Caroline Den Hoed - Academia.edu (original) (raw)
Papers by Caroline Den Hoed
British Journal of Clinical Pharmacology, 2001
Liver Transplantation
For liver transplantations, human leukocyte antigen (HLA) matching is not routinely performed bec... more For liver transplantations, human leukocyte antigen (HLA) matching is not routinely performed because observed effects have been inconsistent. Nevertheless, long-term liver transplantation outcomes remain suboptimal. The availability of a more precise HLA-matching algorithm, Predicted Indirectly Recognizable HLA Epitopes II (PIRCHE-II), now enables robust assessment of the association between HLA matching and liver transplantation outcomes. We performed a single-center retrospective cohort study of 736 liver transplantation patients. Associations between PIRCHE-II and HLAMatchmaker scores and mortality, graft loss, acute and chronic rejection, ischemic cholangiopathy, and disease recurrence were evaluated with Cox proportional hazards models. Associations between PIRCHE-II with 1-year, 2-year, and 5-year outcomes and severity of acute rejection were assessed with logistic and linear regression analyses, respectively. Subgroup analyses were performed for autoimmune and nonautoimmune indications, and patients aged 30 years and younger, and older than 30 years. PIRCHE-II and HLAMatchmaker scores were not associated with any of the outcomes. However, patients who received transplants for autoimmune disease showed more acute rejection and graft loss, and these risks negatively associated with age. Rhesus mismatch more than doubled the risk of disease recurrence. Moreover, PIRCHE-II was inversely associated with graft loss in the subgroup of patients aged 30 years and younger with autoimmune indications. The absence of associations between PIRCHE-II and HLAMatchmaker scores and the studied outcomes refutes the need for HLA matching for liver (stem cell) transplantations for nonautoimmune disease. For Eric Spierings and Caroline M. den Hoed contributed equally to this work.
Gut, 2022
We read with great interest the recent publication from Siegel and colleagues, reporting recommen... more We read with great interest the recent publication from Siegel and colleagues, reporting recommendations from an international consensus meeting for SARSCoV2 vaccination in patients with inflammatory bowel diseases (IBDs). Based on experiences with other vaccines, it is reported that several immunosuppressive agents are associated with suboptimal vaccine response in patients with IBD. We assessed the effect of immunosuppressive blood levels on the SARSCoV2specific immunogenicity of SARSCoV2 vaccination in liver transplant (LT) recipients vaccinated with two doses of the mRNA vaccines: BNT162b2 or mRNA1273 or the vector vaccine ChAdOx1 nCoV19. Excluded were patients with a history of a SARSCoV2 infection. A total of 476 LT recipients (476/795=59.9% of all alive recipients) were eligible for analysis between March and July 2021 at the Erasmus University Medical Centre (Rotterdam, the Netherlands). In total, 36 LT recipients had a history of a SARSCoV2 infection confirmed by PCR before vaccination, 128 LT recipients were not vaccinated and 155 LT recipients were not routinely seen at the outpatient clinic during the study period and, therefore, excluded from this analysis. Immunogenicity to vaccination was measured by using the Liaison SARSCoV2 TrimericS IgG assay (DiaSorin, Italy). Table 1 presents the demographical and clinical characteristics of the study population. Tacrolimus (TAC) was used in 88.2% of the LT recipients as main immunosuppressive agent. Mycophenolate mofetil (MMF) was used in 34% of the LT recipients, mainly in combination therapy with TAC. Seroconversion occurred in 79.0% (376/476) of our LT recipients (see online supplemental table 1 and online supplemental figure 1). Figure 1A shows the immunoglobulin G (IgG) SARSCoV2 antispike antibody response according to the type of vaccine and stratified by the use of MMF. The use of MMF reduced the median level of IgG SARSCoV2 antispike antibodies for all vaccines to below the manufacturer’s cutoff for considering reactive. We did not find any significant associations between the other used immunosuppressive agents and immunogenicity. Figure 1B,C shows the IgG SARSCoV2 