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T Poynard

Publications and source records attributed to T Poynard.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Adolescent↗
PubMed2002

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns.

In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2-63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted.

Clone Cells↗
PubMed2002

Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B.

BACKGROUND: Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon. OBJECTIVES: The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B 'e' antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events. SEARCH STRATEGY: Electronic searches of the controlled trial registers of The Cochrane Hepato-Biliary Group and The Cochrane Library, MEDLINE, BIOSIS, and EMBASE were combined (May 2000). Reading the bibliography of retrieved articles identified further trials. Alfa interferon-manufacturing companies were approached in order to inquire about any published and unpublished randomised trials. SELECTION CRITERIA: The analyses included randomised trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. The trials could be open, single blinded, or double blinded. No patient exclusion criteria were applied. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected the trials and one extracted the data, which were validated. Assessments of the outcome measures were performed at the end of treatment and at six months and at maximal follow up after the end of treatment with alfa interferon. MAIN RESULTS: A total of 13 randomised trials including 790 patients were included. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data. REVIEWER'S CONCLUSIONS: Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

Antiviral Agents↗
PubMed2002

Interferon for acute hepatitis C.

BACKGROUND: Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C. OBJECTIVES: The aim of this review was to assess the efficacy of interferon in acute HCV infection. SEARCH STRATEGY: We searched MEDLINE, the Cochrane Controlled Trials Register, and the abstracts of the American Association for the Study of Liver Diseases (June 2001). We also contacted pharmaceutical companies to obtain unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo or no treatment, and published as an article, abstract, or letter were selected. No language limitations were used. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The following endpoints were analysed: normalization of alanine aminotransferase (ALT) activity at the end of treatment (biochemical ETR); sustained ALT normalization at the end follow-up (biochemical SR); disappearance of serum HCV RNA by polymerase chain reaction assay at the end of treatment (virologic ETR) and at the end of follow-up (virologic SR). Histologic data and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Six randomised trials involving 206 patients with acute hepatitis C met the inclusion criteria. Four trials assessing interferon alfa-2b in 141 patients, all with transfusion-acquired acute hepatitis C, were included. They demonstrated no significant heterogeneity in the outcomes assessed. When compared with no treatment, interferon alfa-2b was associated with an increase in the rates of virologic ETR and SR by 45% (95% CI 31-59%, P < 0.00001) and 29% (95% CI 14-44%, P = 0.0002), respectively. The virologic ETR was 42% (95% CI: 30-56%) in the interferon alfa-2b group versus 4% (95% CI 0-13%, P < 0.00001) in the control group. At the end of follow-up, a virologic SR was seen in 32% (95% CI 21-46%) of interferon-treated patients versus only 4% (95% CI 0-13%, P = 0.00007) of controls. The tolerability of therapy, or the impact of interferon alfa-2b on hepatic histology, was not reported. Two trials assessed interferon beta in a total 65 patients. The efficacy of interferon beta could not be assessed, however, due to heterogeneity of these trials. REVIEWER'S CONCLUSIONS: Interferon alfa is effective in improving biochemical outcomes and achieving sustained virologic clearance in patients with transfusion-acquired acute hepatitis C. The effect on long-term clinical outcomes could not be assessed due to limitations in the current data.

Acute Disease↗
PubMed2002

Interferon for interferon naive patients with chronic hepatitis C.

BACKGROUND: A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication additional trials have been reported. OBJECTIVES: To evaluate the response to interferon in interferon naive patients with chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with normal aminotransferases was also investigated. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library Issue 1, 1999), MEDLINE (January 1966 to December 1999), and reference lists were searched, and pharmaceutical companies were contacted for unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo, no treatment, or different regimens of interferon were selected. Abstracts were excluded. DATA COLLECTION AND ANALYSIS: The primary outcome measure was sustained disappearance of serum HCV RNA (virologic sustained response (SR)). Biochemical and end of treatment responses, liver histology, and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Fifty-four trials enrolling 6545 patients were included. Compared with no treatment, interferon 3 MU thrice weekly for 12 months increased the probability of a virologic SR (Peto odds ratio (OR) 4.60; 95% confidence interval (CI) 1.53 to 13.85). At this dosage and duration of therapy, the rate of virologic SR was 17% (95% CI 10 to 28%) in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months (OR 1.87; 95% CI 1.30 to 2.67). Adverse events were more common with higher doses and prolonged durations of treatment. Compared with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients. However, interferon was no more effective than control in patients with normal aminotransferases. REVIEWER'S CONCLUSIONS: Interferon is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events. Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases is unproven.

Antiviral Agents↗
PubMed2002

Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C.

