Friday, November 27, 2015

Functional Human Liver Cells Grown in the Lab

Functional Human Liver Cells Grown in the Lab


German-Israeli partnership develops a library of highly functional liver cells from varying genetic backgrounds for scientific, clinical and pharmaceutical development
In new research appearing in the prestigious journal Nature Biotechnology, an international research team led by The Hebrew University of Jerusalemdescribes a new technique for growing human hepatocytes in the laboratory. This groundbreaking development could help advance a variety of liver-related research and applications, from studying drug toxicity to creating bio-artificial liver support for patients awaiting transplantations.

The liver is the largest internal organ in the human body, serving as the main site of metabolism. Human hepatocytes – cells that comprise 85% of the liver – are routinely used by the pharmaceutical industry for study of hepatotoxicity, drug clearance and drug-drug interactions. They also have clinical applications in cell therapy to correct genetic defects, reverse cirrhosis, or support patients with a liver-assist device.

Regrettably, while the human liver can rapidly regenerate in vivo, recognized by the ancient Greeks in the myth of Prometheus, this capability to proliferate is rapidly lost when human cells are removed from the body. Thus far, attempts to expand human hepatocytes in the laboratory resulted in immortalized cancer cells with little metabolic function. The scarce supply of human hepatocytes and this inability to expand them without losing function is a major bottleneck for scientific, clinical and pharmaceutical development.

To address this problem, Prof. Yaakov Nahmias, director of the Alexander Grass Center for Bioengineering at the Hebrew University of Jerusalem, partnered with leading German scientists at upcyte technologies GmbH(formerly Medicyte) to develop a new approach to rapidly expand the number of human liver cells in the laboratory without losing their unique metabolic function.

Based on early work emerging from the German Cancer Research Center (DKFZ) on the Human Papilloma Virus (HPV), the research team demonstrated that weak expression of HPV E6 and E7 proteins released hepatocytes from cell-cycle arrest and allowed them to proliferate in response to Oncostatin M (OSM), a member of the interleukin 6 (IL-6) superfamily that is involved in liver regeneration. Whereas previous studies caused hepatocytes to proliferate without control, turning hepatocytes into tumor cells with little metabolic function, the researchers carefully selected colonies of human hepatocytes that only proliferate in response to OSM. Stimulation with OSM caused cell proliferation, with doubling time of 33 to 49 hours. Removal of OSM caused growth arrest and hepatic differentiation within 4 days, generating highly functional cells. The method, described as the upcyte© process (upcyte technologies GmbH), allows expanding human hepatocytes for 35 population doubling, resulting in 1015 cells (quadrillion) from each liver isolation. By comparison, only 109 cells (billion) can be isolated from a healthy organ.

“The approach is revolutionary,” said Dr. Joris Braspenning, who led the German group. “Its strength lies in our ability to generate liver cells from multiple donors, enabling the study of patient-to-patient variability and idiosyncratic toxicity.” The team generated hepatocyte lines from ethnically diverse backgrounds that could be serially passaged, while maintaining CYP450 activity, epithelial polarization, and protein expression at the same level as primary human hepatocytes. Importantly, the proliferating hepatocytes showed identical toxicology response to primary human hepatocytes across 23 different drugs.

“This is the holy grail of liver research,” said Prof. Nahmias, the study’s lead author. “Our technology will enable thousands of laboratories to study fatty liver disease, viral hepatitis, drug toxicity and liver cancer at a fraction of the current cost.” Nahmias noted that genetic modifications preclude using the cells for transplantation, “but we may have found the perfect cell source for the bio-artificial liver project.”

The proliferating hepatocyte library was recently commercialized by upcyte technologies GmbH (Hamburg, Germany), which is expanding the scope of the technology. “upcyte© hepatocytes represent the next generation of cell technology”, said Dr. Astrid Nörenberg, the company’s managing director. “We are poised to become the leading cell supplier for pharmaceutical development and chemical toxicity testing.”

Yissum, the Research and Development Company of the Hebrew University, and upcyte technologies GmbH submitted a joint patent application earlier this year and are actively seeking investment.

Collaborating researchers on this study are affiliated with the Alexander Grass Center for Bioengineering, The Hebrew University of Jerusalem; upcyte technologies GmbH; Tel Aviv Sourasky Medical Center and Tel-Aviv University.

