Sunday, December 31, 2017

Problems and potential with probiotics

ACP InternistConference Coverage | January 2018
Problems and potential with probiotics
By Mollie Durkin
Probiotics are becoming more prevalent in both consumer and health care settings, but the excitement is tempered by problems, including how to define what is and what isn't one.

Researchers also face regulatory challenges to studying probiotics, Dr. Hibberd said. The FDA's current approach to probiotics is that, when they are intended to prevent, mitigate, or cure any disease, they are considered a drug or biologic, subject to approval and regulation.

On the other hand, if the purported health benefit is structure or function (e.g., digestive health), the products do not need regulatory approval. “Consequently, this is why we hear mostly about what's called structure/function claims that really are unhelpful in terms of thinking about when and which [probiotics] to use,” she said.

Another issue is that some probiotic products in grocery stores may list unheard-of organisms. “Some of the ‘strains' in these products are actually not real bacteria at all; they are commercial names,” Dr. Hibberd said. “So that also makes things a lot more complicated.”

Women receive more inpatient resections and ablations for hepatocellular carcinoma than men

World J Hepatol. Dec 28, 2017; 9(36): 1346-1351
Published online Dec 28, 2017. doi: 10.4254/wjh.v9.i36.1346

This study shows gender differences for the inpatient management of HCC. Women are still more likely to undergo resection which is consistent with prior publications. This study also determined that women are more likely to undergo ablation. Women may be more likely to undergo these procedures because of functional status, compensated disease, and increased likelihood of undergoing screening exams that allow them to be diagnosed earlier. Despite advances in treatment of HCC, females are more likely to receive curative treatment with resection and ablation.


Women receive more inpatient resections and ablations for hepatocellular carcinoma than men 
Lindsay Sobotka, Alice Hinton, Lanla Conteh

Introduction
The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. In 2016, it is estimated that more than 35000 people in the United States will be diagnosed[1]. The diagnosis has tripled since the 1980s. Men are three times as likely to be diagnosed with HCC as women[2]. Once diagnosed with HCC, survival rates are dependent on the stage with a 5 year survival of approximately 30.5 and metastatic HCC survival of 3.1[2].

There has been an emphasis on evaluating gender disparities in healthcare; HCC is not an exception. Gender disparities in the treatment for HCC have been noted in the past, specifically in transplantation. Studies reveal that men were more likely to receive a liver transplantation during pre-Model for End Stage Liver Disease (MELD) organ allotment, while women were more likely to die while waiting for organ transplantation[3]. Other studies have concluded that women were more likely to receive resection for earlier stage disease[4].

The aim of this study is to use the Nationwide Inpatient Sample (NIS) to determine if gender disparities still exist in the inpatient treatment for HCC.

We hypothesize that gender disparities continue to exist and seek to identify potential factors associated with this disparity.

Full-Text

Hepatitis C - Treatment failures in a real-world cohort with SOF & (DCV or LDV)

Alimentary Pharmacology & Therapeutics
Version of Record online: 22 DEC 2017

Viral kinetics analysis & virological characterization of treatment failures in a real-world cohort with chronic HCV treated with SOF & an NS5A inhibitor (DCV or LDV)
S. Fourati1,2 | J. Guedj3,4 | S. Chevaliez1,2 | T. H. T. Nguyen3 | F. Roudot-Thoraval5 | I. Ruiz2,6 | A. Soulier1,2 | G. Scoazec6 | A. Varaut6 | L. Poiteau1,2 | M. Francois6 | A. Mallat6 | C. H ezode6 | J.-M. Pawlotsky1,2

Full Text

Summary Background: The combination of sofosbuvir (SOF) plus an NS5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and NS5A inhibitor are rapidly decreasing, the combination of these DAAs will be the standard treatment in most low- to middle income countries in the future.

Aim: To identify key predictors of response that can be used to tailor treatment decisions.

Methods: A cohort of 216 consecutive patients infected with HCV genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (SOF) + daclatasvir (n = 176) or SOF + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear HCV. Results: The overall SVR rate was high (94.4%; n = 204), regardless of the time to viral suppression or low-level viraemia at the end of treatment. The model-based predicted HCV RNA levels at the end of treatment could not differentiate patients who did from those who did not achieve SVR. The presence of NS5A resistance associated substitutions [position 28 (OR = 70.3, P<.001) and/or 31 (OR = 61.6, P = .002)] at baseline was predictive of virological failure in cirrhotic patients but was not associated with on-treatment viral kinetics.

Conclusion: This real-world study confirms the excellent results of clinical trials with therapies based on a combination of SOF plus an NS5A inhibitor. It suggests that a personalized approach including baseline NS5A inhibitor resistance testing may inform treatment decisions in cirrhotic patients.

Full-text article shared by @HenryEChang via Twitter

Treatment of HCV in Children - Position Paper by the Hepatology Committee of European Society of Paediatric Gastroenterology, Hepatology and Nutrition

Treatment of Chronic Hepatitis C Virus Infection in Children. A Position Paper by the Hepatology Committee of European Society of Paediatric Gastroenterology, Hepatology and Nutrition
Indolfi Giuseppe; Hierro, Loreto; Dezsofi, Antal; Jahnel, Jörg; Debray, Dominique; Hadzic, Nedim; Czubowski, Piotr; Gupte, Girish; Mozer-Glassberg, Yael; van der Woerd, Wendy; Smets, Françoise; Verkade, Henkjan J; Fischler, Bjorn

Journal of Pediatric Gastroenterology and Nutrition: Post Acceptance: December 28, 2017
doi: 10.1097/MPG.0000000000001872 

What is known 
Direct-acting antiviral drugs active against hepatitis C virus (HCV) infection are highly effective and safe for treatment of adults with chronic HCV infection.

