| 41. |
- Nasr, Patrik, et al.
(författare)
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Incidence, prevalence and mortality of chronic liver diseases in Sweden between 2005 and 2019
- 2022
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 77:Suppl. 1, s. S82-S82
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Chronic liver diseases affects approximately 844 million individuals and causes an estimated two million deaths per year. The most common causes are chronic viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. With the availability of curative treatments and effective vaccines for viral hepatitis and increasing prevalence of metabolic syndrome-thel andscape of liver diseases is shifting. In this study, we aimed to describe the incidence and prevalence of a wide range of chronic liver diseases as well as their role in mortality in Sweden.Method: In this register-based, nationwide cohort study, aggregated statistics, stratified on categories of age, sex and geographic allocations, on all adult Swedish inhabitants with a diagnosis of liver disease during 2005 to 2019 were obtained from National registers.Results: During 2005 to 2019, there were substantial changes in the epidemiology of liver diseases in Sweden. The incidence of alcohol-related cirrhosis increased by 18% annually (incidence rate 13.1/100, 000 in 2019). The incidence rate of non-alcoholic fatty liver diseasea nd cirrhosis with unspecified etiology increased by 14% and 20% annually respectively (incidence rate 15.2 and 18.7/100, 000). Furthermore, incidence rates of chronic hepatitis C steeply declined, while autoimmune hepatitis increased (3.4/100, 000). In parallel with the increasing incidence of liver cirrhosis, liver malignancies have become more common.The most common causes of liver related mortality were alcohol-related disease without a code for cirrhosis, alcohol-related cirrhosis, and unspecified liver disease with mortality rates of 4.1, 2.9, and 2.8/100, 000. Most liver diseases were more frequent amongst men. Furthermore, varying differences was seen in the incidence ratebetween regions, with some etiologies (e.g. autoimmune liver diseases) being more common in rural areas.Conclusion: The incidence rates of non-alcoholic fatty liver disease, alcohol-related cirrhosis, unspecified liver cirrhosis has increased during the last 15 years, in parallel with a decreasing incidence of viral hepatitis. The incidence of AIH and hepatobiliary malignancies is also increasing. Worryingly, mortality in several liver diseases increased, likely reflecting the increasing incidence of cirrhosis. Significant disparities of liver diseases exist across sex and geographical regions, which needs to be considered when allocating healthcare resources.
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| 42. |
- 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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| 43. |
- Shang, Ying, et al.
(författare)
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Non-alcoholic fatty liver disease does not increase dementia risk although histology data might improve risk prediction
- 2021
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is common in the general population, but its association with dementia is unclear. We aimed to assess the risk of dementia related to NAFLD, and to determine whether histological parameters could improve the predictive capacity of a conventional risk model for dementia in patients with biopsy-proven NAFLD. Methods: A retrospective matched cohort study of 656 NAFLD patients underwent liver biopsy at 2 hospitals between 1971 and 2009. Up to 10 individuals (controls) from the general population (n = 6,436) were matched for age, sex, and municipality to each patient. Dementia was ascertained from National registers until 2014. Using Cox regression, we estimated hazard ratios for dementia with 95% confidence intervals. In the biopsy cohort, the discriminative power of adding histological markers to a conventional risk model was assessed by Harrells C-index and compared with a likelihood-ratio test. Results: During a mean follow-up of 19.7 +/- 8.7 years, 3.3% of the NAFLD patients and 4.9% of the controls developed dementia (p = 0.07). Overall, NAFLD was not significantly associated with incident dementia. In the biopsy cohort, the model of conventional risk factors (age, sex, hypertension, and cardiovascular diseases) had a C-index of 0.912 to predict incident dementia. Adding individual histological parameters significantly increased the prediction of dementia, with the most pronounced improvement for fibrosis stage (C-index = 0.938, p <0.05). Conclusions: Although NAFLD was not associated with the risk of dementia, we found that adding histological markers to a conventional risk model for dementia enhanced the predictive capacity, indicating a shared metabolic origin. Lay summary: Both non-alcoholic fatty liver disease (NAFLD) and dementia are increasing in prevalence because of a more sedentary lifestyle, increased prevalence of obesity and population ageing. However, the link between these 2 diseases is not well studied. We investigated the association between NAFLD and the risk of dementia and found no association. However, liver histology parameters, especially fibrosis, could significantly improve the prediction of dementia risk. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
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| 44. |
- Shang, Ying, et al.
