HCV New Drugs

Sunday, January 1, 2017

Review Screening for hepatocellular carcinoma: What is missing?

Just In Case You Missed It

Check out a new Open Access journal entitled Hepatology Communications published by American Association for the Study of Liver Diseases. Here is a recent article to get you started, view all articles, here.

Review Screening for hepatocellular carcinoma: What is missing?

Authors Neil J. Mehta, Aygul Dogan Celik, Marion G. Peters
First published: 19 December 2016
Full publication history
DOI: 10.1002/hep4.1014

Potential conflict of interest: Dr. Peters has received honoraria for advisory boards from Merck, Hoffmann La Roche, Johnson and Johnson, Gilead Sciences, Abbott, and honararium from Genentech. Spouse works for Hoffmann La Roche.

Abstract

While there are guidelines from all major liver societies for the screening and management of hepatocellular carcinoma (HCC), many issues remain surrounding the actual practice of screening. This review discusses how to diagnose and screen HCC and more importantly, how well we diagnose and screen for HCC. Improved survival and outcomes after HCC diagnosis depend upon accurate diagnosis of cirrhosis and the timeliness of screening. With all oral direct-acting antivirals now widely available for hepatitis C, there are increasing numbers of patients who may be cured but are still at risk of HCC. Some uncontrolled studies suggest that direct-acting antiviral therapy may even increase the risk of HCC. Before we discuss expansion of who should be screened, we need physicians to realize how poorly we screen those patients who are already recommended for screening by guidelines. (Hepatology Communications 2016)

Enhanced PDF
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Abbreviations

AFP: alpha-fetoprotein
ALT: alanine aminotransferase
BCLC: Barcelona Clinic Liver Cancer
CT: computed tomography
EASL: European Association for the Study of the Liver
HBV: hepatitis B virus
HCC: hepatocellular carcinoma
HCV: hepatitis C virus
MRI: magnetic resonance imaging
SVR: sustained virologic response
VHA: Veterans Health Administration

How big is the problem?

The last four decades has seen a rising incidence of hepatocellular carcinoma (HCC) in the United States from 1.5 per 100,000 persons to nearly 14 per 100,000 persons and a 5-year survival under 12%.[1] While most of the increase is associated with aging of the baby-boomer population with hepatitis C, hepatitis B and nonalcoholic fatty liver disease also contribute. In a Markov model of 2.7 million persons infected with the hepatitis C virus (HCV) who are in primary care in the United States, it is estimated that 1.47 million will develop cirrhosis and 350,000 will develop liver cancer over their lifetime. The burden of HCC from HCV is estimated to peak at 12,000 per year by approximately 2030.[2]

Who should be screened

Surveillance is the process of providing a screening test at regular intervals to patients at risk for HCC. Surveillance is deemed cost-effective if the expected HCC risk exceeds 1.5% per year in patients with hepatitis C and 0.2% per year in patients with hepatitis B.[3] All patients with cirrhosis should be screened. While it is possible to perform HCC risk stratification in these patients using clinical risk scores[4, 5] and genomic biomarkers,[6] neither yet appear able to reliably identify those patients with cirrhosis who are at such a low risk of HCC development that screening is not warranted. In addition to screening all patients with cirrhosis, hepatitis B virus (HBV) Asian males ≥ 40 years, Asian females ≥ 50 years, and sub-Saharan Africans ≥ 20 years as well as HBV patients with a family history of HCC should be screened. The European Association for the Study of the Liver (EASL) recommends screening HCV patients with stage 3 fibrosis as well.[7] One of the major problems in deciding who to screen is in identifying those patients who have cirrhosis.[8] If patients are decompensated with ascites, jaundice, encephalopathy, splenomegaly, and muscle wasting, the diagnosis is relatively easy. However, in some patients with Child's A cirrhosis, few signs may be noted, and many such patients have normal liver tests. With decreasing use of liver biopsy, noninvasive markers of fibrosis may miss many patients. Transient elastography can be used to stage fibrosis in a noninvasive manner by measuring shear wave velocity. This technique is not readily available throughout the United States at this time so patients with cirrhosis may not be appropriately diagnosed.

How to screen

Screening is recommended by all liver societies; 6-monthly ultrasounds are recommended by the EASL and American Association for the Study of Liver Diseases[7, 9] and ultrasound and alpha-fetoprotein (AFP) are recommended by the Asian Pacific Association for the Study of the Liver.[10] Screening every 6 months is recommended because the doubling time of HCC is estimated to be 4-6 months.[11] The only randomized controlled trial of screening versus no screening was in 18,816 hepatitis B patients in China.[12] Patients underwent AFP and ultrasound every 6 months; 58.2% were screened and 41.8% were not. There were 86 tumors in the screened patients and 67 tumors in the nonscreened patients. Only the screened patients had subclinical, small, or resectable HCC lesions (Table 1). Survival was markedly better in those who were screened versus those who were not (65.9% versus 31.2% at 1 year; 46.4% versus 0% at 5 years).

AFP is limited as a screening test because of both false positives and false negatives. A third (20%-40%) of patients with HCC have normal AFP, and 20%-30% of patients without HCC have abnormal AFP, especially in those with active inflammation and elevated alanine aminotransferase (ALT) from HCV[5] and HBV.[13] Analyzing nearly 12,000 HCV patients with cirrhosis in the Veterans Health Administration (VHA) system, an AFP-based algorithm was created that also included ALT, platelet count, and age to predict the development of HCC.[5] The authors found that taken alone, a patient with an AFP of 120 ng/mL had an 11% probability of developing HCC within 6 months; however, if that same patient was known to have minimal liver inflammation (ALT 40), platelet count of 100, and be older (age 70), the probability of developing HCC within 6 months rose to 29%. While AFP is not a particularly sensitive screening test and should be considered alongside additional clinical factors, such as ALT, there is no doubt that the higher the AFP, the more likely the diagnosis is HCC. In addition, AFP can be used as a prognostic marker because it predicts overall mortality in HCC,[14] predicts prognosis after resection,[15] and predicts prognosis after liver transplantation.[16-19]

