Epidemiology and management of hepatitis B and C in primary care in the Netherlands: data from the Rijnmond Primary Care database.

BACKGROUND: The Dutch guideline for general practitioners (GPs) advises biannual surveillance of hepatitis B (HBV) patients and referral of every hepatitis C (HCV) patient. We aimed to study the prevalence, incidence, and the management of hepatitis B and C in primary care. METHODS: This is a retrospective cohort study using the Rijnmond Primary Care database (RPCD), including health care data of medical records of GPs of approximately 200,000 patients in the area of Rotterdam, the Netherlands. Patient records were selected based on laboratory results, International Classification of Primary Care (ICPC) codes, and free-text words. RESULTS: In total, 977 patients were included: 717 HBV, 252 HCV, and 8 HBV/HCV coinfected patients. Between 2013 and 2019, the prevalence of HBV and HCV declined from 5.21 to 2.99/1,000 person-years (PYs) and 1.50 to 0.70/1,000 PYs, respectively. We observed that the majority of the patients had been referred to a medical specialist at least once (71% HBV and 89% HCV patients). However, among chronic patients, we observed that 36.2% of the HBV patients did not receive adequate surveillance by their GP (≥2 alanine aminotransferase checks within 3 years) or a medical specialist. In addition, 44.4% of the HCV patients had no record about successful antiviral treatment. CONCLUSIONS: This study demonstrated a declining prevalence in viral hepatitis B and C in primary care in the Netherlands. However, a substantial part of the patients did not receive adequate surveillance or antiviral therapy. It is therefore crucial to involve GPs in case finding and in follow-up after treatment.

Assessment of Adherence to Clinical Guidelines in Patients with Chronic Hepatitis B.

Background and aims: Adherence to guidelines is associated with improved long-term outcomes in patients with chronic hepatitis B (CHB). We aimed to study the degree of adherence and determinants of non-adherence to management guidelines in a low endemic country. Methods: We reviewed the medical records of all CHB patients who visited our outpatient clinic in 2020. Adherence to guidelines was assessed based on predefined criteria based on the EASL guidance, and included the initiation of antiviral therapy when indicated, the optimal choice of antiviral therapy based on comorbidities, an assessment of HAV/HCV/HDV/HIV serostatus, renal function monitoring and enrolment in a HCC surveillance program if indicated. The adherence rates were compared across types of outpatient clinic (dedicated viral hepatitis clinic versus general hepatology clinic). Results: We enrolled 482 patients. Among the 276 patients with an indication for antiviral therapy, 268 (97.1%) received treatment. Among the patients with renal and/or bone disease, 26/29 (89.7%) received the optimal choice of antiviral agent. The assessment of HAV/HCV/HDV/HIV serostatus was performed in 86.1/91.7/94.4/78.4%. Among the 91 patients treated with tenofovir disoproxil, 57 (62.6%) underwent monitoring of renal function. Of the 241 patients with an indication for HCC surveillance, 212 (88.3%) were enrolled in a surveillance program. Clinics dedicated to viral hepatitis had superior adherence rates compared to general hepatology clinics (complete adherence rates 63.6% versus 37.2%, p < 0.001). Conclusions: Follow-up at a dedicated viral hepatitis clinic was associated with superior adherence to management guidelines.

Hepatocellular adenoma in men: A nationwide assessment of pathology and correlation with clinical course.

BACKGROUND & AIMS: Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course. METHODS: Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death. RESULTS: A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision. CONCLUSIONS: Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.

Cost-effectiveness of screening for chronic hepatitis B and C among migrant populations in a low endemic country.

BACKGROUND: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective. METHODS: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed. RESULTS: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections. CONCLUSIONS: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants.

Current policy for allocation of donor livers in the Netherlands advantages primary sclerosing cholangitis patients on the liver transplantation waiting list-a retrospective study.

