Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery. / Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindring och det är oftast förstahandsval vid behandling av patienter med PS. Flera faktorer påverkar tillgängligheten av LD, bl.a. den hastighet som magsäcken tömmer sig med och denna verkar förlångsammad hos personer med PS vilket ger sämre tillgänglighet av LD i blodet och därmed i hjärnan. LD bryts även ner i hög grad av olika enzym ute i kroppen vilket leder till mindre mängd LD som hamnar i hjärnan och till fler nedbrytningsprodukter som orsakar biverkningar. Tillägg av enzymhämmare leder till ökad mängd LD som kan nå hjärnan och omvandlas till DA. Det anses viktigt att undvika höga toppar av LD i hjärnan då dessa verkar bidra till utvecklandet av besvärliga motoriska komplikationer hos patienter med PS. Om LD ges mer kontinuerligt, exempelvis som en kontinuerlig infusion in i tarmen eller i blodet, så minskar dessa motoriska komplikationer. Inopererande av stimulatorer i vissa delar av hjärnan (DBS) har också visat sig minska dessa motoriska komplikationer och även resultera i att man kan minska LD-dosen. Huvudsyftet med den här avhandlingen är att studera LD hos patienter med PS; i blod och fettvävnad då LD ges i tablettform och se om det finns något samband med LD-upptag och hastigheten på magsäckstömningen (MT) och om kontinuerligt given LD påverkar LD-upptaget eller MT; i blod och i ryggmärgsvätska då enzymhämmarna entakapon och karbidopa tillsätts LD; i hjärna vid behandling med DBS och då LD ges både som tablett och som infusion i blodet. Sammanfattningsvis kan vi se att LD-upptaget är mer gynnsamt hos patienter med PS i tidigare skede av sjukdomens komplikationsfas. MT är förlångsammad hos patienter med PS och det är inget tydligt samband mellan LD-upptag och MT eller mellan MT och sjukdomsgrad. Kontinuerligt given LD minskar LDnivåerna. Enzymhämmaren entakapon ökar den maximala koncentrationen av LD i blod och ryggmärgsvätska och effekten är mer tydlig vid tillägg av karbidopa vilket är viktigt att ta i beaktande vid behandling av PS för att undvika höga toppar av LD i hjärnan. LD ökar i hjärnan då man behandlar med LD i tablettform och som infusion i blodet och DA-nivåerna i hjärnan följer LD väl vilket visar på att patienter med PS fortfarande kan omvandla LD till DA trots trolig uttalad brist av de DA-producerande nervcellerna i hjärnan. DBS verkar öka DA i vissa områden i hjärnan och tillsammans med LD-infusion i blodet verkar det även öka LD i hjärnan och det kan förklara varför man kan sänka LDdosen efter DBS-operation.