BACKGROUND: Interferon monotherapy leads to sustained virologic clearance in a minority of patients with chronic hepatitis C. Studies have yielded conflicting results regarding retreatment with interferon in nonresponders and relapsers. OBJECTIVES: To assess the beneficial and harmful effects of retreatment with interferon in chronic hepatitis C nonresponders and relapsers to previous interferon treatment. SEARCH STRATEGY: Trials were identified through electronic databases, manual searches, authors, and pharmaceutical companies (August 2001). SELECTION CRITERIA: Randomised trials comparing interferon versus control or different interferon regimens in chronic hepatitis C patients being nonresponders and relapsers to previous interferon were included. DATA COLLECTION AND ANALYSIS: The primary outcome was failure to achieve a sustained virologic response defined as positive serum hepatitis C virus RNA at least six months following treatment. Secondary outcomes included liver-related morbidity, mortality, biochemical responses, adverse events, and histology. MAIN RESULTS: Ten randomised trials involving 686 nonresponders and eight trials involving 484 relapsers were included; their methodological quality was poor. In nonresponders, interferon reduced the risk of not achieving an end of treatment biochemical response compared with no treatment (relative risk [RR] 0.77, 95% confidence interval [CI] 0.66 to 0.91); however, virologic responses were not reported. In a post hoc subgroup analysis, doses greater than 3 million units (MU) three times weekly offered no advantage compared with 3 MU three times weekly for biochemical sustained response. Failure to obtain a virologic sustained response was less likely with 48 than 24 weeks of therapy (RR 0.87, 95% CI 0.79 to 0.96). Adverse events did not differ significantly regardless of treatment dose or duration. In relapsers, none of the trials compared interferon with no treatment. In a post hoc analysis, doses greater than 3 MU three times weekly were no more effective in achieving a virologic sustained response than 3 MU three times weekly. Compared with 24 weeks, treatment durations of 48 weeks were less likely to fail to achieve a virologic sustained response (RR 0.69, 95% CI Random 0.51 to 0.95), but associated with more frequent dosage reduction (RR 9.07, 95% CI 1.20 to 68.63). No data regarding clinical outcomes or histology was available in either patient group. REVIEWER'S CONCLUSIONS: Retreatment with interferon leads to sustained virologic clearance in a minority of chronic hepatitis C patients with nonresponse or relapse following interferon monotherapy. Treatment durations of 48 weeks are superior to 24 weeks, but doses greater than 3 MU three times weekly are no more effective. No data exists regarding the effect on clinical outcomes.

Antiviral Agents↗
PubMed2002

[Do the interferons have an antifibrotic action? The hepatologist's point of view].

INTRODUCTION: Major progress in the treatment of hepatitis C has been achieved in the last ten years with an obvious histologic impact. The last approved regimen combines ribavirin (10.6 mg per kg) with pegylated interferon (1.5 microgram per kg) which permits to obtain improvement of necrosis and inflammation in 73% of patients with only 8% of fibrosis worsening. CURRENT KNOWLEDGE AND KEYS POINTS: Reversibility of post hepatitis C cirrhosis is now well documented. However, this reversibility has been observed mainly in young cirrhotic patients, particularly in those with sustained virologic response. For older patients with decompensated cirrhosis the reversibility has not been established. Interferon alpha directly or indirectly is indeed an effective anti-fibrotic agent in chronic hepatitis C. The indirect anti-fibrotic effect through the antiviral effect has been considerably improved by the pegylation and the association with ribavirin.

Antiviral Agents↗
PubMed2002

Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis.

BACKGROUND: Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results. AIM: To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis. METHODS: An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end-point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods. RESULTS: Six double-blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0-9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17-41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4-9.7; P < 0.001). The sensitivity analysis showed similar results. CONCLUSIONS: This meta-analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.

Coma↗
PubMed2002

Quantification of fibrosis progression in patients with chronic hepatitis C using a Markov model.

The knowledge of fibrosis progression in chronic hepatitis C and the impact of new treatments on progression is limited by the number of available liver biopsies per patient. Moreover, liver biopsies identify a patient's stage of fibrosis at a given point in time, but cannot quantify the time spent in that stage nor the date of transition to that stage. This paper assesses the potential of Markov modelling to overcome these difficulties. The data from interferon-treated (n=185) and untreated patients (n=102) are analysed to illustrate the power of this technique. The model accurately reproduced the distributions of patients in the different fibrosis stages at two subsequent biopsies. A quantification of the role of cofactors in the progression of the disease, and the impact of interferon treatment are given. In subjects who are 40 years old and have been infected for 10 years, the model predicted that 274 of 1000 untreated patients, but only 42 of 1000 treated patients, would progress from F0 or F1 to F3 or F4 fibrosis over the next 5 years. The model also confirms that as age and duration of infection increase, the risk of fibrosis progression increases, while the impact of treatment with interferon decreases. Hence Markov modelling is an accurate tool in the analysis of fibrosis progression in chronic hepatitis C. It will be valuable for the quantification of the effect of new treatments on fibrosis progression in hepatitis C.

Adolescent↗
PubMed2002

Biochemical markers of liver fibrosis in patients infected by hepatitis C virus: longitudinal validation in a randomized trial.

