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BACKGROUND: Cyst infection may occur in autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD). Antimicrobial agents often fail to control infection, leading to invasive action. We aimed to identify factors predicting escalation of care. METHODS: ADPKD and ADPLD patients were identified from local/national databases (2001-2013). Records were screened for patients meeting criteria for cyst infection (positive cyst aspirate and/or clinical findings). Factors that predict escalated care were identified with multivariate modified Poisson regression. RESULTS: We screened 1773 patients. A total of 77 patients with cyst infection (4.3%) were included for analysis (hepatic 36%; male 49%; age 54 ±; 13 years; ADPKD 95%; dialysis 9%, diabetes 18%, renal transplant 56%, eGFR [IQR 24-78] ml/min/1.73 m2 (excluding patients with a history of renal transplant or receiving dialysis)). A pathogen was identified in 71% of cases. Escherichia coli was the most common pathogen and accounted for 69% of cases. Initial treatment was limited to antibiotics in 87% of patients (n = 67), 40% included a fluoroquinolone. Ultimately, 48% of patients underwent some form of invasive action (escalation of care). Increasing white blood cell count (WBC) (RR 1.04 95%-CI 1.01-1.07, p = 0.008) was associated with escalating care, whereas an increase in time between transplant and infection (RR 0.92 95% CI 0.86-0.97, p = 0.005) and E. coli isolation (RR 0.55 95% CI 0.34-0.89, p = 0.02) were protective. CONCLUSION: High serum WBC, isolation of atypical pathogens and early infection after transplantation are factors that increase the risk of escalation of care in hepatic and renal cyst infection patients.

Item does not contain fulltext Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon-alpha can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and clinicaltrials.gov for articles and abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty-four studies matched our criteria, representing a total of 105 ribavirin-treated and 8 pegylated interferon-treated patients. The majority of patients had a solid organ transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon-treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.

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.To establish long-term outcome and safety of lanreotide.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.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).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.

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, Mann-Whitney 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.

Pain is the major symptom of chronic pancreatitis. The role of genetics in pancreatic pain is unclear. Catechol-O-methyltransferase (COMT) regulates enkephalin levels and influences pain perception. The COMT gene contains functional polymorphisms that have been found to influence human pain perception. The aim of our study was to investigate COMT single-nucleotide polymorphisms (SNP s) and diplotypes in chronic pancreatitis patients and healthy controls.We genotyped four COMT gene SNP s: c.1-98AG (rs6269), c.186CT (p.=) (rs4633), c.408CG (p.=) (rs4818) and c.472GA (p.Val158Met) (rs4680) using a dual-colour discrimination assay in 240 chronic pancreatitis patients and 445 controls. We generated five diplotypes with a frequency0.5% and compared prevalence between patients and controls.There was no significant association between the SNPs in the COMT gene and chronic pancreatitis. The diplotype ATCA÷ACCG was more prevalent in controls compared with patients (OR 0.48, 95% CI 0.24 to 0.93, p=0.03) where the most common diplotype GCGG ÷ATCA served as reference. However, after correction for multiple testing, this is not a significant difference. The distribution of other diplotypes was not significantly different between patients and controls.COMT SNP s and diplotypes are not associated with chronic pancreatitis. As a consequence, our results do not support a significant role for the COMT gene in chronic pancreatitis.

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 (P0.001).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.

Twenty to fifty per cent of patients with chronic hepatitis C (CHC) experience nonresponse to current antiviral therapy, which may relate in part to ribavirin or PEG-interferon pharmacodynamics. We evaluated potential relevance of various factors for nonresponse. Two hundred forty-two naive CHC patients who received in a previous trial at least 24 weeks of antiviral therapy, including PEG-interferon alfa-2b and ribavirin, were analysed. Of them, 53% were infected with hepatitis C virus (HCV) genotype 1-4, 71% exhibited high viral load and 32% had severe fibrosis/cirrhosis. After 24 weeks of treatment, 39 patients (16%) were nonresponders. In multivariate analysis, lower serum ribavirin concentrations, HCV genotype 1-4 and higher baseline γ-GT predicted nonresponse. Week-24 ribavirin concentrations (2.2 vs 2.8 mg/L, P0.001), average ribavirin doses (14.5 vs 15.2 mg/kg per day, P = 0.03) and week-24 haemoglobin decreases (1.7 vs 2.0 mm, P = 0.02) were lower in nonresponders. Nonresponse rates increased progressively at decreasing ribavirin concentrations: 4%, 11%, 13% and 36% in case of serum ribavirin concentrations ≥4, 3-4, 2-3 and ≤2 mg/L, respectively (P = 0.001). Ribavirin concentrations correlated with both week-24 haemoglobin decreases (r = 0.42, P0.001) and ribavirin doses (r = 0.17, P = 0.01). Subgroup analysis in HCV genotype 1-4 patients revealed essentially the same results. Nonresponse was exceptional in HCV genotype 2-3 patients and associated with ribavirin concentrations2 mg/L. Presumed interferon-related factors (average PEG-interferon doses and decreases in leucocytes, granulocytes, platelets and body weight) did not differ between nonresponders and responders. In conclusion, ribavirin- rather than PEG-interferon-related factors are independent and potentially modifiable predictors of nonresponse in treatment-naive CHC patients.

Complications occurred in a 41-year-old woman (case 1) following a first attempt to remove a partial denture by oesophagoscopy. These were: laceration of the oesophagus with subsequent mediastinitis, pneumothorax, and pneumopericardium. With a second oesophagoscopy the denture was removed from the oesophagus using a flexible endoscope with a latex hood. Following antibiotic treatment the patient recovered. With a 45-year-old man (case 2) who had also swallowed a denture, the denture initially could not be localized. It was eventually recovered from the gastric antrum using a flexible scope with a latex hood, also in the second attempt. Psychiatric and mentally handicapped patients run a high risk of denture ingestion. Ingested dental prostheses are often radiolucent, and are difficult to visualize using conventional radiological methods. Extraction of the ingested foreign objects can lead to severe complications. This is why in this type of case, we recommend having an expert remove from a foreign object with the use of a flexible scope fitted with a latex hood. It is advisable to make removable dental prostheses radiopaque or to avoid using them with the identified risk-group.

