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Biomedical subjects

T Poynard

Publications and source records attributed to T Poynard.

At least 73 records · Page 4Linked to original sources

The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C. The International Hepatitis Interventional Therapy Group.

BACKGROUND & AIMS: Black patients with chronic hepatitis C have lower response rates than white patients to interferon monotherapy. The factors responsible for these differences are unknown, as is the impact of combination antiviral therapy on responsiveness among ethnic groups. We evaluated the impact of race on response to therapy in these patients. METHODS: A total of 1744 patients with chronic hepatitis C were randomized in 2 recent clinical trials to receive 24 or 48 weeks of interferon monotherapy or interferon-ribavirin combination therapy. RESULTS: Sustained virologic responses occurred in 27% of 1600 whites, 11% of 53 blacks (P = 0.01 vs. white), 44% of 32 Asians, and 16% of 27 Hispanics. No black patient had a sustained virologic response to interferon monotherapy, but 20% and 23% had sustained responses to 24 and 48 weeks, respectively, of combination therapy. Among black patients, 96% had hepatitis C genotype 1 compared with 65% of white subjects (P < 0.0001). Sustained response rates were similar for black and white patients with genotype 1 infection (23% vs. 22%, respectively). Compared with whites, black patients were older, weighed more, and had higher median Histologic Activity Index scores but did not differ in sex, baseline alanine aminotransferase or hepatitis C virus (HCV)-RNA levels, degree of fibrosis or percentage with cirrhosis, or other demographic variables. White subjects had a significantly greater reduction in HCV-RNA levels than blacks at weeks 4, 12, 24, and 48 of therapy, but only for black patients treated with interferon monotherapy. The decreased reduction of HCV-RNA reduction among blacks was eliminated by combination therapy. CONCLUSIONS: These observations suggest that the impaired responsiveness of black patients to interferon monotherapy can be overcome partially by combination interferon-ribavirin therapy.

Adult↗

Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C.

The extent of liver fibrosis is an important prognostic factor in patients infected with hepatitis C virus. Administration of a combination of interferon and ribavirin produces a superior viral clearance response rate than interferon alone. The effect of this combination regimen on hepatic fibrosis has not been established. To determine the impact of combination regimen or interferon alone on the progression of liver fibrosis we pooled individual data of 1,509 patients with pretreatment and post-treatment biopsies from 3 randomized trials. Fibrosis progression and regression rates between biopsies were calculated by the Kaplan-Meier method and by the fibrosis progression rate per year. The percentage of patients without significant fibrosis (stage 0 or 1) at 96 weeks was 68 +/- 4% (mean +/- SE) when treated by combination regimen for 48 weeks, 64 +/- 4% by interferon alone for 48 weeks, 42 +/- 7% by combination regimen for 24 weeks (lower than both 48-week regimens P <.001), and 24 +/- 9% interferon alone for 24 weeks (lower than the combination regimen for 24 weeks; P =.02). Three factors were independently associated with fibrosis reduction: sustained viral response, duration of treatment, and baseline fibrosis stage (all P <.001 in proportional hazards regression model). These results show that interferon and ribavirin combination therapy significantly reduces the rate of fibrosis progression in patients with hepatitis C. This effect was most prominent in patients who achieved a virologic response, those receiving 48 weeks of therapy, and in patients with significant fibrosis at baseline.

Adult↗

Fibrosis in patients with chronic hepatitis C: detection and significance.

Estimates of the extent of hepatic fibrosis and the rate of fibrosis progression represent important surrogate end points for evaluation of the vulnerability of an individual patient and for assessment of the impact of treatment on natural history in chronic hepatitis C. Using the median fibrosis progression rate, the median expected time to cirrhosis in untreated patients is around 30 years. However, one third of patients have an expected median time to cirrhosis of less than 20 years and one third will only progress to cirrhosis in more than 50 years, if ever. Factors independently associated with fibrosis progression are duration of infection, age, male gender, consumption of alcohol, human immunodeficiency virus co-infection, and low CD4 count. Evaluation of fibrosis progression is useful to decide treatment. Among patients with sustained viral response, fibrosis regresses. Evaluation of fibrosis progression has permitted validation of the concept of suppressive therapy. Among patients without viral clearance, interferon alone or in combination with ribavirin significantly reduces fibrosis progression rate in comparison with progression before treatment and to control groups. There is a major need for noninvasive markers of liver fibrosis. None are clearly useful today for the diagnosis of early stages of fibrosis.

