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Autosomal dominant polycystic kidney disease (ADPKD) is a chronic, progressive condition characterized by the development and growth of cysts in the kidneys and other organs and by additional systemic manifestations. Individuals with ADPKD should have access to lifelong, multidisciplinary, specialist and patient-centred care involving: (i) a holistic and comprehensive assessment of the manifestations, complications, prognosis and impact of the disease (in physical, psychological and social terms) on the patient and their family; (ii) access to treatment to relieve symptoms, manage complications, preserve kidney function, lower the risk of cardiovascular disease and maintain quality of life; and (iii) information and support to help patients and their families act as fully informed and active partners in care, i.e. to maintain self-management approaches, deal with the impact of the condition and participate in decision-making regarding healthcare policies, services and research. Building on discussions at an international roundtable of specialists and patient advocates involved in ADPKD care, this article sets out (i) the principles for a patient-centred, holistic approach to the organization and delivery of ADPKD care in practice, with a focus on multispecialist collaboration and shared-decision making, and (ii) the rationale and knowledge base for a route map for ADPKD care intended to help patients navigate the services available to them and to help stakeholders and decision-makers take practical steps to ensure that all patients with ADPKD can access the comprehensive multispecialist care to which they are entitled. Further multispecialty collaboration is encouraged to design and implement these services, and to work with patient organizations to promote awareness building, education and research.

Objective Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. Design We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. Results Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). Conclusions The single-nucleotide polymorphisms rs10273639 at the PRSS1-PRSS2 locus and rs7057398 and rs12688220 at the CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.

In this new Dutch guideline for hepatitis C virus infection we provide recommendations for the management of hepatitis C infection. Until 2012 the standard for treatment consisted of pegylated interferon alpha (peg-IFN alpha) and ribavirin. The advent of first-generation direct antiviral agents such as boceprevir and telaprevir has changed the concept of treatment of adult chronic hepatitis C genotype 1 infected patients. There are three benefits of boceprevir and telaprevir. They increase the likelihood of cure in 1) naive genotype 1 patients and 2) in patients who did not respond to earlier treatment with peg-IFN alpha and ribavirin, while 3) allowing shortening of treatment duration from 48 weeks to 24 or 28 weeks, which is possible in 40-60% of non-cirrhotic naive (boceprevir and telaprevir) and relapsing patients (telaprevir). The use of boceprevir and telaprevir is associated with multiple side effects and awareness of these side effects is needed to guide the patient through the treatment process. This guideline, formulated on behalf of The Netherlands Association of Hepato-gastroenterologists, The Netherlands Association of Internal Medicine, and The Dutch Association for the Study of Liver Disease, serves as a manual for physicians for the management and treatment of acute and chronic hepatitis C virus monoinfecti

Item does not contain fulltext BACKGROUND: Polycystic liver disease (PLD) is a phenotypical expression of autosomal dominant polycystic kidney disease and isolated polycystic liver disease. Somatostatin analogues, such as lanreotide, reduce polycystic liver volume. AIM: To establish long-term outcome and safety of lanreotide. METHODS: This was an open-label, observational extension study of a 6-month, randomised, placebo-controlled trial with lanreotide (120 mg/month) in PLD. The length of total treatment was 12 months. Primary endpoint was relative change in liver volume, as determined by CT-volumetry after 12 months of treatment. We offered patients a CT scan 6 months after stopping lanreotide. RESULTS: A total of 41/54 (76%) patients participated in the extension study. Liver volume decreased by 4% (IQR -8% to -1%) after 12 months of treatment. The greatest effect was observed during the first 6 months of treatment (decrease of 4% (IQR -6% to -1%)). Liver volume remained unchanged during the following 6 months. We found that liver volume increased by 4% (IQR 0-6%) 6 months after end of treatment (n = 22). CONCLUSIONS: Lanreotide reduces liver volume within the first 6 months of treatment and the beneficial effect is maintained in the following 6 months. Stopping results in recurrence of polycystic liver growth. This suggests that continuous use of lanreotide is needed to maintain its effect. 01 januari 2012

Background and aim: Isolated polycystic liver disease (PCLD) is characterized by the presence of multiple cysts in the liver in the absence of polycystic kidneys. The clinical profile of PCLD is poorly defined and we set up a study for the clinical characteristics of PCLD. Methods: We collected clinical data on 188 PCLD patients (defined as 410 liver cysts) from five tertiary referral centres, and 137 patients were selected for the purpose of this study. We performed molecular analysis of the PCLD associated genes PRKCSH and SEC63 in 91 patients. Results: A total of 118 (86%) patients were female. The majority of patients (88%) had 420 cysts. The median age at diagnosis was 47 years (range 23-84). 37 (41%) patients carried a mutation. Clinical symptoms at presentation were present in 111 (84%) patients. gamma-glutamyl transferase was elevated to 1.4 times upper limit of normal (interquartile range 1.0-2.7). The presence of a mutation and female gender predicted a more severe course: female patients were 9 years younger at the time of diagnosis (47 years; range 23-84) and 91% had symptoms (P < 0.01); likewise, mutation carriers were younger at presentation (39 years; range 35-48) and 95% of this cohort had symptoms (P < 0.01). During follow-up [median 8.2 years (range 0-35)], 10% of untreated and 51% of treated patients developed complications. Mortality in this cohort was 8%, but only 2% died of PCLD-related causes. 58% of patients were treated a median of 2 years (range 0-25) after diagnosis. Conclusion: Symptomatic PCLD patients are mainly females. Females and mutation carriers were younger at diagnosis and had a more severe course of disease.