If a nodule > 1 cm is found on ultrasound, quadruple-phase computed tomography (CT) or magnetic resonance imaging (MRI) is recommended.[3] Quadruple-phase CT is used to differentiate HCC, which is usually supplied by the hepatic artery, from normal liver tissue, which is mainly supplied by the portal vein. HCC is characterized by arterial phase enhancement and portal venous washout at the time the majority of the liver is enhanced. If either the CT or MRI shows the typical characteristics of HCC, then patients should be managed as per regular guidelines (e.g., Barcelona Clinic Liver Cancer [BCLC] staging classification[20]), without biopsy diagnosis. Biopsy of the lesion is recommended only in selected cases if there is an atypical radiologic appearance; this is because there are concerns with liver biopsy. False negative biopsies are common in clinical practice and may lead to delays in both diagnosis and treatment.[21] Tumor seeding along the biopsy tract occurs in 1%-5% of cases, but coaxial biopsy may decrease this rate.[22] Seeding may exclude the patient from consideration of curative treatments, such as resection or transplant. If radiologic appearance and biopsy results are nondiagnostic or if the lesion is <1 cm, short-term follow-up with ultrasound (or CT/MRI if patient is listed for a transplant) in 3-4 months is recommended to assess growth of the lesion.
Singal studied 446 patients with cirrhosis who were prospectively enrolled for 6-monthly ultrasound and AFP.[23] They excluded the first 6 months to avoid lead-time bias. After a median of 3.5 years, 41 patients were identified with HCC, 73.2% of whom had early lesions (BCLC stage 0-B) with the same percentage within Milan criteria and 80.5% within University of California, San Francisco criteria. They found an annual HCC incidence of 2.8% and a cumulative incidence at 3 and 5 years of 5.7% and 9.1%, respectively. The sensitivity of AFP and ultrasound was 90%, which was greater than either alone. However, screening came at a cost: 36 patients with high AFP had normal MRI and CT and 34 patients had a lesion on ultrasound that was not identified from MRI or CT.

Another retrospective study compared 6-monthly and yearly ultrasounds versus no screening in 269 patients with cirrhosis and HCC (Table 1).[24] Those HCC patients who had appropriate screening had smaller lesions (70% within Milan criteria) compared to 37% for those screened yearly and 7% who had no screening. In addition, 3-year survival was better in 6-monthly (39%) screening versus yearly (27%) or no screening (12%). Among 821 Italian HCC patients who were studied retrospectively, no difference was found between 6- and 12-monthly screening compared to no screening.[25] However, a later prospective study from the same group confirmed the benefit of 6-monthly screening over 12-monthly screening in 649 Italian patients with cirrhosis.[26] As shown in Table 1, in those patients with 6-monthly screening, 70% were within Milan criteria compared to 58% of those screened yearly being within Milan criteria (P < 0.001). Screening more frequently (3 versus 6 months) increased detection of small focal lesions but not of HCC.[27] Systematic reviews and meta-analysis of surveillance studies in patients with cirrhosis showed that those who had routine screening usually had earlier stage HCC, were more likely to be candidates for curative treatment, and had better survival compared to unscreened patients.[28, 29]

Table 1. Efficacy of Screening for HCC in Patients with Cirrhosis

	Ultrasound Surveillance Interval
Study Design 1^st Author^(Ref)	Every 6 Months			Every 12 Months			No Screening
Study Design 1^st Author^(Ref)	n	Within Milan (% treatable)	Survival (% or median)	n	Within Milan (% treatable)	Survival (% or median)	n	Within Milan (% treatable)	Survival (% or median)
^a Compared to every 6-month screening *P < 0.001; ^b P = 0.03. ^c Total n included in study was 9,373 in every 6-month arm and 9,443 in no screening arm.
Retrospective Stravitz[24]	172	70%	3 yr: 39%	48	37%	3 yr: 27%	59	7%	3 yr: 12%
Retrospective Trevisani[25]	215	69%	36 mos	155	60%	34 mos	451	31%	14 mos
Prospective Santi[26]	510	70% (82%)	45 mos	139	58%a (70%)	30 mosb	Not studied
Prospective Zhang[12]	86c	45% (79%)	1 yr: 66% 5 yr: 46%	Not studied			67c	0% (49%)	1 yr: 31% 5 yr: 0%

How well do we screen?

Studies from Europe and the United States show that less than 30% of patients with cirrhosis receive screening. In one study of 904 patients with cirrhosis in a US safety net hospital, less than 2% had biannual ultrasounds, 13% had annual ultrasounds, and 67% had only one ultrasound in 3 years.[30] Lower surveillance was noted in the uninsured patients and in African Americans. Surveillance was highest in those who had a yearly visit to a hepatologist, followed by a visit to a primary care doctor; both were better than no follow-up visit.[30] Two large, recent, retrospective studies of patients in the VHA[31] and with commercial insurance[32] found that twice yearly ultrasound screening in patients with cirrhosis was performed 20%-30% of the time. In the VHA study, some of the strongest predictors of not receiving screening included fewer visits with a subspecialist (gastrointestinal/hepatology/infectious disease), increased distance from a patient's home to the nearest VHA center, and a longer time between the date the ultrasound was ordered and the date it was requested to be performed.

Screening of HCV patients after cure

Treatment of hepatitis C markedly decreases the risk of HCC but does not eradicate it. To emphasize this, a study of 33,000 VHA patients identified 10,827 patients who achieved sustained virologic response (SVR) with interferon-based therapies; of those who achieved SVR, 100 developed new HCC.[33] The annual incidence rate of HCC in those with SVR was 0.33% per year compared to 1.32% per year in those without SVR. The predictors of developing HCC in this cohort were cirrhosis at SVR (odds ratio, 6.69; confidence interval, 4.3-10.4), age over 65 years (4.51; 2.0-10.4), age 55-64 years (2.04; 1.3-3.2), Hispanic race compared to Caucasians (2.3; 1.1-1.8), diabetes mellitus (1.8; 1.2-2.9), and alcohol (1.68; 1.08-2.6).

