Review of direct-acting antiviral agents for the treatment of chronic hepatitis C

Expert Opin Investig Drugs.

Review

Posted online on June 4, 2013. (doi:10.1517/13543784.2013.806482)

Nihar Shah ^†1 MD Fellow in Hepatology, Tracey Pierce ² BA Clinical Research Coordinator & Kris V Kowdley ³ MD FACP Director

¹ Digestive Disease Institute, Virginia Mason Medical Center,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA +1 206 223 2319; +1 206 341 1188; kris.kowdley@vmmc.org

² Digestive Disease Institute, Virginia Mason Medical Center,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA

³ Digestive Disease Institute, Virginia Mason Medical Center, Liver Center of Excellence,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA

^†Author for correspondence

Introduction: Rapid breakthroughs in the treatment of hepatitis C virus (HCV) infection have dramatically altered the treatment landscape for this chronic disease. In 2011, the protease inhibitors (PIs) boceprevir and telaprevir in combination with peginterferon (peg-IFN) and ribavirin (RBV) were the first direct-acting antivirals (DAAs) approved in the United States for treatment of genotype (GT) 1 HCV. Several DAAs currently in late-stage clinical trials, including NS3/NS4A serine PIs, NS5A inhibitors, NS5B polymerase inhibitors (both nucleoside and non-nucleoside) and cyclophilin inhibitors, both with and without peg-IFN and RBV, are promising for the treatment of HCV. DAA regimens offer several advantages including that they specifically target HCV viral replication and thus appear to be less dependent on host characteristics, very high SVR rates accompanied by fewer side effects (SE) and lower pill burdens. A review on the treatment of HCV is important and timely as the development on DAAs is progressing rapidly and the health-care providers need to be aware about this as these regimens are anticipated to become clinically available soon.

Areas covered: The literature was searched and reviewed using PubMed as well as data gathered from those presented at the international liver meetings, AASLD and EASL as well as CROI.

Expert opinion: With the potential of eliminating IFN and RBV, several DAAs under clinical development appear to be promising using novel approaches with good antiviral effects, shorter duration and lower SE profile.

Keywords

ABT-267, ABT-333, ABT-450, asunaprevir, boceprevir, cirrhosis, cyclophilin inhibitors, daclatasvir, danoprevir, directly acting antiviral agents, faldaprevir, hepatitis C virus, ledipasvir, mericitabine, NS5A inhibitors, NS5B polymerase inhibitors, null responders, partial responders, pegylated interferon, protease inhibitors, relapsers, resistance, ribavirin, simeprevir, sofosbuvir, SVR, telaprevir, treatment naïve

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Poorer Health for Acetaminophen Overdose Survivors than Other Liver Failure Patients

Journal Liver Transplantation

Press Release

July 09, 2013

Spontaneous survivors of acetaminophen overdose have significantly lower overall health compared to survivors or transplant recipients following acute liver failure caused by non-drug induced liver injury according to a new study published online in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Findings show that acetaminophen overdose survivors report more days of impaired mental and physical health, and activity limitations due to poor health, pain, anxiety and depression.

Patients are diagnosed with acute liver failure (ALF) when severe liver dysfunction occurs, along with blood clotting or bleeding disorders (coagulopathy) and compromised brain function (encephalopathy). Studies report that up to 3,000 patients develop ALF in the U.S. each year and 67% of these patients will survive, but nearly 30% of these patients require emergency liver transplantation. However, long-term consequences of ALF and health-related quality of life (HRQOL) of survivors, remains unclear.

To expand understanding of the quality of life and function of adult ALF survivors, a team led by Dr. Robert Fontana from the University of Michigan Medical Center in Ann Arbor conducted a prospective observational study. Patients diagnosed with ALF between January 1998 and July 2010 were included in the study. Participants agreed to follow-up at one and two years following ALF.

