| 1. |
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| 2. |
- Forsgren, Mikael F, 1983-, et al.
(författare)
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Biomarkers of liver fibrosis : prospective comparison of multimodal magnetic resonance, serum algorithms and transient elastography.
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:7, s. 848-859
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score).RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively.CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.
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| 3. |
- Karlsson, Markus, 1990-
(författare)
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Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a large and unmet need for diagnostic tool that can be used to characterize chronic liver diseases (CLD). In the earlier stages of CLD, much of the diagnostics involves performing biopsies, which are evaluated by a histopathologist for the presence of e.g. fat, iron, inflammation, and fibrosis. Performing biopsies, however, have two downsides: i) biopsies are invasive and carries a small but non-negligible risk for serious complications, ii) biopsies only represents a tiny portion of the liver and are thus prone to sampling error. Moreover, in the later stages of CLD, when the disease has progressed far enough, the ability of the liver to perform its basic function will be compromised. In this stage, there is a need for better methods for accurately measuring liver function. Additionally, measures of liver function can also be used when developing new drugs, as biomarkers for drug-induced liver injury (DILI), which is a serious drug-safety issue.Magnetic resonance imaging (MRI) is a non-invasive medical imaging modality, which have shown much promise with regards to characterizing liver disease in all of the abovementioned aspects. The aim of this PhD project was to develop and validate MR-based methods that can be used to non-invasively characterize liver disease.Paper I investigated if R2* mapping, a MR-method for measuring liver iron content, can be confounded by liver fat. The results show fat does affect R2*. The conclusion was therefore that fat must be taken into account when measuring small amounts of liver iron, as a small increase in R2* could be due to either small amounts of iron or large amounts of fat.Paper II examined whether T1 mapping, which is another MR-method, can be used for staging liver fibrosis. The results of previous research have been mixed; some studies have been very promising, whereas other studies have been less promising. Unfortunately, the results in Paper II belongs to the less promising studies.Paper III focused on measuring liver function by dynamic contrast-enhanced MRI (DCEMRI) using a liver specific contrast agent, which is taken up the hepatocytes and excreted to the bile. The purpose of the paper was to extend and validate a method for estimating uptake and efflux rates of the contrast agent. The method had previously only been applied in health volunteers. Paper II showed that the method can be applied to CLD patients and that the uptake of the contrast agent is lower in patients with advanced fibrosis.Paper IV also used studied liver function with DCE-MRI in patients with primary sclerosing cholangitis (PSC). PSC is a CLD where the bile ducts are attacked by the immune system. When diagnosing PSC patients, it is common to use magnetic resonance cholangiopancreatography (MRCP), which is a method for imaging the bile ducts. Paper IV examined if there was any correlation between number and severity of the morphological changes, seen on MRCP, and measures of liver function derived using DCE-MRI. However, the results showed no such correlation. The conclusion was that the results indicates that MRCP should not be used to predict parenchymal function.Paper V developed a method for translating DCE-MRI liver function parameters from rats to humans. This translation could be of value when developing new drugs, as a tool for predicting which drugs might cause drug-induced liver injury.In summary, this thesis has shown that multimodal quantitative MR has a bright future for characterizing liver disease from a range of different aspects.
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| 4. |
- Ahmad, Awais, 1987-
(författare)
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Autoantibodies in healthy blood donors, rheumatic and autoimmune liver diseases
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autoimmunity is a common phenomenon where the immune system recognises the body's own tissues. Autoimmunity can lead to disease if tissue damage occurs. Autoimmune diseases affect 5–10% of the global population and in many of these autoantibodies can be detected. The autoantibodies can be detected with several different methods. In this thesis, line immunoassays and fluorescence enzyme immunoassay were used to investigate the presence of autoantibodies in blood donors and various disease groups. Line immunoassays use strips while fluorescence enzyme immunoassay uses wells. The strips and wells are coated with proteins that are allowed to react with serum samples from the patient. In the presence of autoantibodies, either a color change (line immunoassay) or a light reaction (fluorescence enzyme immunoassay) occurs.Study I and II: With the EuroLine -Autoimmune Liver Diseases- (IgG) line immunoassay, the presence of autoantibodies associated with autoimmune liver diseases was analysed in blood donors, patients with autoimmune liver diseases and patients with SLE. Autoantibodies could be detected in several blood donors. A very rare autoantibody, anti-LC- 1, was more common in blood donors than in patients with autoimmune liver diseases. Despite the presence of the autoantibodies, no association was seen with abnormal liver values in blood donors or patients with SLE. By raising the cut-off, the number of "false positive" results decreased. However, this could not correct the problem with anti-LC-1, which seems to indicate that there is a problem with the LC-1 antigen so that non-specific reactions are detected. The risk of developing autoimmune liver disease was considered to be low in the SLE patients, as none of these patients developed autoimmune liver disease despite several years of follow-up. Most of the positive findings with the EuroLine immunoassay could not be confirmed with other methods, indicating that this method is very sensitive.Study III: With the EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) line immunoassay, the rare autoantibodies anti-Th/To and anti-NOR90 could be detected as frequently in blood donors as in patients with systemic sclerosis. Most of the other autoantibodies were more common in patients with systemic sclerosis compared to blood donors and other disease groups. Some of these autoantibodies were associated with specific clinical manifestations, including renal involvement in patients with SLE. These findings need to be verified.Study IV: Autoantibodies that bind the U1-RNP protein (anti-U1-RNP) can be detected in patients with SLE. Patients with anti-U1-RNP can be further analysed for the presence of autoantibodies against the protein RNP 70kDa (anti-RNP70). However, the clinical value of further analysis of anti-RNP70 is uncertain. In this study, fluorescence enzyme immunoassay was used to analyse anti-U1-RNP positive samples for anti-RNP70 to evaluate whether it added anything of clinical value in SLE patients. Presence of anti-U1-RNP was associated with low white blood cell counts and less organ damage. However, analysis of anti-RNP70 in patients with SLE did not add any additional clinical information.Conclusion: Euroline -Autoimmune Liver Diseases- (IgG) and EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) are tools that are of value in the diagnosis of autoimmune liver diseases and systemic sclerosis, but the methods have high sensitivity which can lead to false positive results. By raising the cut-off, the risk of this can be reduced. Some rare antibodies were found more frequently in blood donors than in patients with the different disease groups, suggesting potential problems with the antigen source. Subtyping of anti-RNP70 in SLE patients with anti-U1-RNP did not add anything of clinical value.
