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T Poynard

Publications and source records attributed to T Poynard.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effects of interferon therapy in "non responder" patients with chronic hepatitis C.

We reviewed the impact of interferon treatment on viral load, transaminase serum activity and histological features in patients with chronic hepatitis C in whom treatment did not result in a sustained virus eradication. As patients with cirrhosis are often called non responders, we also reviewed the impact of interferon on these end points as well as on hepatocellular carcinoma incidence and survival. This overview provides evidence that interferon in patients who have not cleared hepatitis C virus (HCV) significantly reduces viral load, serum ALT activity, improves histological activity and blocks progression of fibrosis compared to the natural history of the disease. Thus, patients who still have a positive HCV PCR should no longer be called non responders to interferon. Although the number of randomized trials is limited, there is also cumulative data suggesting that interferon could reduce the incidence of hepatocellular carcinoma incidence and mortality.

Alanine Transaminase↗
PubMed1999

Effect of interferon therapy on the natural history of hepatitis C virus-related cirrhosis and hepatocellular carcinoma.

In patients with chronic hepatitis C who have a sustained virologic response to IFN therapy, there is a dramatic effect on the natural history of the disease, with ALT levels becoming normal, histologic activity improving or disappearing, and the progression of fibrosis slowing. A sustained virologic response 6 months after the end of treatment is predictive of a sustained remission 4 years later. From these results, a long-term survival benefit is expected from IFN treatment in patients with an intermediate or rapid rate of fibrosis. For patients with chronic hepatitis C who do not experience a sustained eradication of virus, there is evidence that IFN treatment significantly reduces the viral load and serum ALT level, improves histologic activity, and blocks fibrosis progression, in comparison with the natural history of this disease. Therefore, patients who still have a detectable level of HCV RNA should no longer be considered nonresponders to IFN therapy. Although the number of randomized trials is [figure: see text] small, cumulative data suggest that IFN therapy can reduce the incidence of and the mortality from hepatocellular carcinoma in patients with cirrhosis.

Alanine Transaminase↗
PubMed1999

A short induction regimen of interferon-alpha is not effective for treatment of relapse in chronic hepatitis C: a randomized trial. For the multicentre GER-CYT-01 group.

The aim of this work was to assess the effect of a high-dose (10 million units, MU) short-duration (14 weeks) interferon-alpha2b (IFN-alpha2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty-eight non-cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high-dose, short-duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high-dose, short-duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively (P = NS). At the end of the 72-week follow-up, in the high-dose, short-duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group (P = NS). There was less fibrosis improvement in the high-dose, short-duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) (P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high-dose, short-duration treatment with IFN-alpha has no advantage when compared to a 6-month treatment with 3 MU IFN t.i.w.

Adult↗
PubMed1999

Correlation between hepatitis C virus prevalence and hepatocellular carcinoma mortality in Europe.

In Europe, as worldwide, hepatocellular carcinoma (HCC) death rates are highly variable. Recent studies have reported that hepatitis C virus (HCV) infection may be responsible for the increased mortality from HCC in the UK and in France. We investigate here the potential relationship between HCC mortality and HCV prevalence in Europe. Population and mortality data of HCC were obtained for 22 European countries from the World Health Organization (WHO) databank. Age-standardized death rates were computed. The HCV prevalence among blood donors and the WHO estimate of HCV prevalence were used as two indicators of prevalence in the general population, when data were available. Spearman rank analysis was conducted between HCC mortality and HCV prevalence. For men, age-standardized death rates per 100 000 varied from 0.61 (Greece) to 12.19 (Hungary). HCC mortality among men was positively correlated with HCV prevalence among blood donors and with the WHO estimate: rank correlation coefficients were, respectively, 0.76 (P = 0.02) and 0.72 (P = 0.03). This study showed that the reported differences of HCC mortality in Europe correlate with HCV prevalence.

Carcinoma, Hepatocellular↗
PubMed1999

Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. French-Speaking Club for the Study of Portal Hypertension.

OBJECTIVE: Beta-blockers have been shown to reduce portal pressure in patients with cirrhosis and limit the development of portosystemic shunts in portal hypertensive animals. Thus, a randomized double-blind trial was conducted to evaluate propranolol in the prevention of the development of large oesophageal varices in patients with cirrhosis without varices or with small varices. METHODS: One hundred and two patients received long-acting propranolol (160 mg/day) and 104 patients received a placebo. At inclusion, there was no significant difference between the two groups in terms of clinical characteristics or biochemical tests. At 2 years, the size of varices was estimated on video recordings. RESULTS: One-third of the patients were lost to follow-up, and 95%/97% of the remaining patients were compliant in the propranolol and placebo groups, respectively. At 2 years, the proportion of patients with large varices was 31% in the propranolol group and 14% in the placebo group (P< 0.05). Three and four patients bled in the propranolol and placebo groups, respectively, and nine and ten died, respectively. CONCLUSION: This trial suggests that propranolol administration cannot be recommended for the prevention of the development of large oesophageal varices in patients with cirrhosis; thus other studies are needed in selected subgroups of patients.

