazoprevir). If an RAS is present at positions M28, Q30, L31 or Y93, then the patient requires 16 rather than 12 weeks of treatment with the addition of RBV.1 The details of all these regimens are available in the current American Association for the Study of Liver Diseases (AASLD)/ Infectious Diseases Society of America (IDSA) Guideline document.2

    For genotypes 2 and 3, sofosbuvir/velpatasvir and daclatasvir plus sofosbuvir are available. Again, duration can vary based on presence of cirrhosis and RBV is required in some patients with genotype 3 HCV infection. Genotype 4 regimens include 12 weeks of daily fixed-dose combinations of paritaprevir/ritonavir/ombitasvir with RBV, sofosbuvir/velpatasvir, elbasvir/grazoprevir, and ledipasvir/sofosbuvir.2 Additionally, in the European Association for the Study of the Liver (EASL) guidelines, sofosbuvir/simeprevir and sofosbuvir/daclatasvir are indicated.3 Treatment-naïve genotype 5 and 6 HCV options are daily fixed-dose combinations of sofosbuvir/velpatasvir or ledipasvir/sofosbuvir, both for 12 weeks for those without cirrhosis or with compensated cirrhosis2,3 and sofosbuvir/daclatasvir for 12 weeks.3

    Treatment-experienced patients
    Options for those having failed prior therapy depends on what was previously used and presence of RASs in addition to the same factors stated previously (genotype, presence or absence of cirrhosis). In general, the same options are available if the prior treatment was with pegylated interferon (PEG-IFN) and RBV. This is congruent with the guidelines published by EASL.3

    If sofosbuvir plus RBV with or without PEG-IFN was used previously, ledipasvir/sofosbuvir with RBV for 12 weeks is recommended in those without cirrhosis while the duration is extended to 24 weeks in the presence of compensated cirrhosis. If an NS3 protease inhibitor (simeprevir, telaprevir, boceprevir) was used previously with PEG-IFN and RBV, then daily fixed-dose combinations of ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, daclatasvir plus sofosbuvir or elbasvir/grazoprevir with RBV (at 12 or 16 weeks if baseline NS5A RASs present) are recommended for those with or without compensated cirrhosis.2 Patients who have proved to be particularly difficult to treat are those with genotype 3 who are treatment-experienced and have cirrhosis. Current recommendations for these patients are for sofosbuvir/velpatasvir with weight-based RBV for 12 weeks or daclatasvir plus sofosbuvir with weight-based RBV for 24 weeks. For those with genotype 3 treatment experience who have failed prior sofosbuvir and RBV, whether they have cirrhosis or not, there are less data to support guidance.2

    Those failing newer treatments including simeprevir plus sofosbuvir and NS5A inhibitors (daclatasvir, elbasvir, ledipasvir, ombitasvir, velpatasvir) have less formal recommendations. Essentially the AASLD/IDSA guideline recommends testing for NS3 and NS5A RASs, tailoring treatment to the results, and extending dual DAA therapy to 24 weeks with the addition of RBV (if not contraindicated). Triple or quadruple DAA therapy may also be considered.2 In contrast, the EASL guidelines recommend retreatment with a non-IFN regimen with weight-based RBV for 12 weeks with METAVIR fibrosis scores of F0–F2 but for 24 weeks if with F3 fibrosis or cirrhosis.3

    For genotype 2 or 3 patients who have previously treated with sofosbuvir plus RBV, daclatasvir plus sofosbuvir with or without RBV for 24 weeks or daily fixed-dose combination sofosbuvir/velpatasvir with RBV for 12 weeks are options. Currently, no formal recommendations exist for the retreatment of DAA failures in those with genotypes 5 or 6.2

    EASL guidelines for sofosbuvir failures include retreatment with sofosbuvir/ledipasvir for genotypes 1 and 4–6, sofosbuvir/velpatasvir or sofosbuvir/daclatasvir for all genotypes, ritonavir-boosted paritaprevir with ombitasvir for genotype 4 and the addition of dasabuvir for genotype 1, and sofosbuvir plus simeprevir for genotype 4. If those genotype 1 or 4 patients already failed sofosbuvir plus simeprevir, they can be retreated with a combination of sofosbuvir with ledipasvir, velpatasvir, or daclatasvir. Genotype 1 or 4 patients who have failed NS5A-containing DAA regimens may be retreated with sofosbuvir plus ritonavir-boosted paritaprevir with ombitasvir for genotype 4 or grazoprevir/elbasvir with sofosbuvir for genotypes 1 and 4 or sofosbuvir, simeprevir and daclatasvir for genotypes 1 and 4 for 12 weeks. For those with genotypes 5 or 6 failing an NS5A-containing regimen, the combination of sofosbuvir and velpatasvir with RBV for 24 weeks is recommended.3

