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Norah Terrault

Publications and source records attributed to Norah Terrault.

16 recordsLinked to original sources
PubMed2006

Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection.

Assessment of histological stage is an integral part of disease management in patients infected with the hepatitis C virus (HCV). The aim of this study was to develop a model incorporating objective clinical and laboratory parameters to estimate the probability of severe fibrosis (i.e., Ishak fibrosis > or = 3) in previously untreated African American (AA) and Caucasian American (CA) patients with HCV genotype 1. The Ishak fibrosis scores of 205 CA and 194 AA patients enrolled in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study (Virahep-C) were modeled using simple and multiple logistic regression. The model was then validated in an independent cohort of 461 previously untreated patients with HCV. The distribution of fibrosis scores was similar in the AA and CA patients as was the proportion of patients with severe fibrosis (35% vs. 39%, P = .47). After accounting for the number of portal areas in the biopsy, patient age, serum aspartate aminotransferase, alkaline phosphatase, and platelet count were independently associated with severe fibrosis in the overall cohort, and the relationship with fibrosis was similar in both the AA and CA subgroups. The area under the receiver operating characteristic curve (AUROC) of the Virahep-C model (0.837) was significantly better than in other published models (P = .0003). The AUROC of the Virahep-C model was 0.851 in the validation population. In conclusion, a model consisting of widely available clinical and laboratory features predicted severe hepatic fibrosis equally well in AA and CA patients with HCV genotype 1 and was superior to other published models. The excellent performance of the Virahep-C model in an external validation cohort suggests the findings are replicable and potentially generalizable.

Black or African American↗
PubMed2006

Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.

BACKGROUND & AIMS: Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index. METHODS: We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States. RESULTS: Steatosis was present in 1561 patients (50.9%) and fibrosis in 2688 (87.6%). HCV genotype was 1 in 1694 cases (55.2%), 2 in 563 (18.4%), 3 in 669 (21.8%), and 4 in 142 (4.6%). By stepwise logistic regression, steatosis was associated independently with genotype 3, the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, higher body mass index, and older age. Fibrosis was associated independently with inflammatory activity, steatosis, male sex, and older age, whereas HCV genotype 2 was associated with reduced fibrosis. In the subgroup analyses, the association between steatosis and fibrosis invariably was dependent on a simultaneous association between steatosis and hepatic inflammation. CONCLUSIONS: In this large and geographically different group of CHC patients, steatosis is confirmed as significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis. Control of metabolic factors (such as overweight, via lifestyle adjustments) appears important in the management of CHC.

Adult↗
PubMed2005

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Adult↗
PubMed2005

Update on chronic hepatitis C.

The burden of chronic hepatitis C infection remains significant in the United States and worldwide. Increased knowledge regarding the natural history of acute and chronic infection and the key factors responsible for disease progression, risk for cirrhosis, and risk for hepatocellular carcinoma are critical in guiding secondary and tertiary prevention measures. The past decade has seen substantial improvement of antiviral therapy for chronic hepatitis C virus with an increasing number of individuals achieving viral eradication. Decisions regarding whom, when, and how to use antiviral therapy have become more complex and change as new studies become available. This review focuses on the current status of hepatitis C virus patient management and future treatment directions.

Antiviral Agents↗
PubMed2004

Prediction of survival after liver retransplantation for late graft failure based on preoperative prognostic scores.

The current policy for determining priority for organ allocation is based on the model for end stage liver disease (MELD). We hypothesize that severity of graft dysfunction assessed by either the MELD score or the Child-Turcotte-Pugh (CTP) score correlates with mortality after liver retransplantation (re-OLT). To test this hypothesis, we analyzed the outcome of 40 consecutive patients who received re-OLT more than 90 days after primary orthotopic liver transplantation (OLT). The Kaplan-Meier 1-year and 5-year survival rates after re-OLT were 69% and 62%, respectively. The area under the curve (AUC) values generated by the receiver operating characteristics (ROC) curves were 0.82 (CI 0.70-0.94) and 0.68 (CI 0.49-0.86), respectively (P =.11), for the CTP and MELD models in predicting 1-year mortality after re-OLT. The 1-year and 5-year survival rates for patients with CTP scores less than 10 were 100% versus 50% and 40%, respectively, for CTP scores of at least 10 (P =.0006). Patients with MELD scores less than or equal to 25 had 1-year and 5-year survival rates of 89% and 79%, respectively, versus 53% and 47%, respectively, for MELD scores greater than 25 (P =.038). Other mortality predictors include hepatic encephalopathy, intensive care unit (ICU) stay, recurrent hepatitis C virus (HCV) infection, and creatinine level of 2 mg/dL or higher. Analysis of an independent cohort of 49 patients showed a trend for a correlation between CTP and MELD scores with 1-year mortality, with AUC of 0.59 and 0.57, in respective ROC curves. In conclusion, our results suggest that severity of graft failure based on CTP and MELD scores may be associated with worse outcome after re-OLT and provide a cautionary note for the "sickest first" policy of organ allocation.