Results show that of the 282 ALF patients—125 liver transplantation recipients (10.7% due to acetaminophen overdose) and 157 spontaneous survivors of which 95 were acetaminophen overdose patients and 62 were survivors of non-drug induced liver failure. Patients that survived acetaminophen overdose reported significantly lower general health scores. Acetaminophen overdose survivors had higher rates of substance abuse and psychiatric disease compared to non-acetaminophen overdose survivors and transplant recipients. Participants who were survivors of non-intentional acetaminophen overdose were less likely to have psychiatric comorbidity compared to patients who intentionally overdosed at 48% and 82%, respectively.

The combined group of spontaneous survivors of ALF reported “fair/poor” health and more than 14 days of physical or mental health impairment compared to the general population in the U.S. This group also had more limitation in functional activity due to poor health. “Our findings indicate that adult survivors of ALF have reduced quality of life compared to those of similar age and gender in the general population,” concludes Dr. Fontana. “Additional investigations of brain function by our team are underway to further understanding of the type and severity of cognitive impairment reported by ALF survivors.”

This current study was funded in part by a grant from the National Institute of Diabetes, Digestive and Kidney Diseases (DK U-01-58369) to the United States Acute Liver Failure Study Group (ALFSG), which is led by Dr. William Lee, Professor of Internal Medicine at UT Southwestern Medical Center in Dallas. ALFSG is a National Institutes of Health-funded consortium of investigators in the United States focused on studying acute liver failure.

View the abstract for this article on Wiley Online Library

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Liver stiffness more predictive of decompensation than biopsy results in HIV/HCV coinfection

Provided by Healio

July 9, 2013

Liver stiffness measurement is similarly predictive of overall mortality and more predictive of decompensation than liver biopsy results among patients with HIV/HCV coinfection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated 297 patients coinfected with HCV and HIV who underwent liver biopsy (LB) and liver stiffness measurement (LSM) within 12 months of one another. The midway point between the procedures was considered the baseline date for analysis. Ninety-three percent of participants were receiving therapy with antiretrovirals at baseline, with undetectable plasma HIV RNA levels in 79% of cases and a median CD4 cell count of 514 cells/mcL.

Among evaluable participants after 26 cases were lost to follow-up, overall mortality across the cohort was 1.56 deaths per 100 person-years. Increased risk for death was associated with elevated LSM values (adjusted HR=1.28; 95% CI, 1.12-1.46 per 5 kPa increase) and fibrosis stage at baseline as indicated by LB (aHR=1.56; 95% CI, 1.02-2.4). Liver decompensation occurred at a rate of 1.59 cases per 100 person-years, with LSM (aHR=1.37; 95% CI, 1.21-1.54) and fibrosis stage at baseline (aHR=1.67; 95% CI, 1.15-2.43) as predictive factors.

Integrated discrimination improvement (IDI) analysis indicated that models incorporating LMS values performed 3.9% better in predicting mortality than models incorporating LB, but was not statistically significant (P=.072). For the prediction of liver decompensation, LMS-based models performed 8.4% better than LB-based models (P=.045).

“LSM-based prediction achieves a similar yield [to] LB-based models to predict overall mortality in HIV/HCV coinfected patients, and the former could better predict liver decompensations,” the researchers concluded. “LSM may replace LB as [a] prognostic tool in this setting.”

For more information:

Macías J. TUAB0104: Prediction of Survival and Decompensations of Cirrhosis Among HIV/HCV Coinfected Patients: A Comparison of Liver Stiffness Versus Liver Biopsy. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Poorer antiretroviral response among HIV patients with HBV, HCV coinfection

Provided by Healio

July 9, 2013

Patients with HIV coinfected with hepatitis B or hepatitis C virus experienced poorer outcomes from antiretroviral therapy compared with monoinfected patients in a study presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated data collected from the TREAT Asia HIV Observational Database on 7,455 patients with HIV treated at 22 Asian hospitals. All participants received antiretroviral therapy (ART), with a target HIV viral load (VL) of fewer than 1,000 copies/mL. Among patients with evaluable test results, 10.45% were coinfected with HBV and 15.2% with HCV.