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| 5. |
- Akbari, Camilla, et al.
(författare)
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Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD
- 2024
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsLong-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.MethodsWe conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.ResultsMALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2–8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years).ConclusionsThis study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.Impact and implicationsSeveral implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.
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| 6. |
- Balkhed, Wile, et al.
(författare)
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Repeated measurements of non-invasive fibrosis tests to monitor the progression of non-alcoholic fatty liver disease : A long-term follow-up study
- 2022
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Ingår i: Liver international (Print). - Chichester, United Kingdom : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 42:7, s. 1546-1556
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The presence of advanced hepatic fibrosis is the prime marker for the prediction of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Blood-based non-invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2-3-year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD.Methods. We retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow-up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end-stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow-up: Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate-to-alanine aminotransferase ratio (dAAR).Results: One hundred and thirty-five patients were included with a mean follow-up of 12.6 +/- 8.5 years. During follow-up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow-up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56-0.64 and positive predictive values of 0.28-0.36 at sensitivity fixed at 90%.Conclusions: Change of FIB-4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.
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| 7. |
- Berg, Anna, 1975-, et al.
(författare)
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Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans
- 2001
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 36:10, s. 1016-1021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Functional studies have shown that nitric oxide (NO) inhibits gastric acid secretion in a variety of species, including man. We have performed a morphological study with the intention of localizing the endothelial NO synthase (eNOS) in the human gastric mucosa.Methods: Fifteen healthy subjects voluntarily participated in the study, and mucosal biopsies were obtained from the cardia, corpus and antrum. The presence and localization of eNOS were studied using immunohistochemical techniques.Results: eNOS-immunoreactivity (eNOS-IR) is found in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close contact with parietal cells.Conclusions: eNOS-IR cells in close apposition to parietal cells provide morphological support for paracrine inhibition of gastric acid secretion by NO.
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| 8. |
- Bergquist, Annika, et al.
(författare)
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Impact on follow-up strategies in patients with primary sclerosing cholangitis
- 2023
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Ingår i: Liver international (Print). - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 43:1, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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| 9. |
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| 10. |
- Blomdahl, Julia, 1991-
(författare)
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Non-Alcoholic Fatty Liver Disease : Insights into Alcohol Consumption, Genetics, and Proteomics
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- NAFLD (Non-Alcoholic Fatty Liver Disease) affects approximately a quarter of the global population and is closely linked to type 2 diabetes mellitus and obesity. The disease spectrum ranges from steatosis and steatohepatitis to fibrosis, cirrhosis, and hepatocellular cancer. However, accurately predicting which patients will experience a progressive disease course remains a significant challenge. The variant gene of PNPLA3 is known to be associated with NAFLD and a more progressive disease, although its precise function remains unclear. Patients with NAFLD typically consume small to moderate amounts of alcohol, with recommended thresholds set at a maximum of 210 gram per week for males and 140 grams per week in females. However, the impact of alcohol consumption on liver disease in NAFLD remains disputed, with conflicting research findings. Liver biopsy is considered the gold standard for diagnosing NAFLD. However, due to its impracticality for such a large population with the condition, various non-invasive methods have been explored for diagnosing and evaluating NAFLD. This thesis aimed to investigate the potential effects of moderate alcohol consumption on NAFLD histology, explore the potential role of variant PNPLA3 in NAFLD, and assess the use of proteomics in classifying fibrosis. In Papers I and II, moderate alcohol consumption was assessed through questionnaires, clinical interviews, and measurement of the direct alcohol biomarker phosphatidylethanol (PEth). Paper I, a cross-sectional study including 86 participants, showed an association between moderate consumption and advanced fibrosis. Moderate consumption was defined as consuming more than 66 grams of ethanol