This blog links to hepatitis C news with patient friendly commentary about current HCV treatment options using information extracted from peer-reviewed journals, liver meetings/conferences, and interactive learning activities.
Media Coverage Q&A: First U.S. state-by-state analysis of hepatitis C cases
By Jon Cohen
Apr. 26, 2017 , 12:00 PM
In the infectious disease world, the liver-damaging hepatitis C virus (HCV) long has lived in the shadows of killers such as HIV/AIDS, tuberculosis, and malaria. But curative—and expensive—HCV drugs that have come to market over the past 5 years have focused new attention on the deadly disease.
Now, for the first time, researchers have mapped its U.S. prevalence state-by-state. They hope their model ultimately will help improve targeting of efforts to screen for the virus and treat the more than 3 million people in the country who are living with the infection.
Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States and a leading cause of morbidity and mortality. Previous analyses of the US National Health and Nutrition Examination Survey (NHANES) indicated approximately 3.6 million noninstitutionalized persons with antibody to HCV (anti-HCV). However, state-level prevalence remains less understood and cannot be estimated reliably from NHANES alone.
We used 3 publicly available government data sources to estimate anti-HCV prevalence in each US state among noninstitutionalized persons aged ≥18 years. A small-area estimation model combined indirect standardization of NHANES-based prevalence with logistic regression modeling of mortality data, listing acute or chronic HCV infection as a cause of death, from the National Vital Statistics System during 1999–2012. Model results were combined with US Census population sizes to estimate total number and prevalence of persons with antibody to HCV in 2010.
National anti-HCV prevalence was 1.67% (95% confidence interval [CI], 1.53–1.90), or 3 911 800 (95% CI, 3 589 400– 4 447 500) adults in 2010. State-specific prevalence ranged from 0.71% (Illinois) to 3.34% (Oklahoma). The West census region had the highest region-specific prevalence (2.14% [95% CI, 1.96–2.48]); 10 of 13 states had rates above the national average. The South had the highest number of persons with anti-HCV (n = 1561600 [95% CI, 1 427 700–1 768 900]). The Midwest had the lowest region-specific prevalence (1.14% [95% CI, 1.04%–1.30%]).
States in the US West and South have been most impacted by hepatitis C. Estimates of HCV infection burden are essential to guide policy and programs to optimally prevent, detect, and cure infection. Continue to full text article
International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Candidates Terrault, Norah A. MD, MPH1; McCaughan, Geoff W. MD, BS, PhD2; Curry, Michael P. MD3; Gane, Edward MD4; Fagiuoli, Stefano MD5; Fung, James Y. Y. MD6; Agarwal, Kosh MD7; Lilly, Les MD8; Strasser, Simone I. MBBS, MD9; Brown, Kimberly A. MD10; Gadano, Adrian MD11; Kwo, Paul Y. MD12; Burra, Patrizia MD13; Samuel, Didier MD14; Charlton, Michael MD15; Pessoa, Mario G. MD16; Berenguer, Marina MD17
An expert panel from ILTS reviews the approach to management of HCV in the transplant recipient in the era of direct-acting anti-virals. Considerations range from preemption of recurrence to the treatment of fibrosing cholestatic hepatitis
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C. A link to the above consensus statement was provided by Henry E. Chang.
Factors that predict HCV vertical transmission
The latest issue of Liver International investigates what factors should be optimized using data mining computational analysis to predict HCV vertical transmission.
Neonates born to hepatitis C virus (HCV)-positive mothers are usually not screened for HCV.
Unscreened children may act as active sources for social HCV transmission, and factors contributing for vertical HCV transmitting still remained controversial and needed optimization.
Dr Abd Elrazek and colleagues from Egypt investigated the factors contributing for vertical HCV transmission in Egypt, which has the highest HCV prevalence worldwide.
The researchers prospectively followed the neonates born to HCV-positive mother in the child-bearing period, to identify mother-to-child transmission factors from 2015 to 2016.
HCV vertical transmission was identified in 18% of neonates
Data mining computational analysis was used to quantify the findings.
The team found that among 3000 randomized pregnant women, prevalence of HCV was 2%.
HCV vertical transmission was identified in 18% of neonates.
The researchers identfied that only high viral load at 975.000 IU was the predictor risk for mother-to-child transmission.