Support for this research came from the Förderprogram Biotechnologie Baden-Würtenberg (project N° 720.830-4-03), European Research Council Starting Grant TMIHCV (project N° 242699), HeMiBio: a jointly funded consortium by the European Commission and Cosmetics Europe as part of the SEURAT-1 cluster (project N° HEALTH-F5-2010-266777) and ReLiver a European Union Seventh Framework Program (FP7/2007-2013) under grant agreement n° 304961.

CITATION: Long-term culture and expansion of primary human hepatocytes. Gahl Levy, David Bomze, Stefan Heinz, Sarada Devi Ramachandran, Astrid Noerenberg, Merav Cohen, Oren Shibolet, Ella Sklan, Joris Braspenning & Yaakov Nahmias. Nature Biotechnology (2015) doi:10.1038/nbt.3377.

Wednesday, November 25, 2015

HCV: 4 Weeks Too Short for Treatment With New Drugs

Medscape Medical News

HCV: 4 Weeks Too Short for Treatment With New Drugs
Veronica Hackethal, MD
November 24, 2015

Four weeks of triple or quadruple combination therapy using new drugs for hepatitis C virus (HCV) results in only limited cure rates in patients with early-stage liver fibrosis, according to a study published online November 23 in the Annals of Internal Medicine.

"In this proof-of-concept study involving treatment-naive noncirrhotic patients with chronic HCV genotype 1 infection, 4 weeks of treatment with ledipasvir, sofosbuvir, and GS-9451 with or without GS-9669 was well-tolerated; however, only 30% (15 of 50) of patients achieved [a sustained viral response at 12 weeks]," write Anita Kohli, MD, from the University of Maryland, Baltimore, and colleagues "Thus, a treatment duration of 4 weeks with 3 or 4 potent [direct-acting antivirals] is not sufficient to cure HCV infection in most patients."

Current treatment regimens for HCV require 12 or more weeks of therapy. Shorter-term regimens have the potential to simplify therapy, increase adherence, reduce toxicity, and increase cost-effectiveness.

A previous study with the investigational drugs GS-9451 (a protease inhibitor) and GS-9669 (a nonnucleoside polymerase inhibitor), combined with ledipasvir and sofosbuvir, showed a sustained viral response rate of 95% (39 of 40 patients) in just 6 weeks.

To try to abbreviate therapy further, Dr Kohli and colleagues designed the current trial. The open-label nonrandomized phase 2a trial took place at the National Institutes of Health Clinical Center in Bethesda, Maryland, from January 2014 to May 2015. It included mostly African Americans (76%; 38/50), who are disproportionately affected by the HCV epidemic. Participants had not been previously treated and had early-stage liver fibrosis. Most were male (72%; 36/50) and had HCV 1a genotype (68%; 34/50).

Researchers divided participants sequentially into two groups. Twenty-five participants received a triple drug regimen of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks. The second group of 25 participants received the four-drug regimen of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks. Dosages included ledipasvir 400 mg and sofosbuvir 90 mg as a single combination tablet taken once daily, GS-9451 80 mg once daily, and GS-9669 250 mg once daily. All but one patient completed the trial.

Among participants in the triple-drug group, 10 patients (40%; 95% confidence interval [CI], 21% - 61%) reached a sustained viral response at 12 weeks, defined as unquantifiable HCV RNA levels at week 12, as did five patients (20%; 95% CI, 7% - 41%) in the four-drug group.

At baseline, 10 participants had HCV variants that increased resistance to at least one of the antivirals in the study. All these participants experienced viral relapse.

Adverse events, mostly mild, occurred among 48% (12/25) of patients in the triple-drug group and 72% (18/25) in the four-drug group. None of the patients discontinued therapy because of adverse events.

Lower baseline viral load, younger age, HCV genotype 1b, and absence of resistance mutations were linked to increased likelihood of a sustained viral response at 12 weeks. This subgroup may achieve acceptable response rates using a 4-week regimen, the authors suggest, and the possibility warrants further investigation.

"Our data suggest that for most patients, a treatment duration longer than 4 weeks is required to achieve [a sustained viral response]," they conclude. "However, some patients are capable of achieving [a sustained viral response] with 4 weeks of therapy, which could be attributable to the presence of several favorable factors, such as early fibrosis, low viral burden, and absence of [resistance-associated variables]."

The nonrandomized nature of the study and small sample size could have limited the study.