Pegylated interferon (PEG IFN) and ribavirin are no more recommended for treatment of adults.

What is new 
The fixed-dose combination of sofosbuvir/ledipasvir and the combination of sofosbuvir and ribavirin have been recently approved for treatment of children ≥12 years or weighing >35 Kg with chronic HCV genotype 1, 4, 5 and 6 and 2 and 3 infection, respectively.

PEG IFN and ribavirin are no more recommended for treatment of children older than 12 years of age.

ABSTRACT
Objectives:
In 2017, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12–17 years, weighing more than 35 kg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5 and 6 and genotype 2 and 3 infections, respectively. Although trials with direct acting antivirals (DAAs) are ongoing for younger children, the only available treatment in US and Europe for those < 12 years is still the dual therapy of pegylated interferon (PEG IFN) and ribavirin. There is currently a lack of a systematic approach to the care of these patients. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed an evidence-based position paper for the management of chronic HCV infection in children.Methods:A systematic literature search and meta-analysis were performed using MEDLINE and Embase from June 1, 2007 to June 1, 2017. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcomes. ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.Results:The efficacy of the different DAAs combinations tested was higher, the relapse and the treatment discontinuation rates lower when compared to PEG IFN and ribavirin.Conclusions:This position paper addresses therapeutic management issues including goals, endpoints, indications, contra-indications and the optimal treatment regimen in children with chronic HCV infection.

Objectives:
In 2017, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12–17 years, weighing more than 35 kg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5 and 6 and genotype 2 and 3 infections, respectively. Although trials with direct acting antivirals (DAAs) are ongoing for younger children, the only available treatment in US and Europe for those < 12 years is still the dual therapy of pegylated interferon (PEG IFN) and ribavirin. There is currently a lack of a systematic approach to the care of these patients. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed an evidence-based position paper for the management of chronic HCV infection in children.

Methods:
A systematic literature search and meta-analysis were performed using MEDLINE and Embase from June 1, 2007 to June 1, 2017. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcomes. ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.

Results:
The efficacy of the different DAAs combinations tested was higher, the relapse and the treatment discontinuation rates lower when compared to PEG IFN and ribavirin.

Conclusions:
This position paper addresses therapeutic management issues including goals, endpoints, indications, contra-indications and the optimal treatment regimen in children with chronic HCV infection.

Article - Download PDF

Saturday, December 30, 2017

The Long Road To Safe and Effective HCV Drugs: A Tribute To The People Who Helped Us Get There

The Long Road To Safe and Effective HCV Drugs

Soon we will be ringing in the New Year, will 2018 be your best year yet? I sincerely hope so.

As for me, I had my best year in 2000, the year I successfully treated the hepatitis C virus (HCV).

A time when curing HCV wasn't the norm, today that has all changed.

Although before we look ahead, I thought we might look back. Why? So that we may never forget just how far we've come, and the people who helped us get there.

Finding Support
In the mid-1990s members from around the globe who joined various HCV online support groups shared information, we became a wide circle of close friends. In the U.S. the National Hepatitis C Coalition dedicated a memorial to those friends we lost, which began in 2000 and updated until 2012. The site is no longer online, but the memorial has been saved, you can view it, here. A lovely memorial dedicated to the memory of Canadians who have died of hepatitis C is available online as well.

Today, according to The World Health Organization (WHO); globally, an estimated 71 million people have chronic hepatitis C infection. A significant number of those who are chronically infected will develop cirrhosis or liver cancer. Approximately 399 000 people die each year from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma.

The Long Road To Safe and Effective HCV Drugs
In 1991 the FDA approved the first alfa interferon (Intron A) to treat hepatitis C, with cure rates  between 6 and 10 percent. In 1998 ribavirin was added, cure rates increased for people with HCV genotype 1 to around 23.6%. Finally, in 2001 Pegylated interferon plus ribavirin was approved, cure rates jumped to around 46%, again for genotype 1 patients.

Here in the U.S. because interferon was an injectable, some of us were put through a mound of paperwork before treatment was covered by our insurance provider. In Canada, many patients with normal ALT and AST levels were denied treatment, prompting some patients to consume alcohol before tests were administered. During that time with such low cure rates, some people treated not once, but twice, again requiring more paperwork. A summary of those triumphs, and let downs is represented in a post I keep updated, you can find it here, a record capturing past and current advances on the road to safe and effective HCV therapies.

Side Effects - We All Had Them
Both interferon and ribavirin had side effects, including flu-like symptoms, depression, weight loss, rage, joint pain, depression and other abnormalities of bloodwork; anemia, neutropenia, and thrombocytopenia (low levels of platelets). People needed rescue drugs to remain on therapy, for instance Procrit for anemia, an injectable that promotes red blood cell production and neupogen for severe neutropenia (low white blood cell count). We were confused, frightened, but determined.

Newer Agents - Better Cure Rates With Dangerous Side Effects 
Later, newer agents in clinical trials were looking better, to us anyhow. I remember how excited we were when Incivek, a drug by Vertex, administered in combination with pegylated interferon and ribavirin was FDA approved in 2011. Although side effects during clinical trials were reported, (new side effects) in particular a serious skin reaction, one that could be fatal, we were still encouraged. The SVR rates were high at the time for HCV genotype 1, at 69-75%, as mentioned, compared to Pegylated interferon plus ribavirin alone, at 46%. A large majority of people had liver damage, so treatment was a necessary evil. We didn't have a choice. We celebrated when our friends who treated previously achieved SVR, especially our sickest friends.

