Fatty liver has previously often been associated with excessive alcohol consumption. During the last two decades, the interest in fatty liver occurring in non-drinkers i.e. non-alcoholic fatty liver disease (NAFLD) has increased dramatically. Today, NAFLD is considered as the most common liver disease in the developed world. It is strongly associated with obesity, insulin resistance, and hypertension. Thus, NAFLD is considered as the hepatic manifestation of the metabolic syndrome. The spectrum of NAFLD includes: simple fatty liver without necroinflammatory activity; non-alcoholic steatohepatitis (NASH), a condition characterised by hepatocellular injury, inflammation, and fibrosis; cirrhosis; and in some individuals hepatocellular carcinoma. The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the pathologist uses a four-graded scale: 0–3 or none, slight, moderate and severe. In this thesis we show that there is a considerable inter- and intraindividual variation in such scoring methods and that a more standardised and quantitative approach is preferable. The area/volume of fat in liver biopsies is greatly overestimated when assessed semiquantitatively. Moreover, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis. The long-term clinical and histopathological course of 129 consecutively enrolled NAFLD patients was studied. Mean follow-up (SD) was 13.7 (1.3) years. Survival of NASH patients was reduced compared with a matched reference population. These subjects more often died from cardiovascular and liver-related causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain. During follow-up, 17 patients had been prescribed a statin. At follow-up, patients on medication with statins had significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Although patients under statin treatment exhibited a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage. It is concluded that statins can be prescribed safely in patients with elevated liver enzymes because of NAFLD. Alcohol consumption was evaluated with a validated questionnaire combined with an oral interview. In a multivariate analysis moderate alcohol consumption, particularly when frequency of heavy episodic drinking was analysed, consistent with the diagnosis of NAFLD to be set, was independently associated with fibrosis progression in NAFLD. The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. We evaluated the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in our cohort of NAFLD patients. Although the NAS was independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score was limited due to significant overlap in clinical development between NAS-score groups.

No description available.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 5 uppsatser.

Endoskopiska undersökningar har blivit vanligare och ökat i antal. Detta på grund av den  ökade livslängden. Möjligheten att behandla och att bota sjukdomar har också blivit bättre.  Screening av kolorektalcancer leder också till ett ökat antal patienter. De endoskopiska  undersökningarna har tidigare endast utförts av läkare. För att patienterna inte skall behöva  vänta för länge på undersökning har det införts endoskoperande sjuksköterskor runt om i  världen. Omvårdnaden runt de patienter som behöver genomgå endoskopiska undersökningar  är mycket viktig då undersökningarna kan upplevas som obehagliga och smärtsamma.    Syftet är att belysa vad som finns beskrivet angående patienttillfredsställelse och kvalité vid  endoskopiska undersökningar genomförda av sjuksköterskor.      Metod som valts till detta arbete är forskningsöversikt. Sammanlagt ingår 19 artiklar från  olika delar av världen.    Resultatet visar att patienttillfredsställelsen är god och att många patienter föredrar  endoskoperande sjuksköterskor. Kvalitén på undersökningarna var god och i jämförelse med  läkare är sjuksköterskor mer noggranna och finner flera avvikande fynd. Dock tar de  sjuksköterskeutförda undersökningarna längre tid i jämförelse med undersökningar utförda av  läkare.     Enligt denna forskningsöversikt har artiklarna i detta arbete visat att patienttillfredsställelsen  är god vid endoskopiska undersökningar genomförda av sjuksköterskor. Resultatet av denna  studie visar att sjuksköterskor genomför endoskopiska undersökningar med god kvalité och  med hög säkerhet för patienterna. Detta sammantaget med att väntetiderna för  undersökningarna kan kortas med hjälp av sjuksköterskor kan här ses en vinst för patienterna.

