Hepatitis C Treatment After Kidney Transplant May Extend Lives and Decrease Costs

MedicalResearch.com Interview with:

Mark H. Eckman, MD Posey Professor of Clinical Medicine Director, Division of General Internal Medicine Director, Center for Clinical Effectiveness University of Cincinnati Medical Center Cincinnati, OH

Dr. Eckman

Mark H. Eckman, MD
Posey Professor of Clinical Medicine
Director, Division of General Internal Medicine
Director, Center for Clinical Effectiveness
University of Cincinnati Medical Center
Cincinnati, OH 

MedicalResearch.com: What is the background for this study?

Response: People who are infected with hepatitis C virus and have kidney failure need a kidney transplant.

Recent studies have found that it is possible to transplant kidneys from donors who are infected with hepatitis C virus into patients who need a transplant and are already infected with the virus. In addition, drugs are available to cure most patients of hepatitis C virus, including those who have kidney failure. Infected patients who need a kidney transplant have 2 options. One option is to receive an infected kidney and then use drugs after the transplant to cure themselves and the transplanted kidney of the virus. Another option is to use the drugs first to get rid of the virus and then to receive a kidney from a donor who does not have hepatitis C virus infection.

For the more than 500,000 patients receiving dialysis for end-stage renal disease (ESRD), less than 4% receive kidney transplants. Because of the limited organ availability, hemodialysis is the final treatment for most patients with ESRD. Of the 10% or so of U.S. patients receiving dialysis who are infected with the hepatitis C virus (HCV), some are willing to accept HCV-infected kidneys, in part, because the wait times for such kidneys are shorter than those for HCV-uninfected kidneys. Because the yearly mortality rate for patients receiving hemodialysis is so high, between 4% and 16%, reducing the time to kidney transplant can have a dramatic effect on both survival and quality of life.

Because it may not be possible to do this type of research with actual people, we created a model that allowed us to estimate possible outcomes without using actual people.

The model was a computer program that combined the best available information to approximate what might happen to participants in a real-world clinical trial. Continue reading

Double-Edge Sword of Drug Epidemic

MedicalResearch.com Interview with:
Christine Marie Durand, M.D
.
Assistant Professor of Medicine
Johns Hopkins Medicine 

MedicalResearch.com: What is the background for this study

Response: Most Americans know that the United States faces an epidemic of deaths due to drug overdose.  And many are also aware that there is a critical shortage of organs available for transplant.  Perhaps less widely known is that today, more than 1 in every 8 deceased organ donors died from a drug overdose.  The objective of our study was to look at the outcomes of patients who received transplants with organs donated after an overdose.

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Most Baby Boomers Still Aren’t Screened For Hepatitis C

MedicalResearch.com Interview with:

In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E. CDC/ E.H. Cook, Jr.

Hepatitis Virions
CDC/ E.H. Cook, Jr.

Dr. Monica Kasting PhD first author
Dr. Anna Giuliano PhD
Susan. T. Vadaparampil, Ph.D., M.P.H.
Senior Member/Professor
Center for Infection Research in Cancer
H. Lee Moffitt Cancer Center, Tampa,
Florida.Department of Cancer Epidemiology,
H. Lee Moffitt Cancer Center,
Tampa, Florida 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: In the U.S., approximately 1 in 30 baby boomers are chronically infected with hepatitis C virus. Half of all cases of liver cancer are caused by hepatitis C and liver cancer is one of only three cancer types that are actually increasing in incidence in the US. Because of this, in 2012 the CDC issued a recommendation for universal screening for hepatitis C virus for everyone born between 1945 and 1965 (baby boomers). We wanted to look at the time period after that to see if the rates of screening in that population increased. From 2013-2015 screening among baby boomers only increased by 0.9% (from 11.8% to 12.7%) which indicates we still have a long way to go before we meet our goal of universal screening.  Continue reading

