| 1. |
- Edshage Hallberg, Karin, 1958
(författare)
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Gastroduodenal epithelial transport in patients with cystic fibrosis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cystic fibrosis (CF) is an inherited disease where respiratory failure due to chronic lung infection is the major cause of death. A defective protein, cystic fibrosis transmembrane conductance regulator (CFTR) alters chloride epithelial transport. Exocrine pancreatic insufficiency is found in 90% of the patients, but in spite of pancreatic enzyme supplements, gastrointestinal problems are common. CF patients have evidence of a disturbed intestinal motility and epithelial transport. The aim of this work was to give new insights to the altered function of the CF gut and thereby to improve the understanding of the coupling between the clinical expression and pathology of the disease and the basic defect. We used gastroduodenal manometri combined with intragastric perfusion to investigate fasting motility and motility secretion in 10 CF patients with different genotypes and 12 healthy controls. Eight CF patients showed a normal migrating motor complex. Motility related gastric secretion of acid and bicarbonate did not differ from healthy subjects while gastric net fluid secretion was significantly decreased and bilirubin reflux was significantly increased in the CF patients. Motility related secretion of gastric IgA was studied in ten CF patients and seven healthy controls. The CF patients had significantly lower levels of gastric IgA compared to healthy subjects during phase II and III of the migrating motor complex. Chloride secretion in duodenal biopsies from nine CF patients with different genotypes where investigated in an Ussing chamber. Prostaglandin E2 and acetylcholine induced no changes in chloride secretion in the DF508 homozygotes. In heterozygotes, the induced change in chloride secretion corresponded to the severity of the known mutations. The urinary excretion of orally given lactulose, L-rhamnose and xylose was studied in 19 CF patients and nine healthy controls. Patients who were homozygous or heterozygous for ?F508 had significantly higher lactulose/L-rhamnose excretion ratios, than patients with unidentified genotypes who had excretion ratios in the same range as in healthy controls.Conclusions: Our studies suggest that patients with CF have a normal fasting motility pattern in the upper gastrointestinal tract. Despite this, there were abnormalities in epithelial transport related to genotype, thus indicating a role of CFTR in the transport of fluid, IgA and small molecules. We also found that patients with CF with impaired pancreatic bicarbonate secretion had normal gastric bicarbonate secretion in fasting.
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| 2. |
- Börjesson, Lars, 1963
(författare)
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Neuromuscular function in the normal and inflamed colon. An experimental study in rat
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuromuscular function of the longitudinal muscle layer of distal colon was investigated in segments from normal rats and from rats with colitis induced by dextran sulphate sodium (DSS) at 3% for 3 or 7 days or 5% for 7 days. The study was performed in vitro, on spontaneous tone, or after precontraction. Guanethedine was present to block noradrenergic neurotransmission.Intrinsic nerves were activated by DMPP, an agonist at ganglionic, nicotinic receptors, K+, or McN-A-343, an agonist at preferentially muscarinic, neuronal receptors. The pharmacological analysis of the neurogenic response to the respective compound revealed that DMPP and K+ elicited relaxations being dependent on purinergic and nitrergic neurotransmission, and possibly also on vasoactive intestinal peptide (VIP). In contrast, the relaxation to McN-A-343 was seemingly dependent solely on ATP. While the response to K+ utilized the cGMP and the cAMP transduction systems for relaxation, that to McN-A-343 was independent of these two intracellular pathways. DSS induced dose-dependent inflammation in the distal colon. Tissue weight, optimal preload, response to carbachol, tone and phasic contractile activity was increased in segments from rats treated with 5% DSS. The adaptive relaxatory response to preload was abolished in DSS treated animals, possibly due to impaired nitrergic neurotransmission. In animals treated with 5% DSS, some results indicate prevailing inhibition of the colon muscle mediated by (non-neurogenic) nitric oxide, which could be an effect of the inflammation.It is concluded that non-adrenerig, inhibitory neurotransmission in rat distal colon depend on ATP, nitric oxide and VIP and that activation of muscarinic, neuronal receptors may selectivly release ATP. DSS colitis induce myogenic, neuronal, and possibly also paracrine alterations of the neuromuscular function in rat distal colon
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| 3. |
- Carlsson, Eva, 1959
(författare)
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Body composition and quality of life in patients with IBD, ileostomy and short bowel syndrome