After 180 days of therapy, CD4 counts were significantly lower among patients coinfected with either HBV (adjusted difference=–15.5 cells/mcL; P=.011) or HCV (aDiff=–37.8 cells/mcL; P<.001) compared with monoinfected patients after initiating ART. CD4 increases were smaller among those with HIV subtype CRF01AE compared with subtype B (–35.5 cells/mcL; P=.026).

The target VL was achieved in a median of 1.28 years within the cohort. Patients coinfected with HBV or HCV experienced a longer time to VL than monoinfected participants, but this difference was not statistically significant.

Coinfected patients had poorer survival than monoinfected patients. Multivariate analysis indicated a significant association between mortality and HCV coinfection (adjusted HR=1.81; 95% CI, 1.2-2.71). No association was observed between HIV VL and coinfection with either HBV or HCV.

“In this Asia regional HIV cohort, patients with HBV or HCV coinfection had significantly lower CD4 counts [and] smaller CD4 increases after 180 days of ART,” the researchers concluded. “We need to test, identify and initiate [highly active] ART early in HBV and HCV coinfected [patients] to have a better treatment effect.”

For more information:

Chen YMA. TULBPE13: HBV and HCV Coinfection: Long-term Immunological, Virological and Survival Outcomes Following cART. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Ancient Dinosaur Birds Were Infected With Hepatitis B

Zebra Finches are one of the birds that hold a trace of ancient hepatitis B in their genes. Photo: FurLined

July 9, 2013 1:06 pm

Want to know something sad about the great-great-great-great-…great-great-great grandparent of all modern finches, weavers, crows, jays, robins and all songbirds? She was carrying around the genes of hepatitis B. The virus that today kills around 620,000 people each year worldwide, it turns out, is old. Really old. A recent study analyzing the history of hepatitis B found that the virus was going around infecting birds at least 82 million years ago.

That ancient bird was the precursor to all modern passerines and neoavian birds and lived during the Late Mesozoic, “back when the dinosaurs were still very much alive,” says the pseudonymous blogger GrrlScientist.

Some time around 82 million years ago, says Science News, “a hepatitis B virus infected an ancient bird and got stuck in its genome.” Normally viruses evolve really quickly. But, once its genes got stuck in the genome of the ancient bird, says GrrlScientist, the rate of change for the virus’ genes “slows to the same pace as that of the host’s DNA,” meaning that scientists looking at modern birds’ genes can see what amounts to a fossilized record of the ancient hepatitis B virus. Science News:

The reconstructed Mesozoic-era virus is remarkably similar to the hepatitis B virus that infects people today, the team found.“We’ve had 82 million years of evolution, but they have the same proteins,” says Suh, who now works at Uppsala University in Sweden.

One exception is a notorious protein called X protein. The protein has been implicated in causing liver cancer and is necessary for the virus to replicate in humans. Since X protein is missing from the hepatitis B viruses that infect modern-day birds, many scientists thought that bird viruses had lost the protein during evolution. But the ancient virus doesn’t contain X protein either, which means that the bird version probably never had it, and X marked mammalian hepatitis B viruses only recently.

So, the researchers think that birds got hepatitis B first, and then it later learned to live in mammals. In the study, the scientists say that learning about the virus’ long history can help us understand how it evolved. They also say that it could help with the “in-vitro resurrection of Mesozoic hepadnaviruses.” But maybe we can skip that part.

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Boceprevir an option for patients with HIV and HCV

By: DOUG BRUNK, Ob.Gyn. News Digital Network

07/09/13

FROM THE LANCET INFECTIOUS DISEASES

Among adults infected with both HIV and hepatitis C virus, the addition of boceprevir to a combination of peginterferon and ribavirin significantly increased the rate of sustained virological response compared with those who received placebo, results from a 44-week, multicenter phase II study demonstrated.