Antiviral Agents↗

Cost-effectiveness of 24 or 48 weeks of interferon alpha-2b alone or with ribavirin as initial treatment of chronic hepatitis C. International Hepatitis Interventional Therapy Group.

OBJECTIVE: Initial therapy with ribavirin and interferon alpha-2b results in a higher sustained virological response than interferon alone, but this regimen is expensive. We aimed to examine the cost-effectiveness of 24- or 48-wk initial treatment with combination therapy versus interferon alone for patients who have chronic hepatitis C. METHODS: Data from recent randomized clinical trials comparing combination therapy to interferon alone were applied to a previously published computer cohort simulation to project lifelong clinical and economic outcomes. Natural history and economic estimates were based on published literature, expert panel estimates, and actual variable cost and reimbursement data. RESULTS: Using treatment stopping rules, sustained viral negative response rates would be 33.1% and 39.8% for patients receiving 24 versus 48 wk of ribavirin/interferon, compared with 14.3% for 48 wk of interferon alone. Compared to the interferon alone strategy, 24 or 48 wk of combination therapy should prolong life expectancy by 1.4 to 2.0 yr at marginal cost-effectiveness ratios of $4,400 to $5,400 per discounted quality-adjusted life-year (DQALY) gained. Compared to 24 wk of combination therapy, 48 wk of combination therapy should prolong life expectancy by 0.6 yr at a marginal cost-effectiveness ratio of $7,700 per DQALY gained. The results were robust, with 24 or 48 wk of combination therapy remaining preferred and cost-effective in sensitivity analysis compared with interferon alone. CONCLUSION: For patients with chronic hepatitis C, 24 or 48 wk of ribavirin and interferon should prolong life and be cost-effective when compared with 48 wk, of interferon alone.

Adult↗

Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report.

BACKGROUND: More severe liver disease together with a poor response rate to alpha interferon argue for the use of more potent anti-hepatitis C virus (HCV) therapies in human immunodeficiency virus (HIV)-HCV coinfected patients, but the efficacy and safety of interferon-ribavirin combination therapy in HIV infected subjects are unknown. AIM: To retrospectively evaluate the efficacy and safety of anti-HCV combination therapy in 21 HCV-HIV coinfected patients receiving antiretroviral therapy, and to access the clinical relevance of in vitro inhibition of phosphorylation by ribavirin of potent inhibitors of HIV-that is, zidovudine, stavudine, and zalcitabine. PATIENTS: Twenty one patients were treated with combined antiretroviral therapy including zidovudine (n=8) or stavudine (n=13) (in association with protease inhibitors in 12). All received ribavirin (1000 or 1200 mg/day) and alpha interferon (3 MU three times/week) for chronic hepatitis C infection. All patients had not responded (n=20) or relapsed (n=1) after a previous six month course of alpha interferon therapy. METHODS: HIV viral load (Monitor test) and CD4 cells count were measured at the beginning and every three months during and after ribavirin plus alpha interferon therapy over a mean period of 11 (1) months. Clinical and biological adverse effects were recorded. RESULTS: There was no significant variation in HIV viral load or CD4 cell counts after three or six months of ribavirin therapy compared with baseline values. Of the 21 subjects, three (14%) had an increase in HIV viral load of more than 0.5 log leading to discontinuation of ribavirin in one. Eleven of 21 (52.4%) had initial negative HCV viraemia at three (n=10) or six (n=1) months but only six were polymerase chain reaction negative at the end of therapy, leading to rates for primary response and breakthrough of 23.8% and 28.5%, respectively. Six months after completion of therapy, three patients relapsed (14. 3%) and three (14.3%) had sustained virological response. Median haemoglobin concentration decreased significantly after three and six months of ribavirin therapy (p= 0.0002 and p=0.0003, respectively) leading to withdrawal of therapy in one patient. CONCLUSIONS: These preliminary results show that: (1) despite in vitro interactions between ribavirin, zidovudine, and stavudine, significant variation in HIV replication does not usually occur in HCV-HIV coinfected patients receiving ribavirin and different antiretroviral regimens, including zidovudine and stavudine; (2) alpha interferon and ribavirin combination therapy induced primary and sustained virological responses in 28.5% and 14.3% of treated subjects (who were previous non-responders to interferon therapy), respectively; (3) anaemia is a frequent adverse event. Such results should be confirmed in larger prospective trials.