Adult↗
PubMed2004

Hepatitis C virus and lichen planus: a review.

INTRODUCTION: The relationship between hepatitis C virus (HCV) infection and oral lichen planus (OLP) remains a matter of controversy. It is important to determine whether there is an association between OLP and HCV infection so that guidelines regarding the routine HCV testing of patients with OLP can be developed for clinicians. OBJECTIVES: The objective of this article was to review and summarize the published literature on the association between OLP and HCV and to describe future directions. METHODS: A search of the computerized database MEDLINE (1966-June 2003) was conducted. The bibliographies of articles identified by means of MEDLINE were also searched. Any studies reporting the prevalence of HCV in a group of patients with LP either with or without a control group were included in this review. Also included were studies comparing the clinical and histologic features of LP among patients with and without HCV infection, studies on the presence of HCV within LP lesions, and studies of HCV genotypes among patients with LP. RESULTS: Thirty-two studies conducted in various parts of the world were identified. Study types included prevalence studies on HCV exposure among patients with OLP (0%-62%), prevalence of OLP among patients with HCV infection (1.6%-20%), and case-control studies of this association. In addition, the results from 3 studies on the replication of HCV in the oral mucosa, 3 studies on the genotype of HCV in OLP patients, and 4 studies comparing the clinical and histologic features of OLP in HCV-infected and uninfected individuals have been summarized. CONCLUSION: At present, studies on the association of OLP and HCV provide enough information to raise a number of interesting questions about this association. Important biases-including selection bias; investigator bias due to lack of blinding and the possible resultant nondifferential misclassification of disease; and possible confounding by age in the studies published-make it difficult to draw firm conclusions. However, the need for future studies that take into consideration all these factors in the study methodology is highlighted by this review.

Bias↗
PubMed2003

A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents.

BACKGROUND: The incidence of acute liver failure or serious liver injury in diabetic patients is needed to evaluate the safety of hypoglycemic drug therapy. METHODS: We conducted a retrospective cohort study of 5 health maintenance organizations. Study patients were 171,264 health plan members 19 years or older when they received oral hypoglycemic drugs or insulin between April 1, 1997, and June 30, 1999. We searched for hospital discharge diagnoses and procedures potentially indicative of acute liver injury and reviewed the full-text medical records. Acute liver failure was defined as acute liver disease and (1) hepatic encephalopathy, (2) prothrombin time prolongation greater than 3 seconds or international normalized ratio greater than 1.5, and (3) a total bilirubin level greater than 3.0 mg/dL (>51 micro mol/L). Acute liver injury was diagnosed in individuals who did not meet 1 or more of the criteria for acute liver failure but had alanine transaminase or aspartate transaminase levels greater than 500 U/L. RESULTS: We identified 35 cases of acute liver failure or injury not clearly attributable to a known cause other than use of hypoglycemic agents. The age- and sex-standardized incidence per 1000 person-years was 0.15 for insulin users, 0.08 for sulfonylurea users, 0.12 for metformin users, and 0.10 for troglitazone users. The incidence was higher (on the order of 0.3 per 1000) during the first 6 months of exposure to all hypoglycemic agents. CONCLUSIONS: Acute liver failure or injury not clearly attributable to other known causes occurred on the order of 1 per 10,000 person-years among diabetic patients treated with oral hypoglycemic drugs or insulin.

Acute Disease↗
PubMed2003

Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients.

Three-hundred and twenty-four patients were enrolled in an open-label, multicenter, international study in which pre- and post-liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre- and post-LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81% of the pre-LT and 34% of the post-LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of -4.1 log(10) and -4.3 log(10) copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre-LT patients and 49%, 76%, 75%, and 20% of post-LT patients. The Child-Pugh-Turcotte (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98% of these patients had lamivudine-resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One-year survival was 84% for pre-LT and 93% for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre- and post-LT with lamivudine-resistant HBV.

Adenine↗
PubMed2003

Hepatitis B virus genotypes in the United States: results of a nationwide study.

BACKGROUND & AIMS: Hepatitis B virus (HBV) genotypes may be related to severity of liver disease and treatment response. The aims of this nationwide study were to determine the prevalence of HBV genotypes in the United States and the association between HBV genotypes and patient demographics, mode of infection, and clinical status. METHODS: A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotyping, precore, and core promoter variants by line-probe assays. RESULTS: All 7 HBV genotypes (A-G) were found, with genotypes A and C the most common. The prevalence of HBV genotypes was different in different regions of the United States. A strong correlation was found between HBV genotypes and ethnicity. HBV genotype A was prevalent among white and black patients, whereas genotypes B and C were most common among Asian patients. The predominant genotype among patients born in the United States, Europe, the Far East, and Southeast Asia were A, D, C, and B, respectively. Genotypes A and C were associated with a higher prevalence of hepatitis B e antigen. Precore variant was detected in 27% of patients and core promoter variant in 44% of patients. CONCLUSIONS: Our study suggests that the epidemiology of HBV infection in the United States may have changed over time as a result of immigration from countries with a high prevalence of HBV infection. HBV genotypes may account for the heterogeneity in disease manifestations among patients with chronic HBV infection.