One or more coauthors reports research agreements, grants, personal fees, and/or stock ownership in one or more of the following: National Institutes of Health, Gilead Sciences, Merck, Pfizer, Johnson & Johnson, and Bristol-Myers Squibb. Two coauthors were employees of Gilead Sciences.

Ann Intern Med. Published online November 24, 2015. Abstract

Sofosbuvir, Velpatasvir Promising in Several Hep C Genotypes
New Treatments Not Enough to Eliminate Hepatitis C
Viekira Pak Results Reassuring for Compensated Cirrhosis

Keeping Up With Rapid Advances in Hepatitis C Treatment

Keeping Up With Rapid Advances in Hepatitis C Treatment 

Pharmacy Practice News

At the 2015 American College of Clinical Pharmacy’s Global Conference on Clinical Pharmacy, Linda Spooner, PharmD, BCPS (AQ-ID), FASHP, a professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences University, in Worcester, provided an overview of what pharmacists need to know.
Drug interaction assessments are critical, because some of the new medications won’t work when taken with certain drugs. For example, the fixed-dose combination ombitasvir-paritaprevir-ritonavir plus dasabuvir (Viekira Pak, AbbVie) is most susceptible to drug interactions with immunosuppressants and antiretroviral therapy, mainly due to the influence of ritonavir on multiple enzymes (Ann Pharmacother 2015;49[6]:674-687).


Hepatitis C - NICE publishes final drug recommendations for the treatment of four separate medical conditions

NICE publishes final drug recommendations for the treatment of four separate medical conditions

The National Institute for Health and Care Excellence (NICE) has published its final recommendations on whether six different drug treatments should be routinely funded by the NHS.

Each piece of guidance looked at the cost-effectiveness of a particular drug to treat a specific medical condition. They cover major depressive disorder, hepatitis C, melanoma and psoriasis.

Vortioxetine for the treatment of major depressive disorder

NICE recommends vortioxetine be made available as a third-line treatment for major depressive episodes. 

Vortioxetine (marketed as Brintellix by Lundbeck and Takeda) should be considered as a treatment option for adults whose condition has responded inadequately to two antidepressants within the current episode.

New options for hepatitis C

NICE recommends three new treatments for some adults with hepatitis C:
Ledipasvir-sofosbuvir (Harvoni, Gilead Sciences)
Ombitasvir-paritaprevir-ritonavir with or without dasabuvir (Viekirax with or without Exviera, Abbvie)
Daclatasvir (Daklinza, Bristol-Myers Squibb)

It is recommended that the decision to treat and prescribing decisions are made by multidisciplinary teams in the operational delivery networks put in place by NHS England, to prioritise treatment for people with the highest unmet clinical need.

Pembrolizumab for the treatment of melanoma

NICE recommends pembrolizumab (also called Keytruda and manufactured by Merck, Sharp & Dohme) as a treatment for some patients with advanced melanoma. It is recommended as an option in adults:
for treating advanced melanoma that has not been previously treated with ipilimumab, and
when the company provides pembrolizumab with the discount agreed in the patient access scheme.

Apremilast for the treatment of Psoriasis

NICE does not recommend apremilast (also called Otezla and manufactured by Celgene) for treating some adults with moderate to severe chronic plaque psoriasis.

People whose treatment with apremilast was funded by the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Trinity Scientists Homing in on New Hepatitis C Vaccine

Trinity Scientists Homing in on New Hepatitis C Vaccine

23 November 2015

Trinity researchers have just commenced a major new study to evaluate a new vaccine for the prevention of Hepatitis C infection in HIV patients, who are at increased risk of contracting the common infection.

Around 180 million people worldwide and an estimated 20,000 to 50,000 people in Ireland have Hepatitis C. It is a blood borne viral infection which is spread through direct contact with the blood of an infected individual and can lead to fibrosis (scarring of the liver), liver failure and cancer. Currently, there is no effective vaccine available for Hepatitis C and treatment is costly, often in the region of €50,000 per individual, lengthy, associated with side effects and is not 100% effective.

Numerous recent outbreaks of Hepatitis C in HIV-infected individuals internationally have highlighted the urgent need for a vaccine to prevent infection. HIV-infected individuals are at increased risk of Hepatitis C infection due to similar routes of acquisition. Hepatitis C infection also progresses more rapidly to liver damage in HIV-infected individuals. Approximately 20-30% of people with HIV are co-infected with Hepatitis C.