Adrenergic beta-Antagonists↗
PubMed1999

Hepatitis B virus (HBV) mutations associated with resistance to lamivudine in patients coinfected with HBV and human immunodeficiency virus.

Mutations associated with hepatitis B virus (HBV) resistance to lamivudine have not been extensively addressed in human immunodeficiency virus (HIV)-HBV coinfection. We have studied the HBV polymerase sequences from nine coinfected patients who experienced HBV recurrence while under lamivudine treatment. In seven of these nine patients, Met(550), belonging to the highly conserved YMDD motif, was mutated to Val and was associated with a substitution of Met for Leu(526) in each case. In the two remaining patients, we found a Met(550)-to-Ile change that was associated in only one case with a Leu(526)-to-Met mutation. No mutation was observed in three control patients not receiving lamivudine. This study demonstrates the emergence of particular genetic profiles in HBV-HIV-coinfected patients experiencing a loss of control of HBV infection despite high doses of lamivudine.

Anti-HIV Agents↗
PubMed1999

Response to interferon alpha treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus.

BACKGROUND: Mixed cryoglobulinaemia is closely associated with hepatitis C virus (HCV) infection. AIM: To assess in a prospective open study the efficiency of interferon alpha treatment of cryoglobulinaemia, as reflected by the disappearance of cryoglobulins and clinical manifestations of the disease, and to analyse the factors predictive of a response to interferon. METHOD: Eighty seven consecutive patients with chronic hepatitis C treated for the first time with interferon at a dose of 3 x 10(6) international units three times a week for six months were studied. Forty three patients had cryoglobulins, which were responsible for clinical manifestations in 12. RESULTS: At the end of interferon treatment, cryoglobulins had disappeared in 39% of the patients. A clinical improvement (except for neuropathies) was observed in all patients. Six months after interferon treatment was stopped, the same rate of response (normal alanine aminotransferase values and undectable HCV RNA) was observed in patients with or without cryoglobulins. Only 14% of patients still had undetectable cryoglobulins, and all of them also had undetectable serum HCV RNA. The disappearance of cryoglobulins was found less frequently in patients with clinical symptoms than in asymptomatic ones, but the difference was not significant. Sustained responders were more often men, infected by genotype 2 or 3, with a lower pretreatment viral load. CONCLUSION: The presence of cryoglobulins does not seem to affect the response to interferon in HCV infected patients. The improvement in cryoglobulinaemia is strongly associated with a virological response, reinforcing the hypothesis of a direct role for HCV in the pathogenesis of this disease.

Adult↗
PubMed1999

Low hepatic iron concentration: evaluation of two complementary methods, colorimetric assay and iron histological scoring.

AIMS: To validate a method of assessment of low hepatic iron concentration based on a biochemical colorimetric assay plus histological scoring. METHODS: The within-day and day to day precision of the iron colorimetric assay was determined on frozen rat liver. The coefficient of variation (CV) of iron measurement in two separate samples from the same liver was determined for 21 deparaffinised human biopsies. The intra- and interlaboratory variability of the colorimetric assay and histological scoring were assessed on 38 deparaffinised liver biopsies. RESULTS: For the within-day test, the CV was 11% (5.1 (0.6) mumol/g dry weight (dw), mean (SD) iron concentration). For the day to day test, the CV was 19.5% (8.2 (1.6) mumol/g dw). The CV was 14.7% for iron concentration determined in two separate samples from the same liver. By correlation and kappa concordance tests, the intra- and interlaboratory variability of the hepatic iron colorimetric assay and iron histological scoring was slight. Absence of stainable iron corresponded to a liver iron concentration < or = 20 mumol/g dw. CONCLUSIONS: A combination of two complementary methods, colorimetric measurement and histological scoring, is an accurate and reliable way of determining low iron concentrations in deparaffinised human liver biopsies. In secondary haemosiderosis, such methods would be essential for investigating the role of low iron overload in fibrogenesis and during the response to antiviral treatment in chronic viral hepatitis.

Animals↗
PubMed1999

[Assessment of quality of life of patients with gastroesophageal reflux. Elaboration and validation of a specific questionnaire].

UNLABELLED: Quality of life is frequently impaired in patients with gastro-esophageal reflux. The aim of this study was the validation of a new specific quality of life questionnaire in patients with gastro-esophageal reflux. METHODS: A questionnaire was generated as follows: a) item generation with patients, b) item reduction, c) psychometric validation and comparison to a reference questionnaire (SF36) in patients with symptomatic gastro-esophageal reflux, d) assessment of reproducibility, and e) responsiveness over time. RESULTS: The primary questionnaire was made of 104 items. Two hundred twenty three patients were enrolled, 38 items were selected in 7 dimensions. One item was deleted following a new analysis conducted in 349 patients. Cronbach coefficient ranged from 0.84 to 0.91 for the specific questionnaire and from 0.78 to 0.90 for the SF36 questionnaire. Dimensions of specific questionnaire and SF36 were correlated. Quality of life was more impaired in patients with more frequent symptoms. Severity of endoscopic lesions was partly correlated with impaired quality-of-life. Reproducibility and responsiveness over time were correct. The final valid questionnaire was made of 37 items in 7 dimensions. CONCLUSION: This work is the first validation of a specific questionnaire in French which has the ability to measure quality of life in patients with gastro-esophageal reflux. The use of this questionnaire during therapeutic trials might allow to be more accurate in assessment of treatment efficacy.