The Dark Side
We watched in horror as Bristol-Myers' BMS094 trials were discontinued, the drug was halted in 2012, after one person died and eight more were hospitalized. I remember corresponding with one of the trial participants who dropped out of the trial early, it was a dark time for HCV patients. Hell, the whole decade was a horrific time for patients.

The Stigma
The stigma was alive back in the day, HCV was associated with IV drug use, some of us, not all, were exposed to medical discrimination. As an example, asking for antidepressants under the influence of interferon wasn't always easy (my physician was amazing). Many of our friends in Canada, some here in the U.S. were denied treatment for up to 6 months because of past alcohol or drug use.

Not So Fast
In 2016 a study published in Lancet Infectious Diseases reported the high rate of HCV transmission in persons born between 1945 and 1965, the baby boomer generation (that would be us) was from hospital transmissions and reuse of medical injecting equipment rather than from injecting drugs. This study was important to everyone, because finally people were more likely to get tested. Let's face it, when it comes to stigma associated with HCV, we continue to run around in circles, only to end up back where we started.

Awareness
In 2012, thirteen years after I was diagnosed, HCV was recognized in the U.S. by public health organizations, and awareness with screening strategies were firmly implemented; the CDC recommend all "baby boomers" should be tested one time for HCV.

Watershed Moment
Without scientist Michael Sofia, the devolvement of safe and effective new direct-acting antiviral therapy may have taken a bit longer. Sofia, created Sovaldi, which at the time (2013) was the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3, and approved for use in genotypes 1 and 4, in combination with PEG-IFN and ribavirin. Ugh. We still needed interferon.

Big Pharma - Barriers To Treatment
Although we recognize the enormous contribution made by the pharmaceutical industry; newer HCV drugs developed by Gilead, AbbVie, Merck, and Bristol-Myers Squibb has saved millions of lives around the world. However, before we could celebrate affordability became our next nightmare, Gilead's Sovaldi was set at $84,000 per treatment (price has come down but it took five years) leaving patients with access restrictions by third party payers. Some providers and insurers may still decline treatment for people with ongoing illicit drug or alcohol use, or limit treatment to those with advanced liver disease, although these restrictions are slowly improving across the U.S.

Hepatitis C: State of Medicaid
In October of 2017, the National Viral Hepatitis Roundtable (NVHR) together with The Center for Health Law & Policy Innovation of Harvard Law School (CHLPI) launched, Hepatitis C: State of Medicaid, the document offered: An in-depth evaluation of treatment access in each state’s Medicaid program, while highlighting successes in access expansion as well as ongoing challenges. Over half of Medicaid programs received a “D” or an “F” for imposing discriminatory restrictions on hepatitis C cures.

2017 Global Hepatitis Report
WHO published the Global Hepatitis Report, 2017, outlining the baseline for the drive towards elimination. The report sets out global statistics on viral hepatitis B and C, the rate of new infections, the prevalence of chronic infections and mortality caused by these two high-burden hepatitis viruses, as well as coverage of key interventions, all current as of the end of 2015.

Treat All
According to the HCV treatment guidelines published by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society, the only contraindication to current chronic HCV treatment is in a patient with a short life expectancy that cannot be lengthened with treatment, with liver transplant, or with any other treatments.

Overtime we have learned that treating people with lower-stage fibrosis increases SVR rates, and for persons who inject drugs, adherence and efficacy rates are comparable to those of patients who do not use injected drugs. In other words, treat all.


HCV & The Opioid Epidemic
Newer trends behind the surge of hepatitis C infections in our young people is America’s growing opioid epidemic. To date six U.S. states have declared their opioid-overdose situation an emergency, according to an article recently published in The New England Journal Of Medicine, NEJM also published: The Public and the Opioid-Abuse Epidemic. In addition; Authorities Are Cracking Down on Opioid-Peddling Doctors. Over at MedPage Today Molly Walker writes about - What's Next in Infectious Diseases? reporting that the opioid epidemic will likely continue to drive new HIV and hepatitis C infections.

Disease Progression
The rate of developing cirrhosis can evolve in 10–20% of chronic hepatitis C cases over a period of 20 to 30 years. However, longer duration of infection, infected at a later age in life, alcohol consumption, HCV genotype, male sex, fatty liver disease, diabetes, and coinfection with human immunodeficiency virus (HIV) or chronic hepatitis B (HBV), increases the risk for developing cirrhosis as high as 25% to 50%. In addition, burden of disease can be significant for those people with HCV-related cirrhosis, putting them at risk for hepatocellular carcinoma, liver failure, and in some cases a need for liver transplantation. In 2013, data presented at IDWeek, reported people with hepatitis C virus (HCV) die 15 years earlier and have a 12-times greater risk of death when compared with those without the virus.

New Era Of HCV Drugs
Today we have effective drugs to cure HCV, across all six HCV genotypes, including direct-acting antiviral therapy for people with severe liver damage, such as compensated cirrhosis, or kidney disease. HCV eradication is associated with the reversal of fibrosis, improvement of fibrosis and quality of life, as well as overall reduction of liver cancer, liver failure, risk of liver transplant, and liver-related mortality, including extrahepatic manifestations of HCV in patients who achieve SVR.

More importantly the controversy over direct-acting antiviral therapy increasing the risk of developing liver cancer was addressed at The Liver Meeting 2017. At the end of 2017 Healio reported on this retrospective study that found: Liver cancer incidence after HCV therapy linked to risk factors, not treatment. Read a collection of articles on the subject, here.

On A Personal Note -Thank You
Douglas T. Dieterich, MD, Anna Suk-Fong Lok, MD, Stuart Gordon, MD, Nezam H. Afdhal, MD, Paul Kwo, MD, Mitchell Shiffman, MD, Mark Sulkowski, MD, Donald M. Jensen, MD and each person and site mentioned, here.

