August 16, 2013

Research article

BMC Infectious Diseases 2013, 13:374 doi:10.1186/1471-2334-13-374

Published: 14 August 2013

Fabio Iacomi, Giuseppina Iannicelli, Andrea Franceschini, Paolo Migliorisi, Silvia Rosati, Pierluca Piselli, Paola Sognamiglio, Gabriella De Carli, Sonia Marcellini and Fabrizio Palmieri

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Abstract (provisional)

Background

The prevalence of chronic hepatitis C virus (HCV) infection in the Italian correctional population is estimated to be around 38%. In this setting HCV infection treatment is controversial because of several factors such as active drug substance abuse, psychiatric illness, length of treatment, risk of re-infection, poor adherence and low success rate.

Methods

A retrospective data review of 159 inmates, positive for anti-Hepatitis C virus (HCV) antibody, evaluated to National Institute for Infectious Diseases "L. Spallanzani" (INMI) from January 2006 to December 2009, was conducted to evaluate rate of completion (feasibility) and outcome efficacy of chronic Hepatitis C Virus (HCV) infection treatment with Pegylated Interferon and Ribavirin in five correctional facilities in Rome.

Results

Of the 159 inmates evaluated in the study period, 50, all male (median age 39 years) were treated. Twenty patients (40%) did not complete treatment: 15 showed no response and therapy was stopped, 5 patients (10%) interrupted treatment because of adverse reactions. The global feasibility was 60%. The overall sustained virologic response (SVR) was 50% (32% for genotype 1 and 68% for genotype other than 1). The main predictors of SVR at the Multivariable Logistic Regression Odds Ratio (MLR-OR) were a better pretreatment histological diagnosis (absence of bridging fibrosis or cirrhosis [MLR-OR 11.85; 95% CI 1.96-71.62) and a HCV genotype other than 1 (MLR-OR 5.87; 95% CI 1.49-23.17).

Conclusions

Chronic HCV infection treatment in correctional facilities is feasible and effective and should be strongly recommended, in combination with preventive measures, in appropriately screened patients because it represents an important opportunity to treat a population with a high prevalence of chronic HCV infection among whom treatment options post incarceration may be limited.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

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By Helen Branswell, The Canadian Press May 29, 2013

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Cutting back on alcohol and taking steps to maintain a healthy weight should lower one's liver cancer risk, experts suggest.
Photograph by: Thinkstock , canada.com

TORONTO - Ground is being gained on many fronts in the war against cancer, but one of the deadliest — liver cancer — is still on the rise, the Canadian Cancer Society said Wednesday.

About half of liver cancer cases in Canada are probably preventable, the research and advocacy organization said as it released its annual estimates of the toll cancers will exact in Canada in 2013.

Overall, the society estimates 187,600 people will learn they have a new cancer this year (excluding non-melanoma skin cancers) and 75,500 Canadians will die from some form of the disease.

The big four remain breast cancer, prostate cancer, colorectal cancer and lung cancer, but rates of these diseases are either stable or declining, says Prithwish De, a cancer epidemiologist with the cancer society.

But the same is not true for liver cancer, which currently claims the lives of four out of five people diagnosed with it. Since 1970, the incidence of liver cancer has tripled in Canadian men and doubled in women.

Primary liver cancer — as opposed to cancer that spreads from another site to the liver — is still rare. The society estimates 2,000 people will be diagnosed with it in 2013 and 1,000 people will succumb to the disease. Worldwide, liver cancer is the third leading cause of cancer deaths, after lung and stomach cancer.

The cancer is so deadly because most cases are not found until the disease has progressed beyond the point of cure. When liver cancer is found early it generally responds well to treatment, says Dr. Sean Cleary, a liver surgical oncologist at Toronto's University Health Network.

"One of the problems with this disease is that it does not develop symptoms or patients aren't aware that they have the problem until the disease is very advanced, at a very large and untreatable stage," he said.

Science has made little progress improving the survival chances of people with liver cancer. Over the past 20 years, the survival rate has risen by only between two and three per cent, De says.