Bakgrund: Inflammatorisk tarmsjukdom (IBD) inkluderar Ulcerös kolit och Crohns sjukdom som kännetecknas av återkommande inflammation i tarmen. Etiologin för sjukdomarna är fortfarande okänd och forskning visar en ökning, framför allt i Europa. För att främja hälsa trots en livslång sjukdom behöver individen ta ansvar för att anpassa sin sjukdom genom egenvård, detta för att förebygga exacerbation. Syfte: Syftet med studien var att sammanställa personers upplevelser av att anpassa sitt liv utifrån sin kroniska inflammatoriska tarmsjukdom.  Metod: En beskrivande litteraturstudie baserat på 12 kvalitativa studier. Databaserna som användes vid artikelsökningarna var PubMed och CINAHL. Sökbegränsningarna var engelska, människor och 10 år.  Resultat: En återkommande upplevelse bland personerna med IBD var att livet blev begränsat både gällde skola- och arbetsliv, det sociala livet och kosten. För att anpassa sitt liv med en IBD-sjukdom upplevde personerna att kunskap och stöd från andra var betydande. För att hålla sjukdomen i remission upplevdes behandlingar och kostanpassningar vara en viktig fördel. Upplevelsen av sig själv förändrades där en känsla av att inte vara normal var vanligt, att acceptera och hitta mening i livet var en viktig anpassning och resulterade i ett bättre mentalt välbefinnande. Slutsats: Sjukdomen upplevdes skapa begränsningar i det dagliga livet och ändrade självbilden hos personerna. Att acceptera sitt liv med IBD ansågs vara en viktig anpassning för att skapa möjlighet till att leva sitt liv utan dessa upplevda begränsningar. Enligt författarna kommer resultatet ge sjuksköterskor en ökad förståelse gällande omvårdnaden för personer med en IBD-sjukdom samt möjliggöra en fungerande egenvård för dessa personer. / Background: Inflammatory bowel disease (IBD) include Ulcerative Colitis and Crohn’s disease who are characterized by recurrent inflammation in the bowel. The etiology of the diseases is still unknown, and research shows that it’s increasing, especially in Europe. To promote health despite a lifelong illness, the individual needs to take responsibility for their self-care to keep the disease in check. Aim: The aim of this study was to describe persons experience of adapting their life with their inflammatory bowel disease. Method: A descriptive literature study based on 12 qualitative studies. The databases used were PubMed and CINAHL. The study's limitations were English, humans, and 10 years.  Results: A recurring experience among people with IBD was that life was limited in school, work, social life and diet. Knowledge and support from others were important to adapt to a life with IBD. To keep the disease in remission, treatments and dietary adjustments were perceived as an important advantage. The experience of yourself changed, where a feeling of not being normal was common. Patients who were able to accept their disease, and who also transcended to find a higher purpose, ultimately improved their mental health.   Conclusion: The disease creates limitations in daily life and changes the self-image of people. Accepting a life with IBD was an important adjustment to create the opportunity to live one's life without these perceived limitations. According to the authors, the results will give nurses an increased understanding of caregiving and improved self-care for people with IBD.

<p>Increased visceral pain is often seen in patients with gastrointestinal (GI) inflammation. Some studies, however, have suggested that such pain may persist after resolution of damage or inflammation. Despite the debilitating pain associated with GI inflammation, and its significant impact on affected individuals, few studies have addressed this issue. We hypothesized that altered visceral pain responses would persist after resolution of a bout of colitis in an animal model of colitis. We studied the pain responses to colorectal distention in Wistar rats with dinitrobenzene sulfonic acid (DNBS)-induced colitis, using changes in heart rate as an index of pain. Colonic inflammation had resolved by day 15 after DNBS administration. The assessment of colonic inflammation was based on histological scores, colonic tissue pro-inflammatory cytokine levels and myleoperoxidase activity. Rats examined at 15 days post-DNBS administration exhibited diminished pain responses to colorectal distention as compared to healthy rats. This was associated with significant increases in colonic tissue levels of IL-4 and IL-10 as compared to healthy rats, indicating a possible role for these anti-inflammatory cytokines in counteracting the generation of pain and hyperalgesia. We also studied the effects of hydrogen sulfide (H2S) in our animal model, by administering inhibitors of two of the key enzymes involved in the production of H2S. Our results demonstrated that inhibition of H2S production did not significantly alter the pain responses observed in rats at 15 days post-DNBS administration. In summary, our results demonstrate altered autonomic responses to colorectal distension following resolution of colitis. Further research on the role of anti-inflammatory cytokines and H2S may help to determine the mechanism underlying this effect.</p> / Master of Science (MSc)