HCV Advocate - Our Saving Grace
I offer my sincere gratitude to the dedicated staff at HCV Advocate for providing decades of education and support. In 1999, after numerous emails back and forth to the good people at HCV Advocate, I was encouraged to seek out a specialist. In 2000 under the care of Stuart Gordon, MD and Anna Suk-Fong Lok, MD, (thank you) I entered into a clinical trial at Beaumont Hospital in Royal Oak, Michigan, and achieved my SVR status. Without the Hepatitis C Support Project the long-term effects of living with hepatitis C, for me, most certainly would have taken its toll.

Happy Anniversary HCV Advocate
HCV Advocate made a real difference in the lives of countless people across the globe, changing the course of this serious and sometimes deadly disease, one person at a time. Featured in the January 20th Anniversary Edition of HCV Advocate's Newsletter is a look back at how it all began and the people who made the Hepatitis C Support Project possible.

Wishing you all a happy and healthy New Year!
Tina

Friday, December 29, 2017

Declaring An Opioid Emergency

Audio Interview
Interview with Dr. Lainie Rutkow on legal action taken by states to address the opioid-overdose crisis. 
Lainie Rutkow is an associate professor of health policy and management at the Johns Hopkins Bloomberg School of Public Health. Stephen Morrissey, the interviewer, is the Managing Editor of the Journal. (6:55)


Six U.S. states have declared their opioid-overdose situation an emergency. Though the scope of these declarations has been limited, they could suggest additional responses to multiple facets of the crisis, especially if emergency powers are used in innovative ways.

Perspective
Emergency Legal Authority and the Opioid Crisis
Lainie Rutkow, J.D., Ph.D., M.P.H., and Jon S. Vernick, J.D., M.P.H.
N Engl J Med 2017; 377:2512-2514
DOI: 10.1056/NEJMp1710862

Opioid-overdose deaths in the United States have steadily increased for the past 15 years, with more than 33,000 such deaths reported in 2015.1 The epidemic is unfolding on two fronts: use of prescription opioid pain relievers (OPRs) accounts for approximately half of opioid-overdose deaths, and deaths from heroin and synthetic opioids such as fentanyl, obtained illicitly, have increased dramatically during the past 5 years.

In the face of this public health crisis, various policies have been enacted — particularly at the state level — often to address OPR prescribing and limit opportunities for OPR diversion. For example, all 50 states have established prescription drug monitoring programs (PDMPs) that collect information about individuals’ prescription-drug history in an electronic database. Eleven states have laws regulating pain-management clinics,2 and several states have enacted laws to limit the dosage or duration of OPR prescriptions.

Continue reading: http://www.nejm.org/doi/full/10.1056/NEJMp1710862

The State of the Opioid Crisis Ahead of 2018
By Casey Leins, Staff Writer | Dec. 28, 2017
As officials plan how to address the epidemic in 2018, here is where it stands at the end of the year.
The nation's opioid crisis reached new proportions in 2017, with provisional data revealing that there were 17 percent more deaths from drug overdoses between May 2016 and May 2017, compared to the previous year.

Though the epidemic has grown over the past few years, it reached new heights this year, forcing federal and state governments to take immediate action. In October, President Donald Trump declared a public health emergency over the crisis. Earlier in 2017, the governors of Alaska, Arizona, Florida and Maryland issued a public health emergency. Massachusetts was the first state to declare the epidemic an emergency in 2014, followed by Virginia in 2016.

Continue reading: https://www.usnews.com/news/best-states/articles/2017-12-28/the-state-of-the-opioid-crisis-ahead-of-2018

Direct medical costs associated with the extrahepatic manifestations of Hep C

In Case You Missed It

Direct medical costs associated with the extrahepatic manifestations of Hep C
January's issue of the Alimentary Pharmacology & Therapeutics examines the direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection.

Volume 47, Issue 1
January 2018
Pages 123–128

The economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France. Dr Cacoub and colleagues from France estimated the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them.

Estimates of 13 extrahepatic manifestations prevalence were obtained from a retrospective data analysis of HCV-infected patients in a specialized center, and the baseline prevalence in the general French population, and an international systematic review.

The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs. Using the first approach, the team found increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations.

The researchers observed that the mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 €. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million € per year.

Using a systematic review, the team found that the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 million € for diabetes, 8.6 million € for cryoglobulinemia vasculitis, 6.7 million € for myocardial infarction, 2.4 million € for end-stage renal disease and 1.4 million € for stroke.

Dr Cacoub's team concludes, "Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France." "HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France."
Aliment Pharmacol Ther 2017: 47(1): 123–128
22 December 2017

Direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection in France
P. Cacoub, M. Vautier, A. C. Desbois, D. Saadoun, Z. Younossi
First published: 18 October 2017

Introduction
Patients chronically infected by the hepatitis C virus (HCV) are at risk of developing major liver complications.[1] Up to two-thirds of HCV-infected patients also experienced extrahepatic manifestations that include HCV-related autoimmune and/or lymphoproliferative disorders, and cardiovascular, renal, metabolic and central nervous system diseases.[2-7] The link between extrahepatic manifestations and HCV infection has been demonstrated for many years for lymphoproliferative disorders (mixed cryoglobulinemia, lymphoma), whereas it became more recently evident for cardiovascular, renal and metabolic diseases.[4, 5] Nevertheless, HCV infection showed higher morbidity and mortality rates for extra-hepatic complications, while viral eradication reduced the rate of extra-hepatic complications and deaths.[3, 5]

New oral, interferon-free direct-acting anti-virals (DAA) offer opportunities to cure most patients.[1] Sofosbuvir plus ledipasvir has been shown to improve patient-reported outcomes after achieving sustained virological response (SVR).[8-10] As new all-oral interferon-free DAA regimens for HCV are approved, their effectiveness in a real-world setting and their economic impact on health systems and society require further assessment. Previous analyses have typically focused on the hepatic complications of HCV infection and have not considered the burden of extra-hepatic manifestations.[8, 11] There is a need to accurately characterise the burden of extrahepatic manifestations in HCV-infected patients, and the impact of achieving a SVR on the costs of managing these manifestations outside the United States.[12] The objective of this study was to estimate the annual direct medical costs associated with the extrahepatic manifestations of HCV infection in France.