    Novel regimens expected to be approved in 2017
    There are a number of combination regimens currently in phase III development that are expected to be available in 2017. All of these will be pangenotypic, RBV-free and be effective in genotype 1a patients who have failed a DAA regimen containing an NS5A inhibitor. The regimens may be double combinations of very potent pangenotypic protease inhibitors and NS5A inhibitors or triple combinations of protease inhibitors, NS5A inhibitors and NS5b nucleos(t)ide polymerase inhibitors (see Table 1). There are other future regimens beyond these regimens that are anticipated in 2018 or beyond but they are not yet in phase III development so will not be discussed herein.

    Table 1.
    Direct-acting combination antiviral therapies expected to be approved in 2017.

    GZR + RZV + MK-3682RZV + MK-3682SOF + VEL + GS-9857ABT-493+ABT530
    ManufacturerMerck (Kenilworth, NJ, USA)Merck (Kenilworth, NJ, USA)Gilead (Foster City, CA, USA)AbbVie (Lake Bluff, IL, USA)
    Number of drugsTripletDoubletTripletDoublet
    Drug classesPI + NS5A + NS5bNS5A + NS5bNS5b + NS5A + PIPI + NS5A
    Requires RBV?NoNoNoNo
    Duration of therapy4–12 weeks4–12 weeks12 weeks8–12 weeks
    Genotype efficacyPangenotypicPangenotypicPangenotypicPangenotypic
    DAA-failure with NS5A RASsEffective, but may require addition of RBVEffective, but may require addition of RBVEffectiveEffective
    ABT-493, gleaprevir; ABT-530, pibrentasvir; DAA, direct-acting antivirals; GS-9857, voxilaprevir; GZR, grazoprevir; NS5A, NS5A inhibitor; NS5b, NS5b nucleos(t)ide polymerase inhibitor; PI, NS3/4A protease inhibitor; RAS, resistance-associated substitutions; RBV, ribavirin; RZV, ruzasvir; SOF, sofosbuvir; VEL, velpatasvir

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    Addressing treatment failures is becoming increasingly important in the era of DAA therapy. For genotype 1 infection, the single-pill combination of ledipasvir (NS5A inhibitor) with sofosbuvir (NS5b nucleotide polymerase inhibitor; Harvoni™ Gilead Sciences, Foster City, CA) has shown cure rates >95%.4 According to the Center for Disease Control and Prevention, there are 2.7–3.9 million people in the United States (US) with HCV infection.5 Of these, approximately 75% have genotype 1, highlighting the importance of this patient population sustained virologic response at follow-up week 12.6

    Glecaprevir (ABT-493) + pibrentasvir (ABT-530)
    Glecaprevir (ABT-493) is a pangenotypic NS3/4A protease inhibitor while pibrentasvir (ABT-530) is a pangenotypic NS5A inhibitor active against common single-position NS5A variants. The two compounds are being developed together in a fixed-dose doublet regimen by AbbVie Pharmaceuticals (Lake Bluff, IL). Different durations of therapy are being evaluated between 6–12 weeks and none of the regimens require RBV. The population being studied does not include decompensated cirrhosis due to the previous experience seen in this group with paritaprevir, telaprevir, simeprevir and other first-generation NS3/4 PIs.7

    In the replicon model, the second-generation protease inhibitor glecaprevir showed potent activity against all genotypes with half-maximal effective concentration (EC50) ranging from 0.85–2.8 nm. These numbers are on par or superior to those seen with grazoprevir and paritaprevir. The other drug in the second-generation doublet regimen, pibrentasvir, showed an EC50 range of 1–4 pm across all genotypes, better than other currently available pangenotypic NS5A inhibitors. The SURVEYOR-I study demonstrated 98–100% SVR4 in HCV genotype 1 noncirrhotic treatment-naïve or PEG-IFN/RBV null-responders with the combination of the two drugs.8