Introduction: Functional motility disorders of the colon are poorly defined. Hence, patients with chronic colonic motor dysfunction are treated or undergo surgery without proper diagnosis. Most colonic motility assessment centers around the largest propagating motor pattern in the colon- the High Amplitude Propagating Pressure Wave (HAPW). However, there is no consensus regarding a definition of this important motor pattern. Additionally, no consideration is given to other aspects of colonic motility such as colo-ano-rectal coordination and control by the autonomic nervous system (ANS). The aim of this thesis was to improve understanding of HAPWs and other features of colonic motility in health and constipation, understand how autonomic dysfunction is related to observations in patients, and evaluate the effect of neuromodulation of the ANS. Methods: Motility was assessed in healthy volunteers and patients using water-perfused High Resolution Colonic Manometry (HRCM). To assess the association between ANS and colonic motor activity Heart Rate Variability (HRV) was measured in patients. Spatiotemporal maps were created using HRCM to analyse and quantify colonic motor activity following baseline, and interventions which included proximal balloon distention, meal, and rectal bisacodyl. Low-Level Light Therapy (LLLT) was also applied during HRCM as a method of neuromodulation, to observe its effect on colonic motility. Results: Normal HAPWs are those which have an amplitude of more than 50 mmHg and belong to one of 3 categories: proximally originating, proximal continuing, and transverse/descending. The best intervention sequence to generate these during HRCM assessment is baseline, proximal balloon distention, meal, rectal bisacodyl. Based on their responses to these interventions and the type of HAPWs present, patients could be classified into strong responder, weak responder and non-responder groups. Overall, patients in the strong responder group were most similar to healthy volunteers both with regard to motility and ANS control. Conversely, the weak and non-responders had showed decreased or no motility with decreased parasympathetic input and occasionally sympathetic inhibition. Additionally, other features of motility such as the sphincter of O'Beirne, and lack of colo-ano-rectal coordination were found to lead to constipation even in presence of normal HAPWs. LLLT shows promise in initiating colonic motor activity through neuromodulation of the sacral defecation center. Conclusions: HAPWs can be defined into one of three categories and used to categorize patients based on their HAPW response to different interventions. However, other aspects of colonic motility such as the colo-ano-rectal coordination and autonomic nervous system control of colonic motility should be taken into consideration in diagnosis of constipation, as they can point towards more non-invasive treatment methods such as neuromodulation using LLLT. / Thesis / Master of Science in Medical Sciences (MSMS)

Erosiv esofagit (EE) innebär uppkomst av inflammation och slemhinneskador i matstrupen. Den huvudsakliga orsaken till EE är gastroesofageal reflux (GERD), då det sura maginnehållet stöts upp i matstrupen. Bristande funktion av nedre esofagussfinktern (LES) och diafragmabråck kan också orsaka EE. Obehandlad EE kan leda till komplikationer såsom Barretts esofagus (BE), adenocarcinom, förträngning av matstrupen och gastrointestinala blödningar. Diagnostiken sker med hjälp av endoskopi. Behandlingen av EE går bland annat ut på att påskynda läkning av slemhinneskador i matstrupen. Den består huvudsakligen av läkemedelsterapi och livsstil- och kostförändringar, men även kirurgi kan vara en möjlig behandling. Läkemedelsterapi består av syrahämmande läkemedel som hämmar produktionen av magsyra. Protonpumpshämmare (PPI), till exempel lansoprazol (LPZ), är standardbehandlingen vid syrarelaterade sjukdomar, bland annat EE. PPI har dock begränsningar och upp till 20 % med svårare EE uppnår inte läkning. Vonoprazan (VPZ) tillhör kalium kompetitivasyrablockerare (P-CAB) och är ett nytt syrahämmande läkemedel som är godkänt i bland annat Japan och USA för behandling av EE. Syftet med detta litteraturarbete var att undersöka effekten av 20 mg VPZ jämfört med 30 mg LPZ efter åtta veckors behandling av EE, genom att ta del av publicerade kliniska studier. Fyra olika RCT-studier hämtade från databasen PubMed användes i detta litteraturarbete. Alla fyra studier resulterade i att VPZ inte var sämre än LPZ vid behandling av EE i upp till åtta veckor. Fler patienter i VPZ-gruppen uppnådde läkning av EE i samtliga studier. Dessutom visade VPZ ha bättre effekt hos patienter med svårare EE. Number Needed to Treat (NNT) för de olika studierna varierade mycket, därför kunde inte den användas för att beskriva den kliniska effekten av VPZ vid behandling av EE. Både VPZ och LPZ tolererades väl. Slutsatsen var att VPZ 20 mg en gång dagligen var inte sämre än LPZ 30 mg en gång dagligen vid behandling av EE i 8 veckor. VPZ var effektiv och visade bättre resultat än LPZ när det gäller EE-läkning. Detta gäller speciellt patienter med svårare EE. Båda läkemedlen tolererades väl.