per week or a PEth-value over 50 ng/mL. Notably, individuals with both moderate alcohol consumption and a diagnosis of type 2 diabetes exhibited significantly more advanced fibrosis. Paper II was a cohort study where 82 participants were followed over 17.2 years. Similarly, participants with moderate alcohol consumption displayed significant fibrosis progression. The strongest association was observed in participants with PEth-value of 48 ng/mL or higher, or those with binge drinking. In Paper III, the potential role of variant PNPLA3 was explored, exhibiting impaired autophagic flux and reduced lipophagy in variant PNPLA3 cells. Liver biopsies of NAFLD individuals with variant PNPLA3 displayed an accumulation of lipid droplets positive for both PNPLA3 and LC3 (a common marker of the autophagosome). This suggests that PNPLA3 is part of the lipophagy process, which is impaired in the variant gene and contributes to steatosis. Paper IV examined two independent NAFLD cohorts. In the discovery cohort, 60 participants with biopsy-proven NAFLD were included, while 59 participants were included in the validation cohort. The study evaluated 266 proteins and found that a biomarker model combining ACE2, HGF, and IGFBP-7 distinguished between different fibrosis stages (F0–1 and F2–4) in both cohorts. In summary, measuring phosphatidylethanol is advisable in NAFLD patient evaluations. Elevated PEth-levels (≥48 ng/mL) or alcohol consumption exceeding 66 grams per week should warrant advice to abstain from alcohol. PNPLA3 is implicated in NAFLD pathophysiology, potentially through impaired lipophagy. While its clinical application remains uncertain, genetic profiling for NAFLD risk assessment may become part of future non-invasive approaches. Additionally, proteomics holds promise for non-invasive NAFLD assessment, with the combination of ACE2, HGF, and IGFBP-7 identifying significant fibrosis in two separate cohorts.
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| 11. |
- Bodemar, Göran, 1941-, et al.
(författare)
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Treatment of anaemia in inflammatory bowel disease with iron sucrose
- 2004
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 39:5, s. 454-458
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel disease (IBD)-associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. Methods: Sixty-one patients with IBD and anaemia (average haemoglobin 97 g/L) were treated with iron sucrose (iron dose 1.4 ± 0.5 g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of ≥20 g/L or to normal haemoglobin levels (>120 g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. Results: Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty-four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow-up period of 117 ± 85 (4-291) (mean ± s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. Conclusions: Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow-up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.
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| 12. |
- Ericson, Ann-Charlott, 1965-, et al.
(författare)
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Morphological examination of the termination pattern of substance P-immunoreactive nerve fibers in human antral mucosa
- 2002
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 107:1-3, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- The termination pattern of substance P (SP)-containing axons in human antral mucosa was examined using immunohistochemical techniques at the light and electron microscopic level. SP-immunoreactive (IR) axons were found to extend towards the pit region of the glands, where intraepithelial axons were observed. Electron microscopy showed immunostained axon profiles in close contact with the basement membrane of surface mucous cells. Membrane-to-membrane contacts between labeled axons and myofibroblast-like cells were identified, and SP-IR axons that were apposed to the epithelium were also in contact with subjacent myofibroblast-like cells. The anatomical relationship between SP-IR axons and the cells of the muscularis mucosae was investigated by light microscopy. Immunoreactivity for a-smooth muscle actin (a-sma) was used to visualize the smooth muscle cells, and the a-sma-IR cells were found to create a network that surrounded the gastric glands. Immunostained varicose axons ran alongside and in close apposition to the labeled muscle strands. Ultrastructural examination showed close contacts between SP-IR axon profiles and smooth muscle-like cells. In conclusion, SP-containing neurons may be important for sensory and secretomotor functions in the human antral mucosa.
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| 13. |
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Internmedicin
- 2018. - 6
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Internmedicin beskriver uppkomstmekanismer, förlopp och medicinsk handläggning av den stora grupp sjukdomar som involverar kroppens centrala organsystem, inklusive hjärta-lungor-cirkulation, mage-tarm-lever, benmärg-blod, njurar, rörelseorgan och hormonsekretion.Internmedicin utkom första gången 1978 och har sedan dess varit en uppskattad kunskapskälla för medicinstuderande under hela utbildningen liksom en oumbärlig uppslagsbok för kliniskt verksamma läkare. I denna sjätte reviderade upplaga är en majoritet av kapitlen nyskrivna eller grundligt uppdaterade. Som tidigare utgörs författarlistan av Sveriges ledande kliniska specialister och forskare inom sina respektive områden. Varje sjukdomstillstånd beskrivs detaljerat med uppgifter om bland annat etiologi, symtom, utredning och behandling. Framställningen är rikt illustrerad, och i varje kapitel belyser man den centrala handläggningen med kliniska patientfall.