Thus, patients who have SVR or are cured of their hepatitis C are still at risk of developing HCC, need to be monitored, and should not be discharged from their doctor's practice. Literature over the past year has noted HCC occurring or recurring after SVR in response to direct acting antivirals. Uncontrolled studies reported early recurrence within 6-12 months of SVR,[34, 35] but the Agence Nationale de Recherche sur le Sida reported no difference in HCC incidence in those treated with interferon-based therapies versus direct-acting antivirals.[36] Whether all oral direct-acting antiviral therapy is associated with an increased risk of cancer is not clear, and further long-term randomized studies are required.

In summary, there is an increasing prevalence of HCC with the aging of patients with hepatitis C, the increase of nonalcoholic fatty liver disease, as well as hepatitis B. There is much discussion about screening patients without cirrhosis as these patients can develop HCC. However, this opinion piece highlights that the major problem worldwide is how poorly we appropriately screen and diagnose HCC in patients with cirrhosis. What is most important is to diagnose cirrhosis early so that screening can be initiated because patients with cirrhosis are those with the highest risk of HCC. The outcome of HCC is influenced by the failure to diagnose cirrhosis, the absence of surveillance, and the delay in follow-up and treatment. Screening appropriately leads to early diagnosis, which leads to better management options, a higher proportion of treatable lesions, and better outcomes, including survival.

Ancillary

Thursday, December 29, 2016

Hepatitis C Hot Topics - Research and News of 2016

Hepatitis C Hot Topics - Research and News of 2016

Today we take a look back at the top HCV news stories of 2016. Sit back and review a collection of hepatitis C research articles, guideline updates, conference reports, learning activities, and news from around the web.

Recent News
AbbVie Awaits NDA Approval For Hepatitis C Treatment
Dec. 19, 2016
AbbVie (ABBV), a global biopharmaceutical company, announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the company's investigational, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P), being evaluated for the treatment of chronic hepatitis C virus (HCV). In Phase 3 clinical studies, eight weeks of therapy with G/P achieved high sustained virologic response (SVR) rates across all major genotypes (GT 1-6) in patients without cirrhosis, which represents the majority of HCV patients. In patients with compensated cirrhosis, high SVR rates were achieved after 12 weeks of therapy. High SVR rates were also achieved in patients with limited treatment options, such as those with severe chronic kidney disease (CKD). In historically difficult to treat populations, including those not cured* by prior direct-acting antiviral (DAA) treatment regimens, high SVR rates were achieved with durations as short as 12 weeks.

Of Interest
Press Release
Nov 11, 2016
Eight Weeks of Treatment with AbbVie's Investigational, Pan-Genotypic Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved High SVR Rates Across All Major Genotypes of Chronic Hepatitis C
NORTH CHICAGO, Ill., Nov. 11, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced high SVR₁₂ rates with 8 weeks of treatment with its investigational, pan-genotypic regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) (G/P) across all major chronic hepatitis C virus (HCV) genotypes. In more than 700 genotype 1-6 (GT1-6) chronic HCV infected patients without cirrhosis and who are new to treatment, 97.5 percent (n=693/711) achieved sustained virologic response at 12 weeks post treatment (SVR₁₂), regardless of baseline viral load. The rate of virologic failure was 1 percent (n=9/711).

November 13, 2016
Glecaprevir/Pibrentasvir: High SVR Rates in HCV GT 2, 4, 5, 6 Without Cirrhosis

Dec 8, 2016

Gilead Submits New Drug Application to U.S. Food and Drug Administration for the Investigational Single Tablet Regimen Sofosbuvir/Velpatasvir/Voxilaprevir
Gilead Sciences, Inc. announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg (SOF/VEL/VOX) for the treatment of direct-acting antiviral (DAA)-experienced chronic hepatitis C virus (HCV)-infected patients. The data submitted in the NDA support the use of the regimen for 12 weeks in DAA-experienced patients with genotype 1 to 6 HCV infection without cirrhosis or with compensated cirrhosis.

Of Interest
October 2016
Gilead Announces SVR12 Rates From Four Phase 3 Studies of a Once-Daily, Fixed-Dose Combination of Sofosbuvir, Velpatasvir and Voxilaprevir in Treatment-Naïve and Treatment-Experienced Genotype 1-6 Chronic HCV-Infected Patients
Gilead Sciences, Inc. (NASDAQ: GILD) today announced topline results from four international Phase 3 clinical studies (POLARIS-1, POLARIS-2, POLARIS-3 and POLARIS-4) evaluating an investigational, once-daily, fixed-dose combination of sofosbuvir (SOF), a nucleotide analog NS5B polymerase inhibitor; velpatasvir (VEL), a pangenotypic NS5A inhibitor; and voxilaprevir (VOX; GS-9857), an investigational pangenotypic NS3/4A protease inhibitor, for the treatment of genotype 1-6 chronic hepatitis C virus (HCV) infection.

From The Journals

Journal of Hepatology 2017 Issue
Summary @ MD
Dec 16, 2016
Hepatitis C Still Increases Mortality Rate After Being Cured

NATAP - Full Text Article
Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Of Interest
Correspondence: Prof. Dr. J.K. Rockstroh
2016/2017 - New HCV two and three drug regimens on their way: what do they promise?
Topic Summary
Risk of HBV reactivation after starting DAA therapy
Surveillance for hepatocellular carcinoma (HCC) and risk for HCC after achieving SVR following DAA therapy.
Intravenous drug users and patients on opioid substitution therapy
Patients in the prison setting
HIV/HCV coinfected patients
Patients with renal insufficiency or on hemodialysis
Patients older than 70 years
Patients receiving short treatment durations of 8 week
HCV three drug rescue combinations with licensed drugs
New dual DAA combinations
New three drug combinations

The Lancet Gastroenterology & Hepatology
Dec 12, 2016
Editorial Access to HCV treatments: hurdles not barriers

Infectious Diseases and Therapy
Evidence shows value of treating all stages of chronic HCV
November 1, 2016
Available evidence suggests that HCV treatment with the new direct-acting antivirals (DAAs) should not be limited to patients with advanced liver disease.