Adolescent↗
PubMed2003

Prevalence of HBV precore/core promoter variants in the United States.

Variants in the precore (G(1896)A) and core promoter (A(1762)T, G(1764)A) regions of hepatitis B virus (HBV) may be related to serum HBV DNA levels and severity of liver disease. The aims of this nationwide study were to determine the prevalence of HBV precore/core promoter variants in the United States and the association between these variants and patient demographics, HBV genotypes, serum HBV DNA level, and severity of liver disease. A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotypes as well as precore and core promoter variants by line-probe assays. Quantitative HBV DNA levels were determined using Cobas Amplicor HBV Monitor kits. Precore and core promoter variants were found in 27% and 44% of patients with chronic HBV infection in the United States. Precore and core promoter variants were more common in hepatitis B e antigen (HBeAg)-negative than in HBeAg-positive patients (precore, 38% vs. 9%; core promoter, 51% vs. 36%; respectively, P <.001). The prevalence of these variants was related to ethnicity, place of birth, and HBV genotypes. Patients with core promoter variants were more likely to have hepatic decompensation. Precore and/or core promoter variants were associated with higher serum HBV DNA levels in HBeAg-negative but not in HBeAg-positive patients. In conclusion, HBV precore and core promoter variants are not rare in the United States. Physicians should be aware of the existence of HBV precore and core promoter variants and the clinical condition of "HBeAg-negative chronic hepatitis."

Adult↗
PubMed2002

Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: safety and antiviral properties.

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers.

Adult↗
PubMed2002

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation.

Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNA-positive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 x 10(6) U/d; (2) group B, interferon alfa-2b, 3 x 10(6) U three times weekly; or (3) group C, interferon alfa-2b, 1 x 10(6) U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis.

Antiviral Agents↗
PubMed2002

Motion - the available treatments for hepatitis C are cost effective: arguments for the motion.

The treatment of hepatitis C has evolved over the past decade, and a combination of interferon (IFN), pegylated or standard type, and ribavirin is now acknowledged as the therapy of choice. Questions remain, however, about the duration of treatment and which patients are the most likely to benefit from therapy. Cost effectiveness analyses (CEAs) have been employed to answer these questions. Before the results can be interpreted appropriately, however, clinicians must make themselves aware of the underlying assumptions and the nature of the 'reference' case. Moreover, certain parameters, including quality-of-life evaluations, may not be easily translated from one jurisdiction to another. The costs and benefits of treatment are often very sensitive to such factors as patient age, viral load, histological severity and the viral genotype. Randomized controlled clinical trials, and the CEAs on which they are based, have shown that combination therapy is more cost effective than IFN monotherapy, and that both are cost effective compared with no treatment. Ongoing research on the use of pegylated IFN, weight-adjusted dosing of ribavirin, and the treatment of relapsers and nonresponders will provide valuable data that could be incorporated into future CEAs. Health care resources are vast, but not limitless. Therefore, health care providers need to become aware of how best to allocate resources to the general population. CEAs can facilitate this process by determining which treatment strategies are likely to yield the greatest clinical benefits without excessive expenditures.

Antiviral Agents↗
PubMedDate not supplied

De novo malignancies following liver transplantation: a case-control study with long-term follow-up.

BACKGROUND: Long-term survival data on de novo malignancy are limited following orthotopic liver transplantation (OLT) when compared with controls without malignancies. METHODS: Over a 12 yr period at our institution, 50 of 1043 patients (4.8%) who underwent OLT were identified to have 53 de novo malignancies. The clinical characteristics and survival of these patients were retrospectively reviewed and compared with a control cohort of 50 OLT recipients without malignancy matched with the incidence cases by age, year of OLT, sex, and type of liver disease. RESULTS: Chronic hepatitis C, alcohol and primary sclerosing cholangitis were the three leading causes of liver disease. Skin cancer was the most common malignancy (32%), followed by gastrointestinal (21%), including five small bowel tumors, and hematologic malignancies (17%). The cases and controls were not significantly different in the immunosuppressive regimen (p = 0.42) or the number of rejection episodes (p = 0.92). The five- and 10-year Kaplan-Meier survival rates for the cases were 77% and 34%, respectively, vs. 84% and 70%, respectively, for the controls (p = 0.02 by log-rank test). Patients with skin cancers had survival similar to the controls, but significantly better than non-skin cancers (p = 0.0001). The prognosis for patients with gastrointestinal tumors was poor, with a median survival of 8.5 months after the diagnosis. CONCLUSION: In this single institutional study, de novo malignancies after OLT were uncommon. Patients with non-skin cancer after OLT had diminished long-term survival compared with the controls. Our results differ from other reports in the high incidence of gastrointestinal malignancies with attendant poor prognosis.

Adult↗