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| 14. |
- Kechagias, Stergios, 1969-
(författare)
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Clinical Pharmacokinetics of Small Doses of Ethanol : Role of Gastric Emptying and Other Influences in the Upper Gastrointestinal Tract
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the clinical pharmacokinetics of small doses of ethanol as influenced by conditions in the proximal gut. The bioavailability of orally administered ethanol depends to a large extent on gastric emptying, which is influenced by pre-treatment with drugs and other clinically relevant factors in the upper gastrointestinal tract.The impact of the relative amount of carbohydrate, fat or protein in a test meal on the pharmacokinetics of a small dose of ethanol was studied in nine healthy male subjects. Drinking ethanol after eating a meal was compared with intake of the same dose consumed on an empty stomach or given intravenously. The peak blood alcohol concentration (BAC) and the area under the curve (AUC) were greatest when ethanol was given intravenously (100% availability). Drinking ethanol after a meal resulted in considerably lower peak BAC and AUC compared with drinking on an empty stomach. However, the macronutrient composition of the meal had no significant effect on the pharmacokinetics of ethanol as reflected in almost identical blood alcohol curves after high-fat, high-protein, or high-carbohydrate meals.The decreased bioavailability of ethanol after oral administration compared to intravenous infusion of the same dose can be explained by a first-pass metabolism (FPM). Some investigators attribute this FPM to the presence of alcohol dehydrogenase (ADH) in the gastric mucosa. Gastric ADH activity was studied in mucosal biopsies from 76 patients referred for upper gastrointestinal endoscopy. Those patients (n = 36) infected with H. pylori received treatment to eradicate the bacterium and repeat biopsies were obtained 2 months and one year later. There were no significant differences in gastric ADH activity between males and females and between different age groups. Gastric ADH activity was significantly decreased in the antrum among patients with H. pylori infection. After eradication of H. pylori, gastric ADH activity in the antrum was normalised within two months. No significant differences in the ADH activity were found in biopsies from the corpus. Histological examination of gastric biopsies showed that those exhibiting the most pronounced inflammation and histologic changes had significantly lower ADH activity compared with biopsies judged to have normal histology.Several drugs inhibit gastric ADH in vitro. Among them acetylsalicylic acid (ASA) was suggested to increase the bioavailability of orally administered ethanol. We studied the effect of low-dose ASA on the pharmacokinetics of a small dose of ethanol in 10 healthy men. Low-dose ASA (75 mg) decreased significantly the peak BAC and the time to reach peak BAC was also prolonged. The underlying mechanism appears to be delayed gastric emptying which was assessed by the paracetamol absorption test. To evaluate the effect of accelerating gastric emptying on ethanol pharmacokinetics, the prokinetic substance cisapride was given to the same 10 subjects. When ethanol was ingested 60 min after a meal pre-treatment with cisapride significantly increased peak BAC. However, this increase in BAC after cisapride was modest compared with the BAC reached when the same dose of ethanol was ingested on an empty stomach. The corresponding serum paracetamol curves indicated that a faster rate of gastric emptying was the main factor responsible for the differences in ethanol pharmacokinetics.Analysis of breath alcohol concentration (BrAC) is a practical and non-invasive method to estimate the BAC and this technique is used worldwide for forensic purposes. The reliability of BrAC measurements in subjects with gastroesophageal reflux disease (GERD) has been questioned. We therefore compared simultaneously obtained breath and venous blood alcohol concentrations in 10 patients with severe GERD scheduled for antireflux surgery. In one of the experiments gastroesophageal reflux was provoked by applying abdominal compression. Although some patients complained of pronounced reflux symptoms the breath instrument readings of BrAC did not deviate from the corresponding BAC in the two test situations, that is, with and without provocation of reflux.This thesis has established that measuring alcohol in breath can be used to monitor blood alcohol concentration also in subjects with severe GERD. The relative amount of fat, carbohydrate, or protein in a test meal does not influence the pharmacokinetics of a small dose of ethanol as long as the caloric contents of the meals are similar. The rate of gastric emptying is a major factor determining the bioavailability of orally administered ethanol. Treatment with low-dose ASA (75 mg) delayed gastric emptying and caused a lowering of the peak BAC. The prokinetic drug cisapride, administered under conditions that resemble clinical use, increased the peak BAC by accelerating gastric emptying. However, the drug-induced increase in BAC was much less than the BAC observed after drinking the same dose of ethanol on an empty stomach. H. pylori infection is associated with decreased antral ADH activity related to gastritis. Eradication of H. pylori normalises antral ADH activity within two months.
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| 15. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Established and emerging factors affecting the progression of nonalcoholic fatty liver disease
- 2020
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 111
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease affecting approximately 25% of the global population. Although a majority of NAFLD patients will never experience liver-related symptoms it is estimated that 5-10% will develop cirrhosis-related complications with risk of death or need for liver transplantation. NAFLD is closely associated with cardiovascular disease and components of the metabolic syndrome. However, NAFLD is not uncommon in lean individuals and may in these subjects represent a different entity with separate pathophysiological mechanisms involved implying a higher risk for development of end-stage liver disease. There is considerable fluctuation in the histopathological course of NAFLD that may partly be attributed to lifestyle factors and dietary composition. Nutrients such as fructose, monounsaturated fatty acids, and trans-fatty acids may aggravate NAFLD. Presence of type 2 diabetes mellitus seems to be the most important clinical predictor of liver-related morbidity and mortality in NAFLD. Apart from severity of the metabolic syndrome, genetic polymorphisms and environmental factors, such as moderate alcohol consumption, may explain the variation in histopathological and clinical outcome among NAFLD patients. (c) 2020 Elsevier Inc. All rights reserved.
