Twelve-Week Posttreatment Follow-Up to Predict Sustained Virologic Response for Recurrent Hepatitis C Infection in Liver Recipients

Transplantation. 2012 Jan 18. [Epub ahead of print]

Campos-Varela I, Castells L, Esteban JI, Bes M, Rodríguez-Frías F, Sapisochin G, Allende H, Charco R, Esteban R.

1Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. 3Transfusion Safety Laboratory, Banc de Sang i Teixits (BST), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. 4Biochemistry Laboratory, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 5Liver Transplant Unit, Department of HPB-Surgery and Transplant, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 6Pathology Department, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.

Abstract

BACKGROUND: The current standard for determining sustained virologic response (SVR) in patients treated for hepatitis C virus (HCV) infection is undetectable serum HCV-RNA 24 weeks after treatment. This study evaluates the value of HCV-RNA determination at 12 weeks posttreatment (W+12) to predict SVR in liver transplant (LT) patients treated with pegylated interferon and ribavirin for recurrent HCV infection.

METHODS: This study, performed in 2001 to 2010, included HCV-LT patients with an end-of-treatment response (undetectable serum HCV-RNA) and HCV-RNA testing at 12 and 24 weeks posttreatment (W+12/W+24). HCV-RNA was detected with a qualitative polymerase chain reaction assay (detection limit 50 IU/mL) and, when positive, measured by quantitative PCR (detection limit 600 IU/mL) up to 2006. Since 2007, a real-time PCR-based test (detection limit 15 IU/mL) has been used. The positive predictive value (PPV) was defined as the probability that SVR would occur in patients with undetectable HCV-RNA at W+12 and W+24.

RESULTS: Of 162 patients treated during the study period, 57 (35%) had end-of-treatment response and were included. Of these, 45 (79%) had SVR and 12 (21%) had virologic relapse. At W+12, HCV-RNA was undetectable in 45 (79%) patients, all of whom had SVR, yielding a PPV for SVR at W+12 of 100% (95% confidence interval, 75.8%-100%).

CONCLUSIONS: Undetectable HCV-RNA at W+12 posttreatment has a high PPV for predicting SVR. HCV-RNA testing to assess SVR at this time point seems as valid as W+24 testing and could be considered for predicting SVR in HCV-LT patients receiving treatment with pegylated interferon and ribavirin.

Source

A Score Predicting Survival After Liver Retransplantation for Hepatitis C Virus Cirrhosis.

Transplantation. 2012 Jan 19. [Epub ahead of print]

Andres A, Gerstel E, Combescure C, Asthana S, Merani S, Majno P, Berney T, Morel P, Kneteman N, Mentha G, Toso C.

1Abdominal and Transplantation Surgery, Department of Surgery, University Hospital Geneva, Switzerland. 2Clinical Epidemiology, University Hospital Geneva, Switzerland and the Division of Internal Medicine, University Hospital Geneva, Switzerland. 3Division of Transplantation, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

Abstract

BACKGROUND: Approximately one fourth of patients transplanted for hepatitis C virus (HCV)-induced liver failure progress to cirrhosis within 5 years, potentially requiring retransplantation. Although the relisting decision can be difficult in these patients, a score could help in selection of candidates with the best potential outcomes.

METHODS: A total of 1422 HCV-positive patients having undergone a retransplantation were included in this registry-based study. A multivariate Cox regression was performed, and an Akaike procedure was applied to design a score predicting survival after retransplantation and to allow an internal validation. Retained variables were donor age (DnAge), serum creatinine (Creat), International Normalized Ratio (INR), and serum albumin (Alb) at the second transplantation, recipient age (RecAge) at the first transplantation, and the interval between both transplantations (Int).

RESULTS: The score was designed as 0.23×DnAge+4.86×log Creat-2.45×log Int+2.69×INR+0.10×RecAge-3.27× Alb+40. The receiver operating characteristic area under curve was 0.643 at 3 years, and survivals were 71%, 56%, and 37% for scores <30, 30 to 40, and >40, respectively (log rank <0.0001).

CONCLUSIONS: Overall, the proposed score is specifically designed for HCV-positive patients, accurately predicts survival after a liver retransplantation, and is helpful in the selection of candidates with the best potential outcomes.

Source

Medivir/Tibotec HCV Drug Development

15-Nov-11

Phase II interferon free combination study with TMC435 and PSI-7977

This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on www.clinicaltrials.gov.

TMC435HPC2002 - Phase II Trial of TMC435 in Combination With PSI-7977 in Prior G1 Null Responders to Peg-IFN/RBV, Hepatitis C-Infected Patients: 12 and 24 weeks, with & without rbv (4 arms), INF-free study

This study is currently recruiting participants.
Verified January 2012 by Tibotec Pharmaceuticals, Ireland

TMC435HPC2002 - Phase II Trial of TMC435 in Combination With PSI-7977 in Prior G1 Null Responders to Peg-IFN/RBV, Hepatitis C-Infected Patients

HCV polymerase collaboration

TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.

Nucleotide program

The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.

Source

World Cancer Day: The Five Deadly Types of the Non-Communicable Disease

By Bhaskar Prasad 

February 4, 2012 12:35 AM EST

The World Cancer Day is observed on Feb 4 in honor of the global fight against the non-communicable disease (NCD), which claimed more than 7.6 million lives in 2008 and the World Health Organization says the number is expected to rise above 11 million by 2030.

The data from the World Health Organization Global Status Report on NCDs demonstrate that almost 80 percent of these deaths occur in low and middle income countries and a quarter happen before the age of 60.

The main types of cancer are:

Lung Cancer (1.4 million deaths)

It is the deadliest type of cancer for both men and women. Each year, more people die of lung cancer than of breast, colon, and prostate cancers combined. Cigarette smoking is the leading cause of lung cancer. The more cigarettes you smoke per day and the earlier you started smoking, the greater your risk for lung cancer. There is no evidence that smoking low-tar cigarettes lowers the risk.

Stomach Cancer (740,000 deaths)

Several different types of cancer can affect the stomach. The most common type is called adenocarcinoma, which starts from one of the common cell types found in the lining of the stomach. The rate of most types of gastric adenocarcinoma in the U.S. has gone down over the years. Experts think the decrease may be because people are eating less salted, cured, and smoked foods.

Liver Cancer (700,000 deaths)

In most cases, the cause of liver cancer is cirrhosis, which is the end result of chronic liver damage caused by chronic liver diseases. Alcohol abuse is the most common cause of cirrhosis in the U.S.

Colorectal Cancer (610,000 deaths)

This type of the cancer starts in the large intestine (colon) or the rectum (end of the colon). Nearly all colorectal cancers begin as noncancerous (benign) polyps, which slowly develop into cancer.

Breast Cancer (460,000 deaths)

This type of cancer starts in the tissues of the breast. It can start in the tubes (ducts) that move milk from the breast to the nipple. It can also begin in the parts of the breast, called lobules that produce milk.

It is urgently needed to raise awareness and to bring the growing cancer crisis to the attention of the public, government leaders, and health policymakers.

Stand Up To Cancer and the Union for International Cancer Control (UICC) are launching a Facebook app that they hope will create a digital buzz that will reduce the spread of the disease. UICC notes that urgent action against cancer is vital because of its huge impact on human suffering.

Source