Dr Elrazek's team concluded, "Hepatitis C virus in pregnancy has substantial risk for vertical HCV transmission."
"High viral load in HCV-positive women increases the risk of HCV transmission to neonates."
"Screening pregnant women during early stage of pregnancy, and optimizing the HCV viral load in HCV-positive women might prevent vertical HCV transmission to neonates. GastroHep
Background & Aims
Neonates born to hepatitis C virus (HCV)-positive mothers are usually not screened for HCV. Unscreened children may act as active sources for social HCV transmission, and factors contributing for vertical HCV transmitting still remained controversial and needed optimization. We aimed to investigate the factors contributing for vertical HCV transmission in Egypt; the highest HCV prevalence worldwide. Methods
We prospectively followed the neonates born to HCV-positive mother in the child-bearing period, to identify mother-to-child transmission (MTCT) factors from January 2015 to March 2016. Data mining computational analysis was used to quantify the findings. Results
Among 3000 randomized pregnant women, prevalence of HCV was 46/3000 (1.53%). HCV vertical transmission was identified in eight neonates (17.39%). Only high viral load identified at 975.000 IU was the predictor risk for MTCT. Conclusions
Hepatitis C virus in pregnancy has substantial risk for vertical HCV transmission: High viral load in HCV-positive women increases the risk of HCV transmission to neonates. Screening pregnant women during early stage of pregnancy and optimizing the HCV viral load in HCV-positive women might prevent vertical HCV transmission to neonates.
Point-of-care hep C test developed
By LabOnline Staff
Monday, 24 April, 2017
A research team led by UNSW’s Kirby Institute has evaluated a new test that enables diagnosis of hepatitis C infection in a single visit, with promising results. Their study has been published in The Lancet Gastroenterology & Hepatology.
The researchers conducted the first evaluation of the Xpert HCV Viral Load test, manufactured by molecular diagnostics company Cepheid — a point-of-care hepatitis C virus test that can detect active infection from a finger-stick sample of blood. They established that the test demonstrated good sensitivity and specificity in blood tests collected by finger-stick in participants attending drug health and homelessness services in Australia.
“This test represents a major advance over point-of-care antibody-based tests, which only indicate previous exposure to the virus but cannot detect whether you are actively infected,” said Associate Professor Jason Grebely from The Kirby Institute. “We really need to scale up testing for active hepatitis C infection in order to enhance diagnosis, get people linked to appropriate care and provide highly curative treatment with direct-acting antivirals to prevent advanced liver disease and onward transmission of the virus.”
Importantly, new point-of-care platforms enable detection of hepatitis C virus and diagnosis of active infection in a single visit, rather than having to come back for a second visit to obtain test results. As noted by Associate Professor Grebely, “Requiring people to come back for a second appointment to receive their results can present significant barriers, especially for people living in remote areas and for vulnerable and marginalised populations… who are the people we need to reach the most in order to eliminate hepatitis C.”
The finger-stick test is not yet registered in Australia, but international clinical trials are underway to evaluate this point-of-care assay as a diagnostic test for the detection of active HCV infection.
Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study
Dr Jason Grebely, PhD
Francois M J Lamoury, EiCNAM, Behzad Hajarizadeh, PhD, Yasmin Mowat, BSc, Alison D Marshall, MA, Sahar Bajis, MIPH, Philippa Marks, MPH, Janaki Amin, PhD, Julie Smith, RN, Michael Edwards, MBBS, Carla Gorton, MPH, Nadine Ezard, PhD, David Persing, PhD, Marika Kleman, PhD, Philip Cunningham, PhD, Beth Catlett, BSc, Prof Gregory J Dore, PhD, Tanya L Applegate, PhD on behalf of the LiveRLife Study Group
Published: 21 April 2017
Point-of-care hepatitis C virus (HCV) RNA testing offers an advantage over antibody testing (which only indicates previous exposure), enabling diagnosis of active infection in a single visit. In this study, we evaluated the performance of the Xpert HCV Viral Load assay with venepuncture and finger-stick capillary whole-blood samples.
Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort enrolled at five sites in Australia (three drug and alcohol clinics, one homelessness service, and one needle and syringe programme). We compared the sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA detection by venepuncture and finger-stick collection with the Abbott RealTime HCV Viral Load assay (gold standard).