"Rates of SVR at follow-up week 24 were increased with boceprevir in all subgroups of patients, irrespective of demographic or baseline characteristics," researchers led by Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, reported in the July issue of the Lancet Infectious Diseases. Although SVR after treatment with peginterferon and ribavirin has been associated with improved survival, "this regimen has been relatively ineffective (SVR, 25%-30%) in patients with HIV and HCV genotype 1 infection," they wrote.

"Addition of an HCV protease inhibitor (boceprevir or telaprevir) to peginterferon-ribavirin has emerged as the standard of care for the treatment of HCV genotype 1 infection alone. Use of HCV protease inhibitors in patients infected with HIV and HCV has been restricted by the dearth of available safety and efficacy data."

For the study, which was conducted between Jan. 15 and Dec. 29, 2010, at 30 academic and nonacademic study sites, 99 adults with untreated HCV type 1 genotype infection and controlled HIV were randomized in 1:2 fashion to receive peginterferon 1.5 mcg/kg per week with weight-based ribavirin (600-1,400 mg/day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg of boceprevir three times daily (boceprevir group) for 44 weeks (Lancet Infect. Dis. 2013;13:597-605).

The primary endpoint of interest was sustained virological response (defined as undetectable plasma HCV RNA) at follow-up week 24 after the end of treatment.

Of the 99 patients, 98 received at least one treatment dose. Of these, 64 were in the boceprevir group and 34 were in the control group. The researchers reported that at follow-up week 24, 63% of patients in the boceprevir group achieved SVR, compared with 29% of controls, a difference of 33.1% that reached significance (P = .0008). Compared with controls, a higher proportion of the boceprevir group experienced adverse events, including anemia (41% vs. 26%, respectively), pyrexia (36% vs. 21%), decreased appetite (34% vs. 18%), dysgeusia (28% vs. 15%), vomiting (28% vs. 15%), and neutropenia (19% vs. 6%). In addition, 4 patients in the control group and 3 in the boceprevir group had HIV viral breakthrough, defined as two consecutive HIV RNA values of at least 50 copies/mL.

"Boceprevir did not seem to add significant risk when used in combination with peginterferon-ribavirin therapy, and no new adverse events were reported," the researchers wrote. "HIV control was well maintained in patients taking boceprevir and HIV protease inhibitors. Drug interactions between boceprevir and HIV protease inhibitors did not have a clinically significant effect on HCV response or HIV control in this study. In view of the hepatic and extrahepatic benefits associated with SVR at follow-up week 24 in patients infected with HIV and HCV, boceprevir in combination with peginterferon-ribavirin might be an important therapeutic option for patients with such coinfection."

Merck markets boceprevir under the brand name Victrelis. Merck sponsored and funded the study. Dr. Sulkowski and numerous other coauthors disclosed having received consulting fees and research grants from the company.

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Sorrento Therapeutics and Ben-Gurion University Sign an Agreement for the Development of Anti-Hepatitis C Virus Antibodies

PRESS RELEASE

July 9, 2013, 9:00 a.m. EDT

SAN DIEGO and BEER-SHEVA, Israel, July 9, 2013 /PRNewswire via COMTEX/ -- Sorrento Therapeutics, Inc. (otcqb:SRNE)(otcqb:Sorrento) and B.G. NEGEV TECHNOLOGIES AND APPLICATIONS LTD. announced today that they have entered into an option and license agreement covering several fully human anti-Hepatitis C Virus (HCV) antibody clones identified, in the laboratory of Dr. Leslie Lobel, M.D., Ph.D., from patients who have recovered from HCV infections. Sorrento plans to develop these early findings into a potential therapeutic product. This collaborative effort utilizes the respective strengths of each organization to create an important product opportunity consisting of therapeutic and/or prophylactic agents against HCV infections. Sorrento will be responsible for developing the perspective anti-HCV antibody products.