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with IBD are at risk for intestinal disability (e.g. having a stoma, malnutrition). The general aim of the thesis was to investigate physiological, psychological and social consequences of having IBD and an ileostomy or short bowel syndrome (SBS).Patients and Methods: Six SBS patients were interviewed to investigate practical aspects on daily life. In 21 ileostomates, and 19 patients with SBS, bioelectric impedance spectroscopy (BIS) was compared with other methods for determination of water compartments and fat free mass (FFM). Differences were analysed using the Bland-Altman method. Concerns, health related quality of life (HRQOL), quality of life (QOL) and coping were assessed in 21 patients with an ileostomy and 28 patients with SBS. HRQOL were compared with a matched group from the general population. Results: The differences between methods (BIS, Dual-energy absorptiometry (DXA), Dilution and derived estimates) to assess total body water (TBW) and FFM were pronounced. The mean difference of extracellular water (ECW) between dilution and BIS was less in female ileostomates than male, (p<0.01). Hydration of FFM assessed by BIS gave a mean of 0.77 for ileostomates and 0.75 for SBS patients. Most SBS patients were maintained in a stable clinical condition within normal limits of body weight and BMI.The most serious limitation of every day life for SBS patients was the planning involved to get most out of life. Dominating concerns for the ileostomates were intimacy, access to quality medical care and energy level and for the SBS patients being a burden, further surgery and energy level. Vitality was significantly reduced in ileostomates. In SBS patients all dimensions in HRQOL were significantly reduced except physical function. More than 1/3 of SBS patients rated health worse or much worse than one year ago. Most definitions on " good quality of life " were found in the social dimension. Most " obstacles to good quality of life" were found in the psychological dimension for the ileostomates and in the physical dimension for the SBS patients. Perceived QOL was rated 70/100 for ileostomates and 64/100 for the SBS patients. Confrontation was the dominating coping style.Conclusion: The differences between methods to assess body water compartments and FFM were pronounced. Methods could not be used interchangeably. BIS should be further evaluated with repeated, longitudinal measurements. The high concern for being a burden needs further investigation and how it can be reduced. Concern for intimacy as the concern for loss of sexual drive and sexual performance needs to be further explored. Fatigue needs to be defined. It is also necessary to study how concern changes over time. Integrating items of concern into counselling may result in greater coping ability and improved QOL.Key words; inflammatory bowel disease, Crohn´s disease, ulcerative colitis, short bowel syndrome, quality of life, health related quality of life, coping, concern, body composition, bioelectric impedance spectroscopy, Dual-energy absorptiometry, total body water
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| 4. |
- Ekstedt, Mattias, 1976-
(författare)
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Non-Alcoholic Fatty Liver Disease : A clinical and histopathological study
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 5. |
- Johansson, Jan-Erik, 1963
(författare)
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Gastro-intestinal toxicity related to haemopoietic stem cell transplantation with a special focus on the intestinal barrier function
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The myeloablative, cytotoxic therapy (conditioning treatment) prior to haemopoietic stem cell transplantation (HSCT) has the combined purpose of eliminating leukaemic or cancer cells located in the bone marrow or elsewhere in the body and, in the allogeneic setting, of suppressing the immune response of the recipient to prevent marrow rejection. The unwanted effect is the inevitable elimination of normal, haemopoietic stem cells, a lethal effect which is circumvented by the following administration of haemopoietic stem cells from the patient (autologous HSCT) or from a related or an unrelated donor (allogeneic HSCT). However, normal tissues with a high cell-turnover rate, primarily the gastro-intestinal (GI) tract, will likewise be affected. Besides causing significant GI symptoms, this injury includes a disruption of the intestinal barrier, facilitating the permeation of bacteria and endotoxin through the bowel wall, with subsequent septicaemia and release of cytokines, known to be important mediators of graft-versus-host disease (GVHD), the primary complication of allogeneic HSCT. Accordingly, murine HSCT-models have suggested that after intensification of the conditioning treatment, GVHD has been amplified as a result of aggravated GI toxicity.Using a 51Cr-EDTA resorption test, the present study investigates the intestinal-barrier function in HSCT patients receiving myeloablative or reduced intensity conditioning (RIC). It also investigates whether the