Showing posts with label EASL. Show all posts
Showing posts with label EASL. Show all posts

Wednesday, April 13, 2011

Hepatitis C News; Pediatric tampered vaccines also EASL, CDC Updates and The French Doctor

Fort Collins clinic warns parents of shot mistake given to children

A clinic in Fort Collins is advising parents of children who received a pediatric flu shot from their offices to get tested for some blood-borne diseases including HIV, Hepatitis B and Hepatitis C after their vaccine syringes were shared between patients.

Med Peds Clinic sent out a letter April 6 stating a medical assistant at the office took the pre-measured children's influenza vaccine and only gave half to each child, assuming it was the adult dosage. Children between 6 months and 35 months are only supposed to receive half of the recommended dosage for adults.

Since children are supposed to receive two doses of the pediatric influenza vaccine within a month of each other, the assistant removed the needle from each half-full syringe, assuming it was an adult dose, and replaced it with a sterile needle, but not a new syringe.

Med Peds said the medical assistant then placed the used syringes in a box marked "second doses," which also contained unused, fully filled pediatric vaccines.

The clinic says some of the half-used vaccines were then used inadvertently on children returning for their second shot....continue reading...

What's new in sexual health: 
CDC proposes new guidelines for the treatment of STDs


Although mainly contracted through injection drug use, recent data indicate that hepatitis C virus (HCV) infection obtained through sexual contact may be more prevalent than previously thought, especially among HIV-infected persons. CDC data demonstrate that 10% of persons with acute HCV infection report contact with a known HCV-infected sex partner as their only risk for infection.1 Sexual transmission of HCV has been reported recently among HIV-infected MSM in numerous European cities and in New York City. Common practices associated with these clusters that may account for transmission of the infection include serosorting, group sex, and the use of cocaine and other non-IV drugs during sex. Unprotected sexual contact is also believed to facilitate the spread of HCV.

Continue reading...

From Liz Highleyman, Editor-in-Chief and Publisher @HIV and Hepatitis

BMS-790052/BMS-650032 Combo Cures Hepatitis C without Interferon
SUMMARY: Most prior non-responders with HCV genotype 1 achieved sustained response with a quadruple combination containing 2 experimental agents plus pegylated interferon/ribavirin, and nearly 40% did so using only the 2 oral drugs -- BMS-790052 and BMS-650032 -- researchers reported at EASL 2011.

BMS-790052 + Pegylated Interferon/Ribavirin Works Well for First HCV Treatment
SUMMARY: About 90% of treatment-naive genotype 1 hepatitis C patients achieved sustained response at 12 weeks post-treatment using the experimental HCV protease inhibitor BMS-790052 plus pegylated interferon/ribavirin, researchers reported at EASL 2011.

Immune-Based Therapy GS-9620 Shows Promise for Hepatitis B
SUMMARY: Gilead's GS-9620, an experimental TLR7 agonist, stimulated interferon production and activated B-cells and T-cells in laboratory and human studies, and was active against hepatitis B and a related virus in monkeys and woodchucks, researchers reported at EASL 2011.

HBV Genotype Predicts HBeAg Seroconversion on Tenofovir
SUMMARY: Chronic hepatitis B patients with HBV genotype A and lower HBsAg levels at baseline were more likely to experience HBeAg seroconversion during treatment with tenofovir (Viread), researchers reported at EASL 2011.

From Executive Director: Jules Levin @NATAP

EASL: Sustained Virologic Response and Boceprevir Resistance-Associated Variants Observed in Patients Infected With HCV Genotype 1a/1b When Treated With Boceprevir Plus Peginterferon Alfa-2b/Ribavirin: SVR rates among patients with G1b virus were consistently higher compared with G1a patients in both SPRINT-2 and RESPOND-2 - (04/12/11)

EASL: Frequencies of Resistance-Associated Amino Acid Variants Detected by 454 Sequencing During Combination Treatment With Boceprevir Plus Pegintron (Peginterferon Alfa-2b)/Ribavirin in HCV (GT1)-Infected Subjects - (04/12/11)

EASL: Overall Safety Profile of Boceprevir Plus Peginterferon Alfa-2b/Ribavirin - (04/12/11)

EASL: Anemia During Treatment With Peginterferon Alfa-2b/Ribavirin With or Without Boceprevir is Associated With Higher SVR Rates: Analysis of Previously Untreated and Previous Treatment-Failure Patients - (04/12/11)

EASL: Response-Guided Therapy With Boceprevir Plus Peginterferon Alfa-2b/Ribavirin Reduces Treatment Duration in Previously Untreated and Previous-Treatment-Failure Patients With HCV Genotype 1 - (04/12/11)

HIV rate in SF could be cut sharply with expanded treatment, study predicts
In addition, the study found that adding annual HIV testing for men who have sex with men in the city to universal treatment could bring the reduction in new infections down by 75 percent, the researchers report. "Our findings show that we can obtain even greater reductions in new HIV infections if we do a better job of encouraging people to get tested, continue to improve our linkages to care and offer treatment to all HIV patients."
NIH/National Institute of Mental Health

Back-Story; Yves Benhamou was charged with passing on some hot info about Hepatitis C to an unnamed hedge fund. The French doctor was working as a consultant for "Human Genome Sciences Inc. was charged by the U.S. with insider-trading for allegedly tipping off a hedge fund about negative results of Albuferon drug trials."  

13 Apr 2011 at 9:33 AM

Former Frontpoint Trader Chip Skowron Gets His Day In Court
By Bess Levin
Reuters reports that Chip Skowran, the Frontpoint Partners employee who received tips from French doctor Yves Benhamou about Hepatitis C last year, is expected to show up in court today to discuss insider trading charges. Benhamou information to Skowran didn’t make Frontpoint any money, but allegedly helped it avoid losing $30 million by a timely sale of six million shares of drug maker Human Genome Sciences. (It also may have had something to do with investors redeeming en masse shortly thereafter and the shuttering of the fund.)

Merck plans job cuts
Company to sell 1 line, outsource others
By Marcia Moore and and Robert Stoneback
The Daily Item The Daily Item Wed Apr 13, 2011, 06:15 AM EDT

RIVERSIDE — Seven months after Merck bought back the plant it sold just a few years earlier, company officials Tuesday announced plans to sell off one product line and outsource others by the end of 2013 in an attempt to cut costs.
The plant will continue to focus on Merck’s core business of producing compounds for two antibiotics, Invanz and Primaxin. The plan is to sell the third-party fermentation operations and outsource manufacturing of active pharmaceutical ingredients for a cholesterol drug currently available in Europe and for an AIDs treatment.

New On The Blog 
Hepatitis C: Why Am I So Tired ? Fatigue In HCV

New Compounds Show Promise Against Hepatitis C Infection

Predicting sustained virological response in chronic hep C therapy

Saturday, April 9, 2011

Avalanche of hepatitis C products on the way

Avalanche of hepatitis C products on the way

World News | April 04, 2011

Ian Mason in Berlin

Having had no new drugs for hepatitis C since ribavirin’s approval more than a decade ago, doctors will shortly be spoilt for choice.

A wave of new products are emerging from R andD pipelines, with more than 30 companies developing scores of novel antivirals. At the European Association for the Study of the Liver (EASL) annual congress in Berlin, which ended yesterday (April 3), Mark Thursz of Imperial College, London and vice-secretary of EASL reviewed what to look out for.

The two front runners are both protease inhibitors (PIs) - Victrelis (boceprevir) from Merck & Co and telaprevir from Vertex, Tibotec and Mitsubishi Tanabe Pharma. Launches of both drugs are expected this year and snapping at their heels are second generation PIs such as Boehringer Ingelheim’s BI 201335 – an oral once-daily offering which has just moved into Phase III and been fast-tracked by the US Food and Drug Administration.

Boceprevir is given three times a day; telaprevir every eight hours. Asked how clinicians would choose between the two PIs, Prof Thursz said that although there was no head-to-head data, the products differed in their side effect profiles: “With boceprevir there is more anaemia and dysgeusia (foul taste in the mouth) and with telaprevir, the main side effect is a rash which some patients may not be able to tolerate.”

'Remarkable' results

Overall, he said that results with the new PIs were “remarkable”, offering unprecedented levels of sustained virological response, however the drugs still need to be given against a relatively toxic ‘back-bone’ of pegylated interferon-alfa plus ribavirin. For him, the "light at the end of the tunnel" would be an interferon-free regimen, such as combination therapy with a PI plus an NS5b-polymerase or NS5a inhibitor.

Boehringer’s HCV polymerase inhibitor BI 207127 has been FDA- fast-tracked in combination with the German firm’s aforementioned BI 201335. Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052 – albeit in a quadruple regimen with PEG-IFN/ribavirin.

Prof Thursz sounded a note of caution about potential resistance to PIs. “We are going to face a problem with resistant variants,” he said. “These new drugs will need to be handled by specialists who have some understanding of these patterns of resistance and their future implications.”

Patients not getting proper treatment

He concluded that despite ‘fantastic’ new drugs upcoming for hepatitis C, they would have little impact on the global burden of this potentially eradicable disease unless health policies change (up to 170 million people are estimated to be infected with the virus). France has the highest rates of treatment in the European Union, but even there only 16% of hepatitis C patients currently receive treatment. “In the UK, I am embarrassed to say, only 3% of our hepatitis C patients receive treatment. We cannot expect to have much of an impact if we do not screen and treat patients and get rid of the virus,” he said.