Background Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. Aim To assess the efficacy of prophylactic escitalopram to prevent psychiatric side-effects during peginterferon and ribavirin treatment in a randomised, double-blind, placebo-controlled trial. Methods Seventy-nine hepatitis C patients were treated with peginterferon and ribavirin. Patients received escitalopram (n = 40, 10 mg) or placebo (n = 39), which was initiated together with peginterferon and ribavirin. Primary outcomes were an increase of two points or more on the items reported sadness, inner tension and impaired concentration of the Montgomery-Asberg Depression Rating Scale, and hostile feelings of the Brief Anxiety Scale. Secondary outcome was the development of depression diagnosed by the Mini-International Neuropsychiatric Interview. Measurements were performed at baseline, week 4, 12 and 24 during anti-viral treatment, and 24 weeks thereafter. Results The incidence of psychiatric side-effects was significantly lower in patients treated with escitalopram compared with placebo for all primary and secondary outcomes, except for impaired concentration: reported sadness 27.5 vs. 48.7% (P = 0.052), inner tension 17.5 vs. 38.5% (P = 0.038), impaired concentration 55.0 vs. 66.7% (P = 0.288) and hostile feelings 22.5 vs. 43.6% (P = 0.046) (escitalopram vs. placebo, Chi-squared test). The sum scores of all four endpoints showed an overall beneficial effect of escitalopram (P = 0.009, MannWhitney U-test). Depression occurred in 12.5% of the patients in the escitalopram-group vs. 35.9% in the placebo-group (P = 0.015, Chi-squared test). Conclusions Prophylactic treatment with escitalopram is effective in the prevention of psychiatric side-effects during interferon-based treatment of hepatitis C.

Background: Recently, the Dutch Association of Gastroenterology and Hepatology issued new guidelines for the treatment of chronic hepatitis C virus (HCV). These guidelines reflect the current standard of care. Before these guidelines were published and implemented we (I) studied the current clinical care of HCV patients among Dutch physicians, and (2) identified areas for future refinement in the current treatment. Methods: We conducted a non-targeted survey among Dutch medical specialists in Gastroenterology, Hepatology and Internal Medicine who actively treat HCV patients. The questionnaire contained items about facility, duration and dosing of treatment, and side effect management using clinical vignettes followed by short questions. Results: We received 49 questionnaires from treating HCV specialists. The majority (65%) of respondents treat HCV patients during regular outpatient clinics, while 35% treat these patients in a separate setting dedicated to the care of HCV patients. The majority of physicians follow the stipulated dosage regimens of pegylated interferon (88%) and ribavirin (83%). A minority (13%) exceed the advised dosage of ribavirin. Side effects such as neutropenia are mostly managed by decreasing the interferon dosage (42%). Some 35% of physicians reduce ribavirin if haemoglobin levels drop below 5.4 mmol/1, and 41% initiate erythropoietin treatment. Conclusion: Dutch clinical practice reflects the recently issued HCV guidelines. An important area of refinement in treatment of HCV is the management of side effects.

Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was found that results in a 'gain of trypsin function', many other Mutations in the cationic trypsinogen gene, as well as in the gene encoding for pancreatic secretory trypsin inhibitor, have been found in patients with chronic pancreatitis. Furthermore, mutations in other genes, like the mucoviscoidosis-gene encoding for a chloride channel, and in genes encoding for enzymes involved in the metabolism of ethanol, have been linked to chronic pancreatitis. This article reviews the highlights that have been achieved in this field of pancreatic research. Conclusions: Recent data suggest that genetics may play a role in the pathogenesis of pancreatitis.

Objective Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1 – PRSS2 ( rs10273639 ; near the gene encoding cationic trypsinogen) and CLDN2 – MORC4 loci ( rs7057398 in RIPPLY1 and rs12688220 in MORC4 ). We aimed to refine these findings in a large European cohort. Design We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype–phenotype relationships. Results Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). Conclusions The single-nucleotide polymorphisms rs10273639 at the PRSS1–PRSS2 locus and rs7057398 and rs12688220 at the CLDN2 – MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.