‘Liver-on-a-Chip’ Technology Can Accurately Mimic Hepatitis B Infection

MedicalResearch.com Interview with:

Primary hepatocytes grown in 3D microfluidic “liver-on-a-chip” platform following infection with hepatitis B virus. Credit: Marcus Dorner/Imperial College London

Primary hepatocytes grown in 3D microfluidic “liver-on-a-chip” platform following infection with hepatitis B virus. Credit: Marcus Dorner/Imperial College London

Marcus Dorner, PhD
Non-Clinical Senior Lecturer in Immunology
Wellcome Trust Investigator
Imperial College London
Department of Medicine, Section of Virology
School of Medicine
London United Kingdom 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Hepatitis B virus (HBV) infection globally affects over 250 million people and is currently not curable. This infection can lead to liver cirrhosis and liver cancer and is among the leading causes for liver transplantation. Unfortunately, HBV is among the most difficult viruses to study in the laboratory, since model systems are not very good at recapitulating what happens in infected humans.

We have just described the first model to effectively change this. Using an artificial “Liver-on-a-Chip”, we have developed a tool, which can potentially revolutionise how we study viral infections by merging the study of viruses with tissue engineering. This model is over 10,000-fold more susceptible to HBV infection and accurately mimics, what happens in an infected patient. This can now be utilised to develop novel and potentially curative therapies, which would benefit millions of people currently living with chronic HBV infection.  Continue reading

Hepatitis: 8 Weeks of Once Daily, Combination Pill Found Effective in HCV 1 and 3

MedicalResearch.com Interview with:

In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E. CDC/ E.H. Cook, Jr.

In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E.
CDC/ E.H. Cook, Jr.

Stefan Zeuzem, M.D.
Professor of Medicine
Chief Internal Medicine
Goethe University Hospital
Frankfurt, Germany

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Chronic hepatitis C virus (HCV) infection is a major global public health problem with more than 71 million people infected worldwide, and can result in significant morbidity and mortality, including liver cirrhosis, hepatocellular carcinoma, and death.1

This publication describes the efficacy and safety results from two Phase 3 clinical trials, ENDURANCE-1 and ENDURANCE-3, in patients with chronic HCV genotypes (GT) 1 or 3 infection who were treated with an all-oral, once-daily combination regimen of direct-acting antiviral agents (DAA) glecaprevir (GLE) at 300 mg and pibrentasvir (PIB) at 120 mg.

The findings from ENDURANCE-1 trial show that the GLE/PIB combination regimen (G/P) given for 8 weeks to HCV GT1 chronically infected non-cirrhotic treatment-naïve or treatment-experienced (with sofosbuvir and/or interferon with ribavirin) patients was safe and well-tolerated, achieved high efficacy with a sustained virologic response at post-treatment week 12 (SVR12) rate >99% and was non-inferior to 12-week treatment with G/P.

The trial also included subjects who were co-infected with human immunodeficiency virus (HIV), and all of these subjects achieved SVR12 while maintaining HIV suppression throughout the study. ENDURANCE-3 trial results show that the G/P regimen given for 8 weeks to HCV GT3 chronically infected non-cirrhotic treatment-naïve patients was safe and well-tolerated, achieved high efficacy in this historically difficult to cure GT with an SVR12 rate >94%, and was non-inferior to 12-week treatment with G/P, which in turn was non-inferior to the treatment with 12-week DAA regimen of sofosbivir and daclatasvir.  Continue reading

Xpert HCV Viral Load Test Can Detect Active Hepatitis C Infection From Fingerstick

MedicalResearch.com Interview with:

Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program

Dr. Grebely

Jason Grebely PhD
Associate Professor
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.

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ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries

MedicalResearch.com Interview with:

Paul Y. Kwo, MD, FACG Stanford University School of Medicine

Dr. Paul Y. Kwo

Paul Y. Kwo, MD, FACG
Stanford University School of Medicine

MedicalResearch.com: What is the background for this study?