    The MAGELLAN-I study used a combination of glecaprevir and pibrentasvir to treat those with treatment failures to earlier generation DAAs. The patient population included those with NS3 (30%), NS5A (20%), and both NS3 and NS5A (32%) RASs. Using intention-to-treat (ITT) analysis, for glecaprevir/pibrentasvir at doses of 200 mg/120 mg, the sustained virologic response (SVR) at follow-up week 12 was 100% (n=6). For doses of 300 mg/120 mg, SVR12 was 86% (19/22) and with the addition of RBV 800 mg it was 91% (20/22). Using modified ITT analysis (mITT), those same SVR12s were 100%, 95% and 95%, respectively. Failure was due to both viral breakthrough (n=1) and relapse (n=1).9

    The same glecaprevir/pibrentasvir combination was used in a partially randomized, phase II trial for genotype 3 patients with cirrhosis.10 Doses were 200 mg or 300 mg for glecaprevir (30 patients in each group) and 40 mg or 120 mg for pibrentasvir with or without RBV (31 and 30 patients respectively). Again, the study group included those patients with NS3 and NS5A variants either alone or together. By ITT analysis, SVR12 was 93–94% for combination therapy both with and without the addition of RBV.11 The 40 mg arm of pibrentasvir performed less well and will thus not be pursued further.

    Sofosbuvir/velpatasvir + voxilaprevir (GS-9857)
    The single-pill fixed-dose regimen of sofosbuvir 400 mg and velpatasvir 90 mg is currently approved for all genotypes in the US (Epclusa™; Gilead Sciences, Foster City, CA).12 This regimen must be given for 12 weeks and has not been shown to be effective in patients who have failed NS5A-containing DAA regimens with NS5A RASs. As well, although the compound is approved for decompensated cirrhosis, it must be administered with RBV in this population.12 Gilead Sciences, Foster City, CA, is developing a triplet-combination regimen that would include the addition of a protease inhibitor to sofosbuvir/velpatasvir and offer the possibility of a pangenotypic regimen that would be effective against DAA failures.

    This fixed-dose combination of sofosbuvir/velpatasvir was studied in conjunction with voxilaprevir (GS-9857), a pangenotypic NS3/4A protease inhibitor, for DAA-experienced patients with genotype 1. SVR12 for triple therapy was 100% while triple therapy with the addition of RBV had an SVR12 of 96% with overall SVR12 of 98%. Overall, 75% of patients had baseline RASs (NS5A, NS3 or both). Within this group, SVR12 was 97% but 100% for those without any baseline RASs.13

    The same drug combination was studied for genotypes 1, 2, 3, 4 and 6. SVR12 was 99% overall and 100% for genotype 1 in treatment-naïve patients with (n = 15) or without cirrhosis (n = 30) and treatment-experienced patients with cirrhosis (n = 17) or polymerase inhibitor-experienced patients with or without cirrhosis (n = 28), 100% for genotype 2, 97% for genotype 3 patients with cirrhosis who were treatment-naïve (n = 18) or treatment-experienced (n = 19), and 100% for genotypes 4 and 6. Those without RASs had an SVR12 of 100% while those with NS3, NS5A or both variants had overall SVR12 of 99%.13-15

    MK-3682 + grazoprevir + elbasvir or MK-3682 + grazoprevir + MK-8408
    There are two triplet therapies and at least one doublet regimen in development by Merck (Kenilworth, NJ) that include MK-3682 (a novel NS5b nucleotide polymerase inhibitor) with or without grazoprevir and with either elbasvir or MK-8408 (a novel NS5A inhibitor). MK-3682 was tested in 300 mg and 450 mg doses in the CREST 1 (for genotypes 1 and 2) and CREST 2 (for genotype 3) studies. The CREST 1 study showed mITT SVR24 of 91–100% for genotypes 1 (n = 93 with 46 GT1a and 47 GT1b) with either elbasvir or MK-8408 at both doses for MK-3682. However, only the MK-3682 (450 mg)/grazoprevir/MK-8408 regimen showed efficacy >90% in genotype 2 patients (n = 61). For genotype 3 patients, both the 300 mg and 450 mg doses of MK-3682 showed SVR24 rates >90% (n = 86).16,17

    Importantly, the presence of genotype 1 NS5A RASs had no effect on SVR12 rates, including those at the 28, 30, 31 and 93 positions. However, none of these patients had failed prior NS5A-containing regimens. Patients were also tested for the presence of pre-existing genotype 1 NS3 and NS5b RASs and these had no effect on SVR12 rates. The same was true in genotype 2 patients however the SVR rates in genotype 3 patients with NS5A RASs were slightly lower than in those without RASs. The tolerability and side-effect profile of these regimens proved to be excellent with essentially no late alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations, and very few serious adverse events. The most common side effects seen in the MK-3682 groups were minimal with headache and fatigue.16