But the toll the disease takes could be dramatically lowered if people at high risk of developing the liver cancer took some proactive steps, experts say.

Excess alcohol consumption, obesity and diabetes are known to be risk factors for developing liver cancer. Cutting back on alcohol and taking steps to maintain a healthy weight should lower one's liver cancer risk, they suggest.

Another way to combat the disease is by addressing two related conditions that can be precursors to liver cancer — hepatitis B and C, which are viral infections of the liver. There is currently a vaccine against hepatitis B, but none for hepatitis C.

People who are at high risk of having one or the other infection should consider talking with their doctors about being tested for hepatitis. Treatment can often clear the infections, the experts say.

"Many individuals who are infected with either acute or chronic hepatitis infections may not be aware that they're infected. And we're trying to let Canadians know that there is a way to get tested and find out if you are infected by either hepatitis B or C," says De.

Last year the U.S. Centers for Disease Control urged all baby boomers to have a one-time test for hepatitis C because of the liver cancer risk. The Canadian Liver Foundation later echoed that advice.

But the Public Health Agency of Canada is studying whether it makes sense to issue a similar recommendation in Canada, where the rate of hepatitis C is lower than in the U.S. While it deliberates, the cancer society is content to wait for evidence-based advice.

"Because we're lacking that evidence in Canada it's kind of premature to say whether (across-the-board) screening would be beneficial to that age group," De says.

"And so, from the Canadian Cancer Society's perspective, we'd like to wait until there's a good solid base of evidence before we say anything about screening in specific age cohorts."

Instead, they recommend a discussion about screening for people who had a blood transfusion before 1990, who use or used intravenous drugs or who moved to Canada from parts of the world where hepatitis B and C are common — Asia and sub-Saharan Africa for hepatitis B, Japan and southern Europe for hepatitis C, Cleary says.

Others at risk are people who've had high-risk sexual contacts and received tattoos in non-reputable tattoo parlours, he said.

"Individuals who have those risk factors are definitely candidates for speaking to their doctors about finding out whether testing for hepatitis B or C and whether any other types of counselling would be beneficial for them for reducing their risk of liver cancer," De says.

Source

Risk Seldom the Reason for HCV Testing

Published: Aug 16, 2013

By Michael Smith, North American Correspondent, MedPage Today

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

Action Points

  • Nearly half of people with chronic hepatitis C (HCV) said they were only tested after they had some clinical sign or symptom.
  • Note that less than one fourth of HCV-infected patients gave CDC risk indications as a reason for testing.

Nearly half of people with chronic hepatitis C (HCV) said they were only tested after they had some clinical sign or symptom, a CDC survey showed.

And only about one in five said they were tested because they fit one of the risk categories, such as injection drug use, defined by the CDC , the agency reported in the Aug. 16 issue of Morbidity and Mortality Weekly Report.

The findings come from a survey of nearly 4,700 people with chronic HCV under care in one of four U.S. integrated health-care systems -- the Geisinger Health System of Danville, Pa., the Henry Ford Health System of Detroit, Kaiser Permanente Hawaii of Honolulu, and Northwest Permanente of Portland, Ore.

Chronic HCV accounts for substantial morbidity and mortality in the U.S., the CDC report noted, adding that testing and treating people without symptoms might help reduce the impact.

The agency, recently joined by the U.S. Preventive Services Task Force, has urged a one-time HCV test for everyone born from 1945 to 1965, because research suggests they account for about 75% of infections.

To understand where and why people with current chronic HCV sought initial testing, the agency queried some 8,101 patients in the four health systems, of whom 4,689 (or 57.9%) completed the survey.

Of those, 78.1% were born from 1945 through 1965, 87.4% had a high school diploma or its equivalent, 98.1% had insurance, and 45.5% had jobs, while 23.2% were getting disability payments.

A doctor's office was the most common location for the initial test, reported by 60.4% of respondents, although the rate was slightly higher for those born during 1945 through 1965 at 62.1% and lower (at 54.3%) for those born outside that period.