Response: This guideline, which was jointly authored by Drs. Kwo, Cohen, and Lim provides a framework for physicians to approach the very common problem encountered of a patient whose liver chemistries are abnormal. This is particularly relevant as there remain large pools of individuals who have yet to be diagnosed with chronic hepatitis B and C, non-alcoholic fatty liver disease, advanced liver disease as well as less common conditions, all of whom will require evaluation.

In particular, the rise in the prevalence of non-alcoholic fatty liver disease worldwide will be addressed in part by identifying and evaluating these individuals prior to the development of advanced fibrosis. The guideline takes clinicians through a step-wise approach to the evaluation of elevated aminotransferase (ALT and AST), alkaline phosphatase, and bilirubin levels including appropriate historical questions, important physical examination findings, laboratory , radiological evaluation and finally liver biopsy if required.

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Many High Risk Patients Not Screened for Hepatitis B

MedicalResearch.com Interview with:

Robert Wong MD, MS OakCare Medical Group Assistant Clinical Professor UCSF

Dr. Robert Wong

Robert Wong MD, MS
Assistant Clinical Professor of Medicine
Director of Research and Education
Division of Gastroenterology and Hepatology
Alameda Health System – Highland Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hepatitis B Virus infection is a leading cause of chronic liver disease leading to hepatocellular carcinoma and cirrhosis worldwide. Early detection of chronic HBV through implementation of effective screening programs can improve early treatment to reduce disease progression and risk of hepatocellular carcinoma. Sub-optimal awareness of the importance of HBV screening among patients and providers and sub-optimal awareness of who constitutes as high risk may further contribute to low HBV screening rates. Our current study prospectively evaluated rates of HBV screening and awareness of HBV screening results among patients at high risk for chronic HBV among an ethnically diverse underserved safety-net hospital population.

Among nearly 900 patients that were evaluated, 62% were high risk and eligible for Hepatitis B screening. However, among this high risk population, less than 25% received HBV screening. Furthermore, among patients that have undergone previous HBV testing only 22% of patients were aware of those results.

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Insurers Can Pay High Cost of Hepatitis C Drugs, But Not Benefit If Patient Switches Plans

MedicalResearch.com Interview with:

Darius Lakdawalla PhD Quintiles Chair in Pharmaceutical Development and Regulatory Innovation School of Pharmacy Professor in the Sol Price School of Public Policy University of Southern California

Dr. Darius Lakdawalla

Darius Lakdawalla PhD
Quintiles Chair in Pharmaceutical Development and Regulatory Innovation
School of Pharmacy
Professor in the Sol Price School of Public Policy
University of Southern California 

MedicalResearch.com: What is the background for this study?
Dr. Lakdawalla: New treatments for hepatitis-C are highly effective but also involve high upfront costs.  Because they effectively cure the disease, all the costs of treatments are paid over a short period of time – about three months – but the benefits accrue for the rest of a patient’s life.  This creates problems for the private health insurance system, where patients switch insurers.  The insurer that pays the bill for the treatment might not be around to enjoy the benefits of averting liver damage, liver transplants, and other costly complications associated with hepatitis-C.
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4-Dose Hepatitis B Vaccine Schedule For HIV Patients Induces Longer Protection

MedicalResearch.com Interview with:

Odile Launay MD, PhD Paris Descartes University Assistance Publique Hôpitaux de Paris, Cochin Hospital

Dr. Odile Launay

Odile Launay MD, PhD
Paris Descartes University
Assistance Publique Hôpitaux de Paris, Cochin Hospital 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Launay: In patients with HIV infection, responses to standard HBV vaccination regimens remain suboptimal compared with responses in HIV seonegative individuals. We previously reported that alternative regimens (a 4 injection IMdouble dose regimen and a 4 injection intradermal low dose regimen) improve antibody response compared with the standard HBV vaccination regimen (ANRS HB03 VIHVAC-B study). Further precision on the duration of response achieved with alternative HBV vaccination regimes was needed.

