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- Dulai, Parambir S, et al.
(author)
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Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease : Systematic Review and Meta-analysis.
- 2017
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In: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 65:5, s. 1557-1565
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Research review (peer-reviewed)abstract
- BACKGROUND: Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD.METHODS: Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement.RESULTS: 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19-2.11); stage 2, MRR, 2.52 (95% CI 1.85-3.42); stage 3, MRR, 3.48 (95% CI 2.51-4.83), and stage 4, MRR, 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17-11.95); stage 2, MRR, 9.57 (95% CI 1.67-54.93); stage 3, MRR, 16.69 (95% CI 2.92-95.36); and stage 4, MRR, 42.30 (95% CI 3.51-510.34).LIMITATIONS: Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group.CONCLUSION: The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another. This article is protected by copyright. All rights reserved.
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- Ekstedt, Mattias, et al.
(author)
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Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
- 2015
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In: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 61:5, s. 1547-1554
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Journal article (peer-reviewed)abstract
- Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.
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- Törner, Anna, et al.
(author)
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The underreporting of hepatocellular carcinoma to the Cancer Register and a log-linear model to estimate a more correct incidence
- 2017
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In: Hepatology. - Hoboken, USA : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 65:3, s. 885-892
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Journal article (peer-reviewed)abstract
- The Cancer Register (CR) in Sweden has reported that the incidence of primary liver cancer (PLC) has slowly declined over the last decades. Even though all cancers, irrespective of diagnostic method, should be reported to the CR, the PLC incidence may not reflect the true rate. Improved diagnostic tools have enabled diagnosis of hepatocellular carcinoma (HCC) based on non-invasive methods without histological verification, possibly associated with missed cancer-reports or misclassification in the CR. Our objective was to study the completeness and assess the underreporting of PLC to the CR, and to produce a more accurate estimate based on three registers. The CR, the Cause of Death and the Patient Register were investigated. Differences and overlap were examined, the incidence was estimated by merging data from the registers, and the number reported to none of the registers was estimated using a log-linear capture-recapture model. The results show that 98% of the PLCs reported to the CR were histologically verified; 80% were HCC and 20% intrahepatic cholangiocarcinoma. Unspecified liver cancer decreased over time and constituted <10% of all reported liver cancers. The CR may underestimate the liver cancer incidence by 37% - 45%, primarily due to missed cancer-reports. The estimated annual number of liver cancers increased over time, but the standardized incidence was stable around 11 per 100,000. Hepatitis C associated liver cancer increased and constituted 20% in 2010.Conclusion: There was an underreporting of PLC diagnosed by non-invasive methods. The incidence was considerably higher than estimated by the CR, with a stable incidence over time. Reporting needs to improve and combining registers is recommended when studying incidence. This article is protected by copyright. All rights reserved.
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