Recommended Reading
Extrahepatic manifestations of HCV & Treatment

On This Blog
A collection of current research articles on ailments related to HCV
Categorized article directory on the extrahepatic manifestations of hepatitis C.

Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

World J Hepatol. Dec 28, 2017; 9(36): 1352-1360 Published online Dec 28, 2017.
10.4254/wjh.v9.i36.1352

Impact of sustained virologic response on chronic kidney disease progression in hepatitis C
Elizabeth S Aby, Tien S Dong, Jenna Kawamoto, Joseph R Pisegna, Jihane N Benhammou

AIM
To determine how sustained virological response at 12 wk (SVR12) with direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection affects chronic kidney disease (CKD) progression.

METHODS
A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates.

RESULTS
Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate (eGFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 mL/min ± 0.75 mL/min per 1.73 m2 compared to a decline in eGFR of 11.0 mL/min ± 2.81 mL/min per 1.73 m2 in patients who did not achieve SVR12 (P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in eGFR in those with untreated HCV over 2 years was 2.8 mL/min ± 1.0 mL/min per 1.73 m2, which was not significantly different from the eGFR decline noted in HCV-treated patients who achieved SVR12 (P = 0.43).

CONCLUSION
Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.

Core tip: In hepatitis C patients treated with direct acting antivirals, there is a lesser decline in renal function in those who are treated and achieved sustained virological response at 12 wk (SVR12) compared to those who do not achieve SVR12. However, the decline in renal function is no different between those who achieve SVR12 and those who are never treated. This suggests that viral eradication may not be associated improvement in the progression of renal disease and other factors, such as cryoglobulinemia, may be implicated in renal disease progression.

Efficacy and safety of Harvoni in Japanese patients aged 75 years or over with hepatitis C genotype 1

World J Hepatol. Dec 28, 2017; 9(36): 1340-1345
Published online Dec 28, 2017. doi: 10.4254/wjh.v9.i36.1340
Retrospective Cohort Study

Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75 years or over with hepatitis C genotype 1
Yoshinori Ozono, Kenji Nagata, Satoru Hasuike, Hisayoshi Iwakiri, Kenichi Nakamura, Mai Tsuchimochi, Yuri Yamada, Yuka Takaishi, Mitsue Sueta, Tadashi Miike, Yoshihiro Tahara, Shojiro Yamamoto, Kotaro Shide, Tomonori Hidaka, Yoko Kubuki, Kazunori Kusumoto, Toshimasa Ochiai, Junya Kato, Naoto Komada, Shuichi Hirono, Kazuo Kuroki, Masafumi Shigehira, Kazuya Shimoda

AIM
To evaluate the efficacy and safety of a regimen containing sofosbuvir (SOF) and ledipasvir (LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1.

METHODS
This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects (AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger (aged < 75 years) and elderly (aged ≥ 75 years). Virological data and AEs were analyzed by age group.

RESULTS
The sustained virological response (SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding.

CONCLUSION
Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.

Core tip: Most Japanese patients with hepatitis C are elderly, and those aged ≥ 75 years account for more than 50%. However there are few reports regarding sofosbuvir (SOF) and ledipasvir (LDV) therapy in patients aged ≥ 75 years in the real-world. The present study demonstrated that patients aged ≥ 75 years had a similar virological response and tolerance to SOF/LDV therapy compared with patients aged < 75 years in the real-world cohorts. Therefore, SOF/LDV therapy might be effective and safe in elderly patients.

Non-invasive tests for NAFLD are unreliable in South Asians

Non-invasive tests for NAFLD are unreliable in South Asians
Last Updated: 2017-12-27
By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Blood-test-based non-invasive tests for non-alcoholic fatty liver disease (NAFLD) are unreliable alternatives to liver biopsy in South Asians, new research suggests.

Non-invasive liver tests (NILTs) include those based on biomarkers or on clinical and laboratory data such as NAFLD fibrosis score (NFS); Fibrosis-4 (Fib-4); BMI, AST/ALT ratio, diabetes (BARD); aspartate transaminase (AST)-to-platelet ratio index (APRI); and the AST/alanine transaminase (ALT) ratio, researchers note in Frontline Gastroenterology, online November 16.

Dr. Syn cautioned, "Because the sensitivity of these commonly used tests is lower in patients of South Asian ethnicity, it suggests that a significant number of South Asian patients may be inappropriately reassured that they do not have advanced disease. As with any clinical test, there is a danger that, if a test is applied or interpreted inappropriately, wrong decisions can be made and harm may ultimately come to a patient."