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| 16. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa
- 2005
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 40:7, s. 775-782
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Capsaicin, which acts by binding to the vanilloid receptor-1 (VR1), has been shown to give protection against gastric mucosal injury and to enhance healing of gastric ulcers. Although VR1 has recently been reported to be present in non-neural tissues, it is primarily considered to be expressed in nociceptor sensory neurons of small diameter. The aim of the present study was to evaluate the distribution of VR1 immunoreactivity in the normal human gastric mucosa. Material and methods. Ten volunteers underwent gastroscopy and biopsies were obtained from the corpus and the antrum. The specimens were labelled immunohistochemically using polyclonal goat anti-VR1 and evaluated at the light- and electronmicroscopic level. Moreover, post-embedding immunogold labelling was performed and subsequently analysed at the electronmicroscopic level. Results. In the antrum, VR1 immunoreactivity was located in epithelial cells that fulfilled the criteria of endocrine cells of the "open type". These cells were located primarily in the neck region of the antral glands and the labelling was concentrated on the microvilli of these cells. At the ultrastructural level, round granulae with differences in electron density were identified in the basal compartment of the labelled cells. VR1 immunoreactivity was also identified in axon-like structures that were located in the lamina propria, often in close vicinity of vessels, in the corpus as well as in the antrum. Conclusions. VR1-immunoreactivity was evident in antral epithelial cells exhibiting characteristics of endocrine-like cells. This may indicate that the gastroprotective effects of capsaicin, which hitherto have been attributed to primary afferent neurons, at least partly may be explained by an action on specific epithelial cells in the antrum. © 2005 Taylor & Francis.
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| 17. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride
- 1999
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 48:5, s. 728-732
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Tidskriftsartikel (refereegranskat)abstract
- Aims To examine the influence of cisapride on the pharmacokinetics of ethanol and the impact of gastric emptying monitored by the paracetamol absorption test. Methods Ten healthy male volunteers took part in a cross-over design experiment. They drank a moderate dose of ethanol 0.30 g kg−1 body weight exactly 1 h after eating breakfast either without any prior drug treatment or after taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption of ethanol to monitor gastric emptying. Venous blood was obtained at 5–10 min intervals for determination of ethanol by headspace gas chromatography and paracetamol was analysed in serum by high performance liquid chromatography (h.p.l.c.). Results The maximum blood-ethanol concentration (Cmax ) increased from 3.8±1.7 to 5.6±2.3 mmol l−1 (±s.d.) after treatment with cisapride (95% confidence interval CI on mean difference 0.28–3.28 mmol l−1 ). The area under the blood-ethanol curve (AUC) increased from 6.3±3.5 to 7.9±2.6 mmol l−1 h after cisapride (95% CI −0.74–3.9 mmol l−1 h). The mean blood ethanol curves in the cisapride and no-drug sessions converged at ≈2 h after the start of drinking. Both Cmax and AUC were highest when the ethanol was ingested on an empty stomach (Cmax 9.5±1.7 mmol l−1 and AUC 14.6±1.9 mmol l−1 h), compared with drinking 1 h after a meal and regardless of pretreatment with cisapride. Conclusions A small but statistically significant increase in Cmax occurred after treatment with cisapride owing to faster gastric emptying rate as shown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in Cmax and AUC, was greatest after drinking the alcohol on an empty stomach. The cisapride–ethanol interaction probably lacks any clinical or forensic significance.
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| 18. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity
- 2001
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Ingår i: Alcoholism. - : Wiley. - 0145-6008 .- 1530-0277. ; 25:4, s. 508-512
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric alcohol dehydrogenase may contribute to the metabolism of orally ingested ethanol and decrease the bioavailability of the drug. The aims of this study were to assess the impact of Helicobacter pylori infection and its eradication on gastric alcohol dehydrogenase activity and to relate the findings to gastric histology. Furthermore, the role of age- and sex-related differences in gastric alcohol dehydrogenase activity were studied.Methods: A total of 76 subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and biopsies were obtained from the corpus and antrum. The specimens were used for determining gastric alcohol dehydrogenase activity, histological examination, and urease testing. Subjects with H. pylori infection (n= 36) received medication to eradicate the infection, and repeat biopsies were taken 2 and 12 months later.Results: No significant difference in gastric alcohol dehydrogenase activity was found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity did not differ significantly between the subjects older than 50 years (n= 39) and those 50 years or younger (n= 37). In subjects with H. pylori infection, gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the antrum increased significantly within 2 months (p < 0.01). Antral biopsies with the most pronounced inflammation and histological changes had significantly decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant differences were found in corpus.Conclusions: H. pylori infection is associated with decreased antral alcohol dehydrogenase activity, which seems to be related to the severity of the inflammatory changes in the mucosa. Eradication of H. pylori normalizes antral alcohol dehydrogenase activity within 2 months.