Studies from the USA and Nordic countries indicate primary sclerosing cholangitis (PSC) patients have low mortality on the liver transplantation (LTx) waiting list. However, this may vary among geographical areas. Therefore, we compared waiting list mortality and post-transplant survival between laboratory model for end-stage liver disease (LM) and MELD exception (ME)-prioritized PSC and non-PSC candidates in a nationwide study in the Netherlands. A retrospective analysis of patients waitlisted from 2006 to 2013 was conducted. A total of 852 candidates (146 PSC) were waitlisted of whom 609 (71.5%) underwent LTx and 159 (18.7%) died before transplantation. None of the ME PSC patients died, and they had a higher probability of LTx than LM PSC [HR obtained by considering ME as a time-dependent covariate (HRME 9.86; 95% CI 6.14-15.85)] and ME non-PSC patients (HRME 4.60; 95% CI 3.78-5.61). After liver transplantation, PSC patients alive at 3 years of follow-up had a higher probability of relisting than non-PSC patients (HR 7.94; 95% CI 1.98-31.85) but a significantly lower mortality (HR 0.51; 95% CI 0.27-0.95). In conclusion, current LTx prioritization advantages PSC patients on the LTx waiting list. Receiving ME points is strongly associated with timely LTx.

Factors associated with ethnical disparity in overall survival for patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an important cause of cancer-related death worldwide. Ethnical disparity in overall survival has been demonstrated for HCC patients in the United States (U.S.). We aimed to evaluate the contributors to this survival disparity. The SEER database was used to identify HCC patients from 2004 to 2012. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate overall survival by ethnicity and the contributors to ethnical survival disparity. A total of 33 062 patients were included: 15 986 Non-Hispanic Whites, 6535 Hispanic Whites, 4842 African Americans, and 5699 Asians. Compared to Non-Hispanic Whites, African Americans had worse survival (HR, 1.18; 95%CI, 1.14-1.23), while Asians had a better survival (HR, 0.85; 95%CI, 0.82-0.89), and Hispanic Whites had a similar survival (HR, 1.01; 95%CI, 0.97-1.05). Multivariate Cox analysis identified that tumor presentation- and treatment-related factors significantly contributed to the ethnical survival disparity. Especially, tumor size was the most important contributor (HR, 1.11; 95%CI, 1.07-1.16). There is no ethnical survival disparity in patients undergoing liver transplantation and sub-analysis of patients within the Milan criteria for liver transplantation demonstrated no significant survival disparity between African Americans and non-Hispanic Whites in transplantation adjustment analysis (HR, 1.23; 95%CI, 1.11-1.35 in non-adjustment analysis to HR, 1.05; 95%CI, 0.95-1.15 after adjustment). Finally, no important contributor to the superior overall survival in Asians was identified. In conclusion, poor tumor presentation at diagnosis, limited benefit from resection and restricted utilization of liver transplantation are important contributors to poorer survival of African Americans with HCC.

The global burden of hepatitis E outbreaks: a systematic review.

Hepatitis E virus (HEV) is responsible for repeated water-borne outbreaks since the past century, representing an emerging issue in public health. However, the global burden of HEV outbreak has not been comprehensively described. We performed a systematic review of confirmed HEV outbreaks based on published literatures. HEV outbreaks have mainly been reported from Asian and African countries, and only a few from European and American countries. India represents a country with the highest number of reported HEV outbreaks. HEV genotypes 1 and 2 were responsible for most of the large outbreaks in developing countries. During the outbreaks in developing countries, a significantly higher case fatality rate was observed in pregnant women. In fact, outbreaks have occurred both in open and closed populations. The control measures mainly depend upon improvement of sanitation and hygiene. This study highlights that HEV outbreak is not new, yet it is a continuous global health problem.

Training and competence assessment in GI endoscopy: a systematic review.