In other presentations, early data from Phase I trials of an HCV vaccine were unveiled. Two studies flagged by EASL reported high immunogenicity and good safety profile for a novel T-cell vaccine based on adenovirus vectors (abstracts 750 and 2104). The therapeutic vaccine is being developed by a team at the University of Oxford, UK.

Related; 'Fantastic' data on Novartis' first-in-class hep C antiviral

Hepatitis C Treatments in Current Clinical Development

Alan Franciscus Editor-in-Chief
Updated April 5, 2011
Download PDF

Thursday, April 7, 2011


EASL;Session Title: Category 08c: Viral Hepatitis C: Clinical (therapy)

Presentation Date: 31 MAR, 2011


K.-C. Chang1*, T.-H. Hu2

1Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, 2Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan R.O.C.. *

Background/aims: Antiviral therapy could prevent the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV). However, HCC still develop in a portion HCV patients after sustained virologic response (SVR). The aim of present study is to evaluate the risk factors of HCC development in HCV patients after SVR to peg-IFN combination therapy.

Methods: Seven hundred and six CHC patients receiving peg-IFN and oral ribavirin for 24 or 48 weeks who achieving SVR were analyzed from March 2002 to October 2009. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis.

Results: During a median follow-up period of 32.9 months , HCC developed in 13 patients with SVR. Cumulative incidence of HCC was 0.8 % in 1-yr, 1.2 % in 3-yr, and 3.0 % in 5-yr. Kaplan-Meier analysis revealed that old age (≥60 years) (P < 0.001), male gender (P=0.013), advanced fibrosis (3-4) (P< 0.001), low platelet count (< 100x109/L) (P < 0.001) and AFP levels (≥ 20ng/ml) (P< 0.001) were associated with HCC occurrence. Multivariate analysis revealed old age (hazard ratio (HR):12.47, 95% confidence interval (CI): 1.60-96.67), male gender (HR: 5.71, 95% CI: 1.27-25.91), low platelet count (HR: 3.47, 95% CI: 1.13-10.62) and advanced fibrosis (HR: 8.91, 95% CI: 1.11-71.42) were independent risk factors.

Conclusions: The current study demonstrated that HCV patients with old age, male gender, advanced hepatic fibrosis, and low platelet count at baseline of HCV therapy need more close follow-up even after SVR to peg-IFN combination therapy.


EASL; Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)

Presentation Date: 02 APR, 2011


P. Calès1*, J.-P. Zarski2, C. Michelet3, S. Bertrais4, N. Sturm2, J.-M. Chapplain3, G. Babany5, M. Eddine Charaf5

Background and aims: Maintenance interferon has not been evaluated in patients with chronic hepatitis C, non responders to standard of care, with various degrees of fibrosis stages. Moreover, precise diagnostic means of liver fibrosis, including liver morphometry and quantitative non-invasive blood tests, have not been evaluated in this clinical setting. Our main aim was to evaluate whether quantitative measurements of liver fibrosis outperform histological staging in detecting natural or interferon-induced changes.

Methods: We compared Metavir fibrosis (F) staging and activity grading, morphometry (area and fractal dimension of fibrosis) and 6 blood tests in 157 patients with chronic hepatitis C from two randomized trials testing maintenance interferon for 96 weeks.

Results: Paired liver biopsies and blood tests were available for 101 patients. Treatment effects: there was a significant improvement in Metavir activity grade and a significant decline in FibroMeters specific for cirrhosis and area of fibrosis in the interferon group vs. controls. All relative changes (%) in histological characteristics were significantly greater in F1 vs. other F stages only in the interferon group. Course between measurements at week 0 and 96 in the whole population: dynamic sensitivity: there was a significant progression in area of fibrosis (p=0.026), FibroMeter for significant fibrosis (p=0.020) and cirrhosis (p=0.003) but not with other diagnostic means. Dynamic reproducibility: agreement was good (ric ≥0.72) for Metavir fibrosis score, and for FibroMeters for significant fibrosis, cirrhosis and area of fibrosis. Among histological characteristics, the relative change (%) in area of fibrosis was significantly higher than that of fibrosis fractal dimension (p=0.003) or Metavir fibrosis score (p=0.015). FibroMeter for cirrhosis was the only blood test with a change significantly higher than that of area of fibrosis (p=0.039).

Conclusion: Area of fibrosis by morphometry and blood tests, reflecting fibrosis quantity, have excellent dynamic sensitivity and/or dynamic reproducibility in detecting small changes in liver fibrosis. FibroMeter for cirrhosis has more dynamic sensitivity and reproducibility than area of fibrosis by morphometry. The study also shows that maintenance interferon does not improve fibrosis whatever its stage even with precise quantitative diagnostic methods.
Maintenance Therapy With Peginterferon Alfa-2b Does Not Prevent Hepatocellular Carcinoma in Cirrhotic Patients With Chronic Hepatitis C

Gastroenterology. 2011 Mar 16.
Bruix J, Poynard T, Colombo M, Schiff E, Burak K, Heathcote EJ, Berg T, Poo JL, Mello CB, Guenther R, Niederau C, Terg R, Bedossa P, Boparai N, Griffel LH, Burroughs M, Brass CA, Albrecht JK; EPIC(3) Study Group.

BCLC Group; Liver Unit, Hospital Clinic of Barcelona, University of Barcelona; IDIBAPS, Centro de Investigación Biomédica en Red de Hepatología y Enfermedades Digestivas, Barcelona, Spain.


BACKGROUND & AIMS: Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC(3)) program.

METHODS: Data was analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n = 311) or no treatment (controls, n = 315) for a maximum period of 5 years, or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event.

RESULTS: There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b, compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI], 0.880-2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b, compared with controls (HR, 1.564; 95% CI, 1.130-2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event, compared with controls ( P =.016). There were no new safety observations.

CONCLUSIONS: Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 21419770 [PubMed - as supplied by publisher]


Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)

Presentation Date: 02 APR, 2011


M. Sharma1*, S.A. Kaabi1, N.A. Dweik1, A. John1, K. Matar1, M.A. Mohannadi1, M.F. Derbala1, R. Yacoub1, F. Pasic1, M.T. Butt1, R. Singh2

1Division of Gastroenterology, Department of Internal Medicine, 2Department of Medical Research, Hamad Medical Corporation, Doha, Qatar. *

Background: Screening for Hepatitis C has not been found to be beneficial in healthy individuals.

Aim: To compare the disease pattern and response to treatment among two groups of patients with Hepatitis C. Group 1(Screening Group) comprised of patients detected from the screening survey and Group 2 (Referral Group) were patient referred for treatment from other centres in the same time period. Secondary aims included to compare the above differences in the average and the high risk population among the Group 1 patients.

Methodology: A Community based survey was done to screen for Hepatitis C antibodies in the average and high risk population over a 16 months period in the State of Qatar. Screening was done using a rapid immunochromatographic assay. All patients (Group1 and 2) detected to have at least grade 1 and stage 1 disease on the liver biopsy (as per Scheuer classification), were offered treatment with Pegylated Interferon and ribavirin. .

Results: 13704 people were screened and 272 people were detected to have positive antibodies (Group 1) and 237 patients were referred (Group 2) in the same time period.148 patients in the Group 1 (62 %) and 234 in the Group 2 (98%) consented for further evaluation. Both the groups were similar in age, sex, co-aggravating factors, mean viral load and genotype. ALT and AST were significantly lower in the Group 1 than the Group 2(p=.01). Liver histology revealed milder grade of necroinflammation (grade 0-2) and significantly lesser fibrosis (stage 0-2) in the group 1 (p= .00).The response to treatment (RVR/EVR) was significantly better in the Group 1 than in the Group 2 (72.4 % versus 54.5 %, p=.02).Table 1.Among the Group 1, only ALT was found to be significantly higher (p=.04) in the high risk group but histology and response to treatment was similar to the average risk group.

Click On Table 1 To Enlarge

Conclusion: Screening for hepatitis C results in detection of the disease with relatively preserved liver function tests, lesser fibrosis and necroinflammation and with a better response to the standard treatment.


Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)

Presentation Date: 02 APR, 2011


J. Matsuo1*, H. Okita2, M. Mizui2, K. Katayama1, A. Tabuchi1, T. Akita1, A. Nakashima1, J. Tanaka1, Hiroshima Hepatitis Study Group

1Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University, 2Department of Laboratory Medicine, Japanese Red Cross, Hiroshima, Japan. *

Background/aim: “Asymptomatic” is a main characteristic of Hepatitis C virus (HCV) infection and it has been an important problem at blood donation. Many studies show HCV prevalence among blood donors without physical symptoms. This study is aimed to show what is the natural course and outcomes in asymptomatic HCV carriers= (ASC) found at the blood donations by 18-year cohort study.

Methods: 3,377 HCV positive blood donors from 1991 to 2003 were suggested to consult hepatologists. We followed clinical course and treatment effect of 1,021 cases who came to the hospitals under cooperation of Hiroshima Hepatitis study group. The Ethic Committees of Hiroshima University approved the study.

Results: The mean age was 45.3±11.4, mean observed period was 7.1±6.64 years and the longest observed period was 18.4 years. At the first clinical consultation, chronic hepatitis (CH) was diagnosed among 531(53%) cases, liver cirrhosis (LC) in 5(0.5%) and Hepatocellular carcinoma (HCC) in 1 (0.1%). Liver disease progressed in ASC and 15-year cumulative incidence rate of CH from ASC is 74%(Fig. 1).