Liver Cancer After Treatment For Hepatitis C
November 23, 2016
A collection of 2016 articles retrieved online from press releases, conferences (The Liver Meeting® 2016 and the International Liver Congress 2016) and peer-reviewed journals featuring long-term risk for liver cancer in those who were cured of Hepatitis C.

December 2016

The following article appeared in the December print edition of HCV NEXT, published online at Healio; Screening for HCC in the Post-SVR12 Setting

Gastroenterology & Hepatology
December 2016
Interview
The Possible Association Between DAA Treatment for HCV Infection and HCC Recurrence
Download the PDF
G&H How common is the coexistence of hepatocellular carcinoma and hepatitis C virus infection in a patient?

RB Among patients with hepatitis C virus (HCV) infection and cirrhosis, the risk of hepatocellular carcinoma (HCC) is estimated to be 1% to 3% per year. Thus, in any given year, the risk is relatively low, but over a decade, the risk is considerable. More importantly, with the rise in the number of baby boomers who have had HCV infection for more than 2 decades, we are seeing an increasing prevalence of HCC. Although the rate of new cases of HCV infection is falling, the prevalence of HCV infection with cirrhosis is still rising, as is the number of patients who have HCV infection and HCC.
Continue reading...

Research Article

November 25, 2016
What’s Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment
Patients contemplating hepatitis C virus treatment want a great deal of information to make informed treatment decisions.

Journal Of Gastroenterology and Hepatology
November 2016
Comparative Treatment Effectiveness of Direct Acting Antiviral Regimens for Hepatitis C: Data from the Veterans Administration
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jgh.13652

Journal Of Hepatology

New Perspectives in HCV Infection
October 2016 Issue
Second generation direct-acting antivirals – Do we expect major improvements?
Future landscape of hepatitis C research – Basic, translational and clinical perspectives

Liver International
October 2016
The value of cure associated with treating treatment- naïve chronic hepatitis C genotype 1: Are the new all- oral regimens good value to society?

Gastroenterology
October 1, 2016
Hepatitis C Therapy: Game Over!
Alessio Aghemo, Maria Buti
DOI: http://dx.doi.org/10.1053/j.gastro.2016.09.034
Publication stage: In Press Accepted Manuscript
NS5B polymerase inhibitor sofosbuvir, NS5A inhibitor velpatasvir, and the new protease inhibitor GS-9857 (voxilaprevir)
Download PDF

Hepatology
Emerging complexities with HCV DAA regimens: Less is still way more.
September 2016
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/hep.28832

Clinical Gastroenterology and Hepatology

SVR Linked to Long-Term Reduction in Fibrosis, Cirrhosis
July Issue 2016

Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection

Journal of Viral Hepatitis
August 2016GS-9857 in Patients With Chronic Hepatitis C Virus Genotype 1–4 Infection

Gastroenterology & Endoscopy News

The Changing HCV Landscape:
October 26, 2016
Hepatitis C virus (HCV) continues to be a significant global burden, with more than 170 million people...

Conferences, Learning Activities and Guidelines

International Congress on Drug Therapy in HIV Infection

Generic hepatitis C drugs purchased online achieve high cure rates
October 27, 2016
Use of generic versions of direct-acting antivirals resulted in very high cure rates for people who obtained the products through three buyers’ clubs, indicating that the generic products are effective, according to three presentations at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) this week.

Of Interest
AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

Dec 15, 2016

Generic sofosbuvir-based combinations for hepatitis C may not perform as well as branded sofosbuvir-containing regimens, according to a study conducted in Qatar and presented at the recent 2016 AASLD Liver Meeting. People treated with generics were less likely to be cured and more likely to experience adverse events compared to people who received branded drugs. But the investigators speculate that the generics may have underperformed because many people treated were with suboptimal regimens, and believe this deserves further research.

Watch - An Introduction to Access to Generic Hepatitis C Medicines
November 8, 2016
Following the success of the first two webinars in the Knowledge for Change series covering access to diagnostics and medicines, we were pleased to deliver the next in the series, ‘An Introduction to Accessing Generic Hepatitis C Medicines’ on 1 November. The webinar explored the generics landscape for hepatitis C with discussions on legalities, quality and performance of generics medicines as well as providing examples of how people across the globe are accessing them.

EASL- AASLD Special Conference New perspectives in hepatitis C virus infection - The roadmap for cure
September 23, 2016
Watch Summary Presentation - EASL Recommendations on Treatment of Hepatitis C 2016

EASL Recommendations on Treatment of Hepatitis C
Download 2016 - Update of the HCV EASL recommendations

American Association for the Study of Liver Diseases 67th Annual Meeting 2016

AASLD 2016 Review - Watch Advances in Chronic Hepatitis C: Management and Treatment

November 18, 2016

After each conference this blog links to a series of education-related information on important findings related to ongoing challenges of managing and treating viral hepatitis. Review three programs offering a review of key studies presented at the American Association for the Study of Liver Diseases 67th Annual Meeting 2016.

New at Healio
December 26, 2016

The Take Home - The Liver Meeting 2016
Infectious Disease Week 2016
The Liver Meeting 2016: Beyond HCV

Related
Healio - Highlights from The Liver Meeting

AASLD Coverage @ HIV and Hepatitis

ALL CONFERENCE COVERAGE
HIV and Hepatitis

VIDEO: Cost to treat HCV could be as low as $80 in the US
November 19, 2016
In this exclusive video at The Liver Meeting, Andrew M. Hill, PhD, discusses data from a new study that show the price of a direct-acting antiviral generic regimen could be as low as $80 in the U.S. to cure hepatitis C virus infection in one patient.

American College of Gastroenterology (ACG) 2016 Annual Scientific Meeting

Hep C Treatment Prognosis Continues to Amaze

November 22, 2016

LAS VEGAS — Rapid advances in the treatment of hepatitis C have clinicians seeing outcomes they never thought possible, and experts are optimistic that more complex and challenging patients will respond to therapy.