We report in this paper the results from the follow-up of the study.

The results of this study show that the 4 dose IM regimen induces higher seroconversion rate but also higher long term seroprotection in HIV infected patients

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New Test Suggests Hepatitis E May Be Widely Underestimated

Brittany Kmush, ScM Doctoral Candidate Global Disease Epidemiology and Control Department of International Health Johns Hopkins Bloomberg School of Public Health Baltimore, MDMedicalResearch.com Interview with:
Brittany Kmush, ScM
Doctoral Candidate
Global Disease Epidemiology and Control
Department of International Health
Johns Hopkins Bloomberg School of Public Health
Baltimore, MD 

Medical Research: What is the background for this study? What are the main findings?

Response: Hepatitis E virus (HEV) is a global pathogen responsible for approximately 20 million infections every year in developing countries. In the general population, HEV causes acute, self-limiting hepatitis with only a 1-2% case fatality rate. However, in pregnant women, Hepatitis E virus infection can be very severe, resulting in fulminant hepatic failure and death, with a case fatality rate around 30%. Despite this important burden, Hepatitis E virus remains an under-recognized and under-reported pathogen. The early years of HEV research were plagued by poor quality commercial assays, highly variable in sensitivity and specificity. As a result, there is still no diagnostic assay approved for commercial use in the United States. However, over the past two decades, several new, highly sensitive and specific assays have been developed.

In this study, we re-tested banked sera from a population-based sero-survey of over 1000 participants from rural Bangladesh in order to investigate the comparability of a high-performing first generation test to recently developed, commercially available assay. In the early 2000s, the Walter Reed Army Institute of Research (WRAIR, Bethesda, MD) developed an in-house enzyme immune-assay (EIA) to diagnose Hepatitis E virus infections by detecting anti-HEV total immunoglobulin (Ig) in serum. More recently, Wantai Diagnostics (Beijing, China) developed a commercially available EIA for detecting anti-HEV IgG.

The WRAIR assay estimated the overall population seroprevalence as 26.6% while the Wantai assay produced significantly higher estimated seroprevalence, 46.7%. There was a 77% agreement between the two tests.  Overall, the Wantai assay found a much higher seroprevalence of anti-HEV antibodies compared to the WRAIR assay, using the same serum. Additionally, the majority of the differences between the two tests are from people initially classified by WRAIR as anti-HEV negative that Wantai classified as anti-HEV positive.

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Extent of Liver Damage May Be Underestimated In Hepatitis C Patients

Stuart Gordon, M.D. Director of Hepatology at Henry Ford HospitalMedicalResearch.com Interview with:
Stuart Gordon, M.D.

Director of Hepatology at Henry Ford Hospital
Detroit, Michigan

Medical Research: What is the background for this study? What are the main findings?

Dr. Gordon: The U.S. Centers for Disease Control and Prevention’s Division of Viral Hepatitis estimates 2.7 to 3.9 million people in the United States currently suffer from chronic hepatitis C. But, unfortunately, many of these patients may be unaware of the severity of their liver damage. We looked at evidence of cirrhosis among hepatitis C patients by examining four different parameters: ICD9 codes; liver biopsy reports; evidence of liver failure; and the FIB-4 test, an easily calculated biomarker. By using all four indicators of cirrhosis, we found a far higher prevalence of cirrhosis than would be indicated by any one method.

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HCV Viral Load Testing Not Useful As Measure of New Hepatitis C Drug Effectiveness

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with:
Shyamasundaran Kottilil MBBS, PhD
Division of Infectious Diseases, Institute of Human Virology
University of Maryland, Baltimore
Laboratory of Immunoregulation
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Bethesda, Maryland

Medical Research: What is the background for this study? What are the main findings?

Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels were clinically useful as on-therapy markers of treatment outcome. However, the standard-of-care for HCV treatment has recently evolved from interferon-based regimens to short-duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-making.

We found that Hepatitis C viral loads on treatment and at end of treatment were not predictive of treatment success versus relapse with DAA therapy. Contrary to our experience with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment did not preclude treatment success.

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Opioid Tampering By Health Care Providers Can Lead To Hepatitis C Transmission

MedicalResearch.com Interview with:
ChongGee Teo, MD, PhD
Chief, Laboratory Branch
Division of Viral Hepatitis
CDC

Medical Research: What is the background for this study?

Dr. Teo: Hepatitis C outbreaks in the course of providing healthcare continue to occur. Some happen when hepatitis C virus (HCV) is transmitted to patients following breakdowns in safe injection and infection control practices, and mishaps during surgery. Another route of provider – to patient HCV transmission is diversion, self-injection and substitution of opioids intended for anesthetic use (collectively referred to as “tampering”). A patient acquires infection when an HCV-infected provider, who is an injecting drug user, self-injects from a syringe prefilled with opioid anesthetic, fills the syringe with a volume substitute (e.g., saline or water), and then administers the adulterated preparation to the patient.

The study consisted of two parts:
1) to quantify the extent that anesthetic opioid tampering contributes to hepatitis C outbreaks by analyzing healthcare-associated outbreaks occurring between 1990 and 2012 in developed countries.

2) to estimate the probabilities of provider-to-patient transmission reflecting the “real-world” setting in which a patient presents for health care, unaware of risks posed by procedures conducted by a provider who may or may not be an injecting drug user or HCV infected.

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Combination Medications May Cure Hepatitis C In Six Weeks

MedicalResearch.com Interview with:
Anita Kohli MD

Critical Care Medicine Department
NIH Clinical Center, National Institutes of Health, Bethesda, MD
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research,  National Laboratory for Cancer Research,
Frederick, MD,

Medical Research: What is the background for this study? What are the main findings?

Dr. Kohli: While therapy using for 8-12 weeks of all oral directly acting antivirals (DAAs) has been shown to result in high SVR “cure” rates for hepatitis C, the optimal combination and minimum duration required for treatment of hepatitis C has not been defined. The development of the simplest, short duration regimen for hepatitis C possible with high cure rates is important given the ~180 million people infected globally.

Medical Research: What should clinicians and patients take away from your report?

Dr. Kohli: Combination therapy with  directly acting antivirals may allow for the further shortening of treatment duration for hepatitis C. Using the right combination of DAA’s therapy for as short as six-weeks may results in high rates of SVR.
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Hepatitis C May Be Spread Through Semen, Especially in HIV+ Men

Dr Daniel Bradshaw Chelsea and Westminster Hospital, LondonMedicalResearch.com Interview with:
Dr Daniel Bradshaw
Chelsea and Westminster Hospital, London

Medical Research: What are the main findings of the study?

Dr. Bradshaw: Over 40% of men with hepatitis C (HCV) infection have HCV RNA in their semen, although the level of RNA was much lower than blood (usually 4 log less than blood).
Neither HIV nor acute hepatitis C led to increased shedding of HCV RNA in semen. Interestingly, however, in acute HCV, HIV-positive men with higher blood levels of HCV RNA were more likely to shed RNA in their semen.
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Hepatitis B: Antiviral Therapy May Lower Risk of Liver Cancer

Dr. Stuart Gordon MD Gastroenterologist Henry Ford Hospital Detroit, MI 48202.MedicalResearch.com Interview with
Dr. Stuart Gordon MD
Gastroenterologist
Henry Ford Hospital
Detroit, MI 48202.

MedicalResearch: What are the main findings of the study?