    A regimen earlier in development, two of whose three components are currently unapproved, consists of simeprevir, odalasvir (NS5A inhibitor), and ALS-335 (nucleotide polymerase inhibitor). In a recent press release of 20 patients with treatment-naïve genotype 1 treated with the triplet regimen for 8 weeks, 100% achieved SVR24. Additional promising preliminary results were presented for 6 or 8-week regimens as well as an 8-week regimen of the doublet combination of odalasvir (50 mg every other day) and AL-335 (800 mg daily) for 8 weeks. Adverse effects were mild except for a single serious adverse event (Mobitz type 1 second-degree atrioventricular block), which was attributed to treatment.18

    MicroRNA-122 inhibition
    MicroRNAs regulate messenger RNA levels and translation. Liver-expressed microRNA-122 (miR-122), plays a role in HCV infection of all genotypes by interacting with the HCV RNA genome. Jopling and colleagues19 showed that by sequestering miR-122 in liver cells, the replication of HCV RNA could be diminished. Miravirsen (Santaris Pharma; Copenhagen, Denmark), a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide, designed to sequester miR-122 was studied in a phase IIa trial. Although thought to be pangenotypically effective, this trial enrolled only HCV genotype 1 patients (n=36) who received different subcutaneous doses of miravirsen on a weekly basis. Results showed dose-dependent reduction in HCV RNA levels with some durable response. Of note, no viral resistance was noted.20 Another modified oligonucleotide, RG-101, has also been studied in a small trial. A single subcutaneous dose of either 2 or 4 mg/kg was given to 28 total patients. A total of 6 patients in the 2 mg/kg group and 9 patients in the 4 mg/kg group had undetectable levels at 8 weeks while 7 of the 15 responders maintained this at week 20.21 Overall, microRNA-122 targets have shown some promise in small trials however this compound is currently on clinical hold in the US due to Food and Drug Administration concerns about safety. It is unclear what, if any, role these compounds would play in future HCV therapy.

    Link Of Interest On This Blog
    RG-101
    January 31, 2017 Regulus Announces Continuation of RG-101 Clinical Hold - FDA requests longer-term follow-up data from ongoing studies

    Conclusion
    The value of a single-pill, fixed-dose, RBV-free regimen for all genotypes is obvious as it would obviate the need for genotype and RAS testing prior to treatment and would likely be simple and well tolerated. In addition, the advantage of a shorter duration has been already demonstrated with the use of sofosbuvir/ledipasvir (Harvoni™) in genotype 1 treatment-naïve noncirrhotic patients. The ultimate goal of new regimens will be to remove the complexity of treatment and thus place therapy in the hands of primary care physicians as well as specialists. We think we are well on the road towards this goal and we will likely have multiple drug regimens that afford this simplicity by 2017.

    Unresolved issues remain, however, including the cost and access to these drugs and the continued need to evaluate chronic HCV patients for advanced fibrosis or cirrhosis prior to treatment. These patients may be cured with the same regimen however they require assessment for esophageal varices before and after therapy and screening for hepatocellular carcinoma before and at 6 month intervals after successful treatment. Additionally, the safety and efficacy of these fixed-dose regimens will vary in certain populations such as those with end-stage renal disease and decompensated cirrhosis. There will also continue to be drug–drug interactions which preclude their use with other drugs and thus require attention to these details. As such, we think that therapy will remain in the hands of specialists in the near-term but this may change in later years.

    Footnotes
    Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

    Conflict of interest statement: Research grants paid to Scripps Health: Gilead, Merck, AbbVie, BMS, HCV Target. Honoraria paid to PJP for Advisory Boards and Speaking/Teaching: Gilead, Merck, AbbVie, Intercept.

    Contributor Information
    Ara A. Kardashian, Fellow, Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA, USA.

    Paul J. Pockros, Director of Clinical Research, Scripps Translational Science Institute, Scripps Clinic, 10666 N Torrey Pines Rd, La Jolla, CA 92037, USA.