The participants reported 7,649 reasons for their initial test (respondents could give multiple reasons), including 3,473 "miscellaneous" responses (or 45.4%) that were not part of the CDC's risk indications, including such things as having many sex partners, coming from a country with endemic HCV, or following a doctor's recommendation.

But almost half of the respondents -- some 2,121 -- said they were tested in response to a clinical sign, either an abnormal liver test or liver symptoms such as jaundice.

And 1,045 said they were tested because they fit into a CDC risk category -- 986 of them cited injection drug use and 59 cited hemodialysis.

Another 781 cited some institutional requirement, such as insurance, as a reason for testing.

The CDC report cautioned that the patients in the survey were not nationally representative, so the results can't be applied to the general U.S. population. Among other things, almost all had some form of health insurance.

Also, because only 57.9% of the eligible participants answered the survey, response bias might have arisen and the gap between initial testing and time of interview might have led to recall bias.

The analysis was supported by the CDC. Ko is an employee of the agency.

Primary source: Morbidity and Mortality Weekly Report
Source reference: Centers for Disease Control and Prevention "Locations and reasons for initial testing for hepatitis C infection -- chronic hepatitis cohort study, United States, 2006-2010" MMWR 2013; 62: 645-648.

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Gilead deliberately expose patients to deadly risks

Provided by ACT-UP Paris

Hepatitis C: Shame on Gilead! / HCV: Shame on Gilead!

published online: 12 August 2013

People living with hepatitis C and whose state of health emergency should benefit from drugs under development and not yet available on the market. For this, there is a temporary authorizations device use (ATU).

At noon, the activists of Act Up-Paris traveled to Boulogne-Billancourt to the French headquarters of Gilead Sciences Inc. to remind the company that it must follow the advice of the National Security Agency of the drug (MSNA ). Gilead refuses to give early access to sofosbuvir (SOF) to patients because they are therapeutic impasse with molecules currently available on the market, received a nominative ATU ANSM. The activists put up posters on the French headquarters of the firm are poured fake blood, unfurled a banner "Shame on Gilead" and chanted slogans such as "SOF is our right" or "We need this drug." The attitude of Gilead is denounced by several patient groups and national and international coalitions whose TRT-5, CHV, Treatment Action Group (USA) and the European AIDS Treatment Group (EATG). An online petition has collected more than 400 signatures of natural and legal persons.

Laure Pora, president of Act Up-Paris, said: "For Gilead, monopolistic logic premium on therapeutic requirements; compassionate access sofosbuvir is not the only example. We ask members of the Economic Committee of Health Products, which sets the price of drugs to financially penalize the firm when comes the time to fix the price of sofosbuvir and politicians denounce the attitude of Gilead. We call to sign the online petition  "

Act Up-Paris requires Gilead Sciences immediately provide the sofosbuvir to all persons who have registered ATU.

To gather information on the ATU anti-hepatitis C molecules in development, the group has set up an observatory that can be supplied by patients, relatives, doctors and associations.

Source


Gilead deliberately expose patients to deadly risks

Press Release interassociative group TRT-5 and Collective viral hepatitis

published online: 12 August 2013

People living with hepatitis C and whose state of health emergency should benefit from drugs in development and close to putting them on the market. For this, there is in France a device called Temporary Authorization for Use (ATU), which could save lives by providing early access to such drugs.

On 23 July, the National Security Agency of Medicines (MSNA) had granted 96 nominative ATU - ie based on the state of health of the person - sofosbuvir of a molecule developed by Gilead, to people with received a liver transplant, people waiting for transplants and people with cirrhosis therapeutic impasse. Gilead but refused to give the molecule in the majority.

Data from early access programs (or compassionate) can be used to determine the safest and most effective ways to treat HCV in people who need it most. For example, the cohort ANRS CUPIC provided essential information to understand what cirrhosis patients were more likely to get better, or worse - with treatments based on boceprevir or telaprevir. If Gilead refuses to study sofosbuvir "in real life", the opportunity is lost to minimize damage and maximize profits.