strengthening of the GI immune system by the oral administration of an immunoglobulin preparation would modify intestinal barrier integrity during autologous HSCT. Finally, on the basis of the observation that the impairment of intestinal barrier integrity by non-steroidal anti-inflammatory drugs (NSAID) is due to an early disturbance of energy metabolism in enterocytes, the existence of a similar mechanism in chemotherapy was searched for. Using high-performance liquid chromatography (HPLC) technique and 51Cr-EDTA resorption, the purine-nucleotide content in enterocytes and intestinal permeability was determined in rats after chemotherapy.It was found that the intestinal barrier was disrupted preceding clinical symptoms with myeloablative conditioning, but preserved with RIC. The oral administration of an immunoglobulin preparation revealed ameliorated intestinal barrier integrity during autologous HSCT. In rats, an early-detectable disruption of the intestinal barrier was found which parallels a decrease in purine-nucleotide content in enterocytes, reflecting a metabolic disturbance.A hypothesis may be formed containing an early intestinal-barrier disruption with chemotherapy, initiated by a metabolic disturbance in enterocytes. Since murine data revealed aggravated GVHD with increased intestinal injury, the preserved intestinal integrity with RIC should have the potential of reducing GVHD severity. These observations suggest that the intestinal barrier function has a central role to play in the intestinal damage induced by cytotoxic therapy as well as in GVHD.
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| 6. |
- Karling, Pontus, 1965-
(författare)
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The emotional motor system and gastrointestinal symptoms
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a significant comorbidity between anxiety/depression and functional gastrointestinal syndromes, such as irritable bowel syndrome (IBS) and functional dyspepsia. The pathophysiological link between emotions and the gut is not known. A model of an emotional motor system (EMS) which reacts to interoceptive and exteroceptive stress has been proposed. EMS consists of specific brain structures including anterior cingulate cortex (ACC), amygdala, hippocampus and hypothalamus and mediates their communication to the rest of the body (including the gastrointestinal tract) through the hypothalamus-pituitary-adrenal (HPA) axis, the autonomic nervous system (ANS) and by a pain modulation system. The aim of this thesis was to test the EMS model by studying the relationship between symptoms of anxiety and depression and IBS-like symptoms in patients with recurrent unipolar depression, in patients with IBS and in a sample of a normal Swedish population. The peripheral limb of EMS (ANS, HPA axis and the pain modulations system) was tested in patients with IBS and control subjects. Spectral heart rate variability was used to investigate ANS function in patients with refractory IBS and in healthy controls. The HPA axis function was tested by a weight adjusted low dose dexamethasone suppression test in control subjects. The influence of catecholamine degradation on pain modulation was tested by analyzing val158met catechol-o-methyl transferase (COMT) polymorphism in patients with IBS and in control subjects. We found a significant relationship between symptoms of anxiety/depression and IBS-like symptoms in patients with recurrent unipolar depression, in patients with IBS and in a sample of the normal population. Interestingly, patients with recurrent unipolar depression in remission had no more IBS-like symptoms than controls, indicating that the gastrointestinal symptoms may resolve when depression is treated to remission. Patients with IBS have an increased mid-frequency power in rest and in supine position (after tilt test) compared to healthy controls indicating an increased sympathetic ANS drive. The symptoms of diarrhea and early satiety has in the litterature been associated to the stimulation of corticotropin releasing hormone (CRH) receptors and was also in our study related to HPA axis function tested by a low dose dexamethasone test. Interestingly both hypo- and hyperfunction of the HPA axis was related to these symptoms in control subjects. The val158met COMT polymorphism was associated to IBS-like symptoms. Control subjects with IBS-like symptoms (defined by the upper quartile in total GSRS-IBS score) had a higher frequency of the met/met and a significantly lower frequency of the val/met genotype. Also patients with IBS tended to have a lower frequency of the heterozygous val/met genotype so we conclude that this genotype may be protective against IBS/IBS like symptoms. In addition, the val/val genotype in patients with IBS was associated to diarrhea symptoms. Conclusions: Our results support the model of an emotional motor system in the genesis of functional gastrointestinal symptoms by the finding of the association of IBS-like symptoms and mood disturbances, and by finding alterations in the peripheral limbs of EMS (ANS, HPA axis and catecholamines) in subjects with IBS and IBS-like symptoms.