166/396(41.9%) were sustained viral responder (SVR) with IFN treatment. Without IFN treatment, in 4 cases, HCVRNA disappeared spontaneously. Natural disappearance rate of HCVRNA is 1.5/1000 person-year without IFN (n=600). The cumulative incidence rates of HCC were similar in groups with or without IFN treatment in Kaplan-Meyer's survival analysis. In multivariate analysis with Cox Hazard Model for HCC incidence by sex, initial age, initial diagnosis and with or without IFN treatment, the risk was significantly high in the older and the CH patients diagnosed at the first examimation (Tab.1).



Conclusion: Amazingly over 50% of HCV positive donors had got liver disease already although they had thought themselves healthy enough. We emphasize that HCV positive blood donors are not actulal ASC anymore. Finding earlier stage liver disease in “Asymptomatic” HCV carriers is needed to prevent HCC. Moreover we showed ASC progress into CH with high rate, and consequently continuous follow-up for ASC is indispensable.


EASL; Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)

Presentation Date: 02 APR, 2011


M. Iqbal, R. Mac Nicholas*, C. Mcnulty, J. Hegarty, A. Mc Cormick

Liver Unit, St . Vincents University Hospital, Dublin, Ireland. *

Introduction: Irish anti-D cohort is a unique group of patients identified in 1994, who received contaminated anti-D immunoglobulin in 1977. A large number of women were found to be antibody positive but PCR negative means that they have spontaneously cleared the virus. Spontaneous clearance of hepatitis C occurs in 10 -25% of patients. Controversy remains whether spontaneous clearance of hepatitis C means complete cure of infection or ongoing infection despite negative PCR testing.

Background & aims: Almost 33 years after inoculation and 16 years after the diagnosis, a large number of women who spontaneously cleared the virus are still attending the liver unit at St Vincent's University Hospital. This gives us the opportunity to follow the natural course and outcome of this unique group of patients who remain PCR negative.The aims of this study is to see whether any of these PCR negative patients became PCR positive at any stage or is there any evidence of chronic liver disease or its complication over these years.

Method: This is a retrospective review of all the patients who were exposed to contaminated anti-D and have attended liver unit at St Vincent's University Hospital.

Results: A total of 118 patients were identified of these 45 were indeterminate on RIBA testing and rest were positive. All of these were PCR negative.52 (44%) patients have attended the outpatients in last three years. The mean follow up of these patients was 12 years (range 7-15). The mean age was 58 years. None of these patients were found to be PCR positive on serial testing .Liver function tests remain normal with mean ALT 22 .No evidence of chronic liver disease or its complication were found on clinical, biochemical and radiological examination. 66(56%) patients who were not seen in last three years have a mean follow up of 6 years (range 2-12). These women were also PCR negative on their last testing.

Conclusion: Women who were exposed to contaminated anti D almost 33 year ago and were PCR negative at initial testing remain PCR negative with no evidence of chronic liver disease or its complications.


Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)

Presentation Date: 02 APR, 2011


E. Jenkins*, N. Reau, A. Aronsohn, S. Mohanty, K.G. Reddy, D.M. Jensen

Hepatology, University of Chicago, Chicago, IL, USA. *

Background: Baseline factors can predict treatment efficacy in patients infected with HCV. Some studies, especially in European subjects, have suggested that HCV genotype 1b (G-1b) is more responsive than genotype 1a (G-1a) to standard therapy with PEG/RBV.

Aims: To measure the prevalence of HCV G-1b and G-1a and to determine if subtype affects efficacy of treatment.

Methods: Retrospective analysis of all outpatient HCV patient charts who received HCV therapy between 2005-20010. 208 genotype 1 patients were identified. Subtype, demographics, disease specific data and therapeutic outcome were extrapolated. 32 patients were excluded from evaluation due to the inability to subtype their HCV, having a subtype other than a or b, or having a mixed genotype. Fisher's exact test and polytomous logistic regression were used to test for associations between the variables subtype, SVR and race.

Results: 176 Patients were included in the evaluation. Patient and viral characteristics were well matched as below. Overall, 28% of G-1a patients achieved SVR compared to 26% G-1b (OR G-1a vs G-1b 1.097, p=0.799). There were 84 African American (AA) patients included in the study, (44% G-1a and 53%G-1b). SVR rates were no different between subtypes with 17% of G-1a AA patients achieving SVR compared to 11% G-1b . 37% G-1a vs. 42% G-1b non-AA achieved SVR. The odds of obtaining SVR was significantly lower for AA vs non-AA patients (OR AA vs. non-AA 0.253, p = .0006.)

Baseline Factors......G-1a (n=70).......G - 1b (n=106)

Ave Age............................. 51..................54

Male (%)............................ 37..................53

Cirrhosis (%)...................... 25..................37

ALT................................... 73..................92

Platelet count.................... 207................196

HCV PCR log 10.............6.52...............6.44

Weight kg...........................87...................86

AA (%)............................. 44...................53

SVR (%)............................28...................26

[Table 1]

Conclusions: G-1b subtype is common among AA patients and offers no advantage to treatment with PEG+RBV.


EASL Session Title: Category 08b: Viral Hepatitis C: Clinical (except therapy)

Presentation Date: 02 APR, 2011


W. Nseir1, M. Gali2, S. Abu Mouch3, A. Djibre4, F. Nassar5, N. Assy4,6*

1Holy Family Hospital, 2Internal Medicine, Holy Family Hospital, Nazareth, 3Liver Unit, Hillel Yafe Medical Center, Hillel Yafe, 4Liver Unit, Ziv Medical Center, Safed, 5Internal Medicine, Western Galilee Hospital, Nahariya, 6Technion Institute, Haifa, Israel. *

Background: HCV cell entry is a multi-step process, involving several viral and cellular factors that trigger virus uptake into the hepatocyte. Hepatic LDL receptor and vitamin D receptors are closely related to HCV infection.

Aim: To assess the association between serum lipoproteins and vitamin D levels and sustained viral response (SVR).

Methods: 80 chronic HCV genotype 1 naïve patients (age 47±15 yrs; 43 men, BMI 28±3) received peg interferon alpha-2a (sc 180 µg once weekly) or peg interferon alpha 2b (1.5µg/kg) plus ribavirin 1200 mg/d during 48 weeks. Lipid profile and vitamin D levels were measured.

HCV RNA was assessed by RT-PCR and undetectable HCV RNA at week 24 post treatment was considered as SVR. Patients were divided into two groups (responders Vs non responders according to SVR).

Results: The patients population had a high BMI (28±2), high viral load (>400,000 IU/l) and high fibrosis score (Metavir scores >F2) in 50%, 40%, and 30% respectively.

Overall, 42 % of patients were responders. Responders had significantly lower serum cholesterol levels (152±43 Vs 181±33 mg%, P=0.01), lower LDL levels (83±31 Vs 104±29, mg%, P=0.008), lower HDL levels (42±14 Vs 50±10, mg%, P=0.009), and higher vitamin D levels (42.1±6.0 Vs 27.3±5.2 ng/ml, P< 0.001) than non responders. Triglycerides levels were similar in both groups (179±30 Vs 183±40, mg%, P>0.05). Multivariate logistic regression analysis showed that gender (Women, OR 2.3, P< 0.001), low cholesterol levels (< >180mg/dL; OR 2.5, P< 0.03), low HDL (< >40 mg/dL, OR 3.5, P< 0.001), and high vitamin D levels (< > 20 ng/ml, OR 3.8, P< 0.001) are strongly associated with SVR.

Conclusions: Low HDL serum level and high vitamin D serum levels are strongly associated with sustained viral response in chronic HCV naïve genotype- 1 patients.


EASL Session Title: Category 02b: Cirrhosis and its complications: Clinical aspects

Presentation Date: 31 MAR, 2011


M. Kuehne1*, J. Wiegand1, P. Pradat2, J. Moessner1, F. Zoulim2, C. Trepo2, H.L. Tillmann1,3

1Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany, 2Department of Hepatogastroenterology, Hôtel Dieu Hospital University, Lyon, France, 3Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. *

Background: The clinical course of alcoholic versus non-alcoholic liver cirrhosis has not been well described yet. However, hepatic decompensation may be differentiated either in consequences of fibrosis (i.e. jaundice, variceal bleeding) or in lack of function (i.e. ascites) resulting in variable morbidity and mortality. We therefore evaluated the pattern of decompensation in relation to the etiology of liver cirrhosis.

Patients and methods: 220 cirrhotic German patients hospitalized between 2002 and 2006 were retrospectively evaluated (cohort A). Results were confirmed in a second cohort of German and French patients (cohort B: n=217) and in an overall analysis. Hepatic decompensation was defined as presence of either ascites, jaundice, encephalopathy, variceal bleeding, hepatorenal syndrome, spontaneous bacterial peritonitis, or hepatocellular carcinoma.

Results: In cohort A and B, alcoholic cirrhosis was present in 76.4% and 73.7% of cases. 8.9% of cases were in Child status A, 30.2% status B, and 44.6% status C (p=n.s.).

Compared to non-alcoholic cirrhosis (cryptogen n=37, HCV n=30, HBV n=11, other n=31), alcoholics (n=328) were significantly younger (55.6y ± 11.5 vs. 62.4y ± 12.8, p=0.000), more often male (75.9% vs. 53.2%; p=0.000) and smokers (60.8% vs. 28.8%; p=0.000).