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| 19. |
- Kechagias, Stergios, 1969-
(författare)
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Internmedicin : en introduktion
- 2018. - 6
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Ingår i: Internmedicin. - Stockholm : Liber. - 9789147113262 ; , s. 15-16
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Kechagias, Stergios, 1969-
(författare)
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Leversjukdomar
- 2018. - 6
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Ingår i: Internmedicin. - Stockholm : Liber. - 9789147113262 ; , s. 847-890
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 21. |
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| 22. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Non-invasive diagnosis and staging of non-alcoholic fatty liver disease
- 2022
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Ingår i: Hormones. - Cham, Switzerland : Springer. - 1109-3099 .- 2520-8721. ; 21, s. 346-368
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Forskningsöversikt (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome and is characterized by ectopic accumulation of triglycerides in the cytoplasm of hepatocytes, i.e., steatosis. NAFLD has become the most common chronic liver disease, with an estimated global prevalence of 25%. Although the majority of NAFLD patients will never experience liver-related complications, the progressive potential of NAFLD is indisputable, with 5-10% of subjects progressing to cirrhosis, end-stage liver disease, or hepatocellular carcinoma. NAFLD patients with advanced fibrosis are at the highest risk of developing cardiovascular and cirrhosis-related complications. Liver biopsy has hitherto been considered the reference method for evaluation of hepatic steatosis and fibrosis stage. Given the limitations of biopsy for widescale screening, non-invasive tests (NITs) for assessment of steatosis and fibrosis stage, including serum-based algorithms and ultrasound- and magnetic resonance-based methods, will play an increasing role in the management of NAFLD patients. This comprehensive review presents the advantages and limitations of NITs for identification of steatosis and advanced fibrosis in NAFLD. The clinical implications of using NITs to identify and manage NAFLD patients are also discussed.
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| 23. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease
- 1999
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Ingår i: Journal of Forensic Sciences. - 0022-1198 .- 1556-4029. ; 44:4, s. 814-818
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Tidskriftsartikel (refereegranskat)abstract
- Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (~0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. Ah attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt, Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) of a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same of higher than venous BAC (mg/dL). In the post-peak phase, the BAC al ways exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5- min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.
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| 24. |
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| 25. |
- Nasr, Patrik, et al.
(författare)
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Evaluating the prevalence and severity of NAFLD in primary care: the EPSONIP study protocol
- 2021
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Ingår i: BMC Gastroenterology. - : BMC. - 1471-230X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNon-alcoholic fatty liver disease (NAFLD) affects 20-30% of the general adult population. NAFLD patients with type 2 diabetes mellitus (T2DM) are at an increased risk of advanced fibrosis, which puts them at risk of cardiovascular complications, hepatocellular carcinoma, or liver failure. Liver biopsy is the gold standard for assessing hepatic fibrosis. However, its utility is inherently limited. Consequently, the prevalence and characteristics of T2DM patients with advanced fibrosis are unknown. Therefore, the purpose of the current study is to evaluate the prevalence and severity of NAFLD in patients with T2DM by recruiting participants from primary care, using the latest imaging modalities, to collect a cohort of well phenotyped patients.MethodsWe will prospectively recruit 400 patients with T2DM using biomarkers to assess their status. Specifically, we will evaluate liver fat content using magnetic resonance imaging (MRI); hepatic fibrosis using MR elastography and vibration-controlled transient elastography; muscle composition and body fat distribution using water-fat separated whole body MRI; and cardiac function, structure, and tissue characteristics, using cardiovascular MRI.DiscussionWe expect that the study will uncover potential mechanisms of advanced hepatic fibrosis in NAFLD and T2DM and equip the clinician with better diagnostic tools for the care of T2DM patients with NAFLD.Trial registration: Clinicaltrials.gov, identifier NCT03864510. Registered 6 March 2019, https://clinicaltrials.gov/ct2/show/NCT03864510.
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| 26. |
- Nasr, Patrik, 1987-, et al.
(författare)
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Modifiers of Liver-Related Manifestation in the Course of NAFLD
- 2020
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Ingår i: Current pharmaceutical design. - : BENTHAM SCIENCE PUBL LTD. - 1381-6128 .- 1873-4286. ; 26:10, s. 1062-1078
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Forskningsöversikt (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population. There is a strong association between the severity, of NAFLD and the components of the metabolic syndrome. NAFLD is also independently associated with cardiovascular disease and type 2 diabetes mellitus (T2DM). The progressive potential of non-alcoholic fatty liver disease (NAFLD) is indisputable today, and the histological spectrum of NAFLD ranges from isolated steatosis to nonalcoholic steatohepatitis (NASH), with risk of developing :fibrosis and subsequent cirrhosis and hepatocellular carcinoma. There is a substantial inter-patient variation in disease progression, therefore, this review will focus on potential modifiers of fibrosis progression, development of liver cirrhosis, decompensation and liver-related mortality. The potential drivers of disease progression that is discussed are; T2DM and Insulin Resistance, body weight, alcohol consumption, genetics (including HFE and alfa-1-antitrypsin) as well as histological features predictive of disease progression.
