Hepatitis: Bergmann JF

Bergmann JF, De Knegt RJ, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Minerva Med. · Pubmed #19034255 No free full text.

Abstract: Current guidelines for chronic Hepatitis C recommend peginterferon-alpha and ribavirin combination therapy for 24 or 48 weeks, based on viral factors (genotype, viral load), host factors (stage of liver disease) and virological response during treatment. The main goal of treatment is eradication of Hepatitis C virus (HCV) infection which is defined by HCV RNA negativity 24 weeks after end of treatment (i.e. sustained virological response, SVR). SVR can be achieved in up to 80% of patients. Most patients, however, experience adverse events during therapy which significantly affect drug compliance and treatment outcome. Several strategies have been evaluated in order to optimize outcome of current peginterferon-based therapy, including higher dosing of peginterferon and/or ribavirin, and adjusting therapy duration. Although some patients might benefit from these optimized treatment schedules, viral eradication remains unachievable in a substantial part of patients. In this perspective, there is a clear need for effective alternative or additional agents, especially as the burden of disease is expected to increase over the next decade. Potential novel antiviral targets are now being identified due to improved understanding of the HCV life cycle. Specifically targeted antiviral therapy for Hepatitis C (STAT-C) is in clinical development and has already shown to increase SVR rate. At this moment, however, SVR can only be achieved when combining new molecules with peginterferon therapy. The role of ribavirin has been questioned, but available evidence suggests that ribavirin has significant impact on treatment outcome and should therefore remain part of antiviral therapy. More than a decade of interferon-based therapy and potential new agents will be reviewed.

Bergmann JF. · No affiliation provided · Presse Med. · Pubmed #9989300 No free full text.

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Bergmann JF, Vrolijk JM, van der Schaar P, Vroom B, van Hoek B, van der Sluys Veer A, de Vries RA, Verhey E, Hansen BE, Brouwer JT, Janssen HL, Schalm SW, de Knegt RJ. · Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Liver Int. · Pubmed #17919233 No free full text.

Abstract: BACKGROUND: High-dose peginterferon-alpha (PegIFN-alpha) induction and prolongation of therapy may be an option to improve sustained virological response (SVR) rates among hepatitis C virus (HCV) non-responders, although a higher and a longer dosing of PegIFN-alpha may intensify side effects. METHODS: We randomized 53 patients, who previously failed with standard IFN-alpha+/-ribavirin, to a high-dose induction and an extended regimen with PegIFN-alpha-2b [3.0 microg/kg once weekly (q.w.) 12 weeks-->2.0 microg/kg q.w. 12 weeks-->1.5 microg/kg q.w. 48 weeks] or a standard regimen (1.5 microg/kg q.w. 48 weeks). All patients received daily weight-based ribavirin (800-1200 mg/day). The short-form 36 health survey was used to evaluate health-related quality of life (HRQL). RESULTS: Intention-to-treat analysis showed no significant difference in SVR rate (44% vs. 37%, P=0.62) and relapse rate (9% vs. 31%, P=0.17) between experimental and standard treatment. Overall, 80% of the [positive predictive value (PPV)] patients with rapid virological response (RVR, HCV-RNA negativity at week 4) achieved SVR. No significant dose-related differences in HRQL were seen between both groups. At baseline, genotype 2 or 3 [odds ratio (OR): 7.4, 95% confidence interval (CI): 1.4-33.3, P=0.01] and gamma-glutamyltransferase (GGT) levels <2 x ULN (upper limit of normal) (OR: 6.76, 95% CI: 1.5-31.3, P=0.009) were significantly associated with SVR. Multivariate logistic regression at week 4 showed that only baseline GGT <2 x ULN (OR: 7.3, 95% CI: 1.4-38.5, P=0.01) and RVR (OR: 15.6, 95% CI: 3.2-76.9, P<0.001) were independently predictive for SVR. CONCLUSION: Retreatment with PegIFN-alpha-2b and ribavirin for a minimum of 48 weeks should be considered in all patients unresponsive to previous IFN-based therapies. Baseline GGT values and RVR are highly predictive for retreatment outcome.

Piroth L, Sène D, Pol S, Goderel I, Lacombe K, Martha B, Rey D, Loustau-Ratti V, Bergmann JF, Pialoux G, Gervais A, Lascoux-Combe C, Carrat F, Cacoub P. · Service de Maladies Infectieuses et Tropicales, CHU Dijon, 10 boulevard du Maréchal de Lattre de Tassigny, 21079 Dijon cedex, France. · AIDS. · Pubmed #17545709 No free full text.

Abstract: OBJECTIVE: To describe the characteristics of hepatitis B (HBV) infection in HIV-infected patients and the impact of anti-HBV treatments. PATIENTS AND METHODS: All the patients with past or present chronic HBV infection seen in October 2005 in 17 French hospitals were included. Data were retrospectively collected from their first visit in a time-dependent manner, through a detailed standardized questionnaire. RESULTS: Among 477 HBV-infected patients, 261 (55%) were co-infected with HIV. The HBV-HIV co-infected patients underwent fewer serological, virological and histological evaluations. Initial positive HBe antigenemia (HBe Ag) was more frequent in these patients (57.9 versus 28.6%; P < 10), as was cirrhosis on the initial liver biopsy (17.9 versus 7.6%; P = 0.05). Throughout the mean 5-year follow-up, HBe Ag loss was less frequent (P = 0.04), as was HBe seroconversion (incidence rate 2.6 versus 10/100 patient-years; P < 10). HBe Ag loss was associated with fibrosis improvement (METAVIR score -0.5 +/- 0.4 versus +0.2 +/- 0.6 if persistent positive HBe Ag, P = 0.01). In co-infected patients on tenofovir, adefovir or interferon, HBe seroconversions were seen in patients on combined HBV treatment, the use of which is increasing (58% in 2005). Nevertheless, no significant difference in virological, immunological or biochemical evolution was observed between these different treatments. CONCLUSIONS: In HBV-HIV co-infected patients, the assessment of HBV infection still needs to be improved, the HBV wild-type remains predominant, and HBe Ag loss is rare and associated with a better histological evolution. There is insufficient evidence of the superiority of combined HBV treatment, and this still needs be demonstrated in long term studies.

Bergmann JF. · Lariboisière Hospital, Paris, France. · ACP J Club. · Pubmed #16388555 No free full text.

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Bergmann JF. · Lariboisière Hospital, Paris, France. · ACP J Club. · Pubmed #16388554 No free full text.

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Sellier P, Clevenbergh P, Mazeron MC, Cazals-Hatem D, Evans J, Cervoni J, Badsi E, Bendenoun M, Diemer M, Vincent V, Caulin C, Bergmann JF. · Service de Médecine Interne A, Hôpital Lariboisière, Paris, France. · Scand J Infect Dis. · Pubmed #15307596 No free full text.

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Bergmann JF. · Service de Médecine Interne A, Clinique Thérapeutique, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris Cedex 10. · Gastroenterol Clin Biol. · Pubmed #15041827 No free full text.

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Bergmann JF, Slavenburg S, Roomer R, de Knegt RJ, Drenth JP. · No affiliation provided · Neth J Med. · Pubmed #18219071 links to  free full text

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