antispike antibodies versus TAC and mycophenolic acid (MPA) trough levels including expected values from multivariable linear regression models (see online supplemental table 2). The median IgG SARSCoV2 antibody levels over the TAC trough concentration range were 1090 BAU/mL and TAC trough levels were not associated with an effect on the immunogenicity. The median IgG SARSCoV2 antibody levels over the MPA trough concentration range were below the cutoff considered reactive by the manufacturer. MPA trough levels were significantly associated with lower immunogenicity of SARSCoV2 vaccination. Overall, IgG SARSCoV2 antibody levels were low for recipients using MMF and even for MPA trough levels of ≤1 mg/L. These results complement data of several studies in immunocompromised patients showing an altered antibody response to SARSCoV2 vaccinations in relation to the immunosuppressive drugs used. MPA inhibits both T and B lymphocytes proliferation, thereby suppressing cellmediated immune responses and antibody formation. Other agents showing a significant effect on the differentiation of B lymphocytes are Janus Kinase (JAK) inhibitors and methotrexate, whereas TAC, corticosteroids and mechanistic target of rapamycin (mTOR) inhibitors deplete only the T lymphocytes and indirectly the B lymphocytes. Moreover, the duration of inhibitory effects of immunosuppressive agents on the T and B lymphocytes differs per agent. We suggest discontinuing MMF for at least 6 weeks prior to and after vaccination based on the pharmacodynamical effect of MMF on B lymphocytes as shown by Ganschow et al and our results shown in this cohort. Furthermore, avoiding other agents affecting B lymphocytes in immunocompromised patients is recommended to increase the immunogenicity to SARSCoV2 vaccines. Focusing on the mechanism of action and drug levels of immunosuppressive agents in relation to the immunogenicity is essential in the ongoing debate to select the right target population for additional vaccinations and to define the right moment for (booster) vaccination. The use of MMF, regardless the trough level, is associated with a very poor IgG SARSCoV2 antispike antibodies response to SARSCoV2 vaccination. As a consequence, lowering the dose of MMF has no beneficial effect. Midas B Mulder , Annemiek A van der Eijk, Corine H GeurtsvanKessel, Nicole S Erler, Brenda C M de Winter, Wojciech G Polak, Herold J Metselaar, Caroline M den Hoed Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands the Erasmus MC Transplant Institute, Erasmus MC Transplant Institute, Rotterdam, The Netherlands Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands Department of…
Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant ... more Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic co-administration. By diminishing gut bacteria β-glucuronidase activity, oral antibiotics seem to prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, is advised.
Endoscopy International Open
Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions... more Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleot...
Abstract Infection with Helicobacter pylori is among the world's most common infections. It o... more Abstract Infection with Helicobacter pylori is among the world's most common infections. It occurs worldwide, with substantial differences in prevalence both within and between countries. The bacterium induces chronic active gastritis in all infected subjects and is the main cause of peptic ulcer disease, gastric carcinoma, and MALT lymphoma. H. pylori infection can be diagnosed by non-invasive and invasive methods. Urea breath tests, serum IgG antibody tests, and fecal antigen tests are well-validated, non-invasive tests and are reliable diagnostic tools. Invasive tests such as culture, histology, and rapid urease tests should only be performed when there is an indication for an upper gastrointestinal endoscopy. H. pylori infection can be treated with a combination of anti-microbials and acid-suppressive drugs. Treatment is indicated for patients with peptic ulcer disease and MALT lymphoma and patients who are at increased risk for developing gastric carcinoma.
Gastric Cancer, 2021
Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesio... more Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, sh...