Dr. Gordon: In a large American cohort of Hepatitis B patients, those who took antiviral therapy had a significantly lower risk of developing liver cancer than those who did not take such therapy.
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Hepatitis B: Preventing Transmission from Mother to Baby

Ai Kubo, MPH PhD Kaiser Permanente Division of Research 2000 Broadway Oakland, CA 94612MedicalResearch.com Interview with:
Ai Kubo, MPH PhD
Kaiser Permanente Division of Research
2000 Broadway
Oakland, CA 94612


MedicalResearch: What are the main findings of the study?

Dr. Kubo: The main findings of the study are three folds:

1)  The CDC guideline works for the majority of infants in preventing vertical transmission, if the immunizations are done according to the recommended schedule.

2) It takes an organized effort to case-manage each mother-infant pairs in order to achieve almost complete immunization rates and very low transmission rates.

3) Highest risk group was mothers with extremely high viral load and e-antigen positivity.  This group of women may benefit from additional therapy to prevent the vertical transmission. However, for others, the risk of transmission is extremely low as long as the infants are immunized according to the guideline.
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Hepatitis C: Patient Reported Outcomes After Treatment

Zobair Younossi, MD, MPH Chairman, Department of Medicine, Inova Fairfax Hospital Vice President for Research, Inova Health System Falls Church, Virginia, USAMedicalResearch.com Interview with:
Zobair Younossi, MD, MPH
Chairman, Department of Medicine, Inova Fairfax Hospital
Vice President for Research, Inova Health System
Falls Church, Virginia, USA

 

MedicalResearch: What are the main findings of the study?

Dr. Younossi: We conducted the analysis of the patient reported outcomes (PROs) data that were systematically collected during clinical trials of sofosbuvir-containing regimens. The highlights of our findings are as follows:

  1. Patients with Hepatitis C (HCV)  have a significant impairment of their health related quality of life including those related to activity and fatigue. Their work productivity is also impaired.
  2. Cirrhosis can add additional negative impact on some of these patient reported outcomes.
  3. During treatment, patients with cirrhosis who were treated with an interferon-free sofosbuvir and ribavirin containing regimen did experience mild decline in their patient related outcome scores. However, this decline was similar for HCV patients with or without cirrhosis.
  4. On the other hand, patients with cirrhosis who were treated with an interferon-containing regimen showed a significant decline in their patient reported outcomes scores compared to those with Hepatitis C and without cirrhosis.
  5. Nevertheless, at the end of week 12 follow up, there was no longer a significant deficit in PROs noted regardless of the treatment arm for patients with cirrhosis.
  6. Furthermore, for the patients (HCV and cirrhosis) who achieved a sustained virologic response at 12 weeks, there were significant improvements (compared to baseline) in some PRO scores.
  7. During treatment, changes in patient reported outcomes scores were similar between cirrhotics and non-cirrhotics for both treatment regimens (all p>0.05).

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Hepatitis C: Successful Treatment Without Interferon for HCV 3

Stefan Zeuzem, M.D. Professor of Medicine, Chief Department of Medicine JW Goethe University Hospital Frankfurt GermanyMedicalResearch.com Interview with:
Stefan Zeuzem, M.D.
Professor of Medicine, Chief Department of Medicine
JW Goethe University Hospital
Frankfurt Germany

 

MedicalResearch.com: What are the main findings of the study?

Dr. Zeuzem: Main finding is that also patients infected with HCV 3 can be cured with an IFN-free regimen. However, duration of therapy must be prolonged to 24 weeks.

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New Marker to Predict Recurrence of Hepatocellular Carcinoma

MedicalResearch.com Interview with:
Wei-ping Zhou, MD, PhD
Department of Hepatic Surgery
Eastern Hepatobiliary Surgery Hospital
Shanghai, China
MedicalResearch.com: What are the main findings of the study? 

Answer:  The main finding is that Quantitative HBsAg can be used as a new prognostic factor of Hepatocellular Carcinoma recurrence after partial hepatectomy in patients with a low HBV-DNA level.

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