The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development. Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level. Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies. The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI). The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis. Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function). In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

<b>Background:</b> Comparative assessments of the vascular and upper gastrointestinal risks of different regimens of non-steroidal anti-inflammatory drugs (NSAIDs) are required. <b>Methods:</b> Meta-analyses were conducted, using individual participant data where possible, of placebo-controlled trials of a selective cyclo-oxygenase [COX]-2 inhibitor ('coxib') or traditional NSAID, or randomised trials of a coxib versus traditional NSAIDs. A prespecified subdivision of traditional NSAID regimens of those with antiplatelet activity (mainly naproxen) and those without (mainly diclofenac) was made. Primary outcomes were major vascular events (MVEs; nonfatal myocardial infarction, nonfatal stroke or vascular death) and upper gastrointestinal complications (UGICs; perforation, obstruction or bleed). <b>Findings:</b> Searches identified 788 trials: 200 comparisons of a coxib vs placebo (88,604 participants, mean follow-up 0.60 years), 206 comparisons of a traditional NSAID vs placebo (43,482 participants, 0.46 years) and 149 comparisons of a coxib vs traditional NSAID (137,466 participants, mean follow-up 0.95 years). Compared to placebo, allocation to a coxib increased the risk of MVEs (rate ratio 1.38, 95&percnt; CI 1.14-1.66), vascular mortality (1.58, 1.11-2.24) and UGICs (1.81, 1.17-2.81). Overall, in the population studied, coxibs were associated with three additional major vascular events (one fatal) and two (rarely fatal) upper gastrointestinal complications per 1000 person-years exposure. There was no evidence of heterogeneity by duration of follow-up, coxib type, dose (other than for celecoxib), or patient characteristics, for the primary outcomes. The risk of MVEs for traditional NSAIDs without antiplatelet activity (mostly diclofenac 75mg bd or ibuprofen 800mg tds) were comparable to coxibs (1.40, 1.15-1.72); but the risk of UGICs (1.98, 1.39-2.84) was significantly greater. For traditional NSAIDs with antiplatelet activity (mostly naproxen 500mg bd) there were no significant excess of MVEs (0.84, 0.66-1.08), but UGICs were substantially increased (4.06, 2.85-5.78). Both coxibs and traditional NSAIDs increased risk of hospitalisation for heart failure by about two-fold. <b>Interpretation:</b> The vascular and upper gastrointestinal risks of coxibs and high-dose tNSAID regimens can be predicted, allowing the choice of analgesia to be tailored for particular patients.

No description available.

Within this thesis the role of cognitive processes in irritable bowel syndrome (IBS) will be examined. A systematic review and meta-analysis of the rate of psychiatric comorbidity in IBS participants, relative to controls, was performed. Evidence supported heightened rates of psychiatric disorder. A novel hypothesis regarding overlapping cognitive vulnerability to IBS and psychiatric disorders was found to fit well with the pattern of comorbidity. Competing hypotheses and the potential moderators were examined. Overall, no single model of psychiatric morbidity in IBS could fully account for the results of the meta-analysis. The implications of this meta-analysis for a cognitive approach to IBS are discussed. Cognitive processes were directly investigated in two experiments. First, in a modified exogenous cueing task, which assessed attention to pain words, there was faster orienting towards, and engagement with pain words in IBS participants relative to controls. Next, participants completed a primed lexical decision task, which indexed interpretation biases by measuring response times to targets after ambiguous illness primes. Relative to controls, IBS participants’ responses were slower to target words presented after ambiguous illness primes, and demonstrated priming for targets related to the neutral meaning of the illness prime. In the second study, different IBS and healthy control participants completed an internet-based survey of autobiographical memory. Participants described and rated painful and emotional autobiographical events. IBS participants reported pain memories from a more observer perspective relative to controls, suggesting a possible coping strategy for pain content. Finally, three cognitive styles, alexithymia, rumination and self-blame, were evaluated using existing and novel self-report measures. Overall, when compared with healthy participants, IBS participants reported: less difficulty identifying feelings as indexed by the alexithymia measure; increased pain-focused rumination; and a general, negative self-blame. These results may imply a vigilance-avoidance model of cognitive processing in IBS.