That's why we ask Gilead to give sofosbuvir NOW to those who have the greatest need, including those with advanced (Child-Pugh B or C), cirrhosis, some of which are living with HIV or another disease. For this purpose, a petition was launched in ten days which has raised more than 400 individual signatures and associations worldwide.

Of projects ATU cohort and clinical trial (sofosbuvir ledipasvir +) are under consideration in MSNA, but these projects appear equally restrictive and Gilead refuses to disclose its information to patients' associations. It is thus highly likely that doctors have not requested nominative ATU hoping that their patients could access treatment in a cohort ATU or a test, then they will be excluded.

Neglecting health emergencies, building useful prescription and pharmacovigilance scientific data, the Gilead, which markets life-saving medicines is not up to its ethical and social responsibilities.

Declaration of interest link: TRT-5 in 2013 received a grant of € 15,000 from Gilead.

Source

Virology Journal 2013, 10:259 doi:10.1186/1743-422X-10-259

Research

Tutik Sri Wahyuni, Lydia Tumewu, Adita Ayu Permanasari, Evhy Apriani, Myrna Adianti, Abdul Rahman, Aty Widyawaruyanti, Maria Inge Lusida, Achmad Fuad, Soetjipto, Nasronudin, Hiroyuki Fuchino, Nobuo Kawahara, Ikuo Shoji, Lin Deng, Chie Aoki and Hak Hotta

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Published: 13 August 2013

Abstract (provisional)

Background

Hepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide. The overall prevalence of HCV infection is 2%, representing 120 million people worldwide. Current standard treatment using pegylated interferon and ribavirin is effective in only 50% of the patients infected with HCV genotype 1, and is associated with significant side effects. Therefore, it is still of importance to develop new drugs for treatment of HCV. Antiviral substances obtained from natural products, including medicinal plants, are potentially good targets to study. In this study, we evaluated Indonesian medicinal plants for their anti-HCV activities.

Methods

Ethanol extracts of 21 samples derived from 17 species of medicinal plants explored in the East Java region were tested. Anti-HCV activities were determined by a cell culture method using Huh7.5 cells and HCV strains of 9 different genotypes (1a to 7a, 1b and 2b).

Results

Four of the 21 samples tested showed antiviral activities against HCV: Toona sureni leaves (TSL) with 50% inhibitory concentrations (IC50) of 13.9 and 2.0 mug/ml against the HCV J6/JFH1-P47 and -P1 strains, respectively, Melicope latifolia leaves (MLL) with IC50 of 3.5 and 2.1 mug/ml, respectively, Melanolepis multiglandulosa stem (MMS) with IC50 of 17.1 and 6.2 mug/ml, respectively, and Ficus fistulosa leaves (FFL) with IC50 of 15.0 and 5.7 mug/ml, respectively. Time-of-addition experiments revealed that TSL and MLL inhibited both at the entry and post-entry steps while MMS and FFL principally at the entry step. TSL and MLL inhibited all of 11 HCV strains of all the genotypes tested to the same extent. On the other hand, FFL showed significantly weaker inhibitory activities against the HCV genotype 1a strain, and MMS against the HCV strains of genotypes 2b and 7a to a lesser extent, compared to the other HCV genotypes.

Conclusions

Ethanol extracts of TSL, MLL, MMS and FFL showed antiviral activities against all the HCV genotypes tested with the exception that some genotype(s) showed significant resistance to FFL and to MMS to a lesser extent. These plant extracts may be good candidates for the development of anti-HCV drugs.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

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Provided by MedicalXpress

August 15, 2013

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This image demonstrates that the factor IL-33 (brown cells) is present in livers after chronic damage. Credit: Immunity, Mchedlidze et al.

Chronic liver disease is a leading cause of death in the United States, in part because it often causes the formation of harmful scar tissue—a process known as fibrosis. A study published by Cell Press August 15 in the journal Immunity reveals the central role the immune molecule interleukin 33 (IL-33) plays in the formation of liver fibrosis. The findings suggest that drugs targeting this molecule could serve as a new treatment strategy to protect against liver fibrosis.