Alcoholics were significantly more frequently hospitalized for ascites (cohort A: 56.5% vs. 38.5%, p=0,023; cohort B 53.2% vs. 36.8%, p=0.042; total: 54.6% vs. 37.6%; p=0.002) and showed a higher incidence of spontaneous bacterial peritonitis (total: 8.9% vs. 2.8%; p=0.033) compared to non-alcoholics. Non-alcoholics presented with significantly higher rates of hepatocellular carcinoma (31.2% vs. 17.2%; p=0.002). There were no significant differences in jaundice, variceal bleeding, hepatorenal syndrome, or encephalopathy.

A subgroup analysis of alcoholic vs. viral hepatitis confirmed ascites as dominant decompensation in alcoholics (54.6% vs. 36.6%; p=0.03).

In alcoholic cirrhosis, survival did not differ between cases with or without ascites (p=0.957). However, it was significantly impaired once ascites occurred in non-alcoholic disease (p< 0.001).

Conclusions: Ascites is the leading initial pattern of decompensation in alcoholic cirrhosis whereas hepatocellular carcinoma dominates in non-alcoholics. Non-Alcoholics developing ascites show a poor survival.


EASL; Session Title: Category 02b: Cirrhosis and its complications: Clinical aspects

Presentation Date: 31 MAR, 2011


V. Calvaruso1*, V. Di Marco1, D. Ferraro2, P. Pizzillo2, G. Alaimo1, A. Craxì1

1Gastroenterology and Hepatology, 2Igiene e Microbiologia, University of Palermo, Palermo, Italy. *

Background and aim: To assess the virological and disease factors associated to liver related events and survival in patients with compensated HCV cirrhosis treated with interferon based therapy.

Patients and methods: A cohort of 425 patients with Child-A HCV cirrhosis (mean age 58.0±8.5 years, 61.9% males; 87.1% infected by HCV-Genotype1 and 12.9% by Genotype2/Genotype3; 52.8% with esophageal varices, 27.5% with diabetes) received interferon-based antiviral treatment.

Sustained Virological Response(SVR) was defined as HCV-RNA negative at 6th month of follow-up. All patients underwent ultrasound scan every 6 months and endoscopy were repeated every 2 years.

Results: Overall SVR was 23.8% (17.6% in Genotype 1 patients vs 65.5% in Genotype2/Genotype 3 patients).

During a median follow-up of 48 months, 77 patients (18.1%) developed liver decompensation, 50 patients (11.8%) had hepatocellular carcinoma (HCC) and 55 patients(12.9%) died for liver events.

By Log-Rank test presence of esophageal varices (EV) was statistically associated to an higher occurrence of liver decompensation (p< 0.001) and with mortality liver related (p=0.009), but not with development of HCC (p=0.07).

The absence of SVR was associated with an higher rate of liver decompensation(p< 0.001), HCC(p< 0.001) and mortality(p=0.001).By Cox regression analysis, albumin (OR:0.61, CI95%:0.37-0.98; p=0.043), Bilirubin (OR:1.50, CI95%: 1.02-2.21; p=0.040), platelet count(OR:0.99, CI95%: 0.98-0.99; p=0.005) and SVR (OR:0.26, CI95%: 0.09-0.72; p=0.009) were independently associated with mortality. Adding decompensation and HCC development to the model these two variables became the unique factors independently associated to mortality liver related (OR:4.05, CI95%: 2.27-7.22; p< 0.001) and (OR:3.80, CI95%: 2.21-6.55; p< 0.001) respectively.

Conclusion: In patients with compensated HCV-cirrhosis, the presence of esophageal varices is associated with higher rate of decompensation and mortality but not with HCC occurrence.

SVR is a favourable factor of free-of-event survival by univariate analysis but only the liver events occurrence is independently associated to mortality. Development of HCC doesn't act only as a decompensation hastener but it results independently associated to mortality.

Wednesday, April 6, 2011

Treatment For Liver Cancer – Study On The Outcome And Survival From Liver Transplant Released

Treatment For Liver Cancer – Study On The Outcome And Survival From Liver Transplant Released

Donation After Cardiac Death May Broaden the Scope of Organ Donor Selection

Findings from two new studies presented today at the International Liver Congress(TM) confirm that there are options for clinicians to expand the pool of liver grafts for use in patients with liver disease.

A UK retrospective study analysed liver transplant donation after cardiac death (DCD) between May 2001 and October 2010.[1] 186 DCD allografts were used for transplantation and included 19 paediatric recipients. Overall the study found positive outcomes of transplant, with an overall patient survival of 89.9%, 85.6% and 83.6% at one, three and five years respectively.

The second Italian Liver Match cohort study, evaluated the survival of liver grafts from HBcAb+ve donors in patients (recipients) with hepatitis, by analysing data from 1477 adult liver transplantations from June 2007 to May 2009.[2] Of these, 1237 were HBcAb negative and 240 HBcAb positive donors, with unadjusted two-year graft survival of 80 and 69 percent respectively. The two-year study found HBcAb positive donor grafts survive better when allocated to HBsAg positive recipients but have worse outcomes when given to all categories of HBsAg negative recipients, regardless of their HBcAb/HBsAb status. In addition, as graft loss was unrelated to hepatitis HBV recurrence it is unlikely that this is due to insufficient HBV prophylaxis.

Currently, the optimal use of hepatitis B core antibody positive (HBcAb+ve) donor liver graft is mandatory in a number of European countries such as Italy, but current recommendations are not supported by strong evidence-based data. This study highlights that organ allocation needs to be considered on a like for like basis and the potential need for adjustment of current organ allocation policies in Mediterranean countries.

Daniele Prati, EASL’s Scientific Committee Member and Press Committee Chairman commented: “Too many patients continue to die while waiting for a liver transplantation. Finding organ donors is an ongoing challenge and any research that helps to expand the pool of available organs is welcome. As clinicians we always want the best possible outcomes for our patients and both studies provide encouraging results and additional viable options.

Dimple Natali: Onsite tel: +44-79-00-13-89-04,
Vicky O’Connor Offsite tel: +44-207-331-5342

HCV News;Roche Joins in Spanish Research Cooperation for Personalized Treatment of Hepatitis B and C

New On The Website; 2011 EASL; Easy To Understand Summary of the investigational Hepatitis C drugs
Watch For Updates On The Sidebar Of This Blog


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Factors affecting HCV viral load response to the non-nucleoside polymerase inhibitors ABT-072 and ABT-333 -

Adherence To Assigned Dosing Regimen and Sustained Virologic Response Among Hepatitis C-Genotype 1 Previously Untreated and Peginterferon/Ribavirin Treatment-Failure Patients Treated With Boceprevir Plus Peginterferon Alfa-2b/Ribavirin (patients with >80% adherence to all dosing achieved 90% cure rates. My guess is if adherence is 100% SVR rates will be higher)
Four-Week Treatment with GS-9256 and Tegobuvir (GS-9190) +/- RBV +/- PEG, Results in Enhanced Viral Suppression on Follow-up PEG/RBV Therapy, in Genotype 1a/1b HCV Patients -

Genotypic and Phenotypic Characterization of NS3 Variants Selected in HCV-Infected Patients Treated with ABT-450 -

Characterization of Virologic Escape in HCV Genotype 1 Null Responders Receiving a Combination of the NS3 Protease Inhibitor BMS-650032 and NS5A Inhibitor BMS-790052 -

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Among 1 Genotype HCV–Infected Patients Not Achieving SVR With Boceprevir-Based Regimen, Resistance-Associated Variants More Common in Those With Poor Response to 4-Week PegIFN/RBV Lead-in

SOCRATES: Combining Sorafenib and TACE for Treatment of Advanced Hepatocellular Carcinoma Yields Promising Efficacy Results

ZENITH Interim Results: Potent Antiviral Activity With 12 Weeks of VX-222 + Telaprevir + PegIFN/RBV Quad Therapy, but Virologic Breakthrough Common With VX-222 + Telaprevir Dual Therapy

From Medscape Medical News

Telaprevir Add-On Effective After Initial HCV Therapy Fails

Daniel M. Keller, PhD

April 6, 2011 (Berlin, Germany) — Telaprevir added to standard pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) therapy for hepatitis C virus (HCV) infection was superior to retreatment with peg-IFN/RBV plus placebo in patients for whom standard therapy had failed in the past, researchers announced here at the European Association for the Study of the Liver (EASL) 46th Annual Meeting.

The safety and tolerability of adding telaprevir were similar to results seen in previous trials. Adverse events leading to permanent discontinuation of the drugs consisted mainly of anemia and rash, and were more prevalent in the telaprevir groups than in the control group.

Standard combination therapy with peg-IFN/RBV fails in approximately 60% of patients with HCV genotype 1, which is one of the more difficult genotypes to eradicate, noted Stefan Zeuzem, MD, chief of the Department of Medicine and professor of medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, who presented the study results.

The aim of the Re-Treatment of Patients With Telaprevir-Based Regimen to Optimize Outcomes (REALIZE) trial was to test the addition of telaprevir, a new small-molecule HCV protease inhibitor, to peg-IFN/RBV in 662 patients with HCV genotype 1 for whom peg-IFN/RBV had previously failed to produce sufficient and sustained viral suppression.

The primary objective of this pivotal phase 3 international, multicenter, double-blind, placebo-controlled trial was to compare the proportion of patients achieving a sustained virologic response (SVR) with telaprevir plus peg-IFN/RBV and the proportion achieving an SVR with placebo plus peg-IFN/RBV. All SVRs were below 25 IU HCV RNA (undetectable level).

