Hepatitis: Chamuleau RA

Chamuleau RA. · Afdeling Hepatologie van het Academisch Medisch Centrum, Universiteit van Amsterdam. · Ned Tijdschr Tandheelkd. · Pubmed #17822245 No free full text.

Abstract: Chronic hepatitis B and C are life-threatening diseases, treated with variable success. Peginterferon-alpha is one of the standard therapies for chronic hepatitis B as well as C. To prevent the development of resistant viruses, combination treatment is preferable to monotherapy. Therefore, in chronic hepatitis B virus peginterferon-alpha combined with nucleoside inhibitors is used. The treatment of chronic hepatitis C virus with a combination of peginterferon-alpha and ribavirine can be improved by new protease inhibitors.

van de Kerkhove MP, Di Florio E, Scuderi V, Mancini A, Belli A, Bracco A, Scala D, Scala S, Zeuli L, Di Nicuolo G, Amoroso P, Calise F, Chamuleau RA. · Surgical Laboratory (IWO-I), Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands. · Cell Transplant. · Pubmed #14579924 No free full text.

Abstract: Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 x 10(9) viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.

Damen M, Weegink CJ, Mauser-Bunschoten EP, Cuypers HT, Hermus MC, Sillekens P, Haan E, van den Berg HM, Bresters D, Lelie PN, Chamuleau RA, Reesink HW. · Academic Medical Center, Dept of Liver Disease, Amsterdam The Netherlands. · Scand J Gastroenterol. · Pubmed #11218246 No free full text.

Abstract: BACKGROUND: In patients with chronic hepatitis C (HCV) Interferon-alpha (IFN) treatment for 12-18 months is more effective than 6 months in inducing a sustained virological response. METHODS: In a multicenter, randomized, controlled trial, 88 patients with chronic HCV were enrolled (47 treated with IFN-alpha2b and 41 constituted an untreated control group). Treatment consisted of 5 million units (MU) IFN thrice a week (tiw) for 8 weeks and subsequently 2.5 MU IFN tiw for 16 weeks ('standard treatment'). After week 24 ('long-term treatment'), in virological non-responders treatment was continued using 5 MU IFN tiw for up to week 156, whereas in virological responders IFN was discontinued. In case of a virological relapse, treatment with 5 MU IFN tiw was restarted and continued up to week 156. RESULTS: Sustained virological response rate was 6/47 (13%) after standard treatment and increased to 19/47 (40%) after long-term treatment (McNemar paired test; P = 0.002). Of the 18 patients with a breakthrough or relapse during or after standard treatment, 14 (78%) became sustained virological responders upon long-term treatment. Of the 4 patients who did not have a sustained virological response after long-term treatment, 3 did not receive complete treatment due to side effects and/or non-compliance. In patients who failed to respond to standard treatment, no virological response was observed during long-term treatment. In the control group, no spontaneous clearance of HCV was observed. CONCLUSIONS: Long-term IFN (re)treatment enhanced the virological sustained response rate significantly and was particularly effective in patients with a breakthrough or relapse following standard treatment.

Weegink CJ, Sentjens RE, Van Der Heyden JF, Chamuleau RA, Tytgat GN, Beld MG. · Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #14624162 No free full text.

Abstract: Needlestick accidents continue to be a hazard for healthcare workers. We report the development of acute hepatitis C infection in a physician after needlestick injury. Hepatitis C virus (HCV)-RNA, seroconversion and a raised plasma alanine aminotransferase (ALAT) level were found in plasma three months after the accident. Treatment with interferon alfa and ribavirin was started. While the physician was on treatment, HCV-RNA test results from plasma taken the day treatment was started became available. HCV-RNA was undetectable by quantitative bDNA assay, undetectable by qualitative polymerase chain reaction (PCR) and undetectable by transcription mediated amplification (TMA). A dilemma arose at this point: should the patient stop the treatment or continue the planned therapy? The physician decided to continue a 24-week course of treatment. Six months after the end of treatment, the physician was still HCV-RNA-negative and with a normal plasma ALAT level. The rationale of the decision to continue therapy is discussed. This information may be useful for clinicians confronted with a similar dilemma.

ter Borg F, ten Kate FJ, Cuypers HT, Leentvaar-Kuijpers A, Oosting J, Wertheim-van Dillen PM, Honkoop P, Rasch MC, de Man RA, van Hattum J, Chamuleau RA, Tytgat GN, Jones EA. · Department of Gastrointestinal and Liver Diseases, University of Amsterdam, The Netherlands. · J Clin Pathol. · Pubmed #10961179 links to  free full text

Abstract: AIMS: To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. METHODS: The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. RESULTS: Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. CONCLUSIONS: The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Weegink CJ, Chamuleau RA, Reesink HW, Molenaar DS. · No affiliation provided · J Gastroenterol. · Pubmed #11686485 No free full text.

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