    References - Full Text

    Neuropsychiatric Symptoms in Patients With HCV Cured of Infection

    Neuropsychiatric Symptoms in Patients With HCV Cured of Infection


    Disabling chronic fatigue is reported in approximately 60% of patients with confirmed hepatitis C virus (HCV) infection,1,2 as well as decreased quality of life (QoL)3,4 and cognitive dysfunction (eg, deficits in attention and verbal learning).5,6 While these neuropsychiatric symptoms may be expected in patients with ongoing HCV infection, it is questionable whether these effects are also present in HCV-exposed patients who currently are cured of the infection (polymerase chain reaction-negative [PCR-]).

    A study7 recently published in the Journal of Viral Hepatitis found no evidence linking the presence of HCV infection with these neuropsychiatric symptoms. Instead, researchers suggest that the fatigue and impairment in health-related quality of life (HRQoL) and cognitive and mental function commonly found in HCV-exposed patients may be explained by either an HCV infection-triggered autoimmune response persisting beyond virus clearance or the development of a virus variant in the brain.7

    Links
    Posted On This Blog January 25, 2017
    Journal of Viral Hepatitis
    View Full Text Article
    Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?!
    Accepted manuscript online: 24 January 2017
    DOI: 10.1111/jvh.12674

    Really Rapid Review — CROI 2017, Seattle

    NEJM Journal Watch

    The Conference on Retroviruses and Opportunistic Infections (CROI) returned to Seattle this past week for its 24th meeting. It’s the 4th time CROI has been held in Seattle, an excellent city for a meeting of this size, which includes “only” 4200 people. The convention center is pleasant and user-friendly — big but not cavernous, actually encourages interactions with colleagues — and there are numerous hotels and restaurants within walking distance, plus more Starbucks per square foot than any place on the planet.

    From a content perspective, the big change for CROI 2017 was the return of numerous studies on antiretroviral therapy, studies involving both approved and investigational agents. The last several years, by contrast, had relative dominance of pre-exposure prophylaxis and hepatitis C studies. With PrEP, one had the sense at the meeting that we’re now waiting for the next strategies (long-acting injectables, for example).

    As for hepatitis C, well that’s been all but solved (except for the implementation part). How do you improve on 97%-plus cured. Hooray!

    Links
    Conference Coverage
    Conference on Retroviruses and Opportunistic Infections (CROI)
    February 13-16, 2017, Seattle WA
    NATAP
    hivandhepatitis.com
    http://www.aidsmap.com/croi-2017
    http://www.medpagetoday.com/meetingcoverage/croi

    What are the Most Accurate Non-invasive Techniques for Measuring Liver Fibrosis and Steatosis?

    What are the Most Accurate Non-invasive Techniques for Measuring Liver Fibrosis and Steatosis?

    Magnetic resonance elastography (MRE) is more accurate than transient elastography (TE) in identifying liver fibrosis of stage 1 or more, researchers report in the February issue of Gastroenterology, using biopsy analysis as the standard. They also show that MRI-based proton density fat fraction (MRI-PDFF) analysis is more accurate than TE-based controlled attenuation parameter (CAP) assessment in detecting all grades of steatosis in patients with non-alcoholic fatty liver disease (NAFLD).

    It is important to accurately measure the level of fibrosis in livers of patients with NAFLD, as it associates with long-term outcomes. Steatosis quantification is also important. Nonalcoholic steatohepatitis (NASH) is a strong indicator of disease progression, but until recently, only liver biopsies have been sufficient to identify inflammation.
    Continue reading....

    Related Posts:
    Does FibroScan Accurately Assess Liver Fibrosis?

    Monday, February 20, 2017

    Healthcare, patient groups oppose hep-C drug patents

    Healthcare, patient groups oppose hep-C drug patents
    MUMBAI: Healthcare aid and patient groups have come together in patent courts to fight against ``abusive strategies'' of Big Pharma, to ensure access to affordable treatment in hepatitis C. The Initiative for Medicines, Access & Knowledge (I-MAK) together with Delhi Network of Positive People and international medical humanitarian organisation, Medecins Sans Frontieres filed three cases on crucial new hepatitis C medicines: two patent challenges on daclatasvir, one on velpatasvir and a further challenge on sofosbuvir.

    The patent challenges could remove barriers to production and distribution of affordable generic versions of direct-acting antiviral (DAA) medicines, including Gilead's sofosbuvir and velpatasvir, and Bristol-Myers Squibb's daclatasvir.

    Continue reading....