<p>Inflammatoriska tarmsjukdomar (IBD) är en av samhällets nya folksjukdomar och ses som ett stort problem. IBD innefattar flera olika sjukdomar som påverkar mag- tarm kanalen, där Ulcerös kolit och Morbus crohn är de största och vanligast förkommande sjukdomarna, dessa kommer att belysas i denna litteraturstudie. IBD sjukdomarna är kroniska, inflammatoriska och uppträder i skov. Syftet med denna studie var att undersöka hur dessa tarmsjukdomar påverkar vuxna individers livskvalitet både psykiskt och fysiskt. Resultatet visar att sjukdomarna påverkar individernas livskvalitet och kan bidra till ångest, depression och social isolering. Mer individanpassad omvårdnad och information borde ges och är viktiga faktorer för hälso- och sjukvården att tänka på vid mötet med individer med dessa diagnoser. Fortsatt forskning kring området bör innefatta just hur stöd kan ges för att individen skall uppleva tillfredställande livskvalitet.</p> / <p>Inflammatory bowel disease (IBD) is a group of widespread diseases and is to be considered a rising problem. IBD involve several gastrointestinal diseases, where Ulcerative colitis and Crohn disease are the most common. These will be illuminated in this literature review. IBD is chronical, involves inflammation and appears in relapsing episodes. The aim of this literature review was to investigate how these gastrointestinal diseases affect the adult individual, both physical and psychological, regarding quality of life. The result showed how IBD might cause anxiety, depression and social isolation. It is of importance that the healthcare system provides individual nursing care and adequate information to individuals suffering from these conditions. Continuing research regarding what way of support these individuals need in order to improve quality of life, ought to be carried out.</p>

Inflammatoriska tarmsjukdomar (IBD) är en av samhällets nya folksjukdomar och ses som ett stort problem. IBD innefattar flera olika sjukdomar som påverkar mag- tarm kanalen, där Ulcerös kolit och Morbus crohn är de största och vanligast förkommande sjukdomarna, dessa kommer att belysas i denna litteraturstudie. IBD sjukdomarna är kroniska, inflammatoriska och uppträder i skov. Syftet med denna studie var att undersöka hur dessa tarmsjukdomar påverkar vuxna individers livskvalitet både psykiskt och fysiskt. Resultatet visar att sjukdomarna påverkar individernas livskvalitet och kan bidra till ångest, depression och social isolering. Mer individanpassad omvårdnad och information borde ges och är viktiga faktorer för hälso- och sjukvården att tänka på vid mötet med individer med dessa diagnoser. Fortsatt forskning kring området bör innefatta just hur stöd kan ges för att individen skall uppleva tillfredställande livskvalitet. / Inflammatory bowel disease (IBD) is a group of widespread diseases and is to be considered a rising problem. IBD involve several gastrointestinal diseases, where Ulcerative colitis and Crohn disease are the most common. These will be illuminated in this literature review. IBD is chronical, involves inflammation and appears in relapsing episodes. The aim of this literature review was to investigate how these gastrointestinal diseases affect the adult individual, both physical and psychological, regarding quality of life. The result showed how IBD might cause anxiety, depression and social isolation. It is of importance that the healthcare system provides individual nursing care and adequate information to individuals suffering from these conditions. Continuing research regarding what way of support these individuals need in order to improve quality of life, ought to be carried out.

Background and aim: Persistent stress and life events affect the course of ulcerative colitis (UC) by largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immuno-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis. Corticotropin releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models. Further cholinergic signalling during stress has been reported to increase bowel ion secretion in humans and uptake of HRP in rodents via activation of mast cells. The overall aim of this thesis was to examine the role of CRH-mediated and cholinergic signalling, and their interaction with mast cells and eosinophils, in the regulation of the mucosal barrier function in the normal human colon and in UC. In vivo studies or the use of surgical specimens for such studies have major shortcomings. Therefore a method with endoscopic biopsies in Ussing chambers was established for studies of protein antigen uptake and electrophysiology in human colonic biopsies, and used in subsequent investigations. Materials and methods: In the four studies a total of 91 healthy volunteers, 3 patients with rectal cancer, and 15 UC patients were included. Biopsies from the sigmoid colon were assessed for macromolecular permeability (Horseradish peroxidase (HRP), and 51Cr-EDTA), and electrophysiology during challenge with sodium caprate (C10), CRH or carbachol. Experiments were repeated with CRH receptor antagonists, carbachol receptor antagonists, mast cell stabilizers and nerve conductance blockers in Ussing chambers. The biopsies were examined by electron and light microscopy for endocytosis of HRP, morphological changes and receptor expression. Moreover, the human mast cell line, HMC-1; was used in studying expression of CRH receptors on mast cells. Results: Endoscopic biopsies of human colon were viable in Ussing chambers, and the technique was shown to be a reliable tool for studies of mucosal permeability to HRP. CRH stimulates transcellular uptake of HRP in human colon via CRH receptor subtypes R1 and R2 on subepithelial mast cells. Further, carbachol acts on muscarinic receptors, located on subepithelial eosinophils. Activated muscarinic M2 and M3 receptors on increased numbers of CRHproducing eosinophils in UC, lead to activation of mast cells and increased macromolecular uptake across the colonic mucosa. This signalling cascade is previously unrecognized, and may be involved in the inflammatory process in UC. Conclusions: In conclusion, we have demonstrated a chain of events leading to increased permeability to the protein antigen HRP in biopsies from healthy volunteers and patients with UC. The important steps begin with a cholinergic signal to muscarinic receptors on the CRH containing eosinophils. The next step includes activation of CRH receptors on mast cells leading to degranulation and increased macromolecular uptake across the epithelium. This explanatory model will have implications for understanding of the pathogenesis of UC and future treatment of the disease.

Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression. In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis. The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment. To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment. The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation. In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis. / Kolorektal cancer är en tumör i kolon eller rektum. I Sverige diagnosticerades år 2014 ca6300 individer med denna cancertyp och ca 2550 personer dör årligen till följd av kolorektalcancer. Operation är det huvudsakliga behandlingsalternativet för kolorektal cancer och vidfjärrmetastaser är överlevnaden &lt; 10 %. Det är därför viktigt att hitta markörer somtillsammans med TNM-stadium kan ge tidig information om sjukdomens prognos och lämpliguppföljning av patienter. Utveckling av kolorektal cancer sker genom ackumulering av genetiska mutationer ochepigenetisk nedreglering av tumörsuppressorgener. Därutöver spelar interaktionen mellantumören och dess närmaste omgivning, innehållande tillväxt- och inflammatoriska faktorer,en viktig roll i tumörens utveckling och metastasering. Syftet med avhandlingen var att studera associationen mellan CD93, PLA2G4C, PDGF-D samtinflammatoriska cytokiner och kolorektal cancer progression. En prospektiv studie visade att CD93 och PLA2G4C SNP var potentiellt viktiga förbedömningav kolorektal cancer prognos. T/T genotypen av SNP rs2749817 i CD93 var associerad medhögre uttryck av CD93 i kolorektal cancer vävnad, främst bland patienter i stadium IV.Därutöver observerades fler återfall efter operation hos patienter med T/T genotypen. Aallelen hos PLA2G4C SNP rs1549637 är en möjligtvis bättre markör för cancerspecifiköverlevnad vid stadium II än faktorer som idag används för att selektera patienter tilladjuvant behandling. Sammantaget antyder detta att T/T genotypen av CD93 och A allelenav PLA2G4C kan vara genetiska markörer relaterade till allvarlig tumörsjukdom ochspridning. Därutöver kan de eventuellt selektera patienter som kräver tätare uppföljning ochadjuvant behandling. För att studera den förmodade inblandningen av PDGF-D i kolorektal cancer undersöktesdess effekt på PDGF-D signalering in vitro. PDGF-D signaleringen förändradegenexpressionen av gener involverade i tumörutveckling och spridning, vilken kundeblockeras av tyrosinkinashämmaren imatinib. Det antyder att PDGF-D signalering kan vara enviktig faktor vid kolorektal cancer progression och ett potentiellt mål för behandling. Analysen av ett flertal inflammatoriska cytokiner visade en korrelation mellan högacytokinnivåer och ökad cancerspecifik och total dödlighet två år efter operation. Höga CCL1och CCL24 nivåer var de enda faktorerna som förblev signifikant associerade medcancerspecifik mortalitet vid fördjupad statistisk analys och bör studeras vidare. Sammanfattningsvis presenterar denna avhandling cirkulerande och genetiska faktorersåsom CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 som eventuellt är viktiga vid bedömning avkolorektal cancer progression tillsammans med TNM stadium.