Patients were divided into 3 categories: null responders did not show at least a 2 log10 drop in serum HCV RNA at week 12 of previous standard therapy; partial responders experienced at least a 2 log10 drop at week 12 of previous therapy but still had detectable HCV RNA in the blood at week 24; and relapsers achieved viral levels below the limit of detection at 42 weeks but then had a recurrence of detectable virus.
The groups were well matched at baseline. Approximately 70% were men, median age was approximately 50 years, 93% were white, HCV RNA was above 800,000 IU/mL in 86% to 89%, and almost 60% were in the advanced stages of disease with bridging fibrosis or cirrhosis (26%). About half were infected with genotype 1a and about half with genotype 1b. About 30% were previous nonresponders, 20% were partial responders, and 50% were previous relapsers.

Patients were randomly assigned to 1 of 3 treatment groups: 266 patients received telaprevir + peg-IFN/RBV for 12 weeks, then placebo + peg-IFN/RBV for 4 weeks (T12/PR48); 264 patients received a lead-in of placebo + peg-IFN/RBV for 4 weeks, then telaprevir + peg-IFN/RBV for 12 weeks (lead-in T12/PR48); and 132 patients received placebo + peg-IFN/RBV for 16 weeks (placebo/PR48).
In these 3 groups, drug doses were as follows: telaprevir 750 mg every 8 hours; peg-IFN 180 µg/week; and RBV 1000 to 1200 mg/day. The groups were followed-up and assessed for SVR at week 72. The primary statistical calculations were on previous relapsers and on previous nonresponders (a combination of previous partial responders and null responders).

Dr. Zeuzem reported that among previous relapsers, 83% to 88% achieved an SVR when treated with telaprevir plus peg-IFN/RBV. Less than 10% of them relapsed by week 72. In contrast, only 41% of previous nonresponders achieved an SVR with telaprevir, but this figure was still a 4-fold increase over the proportion with an SVR when retreated with peg-IFN/RBV and placebo. Overall, about 35% of patients in the 2 telaprevir groups failed to achieve an SVR; those failures occurred mainly among previous partial and previous null responders.

Addition of Telaprevir to Peg-IFN/RBV Enhances SVR Rates

Patient Group


% (n/N)

Lead-in T12/PR48,

% (n/N)


% (n/N)

Previous Relapsers
SVRa83 (121/145)c88 (124/141)c24 (16/68)
Relapseb7 (10/135)7 (9/138)65 (30/46)

Previous Nonresponders
SVRa41 (50/121)c41 (51/123)c9 (6/64)
Relapseb23 (16/69)25 (18/72)33 (3/9)

aSVR assessed 24 weeks after planned treatment completion

bRelapse: detectable virus at week 72 in patients with undetectable HCV RNA at end of assigned treatment

P < .001, comparison vs placebo/PR48

"The SVR rates tended to be higher in genotype 1b–infected patients, in particular in prior partial responders and prior null responders," Dr. Zeuzem reported. "The lead-in phase [group] showed numerically slightly higher [SVR] rates in the prior relapsers and the prior nonresponders, but there was an opposite trend for the prior partial responders."
When the data were analyzed by the degree of baseline fibrosis, all subgroups of patients responded better to telaprevir than to peg-IFN/RBV plus placebo. For example, among previous relapsers, 86%, 85%, and 84% achieved an SVR with telaprevir if they had no fibrosis, bridging fibrosis, or cirrhosis, respectively, compared with 32%, 13%, and 13%, respectively, with peg-IFN/RBV plus placebo. The addition of telaprevir added little or no benefit over peg-IFN/RBV alone for previous partial or null responders with cirrhosis.

Dr. Zeuzem noted that adverse events, which occurred at least 10% more frequently in the telaprevir groups than in the placebo group, were fatigue, pruritis, rash, anemia, nausea, diarrhea, and anorectal symptoms (described as pruritis, discomfort, or hemorrhoids).
The majority of adverse effects were grade 1 or 2, with some grade 3 rash in the pooled telaprevir groups. Rash was primarily eczematous, which resolved when therapy ended. Anemia was managed with RBV dose reduction when necessary, which occurred in 25% of the telaprevir-treated patients. Per protocol, erythropoiesis-stimulating agents were not permitted. In the telaprevir groups, 11% to 15% discontinued treatment because of adverse events; in the placebo group, 3% did.

Dr. Zeuzem concluded that "telaprevir/peg-interferon-ribavirin triple therapy was clearly superior to the standard peg-interferon/ribavirin treatment alone" in all 3 treatment-experienced populations."
He said a 4-week lead-in phase with peg-IFN/RBV did not reduce virologic failure or relapse rates and did not improve SVR rates. He noted that the safety of telaprevir was similar to that observed in previous studies. Adverse events, mainly anemia and rash, led to permanent discontinuation of study drugs more frequently in the telaprevir groups than in the control group.

Mark Thursz, MD, professor of hepatology at Imperial College, London, United Kingdom, and vice secretary of EASL, said: "I think these are very responsible conclusions . . . and I feel that the data that are coming out on this particularly difficult-to-treat group of patients — those who had previous treatment and failed — these are really exciting results. Overall, something like 60% of patients were successfully treated [and] reached an SVR in the REALIZE trial." He added that "partial responders [did] so-so; null responders, not so good. This is disappointing but not entirely surprising. They are particularly difficult groups to treat."
Dr. Thursz, who was not involved in the REALIZE trial, said that for patients for whom previous therapy has failed, "now we have treatment options to offer them, assuming that the commissioning authorities will pay for [the drugs] for those who don't pay for their own therapy."

In response to a question from the audience about the rashes and the possibility of Stevens–Johnson syndrome, Dr. Zeuzem said that of the several thousand people exposed to telaprevir, "to the very best of my knowledge, there is only 1 case of Stevens–Johnson syndrome described, but this case occurred after telaprevir was already discontinued, so a causal relationship cannot be justified from this single case. But I know that this single case has made many people very nervous."
Although anemia was more frequent in the telaprevir groups, "we have learned to manage anemia in this group of patients," Dr. Thursz said. "Most patients can tolerate more anemia than the pharmaceutical companies can."

Telaprevir is being developed by Vertex Pharmaceuticals. The US Food and Drug Administration has granted the drug priority review, which is expected on May 23.

Dr. Zeuzem reports relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex. Dr. Thursz has disclosed no relevant financial relationships.
European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 30, 2011.
HCV Advocate Newlsetter: April 2011

In This Months Issue;

Why We Should Test: Editorial
Alan Franciscus, Editor-in-Chief

HCV Snapshots
Lucinda K. Porter, RN

Liver Transplantation: HCV Recurrence and Treatment
Liz Highleyman

HealthWise: Humor, Health, and Hepatitis C
Lucinda K. Porter, RN

Around The World

Japanese drugmakers face radiation challengeDaiichi Sankyo and Eisai Pharmaceuticals, two major Japanese drugmakers with operations in New Jersey, are coping with a new post-earthquake business challenge: Trying to ensure that their medicines and manufacturing materials are protected from the effects of radiation.

Roche Joins in Spanish Research Cooperation for Personalized Treatment of Hepatitis B and C
By Benzinga Staff
April 06, 2011 8:03 AM

Roche Diagnostics (RHHBY) is cooperating with the Spanish Vall d'Hebron Institute of Research, the Networking Biomedical Research Centre in Liver and Digestive Diseases, and the software producer Advanced Biological Laboratories Therapy Edge Spain in a study designed to resolve the current limitations that prevent the individualization of anti-HBV and anti-HCV (hepatitis B and C) treatments.

The project will utilize Roche's 454 Sequencing Systems and bioinformatics analysis, together with other genetic and molecular analytical techniques. Ultimately, the research project aims to identify personalized treatment for each individual while minimizing the healthcare costs and side effects experienced by subjects.

The ETF market can be confusing and hard to beat, but ETF Professor's trading ideas help you make profit consistently

(c) 2011 All rights reserved. This material may not be published in its entirety or redistributed without the approval of Benzinga.
Read more:

WWE's hepatitis controversy, Messi's sensational shots in global sports video charts
A documentary linking WWE's latest Hall of Famer to the transmission of Hepatitis C and a clip of Lionel Messi's incredible pre-match practice shot are among the world's most viewed sports videos for the week ending April 5.

"Don't Bleed On Me" makes a connection between the dead-end wrestling career of promising rookie Devon "Hannibal" Nicholson and the blood-letting antics of 2011 Hall of Fame inductee Abdullah the Butcher.

Once-Daily Nevirapine for HIV Wins FDA Nod
An extended-release version of the reverse transcriptase inhibitor nevirapine (Viramune XR) has received FDA approval for once-daily dosing in patients with HIV-1 infection, manufacturer Boehringer Ingelheim announced.

In Case You Missed It

Antiviral Therapy Lowers Insulin Resistance in HCV Genotype 1 Infection

NEW YORK (Reuters Health) Mar 03 - Resolution of chronic hepatitis C virus (HCV) genotype 1 infection after treatment with peginterferon and ribavirin is associated with improvement in insulin sensitivity among patients with evidence of insulin resistance before antiviral therapy.

However, factors other than medications may be at work, researchers report in the February issue of Gastroenterology.

Dr. Hari Conjeevaram of The University of Michigan, Ann Arbor, and colleagues note that the insulin resistance associated with the condition might result from liver disease, metabolic factors or hepatitis C virus itself. Moreover, the effect of antiviral treatment on insulin sensitivity isn't well known.

They also point out that insulin resistance may affect the progression of liver disease, but it's uncertain "whether insulin resistance is the cause or the effect of worsening liver function or fibrosis."

To investigate, the team studied data from a prospective trial of a 48-week course of combination peginterferon and ribavirin therapy in 341 patients infected with HCV genotype 1.