Nederlands Tijdschrift voor Geneeskunde, 2018
Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise... more Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise during glucocorticoid use, and for which preventative measures can be taken, include reactivation of latent tuberculosis and hepatitis B, pneumococcal and Pneumocystis jiroveci pneumonia, influenza, herpes zoster and Strongyloides stercoralis hyperinfection syndrome. The risk of such infections depends upon the duration of glucocorticoid use and dosage, as well as comorbidity and comedication. It is important to enquire about vaccinations, travel, exposure and previous infections when taking a case history. Possible infectious complications should be considered in patients who are receiving high-dose glucocorticoids treatment amounting to more than 420 mg PED per 4 weeks. Preventative measures are not usually required in patients who receive a short high-dosed treatment (30 mg PED in 7 days) or prednisolone at a dosage of < 15 mg/day.
Nederlands Tijdschrift voor Geneeskunde, 2019
Nederlands tijdschrift voor geneeskunde, 2018
Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise... more Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise during glucocorticoid use, and for which preventative measures can be taken, include reactivation of latent tuberculosis and hepatitis B, pneumococcal and Pneumocystis jiroveci pneumonia, influenza, herpes zoster and Strongyloides stercoralis hyperinfection syndrome. The risk of such infections depends upon the duration of glucocorticoid use and dosage, as well as comorbidity and comedication. It is important to enquire about vaccinations, travel, exposure and previous infections when taking a case history. Possible infectious complications should be considered in patients who are receiving high-dose glucocorticoids treatment amounting to more than 420 mg PED per 4 weeks. Preventative measures are not usually required in patients who receive a short high-dosed treatment (30 mg PED in 7 days) or prednisolone at a dosage of < 15 mg/day.
Nederlands tijdschrift voor geneeskunde, 2019
BACKGROUND Acute liver failure resulting from the use of food supplements is rare. However, due t... more BACKGROUND Acute liver failure resulting from the use of food supplements is rare. However, due to the rapid rise in the use of food supplements, the incidence of liver damage is increasing. CASE DESCRIPTION We describe the cases of two women with menopausal symptoms who developed liver failure shortly after starting to take food supplements containing plant extracts. Both women consequently underwent a liver transplant. CONCLUSION Food supplements are not regarded as medicines, but fall under regulations pertaining to foodstuffs. This means they can be put on the market without their safety having first been checked. The old Dutch saying 'if it doesn't do any good, it won't do any harm' is certainly not applicable here. Is it time for a new law?
Huisarts en wetenschap, 2021
Bij een echo van de buik wordt vaak leververvetting (steatosis hepatis) gerapporteerd. De patiënt... more Bij een echo van de buik wordt vaak leververvetting (steatosis hepatis) gerapporteerd. De patiënt kan dannon-alcoholic fatty liver disease(NAFLD) hebben, een aandoening die geen klachten geeft, maar wel een belangrijke risicofactor voor hart- en vaatziekten vormt. NAFLD kan zich ook ontwikkelen totnon-alcoholic steatohepatitis(NASH), die kan leiden tot leverfibrose en -cirrose, en het zeldzame hepatocellulair carcinoom (HCC). Hoe komt u tot de diagnose NAFLD en wat kunt u de patiënt adviseren?
Cancer Treatment Reviews
BACKGROUND Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment... more BACKGROUND Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.
Scientific reports, Jan 31, 2017
Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and conti... more Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and continues to rise worldwide. While etiological understanding is needed for prevention, epidemiological studies indicated that colonization with Helicobacter pylori (H. pylori) may affect body mass index (BMI), but with inconsistent results. Here, we examine the relationship between H. pylori colonization and BMI/obesity. Cross-sectional analyses were performed in two independent population-based cohorts of elderly from the Netherlands and Germany (n = 13,044). Genetic risk scores were conducted based on genetic loci associated with either H. pylori colonization or BMI/obesity. We performed a bi-directional Mendelian randomization. Meta-analysis of cross-sectional data revealed no association between anti-H. pylori IgG titer and BMI, nor of H. pylori positivity and BMI. Anti-H. pylori IgG titer was negatively associated with obesity (OR 0.99972; 95% CI 0.99946-0.99997, p = 0.03) and with obesi...
Gut, Jan 6, 2018
International guidelines recommend endoscopic surveillance of premalignant gastric lesions. Howev... more International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression. Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17. 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or inv...