In a population prevalence questionnaire study we demonstrated that constipation and fecal incontinence are common problems in the general Swedish population with a similar magnitude as in other Western countries. 95.6% of the population had between three bowel movements per day and three per week. Constipation was mostly defined by “hard stools” and “the need of using laxatives”. Irritable Bowel Syndrome (IBS) is characterized by abdominal pain/discomfort and abnormal bowel habits. The diagnostic criteria of IBS are based on clinical symptoms. Division of IBS patients into symptom subgroups appears important as their bowel symptoms are characterized by heterogeneity. International criteria to subgroup IBS (Rome II) are based on expert consensus and not on evidence. We investigated the variation of stool consistency and defecatory symptoms in 135 IBS patients by symptom diary cards. Most patients had alternating stool consistency. When subgroups were based on stool consistency, all kinds of defecatory symptoms (straining, urgency, and feeling of incomplete evacuations) were frequently present in all subgroups. Stool frequency was in the normal range in the majority of patients. We propose that IBS subgroups should be based on stool consistency. We suggest that Rome II supportive criteria must be reconsidered as the determination of presence or absence of specific symptoms does not work as an instrument for categorization of IBS patients into diarrhoea- and constipation-predominant. We also propose that abnormal stool frequency should be excluded to define subgroups of IBS. Alternating stool consistency and presence of different defecatory symptoms, regardless of stool consistency should be included as criteria for IBS. Stress is known to play an important role in the onset and modulation of IBS symptoms. From experimental studies there is evidence for a stress-dependent alteration of visceral sensitivity. The biological mechanisms responsible for the causal link between stress and IBS symptoms are not completely understood, but the hypothalamic-pituitary-adrenocortical axis and the autonomous nervous system seem to play a prominent role in the pathophysiology of IBS. We investigated visceral sensitivity and the effect of repeated maximal tolerable rectal distensions on salivary cortisol levels and skin conductance in patients with IBS, chronic constipation and healthy volunteers. We found that the expectancy of the experimental situation per se (provocation of bowel symptoms by rectal distensions) compared to non-experimental days at home measured as salivary cortisol had a high impact on the level of arousal in IBS. IBS patients had higher skin conductance values than controls in the beginning of distension series and lower rectal thresholds for first sensation, urge and discomfort than healthy controls and constipation patients. IBS patients demonstrated habituation to repeated subjective maximal tolerable rectal distensions according to sympathetic activity although patients continued to rate their discomfort as maximal. Constipation patients had lower sympathetic activity than IBS patients before and during repeated rectal distensions. None of the groups demonstrated a significant increase in cortisol after repetitive rectal distensions. We conclude that Rome II supportive criteria for IBS should be reconsidered according to our findings. IBS patients are more sensitive to pre-experimental stress than healthy controls and patients with constipation. This should be considered in the design of experimental IBS studies. IBS patients habituated to subjective maximal tolerable, repetitive rectal distensions with decreasing sympathetic activity. Since responses to repeated stimuli of close-to-pain intensities are resistant to habituation this finding could be caused by psychological influences on perception, that is, perceptual response bias.

Autoimmune hepatitis (AIH) was identified as an entity by the Swedish professor Jan Waldenström in the 1950s. It was then denoted lupoid hepatitis, characterized by liver inflammation and most often affecting young women. During the years the diagnosis has become more defined (as the non A non B hepatitis has been identified as Hepatitis C) and now can be safely separated from other diseases with liver inflammation. Studies of epidemiological data and long term prognosis have been scarce in the literature. Within a collaboration between the university hospitals in Sweden, we collected what we believe is the largest cohort in the world of patients with AIH. Data from the medical records of 473 individuals was, after AIH-score calculations where the diagnosis was confirmed, collected in a data base, in which most of the analysis was done. Data from the Swedish national registers of cancer, death cause, and birth register was searched for these patients as well as controls. The aim of the thesis was to explore epidemiological and clinical outcome of AIH.The onset of AIH may be at any age, but the incidence seems to increase after 50 years of age; 75% are females, the overall incidence (0.85/ 100,000 inhabitants and year) and prevalence (11/100,000 inhabitants) are figures that are within the range of another but smaller Scandinavian study. Approximately 30 % had cirrhosis already at diagnosis and 87% displayed at some time positive auto-antibodies indicating AIH (Smooth muscle ab and or antinuclear ab).  Indications of future risk for liver transplantation or death is an advanced AIH at diagnosis with liver cirrhosis, decompensated liver disease, elevated PK INR as well as age. Acute hepatitis-like onset seems to carry a lower risk for later liver transplantation or death. Current Swedish national therapy traditions with immune suppression seem to be well tolerated. Five and ten years overall life expectancy does not differ from controls. Thirty-five women gave birth to 63 children, for 3 after liver transplantation of the mother. Thirteen of the women had liver cirrhosis. Current pharmacological treatment seems to be safe both for the patient and the foetus. Thirty percent of the patients experienced flair after delivery. It has been supposed that there is an overrisk for hepatocellular cancer (HCC) associated with AIH. Our figures are the first in the world to be presented that confirms a twenty-three fold overrisk (95% Confidence Interval 7.5-54.3) for hepatobiliar cancer. We found as well an overrisk of non-Hodgkin lymphomas of 13.09 (95% CI 4.2-30.6).Conclusion:  Our epidemiological results confirm that AIH is a fairly uncommon disease, and that many already at time of diagnosis have an advanced disease with liver cirrhosis. There is a clear overrisk for HCC and lymphoma. For those women with AIH who become pregnant the prognosis for the child as well as for the mother is good, even for those women who already have compensated cirrhosis. There is a risk for relapse after delivery. The overall survival for AIH patients with current therapy is good.