    HCV Screening Shouldn't Just Focus on At-Risk Populations

    HCV Screening Shouldn't Just Focus on At-Risk Populations
    FEB 20, 2017 | CAITLYN FITZPATRICK
    At the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle, Washington, researchers from MedStar Health Research Institute in Maryland presented new data on hepatitis C virus (HCV)-positive non-baby boomers.

    It’s widely acknowledged that those individuals belonging to the baby boomer age group (those born between 1946 and 1964) are at higher risk of acquiring HCV infection. According to the Centers for Disease Control and Prevention (CDC), these individuals are five times more likely to be infected with HCV. However, other at-risk populations may not be getting adequately tested for the virus.

    Listen - Liver transplant and organ donation

    Mayo Clinic Radio: Liver transplant and organ donation / clinical trials / constipation

    According to the U.S. Department of Health and Human Services, more than 14,000 people are waiting for a liver transplant today in the U.S. Liver transplant usually is reserved as a treatment option for people who have significant complications due to end-stage chronic liver disease. In rare cases, sudden failure of a previously normal liver may occur. The liver is just one of several organs, including kidney, heart and lung, that have long transplant waiting lists. On the next Mayo Clinic Radio program, transplant surgeon Dr. Charles Rosen will discuss liver transplant and the importance of organ donation. Also on the program, Toni Mangskau, clinical trials referral coordinator at Mayo Clinic’s Cancer Education Center in Rochester, Minnesota, will explain how clinical trials are conducted. And gastroenterologist Dr. Michael Camilleri will offer prevention tips for the common problem of constipation.


    Links
    Access archived shows.

    Why should we worry about conflict of interest?
    Janice Boughton, MD | Physician | February 19, 2017
    A recent issue of the Journal of the American Medical Association (JAMA) reads like an expose. Well, at least three of the research articles do. So exciting! I don’t want medicine — my field — to be ethically unsavory, but it is sometimes. It makes me proud to see that it polices itself and that such information is published in a high profile journal.
    The third article was even more concerning from a financial standpoint. In the last few years, we have seen major changes in the way we treat hepatitis C and elevated cholesterol levels. Guidelines released in 2013 by the American Heart Association recommended that we extend the number of people who will be treated with cholesterol-lowering “statin” drugs to anyone with a 10-year risk of atherosclerotic cardiovascular disease (heart attacks and the like) of over 7.5%. Guidelines released in 2015 for the treatment of hepatitis C, a chronic liver disease caused by a blood-borne virus, suggested that we treat everyone with hepatitis C with extremely expensive drugs which, kudos to pharmaceutical researchers, can cure the disease.
    Continue reading....

    SF working on ambitious plan to eliminate hepatitis C

    February 19, 2017
    San Francisco is trying to become the first city in the nation to eliminate hepatitis C, rolling out an ambitious plan that would involve curing everyone who already has it and stopping further spread of the infectious disease, which can cause severe liver damage.

    Just two or three years ago, the plan, called End Hep C SF, would have been impossible. But a new cure that is effective and relatively easy to take, combined with growing enthusiasm for programs to increase access to health care, has doctors and public health officials convinced that they can wipe out the virus over the next decade.

    Continue reading...

    February 2017 - WHO guidelines on testing for chronic HBV and HCV infection

    Publication details
    Number of pages: 204
    Publication date: February 2017
    Languages: English
    ISBN: 978-92-4-154998-1

    Downloads
    Guidelines on hepatitis B and C testing

    Overview
    Testing and diagnosis of hepatitis B (HBV) and C (HCV) infection is the gateway for access to both prevention and treatment services, and is a crucial component of an effective response to the hepatitis epidemic. Early identification of persons with chronic HBV or HCV infection enables them to receive the necessary care and treatment to prevent or delay progression of liver disease. Testing also provides an opportunity to link people to interventions to reduce transmission, through counselling on risk behaviours and provision of prevention commodities (such as sterile needles and syringes) and hepatitis B vaccination.

    These are the first WHO guidelines on testing for chronic HBV and HCV infection and complement published guidance by WHO on the prevention, care and treatment of chronic hepatitis C and hepatitis B infection. These guidelines outline the public health approach to strengthening and expanding current testing practices for HBV and HCV, and are intended for use across age groups and populations.