British Journal of Clinical Pharmacology, 2001
Liver Transplantation
For liver transplantations, human leukocyte antigen (HLA) matching is not routinely performed bec... more For liver transplantations, human leukocyte antigen (HLA) matching is not routinely performed because observed effects have been inconsistent. Nevertheless, long-term liver transplantation outcomes remain suboptimal. The availability of a more precise HLA-matching algorithm, Predicted Indirectly Recognizable HLA Epitopes II (PIRCHE-II), now enables robust assessment of the association between HLA matching and liver transplantation outcomes. We performed a single-center retrospective cohort study of 736 liver transplantation patients. Associations between PIRCHE-II and HLAMatchmaker scores and mortality, graft loss, acute and chronic rejection, ischemic cholangiopathy, and disease recurrence were evaluated with Cox proportional hazards models. Associations between PIRCHE-II with 1-year, 2-year, and 5-year outcomes and severity of acute rejection were assessed with logistic and linear regression analyses, respectively. Subgroup analyses were performed for autoimmune and nonautoimmune indications, and patients aged 30 years and younger, and older than 30 years. PIRCHE-II and HLAMatchmaker scores were not associated with any of the outcomes. However, patients who received transplants for autoimmune disease showed more acute rejection and graft loss, and these risks negatively associated with age. Rhesus mismatch more than doubled the risk of disease recurrence. Moreover, PIRCHE-II was inversely associated with graft loss in the subgroup of patients aged 30 years and younger with autoimmune indications. The absence of associations between PIRCHE-II and HLAMatchmaker scores and the studied outcomes refutes the need for HLA matching for liver (stem cell) transplantations for nonautoimmune disease. For Eric Spierings and Caroline M. den Hoed contributed equally to this work.
Gut, 2022
We read with great interest the recent publication from Siegel and colleagues, reporting recommen... more We read with great interest the recent publication from Siegel and colleagues, reporting recommendations from an international consensus meeting for SARSCoV2 vaccination in patients with inflammatory bowel diseases (IBDs). Based on experiences with other vaccines, it is reported that several immunosuppressive agents are associated with suboptimal vaccine response in patients with IBD. We assessed the effect of immunosuppressive blood levels on the SARSCoV2specific immunogenicity of SARSCoV2 vaccination in liver transplant (LT) recipients vaccinated with two doses of the mRNA vaccines: BNT162b2 or mRNA1273 or the vector vaccine ChAdOx1 nCoV19. Excluded were patients with a history of a SARSCoV2 infection. A total of 476 LT recipients (476/795=59.9% of all alive recipients) were eligible for analysis between March and July 2021 at the Erasmus University Medical Centre (Rotterdam, the Netherlands). In total, 36 LT recipients had a history of a SARSCoV2 infection confirmed by PCR before vaccination, 128 LT recipients were not vaccinated and 155 LT recipients were not routinely seen at the outpatient clinic during the study period and, therefore, excluded from this analysis. Immunogenicity to vaccination was measured by using the Liaison SARSCoV2 TrimericS IgG assay (DiaSorin, Italy). Table 1 presents the demographical and clinical characteristics of the study population. Tacrolimus (TAC) was used in 88.2% of the LT recipients as main immunosuppressive agent. Mycophenolate mofetil (MMF) was used in 34% of the LT recipients, mainly in combination therapy with TAC. Seroconversion occurred in 79.0% (376/476) of our LT recipients (see online supplemental table 1 and online supplemental figure 1). Figure 1A shows the immunoglobulin G (IgG) SARSCoV2 antispike antibody response according to the type of vaccine and stratified by the use of MMF. The use of MMF reduced the median level of IgG SARSCoV2 antispike antibodies for all vaccines to below the manufacturer’s cutoff for considering reactive. We did not find any significant associations between the other used immunosuppressive agents and immunogenicity. Figure 1B,C shows the IgG SARSCoV2 antispike antibodies versus TAC and