Adult↗

Appropriateness of liver biopsy.

This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heterogeneous opinions concerning the appropriateness of liver biopsy. Appropriateness should be evaluated for different techniques such as percutaneous liver biopsy, guided or not by ultrasonography, and the types of needles, automatic or not. The present paper reviews the evaluation of liver biopsy appropriateness in the real world, the adverse events and mortality of liver biopsy, and the appropriateness of liver biopsy in alcoholic liver disease and chronic hepatitis C. The authors conclude that liver biopsy is used extensively, but its appropriateness has not been evaluated perfectly. Therefore, further evaluation of the appropriateness of liver biopsy in the practical algorithm of such diseases is needed.

Biopsy↗

Estimating future hepatitis C morbidity, mortality, and costs in the United States.

OBJECTIVES: This study estimated future morbidity, mortality, and costs resulting from hepatitis C virus (HCV). METHODS: We used a computer cohort simulation of the natural history of HCV in the US population. RESULTS: From the year 2010 through 2019, our model projected 165,900 deaths from chronic liver disease, 27,200 deaths from hepatocellular carcinoma, and $10.7 billion in direct medical expenditures for HCV. During this period, HCV may lead to 720,700 years of decompensated cirrhosis and hepatocellular carcinoma and to the loss of 1.83 million years of life in those younger than 65 at a societal cost of $21.3 and $54.2 billion, respectively. In sensitivity analysis, these estimates depended on (1) whether patients with HCV and normal transaminase levels develop progressive liver disease, (2) the extent of alcohol ingestion, and (3) the likelihood of dying from other causes related to the route of HCV acquisition. CONCLUSIONS: Our results confirm prior Centers for Disease Control and Prevention projections and suggest that HCV may lead to a substantial health and economic burden over the next 10 to 20 years.

Adolescent↗

Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C.

OBJECTIVE: To assess the prevalence of clinical and biologic extrahepatic manifestations of hepatitis C virus (HCV) infection and to identify associations between clinical and biologic manifestations. METHODS: To analyze the natural history of extrahepatic manifestations of HCV infection, we reviewed only the data recorded prospectively during the first visit of 1,614 patients with chronic HCV infection, coming from a single monocenter cohort. Exclusion criteria were positivity for hepatitis B surface antigen or human immunodeficiency virus. The prevalence of dermatologic, rheumatologic, neurologic, and nephrologic manifestations; diabetes; arterial hypertension; autoantibodies; and cryoglobulins were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunologic, virologic, and liver histologic factors associated with the presence of extrahepatic manifestations. RESULTS: At least 1 clinical extrahepatic manifestation was observed in each of 1,202 patients (74%). Five manifestations had a prevalence >10%: arthralgia (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%). Four biologic abnormalities had a prevalence >5%: cryoglobulins (40%), antinuclear antibodies (10%), low thyroxine level (10%), and anti-smooth muscle antibodies (7%). Only vasculitis, arterial hypertension, purpura, lichen planus, arthralgia, and low thyroxine level were associated with cryoglobulin positivity. By univariate and multivariate analyses, the most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations were age, female sex, and extensive liver fibrosis. CONCLUSION: Extrahepatic clinical manifestations are frequently observed in HCV patients and involve primarily the joints, muscles, and skin. The most frequent immunologic abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies. The most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations are advanced age, female sex, and extensive liver fibrosis.

Adult↗

Impact of hepatitis B and C virus on kidney transplantation outcome.