Healio

See more from American College of Gastroenterology Annual Meeting

National AIDS Treatment Advocacy Project (NATAP)

View All 2016 HCV and HIV conference reports at NATAP

2016 Updates

HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C

HCV Guidelines Update: People with HCV Should Be Tested for HBV Before Starting Antiviral Therapies
September 16, 2016
All patients beginning hepatitis C (HCV) treatment using direct acting antiviral (DAA) therapies should be assessed for hepatitis B (HBV), according the American Association for the Study of Liver Diseases/Infectious Diseases Society of America Guidance Panel, which provides up-to-date guidance on the treatment of hepatitis C on its website, HCVguidelines.org.

AASLD Offers Two New Practice Guidelines
New Practice Guidelines covering the treatment of hepatocellular carcinoma and portal hypertensive bleeding in cirrhosis have been released by AASLD.

These evidence-based guidelines are developed and updated regularly by a committee of experts and include recommendations of preferred approaches to the diagnostic, therapeutic, and preventative aspects of care.

Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management was published in December. Treatment of Hepatocellular Carcinoma has a January 2017 publication date.

For details about AASLD’s practice guidelines, click here.

FDA MedWatch/Direct-Acting Antivirals for Hepatitis C: Drug Safety Communication - Risk of Hepatitis B Reactivating
October 4, 2016

The FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death. HBV reactivation usually occurred within 4-8 weeks.

July 6, 2016

This version of the Guidance has been updated to reflect several important developments, including the recent approval of sofosbuvir/velpatasvir, together with new information regarding the use of testing for HCV resistance associated variants....
Read more

February 24, 2016

This version of the Guidance has been updated to reflect several important developments, including the recent approval of elbasvir/grazoprevir, together with new information regarding the use of testing for HCV resistance associated variants....
Read more

Emerging Hepatitis C Treatment Strategies For Difficult‐to‐Cure Patients
November 12, 2016
Sit back and watch a panel of HCV experts discuss the recent updates and changes to AASLD-IDSA recommendations for testing, managing, and treating hepatitis C. Other topics include: efficacy of various DAA regimens in patients who have failed prior DAA therapies and efficacy and safety of different DAA regimens in the new difficult-to-cure patients.

Top Hepatitis Stories From Around The Web

Healio
HCV Next Cover Story - 2017 A Year in Transition
2017: A Year in Transition
"HCV Next" features cutting edge news on the latest HCV research developments. With in-depth articles on a range of topics; diagnosis, hepatitis c treatment regimens, side effects, drug/drug interaction, guidelines, practice management issues, to name a few.
Begin here.....

HIVandHepatitis.com
Top 10 HIV and Hepatitis Stories of 2016

Simplification and optimization of antiretroviral therapy for HIV, wider use of pre-exposure prophylaxis (PrEP), a growing appreciation that people with undetectable viral load do not transmit HIV, and an expanded armamentarium of treatments for hepatitis C were among the top HIV and viral hepatitis headlines this year. Here's a look back at some of our biggest news from 2016.

Hepatitis B Foundation

Ten Things You Should Know About Hepatitis B and Do in 2017
It’s 2017, and experts around the world continue to study the complex life cycle of the hepatitis B virus in order to find a chink in its armor that will lead to a cure. In 2016, there were successes and disappointments in the research and healthcare arena. Here is what you need to know about hepatitis B in 2017.

Healio: Top Ten Most Read Articles In 2016
ILC coverage, HCV guidelines, FDA approvals among 2016 hot topics in hepatology

New data presented at the 2016 International Liver Congress, new guidelines on the management of hepatitis C virus infection from EASL and the WHO, and several new FDA approvals were among the most popular news topics covered by Healio.com/Hepatology this year.

HEP Your Guide To Hepatitis

Here are the stories and blogs with the most shares across social media this year;
2016 Top Shared Stories

1. FDA Approves Gilead’s Hepatitis C Regimen Epclusa (Sofosbuvir/Velpatasvir)
Posted: June 28

2. Epclusa: The Newest Hepatitis C Treatment
Posted: June 28

3. Looks Like Boomers Didn’t Get Hepatitis C From Youthful Drug Use After All
Posted: April 13

4. Hepatitis C Is Now the Biggest Killer Among All Infectious Diseases
Posted: May 4

5. Success for 8 Weeks of Gilead’s All-Genotype Hepatitis C Regimen
Posted: April 25

6. Zepatier: The Newest Hepatitis C Drug
Posted: February 1

7. After Curing Hepatitis C, Risk of Liver Cancer Remains Elevated
Posted: June 15

8. All Veterans With Hepatitis C, Without Restrictions, to Get Treatment
Posted: March 15

9. Near Perfect Hepatitis C Cure Rate For Ravidasvir and Sovaldi Among Those With Genotype 4
Posted: March 6

10. Hepatitis C is Killing Americans in Record Numbers While Patients Cannot Access Life Saving Medicine
Posted: May 16

11. Harvoni is Safe and Effective in Seniors With Hepatitis C
Posted: March 30

12. Hep C Relapses Are Uncommon Among Those Proclaimed Cured, But Reinfection is a Concern
Posted: March 7

13. Tattoos and Hepatitis C: What Are the Risks?
Posted: July 14

14. How Long Does Recovery From Hep C Treatment Take?
Posted: July 13

15. Hepatitis C Treatment Side Effects
Posted: May 31

Specialty Pharmacy Times
Lauren Santye, Assistant Editor
Publish Date: Wednesday, December 28, 2016
AbbVie Hepatitis C Drug Granted Breakthrough Therapy Designation
Experimental hepatitis C medication treats genotypes 1 through 6.

A Patient's Long, Difficult Journey to a Cure for Hepatitis C

Burdened by the symptoms of hepatitis C, an Australian man faced an uncertain future before new antiviral drugs offered hope.

Zepatier Tops Other Hepatitis C Drugs in Safety Comparison

Researchers compare top selling hep C medications Zepatier, Sovaldi, Harvoni, and Viekira Pak.

Merck Wins Nearly $2.5 Billion from Gilead in Hepatitis C Drug Royalties Verdict

Jury declares Merck’s acquired HCV drug patent valid.

First Drug for All Major Hepatitis C Genotypes Approved by FDA

Epclusa showed up to 99% viral suppression after 12 weeks across major hepatitis C genotypes.