“A safe, affordable and effective vaccine for Hepatitis C would have a huge impact on combatting Hepatitis C given the multitude of people who are unaware of their diagnosis and represent a potential source for new infections,” said Dr Ciaran Bannan, a research fellow in Trinity College Dublin and the Department of GU Medicine and Infectious Diseases at St James’ Hospital who is leading the research with Professor Colm Bergin, Clinical Professor of Infectious Diseases, School of Medicine.

The study, which is the first phase-1 vaccine study in HIV infected people in Ireland, is also the first of a planned number of early intervention studies to be carried out in the Wellcome Trust-HRB Clinical Research Facility, a joint enterprise between Trinity College Dublin and St James’s Hospital.

The research team are evaluating the safety and the ability of a new vaccine to produce an immune response against Hepatitis C. Previous healthy volunteer studies in the University of Oxford have shown encouraging results. If effective, this vaccine could also be made available to other high risk groups such as intravenous drug users.

The study, which will run for 20 months, will follow 20 patients have in Dublin and St Gallen, Switzerland. Patients will be given two vaccines eight weeks apart and then followed closely to assess safety and the development of immune responses to Hepatitis C following vaccination. The vaccines being tested in this study are called AdCh3NSmut1 and MVA-NSmut and have been developed by ReiThera Srl and GlaxoSmithKline Biologicals SA.

This study is the result of collaboration between the University of Oxford, Kantonsspital, St. Gallen and GlaxoSmithKline Biologicals SA and has been funded by an EU Seventh Framework Program (FP7) grant.

Tuesday, November 24, 2015

AbbVie's TECHNIVIE™ Receives Health Canada Approval for Genotype 4 Chronic Hepatitis C Infection

AbbVie's TECHNIVIE™ Receives Health Canada Approval for Genotype 4 Chronic Hepatitis C Infection

TECHNIVIE provides an opportunity to treat adults who have genotype 4 (GT4) chronic hepatitis C virus (HCV) infection without cirrhosis, a population historically considered difficult-to-treat

TECHNIVIE is the first and only all-oral, interferon-free, direct-acting antiviral treatment approved in Canada for adult patients with GT4 chronic HCV infection

Approval is supported by a Phase II clinical trial of 135 chronic HCV GT4 patients, which demonstrated 100 percent sustained virologic response rates at 12 weeks post-treatment (SVR 12) in patients who took TECHNIVIE with ribavirin (RBV)

MONTREAL, Nov. 24, 2015 /CNW/ - AbbVie, a global, biopharmaceutical company, today announced that Health Canada granted a Notice of Compliance (NoC) to TECHNIVIE (ombitasvir/paritaprevir/ritonavir tablets) in combination with ribavirin (RBV) for the treatment of adults with genotype 4 (GT4) chronic hepatitis C virus (HCV) infection without cirrhosis who are either treatment naïve or previously treated with peginterferon and ribavirin.

"Over the last several years, there has been a major focus on hepatitis C genotype 1 disease. The optimal protocol for treating hepatitis C genotype 4 patients was not well defined. As a practicing hepatologist, I am thrilled that finally there is a cure for people living with hepatitis C genotype 4, which is relatively hard to eradicate," explains Dr. Magdy Elkhashab, Gastroenterologist/Hepatologist, Director of the Toronto Liver Centre. "This new therapy, which is given orally, can cure the disease in genotype 4 patients in almost 100% of cases. These are really exciting times. When I started my practice 20 years ago, I saw cure rates of 4 to 6%. I can truly say that I have seen the whole hepatitis C story unfold."

HCV GT4 has historically been difficult to treat. Egypt has the highest prevalence with more than 90% of infections due to genotype 4. Genotype 4 has been spreading in several Western countries, including Canada, due to variations in population structure, immigration, routes of transmission, travel and tourism. 1,2

"The approval of TECHNIVIE by Health Canada is further proof of AbbVie's ongoing commitment to help address the burden of hepatitis C. We are determined to provide best-in-class solutions for people living with hepatitis C in Canada, especially through our support program AbbVie Care," said Stéphane Lassignardie, general manager, AbbVie Canada.

