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Alimentary Pharmacology & Therapeutics 05/2013; 37(9):920. · 3.77 Impact Factor
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ABSTRACT: BACKGROUND: Ten percent of patients with autoimmune hepatitis (AIH) are nonresponsive or intolerant to thiopurine therapy. A skewed metabolism, leading to the preferential generation of (hepato)toxic thiopurine metabolites (6-MMPs) instead of the metabolic active 6-tioguanine (thioguanine) nucleotides (6-TGNs), may explain this unfavourable outcome. Co-administration of allopurinol to low-dose thiopurine therapy may effectively revert this deviant metabolism, as has been shown in inflammatory bowel disease. AIM: To describe the effect of adding allopurinol to low-dose thiopurine therapy in patients with AIH with intolerance or nonresponse to normal thiopurine dosages due to a skewed metabolism. METHODS: We describe the clinical efficacy and tolerability of allopurinol-thiopurine combination therapy with allopurinol 100 mg and low-dose thiopurine (25-33% of the original dosage) in eight AIH patients with a skewed thiopurine metabolism. Patients were switched because of dose-limiting intolerance (n = 3), nonresponse (n = 3) or loss of response (n = 2) to conventional thiopurine treatment. RESULTS: All eight patients showed biochemical improvement with a reduction in median alanine aminotransferase (ALT) levels of 62 U/L at start to 35 U/L at 1 month (P = 0.03). This clinical benefit was sustained in seven patients. Allopurinol-thiopurine combination therapy effectively bypassed thiopurine side effects in four of five patients. Median 6-tioguanine nucleotides levels increased from 100 to 200 pmol/8 × 10(8) red blood cells (RBC) at 3 months (P = 0.04). Median 6-MMP levels decreased in all patients from 6090 to 175 pmol/8 × 10(8) RBC (P = 0.01). CONCLUSION: Allopurinol safely and effectively optimises thiopurine therapy in patients with autoimmune hepatitis with intolerance and/or nonresponse due to an unfavourable thiopurine metabolism.
Alimentary Pharmacology & Therapeutics 01/2013; · 3.77 Impact Factor
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ABSTRACT: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown aetiology usually requiring long-term immunosuppressive therapy. We present the case of an AIH patient who received long-term corticosteroids and azathioprine. As treatment for concomitant osteoporosis she was also treated with potent intravenous bisphosphonate (BP). This treatment was complicated by the development of BP-related osteonecrosis of the jaw (BRONJ). BRONJ is an uncommon complication of BP treatment regimes that occurs at increased frequency in the presence of other risk factors, including chronic inflammatory conditions. Our patient suffered from a severe and complicated clinical course of BRONJ which, despite adequate therapy, resulted in death of the patient. Here we discuss the risk factors for the development and clinical course of BRONJ in AIH and the implications for management of these patients.
Case Reports in Gastroenterology 01/2012; 6(2):309-13.
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A M C Baven-Pronk,
M J Coenraad,
H R van Buuren,
R A de Man,
K J van Erpecum,
M M H Lamers,
J P H Drenth,
A P van den Berg,
U H Beuers,
J den Ouden,
G H Koek, C M J van Nieuwkerk,
G Bouma,
J T Brouwer,
B van Hoek
Alimentary Pharmacology & Therapeutics 09/2011; 34(6):684-685. · 3.77 Impact Factor
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A M C Baven-Pronk,
M J Coenraad,
H R van Buuren,
R A de Man,
K J van Erpecum,
M M H Lamers,
J P H Drenth,
A P van den Berg,
U H Beuers,
J den Ouden,
G H Koek, C M J van Nieuwkerk,
G Bouma,
J T Brouwer,
B van Hoek
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ABSTRACT: Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment.
To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes.
Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression.
Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001).
Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.
Alimentary Pharmacology & Therapeutics 06/2011; 34(3):335-43. · 3.77 Impact Factor
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The Netherlands Journal of Medicine 02/2008; 66(1):40-1. · 2.07 Impact Factor
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ABSTRACT: The prevalence of the genotypes of the hepatitis C virus (HCV) differs according to geographical location. In the United States and in European countries, the majority of patients are infected with genotype 1, 2 or 3. There is a lack of data on the distribution of HCV genotypes in The Netherlands.
The current survey determined the distribution of HCV genotypes amongst recently genotyped patients seen by physicians treating hepatitis C in The Netherlands.
Almost half of the 351 patients (49.3%) were infected with genotype 1. Genotype 3 was the second most dominant genotype with a prevalence of 29.3%. Genotypes 2 and 4 were found in 9.7 and 10.5% of the patients, respectively. For 61.5% of the patients (n=216), the subtype was available. For genotype 1 the prevalence of subtype 1a and 1b was very similar, while for genotype 3 a large majority of patients were infected with subtype 3a.
This survey gives the first estimation of the distribution of HCV genotypes amongst unselected HCV patients in The Netherlands.
The Netherlands Journal of Medicine 05/2006; 64(4):109-13. · 2.07 Impact Factor
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Journal of Pediatric Gastroenterology and Nutrition 10/2002; 35(3):363-5. · 2.30 Impact Factor
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H L A Janssen,
A Wijnhoud,
E B Haagsma,
S.H.M. Uum, C M J van Nieuwkerk,
R P Adang,
R.A.F.M. Chamuleau,
J van Hattum,
F.P. Vleggaar,
B E Hansen,
F R Rosendaal,
B. van den Hoek