(författare)
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Risk of cardiovascular disease and loss in life expectancy in NAFLD
- 2022
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Ingår i: Hepatology. - : Wiley. - 0270-9139 .- 1527-3350. ; 76:5, s. 1495-1505
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Conflicting evidence exists on cardiovascular disease (CVD) risk in patients with NAFLD, and data are lacking on whether NAFLD increases mortality after a CVD event. Moreover, life expectancy in NAFLD has not been studied. We therefore examined CVD risk and life expectancy in patients with NAFLD compared with the general population. Approach and Results In this nationwide population-based cohort, all patients with NAFLD diagnosis and without baseline CVD (ascertaining from the Swedish National Patient Register from 1987 to 2016, n = 10,023) were matched 10:1 on age, sex, and municipality to individuals from the general population (controls, n = 96,313). CVD diagnosis and mortality were derived from national registers. Multistate models and flexible parametric survival models were used to estimate adjusted hazard ratios (aHRs) for CVD risk and loss in life expectancy due to NAFLD. We identified 1037 (10.3%) CVD events in patients with NAFLD and 4041 (4.2%) in controls. CVD risk was 2.6-fold higher in NAFLD compared with controls (aHR = 2.61, 95% CI = 2.36-2.88) and was strongest for nonfatal CVD (aHR = 3.71, 95% CI = 3.29-4.17). After a nonfatal CVD event, the risk for all-cause mortality was similar between patients with NAFLD and controls (aHR = 0.89, 95% CI = 0.64-1.25). Life expectancy in patients with NAFLD was, on average, 2.8 years lower than controls, with the highest loss of life-years when NAFLD was diagnosed in middle age (40-60 years). Conclusions NAFLD was associated with a higher risk of nonfatal CVD but did not affect post-CVD mortality risk. Patients diagnosed with NAFLD have a lower life expectancy than the general population.
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| 45. |
- Sharma, Rajani, et al.
(författare)
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Cancer Risk in Patients With Autoimmune Hepatitis : A Nationwide Population-Based Cohort Study With Histopathology
- 2022
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 191:2, s. 298-319
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969-2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR) = 2.69) and lymphoma (HR = 1.89). Sibling analyses yielded similar risk estimates for any cancer (HR = 1.84) and HCC (HR = 23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.
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| 46. |
- Sharma, Rajani, et al.
(författare)
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Increased Mortality Risk in Autoimmune Hepatitis : A Nationwide Population-based Cohort Study With Histopathology
- 2021
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:12, s. 2636-2647.e13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting.METHODS: This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death.RESULTS: During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI=31.1-33.6) for AIH individuals and 14.1% (95%CI=13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI=2.17-2.41), which remained elevated ≥20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR=4.55; 95%CI=3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR=1.27; 95%CI=1.15-1.40), liver disease (HR=66.24; 95%CI=48.19-91.03) and extrahepatic malignancy (HR=1.69; 95%CI=1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death.CONCLUSION: AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.
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| 47. |
- Simon, Tracey G., et al.
(författare)
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Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease : A Population-Based Cohort Study
- 2021
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Ingår i: Hepatology. - : Wiley-Interscience Publishers. - 0270-9139 .- 1527-3350. ; 74:5, s. 2410-2423
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Recent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity.Approach and Results: We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to <= 5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person-years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18-1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; P-trend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers.Conclusions: Compared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.
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| 48. |
- Simon, Tracey G., et al.