Virologic cure is defined as a sustained virologic response (SVR), which is when the virus is no longer detectable in the patient's blood 12 weeks after treatment (SVR12).3

About the PEARL-I Study
This approval of TECHNIVIE is based on data from the PEARL-I study, which demonstrated 100 percent sustained virologic response rates at 12 weeks post-treatment (SVR12) in patients who received TECHNIVIE and RBV for 12 weeks. PEARL-I is an open-label Phase 2b study that evaluated the efficacy and safety of TECHNIVIE in GT4 chronic HCV patients without cirrhosis. The study included GT4 patients who were new to therapy (n=42/42) or who had failed previous treatment with pegylated interferon (pegIFN) and RBV (n=49/49). Additionally, 91 percent of patients who were new to therapy achieved SVR12 (n=40/44) after taking TECHNIVIE without RBV. In the treatment-naïve group without RBV, on-treatment virologic failure was reported in one patient (two percent), and two patients (five percent) experienced post-treatment relapse. There were no virologic failures in the other treatment arms.

There were no discontinuations due to adverse events in these patients. The most commonly reported treatment-emergent adverse events (greater than 10 percent) observed in patients receiving TECHNIVIE with RBV were asthenia, fatigue, and headache.

TECHNIVIE is an all-oral antiviral treatment consisting of the fixed-dose combination of ombitasvir/paritaprevir/ritonavir (12.5/75/50 mg) taken as 2 tablets once daily and taken with food, which is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice daily), taken with food. The combination of two direct-acting antivirals, each with distinct mechanisms of action, targets and inhibits specific HCV proteins in the viral replication process.

About AbbVie Care
Canadians prescribed TECHNIVIE will have the opportunity to be enrolled in AbbVie Care, AbbVie's signature care program. AbbVie Care provides support to people living with hepatitis C. The program is designed to provide a wide range of customized services including reimbursement and financial support, pharmacy services coordination with pharmacies trained in hepatitis C, lab work reminders and coordination, personalized education and ongoing disease management support throughout the treatment and beyond.

For more information, call 1-844-471-CARE (2273) or consult

Important Safety Information4

TECHNIVIE (ombitasvir/paritaprevir/ritonavir tablets) is a prescription medicine used with ribavirin to treat adults with genotype 4 chronic (lasting a long time) hepatitis C (hep C) virus infection without cirrhosis.

To help avoid side effects and make sure you are using your medicines correctly, talk to your doctor before you take TECHNIVIE. Talk about any health problems you may have, including if you:
are taking birth control medicines of any kind or using a medicine that has ethinyl estradiol. Ethinyl estradiol is usually found in birth control pills. However, not all birth control pills have ethinyl estradiol. You must not use medicines that have ethinyl estradiol while taking TECHNIVIE. Your doctor will ask you to stop or change to a different type of birth control while you are taking TECHNIVIE.
have had a liver transplant.
have liver problems other than HCV infection.
are breastfeeding or plan to breastfeed. It is not known if TECHNIVIE passes into your breast milk. You and your doctor should decide if you will take TECHNIVIE or breastfeed. You should not do both.

Pregnancy and Birth Control
Females must have a negative pregnancy test before starting TECHNIVIE and ribavirin, every month while on the medicine, and for 6 months after stopping them.
You or your partner should not become pregnant while taking TECHNIVIE with ribavirin and for 6 months after you have stopped taking them.
You and your partner must use 2 kinds of birth control while taking TECHNIVIE and ribavirin and for 6 months after you have stopped taking them.
Talk to your doctor about the kind of birth control that you can use.
If you or your partner becomes pregnant while taking TECHNIVIE and ribavirin or within 6 months after you stop taking them, tell your doctor right away.

Other warnings you should know about:
Rises in liver tests have occurred when TECHNIVIE was taken in studies. Contact your doctor right away if you have symptoms like those listed below since these may mean you have a serious problem with your liver:
loss of appetite (do not feel like eating),
stomach ache,
nausea (feeling sick in the stomach),
feeling tired or weak,
yellowing of the skin and eyes,
dark urine and pale stool.

It is not known if taking TECHNIVIE is safe or will work in children under 18 years of age.
Your doctor may do blood tests before you start taking, and while you are on your medicines. This is to help check if the medicines are working for you.

Tell your doctor all the medicines, drugs, vitamins and minerals, natural supplements or alternative medicines you are already taking, as interactions are possible with TECHNIVIE.

The complete TECHNIVIE Product Monograph is available on the manufacturer's, or by calling 1-888-704-8271.

Additional information about AbbVie's chronic hepatitis C clinical program can be found

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit and Follow @abbvieon Twitter or view careers on our Facebook or LinkedIn page.