"Currently, the therapeutic options for liver fibrosis are limited and not curative," says senior study author Stefan Wirtz of Friedrich-Alexander University Erlangen-Nuremberg. "We identified novel immunological factors that contribute to the development of liver fibrosis, opening up new avenues for the treatment of this serious condition."

Liver fibrosis refers to the accumulation of harmful deposits of extracellular matrix (ECM) proteins, and it can eventually lead to organ failure. Past studies have suggested that this kind of damage is associated with abnormal immune responses in the liver, but very little was known about the molecules and cells that contribute to fibrosis.

In the new study, Wirtz and his team found that the amount of IL-33 in the blood was higher than normal in patients with liver disease. Following up on this observation, they discovered that injection of IL-33 into mice caused ECM proteins to build up in the liver, whereas mice that were genetically modified to lack IL-33 were largely protected from fibrosis. The researchers went on to identify the immune networks underlying IL-33's harmful effects and discovered that this molecule activates immune cells called type 2 innate lymphoid cells (ILC2), which had never before been linked to liver disease.

"Our findings reveal IL-33 as a novel biomarker that could potentially lead to early detection of fibrosis in patients, which may be extremely valuable for preventing further damage to the liver," Wirtz says. "Moreover, the study shows that drugs targeting IL-33 or ILC2 responses could be a promising strategy to protect against fibrosis and chronic liver disease."

Explore further: How does fibrosis occur in Crohn's disease?

More information: Immunity, Mchedlidze et al.: "Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis." dx.doi.org/10.1016/j.immuni.2013.07.018

Journal reference: Immunity

Provided by Cell Press

Source

Provided by Healio

Macias J. Clin Infect Dis. 2013;doi:10.1093/cid/cit537.

August 15, 2013

Hepatitis C therapy is necessary in patients with advanced fibrosis who are coinfected with hepatitis C and HIV because they are at risk for liver decompensations, researchers in Spain have suggested.

“Liver fibrosis progresses fast among HIV/HCV-coinfected patients and, as a consequence, after the first decompensation patients die soon,” the researchers wrote in Clinical Infectious Diseases. “This grim prognosis can be altered by therapy against HCV. Individuals with HIV infection and compensated HCV-related cirrhosis achieving sustained virological response to therapy against HCV are at a reduced risk of liver events.”

The retrospective cohort study included 892 patients with HIV/HCV coinfection who were treated from November 1990 to June 2012. They had not previously received HCV therapy or had received treatment but not reached sustained virological response. All patients had advanced fibrosis diagnosed by liver biopsy or liver stiffness measurement. The researchers evaluated the number of liver decompensations recorded during the follow-up period.

Among the 317 patients who had liver biopsy, 40 patients experienced liver decompensation, with a rate of 2.3 decompensations per 100 person-years. At 5 years, the probability of remaining free of liver decompensation was 90%. Twelve patients with fibrosis stage 3 at baseline developed liver decompensation, for an incidence of 1.4 per 100 person-years. Twenty-eight patients with cirrhosis at baseline developed liver decompensation, for an incidence of 3.1 per 100 person-years.

Among the 575 patients who had liver stiffness measurement, 53 patients experienced liver decompensation, with a rate of 3.98 decompensations per 100 person-years. At 5 years, the probability of remaining free of liver decompensation was 77%. Six individuals with a liver stiffness measurement of ≥9.5 kiloPascal (KPa) and <14.5 KPa and 47 patients with a measurement of ≥14.6 KPa at baseline experienced decompensations of cirrhosis. The incidence rates were 0.9 per 100 person-years and 4 per 100 person-years, respectively.

“Liver decompensations among HIV/HCV-coinfected patients can emerge shortly after the detection of advanced fibrosis,” the researchers wrote. “In those patients, immediate anti-HCV therapy should be considered.”

Disclosure: Some of the researchers report financial relationships with Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Jansen Cilag, Merck Sharp & Dome, Roche, Schering-Plough and ViiV.

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