Of 210 participants enrolled between Feb 8, 2016, and July 27, 2016, 150 participants had viral load testing results for the three assays tested. HCV RNA was detected in 45 (30% [95% CI 23–38]) of 150 participants based on Abbott RealTime. Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in plasma collected by venepuncture was 100·0% (95% CI 92·0–100·0) and specificity was 99·1% (95% CI 94·9–100·0). Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick was 95·5% (95% CI 84·5–99·4) and specificity was 98·1% (95% CI 93·4–99·8). No adverse events caused by the index test or the reference standard were observed
The Xpert HCV Viral Load test can detect active infection from a finger-stick sample, which represents an advance over antibody-based tests that only indicate past or previous exposure.
National Health and Medical Research Council (Australia), Cepheid, South Eastern Sydney Local Health District (Australia), and Merck Sharp & Dohme (Australia).
Lancet Xpert HCV Viral Load Test Can Detect Active Hepatitis C Infection From Fingerstick
Posted on April 25, 2017
Jason Grebely PhD
Senior Research Fellow (UNSW)
Viral Hepatitis Clinical Research Program
MedicalResearch.com: What is the background for this study? What are the main findings? Response: Globally, testing and diagnosis of hepatitis C virus infection remain low. Although point of care tests for HCV infection exist, but many of these tests only measure HCV antibodies (previous exposure), not HCV RNA (active infection). Given that 25% of individuals spontaneously clear HCV infection, efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing.
We conducted the first evaluation of the Xpert HCV Viral Load test (manufactured by Cepheid) – a point-of-care hepatitis C virus test that can detect active infection – from a finger-stick sample of blood. We established that there is good sensitivity and specificity of the Xpert HCV Viral Load point-of-care test using blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia.
MedicalResearch.com: What should readers take away from your report? Response: This test represents a major advance over point of care antibody-based tests, which only indicate previous exposure to the virus but cannot detect whether you are actively infected. This new point of care platform enables detection of hepatitis C virus and diagnosis of active infection in a single visit, rather than having to come back for a second visit to obtain test results. Data have shown that on-site HCV testing with integrated care improves linkage to HCV care.
We really need to scale up testing for active hepatitis C infection in order to enhance diagnosis, get people linked to appropriate care, and provided highly curative treatment with direct-acting antivirals to prevent advanced liver disease and onward transmission of the virus.
MedicalResearch.com: What recommendations do you have for future research as a result of this study? Response: Further validation studies are needed to further evaluate the performance of this assay in different settings and populations (eg, patients given DAA therapy, those with a sustained virological response, or those with HIV/HCV co-infection). Also, future research should evaluate the effectiveness of integrating point of care testing into interventions to enhance linkage to HCV care and treatment.
Disclosures: JG is a consultant and adviser and has received research grants from AbbVie, Bristol-Myers Squibb, Cepheid, Gilead Sciences, and Merck/MSD.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community. Interview Source
New Haven: Achillion Pharmaceuticals [Nasdaq: ACHN] presented data on its three drug combination to treat Hepatitis C, at The International Liver Congress in Amsterdam in late April, just a week before the national kick-off of Hep C Awareness Month.
Jansen is financially responsible for all clinical trials and they initiated the Phase II clinical trial, last May of 300 participants of the drug combination, simeprevir, odalasvir and AL-335.
Jansen previously developed simeprevir and odalasvir, but required Achilion’s A-335 to achieve the effectiveness needed to cure Hep C.
The clinical results presented could be described as really good and really not so good.... Continue reading
Direct-acting antiviral regimens have revolutionized the treatment of Hepatitis C Virus (HCV) yet controversy exists regarding the optimal timing for treating HCV infected liver transplant candidates. This commentary addresses the complexities of treating these patients at the appropriate time given the unpredictable nature of liver transplant timing.