Insulin resistance was estimated by the homeostasis model assessment index (HOMA2-IR) based on fasting glucose and insulin levels. Using these criteria, 40% had a HOMA2-IR beyond 2 and were deemed insulin resistant at baseline.

Insulin resistance was associated with higher body weight, higher serum triglycerides, and greater degrees of fibrosis and steatosis on liver biopsy. "All of which," say the investigators, "are well-known risk factors for diabetes and insulin resistance."

In the insulin-resistant group, HOMA2-IR values declined on average by 8% at 24 weeks and by 23% by the end of therapy. These results are in line with those of other investigators. The degree of decline in this group didn't differ significantly by virologic response.

Other findings, the team adds, "suggest that improvements in calculated values for insulin resistance are due at least in part to weight loss and the effects of peginterferon and ribavirin treatment, rather than the degree of decline in HCV RNA levels."

But, importantly, they point out, "only patients who ultimately had a sustained viral response had a significantly lower HOMA2-IR at week 24 when compared with baseline, suggesting that viral eradication may affect insulin response to a greater extent than weight loss and simple viral suppression during interferon treatment."

Overall, the researchers conclude that there appears to be "a direct role for HCV in inducing a decrease in insulin sensitivity." The finding, they add, "provides strong support for recommending therapy in patients with chronic hepatitis C and insulin resistance or diabetes."


Healthy You

University of Cincinnati Academic Health Center

Elevated levels of sodium blunt response to stress, study shows

CINCINNATI—All those salty snacks available at the local tavern might be doing more than increasing your thirst: They could also play a role in suppressing social anxiety.

New research from the University of Cincinnati (UC) shows that elevated levels of sodium blunt the body's natural responses to stress by inhibiting stress hormones that would otherwise be activated in stressful situations. These hormones are located along the hypothalamic-pituitary-adrenal (HPA) axis, which controls reactions to stress.

The research is reported in the April 6, 2011, issue of The Journal of Neuroscience, the official journal of the Society for Neuroscience.

"We're calling this the Watering Hole Effect," says Eric Krause, PhD, a research assistant professor in the basic science division of UC's department of psychiatry and behavioral neuroscience and first author of the study. "When you're thirsty, you have to overcome some amount of fear and anxiety to approach a communal water source. And you want to facilitate those interactions—that way everyone can get to the water source."

Krause and his team dehydrated laboratory rats by giving them sodium chloride, then exposed them to stress. Compared with a control group, the rats that received the sodium chloride secreted fewer stress hormones and also displayed a reduced cardiovascular response to stress.

"Their blood pressure and heart rate did not go up as much in response to stress as the control group's, and they returned to resting levels more quickly," says Krause.

"Also, in a social interaction paradigm with two rats interacting, we found them to be more interactive and less socially anxious."

Further research, through examination of brain and blood samples from the rats, showed that the same hormones that act on kidneys to compensate for dehydration also act on the brain to regulate responsiveness to stressors and social anxiety.

The elevated sodium level, known as hypernatremia, limited stress responses by suppressing the release of the pro-stress hormone angiotensin II. Conversely, it increased the activity of oxytocin, an anti-stress hormone.

Further research, Krause says, will examine these hormones and neurocircuits to investigate their role in social anxiety disorders and autism, a neurological disorder whose characteristics include social impairment.

"Oxytocin deficiency has been implicated in autism in previous studies," says Krause. "We'd like to investigate the possibility that dysregulation in fluid balance during pregnancy could result in autistic disorders."

Krause's team also included Annette de Kloet, Jonathan Flak, Michael Smeltzer, Matia Solomon, Nathan Evanson, Stephen Woods, Randall Sakai and James Herman.

Fatty liver -- how a serious problem arises

Published: Wednesday, April 6, 2011 - 08:36 in Health & Medicine

Excess fat around the hips and belly may not really be compatible with current beauty ideals, but, to a certain degree, it is a normal, even vital energy store of our body. However, it is a different matter if the organism stores fat in organs such as the liver, pancreas or muscles. This is a clear sign of a metabolic disorder. Up to 80 percent of obese people develop fatty liver disease, which is regarded a typical characteristic of the dangerous metabolic syndrome. Deposition of fat in the liver may lead to chronic liver inflammation and even to liver cancer. In addition, fatty liver is considered to be an independent risk factor for coronary heart disease and atherosclerosis.

The great medical relevance of fatty liver as a severe condition accompanying insulin resistance and type II diabetes caused the research group headed by Dr. Stephan Herzig of the Division of Molecular Metabolic Control to investigate how this syndrome arises. Which molecular switches are turned on or off in a cell when food delivers too much energy-rich fat molecules, or triglycerides?

To this end, the investigators determined the level of particular proteins involved in specific gene activation in the liver tissue of mice. These proteins, which are known as transcriptional co-activators, regulate which proteins are read and transcribed into messenger RNA molecules in a cell. In overweight mice, the researchers observed that a high triglyceride level in the liver was always associated with reduced production of a co-activator called TBL1. This was found both in animals that developed fatty liver for hereditary reasons and in those animals that received calorie-rich food.

TBL1 was originally discovered in connection with a rare hereditary hearing disorder. In the liver, but not in other tissues, an oversupply of fat reduces the production of TBL1. As a result, fat burning in the liver is reduced so that more fat molecules are deposited in liver cells. "This, in turn, may lead to a further reduction of TBL1," says Stephan Herzig.

Not only in mice is TBL1 linked to the liver fat (lipid) metabolism. The group found the same pattern in human liver tissue samples: the higher their triglyceride levels, the lower their TBL1 levels.

Stephan Herzig expects a practical use of these results. "We might be able in the future to use TBL1 levels for identifying those obese persons who have a special risk of developing fatty liver. We could then give specific dietary recommendations to counteract this."

The research was funded by grants from the National Institutes of Health and the American Heart Association. The authors declare no competing financial interests.
Marijuana Allergies: Reactions May Be More Common Than Thought

SAN FRANCISCO – Marijuana hypersensitivity might be more common than previously thought, according to the results of a case series.

Though there are only a few case reports in the literature, "Marijuana allergy, I think, is fairly common," said lead investigator Dr. Gordon Sussman, acting division director of clinical allergy and immunology at the University of Toronto. Even so, "It’s something physicians don’t really generally ask about. People should consider it in the diagnosis of rhinitis [and other allergic symptoms], and even in people that have asthma and anaphylaxis."

Dr. Gordon Sussman says allergic reactions to marijuana shouldn't be a surprise because it is a weed, and weeds are generally known to be allergenic.

The 17 patients who were included in the series reported that marijuana gave them runny noses or other problems; all ended up having positive marijuana skin prick test results, he reported. One patient in the series had an anaphylactic reaction after drinking marijuana tea.

That was the first patient in whom Dr. Sussman diagnosed a marijuana allergy. "I asked him in a detailed history what it could have been, and he actually had drunk marijuana tea. We knew at that point he had an IgE-mediated reaction to marijuana," he said.

Curiosity piqued, and Dr. Sussman began asking allergy patients about marijuana use and reactions. A significant percentage reported symptoms from both contact and inhalation.

To confirm the diagnosis, he and his colleagues did skin-prick tests on the 17 patients between 21 and 58 years old, mostly men. They extracted buds or flowers in 5 mL of water for 15 minutes and pricked beneath drops placed on patients’ skin.

After 15 minutes, the 17 patients had wheals of 4-19 mm and surrounding flares. Fifteen presented with inhalation symptoms, including rhinitis and conjunctivitis, periorbital angioedema, wheezing, sinusitis, and throat swelling. Thirteen also reported hives from contact.

The anaphylaxis patient presented with anxiety, chest tightness, wheezing, GI cramping, and vomiting after drinking the tea.

"I don’t think it’s a contaminant; I’m pretty sure it’s an allergen in the marijuana they are reacting to," Dr. Sussman said, adding that such reactions shouldn’t be a surprise because "marijuana is a weed, and weeds are generally known to be allergenic."

Asking about marijuana use and past reactions should be a routine part of allergy work-ups, especially with expanding medical marijuana use. "People could actually be sensitized to marijuana and have a serious reaction. It’s important for people to recognize this," Dr. Sussman said.

The researchers’ next step is to identify the actual allergens responsible for the reactions using a marijuana extract from a U.S. federal laboratory, serum from positive patients, and Western blot assays.

There was no outside funding for the study. Dr. Sussman said he had no disclosures.

New On The Blog;

Can chronic hepatitis C resolve spontaneously?
This article describes two female patients with transfusion-acquired CHC diagnosed by both positive hepatitis C virus (HCV)-Ab and hepatitis C virus–polymerase chain reaction (HCV–PCR) tests.
Both patients cleared the infection spontaneously after more than 5 and 25years of CHC infection, respectively.

Hepatitis C; IL28B-Genotype Testing Now and in the Era of Direct-Acting Antiviral Agents
Peginterferon alpha and ribavirin treatment for 48 weeks leads to a sustained virological response (SVR) in 40%–50% of subjects infected with hepatitis C virus (HCV) genotype 1 or 4 (G1/4) while treatment for 24 weeks produces SVR in 70%–80% of patients infected with HCV genotype 2 or 3. The variability in response to treatment, especially between patients of different racial groups, suggested that human genetic variability might explain differences in treatment response and led to investigations of the role of host genetics in achieving an SVR.