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| 27. |
- Nasr, Patrik, 1987-
(författare)
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Non-Alcoholic Fatty Liver Disease : Aspects on Diagnosis and Long-term Prognosis
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population and is commonly recognized as the hepatic manifestation of the metabolic syndrome. The histological spectrum of NAFLD ranges from isolated steatosis to non-alcoholic steatohepatitis (NASH), with risk of developing fibrosis and subsequent cirrhosis and hepatocellular carcinoma. The gold standard for diagnosing NAFLD is liver biopsy. However, because of its invasive nature, several non-invasive methods have been developed and validated in evaluating fat and fibrosis in patients with NAFLD.Liver fat content can be assessed using various methods. The conventional histopathological method consists of a visual semiquantitative approach in which the pathologist uses a four-point scale: grade 0 corresponds to fat deposition in <5% of hepatocytes and grade 1−3 (which is needed for the diagnosis of NAFLD) corresponds to ≥5%. An alternate approach is to quantitatively assess steatosis using stereological point counting (SPC) – which rely on liver biopsy. However, in vivo proton magnetic resonance spectroscopy (1H-MRS) is a reliable noninvasive method that can be used to quantitatively assess total hepatic lipid content, or proton density fat fraction (PDFF).In Paper I we compared the conventional semiquantitative histological method (grade 0-3) with SPC and 1H-MRS. We found a strong positive correlation between 1H-MRS and SPC, whereas the correlations between 1H-MRS or SPC and histopathological grading were substantially weaker. Using the widely used cut-off value of PDFF ≥5%, all participants were found to have steatosis (specificity 100%, sensitivity 53%). Reducing the cut-off value to 3% maintained 100% specificity while increasing sensitivity to 79%.In Paper IV we evaluated quantitative steatosis, by SPC, in 106 biopsy-proven NAFLD patients during a 20-year follow-up. SPC was independently associated with an increased risk of all-cause mortality and development of T2DM. Moreover, in the 59 patients with sequential biopsies (approximately 10 years apart), a reduction of quantitative hepatic steatosis decreased the all-time risk of developing T2DM.NASH is commonly seen as a histological feature portending a worse prognosis in NAFLD. Interestingly, no dual biopsy study has ever shown that NASH predicts fibrosis progression. Yet, NASH is seen as a surrogate marker in pharmaceutical trials – were resolution in NASH is equivalent to future resolution of fibrosis.In Paper II we conducted a long-term follow-up study (20 years) in a large cohort of biopsy-proven NAFLD patients (n=646), in a collaboration with Karolinska Institute. We could not ascertain that NASH had any effect on all-cause, or disease-specific mortality. However, higher stages of fibrosis predicted all-cause and disease specific mortality. In Paper III, we present 129 biopsy-proven NAFLD patients, in which we had prospective, longitudinal data. They were included between 1988 and 1993. All patients alive, were re-invited 2003-2005 and 2013-2015. Dual biopsies were present in 68 patients, and three consecutive biopsies were available in 33 patients. Results showed that NAFLD is a highly heterogeneous disease, with 9.3% developing end-stage liver disease and 16% progressing to advanced stages of fibrosis without any clinically significant baseline data predicting disease progression. In summary, when using 1H-MRS as a diagnostic method for NAFLD, the diagnostic cut-off should be reduced from 5% to 3%. Furthermore, quantitative amount of hepatic steatosis could be used to stratify patients with NAFLD related to future risk of developing T2DM. Moreover, we have shown that NASH does not predict future all-cause or disease-specific mortality nor end-stage liver disease, therefore a different surrogate marker should be used in clinical trials when assessing NAFLD improvement, so to not imbue false reliance in new therapies. Lastly, we have shown that NAFLD has a more dismal prognosis than previously reported, and that it is unexpectedly difficult to predict fibrosis progression in individual NAFLD patients, emphasizing the need for robust non-invasive biomarkers suitable to monitor large number of patients.
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| 28. |
- Nasr, Patrik, 1987-, et al.
(författare)
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The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.
- 2020
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Ingår i: Liver international. - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 40:5, s. 1069-1078
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC.RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.
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| 29. |
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| 30. |
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| 31. |
- Norén, Bengt, 1955-, et al.
(författare)
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Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy
- 2008
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Ingår i: European Journal of Radiology. - : Elsevier. - 0720-048X .- 1872-7727. ; 66:2, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- 31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.
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| 32. |
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| 33. |
- Qadri, Sami, et al.
(författare)
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Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:5, s. e2008-e2020
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Tidskriftsartikel (refereegranskat)abstract
- Context: Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. Objective: To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. Design: Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3). Setting: Tertiary referral center. Patients: We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m(2)]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS. Main Outcome Measures: Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage >= F3 fibrosis or nonalcoholic steatohepatitis with >= F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)]. Results: The scores with an AUROC >= 0.85 to identify >= F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out >= F3 fibrosis in groups with BM Is <30.0, 30.0 to 39.9, and >= 40.0 kg/m(2). This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose >= F3 fibrosis. Conclusions: In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.