Experts Call for End of Restricted Access to Hepatitis C Antivirals for Drug Users

Achieving global elimination of the virus starts with illicit drug users accessing curative hepatitis C virus treatments.

Is Prior Authorization Creating a Barrier to Eradicating Hepatitis C?

Nearly 1 of 4 initial requests for Harvoni were denied in a recent study of hepatitis C drug coverage.

Pharmacist Pleads Guilty in Hepatitis C Drug Fraud Case

Tennessee pharmacist admits to falsifying prior authorizations, medical lab reports, and drug test results for at least 51 hepatitis C patients prescribed Sovaldi, Harvoni, Viekira Pak, and Daklinza.

Black Plague Left Clues for Fighting Hepatitis C, HIV

Aberrant protein mutation associated with the black plague may lead to treatments for HIV and hepatitis C.

Improved Hepatitis C Screening Still Needed for Baby Boomers

Baby boomer generation are five times more likely to be diagnosed with hepatitis C virus.

Most Physicians Believe High-Cost Hepatitis C Drugs Are Worth the Price Tag

Debate continues surrounding cost versus cure in hepatitis C treatment.

Express Scripts Adds Hepatitis C Drug Harvoni to 2017 National Formulary

After 2 years of exclusion, Harvoni has been added to the Express Scripts national formulary for the treatment of hepatitis C.

New Hepatitis C Drug Expected to Challenge Dominance of Gilead in HCV Market

Zepatier is priced considerably lower with similar efficacy to Harvoni and Sovaldi.

As Out-of-Pocket Costs Rise, Hepatitis C Drug Adherence Drops

Manufacturer coupons found to show significant benefits reducing Sovaldi cost share.

GoodRx
2016 Year in Review: Good News, Bad News, and Looking Ahead to 2017
The two largest prescription insurance companies, Express Scripts and Caremark, dropped coverage for 40 popular drugs in 2016. Most notably, medications like the popular insulin Lantus, and venlafaxine ER (Effexor XR) for depression have been dropped by Caremark. Express Scripts dropped Taltz for psoriasis, and Orencia for rheumatoid arthritis, among others, and Viekira Pak now has only limited coverage. Insurers are also restricting coverage for many of the expensive (but effective) hepatitis C drugs like Zepatier and Olysio, leaving only Sovaldi and Harvoni as options.

Wishing you all a safe and healthy 2017!
Tina

This Army Vet Is Fighting Hep C With Big Pharma’s Help

This Army Vet Is Fighting Hep C With Big Pharma’s Help

by Doni Bloomfield
@DoniBloomfield

More stories by Doni Bloomfield
‎December‎ ‎29‎, ‎2016‎ ‎5‎:‎00‎ ‎AM‎ ‎EST

Burkett specializes in lining up testing and treatment for patients, and most of his work is funded by companies including Gilead Sciences Inc., AbbVie Inc. and Merck & Co. that have sold almost $50 billion of the new antivirals since they began hitting the market in 2013. Stiff competition has driven prices down and discounts up, and many insured patients have already been treated. That’s been bad news for the market leader, Gilead, which must increasingly find patients through the social service networks that target drug users and the poor. Many patients don’t even know they have the infection, which can take years to show symptoms.

“They are seeing patient volume declines even though there are 1 or 2 million patients out there,” said Michael Yee, an analyst with RBC Capital Markets. “They have to go out and find those 1 to 2 million.”
Continue reading...

Wednesday, December 28, 2016

Faldaprevir–Deleobuvir - Hepatitis C Virus Genotype-1b-Infected Patients w-Cirrhosis and Moderate Hepatic Impairment

Research Article

In conclusion, in this small study in treatment-naïve and treatment-experienced patients with chronic HCV genotype-1b infection and mild or moderate hepatic impairment, the response to 24 weeks of treatment with faldaprevir, deleobuvir and ribavirin was not durable, with 74% of patients achieving SVR4 but only 57% achieving SVR12. Since this study was initiated, the HCV field has changed rapidly with the advent of new DAAs and all-oral DAA combinations. Because of this and based on the results of the phase 3 HCVerso1 and HCVerso2 trials [16], the development of the faldaprevir–deleobuvir combination has been terminated.

HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment
Christoph Sarrazin , Michael Manns, Jose Luis Calleja, Javier Garcia-Samaniego, Xavier Forns, Renee Kaste, Xiaofei Bai, Jing Wu, Jerry O. Stern

Abstract
This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and ‘other’ (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%–83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%–76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL^-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL^-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL^-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53–61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis.
Trial Registration: ClinicalTrials.gov NCT01830127.

Discussion Only
View Full Text Research Article Here
In this small study in treatment-naïve and treatment-experienced patients with chronic HCV genotype-1b infection and mild or moderate hepatic impairment, the overall safety and efficacy profiles for 24 weeks of treatment with deleobuvir and faldaprevir in combination with ribavirin were generally consistent with the safety and efficacy profiles observed in non-cirrhotic patients [16].

Overall the majority of patients achieved SVR4 (74%) and SVR12 (57%); however, response rates were lower than rates achieved with other all-oral DAA regimen in HCV-infected patients with cirrhosis (>90% SVR12) [18, 19]. Notably, the trough concentrations of deleobuvir and faldaprevir over 4 weeks of treatment were not substantially different between the CPA and CPB groups and similar proportions of patients achieved SVR4 and SVR12. The proportion of patients who were SVR4 but not SVR12 responders was higher than reported in phase 3 studies in non-cirrhotic patients. In non-cirrhotic patients, 95% of patients achieving SVR4 went on to achieve SVR12 [16]; whereas, in the present study, only 77% (20/26) of patients with SVR4 also achieved SVR12 (Table 2).