Adult↗
PubMed1999

Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C.

The limited efficacy of alpha interferon (IFN) monotherapy for hepatitis C virus (HCV) infection has led to the investigation of alternative treatment approaches, including combining interferons with other antiviral agents. In several small, pilot studies, the combination of IFN plus ribavirin was significantly more effective than IFN monotherapy for the initial treatment of HCV. The encouraging results from these studies provided the rationale for conducting two (one US, one International) large, multicenter, randomized, placebo-controlled clinical trials of IFN plus ribavirin therapy for the initial treatment of HCV patients. Of patients receiving therapy [corrected] for 24 weeks, 31% (US) and 35% (International) achieved sustained virologic remission with interferon plus ribavirin [corrected], compared with only 6% (US) receiving interferon [corrected] plus placebo. Sustained virologic response rates were improved in patients treated for 48 weeks (interferon plus ribavirin, 38% [US]; 43% [International] compared to interferon plus placebo, 13% [US]; 19% [International]) [corrected]. Improvement was also observed in terms of biochemical and histologic end points in those receiving combination therapy. Pretreatment variables (HCV genotype, viral burden, stage of fibrosis) were less important as predictors of treatment outcome in patients receiving combination therapy. The safety profile of combination therapy reflected the individual safety profiles of IFN and ribavirin, without synergism. Combination therapy with IFN plus ribavirin was more effective than IFN monotherapy for the initial treatment of HCV in terms of virologic, biochemical, and histologic end points. The combination appears to be well tolerated with a predictable safety profile.

Adult↗
PubMed1999

[Descriptive epidemiology of patients with alcoholic liver disease hospitalized in a hepato-gastroenterology service].

OBJECTIVE: To improve the detection of early stage alcoholic liver disease and to identify the importance of this disease, this study compared epidemiological characteristics, the reasons for and the duration of hospitalization, in-patient mortality and the frequency of multiple hospitalizations in alcoholic patients without cirrhosis and in patients with alcoholic cirrhosis hospitalized in the hepatogastroenterology department of Antoine-Beclere Hospital. MATERIAL AND METHODS: From January 1982 to December 1995, all patients with a daily alcohol intake in the previous year of at least 50 g per day and all patients with alcoholic cirrhosis whatever their drinking habits were studied. RESULTS: Three thousand three hundred and forty six patients were included. The daily alcohol intake in the previous five years was 118 +/- 81 g and the duration of alcohol abuse was 22 +/- 13 years. Two thousand one hundred eight patients had liver biopsy; 37% had histologically proven or probable cirrhosis. Forty one percent of the patients without cirrhosis who had liver biopsy already had steatofibrosis and/or acute alcoholic hepatitis. 32.5% of the patients had hepatitis B virus markers. 7.7% of the patients were positive for anti hepatitis C virus antibody. Thirty two percent of the patients with cirrhosis were women versus 22% of the patients without cirrhosis (P < 0.01). Alcoholism was the reason for the first hospitalization in sixty percent of the patients without cirrhosis and in twenty percent of the patients with cirrhosis (P < 0.01). On the other hand, ascites were the first reason for the first hospitalization in patients with cirrhosis (28%). The two main causes for multiple hospitalizations were also ascites and alcoholism. CONCLUSION: Two thirds of heavy drinkers did not have cirrhosis on admission since alcoholism was the first reason for multiple hospitalizations in these patients, therefore the management of alcoholism in out-patients must be improved.

Alcoholism↗
PubMed1999

[Hepatitis C: natural history, biology, treatment monitoring].

This article presents the laboratory tests used to diagnose hepatitis C, to evaluate the severity of the chronic fibrosing disease, and to monitor the efficacy of treatment. Histological examination of liver biopsies is of the utmost importance for evaluating the development of fibrosis. Factors that precipitate fibrosis are reviewed. The annual rate of fibrosis progression can be assessed based on the estimated duration of hepatitis C virus contamination and on the fibrosis score established using the METAVIR classification. This allows to distinguish slow, fast, and intermediate fibrosis and to estimate the mean time to cirrhosis development. Combined use of interferon alpha (3 million units three times a week) and of Ribavirine (1000-1200 mg per day orally according to body weight) for 6 to 12 months is currently the standard treatment for hepatitis C. Treatment efficacy varies with a number of virus-related factors (genotype, viral burden) and patient-related factor (hepatic fibrosis, age, sex). In nonresponders, the value of treatment should not be assessed in terms of efficacy but in terms of slowing of fibrosis progression.

Antiviral Agents↗
PubMed1998

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.

Administration, Oral↗