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| 7. |
- Simrén, Magnus, 1966
(författare)
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Irritable bowel syndrome. Pathophysiological and clinical aspects
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Irritable bowel syndrome (IBS) is characterized by abdominal pain and/or discomfort related to abnormal bowel habits. Gastrointestinal (GI) motility disturbances, visceral hypersensitivity and psychological factors are involved in the pathophysiology of IBS. A number of unresolved issues regarding pathophysiology and the clinical presentation of IBS were studied.In IBS patients high-resolution manometry disclosed a higher proportion of duodenal individual pressure waves that propagated in a retrograde direction. This was especially pronounced postprandially. Combined high-resolution analysis and a detailed cluster analysis demonstrated abnormal findings in 22/26 (85%) patients compared with 10/26 (38%) with conventional manometric analysis. After duodenal lipid infusion, IBS patients increased their perceptual sensitivity in the sigmoid colon (barostat study) and showed an altered viscerosomatic referral pattern. This reaction was significantly more pronounced than in the controls.Abnormal levels of motilin in plasma and peptide YY (PYY) in the ascending colon were observed in IBS compared with the controls. IBS patients who presented predominantly with diarrhea, compared with those with constipation, exhibited lower plasma levels of motilin and higher levels of corticotropin releasing factor (CRF) and lower levels of neuropeptide Y (NPY) in colonic biopsies.A relationship between GI symptoms and food intake was reported by 63% of IBS patients. Female sex and anxiety predicted a high degree of subjective food intolerance.Quality of life (QOL) was reduced in IBS patients at referral centers compared with primary care. This difference was only obvious in females. Fatigue was related to other aspects of QOL, such as depression, anxiety, well-being and gastrointestinal symptom severity as well as gender.Conclusions: Food-related GI symptoms are common in IBS and may in part be explained by an exaggerated sensory component of the gastrocolonic response. IBS patients show an abnormal propagation pattern of individual duodenal pressure waves. Abnormal levels of motilin, CRF, PYY and NPY may be involved in the pathophysiology of IBS. IBS female patients seen at referral centers constitute a highly selected group with reduced QOL. Fatigue is a common symptom in IBS related to general well-being and psychological and subjective gastrointestinal symptoms.
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| 8. |
- Wallon, Conny, 1966-
(författare)
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Neuro-immune regulation of macromolecular permeability in the normal human colon and in ulcerative colitis
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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 stresshas 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.
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| 9. |
- Walter, Susanna, 1969-
(författare)
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Irritable Bowel Syndrome : Diagnostic Symptom Criteria and Impact of Rectal Distensions on Cortisol and Electrodermal Activity
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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 hadalternating 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.
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| 10. |
- Werner, Mårten, 1967-
(författare)
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Autoimmune hepatitis in Sweden
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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