INTRODUCTION: Training procedural skills in GI endoscopy once focused on threshold numbers. As threshold numbers poorly reflect individual competence, the focus gradually shifts towards a more individual approach. Tools to assess and document individual learning progress are being developed and incorporated in dedicated training curricula. However, there is a lack of consensus and training guidelines differ worldwide, which reflects uncertainties on optimal set-up of a training programme. AIMS: The primary aim of this systematic review was to evaluate the currently available literature for the use of training and assessment methods in GI endoscopy. Second, we aimed to identify the role of simulator-based training as well as the value of continuous competence assessment in patient-based training. Third, we aimed to propose a structured training curriculum based on the presented evidence. METHODS: A literature search was carried out in the available medical and educational literature databases. The results were systematically reviewed and studies were included using a predefined protocol with independent assessment by two reviewers and a final consensus round. RESULTS: The literature search yielded 5846 studies. Ninety-four relevant studies on simulators, assessment methods, learning curves and training programmes for GI endoscopy met the inclusion criteria. Twenty-seven studies on simulator validation were included. Good validity was demonstrated for four simulators. Twenty-three studies reported on simulator training and learning curves, including 17 randomised control trials. Increased performance on a virtual reality (VR) simulator was shown in all studies. Improved performance in patient-based assessment was demonstrated in 14 studies. Four studies reported on the use of simulators for assessment of competence levels. Current simulators lack the discriminative power to determine competence levels in patient-based endoscopy. Eight out of 14 studies on colonoscopy, endoscopic retrograde cholangiopancreatography and endosonography reported on learning curves in patient-based endoscopy and proved the value of this approach for measuring performance. Ten studies explored the numbers needed to gain competence, but the proposed thresholds varied widely between them. Five out of nine studies describing the development and evaluation of assessment tools for GI endoscopy provided insight into the performance of endoscopists. Five out of seven studies proved that intense training programmes result in good performance. CONCLUSIONS: The use of validated VR simulators in the early training setting accelerates the learning of practical skills. Learning curves are valuable for the continuous assessment of performance and are more relevant than threshold numbers. Future research will strengthen these conclusions by evaluating simulation-based as well as patient-based training in GI endoscopy. A complete curriculum with the assessment of competence throughout training needs to be developed for all GI endoscopy procedures.

Simulated colonoscopy training leads to improved performance during patient-based assessment.

BACKGROUND: Virtual reality (VR) endoscopy simulators are increasingly being used in the training of novice endoscopists. There are, however, insufficient data regarding the effect of simulator training on the early learning curve of novice endoscopists. OBJECTIVE: The aim of this study was to assess the clinical performance of novice endoscopists during colonoscopy after intensive and prolonged training on a VR endoscopy simulator. DESIGN: Prospective study. SETTING: Single university medical center. PATIENTS: Patient-based assessment (PBA) of performance was carried out on patients routinely scheduled for colonoscopy. INTERVENTIONS: Eighteen trainees without any endoscopic experience were included in the study. They were divided into 2 groups. The simulator-training program consisted of either 50 (group I) or 100 (group II) VR colonoscopies. After 10, 30, and 50 (group I) and after 20, 60, and 100 (group II) VR colonoscopies, trainees underwent both simulator-based assessment and PBA. MAIN OUTCOME MEASUREMENTS: Cecal intubation time, colonic insertion depth, and cecal intubation rate. RESULTS: Eighteen novices participated in the study. All completed VR training and assessments. The mean cecal intubation time on the SBA decreased from a baseline of 9.50 minutes to 2.20 minutes at completion of the training (P = .002). Colonic insertion depth during PBA improved from 29.4 cm to 63.7 cm (P < .001). The learning effect of simulator training ceased after 60 colonoscopies. LIMITATIONS: Single-center study, no formal sample size calculation. CONCLUSIONS: VR training by using a colonoscopy simulator leads to a significant improvement in performance with the simulator itself and, more importantly, to significantly improved performances during patient-based colonoscopy. This study demonstrates the rationale for intensive simulator training in the early learning curve of novices performing colonoscopy.

Quality evaluation through self-assessment: a novel method to gain insight into ERCP performance.

BACKGROUND: The American Society for Gastrointestinal Endoscopy Committee on Outcomes Research has recommended monitoring nine endoscopic retrograde cholangiopancreatography (ERCP)-specific quality indicators for quality assurance in ERCP. With the development of a self-assessment tool for ERCP (Rotterdam Assessment Form for ERCP-RAF-E), key indicators can easily be assessed. OBJECTIVE: The aim of this study was to test in daily practice an easy-to-use form for assessment of procedural quality in ERCP and to determine ERCP quality outcomes in a tertiary referral hospital. DESIGN: This was a prospective study carried out in a tertiary referral hospital. In January 2008, a quality self-assessment programme was started. Five qualified endoscopists participated in this study. All ERCPs were appraised using RAF-E. Primary parameters were common bile duct (CBD) cannulation rate and procedural success. The indication was classified and procedural difficulty was graded; success rates of therapeutic interventions were measured for all different difficulty degrees. RESULTS: A total number of 1691 ERCPs were performed. 1515 (89.6%) of these were appraised using RAF-E. Median CBD cannulation success rate was 94.1%. Successful sphincterotomy was accomplished in almost all patients (median 100%; range 98.2-100%). Stent placement was successful in 97.8% and complete stone extraction, if indicated, was achieved in 86.8%. CONCLUSIONS: Quality indicators for ERCP can be measured using the Rotterdam self-assessment programme for ERCP. Outcome data in ERCPs obtained with this RAF-E provide insight into the quality of individual as well as group performance and can be used to assess and set standards for quality control in ERCP.

Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review.

Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self-limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in-depth emphasis of this clinical issue and a discussion of future development are also presented.

Is bone scintigraphy indicated in surgical work-up for hepatocellular carcinoma patients?

BACKGROUND: Patients with hepatocellular carcinoma (HCC) undergo extensive staging investigations when being assessed for surgical resection. The aim of this study was to assess the use and yield of baseline bone scintigraphy in patients with HCC necessitating high-risk surgical resection. MATERIAL AND METHODS: All patients diagnosed with HCC between 2000 and 2010 within a tertiary referral center were reviewed. Recurrence and survival rates were compared between patients with and without bone scintigraphy in their preoperative work-up. RESULTS: A total of 366 patients were diagnosed with resectable HCC. In the work-up for resection 137 HCC patients (41%) underwent bone scintigraphy, which showed bone metastases in 3 (2%). There was no significant difference in long-term survival between patients with and without bone scintigraphy. None of the patients with a positive bone scintigraphy died due to skeletal bone metastases. Only one patient had an indication for bone scintigraphy based on clinical suspicion. Two patients were found to have asymptomatic skeletal metastases prior to surgery. Symptomatic skeletal metastases were identified at an estimated cost of €27,008 per case. CONCLUSIONS: Clinically unsuspicious bone lesions turned out to be metastases in two patients, with an estimated cost of €27,008 per case. Recurrence rate and disease-free and overall survival showed no significant difference between patients with and without preoperative baseline bone scintigraphy. There is no justification for routine preoperative bone scintigraphy to detect asymptomatic skeletal metastases in patients with resectable HCC.

The Global Rating Scale in clinical practice: a comprehensive quality assurance programme for endoscopy departments.

BACKGROUND: The Global Rating Scale is an endoscopy quality assurance programme, successfully implemented in England. It remains uncertain whether it is applicable in another health care setting. AIM: To assess the applicability of the Global Rating Scale as benchmark tool in an international context. METHODS: Eleven Dutch endoscopy departments were included for a Global Rating Scale-census, performed as a cross-sectional evaluation, July 2010. Two Global Rating Scale-dimensions - 'clinical quality' and 'patient experience' - were assessed across six items using a range of levels: from level-D (basic) to level-A (excellent). Construct validity was assessed by comparing department-specific colonoscopy audit data to GRS-levels. RESULTS: For 'clinical quality', variable scores were achieved in items 'safety' (9%=B, 27%=C, 64%=D) and 'communication' (46%=A, 18%=C, 36%=D). All departments achieved a basic score in 'quality' (100%=D). For 'patient experience', variable scores were achieved in 'timeliness' (18%=A, 9%=B, 73%=D) and 'booking-choice' (36%=B, 46%=C, 18%=D). All departments achieved basic scores in 'equality' (100%=D). Departments obtaining level-C or above in 'information', 'comfort', 'communication', 'timeliness' and 'aftercare', achieved significantly better audit outcomes compared to those obtaining level-D (p<0.05). CONCLUSION: The Global Rating Scale is appropriate to use outside England. There was significant variance across departments in dimensions. Most Global Rating Scale-levels were in line with departments' audit outcomes, indicating construct validity.

Can a decision-making model be justified in the management of hepatocellular adenoma?

During recent years, there was a great development in the area of hepatocellular adenomas (HCA), especially regarding the pathological subtype classification, radiological imaging and management during pregnancy. This review discusses the current knowledge about diagnosis and treatment modalities of HCA and proposes a decision-making model for HCA. A Medline search of studies relevant to epidemiology, histopathology, complications, imaging and management of HCA lesions was undertaken. References from identified articles were hand-searched for further relevant articles.

Screening and early treatment of migrants for chronic hepatitis B virus infection is cost-effective.