Tuesday, April 5, 2011

Hepatitis C In The News For April 5; Mericitabine (formerly RG7128)

View all the slides, data and coverage of the EASL at NATAP .
Also from NATAP
Brief Recap Report from EASL Liver Conference in Berlin: state of HCV Now- policy, treatment, access

New Capsule Summaries at CCO
You can view the EASL updates on this blog here also.
From HIV and Hepatitis
Mericitabine (formerly RG7128)
First Sustained Response Data for Polymerase Inhibitor Mericitabine
SUMMARY: 76% of treatment-naive genotype 1 or 4 hepatitis C patients achieved 12-week sustained response to mericitabine (formerly RG7128) plus pegylated interferon/ribavirin, according to a report at EASL 2011.
Polymerase Inhibitor PSI-7977 Works with Interferon or Companion Drug
SUMMARY: Almost all treatment-naive hepatitis C patients treated with Pharmasset's candidate PSI-7977 plus pegylated interferon/ribavirin experienced 12-week sustained response, and more than 90% treated with a PSI-7977 + PSI-938 all-oral combo had undetectable HCV at 14 days, researchers reported at EASL.
Telaprevir Improves HCV Cure Rates Regardless of IL28B Status
SUMMARY: The Vertex experimental protease inhibitor telaprevir, taken with pegylated interferon plus ribavirin, increased sustained response in people with all IL28B gene patterns, researchers reported at EASL 2011.
Pegylated Interferon Lambda Boosts Response with Few Side Effects
SUMMARY: Hepatitis C patients taking an experimental interferon formulation -- pegylated interferon lambda -- had higher rates of rapid and early virological response, with fewer flu-like symptoms and blood cell deficiencies, according to a report at EASL 2011.
I know we have all read this......but I just love to see it in print
Quadruple therapy shows 100 percent SVR for HCV patients

Exciting new data presented today at the International Liver CongressTM 2011 show that quadruple treatment in chronic hepatitis C (HCV) patients suppressed the emergence of resistant variants and resulted in a 100% rate of sustained virological response - undetectable HCV RNA - 12 weeks after therapy (SVR12).1.

In the quadruple treatment study, HCV patients were given four drugs in combination; pegylated Interferon-alpha (PegIFN-alpha); ribavirin (RBV); and two different direct-acting antivirals (DAAs) BMS-650032 (an HCV NS3 protease inhibitor) and BMS-790052 (an HCV NS5A replication complex inhibitor).

The current standard of care (SoC) for HCV treatment is PegIFN-alpha plus RBV � a dual treatment. The addition of DAAs (currently in phase-III clinical trials) marks the next step in therapy evolution � a triple treatment. However, the new data presented today suggests that quadruple treatment could be the next generation of therapy for chronic HCV patients.

Professor Heiner Wedemeyer, EASL'S Secretary General, said: "Quadruple treatment is possibly the future of HCV therapy; this study goes a way to confirming that. While it's expected that the first DAAs and triple treatment will be approved for use later this year, quadruple treatment appears to have a more profound effect on virological response, with less of a resistance problem".

The study may also provide new hope for a growing number of HCV patients who cannot be effectively treated for chronic hepatitis with current therapys.

The Phase-IIa trial looked at a cohort of 21 HCV genotype 1 null responders (patients who have failed to respond to prior therapy), of whom 19 had an unfavourable IL28B genotype, which predisposes HCV patients to therapy failure.

Only about 30% of null responders to PegIFN-alpha/RBV therapy achieve sustained virological response (SVR) when retreated with PegIFN-alpha/RBV plus telaprevir, demonstrating a high unmet medical need.1

You can view the slides at NATAP  here...

In The News

Tainted Prep Pads

Pharmalot has a great article on the tainted wipes this HCV community has been following from the beginning..check it out.

FDA Tries To Wipe Up A Wipe Maker
After nearly two years of failed inspection reports and an order last week from the FDA to halt production and distribution, a little-known company that was accused of making contaminated medical pads and wipes shut its doors yesterday. But the move came only after US Marshals showed up with seizure orders, as MSNBC notes.
The move came three months after H  &  P Industries and a related company, Triad Group, recalled a huge amount of alcohol wipes and pads potentially contaminated with Bacillus cereus, which was blamed for serious infections and at least one death - a two-year-old boy in Texas (look here). Triad also recalled potentially contaminated lubricating jelly used in medical procedures and exams, and iodine prep wipes (see this)........Continue Reading....

Side Note; Dr. Gordon was my doctor when I treated in 1999..........

Hepatitis C drugs could be cure

DETROIT — — Two three-drug regimens appear to cure most people of the most common type of hepatitis C in the U.S.

“We’re closing in on a cure,” said Dr. Stuart Gordon, a hepatitis C researcher at Henry Ford Hospital in Detroit. Gordon coauthored one of the drug studies, which appeared in the New England Journal of Medicine.

The cocktails consist of two new drugs: boceprevir from Merck & Co., and telaprevir from Vertex Pharmaceuticals. Each is paired with two drugs used to treat hepatitis C for more than a decade — interferon and ribavirin.

Although interferon and ribavirin have worked in some people, thousands took the drugs only to see the virus return. Adding a third drug appears to significantly boost a person’s chance of beating the disease for good.

“I can go and go and go,” said Detroiter Rhonda Gilbert, who is living without a trace of the disease for the first time in a decade. She takes no medicines for it now after participating in a Ford study with the boceprevir cocktail.

Merck & Co. of Whitehouse Station, N.J., and Vertex Pharmaceuticals of Cambridge, Mass., hope to hear in the next two months about whether they can distribute the drugs that make up three-drug cocktails shown to be effective in eradicating the disease.
The companies already have fast-track status from the Food and Drug Administration.
Gordon expects to prescribe both regimens once they are approved.
He considers the therapies “a major advance in the cure of a very common disease.”

An estimated 4 million Americans have hepatitis C, according to the federal Centers for Disease Control and Prevention.
Many are unaware that they have the disease because the virus is slow-growing and can linger for years without symptoms.

“ ‘Cure.’ That’s the four-letter word we’ve been somewhat reluctant to use, but we’re increasingly more comfortable using now,” said Gordon, chief of the division of hepatology at Henry Ford Hospital.
Chances of a recurrence are “almost negligible,” Gordon said, citing the sustained response in clinical trials.
In the New England Journal of Medicine, Gordon and researchers at 10 U.S. and European centers report that two-thirds of the 403 patients eliminated all traces of the hepatitis C virus as long as six months.
Similar results were reported in another trial last year of the other regimen.

Telaprevir and boceprevir have different side effects. Telaprevir is associated with a rash, and boceprevir can cause an altered, metallic sense of taste.


PlantPharm Biomed On Target To Introduce First Plant-Based Hepatitis B Vaccine
Article Date: 05 Apr 2011

PlantPharm Biomed, a leader in plant-derived biomanufacturing, is on the cusp of introducing one of the first Plant-Made Pharmaceuticals (PMPs) with the release of an oral Hepatitis B vaccine proven to work in human subjects in a double-blind, placebo controlled Phase I clinical trial. The company is currently seeking FDA approval of the product, with other Plant-Made Pharmaceuticals products to follow.

Plant-Made Pharmaceuticals offer a faster, lower cost, more efficient method of producing pharmaceuticals, however, the industry has been struggling for years to find a method of production that is safe and effective. To achieve success, pharmaceutical proteins in plants must be grown in a zero-tolerance, 100% containment method for the public safety, with no potential to co-mingle with the food or seed supply. PlantPharm Biomed developed a proprietary, closed-environment growing system that has been perfected in cooperation with NASA. This biomanufacturing technology includes 30 patents and registrations worldwide, and the controlled environment production of fast growth, pathogen-free seed potatoes has been perfected by the company for more than a decade. PlantPharm is pleased to announce that the technology is now ready for use in biomanufacturing Plant-Made Pharmaceuticals.

Recognized with Current Good Manufacturing Practices (cGMP) certification and supported the US National Institutes of Health (NIH), PlantPharm's technology is designed to control all plant growth needs in a completely closed production system that is computer-controlled to provide for as many as six crops annually. Plants are grown with precise duplication of conditions to provide for optimum production for each harvest, and with full containment security for prevention of plant genetic migration into the wild.

PlantPharm Biomed is on track to be the first-to-market with an oral dose hepatitis B vaccine produced completely in potato plants. The global demand is evident for a low-cost, shelf-stable, orally administered vaccine. According to the World Health Organization (WHO), goals to reduce hepatitis B infections by 2012 are at risk due to immunization and surveillance gaps. Nearly 2 billion people are infected with hepatitis B, and 350 million more have chronic infections. With PlantPharm's patented technology, cost of production for a hepatitis B vaccine will reduce the per dose costs to recipients by nearly 50%. The dosage is also oral rather than injected, making it is easier to administer in mass quantities with a greater shelf life than liquid vaccines, a particular problem in places with inadequate refrigeration and infrastructure limitations, such as in third-world countries.

PlantPharm Biomed

Liver Cancer

Jennerex And Transgene Announce The Presentation Of Positive Clinical Data Of JX-594 In Patients With Liver Tumors
05 April 2011
Jennerex, Inc., a private clinical-stage biotherapeutics company focused on the development and commercialization of first-in-class targeted oncolytic products for cancer, and Transgene (Paris:TNG) (NYSE Euronext Paris...

