The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients,... Show moreThe prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity. Show less
Dijk, M. van; Brakenhoff, S.M.; Isfordink, C.J.; Cheng, W.H.; Blokzijl, H.; Boland, G.; ... ; Knegt, R.J. de 2021
Background: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is... Show moreBackground: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to harvest detailed data on the Dutch HCV epidemic. This study aims to provide a well-supported timeline towards HCV elimination in The Netherlands. Methods: A previously published Markov model was used, adopting published data and unpublished CELINE project data. Two main scenarios were devised. In the Status Quo scenario, 2020 diagnosis and treatment levels remained constant in subsequent years. In the Gradual Decline scenario, an annual decrease of 10% in both diagnoses and treatments was implemented, starting in 2020. WHO incidence target was disregarded, due to low HCV incidence in The Netherlands (& LE;5 per 100,000). Results: Following the Status Quo and Gradual Decline scenarios, The Netherlands would meet WHO's elimination targets by 2027 and 2032, respectively. From 2015 to 2030, liver-related mortality would be reduced by 97% in the Status Quo and 93% in the Gradual Decline scenario. Compared to the Status Quo scenario, the Gradual Decline scenario would result in 12 excess cases of decompensated cirrhosis, 18 excess cases of hepatocellular carcinoma, and 20 excess cases of liver-related death from 2020-2030. Conclusions: The Netherlands is on track to reach HCV elimination by 2030. However, it is vital that HCV elimination remains high on the agenda to ensure adequate numbers of patients are being diagnosed and treated. Show less
Background and Aims Previous small studies have appraised the gut microbiome (GM) in steatosis, but large-scale studies are lacking. We studied the association of the GM diversity and composition,... Show moreBackground and Aims Previous small studies have appraised the gut microbiome (GM) in steatosis, but large-scale studies are lacking. We studied the association of the GM diversity and composition, plasma metabolites, predicted functional metagenomics, and steatosis.Approach and Results This is a cross-sectional analysis of the prospective population-based Rotterdam Study. We used 16S ribosomal RNA gene sequencing and determined taxonomy using the SILVA reference database. Alpha diversity and beta diversity were calculated using the Shannon diversity index and Bray-Curtis dissimilarities. Differences were tested across steatosis using permutational multivariate analysis of variance. Hepatic steatosis was diagnosed by ultrasonography. We subsequently selected genera using regularized regression. The functional metagenome was predicted based on the GM using Kyoto Encyclopedia of Genes and Genomes pathways. Serum metabolomics were assessed using high-throughput proton nuclear magnetic resonance. All analyses were adjusted for age, sex, body mass index, alcohol, diet, and proton-pump inhibitors. We included 1,355 participants, of whom 472 had steatosis. Alpha diversity was lower in steatosis (P = 1.1 center dot 10(-9)), and beta diversity varied across steatosis strata (P = 0.001). Lasso selected 37 genera of which three remained significantly associated after adjustment (Coprococcus3: beta = -65; Ruminococcus Gauvreauiigroup: beta = 62; and Ruminococcus Gnavusgroup: beta = 45, Q-value = 0.037). Predicted metagenome analyses revealed that pathways of secondary bile-acid synthesis and biotin metabolism were present, and D-alanine metabolism was absent in steatosis. Metabolic profiles showed positive associations for aromatic and branched chain amino acids and glycoprotein acetyls with steatosis and R. Gnavusgroup, whereas these metabolites were inversely associated with alpha diversity and Coprococcus3.Conclusions We confirmed, on a large-scale, the lower microbial diversity and association of Coprococcus and Ruminococcus Gnavus with steatosis. We additionally showed that steatosis and alpha diversity share opposite metabolic profiles. Show less
Dietary lifestyle intervention is key in treating non-alcoholic fatty liver disease (NAFLD). We aimed to examine the longitudinal relation between well-established dietary patterns as well as... Show moreDietary lifestyle intervention is key in treating non-alcoholic fatty liver disease (NAFLD). We aimed to examine the longitudinal relation between well-established dietary patterns as well as population-specific dietary patterns and NAFLD. Participants from two subsequent visits of the Rotterdam Study were included. All underwent serial abdominal ultrasonography (median follow-up: 4.4 years) and filled in a food frequency questionnaire. Secondary causes of steatosis were excluded. Dietary data from 389 items were collapsed into 28 food groups and a posteriori dietary patterns were identified using factor analysis. Additionally, we scored three a priori dietary patterns (Mediterranean Diet Score, Dutch Dietary Guidelines and WHO-score). Logistic mixed regression models were used to examine the relation between dietary patterns and NAFLD. Analyses were adjusted for demographic, lifestyle and metabolic factors. We included 963 participants of whom 343 had NAFLD. Follow-up data was available in 737 participants. Incident NAFLD was 5% and regressed NAFLD was 30%. We identified five a posteriori dietary patterns (cumulative explained variation [R-2] = 20%). The patterns were characterised as: vegetable and fish, red meat and alcohol, traditional, salty snacks and sauces, high fat dairy & refined grains pattern. Adherence to the traditional pattern (i.e. high intake of vegetable oils/stanols, margarines/butters, potatoes, whole grains and sweets/desserts) was associated with regression of NAFLD per SD increase in Z-score (0.40, 95% CI 0.15-1.00). Adherence to the three a priori patterns all showed regression of NAFLD, but only the WHO-score showed a distinct association (0.73, 95% CI 0.53-1.00). Hence, in this large elderly population, adherence to a plant-based, high-fibre and low-fat diet was related to regression of NAFLD. Show less
Nearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation... Show moreNearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population. Show less