mycophenolic acid (MPA) trough levels including expected values from multivariable linear regression models (see online supplemental table 2). The median IgG SARSCoV2 antibody levels over the TAC trough concentration range were 1090 BAU/mL and TAC trough levels were not associated with an effect on the immunogenicity. The median IgG SARSCoV2 antibody levels over the MPA trough concentration range were below the cutoff considered reactive by the manufacturer. MPA trough levels were significantly associated with lower immunogenicity of SARSCoV2 vaccination. Overall, IgG SARSCoV2 antibody levels were low for recipients using MMF and even for MPA trough levels of ≤1 mg/L. These results complement data of several studies in immunocompromised patients showing an altered antibody response to SARSCoV2 vaccinations in relation to the immunosuppressive drugs used. MPA inhibits both T and B lymphocytes proliferation, thereby suppressing cellmediated immune responses and antibody formation. Other agents showing a significant effect on the differentiation of B lymphocytes are Janus Kinase (JAK) inhibitors and methotrexate, whereas TAC, corticosteroids and mechanistic target of rapamycin (mTOR) inhibitors deplete only the T lymphocytes and indirectly the B lymphocytes. Moreover, the duration of inhibitory effects of immunosuppressive agents on the T and B lymphocytes differs per agent. We suggest discontinuing MMF for at least 6 weeks prior to and after vaccination based on the pharmacodynamical effect of MMF on B lymphocytes as shown by Ganschow et al and our results shown in this cohort. Furthermore, avoiding other agents affecting B lymphocytes in immunocompromised patients is recommended to increase the immunogenicity to SARSCoV2 vaccines. Focusing on the mechanism of action and drug levels of immunosuppressive agents in relation to the immunogenicity is essential in the ongoing debate to select the right target population for additional vaccinations and to define the right moment for (booster) vaccination. The use of MMF, regardless the trough level, is associated with a very poor IgG SARSCoV2 antispike antibodies response to SARSCoV2 vaccination. As a consequence, lowering the dose of MMF has no beneficial effect. Midas B Mulder , Annemiek A van der Eijk, Corine H GeurtsvanKessel, Nicole S Erler, Brenda C M de Winter, Wojciech G Polak, Herold J Metselaar, Caroline M den Hoed Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands the Erasmus MC Transplant Institute, Erasmus MC Transplant Institute, Rotterdam, The Netherlands Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands Department of…
Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant ... more Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic co-administration. By diminishing gut bacteria β-glucuronidase activity, oral antibiotics seem to prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, is advised.
Endoscopy International Open
Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions... more Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleot...
Abstract Infection with Helicobacter pylori is among the world's most common infections. It o... more Abstract Infection with Helicobacter pylori is among the world's most common infections. It occurs worldwide, with substantial differences in prevalence both within and between countries. The bacterium induces chronic active gastritis in all infected subjects and is the main cause of peptic ulcer disease, gastric carcinoma, and MALT lymphoma. H. pylori infection can be diagnosed by non-invasive and invasive methods. Urea breath tests, serum IgG antibody tests, and fecal antigen tests are well-validated, non-invasive tests and are reliable diagnostic tools. Invasive tests such as culture, histology, and rapid urease tests should only be performed when there is an indication for an upper gastrointestinal endoscopy. H. pylori infection can be treated with a combination of anti-microbials and acid-suppressive drugs. Treatment is indicated for patients with peptic ulcer disease and MALT lymphoma and patients who are at increased risk for developing gastric carcinoma.
Gastric Cancer, 2021
Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesio... more Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, sh...