"Sorrento has already achieved many successes using its proprietary G-MAB� library to identify, characterize and develop fully human antibodies against difficult targets relevant to infectious agents. We are excited to be working with Dr. Lobel to add a program targeting HCV to our existing portfolio of therapeutic antibodies for the prevention and/or treatment of major infectious diseases", said Henry Ji, Ph.D., President and CEO of Sorrento.

"We are pleased to be collaborating with Sorrento to develop our fully human anti-HCV antibody clones into potential anti-HCV therapeutics", said Leslie Lobel, M.D., Ph.D., Professor and Vice Chair of the Department of Microbiology, Immunology and Genetics at the Ben Gurion University of the Negev.

About Hepatitis C Virus Infections

According to the Centers for Disease Control (CDC), more than 170 million people worldwide are chronically infected with HCV, including approximately 3.2 million people in the United States. The combined incidence and prevalence of HCV infection is estimated to reach over 13 million people in the United States, EU, and Japan alone, of which only 13% are estimated to be diagnosed and treated.[1] In 2009, the total annual medical costs in the United States for people with hepatitis C are estimated to reach over $30 billion. In the next 20 years, total annual medical costs are expected to increase to approximately $85 billion.[2]

HCV is spread through direct contact with contaminated blood and ultimately leads to serious liver diseases, including liver damage, cirrhosis, liver failure or liver cancer which are all long term consequences of untreated chronic HCV infection.[3] Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.[4],[5] With proper treatment, chronic hepatitis C can be cured; however, patients remain at an increased risk for progressive liver disease if they have not achieved complete viral clearance.[6],[7]

About Sorrento Therapeutics, Inc.

Sorrento Therapeutics, Inc. is a publicly-traded, development-stage biopharmaceutical company engaged in the discovery, acquisition, development and commercialization of proprietary drug therapeutics for addressing significant unmet medical needs in the Unites States, Europe and additional international markets. Sorrento Therapeutics' primary therapeutic focus is oncology but it is also developing therapeutics products for other indications, including inflammation, metabolic, and infectious diseases. Sorrento Therapeutics' proprietary G-MAB� fully-human antibody library platform was designed to facilitate the rapid identification and isolation of highly specific antibody therapeutic product candidates that bind to disease targets appropriate for antibody therapy. More information is available at www.sorrentotherapeutics.com

About Ben-Gurion University of the Negev

Created in 1969 with the mandate to bring development to the region, BGU is internationally-recognized for its unique pioneering spirit that combines outstanding academics and research with a commitment to the community. With more than 20,000 students, five Faculties and a number of internationally-acclaimed research institutes, the University has become a world leader in interdisciplinary research in cutting-edge fields that range from desert studies to nano- and biotechnology, Hebrew literature to international medicine.

About B.G. NEGEV TECHNOLOGIES AND APPLICATIONS LTD

BGN Technologies is the technology transfer company of Ben-Gurion University of the Negev, responsible for the commercialization of know-how and inventions of the University's researchers. Through the development of novel technologies and creative partnering with industry and investors, BGN brings value to the technological marketplace. BGN files worldwide patent applications and manages BGU's large patent portfolio.

Forward-Looking Statements

This press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those projected. Words such as "assumes," "plans," "believes," "expects," "anticipates," and "will," and similar expressions, are intended to identify forward-looking statements. Forward-looking statements include statements about the clinical trial results from third parties, and the preclinical and clinical development of Sorrento's human antibody therapeutics. All such forward-looking statements are based on Sorrento's current beliefs and expectations, and should not be regarded as a representation by Sorrento that any of its plans will be achieved. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in Sorrento's businesses; the scope and validity of patent protection for Sorrento's platform technologies, and the risk that the development or commercialization of product candidates may infringe the intellectual property rights of others; the potential that Sorrento may require substantial additional funding in order to obtain regulatory approval for and commercialize Sorrento's proprietary G-MAB� fully-human antibody library platform technologies or product candidates; and additional risks set forth in Sorrento's filings with the Securities and Exchange Commission. These forward-looking statements represent Sorrento's judgment as of the date of this release. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Sorrento undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

[1] BioMedTracker, DataMonitor, 2013.[2] Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009[3] Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010.[4] Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009; 50(6):1750-1755.[5] Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012; 156:271-278.[6] Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008; 50(Suppl 4):357A (Abstract 115).[7] Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

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SOURCE Sorrento Therapeutics, Inc.