    Viral Hepatitis - World Day of Social Justice: fighting for our right to health

    http://blogs.biomedcentral.com/on-health/2017/02/20/world-day-of-social-justice-fighting-for-our-right-to-health/

    World Day of Social Justice: fighting for our right to health

    Sorafenib benefit dependent on hepatitis status in patients with HCC

    February 19, 2017
    Sorafenib improved OS among patients with hepatocellular carcinoma who were hepatitis C positive but hepatitis B negative, suggesting that the beneficial effects of sorafenib may be based on hepatitis status, according to results of a meta-analysis.

    Of Interest
    MicroRNA-125a-5p is a downstream effector of sorafenib in its antiproliferative activity toward human hepatocellular carcinoma cells.
    Article ID: 669739
    Released: 17-Feb-2017 3:05 PM EST
    Source Newsroom: Sbarro Health Research Organization (SHRO)

    Sorafenib is a multikinase inhibitor with specific activity against Raf kinase and several receptor tyrosine kinases. The addition of sorafenib to hepatocellular carcinoma cells increased cellular expression of miR-125a. Upregulation of this miRNA inhibited cell proliferation and induced cell cycle arrest by targeting c-Raf, part of the ERK pathway that is involved in cell proliferation and sirtuin-7, (SIRT-7) a NAD(+)-dependent deacetylase that inhibits transcriptional activation of the cell cycle inhibitor p21. Therefore, sorafenib inhibits Raf activity and upregulates miR125 that, in turn, targets c-Raf and SIRT7; this dual inhibition of Raf activity and expression together with p21-dependent cycle arrest coherently combine to explain the antiproliferative activity of the drug.

    Newswise — Treatment options for liver cancer are often limited and almost exclusively involve transplantation if possible, or local chemoembolization and radiofrequency ablation. Medical treatments for more advanced stages have been explored during recent decades, but only the drug sorafenib, a small molecule multi-kinase inhibitor, has shown promising results and been approved for use by international medical agencies. Unfortunately, only 25% of patients respond to sorafenib treatment, so researchers have endeavored to understand its mechanism of action and discover a way to boost its effectiveness.

    A recent study, published in the journal Journal of Cellular Physiology, describes further scientific insight into the involvement of a small non coding RNA, miR-125a, in the anti-cancer effects of sorafenib in the treatment of liver cancer, or hepatocellular carcinoma. These results are interesting as miRNAs have multiple available intracellular targets and could contribute to the amplification of the effects of sorafenib.

    The link between small kinase inhibitors such as sorafenib, and the existing molecular pathways that govern cell proliferation such as miR-125a, may be useful to potentiate the anticancer activity of sorafenib. Clinical applications of this knowledge might seek to identify and increase the number of liver cancer patients that respond positively to the drug.

    The study includes work done by Prof. Michele Caraglia and Aniello Russo, of the University of Campania “L. Vanvitelli” in Naples, and Caserta, Italy, in collaboration with Prof. Antonio Giordano, Director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia.

    “Sorafenib is still the only drug indicated in the treatment of hepatocellular carcinoma, which highlights the difficulty in the medical treatment of liver cancer,” says Prof. Antonio Giordano. “Sorafenib is effective because it acts upon multiple intracellular targets and interferes with both cancer proliferation and tumor blood supply. However, its activity is limited to only 25% of patients that are sensitive to its effects. This strongly pushes the researchers to define the mechanism of action of the drug,” Giordano concludes.

    “MicroRNAs can act as either cancer-fighting tumor suppressors, or as cancer-causing oncogenes,” says Professor Michele Caraglia. "We have found that the expression of miR-125a is strongly involved in the mechanism of action of sorafenib and its ability to regulate cancer cell proliferation. These findings suggest the possible use in the future of miR125a in combination with sorafenib in order to potentiate the anti-cancer activity of the drug,” Caraglia concludes.

    The study results open a new scenario of intervention in the treatment of hepatocellular carcinoma in which small molecules such as sorafenib can be used in association to nucleic acids such as miR-125a. The latter could be administered to patients systemically encapsulated in novel drug delivery options such as nanocarriers. Researchers plan to further study the in vivo efficacy of these strategies to increase treatment options for this difficult form of cancer.

    Citations
    Potenza N, Mosca N, Zappavigna S, Castiello F, Panella M, Ferri C, Vanacore D, Giordano A, Stiuso P, Caraglia M, Russo A. MicroRNA-125a-5p Is a Downstream Effector of Sorafenib in its Antiproliferative Activity Toward Human Hepatocellular Carcinoma Cells. J Cell Physiol. 2016 Dec 16. doi: 10.1002/jcp.25744.