Liver Research
Non-invasive markers of liver fibrosis in fatty liver disease are unreliable in people of South Asian descent
Sampath De Silva1, Wenhao Li1, Polychronis Kemos1, James H Brindley1, Jibran Mecci1, Salma Samsuddin1, Joanne Chin-Aleong2, Roger M Feakins2, Graham R Foster1, Wing-Kin Syn1,3,4, William Alazawi1

Abstract
Objective
Liver biopsy is the most accurate method for determining stage and grade of injury in non-alcoholic fatty liver disease (NAFLD). Given risks and limitations of biopsy, non-invasive tests such as NAFLD fibrosis score, aspartate transaminase (AST) to platelet ratio index, Fib-4, AST/alanine transaminase ratio and BARD are used. Prevalence and severity of NAFLD and metabolic syndrome vary by ethnicity, yet tests have been developed in largely white populations. We tested our hypothesis that non-invasive tests that include metabolic parameters are less accurate in South Asian compared with white patients.

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HCC Risk Scores: Useful or Not?

HCC Risk Scores: Useful or Not?
Morris Sherman, MBBCh, PhD, FRCP
Semin Liver Dis 2017;37:287 – 295

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Continue to article:  https://jumpshare.com/v/n3Sc7TkoqWjSO4lOqWpU

Case Report: Severe Steroid-responsive Skin Disorders Related to Harvon for HCV.

Intern Med. 2017 Dec 27. doi: 10.2169/internalmedicine.9744-17. [Epub ahead of print]

Severe Steroid-responsive Skin Disorders Related to Ledipasvir and Sofosbuvir for HCV.
Tadokoro T1, Morishita A1, Fujita K1, Oura K1, Sakamoto T1, Nomura T1, Tani J1, Yoneyama H1, Masaki T

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Abstract
Combination therapy with ledipasvir and sofosbuvir (LDV/SOF), direct-acting antiviral agents, is highly effective against hepatitis C virus genotype 1 infection. Although LDV/SOF is safer than conventional treatment, reports have indicated that LDV/SOF was discontinued in certain cases due to severe skin disorders. A 68-year-old woman presented with a rash after starting LDV/SOF treatment. We interrupted LDV/SOF and began the oral administration of prednisolone (PSL). After the rash improved, we re-started LDV/SOF with PSL. After treatment, the rash clearly improved; we checked for a sustained virologic response 12 weeks after treatment. Steroids may therefore be an effective treatment option for controlling the side effects of LDV/SOF.

KEYWORDS:
Case reports; drug eruption; hepatitis C; ledipasvir and sofosbuvir; steroid
PMID: 29279506 DOI: 10.2169/internalmedicine.9744-17 

Friday, December 22, 2017

Blog Updates & Reports: Chronic Illness and Expectations - Hepatitis B Experimental Treatments - Treatment for acute HCV infection

2017 December: Blog Updates & Reports
For your reading pleasure, check out a few blog updates and reports released this week on the topic of viral hepatitis.

Blog Updates
A number of modeling experts the agency works with are predicting that this year’s flu season will peak around the end of this month, Dr. Daniel Jernigan, head of the agency’s influenza division, told STAT. That means lots of people will be sick over the holidays; lots already are. And the multi-generational family gatherings that are part and parcel of the holidays will fuel the spread of the nasty virus.

It’s Flu Season! Did you get your shot?
Flu season is upon us! It usually ranges from the winter into early spring. It’s important that you get your flu shot, especially if you or a family member has a chronic disease such as hepatitis B.

The Latest Issue: Weekly Bull
Did you know that there are now 8 genotypes and 84 subtypes of HCV, all of which respond to Vosevi? Also in the news, Telemedicine, transplanting infected livers, and treating seniors.

INHSU 2017 Recap
At the International Symposium on Hepatitis Care in Substance Users held in New Jersey in September 2017, Dr. Jason Grebely provided an excellent debrief summarizing the main themes of the conference which we will try to summarize in this blog post.

Top 10 HIV and hepatitis C stories of 2017
Negotiations with Canada’s provincial and territorial governments this year brought down the price of new and effective hepatitis C drugs, making it possible to end the practice of “rationing” treatment to those with severe liver damage.

2017 Top Hepatitis Treatment Stories
Hepatitis treatment news stories with the most views this year over at Hep blogs.

Investment in hep C treatment programs needed to support elimination goal
Hepatitis Australia is urging government to invest in programs designed to increase the uptake of PBS-listed direct acting antivirals that cure hepatitis C.

Another Inspiring Story from Texas
By Greg Jefferys
Every story is precious and every person feels such relief and joy at having cleared this wicked disease.

Hepatitis C Treatment: What does it really cost?
By Greg Jefferys
I received a press release from MSF saying they had access to Hepatitis C treatment for the price of US$120 for a 12 week treatment.

How Hepatitis C Damages Your Health
By Greg Jefferys
A closer look at how HCV damages the body.

What I Don’t Want for Christmas: Hepatitis A
By Lucinda K. Porter, RN
Hepatitis A outbreaks are occurring all over the world, including in the United States. However, hepatitis A can be easily prevented.

Weekly Special: Harm Reduction – Alcohol
Alcohol is one of the most addictive and destructive substances. Our fact sheet discusses how to apply harm reduction strategies to alcohol use.

Celebrating the Holidays with Hepatitis B
The holidays are a joyous time as family and friends gather for parties, dinners and get-togethers. However, they can also be a difficult, stressful time on so many levels, and especially for those who might not yet have disclosed their hepatitis B to loved ones

Facing Changes During the Holidays
By Karen Hoyt - December 21, 2017
With each season of life, there are bound to be changes. Some of them are felt more during the holidays. When we’re weighed down with health decisions from a sick liver, we...

By Carleen McGuffey - December 20, 2017
When I first found out I had hepatitis C I only told James, my husband of 20 years. He has been and currently is an excellent support, caretaker, strength, and provider throughout...