The impact of hepatitis B (HBV) and C (HCV) on patient survival after kidney transplantation is controversial. The aims of this study were (1) to assess the independent prognostic values of HBsAg and anti-HCV in a large renal transplant population, (2) to compare infected patients with noninfected patients matched for factors possibly associated with graft and patient survival, and (3) to assess the prognostic value of biopsy-proven cirrhosis. Eight hundred thirty-four transplanted patients were included: 128 with positive HBsAg (group I), 216 with positive anti-HCV (group II), and 490 without serological markers of HBV and HCV (group III). Fifteen percent and 29% of patients were HBsAg-positive and anti-HCV-positive, respectively. Ten-year survivals of group I (55 +/- 6%) and group II (65 +/- 5%) were significantly lower than survival of group III (80 +/- 3%, P <.001). At 10 years, among overall patients with HCV screening (n = 834), four variables had independent prognostic values in patient survival: age at transplantation (P <.0001), year of transplantation (P =.02), biopsy-proven cirrhosis (P =.03), and presence of HCV antibodies (P =.02). In the case control study, comparison of infected patients with their matched control patients showed that age at transplantation (P <.05), HBsAg (P =.005), and anti-HCV (P =.005) were independent prognostic factors. HCV, biopsy-proven cirrhosis, and age are independent prognostic factors of 10-year survival in patients with kidney grafts. The case-control study showed that anti-HCV and HBsAg were independently associated with patient and graft survivals. In infected patients, a routine liver histological analysis would improve selection of patients for renal transplantation.

Adult↗

Modeling the hepatitis C virus epidemic in France.

A backcalculation approach allows a reconstruction of the history of hepatitis C virus (HCV) infection in France and predictions of mortality from hepatocellular carcinoma (HCC) related to the virus. The model uses information from the literature about the natural history of the disease, epidemiological data about infected subjects in three French cohorts, and mortality data from national statistics. It seeks to determine the annual transition probabilities from chronic hepatitis to cirrhosis and the HCV incidence per year in the past. These unknowns are found by fitting the observed deaths from HCC that are attributable to HCV. Optimal values for these unknowns then allow to project the number of HCC deaths attributable to HCV for each year through 2025 (for patients infected before 1996). The model traces the HCV epidemic in France back to around the 1940s. It predicts that HCC mortality related to HCV will continue to increase through 2020 in the absence of treatment, with a 150% increase in the yearly incidence among men and 200% among women. The model also confirms that progression to cirrhosis depends strongly on sex and age. At any age, the annual probability of progression is 10 times greater for men than for women. Moreover, for men aged between 61 and 70 years, this probability is 300 times greater than that for men aged between 21 and 40 years.

Adult↗

Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis.

In cirrhotic patients with gastrointestinal bleeding, antibiotic prophylaxis decreases the incidence of infections but most randomized trials have not shown an increase in survival. The aim of this meta-analysis was to assess the efficacy of antibiotic prophylaxis in the prevention of infections and its effect on survival rate in cirrhotic patients with gastrointestinal bleeding. Four end points were assessed: infection, bacteremia and/or spontaneous bacterial peritonitis (SBP), incidence of SBP, and death. For each end point, heterogeneity and treatment efficacy were assessed by Der Simonian and Peto methods. Five trials including 534 patients, 264 treated with antibiotic prophylaxis for 4 to 10 days and 270 without, were identified. Mean follow-up was 12 days. Antibiotic prophylaxis significantly increased the mean percentage of patients free of infection (32% mean improvement rate, 95% confidence interval [CI]: 22-42, P <.001), bacteremia and/or SBP (19% mean improvement rate, 95% CI: 11-26, P <.001), and SBP (7% mean improvement rate, 95% CI: 2.1-12.6, P =.006). Antibiotic prophylaxis also significantly increased the mean survival rate (9. 1% mean improvement rate, 95 % CI: 2.9-15.3, P =.004), without significant heterogeneity. In cirrhotic patients with gastrointestinal bleeding, short-term antibiotic prophylaxis significantly increases the mean percentage of patients free of infection and significantly increases short-term survival rate.

Antibiotic Prophylaxis↗

Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group.

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count </=200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (</=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.

Adult↗

Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients.