Comparing East vs West in Hep C Patient Understanding

Provided by Eye for Pharma

Posted by Mary Assimakopoulos on Jul 8, 2013

In this month’s column we look at Hepatitis C and examine the differences (and similarities) between the causes of non-adherence in China and the US.

In this month’s column we look at Hepatitis C, an infectious disease spread mainly by blood-to-blood contact which affects the liver. We recently conducted research amongst Hep C sufferers in China and the USA. Although there are differences in the way patients from these countries feel about their disease and their experiences of having Hep C, they share commonalities in terms of the problems they encounter on their patient journey.

First of all, because Hep C often remains asymptomatic for many years, the virus can go undetected for a long time. We found that only 16% of US patients and just 4% of China patients seek direct help because they suspect they might have caught an infectious disease. Only a third of patients are aware that by participating in high-risk activities such as sexual activity and intravenous drug use they could be putting themselves at risk.  The majority of patients in both markets are diagnosed through routine blood tests or a blood test given for other reasons (for example, blood tests are required in China when getting married or joining the army). This means that many patients fail to present until they are at a more advanced stage in their illness. It also means that diagnosis can come as quite a shock.

Patients in the USA are concerned about passing the virus onto others and the long-term effect having Hep C will have on their health. Christopher, 50, from the US was diagnosed nearly 10 years ago. He openly admits he was a heavy drug user, and knows this was his route of infection. He says, “a few years after my diagnosis, I really started to see the signs of the hepatitis C. I didn’t realise how much it would affect me”. He is suffering adversely with his disease and has fatigue, pain associated with his liver and severe depression. When talking about this, he says, “I was depressed anyway, but I didn’t want to be this depressed. I can’t work anymore and sometimes I cannot do simple things in the day. I just want to go back to how I used to be, living a full life.”

“‘I feel other people discriminate against me […] I find it hard to communicate with other people’”

In China, patients are more concerned about people finding out about their illness and being treated differently. One patient we spoke to who had contracted Hep C from an infected syringe when donating blood, said that friends and colleagues were unwilling to come close to him or eat with him at work. He said“I feel other people discriminate against me … On the one side I can’t get close to others as I am afraid I’ll infect them and on the other side they are also afraid I will infect them... I find it hard to communicate with other people”.

Secondly, our research found that even when diagnosed, many patients are not necessarily being treated. There are two reasons for this. In the US, patients are being “warehoused” whilst they wait for new treatments to be made available. A new generation of protease-inhibitors (PIs) which come with fewer side effects are currently in the final phases of development. A range of interferon-free regimens are also being developed, which will be even less invasive. Many physicians are encouraging patients to wait for these new drugs to become available, if appropriate, before starting treatment. For example, George, 69, from the USA, is not currently being treated as his doctor has encouraged him to wait until new products are available to him. He says, “My doctor tells me to hold the fort as there is something for me in the pipeline.”

In China, these new drugs will not be launched for some time. Patients are not being treated because they feel their symptoms are currently “too mild”. Zhang-Wei, 30, from China, was diagnosed with HCV 12 years ago, after contracting it through drug use. He is quite content about not receiving treatment (a joint decision between him and the doctor) as he is pleased to be able to save his money. He says he would only change this attitude if his condition worsened. He says, “when my condition gets worse, I know I have to receive treatment. My doctor will discuss the treatment with me, and I know I will have to accept it in order to live.”