By Kimberly Morgan Bossley - December 19, 2017
My Grateful Heart A grateful heart does not mean it comes from a perfect life, great health, or monitory riches. A grateful heart is one that has fought through the pits of...

Preventing overdose deaths is not one-size-fits-all
December 22, 2017,
Scott Weiner, MD, Contributor
By now, we all know that the number of opioid-related deaths in the United States has reached epidemic proportions. Despite the Centers for Disease Control and Prevention declaring an epidemic in 2011, the death rate has continued to increase every year, with more than 30,000 deaths per year now attributed to opioids.

Related: Opioid crisis trims U.S. life expectancy, boosts hepatitis C: CDC

Boston-area paramedics on front lines of U.S. opioid crisis
The paramedics find them everywhere - slumped over car steering wheels, barely breathing in doughnut shop bathrooms or dead in derelict apartments and expensive mansions.

The Weekly Special is our Harm Reduction Fact Sheet – Opioids. Learn about opioids–the effects they have on the body, the side effects and why they are addictive.

Answer these 5 questions to help make your New Year’s resolutions stick
Marcelo Campos, MD
t’s that time of the year again when we start thinking about the (in)famous New Year’s resolutions. Change can be a frustrating experience for many. So, I decided to investigate what may increase your chances of success.

When to get tested for hepatitis C after exposure
Learn what the window period is for hepatitis C infection, and when someone should consider testing. We look at available tests and when symptoms appear.

A healthy liver is crucial for maintaining a person's overall health, but expensive cleanses or diets are just not necessary. In some cases, they may even be dangerous. A healthy lifestyle, balanced diet, and regular consultations with a doctor are far more valuable to the health of the liver than any fad diet or cleanse. Liver cleanses offer no proven benefits. To protect liver health, people can adopt a more comprehensive, long-term health strategy.

In The Journals
Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.
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SVR Reduced HCC by 71%
from Jules: there never was any doubt that SVR would reduce or eliminate risk for HCC. In this study cirrhosis prior to treatment had a higher HCC risk then for those without cirrhosis, but that is to be expected and merely reinforces how crucial it is to treat HCV as early as possible...
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Diagnosing Liver Fibrosis and Cirrhosis: Serum, Imaging, or Tissue?
When assessing a patient with chronic liver disease, one of the foremost questions in a clinician’s mind is the stage of fibrosis. The degree of fibrosis predicts risk of complications and guides management, including hepatocellular carcinoma and variceal surveillance. Traditionally, the liver biopsy has staged fibrosis. Recently, several serum tests and imaging modalities have become available to assess fibrosis noninvasively. Clinicians now have options to consider for fibrosis assessment.
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For Your Viewing Pleasure
A critical review of endpoints for non-cirrhotic NASH therapeutic trials 
Prof. Vlad Ratziu discusses his article "A critical review of endpoints for non-cirrhotic NASH therapeutic trials" for the upcoming NAFLD special issue of the Journal of Hepatology

Webinar - Hepatitis C Among Pregnant Women
This webinar is now archived.
Click here for the slides. Click here for the recording.
(Click the link and then enter name and email address to view the webinar).

Reports 

December 2017 infohep bulletin
Latest treatment news and information for patient advocates and people working in hepatitis in Europe.


Hepatitis C Coalition 
Hepatitis C Coalition new report on the Operational Delivery Networks
CONTENTS
How Hepatitis Services are delivered
Relevant policies
Project process and topics discussed
List of ODN visits
Overview of findings
Run rates
Finances and CQUIN
Delivering the clinical service and MDTs
Data and sharing of information with NHS England
Prisons and outreach
Diagnosis and referral
Future of the ODNs 
Begin here....

Wishing you all a Very Merry Christmas!
Tina 

Opioid crisis trims U.S. life expectancy, boosts hepatitis C: CDC

CDC Reports - Mortality in the United States, 2016
This report presents final 2016 U.S. mortality data on deaths and death rates by demographic and medical characteristics. These data provide information on mortality patterns among U.S. residents by variables such as sex, race and ethnicity, and cause of death. Life expectancy estimates, age-specific death rates, age-adjusted death rates by race and ethnicity and sex, 10 leading causes of death, and 10 leading causes of infant death were analyzed by comparing 2016 and 2015 final data

In 2016, a total of 2,744,248 resident deaths were registered in the United States—31,618 more deaths than in 2015. From 2015 to 2016, the age-adjusted death rate for the total population decreased 0.6%, but life expectancy at birth decreased 0.1 year. Age-specific death rates between 2015 and 2016 increased for younger age groups and decreased for older age groups. The age-adjusted death rate decreased for non-Hispanic white females and increased for non-Hispanic black males.

The 10 leading causes of death in 2016 remained the same as in 2015, although two causes exchanged ranks. Unintentional injuries, the fourth leading cause in 2015, became the third leading cause in 2016, while chronic lower respiratory diseases, the third leading cause in 2015, became the fourth leading cause in 2016. Age-adjusted death rates decreased for seven leading causes and increased for three. Life expectancy at birth decreased 0.1 year from 78.7 years in 2015 to 78.6 in 2016, largely because of increases in mortality from unintentional injuries, suicide, and Alzheimer’s disease, with unintentional injuries making the largest contribution. This is the second year in a row life expectancy has declined (1). Changes in death rates at younger ages have a larger impact on life expectancy than changes at older ages. The increases in death rates at the younger ages from 2015 to 2016 resulted in the decrease in life expectancy observed during that period.

In 2016, a total of 23,161 deaths occurred in children under age 1 year, which was 294 fewer infant deaths than in 2015. The leading causes of infant death were the same in 2016 and 2015. The only significant change among the 10 leading causes of infant death was a 7.3% decrease in the IMR for maternal complications.