Direct-acting antiviral (DAA) regimens have revolutionized our approach to hepatitis C virus (HCV) management. Guidance from American Association for the Study of Liver Diseases/Infectious Diseases Society of America, European Association for the Study of the Liver, and Asian Pacific Association for the Study of the Liver1-3 now outline simple and highly effective pathways to cure for nearly all patients with HCV. Safety and efficacy of DAA regimens, even among those with decompensated cirrhosis, creates new opportunities for cure in patients who would have been previously ineligible for treatment.4 Although HCV remains a leading indication for liver transplant worldwide, there has been a paucity of data and subsequent guidance for management of liver transplant candidates with HCV. Paradoxically, we have found that simple, effective treatment regimens have spawned perhaps unanticipated complexities of HCV management in liver transplant candidates. These complexities arise because goals of therapy span beyond solely targeting viral eradication but require a comprehensive understanding of the dynamic and sometimes unpredictable nature of liver transplantation (LT) candidacy. Anticipated wait time, risk of hepatocellular carcinoma (HCC) recurrence or progression, physiologic response to cure as well as availability of HCV-positive donors all impact decisions to treat. In this issue of Transplantation, Terrault et al5 define these issues and offer much needed guidance by addressing clinical questions of interest in the International Liver Transplant Society Consensus Statement in Management of Liver Transplantation Candidates.
Data remains sparse and, at times, conflicting regarding the management of HCV in patients with HCC who are awaiting LT. In the single published study evaluating DAA-based treatment outcomes in waitlisted patients with HCV and HCC, duration of time with a negative viral load was found to be a significant predictor of HCV recurrence posttransplant.6 This concept has not yet been validated in newer DAA regimens and minimum duration of an undetectable viral load required before transplant to ensure posttreatment eradication has yet to be defined. Timing matters in HCV treatment pre-LT; however, we are still unsure of how much time we need and how much time we have. In addition, recent controversy regarding a potentially negative impact DAA treatment may play in aggressive cancer recurrence has added another wrinkle in complexity of the decision to treat waitlisted patients with HCC.7,8 Terrault et al5 describe the quality of data that associates a link between HCC recurrence and DAA therapy as low and insufficient to withhold therapy; however, pending further data, they recommend the association should at least be considered. Although the consensus statement recommends HCV treatment in waitlisted patients with HCC, severe limitations of data require this recommendation to be conditional and should be individualized based on patient characteristics and transplant center.
HCV treatment in the setting of waitlisted patients with decompensated cirrhosis is also thoughtfully addressed. Successful HCV treatment may improve survival on the waiting list and may allow for avoidance of OLT altogether.9 These benefits must be balanced with potential unintended negative consequences of treatment. This includes reduced SVR rates in CTP B and C cirrhosis with risk of resistant variant generation as well as negligible clinical benefit achieved after SVR in patients who lack hepatic regenerative capacity. Finally, it may be disadvantageous to treat and create a small improvement in Model for End Stage Liver Disease (MELD)/Child-Turcotte-Pugh (CTP) resulting in a demotion of priority on the waitlist, yet insufficient clinical improvement to avoid LT.4 What remains elusive is a true understanding of the “point of no return,” that is, the degree of liver dysfunction where HCV therapy does not yield any clinical benefit. The consensus statement frames this question based on available metrics, such as MELD, CTP, and transplant center characteristics; however, due to limitations in available data, the strength of these recommendations remain weak. Why is a point of no return so difficult to define? First, HCV treatment in patients with decompensated cirrhosis is only a recently available option, and experience remains limited. Second, the point of no return is simple in theory, but complex in practice. MELD and CTP scores were not designed to answer this question, and we may be using imprecise tools to predict a clinical outcome that relies on regenerative capacity of the liver after viral eradication. Finally, the point of no return is intrinsically related to regional transplant landscape and policy. Waitlist time, DAA availability and allocation schemes will all impact how much benefit HCV treatment will yield. The consensus statement has provided a useful foundation for consideration of this topic, but further study will be necessary to identify more precise, site-specific tools to guide us in this difficult decision to treat.
Finally, the consensus statement supports selective use of anti–HCV-positive grafts in HCV-positive recipients as well as early treatment for all LT patients with HCV.5,10 The efficacy and safety of DAA therapy post-LT has also allowed Terrault and colleagues to boldly offer consideration to use HCV-positive grafts in HCV negative recipients. The Consensus Statement stresses the need for comprehensive informed consent and defines appropriate settings for use such as high medical urgency and severe limitations in organ availability. Although data are limited and firm guidelines for use cannot yet be made, innovative thought leveraging DAA therapy such as this may significantly increase access and optimize use of available organs. However, the concept of knowingly transmitting an infectious disease into an unexposed patient is subject to some degree of moral relativism and thus may not be universally applied even though there is some precedent with infections, such as cytomegalovirus. Nonetheless, routine use of HCV-positive grafts in any recipient underscores the importance of universal access to HCV therapy post-LT.