This is consistent with data from other all-oral combinations that require longer treatment durations (24 weeks rather than 12 weeks) to achieve SVR in patients with cirrhosis than in those without cirrhosis [2, 18, 19]. Response at treatment Week 4 appeared to predict SVR12 after 24 weeks of treatment, although the small number of patients precluded statistical analysis. This was particularly notable in patients with moderate hepatic impairment (CPB), where none of the 4 patients having Week 4 HCV RNA <25 IU.mL-1, but with target detected, achieved SVR12, whereas 8/9 (89%) of those with undetectable HCV RNA at Week 4 achieved SVR12. It is conceivable that the combination of faldaprevir and deleobuvir with ribavirin is not sufficient to prevent on-going viral replication in patients where residual virus is detected at Week 4. Of note, with more potent DAA combinations, detectable Week 4 HCV RNA is not predictive of treatment failure [2, 18, 19]. Consistent with a more severe disease state, discontinuations, AEs and SAEs were more common in patients with moderate hepatic impairment than in those with mild hepatic impairment. The higher rates of AEs in CPB patients is likely related to these patients having more severe liver disease and a more unstable condition. SAEs reported in CPB patients were primarily related to worsening of the underlying disease (including hepatic cirrhosis, acute hepatic failure, hepatic encephalopathy, ascites, haemorrhage and general physical health deterioration).

In conclusion, in this small study in treatment-naïve and treatment-experienced patients with chronic HCV genotype-1b infection and mild or moderate hepatic impairment, the response to 24 weeks of treatment with faldaprevir, deleobuvir and ribavirin was not durable, with 74% of patients achieving SVR4 but only 57% achieving SVR12. Since this study was initiated, the HCV field has changed rapidly with the advent of new DAAs and all-oral DAA combinations. Because of this and based on the results of the phase 3 HCVerso1 and HCVerso2 trials [16], the development of the faldaprevir–deleobuvir combination has been terminated.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168544

HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection

HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection
Fei Chen, Jian Zhang, Bo Wen, Shan Luo, Yingbiao Lin, Wensheng Ou, Fengfan Guo, Ping Tang, Wenpei Liu & Xiaowang Qu

Received:15 July 2016

Accepted:23 November 2016

Published online:23 December 2016

Scientific Reports 6, Article number: 39409 (2016)
doi:10.1038/srep39409
Download Citation

Abstract

Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common among high-risk individuals. To characterize the virological and immunological features of patients with HBV/HCV dual infection, we enrolled 1,049 individuals who have been identified as injection drug users. Patients were divided into single and dual infection groups according to the serological markers. We found the average HCV RNA level was significantly lower; however, HBV viral load was significantly higher in HBV/HCV dual-infected patients (n = 42) comparing HCV single infection (n = 340) or HBV single infection (n = 136). The level of anti-HBs in patients who experienced spontaneous HBV clearance was higher than that in HCV single-infected patients with HBV spontaneous clearance. The level of anti-HCV E2 in HBV/HCV dual infection was lower than that detected in HCV single infection. Serum levels of IL-6, IL-8, and TNF-α were significantly lower in HBV/HCV dual-infected patients than in patients infected with HBV or HCV alone. Taken together, two viral replications are imbalanced in dual infected patients. The anti-HBs and anti-HCV E2 antibody production were impaired and proinflammatory IL-6, IL-8, and TNF-α also downregulated due to dual infection. These findings will help further understanding the pathogenesis of HBV/HCV dual infection.

Discussion Only

Full Text Available at Nature.

In this study, we found that HBV DNA levels were higher and HCV viral load were lower in HBV/HCV dual infection as compared with HBV or HCV single infection. Our results clearly suggest a competition between HBV and HCV infection when the liver is infected with both viruses, and HBV replication is dominant in dual-infected subjects.

The different HBV and HCV replication levels are typically attributed to direct interference9,11,18. However, we believe that the observed difference in the two viral replications derived from a competition for uninfected hepatocytes rather than from viral interference. It is well known that the prevalence of HBV infection is much higher than that of HCV infection in the Chinese general population16,31. Furthermore, our previous study, which examined HBV and HCV infection patterns between IDUs and the general population using the similar cohort with this study, demonstrated that HBV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations32. From these studies, we infer that most of the patients with HBV/HCV dual infection infected HBV were though perinatal, while some of these patients were infected though injection drug use. However, the study herein shows that HCV was acquired at a later age. Therefore, it is conceivable that the HBV/HCV dual-infected individuals were already infected with HBV before contracting HCV infection. As the majority of the hepatocytes are already infected with HBV, these cells are generally resistant to viral superinfection. Only a small number of hepatocytes are uninfected, which may be available for HCV infection. Besides, HBV has a long-lived nuclear form of its genome (covalently closed circular DNA) that is able to persist in the face of potent inhibition of viral replication. In contrast, HCV does not have a long-lived genome form; HCV is therefore much more susceptible to eradication by potent immunity33. Moreover, a lower HCV level may reflect a small number of HCV-infected cells, which is a possible explanation for the dominant HBV replication in our cohort.

Further to the rationale for our study results is an explanation for the higher HBV DNA levels in the dual-infected patients than in HBV single-infected patients. Patients with HBV single infection, especially those who acquired the infection in adulthood, likely experienced spontaneous viral clearance, and the number of infected cells was significantly reduced as the natural course of the virus progressed. On the other hand, the subjects with dual infection were likely to have been repeatedly infected with HBV during transmission of HCV, leading to more HBV-infected cells despite the ongoing viral clearance. Due to no treatment guidelines for HBV/HCV dual-infection patients, so it is important to determine the “dominant” virus by serological and virological testing prior to initiating therapy. For patients with dominant HCV infection, IFN or pegylated IFN in addition to ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. For patients with dominant HBV infection, pegylated IFN plus ribavirin and a nucleos(t)ide analog appears to be a feasible option2,34,35,36.

Wiedmann et al. showed that chronic HCV-infected patients tended to have poor HBV vaccination response and low anti-HBs antibody levels25. In this study, we found both the percentage of anti-HBs antibody titers ≥10 mIU/mL and anti-HBs levels in the HCV single-infected patients with HBV spontaneous clearance were lower than that found in patients who experienced spontaneous HBV clearance. The results of various studies revealed that higher concentrations of serum antibody may lead to a longer duration of immunity. The anti-HBs titer correlated to the frequency of IFN-γ-producing HBs-specific T cells. Reports show that HBs-specific T cell and antibody responses did not differ between vaccines and HBV-recovered patients37,38. This finding suggests that greater levels of antibody production would lead to enhanced immunity, and that HCV infection may directly or indirectly influence HBV surface antibody production. Therefore, it is necessary to strengthen the HBV vaccine and increase the monitoring of the anti-HBs antibody levels in the high risk population of HCV infection.