Key findings
Data from the National Vital Statistics System
- Life expectancy for the U.S. population in 2016 was 78.6 years, a decrease of 0.1 year from 2015.
- The age-adjusted death rate decreased by 0.6% from 733.1 deaths per 100,000 standard population in 2015 to 728.8 in 2016.
- Age-specific death rates between 2015 and 2016 increased for younger age groups and decreased for older age groups.
- The 10 leading causes of death in 2016 remained the same as in 2015, although unintentional injuries became the third leading cause, while chronic lower respiratory diseases became the fourth.
- The infant mortality rate of 587.0 infant deaths per 100,000 live births in 2016 was not significantly different from the 2015 rate.
- The 10 leading causes of infant death in 2016 remained the same as in 2015.
This report updates statistics on deaths from drug overdoses in the United States and includes information on trends since 1999 as well as key findings for 2016.

The rates of drug overdose deaths continued to increase. In 2016, the age-adjusted rate of drug overdose deaths (19.8 per 100,000) was more than three times the rate in 1999 (6.1). Rates increased for both males (from 8.2 in 1999 to 26.2 in 2016) and females (from 3.9 in 1999 to 13.4 in 2016). Rates also increased for all age groups studied. In 2016, among persons aged 15 and over, rates were highest for adults aged 25–34, 35–44, and 45–54, at about 35 per 100,000. From 2015 to 2016, drug overdose death rates increased 28% for persons aged 15–24, 29% for persons aged 25–34, 24% for persons aged 35–44, 15% for persons aged 45–54, 17% for persons aged 55–64, and 7% for persons aged 65 and over. In 2016, 22 states and the District of Columbia had age-adjusted drug overdose death rates that were statistically higher than the national rate; 5 states had rates that were comparable to the national rate; and 23 states had lower rates.

The pattern of drugs involved in drug overdose deaths has changed in recent years. The rate of drug overdose deaths involving synthetic opioids other than methadone (drugs such as fentanyl, fentanyl analogs, and tramadol) doubled in a single year from 3.1 per 100,000 in 2015 to 6.2 in 2016. Rates of drug overdose deaths involving heroin increased from 4.1 in 2015 to 4.9 in 2016. Rates of drug overdose deaths involving natural and semisynthetic opioids increased from 3.9 in 2015 to 4.4 in 2016.

Key findings 
Data from the National Vital Statistics System, Mortality
- In 2016, there were more than 63,600 drug overdose deaths in the United States.
- The age-adjusted rate of drug overdose deaths in 2016 (19.8 per 100,000) was 21% higher than the rate in 2015 (16.3).
- Among persons aged 15 and over, adults aged 25–34, 35–44, and 45–54 had the highest rates of drug overdose deaths in 2016 at around 35 per 100,000.
- West Virginia (52.0 per 100,000), Ohio (39.1), New Hampshire (39.0), the District of Columbia (38.8), and Pennsylvania (37.9) had the highest observed age-adjusted drug overdose death rates in 2016.
- The age-adjusted rate of drug overdose deaths involving synthetic opioids other than methadone (drugs such as fentanyl, fentanyl analogs, and tramadol) doubled between 2015 and 2016, from 3.1 to 6.2 per 100,000.
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Media
Opioid crisis trims U.S. life expectancy, boosts hepatitis C: CDC
Julie Steenhuysen
CHICAGO (Reuters) - The opioid crisis is rippling through the U.S. healthcare system, causing a spike in rates of hepatitis C related to increased opioid injections and reducing overall life expectancy among Americans, which has fallen for the second year in a row, U.S. health officials said on Thursday. Researchers used a national database that tracks substance abuse admissions to treatment facilities in all 50 U.S. states. They found a 133 percent increase in acute hepatitis C cases that coincided with a 93 percent increase in admissions for opioid injection between 2004 to 2014.

By Nick Wing
A new report shows back-to-back years of declining life expectancy, and the CDC says a third straight year appears to be on the way.
The average American life expectancy ticked downward for the second straight year in 2016, on the back of surging drug overdose deaths, according to data released Thursday by the National Center for Health Statistics at the U.S. Centers for Disease Control and Prevention. And while the nation hasn’t experienced a back-to-back drop in life expectancy since the 1960s, the CDC says the opioid crisis is shaping up to extend this decline for a third consecutive year, a milestone that hasn’t been seen since the Spanish flu pandemic in 1918.

Wednesday, December 20, 2017

Hepatitis Alert: HCV Elimination—Closing the Gaps in Screening, Care Linkage, and Treatment

Learn strategies to increase screening, diagnosis, engagement in care, and treatment for HCV.

Webinar Series
Hepatitis Alert: HCV Elimination—Closing the Gaps in Screening, Care Linkage, and Treatment
In this downloadable slideset, Norah Terrault, MD, MPH, and Stacey Trooskin, MD, PhD, review important strategies for closing gaps along the HCV care continuum with a focus on overcoming barriers to reach and treat persons who inject drugs.

Source: Viral Hepatitis Alerts—A CME/CE/CPE-Certified Webinar Series
Date Posted: 12/19/2017
Free registration required

Downloadable Slidesets
Alert 1: First-Line HCV Treatment
Alert 2: Treating DAA-Experienced Pts With HCV
Alert 3: HCV Elimination Downloadable Audio
Alert 1: First-line HCV Treatment
Alert 2: Treating DAA-Experienced Pts With HCV

Clinical Thought
First-line HCV Therapy Treating DAA-Experienced Pts With HCV
Begin here: https://www.clinicaloptions.com/Hepatitis.aspx