Liver Cancer;PS-Targeting Antibody Significantly Improves Anti-Tumor Effect of Sorafenib
Peregrine's PS-Targeting Antibody Significantly Improves Anti-Tumor Effect of Sorafenib in Models of Advanced Liver Cancer

AACR Data Presentation Supports Phase I/II Investigator-Sponsored Clinical Trial in Advanced Liver Cancer

TUSTIN, CA and ORLANDO, FL--(Marketwire - April 5, 2011) - Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that its phosphatidylserine (PS)-targeting antibody significantly enhanced the anti-tumor effects of sorafenib (Nexavar®) in models of hepatocellular carcinoma (HCC), with 69% less tumor growth compared to sorafenib alone. This study, one of four poster presentations on Peregrine's PS-targeting antibodies at the Annual Meeting of the American Association of Cancer Research (AACR), was the basis for initiating a Phase I/II investigator-sponsored trial (IST) evaluating the company's lead antibody bavituximab with sorafenib in patients with advanced HCC. Bavituximab is currently in three randomized Phase II clinical trials in lung cancer and pancreatic cancer and several ISTs for additional oncology indications.

AACR: Diabetes Linked to Cancer Risk and Mortality
Diabetes tied to lower risk of prostate cancer but higher risk of other cancers in men and women

MONDAY, April 4 (HealthDay News) -- Diabetes appears to be associated with a decreased risk of prostate cancer in men but an increased risk of other cancer types in both men and women, according to research presented at the annual meeting of the American Association for Cancer Research, held April 2 to 6 in Orlando, Fla.

In a prospective study, Gabriel Lai, Ph.D., of the National Cancer Institute in Rockville, Md., and colleagues evaluated 295,287 men and 199,665 women. The investigators found that diabetes was associated with an 8 percent increased risk for cancer among women and a 4 percent decreased risk for men. However, after excluding prostate cancer from the assessment, the investigators found that diabetes was associated with a 9 percent increased risk for cancer in men.

The investigators also found that diabetes was associated with an 11 percent increased risk of mortality in women and a 17 percent increased risk in men. In both men and women, diabetes was associated with a significant increase in risk for colon (hazard ratio [HR], 1.15), rectal (HR, 1.28), and liver cancers (HR, 2.40). In women, diabetes was associated with an increased risk for stomach (HR, 1.74), anal (HR, 2.44), and endometrial cancers (HR, 1.20). However, in men, diabetes was tied to an elevated risk for pancreatic (HR, 1.47) and bladder (HR, 1.10) cancers. In another study, Katherine McGlynn, Ph.D., of the National Cancer Institute, and colleagues found that metabolic syndrome was associated with an increased risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

"Follow-up studies to identify the biologic mechanisms involved should be performed to build upon confirmed findings," Lai said in a statement

Off The Cuff

Staying Healthy -- It's Complicated
A personal wake-up call gave health policy expert David Nash, MD, MBA, a new perspective on the health and economic impact of diabetes and pre-diabetes.

Merck, J&J’s New Hepatitis C Treatment Fetches $31,000 in France

U.S. Pricing Of New HCV Drugs

J&J and Vertex Pharmaceuticals Inc. (VRTX)’s telaprevir costs 22,000 euros under a French program for seriously ill patients for whom there is no other effective treatment on the market, according to patient association SOS Hepatites. Merck & Co. said its boceprevir costs 30,000 euros under the same program.

The price may drop once the drugs are approved for the broader market, Merck and J&J executives said. Still, the French model shows the new drugs may triple the cost of hepatitis C treatment, leaving England, Russia and eastern Europe likely to delay use or restrict which patients are allowed access, said Antonio Craxi, director of gastroenterology and internal medicine at the University of Palermo.

In the U.S., the new drugs may be priced at $35,000 to $40,000, estimates Howard Liang, a Boston-based analyst at Leerink Swann & Co.
“A cure saves a lot of money down the road,” Liang said in an interview. “It’s a shock to physicians, but I think it can be justified because it’s a cure.”

Meanwhile, the next generation of drugs with even higher cure rates and fewer side effects is likely to reach the market within three years, Liang said.

Swedish drugmaker Medivir AB (MVIRB) has said it expects to begin selling a competitor pill to be used with interferon by 2013. Boehringer Ingelheim GmbH, Gilead Sciences Inc. (GILD) and Bristol- Myers Squibb Co. are among a dozen companies aiming for drug cocktails to replace the existing interferon combination........Read More...

U.S.: When a Half-Truth Is the Best Medicine

Meghan MacLean Weir, pediatrician and author

"In discussing a diagnosis with worried parents…I try to defuse the anxiety in the room so that we can deal with things as they actually are…But every once in a while I am faced with a patient…[where] I find it hard to know exactly what to say…New doctors are not given a handbook that says how much of the truth we need to tell. We are not meant to lie to our patients, of course, even when lies might be kinder. But neither are we meant to inflict harm…I find it difficult to engage in this kind of half-truth, but I also realize that sometimes it is the best thing I can do."...continue reading


Monday, April 4, 2011

Issues Clinical Practice Guidelines for Management of HCV

From Medscape Medical News

EASL Issues Clinical Practice Guidelines for Management of HCV

Daniel M. Keller, PhD

April 4, 2011 (Berlin, Germany) — Here at the opening session of the European Association for the Study of the Liver (EASL) 46th Annual Meeting, new guidelines were announced to help healthcare providers, patients, and interested individuals make decisions about the management of patients with acute and chronic hepatitis C virus (HCV) infections.
The guidelines encompass all aspects of the diagnosis and treatment of chronic HCV infection and address the use of diagnostic, therapeutic, and preventive techniques. They are the fifth in a series that the EASL has issued for liver diseases.
As evidenced by a wealth of clinical trial presentations that are being made here at the conference on new drugs in development to treat HCV, it is expected that many more treatments will be licensed in the next few years.

However, the guidelines issued here are restricted to therapies that have been approved at the time of publication. EASL has committed to update the guidelines on a regular basis upon approval of additional therapies.

Antonio Craxi, MD, professor of gastroenterology and internal medicine at the University of Palermo in Italy, and director of gastroenterology and hepatology at the university's Academic Department of Internal Medicine, coordinated the development of the guidelines. He discussed them in a news conference and said that part of the rationale for them is to set standards of diagnosis and treatment for specific patient profiles. They were developed by an expert panel that reviewed the scientific literature on the subject through December 2010. If clinical data were unavailable, expert experience and opinion were included.
The guidelines comprise sections on diagnosis, therapy, follow-up to therapy, measures to improve treatment success rates, and factors to consider when deciding on retreatment if therapy has failed.

Dr. Craxi emphasized that history and physical examination of the patient must be part of diagnosis, and that diagnosis cannot rely solely on serology that identifies anti-HCV antibodies or the level of HCV RNA in the blood.
"We had to . .  decide on a very crucial point — whether a biopsy was still necessary to assess the severity of liver disease," Dr. Craxi said.

Although biopsy remains the reference method for assessing the degree of fibrosis, most patients dislike it, and it carries risk for complications. "It won't be acceptable to have a liver biopsy as a prerequisite for all treatment," he said, noting that it can usually be dispensed with for HCV genotypes 2 and 3, which are easier forms of the virus to eradicate with current therapy. And a biopsy is not always necessary for the more difficult-to-treat genotypes 1 and 4, since other methods such as transient elastography (FibroScan) and serum biomarkers are available to determine the degree of liver fibrosis.

Eradication of HCV Infection Is Therapeutic Goal
Eliminating virus from the body can prevent complications such as fibrosis, cirrhosis, liver cancer, and death. The desired end point of therapy is a sustained virological response, determined by undetectable HCV RNA in the blood 24 weeks after the end of therapy, Dr. Craxi noted.
The current standard approach is treatment with a combination of pegylated interferon alfa plus ribavirin. The University of Palermo investigator said large studies have shown that the 2 commercially available pegylated interferons are equivalent, and neither is recommended over the other.
He pointed out that the new guidelines consider the virological response to pegylated interferon/ribavirin to guide therapy, taking into account the speed of response and the degree of viral suppression. "For the first time, there is a clear statement that patients with a rapid response and with genotype 1 can be treated for 24 weeks [and that treatment can be extended] beyond 24 weeks for patients who have a delayed viral response."

Separate decision maps in the published guidelines, which will appear in the Journal of Hepatology, delineate response-guided therapy for genotypes 1 and 4 and for genotypes 2 and 3.
Previous American guidelines were issued more than 5 years ago, Dr. Craxi noted, and they did not involve response-guided therapy. Additionally, ribavirin dosage adjustment according to patient weight is now recommended, since heavier weight adversely affects the response to therapy.
The expert panel made recommendations for the follow-up of untreated patients with or without cirrhosis and for the retreatment of patients for whom previous therapy failed. Dr. Craxi said that patients with resistant disease might respond to some of the new small-molecule drugs currently in development, and it might be worthwhile to delay treatment for some of them until the new drugs are available, depending on their current state of health.

Mark Thursz, MD, EASL vice secretary and professor of hepatology at Imperial College, London, United Kingdom, noted that not recommending a liver biopsy for every patient is an important development for patients. "It's no longer necessary for every patient. In fact, it's probably only appropriate when there's a doubt about the contribution of different diseases," such as heavy alcohol consumption and HCV, or obesity and HCV. Response-guided therapy can also be positive for patients, sparing some of them unnecessary adverse effects if they can be treated for a shorter time. It should have a positive economic impact, as well, he noted.

Dr. Thursz said he reviewed the guidelines before publication but was not involved in their development.

Dr. Craxi reports receiving research support and lecture fees from, and taking part in clinical trials for, Roche, MSD, Siemens, and Abbott. Dr. Thursz has disclosed no relevant financial relationships.
European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 31, 2011.