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% +/- 18.6% of the patients, had sustained HBV-DNA suppression. All the 22 tested patients with HBV resistance developed mutation at position 550 in the YMDD motif of the DNA polymerase. None of the following variables were associated with an increased risk of lamivudine resistance: age, associated protease inhibitor therapy, Center for Disease Control (CDC) stage C, known HIV-infection duration, serum HBV-DNA level at baseline, CD4 cell count and serum alanine transaminase levels at baseline and at HBV-replication suppression (2 months of lamivudine). Lamivudine (300 mg/d) is effective for the inhibition of HBV replication in HIV-infected patients. However, emergence of lamivudine-resistant HBV may occur in 20% of patients per year.

Adult↗

Focal nodular hyperplasia of the liver on ferumoxides-enhanced MR imaging: features on conventional spin-echo, fast spin-echo and gradient-echo pulse sequences.

The aim of this study was to assess the efficacy of a superparamagnetic iron oxide, ferumoxides, in the detection and characterization of focal nodular hyperplasia (FNH) on MR conventional spin-echo (SE), fast spin-echo (FSE) and gradient-echo (GRE) images. Fourteen adults with 27 FNHs were evaluated at 1.5 T before and after injection of ferumoxides. T1-weighted and T2-weighted SE, T2-weighted FSE and T2(*)-weighted GRE sequences were used and analysed qualitatively and quantitatively. One hundred percent of FNHs showed a significant postcontrast decrease in signal intensity on T2- and T2*-weighted images. Heavily T2-weighted SE images showed the maximum decrease in FNH signal-to-noise ratio (S/N). Postcontrast GRE T2(*)-weighted images improved the detection of the central scar and the delineation of FNHs and demonstrated the best lesion-to-liver contrast-to-noise ratio (C/N). Postcontrast T1-weighted SE images showed the least lesion-to-liver C/N. Ferumoxides-enhanced MR imaging can help detect and characterize FNH. Conventional pre- and postcontrast T2-weighted SE images and postcontrast GRE T2*-weighted images should be used preferentially.

Adult↗

Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view. The Multivirc Group.

BACKGROUND & AIMS: Impact of hepatitis C treatment has never taken into account the dynamics of fibrosis progression. This study assessed the impact of interferon on liver fibrosis progression in patients with chronic hepatitis C according to 3-month aminotransferase activity response. METHODS: We recruited 287 patients, 185 treated and 102 control, with paired biopsy specimens. Before follow-up, the fibrosis progression rate per year was estimated as the ratio between fibrosis stage in METAVIR units (1 U, 1 stage; 4 U, cirrhosis) and the duration of infection. During follow-up, fibrosis progression was assessed by the observed difference between stages divided by duration between biopsies. RESULTS: The median fibrosis progression rate in treated patients decreased compared with the rate before treatment from 0.103 F METAVIR U/yr (95% confidence interval [CI], 0.087-0.120) to 0.000 (95% CI, 0.000-0.000; P </= 0.0001). Among 91 treated responders, fibrosis stage worsened in 19 (22%), compared with 21 (22%) of 94 treated nonresponders and 57 of 102 controls (56%; P </= 0.0001 compared with treated patients), and improved in 26 (29%), 17 (18%), and 8 (8%; P = 0.0002 compared with 29% and P = 0.03 compared with 18%), respectively. These observed differences persisted after genotype, viremia, sex, age at infection, duration of infection, and alcohol consumption were taken into account. CONCLUSIONS: Interferon treatment changes the natural fibrosis progression rate in patients with chronic hepatitis C independently of genotype and early response.

Adult↗

Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls: 5-year survival. Multi-centre group.

BACKGROUND/AIMS: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for "prioritisation", favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis. METHODS: We compared the survival of 169 transplanted patients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients. RESULTS: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58-74%) vs. 52% (44-60; p = 0.03) in the matched group and 54% (51-57; p = 0.01) in the simulated controls. Transplantation was associated with survival (relative risk = 1.51; p = 0.02), independently of risk score (risk = 2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11-15) benefited most in terms of 5-year survival: 58% (44-72) vs. 31% (17-45; p = 0.008) in the matched and 35% (30-40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference. CONCLUSIONS: Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial.

Case-Control Studies↗