Nederlands Tijdschrift voor Geneeskunde, 2018
Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise... more Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise during glucocorticoid use, and for which preventative measures can be taken, include reactivation of latent tuberculosis and hepatitis B, pneumococcal and Pneumocystis jiroveci pneumonia, influenza, herpes zoster and Strongyloides stercoralis hyperinfection syndrome. The risk of such infections depends upon the duration of glucocorticoid use and dosage, as well as comorbidity and comedication. It is important to enquire about vaccinations, travel, exposure and previous infections when taking a case history. Possible infectious complications should be considered in patients who are receiving high-dose glucocorticoids treatment amounting to more than 420 mg PED per 4 weeks. Preventative measures are not usually required in patients who receive a short high-dosed treatment (30 mg PED in 7 days) or prednisolone at a dosage of < 15 mg/day.
Nederlands Tijdschrift voor Geneeskunde, 2019
Nederlands tijdschrift voor geneeskunde, 2018
Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise... more Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise during glucocorticoid use, and for which preventative measures can be taken, include reactivation of latent tuberculosis and hepatitis B, pneumococcal and Pneumocystis jiroveci pneumonia, influenza, herpes zoster and Strongyloides stercoralis hyperinfection syndrome. The risk of such infections depends upon the duration of glucocorticoid use and dosage, as well as comorbidity and comedication. It is important to enquire about vaccinations, travel, exposure and previous infections when taking a case history. Possible infectious complications should be considered in patients who are receiving high-dose glucocorticoids treatment amounting to more than 420 mg PED per 4 weeks. Preventative measures are not usually required in patients who receive a short high-dosed treatment (30 mg PED in 7 days) or prednisolone at a dosage of < 15 mg/day.
Nederlands tijdschrift voor geneeskunde, 2019
BACKGROUND Acute liver failure resulting from the use of food supplements is rare. However, due t... more BACKGROUND Acute liver failure resulting from the use of food supplements is rare. However, due to the rapid rise in the use of food supplements, the incidence of liver damage is increasing. CASE DESCRIPTION We describe the cases of two women with menopausal symptoms who developed liver failure shortly after starting to take food supplements containing plant extracts. Both women consequently underwent a liver transplant. CONCLUSION Food supplements are not regarded as medicines, but fall under regulations pertaining to foodstuffs. This means they can be put on the market without their safety having first been checked. The old Dutch saying 'if it doesn't do any good, it won't do any harm' is certainly not applicable here. Is it time for a new law?
Huisarts en wetenschap, 2021
Bij een echo van de buik wordt vaak leververvetting (steatosis hepatis) gerapporteerd. De patiënt... more Bij een echo van de buik wordt vaak leververvetting (steatosis hepatis) gerapporteerd. De patiënt kan dannon-alcoholic fatty liver disease(NAFLD) hebben, een aandoening die geen klachten geeft, maar wel een belangrijke risicofactor voor hart- en vaatziekten vormt. NAFLD kan zich ook ontwikkelen totnon-alcoholic steatohepatitis(NASH), die kan leiden tot leverfibrose en -cirrose, en het zeldzame hepatocellulair carcinoom (HCC). Hoe komt u tot de diagnose NAFLD en wat kunt u de patiënt adviseren?
Cancer Treatment Reviews
BACKGROUND Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment... more BACKGROUND Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.
Scientific reports, Jan 31, 2017
Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and conti... more Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and continues to rise worldwide. While etiological understanding is needed for prevention, epidemiological studies indicated that colonization with Helicobacter pylori (H. pylori) may affect body mass index (BMI), but with inconsistent results. Here, we examine the relationship between H. pylori colonization and BMI/obesity. Cross-sectional analyses were performed in two independent population-based cohorts of elderly from the Netherlands and Germany (n = 13,044). Genetic risk scores were conducted based on genetic loci associated with either H. pylori colonization or BMI/obesity. We performed a bi-directional Mendelian randomization. Meta-analysis of cross-sectional data revealed no association between anti-H. pylori IgG titer and BMI, nor of H. pylori positivity and BMI. Anti-H. pylori IgG titer was negatively associated with obesity (OR 0.99972; 95% CI 0.99946-0.99997, p = 0.03) and with obesi...
Gut, Jan 6, 2018
International guidelines recommend endoscopic surveillance of premalignant gastric lesions. Howev... more International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression. Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17. 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or inv...