A liver fibrosis index was recently prospectively validated in a cross-sectional study where patients infected by hepatitis C virus (HCV) had only one biopsy and no longitudinal follow-up. The aim of this study was to retrospectively assess the diagnostic value of this index in patients included in a randomized trial of interferon (IFN) using repeated measurements, two biopsies and hyaluronic acid as a comparative reference. One-hundred and sixty-five patients who had had two interpretable liver biopsies and at least one stored serum sample before IFN treatment were selected. Seventy-eight patients received 3 MU of IFN-alpha thrice weekly for 24 weeks and 87 followed a reinforced regimen for 48 weeks. A fibrosis index combining five biochemical markers (alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase (GGT) and total bilirubin adjusted for gender and age) as well as hyaluronic acid was assessed on 461 samples available at baseline, at the end of treatment and at the end of follow-up (72 weeks). There was a significant decrease of the fibrosis index score among the 17 sustained virologic responders, from 0.33 +/- 0.06 (mean +/- SE) at baseline to 0.18 +/- 0.06 at 72 weeks in comparison with 92 nonresponders (from 0.41 +/- 0.03 at baseline to 0.44 +/- 0.03 at 72 weeks; P < 0.001) and in comparison with 56 relapsers (from 0.36 +/- 0.03 at baseline to 0.32 +/- 0.03 at 72 weeks; P=0.05). No significant differences were observed for hyaluronic acid.Hence, this fibrosis index could be used as a surrogate marker of the antifibrotic effect of treatments in patients with chronic hepatitis C.

Adult↗
PubMed2002

Fatigue in patients with chronic hepatitis C.

In numerous studies of symptoms in patients with chronic hepatitis C there has been no systematic assessment of both fatigue and extrahepatic manifestations. Our objective was to assess the prevalence of fatigue in patients with hepatitis C virus (HCV) infection, and to identify associations between fatigue and clinical and biological hepatic and extrahepatic manifestations. We studied 1614 patients. Data were prospectively recorded during the first visit of patients infected with HCV and the prevalence of fatigue and its association with dermatological, rheumatological, neurological and nephrological manifestations; diabetes; arterial hypertension; auto-antibodies, and cryoglobulinaemia were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunological, virological, and histological factors associated with the presence of fatigue. Fatigue was present in 53% of patients (95% confidence interval 51-56). In 17% of patients (95% confidence interval 15-19) fatigue was severe, impairing activity. Five other extrahepatic manifestations had a prevalence above 10% including, in decreasing order: arthralgia, paresthesia, myalgia, pruritus, and sicca syndrome. In univariate and multivariate analyses, fatigue, in comparison with the absence of fatigue, was associated with female gender, age over 50 years, cirrhosis, depression and purpura. Independent of these associations, fatigue was associated with arthralgia, myalgia, paresthesia, sicca syndrome and pruritus. The prevalence of fibromyalgia (as defined by the association of fatigue with arthralgia or myalgia) was 19% (95% confidence interval 17-21). There was no significant association between fatigue and the following characteristics: viral load or genotype, alcohol consumption, abnormal thyroid function, and type and level of cryoglobulinaemia. Hence, fatigue is the most frequent extrahepatic manifestation in patients infected with HCV. Fatigue is independently associated with female gender, age over 50 years, cirrhosis, depression and purpura.

Adolescent↗
PubMed2002

A constellation of cardiovascular risk factors is associated with hepatic enzyme elevation in hyperlipidemic patients.

Abnormal circulating levels of hepatic enzymes are frequently found in subjects displaying hyperlipidemia or obesity or both. At present, there is a paucity of information on the principal cardiovascular risk factors that are associated with elevated plasma levels of hepatic enzyme activity in hyperlipidemic patients. We analyzed the potential relationships between serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) and cardiovascular and metabolic risk factors in a cohort of 8,501 men and women referred to our outpatient clinic for hyperlipidemia by their general practitioner. In this cohort, 27.6% of patients displayed serum levels of ALT above the upper limit of normal values. Both men and women who exhibited ALT levels superior to the upper limit of the normal range had elevated systolic (SBP) and diastolic blood pressure (DBP), body mass index (BMI), alcohol intake, and serum levels of blood glucose, uric acid, total cholesterol, and triglycerides (P <.0035 for all parameters). In a multivariate analysis, BMI, uric acid, and blood glucose remained significantly associated with ALT levels in men and women. We conclude that cardiovascular and metabolic features characterizing the plurimetabolic syndrome, including serum uric acid levels, are associated with significant elevation of hepatic enzyme activities. Because these abnormalities may not only be reversible but also associated with a poor prognosis, further studies are needed to identify those dyslipidemic patients who are at risk for the development of severe hepatic tissue damage.

Adult↗
PubMed2002

Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study.

BACKGROUND: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.

Albumins↗
PubMed2001

Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.

BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.

Adenine↗