Accessed on November 10, 2015

2 PUBMED. Hepatitis C genotype 4: What we know and what we don't yet know. Kamal SM, Nasser IA.
Accessed on November 10, 2015

3 AASLD/IDSA/IAS–USA. When and in Whom to Initiate HCV Therapy.

Accessed on November 10, 2015

4 TECHNIVIE (ombitasvir/paritaprevir/ritonavir tablets) Product Monograph. Date of Preparation:October 20, 2015
Accessed on November 10, 2015

Monday, November 23, 2015

Expensive drugs that cure hepatitis C are worth the cost, even at early stages of liver fibrosis

Related: November 2015 Updates
Reducing the cost of new hepatitis C drugs
An index of articles pointing the reader to the current controversy over the high price of Sovaldi, Harvoni (ledipasvir/sofosbuvir) and AbbVie Viekira Pak.

Expensive drugs that cure hepatitis C are worth the cost, even at early stages of liver fibrosis


It is worthwhile to give patients expensive new drugs that can cure their hepatitis C much earlier than some insurers are now willing to pay for them, according to a UC San Francisco study that models the effects of treating the disease early versus late in its development.

Researchers said they were surprised by the findings, since the drugs can cost up to $100,000 for a full course of treatment. But when they factored in the long-term medical cost of delaying treatment for hepatitis C, they found the savings, in combination with improvements in the quality of patients' lives, were enough under current standards to justify using them even at early stages of liver fibrosis. Researchers said the drugs were therefore cost effective.

Cost effectiveness is a measure of broad social benefit that health economists use to make decisions about whether medical treatments are warranted. The researchers said the balance was tipped in favor of the drugs because the hepatitis C virus can cause so much damage. Hepatitis C is one of the leading causes of liver cancer, liver transplants and liver-related death, yet the drugs can prevent much of that with an early cure. Moreover, even if costly hepatitis C treatments are delayed, they eventually will be given to many patients once the infection causes enough damage to their livers.

About 3.2 million people have hepatitis C in the United States. The vast majority were infected by blood transfusions before testing of blood donors became available in 1992. Today, most people get infected from injecting drugs.

Left unchecked, hepatitis C causes varying degrees of liver fibrosis in a majority of those infected, and causes cirrhosis in 20 to 30 percent. This damage is classified in five stages of increasing severity, from zero to four. Using sofosbuvir-ledipasvir, which is sold as Harvoni, and is one several new drugs for hepatitis C, researchers compared the costs of treating patients at all stages of fibrosis, zero through four, with the cost of waiting until stages three or four, which is when some patients are usually treated.

They found that, at current drug prices, treating half of those who are currently infected and are aware of their status but have not yet been treated would cost about $53 billion over five years, while treating these patients only at stages three and four would cost $30 billion. Since many of those patients are likely to be given the drugs at later stages of their disease, much of this cost is likely unavoidable, even if it gets delayed. But treating people early would at least avoid the costs of treating the damage from long-term infection. Researchers estimated the lifetime health care savings from treating all stages of liver fibrosis, compared to treating just three and four, at $3.3 billion.

"The budgetary implications of widespread treatment are quite large at current drug prices," said James G. Kahn, MD, MPH, a professor in the UCSF department of epidemiology and biostatics, as well as medicine. "However, these costs are time-limited, and they are lower than some other treatments that are less effective. In the U.S., we spend more than $140 billion a year treating cancer, often with less health benefit than is provided by the new hepatitis C treatments."

The researchers said it was important to broaden the discussion beyond cost-effectiveness, to include the price of drugs.

"The benefits of early therapy are significant, since it increases the number of healthy life years for patients and decreases their chances of getting serious liver diseases, like liver failure and liver cancer," said Harinder Chahal, PharmD, MSc, an assistant adjunct professor in the UCSF department of clinical pharmacy. "But the current prices are keeping early treatment out of reach for many patients, and this needs to be addressed."


Other authors include Rena Fox, MD, and Jeffrey Tice, MD, of UCSF; Elliot Marseille, PhD, of Health Strategies International; and Daniel Ollendorf, PhD, and Steve Pearson, MD, MSc, of the Institute for Clinical and Economic Review in Boston.

The study was supported by the Blue Shield of California Foundation, the California Health Care Foundation, the UCSF Clinical and Translational Sciences Institute and the National Institute on Drug Abuse.

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospital San Francisco. Please visit

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