(författare)
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Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease
- 2023
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:3, s. 573-580
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Longitudinal evidence is lacking regarding the long-term risk of major adverse cardiovascular events (MACE) in children and young adults with non-alcoholic fatty liver disease (NAFLD).DESIGN: This nationwide cohort study included all Swedish children and young adults ≤25 years old with histologically confirmed NAFLD and without underlying cardiovascular disease (CVD) at baseline (1966-2016; n=699). NAFLD was defined from prospectively recorded histopathology, and further categorised as simple steatosis or non-alcoholic steatohepatitis (NASH). NAFLD patients were matched to ≤5 population controls without NAFLD or CVD (n=3353). Using Cox proportional hazards modelling, we calculated multivariable-adjusted HRs (aHRs) and 95% CIs for incident MACE (ie, ischaemic heart disease, stroke, congestive heart failure or cardiovascular mortality). In secondary analyses, we also explored rates of incident cardiac arrhythmias.RESULTS: Over a median follow-up of 16.6 years, incident MACE was confirmed in 33 NAFLD patients and 52 controls. NAFLD patients had significantly higher rates of MACE than controls (3.1 vs 0.9/1000 person-years (PY); difference=2.1/1000 PY; aHR=2.33, 95% CI=1.43 to 3.78), including higher rates of ischaemic heart disease (difference=1.4/1000 PY; aHR=3.07, 95% CI 1.62 to 5.83) and congestive heart failure (difference=0.5/1000 PY; aHR=3.89, 95% CI=1.20 to 12.64). Rates of incident MACE outcomes appeared to be further augmented with NASH (aHR=5.27, 95% CI=1.96 to 14.19). In secondary analyses, NAFLD patients also had significantly higher rates of cardiac arrythmias (aHR=3.16, 95% CI=1.49 to 6.68).CONCLUSION: Compared with matched population controls, children and young adults with biopsy-proven NAFLD had significantly higher rates of incident MACE, including ischaemic heart disease and congestive heart failure. Research to better characterise cardiovascular risk in children and young adults with NAFLD should be prioritised.
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| 49. |
- Simon, Tracey G., et al.
(författare)
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Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease : a nationwide histology cohort study
- 2023
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Ingår i: Cardiovascular Diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior studies suggest a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and incident arrhythmias, including atrial fibrillation (AF). However, robust data are lacking from cohorts with liver histology, which remains the gold standard for staging MASLD severity.Methods: This population-based cohort included all Swedish adults with histologically-confirmed MASLD and without prior cardiac arrhythmias (1966-2016; n = 11,206). MASLD was defined from prospectively-recorded histopathology, and characterized as simple steatosis, non-fibrotic steatohepatitis (MASH), non-cirrhotic fibrosis, or cirrhosis. MASLD patients were matched to <= 5 controls without MASLD or arrhythmias, by age, sex, calendar year and county (n = 51,856). Using Cox proportional hazards modeling, we calculated multivariable-adjusted hazard ratios (aHRs) for incident arrhythmias (including AF, bradyarrhythmias, other supraventricular arrhythmias, ventricular arrhythmias/cardiac arrest).Results: Over a median follow-up of 10.8 years, incident arrhythmias were confirmed in 1351 MASLD patients (10.3/1000 person-years [PY]) and 6493 controls (8.7/1000PY; difference = 1.7/1000PY; aHR = 1.30, 95%CI 1.22-1.38), and MASLD patients had significantly higher rates of incident AF (difference = 0.9/1000PY; aHR = 1.26, 95%CI 1.18-1.35). Rates of both overall arrhythmias and AF were significantly elevated across all MASLD histological groups, particularly cirrhosis (differences, 8.5/1000PY and 5.3/1000PY, respectively). In secondary analyses, MASLD patients also had significantly higher rates of incident ventricular arrhythmias/cardiac arrest (aHR = 1.53, 95%CI 1.30-1.80), bradyarrhythmias (aHR = 1.26, 95%CI 1.06-1.48), and other supraventricular arrhythmias (aHR = 1.27, 95%CI 1.00-1.62), compared to controls.Conclusions: Compared to matched controls, patients with biopsy-confirmed MASLD had modest but significantly higher incidence of cardiac arrhythmias, including AF, bradyarrhythmias, other supraventricular arrhythmias and ventricular arrhythmias/cardiac arrest. Excess risk was observed across all stages of MASLD and was highest with cirrhosis.
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| 50. |
- Simon, Tracey G., et al.
(författare)
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Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis : Results From a Nationwide Swedish Population
- 2019
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 171:5, s. 318-327
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown.Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis.Design: Prospective propensity score (PS)-matched cohort.Setting: Swedish registers, 2005 to 2013.Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults.Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs).Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The in- verse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -62 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users.Limitation: Lack of lipid, fibrosis, or HCC surveillance data.Conclusion: In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.
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