Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases

Ginès, Pere; Castéra, Laurent; Lammert, Frank; Graupera, Isabel; Serra-Burriel, Miquel; Allen, Alina M.; Wong, Vincent Wai‐Sun; Hartmann, Phillipp; Thiele, Maja; Caballería, Llorenç; Knegt, Robert J. de; Grgurević, Ivica; Augustín, Salvador; Tsochatzis, Emmanuel; Schattenberg, Jörn M.; Guha, Indra Neil; Martini, Andréa; Morillas, Rosa María; García–Retortillo, Montserrat; Koning, Harry J. de; Fabrellas, Núria; Pich, Judit; T., Ann; Díaz, MA; Roulot, Dominique; Newsome, Philip N.; Manns, Michael P.; Kamath, Patrick S.; Krag, Aleksander

doi:10.1002/hep.32163

Cited by 155 publications

(130 citation statements)

References 40 publications

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“…31 Our approach of evaluating liver fibrosis in the general population, irrespective of underlying etiology, is consistent with other efforts to understand the role of liver fibrosis broadly in human disease. 13,14,32,33 Furthermore, this approach is consistent with emerging liver fibrosis screening paradigms 8,34 and accounts for the real-world overlap between chronic liver conditions such as alcoholic and presumed non-alcoholic fatty liver disease. 35…”

Section: Methodssupporting

confidence: 64%

Association between Liver Fibrosis and Incident Dementia in the UK Biobank Study

Parikh

Kamel

Zhang

et al. 2022

Preprint

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Background: There is growing recognition of the role of chronic liver disease in brain health, but the impact of liver fibrosis on dementia risk was unclear. We evaluated the association between liver fibrosis and incident dementia using data from a large prospective cohort study. Methods: We performed a retrospective cohort study using data from the UK Biobank study, which prospectively enrolled approximately 500,000 adults starting 2007 and continues to follow them. Liver fibrosis was defined using validated cutoffs of the Fibrosis-4 (FIB-4) liver fibrosis score. The primary outcome was incident dementia, ascertained using a validated approach based on participants' hospital record and mortality data. Secondary outcomes were Alzheimer's disease and vascular dementia. We excluded participants with prevalent dementia. We used Cox proportional hazards models to evaluate the association between liver fibrosis and incident dementia while adjusting for potential confounders. In additional models, the FIB-4 score was used as a continuous independent variable. Prespecified interaction analyses tested for effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status. Results: Among 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Standard liver chemistries were largely in the normal range. However, 2.17% (95% CI, 2.13-2.22%) had liver fibrosis based on their FIB-4 score. The rate of dementia per 1,000 person-years was 1.76 (95% CI, 1.50-2.07) in participants with liver fibrosis and 0.52 (95% CI, 0.50-0.54) in those without. After adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with an increased risk of dementia (HR, 1.52; 95% CI, 1.22-1.90). An independent association was also noted between FIB-4, treated as a continuous variable, and dementia (HR per unit, 1.29; 95% CI, 1.20-1.39). Effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status was not seen. Conclusion: Liver fibrosis in middle age was associated with an increased risk of incident dementia, independent of metabolic syndrome and shared risk factors. Liver fibrosis may be an underrecognized risk factor for dementia.

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Section: Methodssupporting

confidence: 64%

Association between Liver Fibrosis and Incident Dementia in the UK Biobank Study

Parikh

Kamel

Zhang

et al. 2022

Preprint

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“… 4 , 10 However, some guidelines and consensus reports state that screening of hepatic steatosis and fibrosis can be considered with a multistep approach in at-risk groups (i.e., patients with MetS or type 2 diabetes mellitus and/or high-risk alcohol consumption) who have much higher prevalence of liver fibrosis than the general population. 5 , 11 , 12 For example, regarding the evaluation of patients with type 2 diabetes mellitus and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging proton density fat fraction are recommended, and the stage of fibrosis must be assessed appropriately. 5 Older age, obesity, diabetes mellitus, and aspartate transaminase to alanine transaminase ratio greater than one are significant predictors of severe liver fibrosis.…”

mentioning

confidence: 99%

“…There are several ongoing projects evaluating the implementation of different methods of screening for liver fibrosis in populations in different areas of the world. 12 If these are proven effective, diagnosing liver fibrosis in asymptomatic subjects will provide an opportunity to prevent disease progression. 12 …”

mentioning

confidence: 99%

Metabolic Syndrome: A Warning Sign of Liver Fibrosis

Seo

2022

Journal of Obesity & Metabolic Syndrome

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“…Ideally, NAFLD patients should undergo screening for the presence of advanced fibrosis/cirrhosis using non-invasive methods to stratify for the presence of advanced fibrosis or cirrhosis. Currently, about 60% of the European population is considered at risk of having chronic liver disease, and many studies are underway to develop the most suitable diagnostic algorithm to reliably recognize patients who are at risk for advanced liver fibrosis [ 125 , 126 ]. Stepwise or even concomitant use of two unrelated non-invasive tests might be the most favorable strategy to increase the reliability of the obtained result, i.e., predicted stage of liver fibrosis, as supported by guidelines [ 16 , 124 , 125 , 126 , 127 , 128 ].…”

Section: Diagnostic Approachmentioning

confidence: 99%

“…Currently, about 60% of the European population is considered at risk of having chronic liver disease, and many studies are underway to develop the most suitable diagnostic algorithm to reliably recognize patients who are at risk for advanced liver fibrosis [ 125 , 126 ]. Stepwise or even concomitant use of two unrelated non-invasive tests might be the most favorable strategy to increase the reliability of the obtained result, i.e., predicted stage of liver fibrosis, as supported by guidelines [ 16 , 124 , 125 , 126 , 127 , 128 ]. However, even transient elastography (TE) as the non-invasive method considered among the most reliable in stratifying the patients according to their risk of having advanced fibrosis, as supported by the largest body of scientific evidence, is not without limitations [ 129 ].…”

Section: Diagnostic Approachmentioning

confidence: 99%

Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach

Grgurević

Božin

Mikuš

et al. 2021

Cancers

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Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of liver morbidity worldwide and, as such, represents the pathogenic background for the increasing incidence of hepatocellular carcinoma (HCC). The annual incidence of NAFLD-related HCC is expected to increase by 45–130% by 2030. Diabetes mellitus is the most important risk factor for HCC development in NAFLD, with the risk further increased when associated with other metabolic traits, such as obesity, arterial hypertension and dyslipidemia. The highest risk of HCC exists in patients with advanced fibrosis or cirrhosis, although 20–50% of HCC cases arise in NAFLD patients with an absence of cirrhosis. This calls for further investigation of the pathogenic mechanisms that are involved in hepatocarcinogenesis, including genetics, metabolomics, the influence of the gut microbiota and immunological responses. Early identification of patients with or at risk of NAFLD is of utmost importance to improve outcomes. As NAFLD is highly prevalent in the community, the identification of cases should rely upon simple demographic and clinical characteristics. Once identified, these patients should then be evaluated for the presence of advanced fibrosis or cirrhosis and subsequently enter HCC surveillance programs if appropriate. A significant problem is the early recognition of non-cirrhotic NAFLD patients who will develop HCC, where new biomarkers and scores are potential solutions to tackle this issue.

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Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases

Cited by 155 publications

References 40 publications

Association between Liver Fibrosis and Incident Dementia in the UK Biobank Study

Association between Liver Fibrosis and Incident Dementia in the UK Biobank Study

Metabolic Syndrome: A Warning Sign of Liver Fibrosis

Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach

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