The new era of DAA therapy has expanded candidacy for HCV treatment to include our sickest patients who are in need of LT. The consensus statement in this issue of Transplantation marks unprecedented progress in HCV therapy and also defines where our understanding is limited. Our tools to determine the optimal timing for therapy seem rudimentary in comparison to the technologically advanced DAAs, and further study to equilibrate the two is crucial. We know how to treat our patients with HCV who are awaiting transplantation, now we just need to know when to treat them.
1. AASLD-IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. http://www.hcvguidelines.org/. Accessed February 13, 2017. Cited Here...
2. European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015;63:199–236. Cited Here... | PubMed | CrossRef
3. Omata M, Kanda T, Wei L, et al. APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int. 2016;10:702–726. Cited Here... | PubMed
4. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618–2628. Cited Here... | View Full Text | PubMed | CrossRef
5. Terrault NA, McCaughan GW, Curry MP, et al. International Liver Transplantation Society Consensus Statement on hepatitis C management in liver transplant candidates. Transplantation. 2017;101:945–955. Cited Here... | View Full Text | CrossRef
6. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148:100–107.e1. Cited Here... | PubMed | CrossRef
7. Pol S. Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: data from three ANRS cohorts. J Hepatol. 2016;65:734–740. Cited Here... | PubMed | CrossRef
8. Reig M, Mariño Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65:719–726. Cited Here... | PubMed | CrossRef
9. Belli LS, Berenguer M, Cortesi PA, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol. 2016;65:524–531. Cited Here... | PubMed | CrossRef
10. Northup PG, Argo CK, Nguyen DT, et al. Liver allografts from hepatitis C positive donors can offer good outcomes in hepatitis C positive recipients: a US National Transplant Registry analysis. Transpl Int. 2010;23:1038–1044. Cited Here... | View Full Text | PubMed | CrossRef
Illegal Cancer Treatments: FDA Warning - Fraudulent Claims of Diagnosis, Treatment, Prevention or Cure
AUDIENCE: Oncology, Patient, Consumer
ISSUE: FDA issued warning letters addressed to 14 U.S.-based companies illegally selling more than 65 products that fraudulently claim to prevent, diagnose, treat or cure cancer.
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses. The illegally sold products cited in the warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas and diagnostics (such as thermography devices). They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing or curing cancer, killing/inhibiting cancer cells or tumors, or other similar anti-cancer claims. See the list of illegally sold cancer treatments.
BACKGROUND: The products are marketed and sold without FDA approval, most commonly on websites and social media platforms.
RECOMMENDATION: Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment. Avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult with their health care professional about proper prevention, diagnosis and treatment of cancer.
FDA takes action against 14 companies for selling illegal cancer treatments
The U.S. Food and Drug Administration today posted warning letters addressed to 14 U.S.-based companies illegally selling more than 65 products that fraudulently claim to prevent, diagnose, treat or cure cancer. The products are marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs. “We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a health care professional about proper prevention, diagnosis and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses. The illegally sold products cited in the warning letters posted today include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas and diagnostics (such as thermography devices). They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anti-cancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent products making cancer claims on websites, social media and in stores. Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due in part to the ease with which companies can move their marketing operations to new websites. The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages health care professionals and consumers to report adverse reactions associated with these or similar products to the agency’s MedWatch program.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Reporting Program: Complete and submit the report Online: www.fda.gov/MedWatch/report Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
There was also no consistency with regard to the DAA regimen most likely to lead to HBV reactivation, suggesting a potential class-effect with DAA agents, researchers from the U.S. Food and Drug Administration (FDA) report in a paper online today in Annals of Internal Medicine.
HBV reactivation associated with DAA therapy is a “newly identified safety concern in patients previously infected with HBV. Patients with a history of HBV infection require clinical monitoring while receiving DAA therapy,” write Dr. Susan Bersoff-Matcha and colleagues.
Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus
Susan J. Bersoff-Matcha, MD; Kelly Cao, PharmD; Mihaela Jason, PharmD; Adebola Ajao, PhD; S. Christopher Jones, PharmD, MS, MPH; Tamra Meyer, PhD, MPH; and Allen Brinker, MD, MS
Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV–HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis.
Objective: To assess whether HBV-R is a safety concern in patients receiving HCV DAAs.
Design: Descriptive case series.
Setting: U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).
Patients: 29 patients with HBV-R receiving HCV DAAs.
The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV chacteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others.
The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported.
Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV–HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the second most common cause of cancer deaths worldwide. The top three causes of HCC are hepatitis B virus (HBV), hepatitis C virus (HCV), and alcoholic liver disease. Owing to recent advances in direct-acting antiviral agents, HCV can now be eradicated in almost all patients. HBV infection and alcoholic liver disease are expected, therefore, to become the leading causes of HCC in the future. However, the association between alcohol consumption and chronic hepatitis B in the progression of liver disease is less well understood than with chronic hepatitis C. The mechanisms underlying the complex interaction between HBV and alcohol are not fully understood, and enhanced viral replication, increased oxidative stress and a weakened immune response could each play an important role in the development of HCC. It remains controversial whether HBV and alcohol synergistically increase the incidence of HCC. Herein, we review the currently available literature regarding the interaction of HBV infection and alcohol consumption on disease progression.
Effectiveness and Safety of Sofosbuvir-based Regimens Plus an NS5A Inhibitor for Patients With HCV Genotype 3 Infection and Cirrhosis
Results of a Multicenter Real-life
S. Alonso; M. Riveiro-Barciela; I. Fernandez; D. Rincón; Y. Real; S. Llerena; F. Gea; A. Olveira; C. Fernandez-Carrillo; B. Polo; J. A. Carrión; A. Gómez; M. J. Devesa; C. Baliellas; Á. Castro; J. Ampuero; R. Granados; J. M. Pascasio; A. Rubín; J. Salmeron; E. Badia; J. M. M. Planas; S. Lens; J. Turnes; J. L. Montero; M. Buti; R. Esteban; C. M. Fernández-Rodríguez
J Viral Hepat. 2017;24(4):304-311.
Abstract and Introduction Abstract
Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.
View Full Text @ Medscape Free registration required
Management of Cirrhotic Patients After Successful HCV Eradication Kwok, R.M. & Tran, T.T.
Curr Treat Options Gastro (2017).
First Online: 24 April 2017
Chronic hepatitis C (HCV) is a hepatotropic virus which, when untreated, can lead to progressive inflammation and fibrosis resulting in cirrhosis, hepatocellular carcinoma (HCC), and decompensations related to end-stage liver disease. The relatively recent introduction of all oral, interferon-free, direct-acting antiviral medications against HCV has transformed the management of these patients. Previous treatment regimens were prolonged, poorly tolerated, and frequently did not result in cure. Current therapies achieve sustained viral response (SVR) in the vast majority of patients including those with decompensated liver disease; a previously challenging population to treat. These successes will result in significant numbers of cirrhotic patients requiring management after SVR. Although many complications of cirrhosis are improved in this setting, regular follow-up of HCC, esophageal varices, and other sequelae of cirrhosis will be necessary. This chapter will review the management of cirrhosis in HCV patients achieving cure.
Generic hepatitis C drugs continue to produce high cure rates
Published: 24 April 2017
Treatment with generic versions of direct-acting antiviral drugs continues to produce similar cure rates to those reported in clinical trials, Dr James Freeman reported last week at the International Liver Congress in Amsterdam.
Dr James Freeman, an Australian general practitioner based in Hobart, Tasmania, was reporting on the outcomes of people with hepatitis C who imported generic versions of direct-acting antivirals manufactured in India and elsewhere because they couldn’t afford treatment in their own country, or were denied treatment on grounds of cost.
Importation of medicines for personal use is permitted under customs regulations in Australia and the United Kingdom, and many other countries have regulations permitting the importation of small amounts of medicines for personal use or their carriage through customs in personal luggage. The FixHepC buyer’s club provided advice and information on how to do this safely and legally, starting in Australia, but soon responding to enquiries from people in Europe, North America, New Zealand and South East Asia. Continue reading.....
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"