BACKGROUND & AIMS: Persons with chronic hepatitis B virus (HBV) infection are at risk of developing cirrhosis and hepatocellular carcinoma. Early detection of chronic HBV infection through screening and treatment of eligible patients has the potential to prevent these sequelae. We assessed the cost-effectiveness in The Netherlands of systematically screening migrants from countries that have high and intermediate HBV infection levels. METHODS: Epidemiologic data of the expected numbers of patients with active chronic HBV infection in the target population and information about the costs of a screening program were used in a Markov model and used to determine costs and quality-adjusted life years (QALY) for patients who were and were not treated. RESULTS: Compared with the status quo, a 1-time screen for HBV infection can reduce mortality of liver-related diseases by 10%. Using base case estimates, the incremental cost-effectiveness ratio (ICER) of screening, compared with not screening, is euros (euro) 8966 per QALY gained. The ICER ranged from euro7936 to euro11,705 based on univariate sensitivity analysis, varying parameter values of HBV prevalence, participation rate, success in referral, and treatment compliance. Using multivariate sensitivity analysis for treatment effectiveness, the ICER ranged from euro7222 to euro15,694; for disease progression, it ranged from euro5568 to euro60,418. CONCLUSIONS: Early detection and treatment of people with HBV infection can have a large impact on liver-related health outcomes. Systematic screening for chronic HBV infection among migrants is likely to be cost-effective, even using low estimates for HBV prevalence, participation, referral, and treatment compliance.

Hepatocellular adenoma: cost-effectiveness of different treatment strategies.

PURPOSE: To determine the effectiveness, costs, and cost-effectiveness of strategies for the management of hepatocellular adenoma (HA) in women who are otherwise healthy. MATERIALS AND METHODS: A Markov model was developed to estimate the quality-adjusted life expectancy (in quality-adjusted life-years [QALYs]), lifetime costs (in 2007 U.S. dollars), and net health benefits (QALY equivalent) of surgery, transarterial embolization (TAE), radiofrequency ablation (RFA), and watchful waiting. Model parameters and their distributions were derived from the literature and the hospital database. RESULTS: In patients with HA tumors suitable for RFA, RFA had the highest effectiveness (23.89 QALYs) and lowest costs ($2965). The treatment decision was sensitive to RFA-related mortality. In patients with tumors unsuitable for RFA, watchful waiting combined with TAE in cases of hemorrhage had the highest effectiveness (23.83 QALYs) and lowest costs ($8493). The treatment decision was sensitive to probability of tumor growth, probability of hemorrhage, and hemorrhage-related mortality. CONCLUSION: According to the model results, the most favorable treatment strategy for patients with small HAs was RFA. In patients with HA unsuitable for RFA, watchful waiting was the optimal strategy.

Potential impact of long-term nucleoside therapy on the mortality and morbidity of active chronic hepatitis B.

UNLABELLED: The potential impact of long-term antiviral therapy on the burden of chronic hepatitis B has hardly been documented. The aim of this study was to estimate the effects of prolonged antiviral therapy and antiviral resistance on the mortality and morbidity of active chronic hepatitis B patients. A population cohort of chronic hepatitis B patients in the Netherlands was constructed and stratified according to 10-year age groups, prevalence of hepatitis B surface antigen, hepatitis B virus DNA level, alanine aminotransferase level, hepatitis B e antigen status, and presence of cirrhosis. A Markov model was created to mathematically simulate the cohort's progression through a finite series of health states. The analysis was performed on the basis of four scenarios: natural history, long-term therapy with a high-resistance profile drug without or with salvage, and therapy with a low-resistance profile drug. It has been estimated that there were 64,000 people (0.4%) suffering from chronic hepatitis B infection in the Netherlands in 2005, with 6521 (10%) of them having high viremia and elevated alanine aminotransferase levels. Within a 20-year period, 1725 (26%) of the 6521 patients in the active chronic hepatitis B cohort will die because of liver-related causes. Of the 5685 without cirrhosis at entry, 1671 (29%) will develop cirrhosis. Of those 836 with cirrhosis at entry, 619 (74%) will die within a 20-year period. If this active chronic hepatitis B cohort is fully detected and treated, mortality related to liver disease can be reduced by 80% if a low-resistance profile drug is chosen from the start. The effect is due to both the reduction in complications of cirrhosis and the prevention of the development of cirrhosis. CONCLUSION: Long-term antiviral therapy with a strategy that minimizes or controls resistance will have a major preventive effect on liver-related mortality and morbidity.