Moorman et al. showed an impaired response to HBV vaccination in chronic HCV-infected patients, which was partly attributed to the upregulated expression of PD-1 and PD-L1 on CD4+ T cells26. We also found that the anti-HCV E2 antibody response was weaker in HBV/HCV dual infection than in HCV single infection. The HCV envelope glycoproteins E2 are codified by E2 genomic regions. Envelope glycoprotein E2 comprises two hypervariable regions. The two hypervariable regions are subject to immune pressure, which leads to the formation of escape mutants. Patients infected with HCV develop a humoral immune response against HCV envelope proteins; therefore, anti-HCV E1 and E2 may have the capability of neutralizing HCV infection39. This finding suggests that HBV infection may negatively impact HCV antibody response. Of great consideration, our findings do not support the suggestion that the upregulation of expression of immune checking molecules was partially responsible for lower anti-HBs or anti-HCV E2 levels in the dual infection, since viral proteins are also expressed in single infection if they inhibited the immune response. We believe that the HBV/HCV dual infection placed a heavier burden on the immune system of the host, and that the antibody production has to deal with two viral infections, which leads to a weak antibody response to each virus.

Pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α are involved in HBV- or HCV-induced liver inflammation and treatment outcomes27,40,41,42,43. The expression levels of these cytokines in HBV/HCV dual infection are unclear. Here, we showed that the serum levels of IL-6, IL-8, and TNF-α expression were significantly lower in HBV/HCV dual infection compared with HCV or HBV single infection, which is consistent with an in vitro study that showed that co-culturing HBV and HCV core proteins with human dendritic cells significantly increased the production of immune-suppressive cytokine, IL-10, and decreased the expression of pro-inflammatory cytokines. IL-6, IL-12, and TNF-α. In addition, the results of this study suggested that viral core proteins can synergistically induce the immune tolerance of dendritic cells and overproduce IL-10, which can inhibit the production of pro-inflammatory cytokines such as IL-6 and TNF-α28.

In summary, our study showed that there likely exists competition for uninfected hepatocytes when the liver is infected with both HBV and HCV. The viral dominance in dual infection was largely determined by the virus that firstly established the infection. Hepatitis B replication was dominant in this cohort because HBV was likely the first to infect the majority of liver cells. In addition, dual infection placed a heavier burden on the immune system of the host and weakened the antibody production capacity, leading to a lower level of protective antibody to each virus. Taken together, our data may contribute to further understanding the biology of viral infection and immune response in patients with a dual infection of HBV and HCV.

http://www.nature.com/articles/srep39409

Monday, December 26, 2016

Hepatitis C - Screening for HCC in the Post-SVR12 Setting

2018 - Updates

Letter to the editor

Jan 2018

Hepatocellular Carcinoma Screening in Patients Treated for Hepatitis C

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...
Full Text

Liver cancer incidence after HCV therapy linked to risk factors, not treatment

Direct-acting antiviral treatment for hepatitis C did not correlate with an increased risk for hepatocellular carcinoma in a large cohort study of both treated and untreated patients with or without cirrhosis. Those with incident HCC after DAA treatment had higher risk factors at baseline.

Dec 2016

Healio

The following articles appeared in the December print edition of HCV NEXT, published online at Healio.

Table of Contents
5 Questions
A Conversation With Zobair M. Younossi, MD, MPH

Cover Story
Screening for HCC in the Post-SVR12 Setting

Editorial
HCV Testing Needs Expansion Beyond Baby Boomers

The Take Home
The Liver Meeting 2016

Infectious Disease Week 2016

The Liver Meeting 2016: Beyond HCV

Trend Watch
CMS: Harvoni Outpaces Other Drugs in Total Spending
Canadian Patients With HCV Often Restricted From DAA Treatment

Begin here.....

Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Journal of Hepatology 2017 vol. 66 j 19–27

Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Hamish Innes, Scott McDonald, Peter Hayes, John F. Dillon, Sam Allen, David Goldberg, Peter R. Mills, Stephen T. Barclay, David Wilks, Heather Valerio, Ray Fox, Diptendu Bhattacharyya, Nicholas Kennedy, Judith Morris, Andrew Fraser, Adrian Stanley, Peter Bramley, Sharon J. Hutchinson

Download Full Text Research Article @ NATAP, abstract follows:

Abstract
Background & Aims
The number of people living with previous hepatitis C infection that have attained a sustained viral response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear.

Methods
Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality.

Results
We identified 1824 patients, followed on average for 5.2 years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18)

Conclusions
Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population.

Lay summary
Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk.

Keywords:

Excess mortality, Hepatitis C, Cure, Epidemiology

Thursday, December 22, 2016

Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

HCV Treatment Published on Thursday, 15 December 2016

Written by Michael Carter

Contact hcvnewdrugs@gmail.com

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The above links offer data about interferon-free regimens approved to treat HCV, with learning activities, editorials, and tips from patient bloggers who understand the ups and downs of liver disease, in addition to a list of outstanding hepatitis C websites, blogs and support forums.

On Twitter
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading articles about the treatment and management of hepatitis C.

The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"

Latest Update Feb 12, 2019

Lancet Study:

Direct-acting antivirals reduce risk of premature mortality and liver cancer for people with chronic hepatitis C

These findings firmly counter those of a Cochrane review of direct-acting antiviral treatment trials that could neither confirm nor reject if direct-acting antivirals had an effect on long-term HCV-related morbidity and mortality. They also provide the best evidence to date to support guidance documents that recommend direct-acting antiviral treatment for all patients with chronic HCV infection.

The Controversy
Rebuttal over Cochrane Review of DAAs
A systematic review published by the Cochrane Collaboration suggested achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits. View each rebuttal and all ongoing media coverage.

Risk Of Developing Liver Cancer After HCV Treatment

Sunday, January 1, 2017

Thursday, December 29, 2016

Wednesday, December 28, 2016

Monday, December 26, 2016

Thursday, December 22, 2016