Chronic hepatitis C virus (HCV) is transmitted by blood-blood contact and this leads to high HCV prevalence in risk populations such as haemophilia patients and intravenous drug users. The prevalence in the general Dutch population is unknown, although it appears to be very low in screened blood donors (0.0169%).The objective of this study is to estimate the prevalence of HCV in a general population sample living in an urbanized region in the Netherlands.We randomly selected 2200 EDTA blood samples that had been submitted for analysis of biochemical parameters to a regional servicing laboratory for general practitioners (SHO, Arnhem/Nijmegen, the Netherlands). HCV antibody testing was performed using a three-step approach. For initial screening, an enzyme immunoassay (Bioelisa HCV 4.0, Biokit, Spain) was used. Positive samples were subjected to a second, microparticle enzyme-linked immunoassay (AxSYM HCV version 3.0, Abbott laboratories, IL , USA). Genotypes were determined by Line Probe Assay.A total of four persons (two females, two males) (0.2%) tested positive for HCV antibodies. The average OD/cut-off ratio of the screening assay was 2.9 (range 1.0 to 7.3) and serological findings were confirmed using a specific second immunoassay. HCV RNA (genotype 1b) was found in the sera of two persons.The HCV prevalence in our sample of the Dutch population was 0.2% which accords with earlier estimates from prevalence studies in the Netherlands.

In conscious dogs with complete atrioventricular block, overdrive pacing of the idioventricular rhythm normally results in overdrive suppression (OS). Frequently, however, we observed another response to overdrive, that is, QRS complex or complexes with unexpectedly short coupling intervals followed by normal OS. We have named such a QRS complex a "premature escape beat" (PEB). Based on the response of PEBs to electrical stimulation, we postulate that PEBs are based on triggered activity resulting from delayed afterdepolarizations. This hypothesis was tested in 82 experiments by 1) stimulation under control conditions and in combination with 2) subtoxic and toxic amounts of ouabain 20-50 micrograms/kg, 3) lidocaine 3 mg/kg, and 4) doxorubicin 16-24 mg/m2. The stimulation protocol, which was repeated at random five to 10 times, consisted of 10 and 50 stimuli using interstimulus intervals of 200, 400, 600, and 800 msec. This protocol was not only performed during spontaneous idioventricular rhythm but also during a continuously paced rhythm with interstimulus intervals of 800 msec. It was found that 1) the chance to induce a PEB or PEBs increased and 2) their first postpacing interval significantly decreased using short or fast drives, or both. Ouabain increased significantly and in a dose-dependent manner 1) the ability to induce PEBs and 2) the number of PEBs per stimulation-train, and also shortened their first postpacing interval. Opposite effects were seen after lidocaine, doxorubicin, and continuous pacing as follows: 1) a lower incidence of PEBs and 2) lengthening of their first postpacing interval. These results support our hypothesis that PEBs are based on triggered activity resulting from delayed afterdepolarizations.

A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease.To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour.We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics.The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes.The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.

Contains fulltext : 52563.pdf (Publisher’s version ) (Closed access) Clinical features of liver involvement due to Listeria monocytogenes infection in adults are rarely reported in literature. This is surprising, regarding the current opinion that the portal system is extensively involved in the first stages of pathogenesis in invasive L. monocytogenes disease. A literature search in the PubMed and Embase database revealed 34 cases with clinical features of hepatic involvement due to listeriosis. We systematically analyzed all case reports with respect to clinical manifestations, treatment and outcome. In addition, we added clinical information on a patient diagnosed with a solitary liver abscess due to L. monocytogenes, who was seen at our institution. This review describes the different presentations of liver-involvement reported in listeriosis; solitary liver abscess, multiple liver abscesses and diffuse or granulomatous hepatitis. Distinction between these different forms of liver involvement is clinically relevant as they have a different outcome. We delve into the different pathogenic events leading to different forms of liver involvement. In addition, diagnostic modalities and possible treatments are reviewed.

Polycystic liver disease (PCLD, MIM 174050) is a dominantly inherited condition characterised by the presence in the liver of multiple cysts of biliary epithelial origin. It must be distinguished from autosomal dominant polycystic kidney disease type 1 (ADPKD-1, MIM 173900) and type 2 (ADPKD-2). Both disorders may be complicated by polycystic liver disease, but renal involvement is absent in PCLD. PCLD is often asymptomatic, but if symptoms arise, they are usually due to the mass effect of cysts. The phenotype is more severe in females and correlates with the number of pregnancies or estrogen use. The gene for PCLD has been assigned to chromosome 19p13.2-13.1. Two separate large-scale positional cloning efforts have managed to identify PRKCSH as the gene underlying PCLD. Up to now, all mutations found in PRKCSH introduce stopcodons in the m-RNA, resulting in premature termination of translation to protein. This suggests a loss of function of the encoding protein. The protein, designated by us as hepatocystin, is predicted to be localised in the endoplasmic reticulum. Multiple biological roles have been suggested for hepatocystin, such as a substrate for phosphorylation by protein kinase C, binding to advanced glycation endproducts, and a function as the non-catalytic beta-subunit of glucosidase-II. The role of hepatocystin in PCLD, however, remains to be elucidated.

A 63-year-old male was referred because of colicky pain due to an intussusception of a Meckel's diverticulum and of the ileum into the cecum.