“Pharma companies with Hep C treatments have a number of opportunities to influence patient outcomes at key stages in the patient journey”

The decision not to start treatment is understandable. The treatment programme is very intensive and comes with many side effects, and we highlight this as the third roadblock to effective outcomes. The treatment programme lasts a long time and carries a high pill burden. Patients have to be prepared to experience chronic fatigue, muscle ache, depression and anxiety, insomnia and headaches. For patients in China, who may also be self-pay, treatment also carries a high cost burden. If a patient is not covered by private medical insurance, they may be unable to afford it. Unsurprisingly, many patients in our survey had not been able to comply with the programme at some stage, with one quarter of US patients and one third of patients in China stating that the side effects had been worse than they expected.

Pharma companies with Hep C treatments have a number of opportunities to influence patient outcomes at key stages in the patient journey. They can help to raise awareness about the disease so that people present earlier. Increased awareness could also help to break down misconceptions about Hep C and reduce the discrimination experienced by patients who have been diagnosed, particularly in China.  They can help physicians educate recently diagnosed patients about their illness and about the benefits of undergoing treatment. To influence earlier treatment they should be mindful that both the patient and the physician will make decisions about treatment, and both will need to be convinced of the benefit of doing so. Finally, pharma can help physicians set expectations about the treatment programme and ensure that patients have a support network in order to help them adhere over a long period. For patients in China, pharma has to convince the patient of both the benefits of treatment and of the effectiveness of the drug they are given in order to convince them to spend money on it. They may need to work with financiers in putting together a payment programme to help patients overcome affordability issues.

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Contact Mary Assimakopoulos marya@researchpartnership.com for more information.

Living with Hep C is an online patient survey which was undertaken amongst 611 patients diagnosed with Hep C in the USA and China. In-depth follow-up interviews were conducted with a small sample of patients in both markets. The survey was carried out by the Research Partnership.

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Coffee Reduces Risk for Hepatocellular Carcinoma: An Updated Meta-Analysis

Clin Gastroenterol Hepatol. 2013 May 6. pii: S1542-3565(13)00609-5. doi: 10.1016/j.cgh.2013.04.039. [Epub ahead of print]

Bravi F, Bosetti C, Tavani A, Gallus S, La Vecchia C.

Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy; Department of Clinical Sciences and Community Health, Università degli Studi di Milan, Milan, Italy.

Abstract

BACKGROUND & AIMS: Coffee consumption has been proposed to reduce risk for hepatocellular carcinoma (HCC). We performed a meta-analysis of articles published through 2012 to provide updated information on how coffee drinking affects risk for HCC.

METHODS: We performed a PubMed/MEDLINE search of the articles published from 1966 through September 2012 for original articles, in English, on case-control or cohort studies that associated coffee consumption with liver cancer or HCC. We calculated the summary relative risk (RR) for any, low, and high consumption of coffee vs no consumption. The cut-off point for low vs high consumption was set to 3 cups per day in 9 studies and 1 cup per day in 5 studies.

RESULTS: The summary RR for any coffee consumption vs no consumption was 0.60 from 16 studies, comprising a total of 3153 HCC cases (95% confidence interval [CI], 0.50-0.71); the RRs were 0.56 from 8 case-control studies (95% CI, 0.42-0.75) and 0.64 from 8 cohort studies (95% CI, 0.52-0.78). Compared with no coffee consumption, the summary RR was 0.72 (95% CI, 0.61-0.84) for low consumption and 0.44 (95% CI, 0.39-0.50) for high consumption. The summary RR was 0.80 (95% CI, 0.77-0.84) for an increment of 1 cup of coffee per day. The inverse relationship between coffee and HCC risk was consistent regardless of the subjects' sex, alcohol drinking, or history of hepatitis or liver disease.

CONCLUSIONS: Based on a meta-analysis of 16 studies, the RR for any coffee consumption vs no consumption is 0.60. The association might partly or largely exist because patients with liver and digestive diseases reduce their coffee intake. However, coffee has been shown to affect liver enzymes and development of cirrhosis, and therefore could protect against liver carcinogenesis.

Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 23660416 [PubMed - as supplied by publisher]

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