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| 34. |
- Ratziu, V, et al.
(författare)
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Histological progress of non-alcoholic fatty liver disease : a critical reassessment based on liver sampling variability.
- 2007
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 26, s. 821-830
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Tidskriftsartikel (refereegranskat)abstract
- Background: In non-alcoholic fatty liver disease, histological lesions display a significant sampling variability that is ignored when interpreting histological progression during natural history or therapeutic interventions. Aim: To provide a method taking into account sampling variability when interpreting crude histological data, and to investigate how this alters the conclusions of available studies. Methods: Natural history studies detailing histological progression and therapeutic trials were compared with the results of a previously published sampling variability study. Results: Natural history studies showed an improvement in steatosis, which was significantly higher than expected from sampling variability (47% vs. 8%, P < 0.0001). In contrast, no study showed a change in activity grade or ballooning higher than that of sampling variability. There was only a marginal effect on fibrosis with no convincing demonstration of a worsening of fibrosis, a conclusion contrary to what individual studies have claimed. Some insulin sensitizing drugs and anti-obesity surgery significantly improved steatosis, while most did not significantly impact on fibrosis or activity. Conclusions: Sampling variability of liver biopsy is an overlooked confounding factor that should be considered systematically when interpreting histological progression in patients with non-alcoholic fatty liver disease.
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| 35. |
- Rendek, Zlatica, 1983-
(författare)
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Faecal Calprotectin Diagnostics : Focus on Primary Care and Suspected Sources of Error
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with gastrointestinal symptoms often present a diagnostic challenge for general practitioners. Faecal calprotectin (FC) is commonly used as a marker of intestinal inflammation and is useful for differentiating between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), as well as for the follow-up of patients with IBD and monitoring treatment response. However, several other causes of increased FC levels have been acknowledged, including intake of non-steroidal anti-inflammatory drugs or proton pump inhibitors and respiratory infections. Currently, there is insufficient knowledge about how these factors affect FC levels. It is crucial that physicians who use calprotectin as a diagnostic tool have the ability to conduct a sound evaluation of the test result to ensure accurate clinical decisions, and potentially avoid unnecessary referrals and invasive investigations.The aim of this thesis was to investigate the contribution of FC in the diagnostics of gastrointestinal disease in primary care, its diagnostic value and accuracy as a predictor of gastrointestinal disease and the influence of different sources of error on calprotectin levels. In particular, the effects of oral diclofenac (a non-steroidal anti-inflammatory drug [NSAID]), omeprazole (a proton pump inhibitor [PPI]) and respiratory tract infection on FC levels are investigated. The normalization interval after cessation of diclofenac and omeprazole is assessed.The first study is a retrospective analysis of data on all FC tests on adults conducted in primary care in Östergötland County in 2010. A higher proportion of patients with a positive FC result were diagnosed with IBD and organic gastrointestinal disease compared with those with a negative FC result. Predictors of IBD were positive FC, diarrhoea, rectal bleeding and male sex. Predictors of organic gastrointestinal disease were found to be positive FC, age >35 years, abnormal clinical findings and duration <3 months. FC had the highest sensitivity and negative predictive value compared with demographic factors, symptoms and duration. Intake of NSAIDs, PPIs and acetyl salicylic acid showed marginal effects on the diagnostic accuracy of FC for IBD and organic gastrointestinal disease. Among patients with a negative FC test, on whom no further investigations were performed, no missed diagnoses of IBD or organic gastrointestinal disease were detected at a 5-year follow-up.The second study investigates the effect of diclofenac intake on FC levels. We found that shortterm intake of oral diclofenac was associated with increased FC levels and that FC returned to normal within 2 weeks of cessation.The third study reports on a randomized open-label clinical trial and investigates the effect of omeprazole, diclofenac and co-administration of these drugs on FC levels. The findings regarding diclofenac were consistent with those of the second study. Short-term intake of omeprazole alone or when co-administered with diclofenac was associated with increased FC levels. The normalization interval was 3 weeks after cessation.The fourth study, a prospective cohort study, examines the effect of an acute respiratory tract infection on the FC level. Faecal and salivary calprotectin levels were not found to be increased during respiratory tract infections. This study did not confirm any correlation between calprotectin levels in saliva and faeces during infection.In conclusion, FC reliably rules out IBD and contradicts the presence of other organic gastrointestinal diseases in patients with gastrointestinal symptoms attending primary care. Patients with a positive FC test together with other symptoms, such as diarrhoea, rectal bleeding, short duration or age >35 years should be prioritized for further investigations. Short-term intake of diclofenac, omeprazole, or their co-administration in healthy individuals is associated with increased FC levels. In patients with an increased FC level on diclofenac, it is sufficient to repeat the FC test 2 weeks after cessation. In patients on omeprazole alone or when co-administered with diclofenac, the FC test should be repeated 3 weeks after cessation. Acute respiratory tract infections were not found to be associated with increased faecal or salivary calprotectin levels.
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