Made available in DSpace on 2016-01-26T12:51:54Z (GMT). No. of bitstreams: 1 elisabetemelo_tese.pdf: 1119413 bytes, checksum: 4be114b65ecba8ea4e5468dff03f2f12 (MD5) Previous issue date: 2006-08-14 / Hepatopulmonary syndrome (HPS), caused by abnormal intrapulmonary vasodilatation (IPVD), when associated with severe hypoxemia has been related to increased morbid-mortality in liver transplant candidates. The progression of hypoxemia in cirrhotic patients with IPVD is not well known. The aim of this study is to determine the probability of developing hypoxemia (Pa02 <70mmHg) in IPVD patients waiting for liver transplantation over two years. Thirty-two transplant candidates with IPVD detected by contrast-enhanced echocardiography (GI) were prospectively studied and the Pa02 of then was measured at the start and at the end of 12 and 24 months. Eleven patients without IPVD were taken as control group (GII). Paired t test showed that mean Pa02 was significantly lower at 24 months compared with basal mean at GI (78,5 ± 18,9 vs 94,05 ± 14,9; p=0,001). GI patients had significantly lower mean Pa02 at 12 months (84,6 ± 14,8 vs 95,7 ± 7,3; p=0,003) and at 24 months (78,5 ± 19,0 vs 88,7 ± 7,1; p=0,036) compared with GII patients. The Kaplan-Meier estimated ratio for the appearance of hypoxemia was approximately 10% ±5% at 12 months and 28% ± 10% at 2 years. The mean variation for Pa02 in GI patients was 4,6±13,4mmHg at 12 months and 15,5±15,5mmHg at the end of two years. There was no appearance of either hypoxemia or IPVD in GII patients. The variables: age, Child-Pugh score, smoking habit, pré-transplant Pa02 and PaC02 values did not discriminated patients who presented hypoxemia during the period of two years study. In conclusion, we demonstrate prospectively the progressive course of HPS, even on it s subclinical stage; the estimated risk for the appearance of hypoxemia in patients with IPVD was at least 30% at the end of 2 years. The identification of the early appearance of hypoxemia can lead to a better understanding of the hepatopulmonary syndrome natural history and may be helpful to optimize timing and to predict the outcomes of liver transplantation. / A síndrome hepatopulmonar (SHP) é causada por dilatação anormal da vasculatura intrapulmonar (DVP) em indivíduos com doença hepática, tendo como consequência graus variados de hipoxemia arterial. A hipoxemia grave aumenta a morbimortalidade em candidatos a transplante de fígado, e sua progressão na história natural da SHP não é bem conhecida. O objetivo deste estudo é determinar a probabilidade de desenvolvimento de hipoxemia (Pa02 <70mmHg) em pacientes com DVP em lista de espera para o transplante de fígado, em um período de dois anos. Foram estudados prospectivamente 32 pacientes com DVP (GI), detectada pela ecocardiografia com contraste e a Pa02 foi medida ao início, aos 12 e aos 24 meses do estudo. Como grupo controle (GII), foram incluídos 11 pacientes sem DVP. Os testes t de Student e exato de Fisher foram usados para comparação dos resultados. A curva de Kaplan-Meier foi empregada para verificar a probabilidade de hipoxemia nos dois grupos. A média da Pa02 aos 12 e 24 meses foi significativamente menor no GI quando comparada ao GII (84,6±14,8mmHg vs 95,7±7,3mmHg; p=0,003 e 78,5±19,0mmHg vs 88,7±7,1mmHg; p=0,036, respectivamente). No GI há evidência de que a média dos valores da Pa02 aos 24 meses é menor do que a média basal (78,5±18,9 vs 94,0±14,9; p=0,001). A razão estimada para o aparecimento da hipoxemia foi aproximadamente 10%±5% aos 12 meses e 28%±10% aos 24 meses (Curva Kaplan-Meier), para o GI. A média da variação da Pa02 no GI foi de 4,6&#61617;13,4mmHg aos 12 meses e de 15,5&#61617;15,5mmHg aos 24 meses. Nenhum paciente apresentou hipoxemia nem DVP no GII durante o período de estudo. Os parâmetros: idade, Child-Pugh, tabagismo, Pa02 e PaC02 iniciais, não identificaram os indivíduos com DVP que desenvolveram hipoxemia em dois anos de observação. Conclui-se que: Demonstramos o curso progressivo da SHP, mesmo em condições subclínicas; O risco estimado para hipoxemia em portadores de DVP foi de pelo menos 30% em dois anos; A identificação precoce do aparecimento da hipoxemia pode levar a um melhor entendimento da história natural da SHP e ser útil para a otimização da indicação do transplante de fígado e obtenção de melhores resultados.