Health-related Quality of Life in Patients With Nonalcoholic Fatty Liver Disease: A Prospective Multi-center UK Study.

BACKGROUND & AIMS: It is unclear whether health-related quality of life (HRQoL) is impaired in patients with nonalcoholic fatty liver disease (NAFLD) without advanced fibrosis and how this compares with the general population. We aimed to assess HRQoL in patients with NAFLD in comparison to the general population and any associations of fibrosis severity and metabolic comorbidities with impairments in HRQoL. METHODS: We prospectively enrolled 513 consecutive patients with NAFLD who completed the EuroQol 5-dimensional questionnaire (EQ-5D) and Chronic Liver Disease Questionnaires (CLDQ). Demographic and clinical information, liver biopsy results, and/or liver stiffness (LS) by transient elastography were recorded. A general population sub-cohort of the Health Survey for England 2018 was used as a comparator (n = 5483), and a 1:1 propensity-score (PS) matching was performed, according to age, sex, body mass index, and type 2 diabetes mellitus (T2DM). RESULTS: EQ-5D-5L utility was significantly lower in 466 PS-matched patients with NAFLD compared with PS-matched controls (0.77 ± 0.27 vs 0.84 ± 0.19; P < .001), even in those without advanced fibrosis (F ≤2 or LS <8kPa) (0.80 ± 0.24 vs 0.84 ± 0.19; P = .024). HRQoL measures (EQ-5D-5L, EQ-VAS, CLDQ) did not differ between patients with NAFLD with and without advanced fibrosis. LS was independently associated with lower EQ-5D-5L in all patients with NAFLD but not in those without advanced fibrosis. In the latter, lower EQ-5D-5L was associated with female sex, T2DM, and depression. CONCLUSIONS: Patients with NAFLD, even those without advanced fibrosis, have worse HRQoL compared with the general population. In patients with NAFLD without advanced fibrosis, HRQoL is independently associated with non-liver comorbidities but not LS. Multi-disciplinary management is therefore required in NAFLD, irrespective of fibrosis severity.

Comparison of point-shear wave elastography (ElastPQ) and transient elastography (FibroScan) for liver fibrosis staging in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: ElastPQ is a point shear wave elastography technique used to non-invasively assess liver fibrosis. We compared liver stiffness measurements (LSM) by ElastPQ and fibroscan transient elastography (F-TE) in a cohort of patients with non-alcoholic fatty liver disease (NAFLD). We further evaluated the performance of ElastPQ in a subgroup of patients with available liver histology. MATERIALS AND METHODS: We included patients with NAFLD who presented in a dedicated multidisciplinary clinic. Anthropometric parameters, blood tests and elastography measurements were obtained using F-TE and ElastPQ as part of routine clinical care. RESULTS: We enrolled 671 patients with NAFLD, mean age 55.8 ± 13 years, body mass index (BMI) 31.5 ± 5.7 kg/m2 , 56.6% males, 41% diabetes, 53.7% hypertension, 68% dyslipidaemia. ElastPQ showed an excellent correlation with F-TE (Spearman's r = 0.80, p < .001), which was better for mild/moderate stages of fibrosis. Independent predictors of a >2 kPa discrepancy between the two techniques were a larger waist circumference and F-TE ≥10 kPa. In the subgroup of 159 patients with available histology, ElastPQ showed similar diagnostic accuracy with F-TE in staging liver fibrosis (ElastPQ area under the curves 0.84, 0.83, 0.86 and 0.95, for F ≥ 1, F ≥ 2, F ≥ 3 and F = 4 respectively). Optimal cut-off values of ElastPQ for individual fibrosis stages were lower than those of F-TE. CONCLUSIONS: ElastPQ shows an excellent correlation with F-TE in patients with NAFLD, which was better for lower LSM. The optimal cut-off values of ElastPQ are lower than those of F-TE for individual stages of fibrosis. ElastPQ has similar diagnostic accuracy to F-TE for all stages of fibrosis.

Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and expose patients to increased risk of hepatic and cardiovascular (CV) morbidity and mortality. Both environmental factors and genetic predisposition contribute to the risk. An inappropriate diet, rich in refined carbohydrates, especially fructose, and saturated fats, and poor in fibers, polyunsaturated fats, and vitamins is one of the main key factors, as well as the polymorphism of patatin-like phospholipase domain containing 3 (PNPLA3 gene) for NAFLD and the apolipoproteins and the peroxisome proliferator-activated receptor (PPAR) family for the cardiovascular damage. Beyond genetic influence, also epigenetics modifications are responsible for various clinical manifestations of both hepatic and CV disease. Interestingly, data are accumulating on the interplay between diet and genetic and epigenetic modifications, modulating pathogenetic pathways in NAFLD and CV disease. We report the main evidence from literature on the influence of both macro and micronutrients in NAFLD and CV damage and the role of genetics either alone or combined with diet in increasing the risk of developing both diseases. Understanding the interaction between metabolic alterations, genetics and diet are essential to treat the diseases and tailoring nutritional therapy to control NAFLD and CV risk.

Relapsing pericarditis: Peripheral blood neutrophilia, lymphopenia and high neutrophil-to-lymphocyte ratio herald acute attacks, high-grade inflammation, multiserosal involvement, and predict multiple recurrences.

AIMS: To identify peripheral blood cellular correlates of active pericarditis and to verify whether peripheral blood neutrophils, lymphocytes and the neutrophil to-lymphocyte ratio (NLR) are associated with disease phenotype or prognosis. METHODS: Observational prospective study on a cohort of 63 patients with idiopathic pericarditis followed for 12 months after each pericarditis recurrence. Two distinct analyses were performed: the "index attack" analysis focused on the first pericarditis episode in each patient, while the "all attacks" analysis included all episodes occurring during the study. RESULTS: Absolute and relative neutrophilia and lymphopenia, together with high NLR, were observed during active pericarditis, as compared with disease remission, at both analyses. Neutrophils showed a positive correlation with plasma C-reactive protein levels, while lymphocyte count showed a negative correlation. Relative neutrophil count was higher, and lymphocyte count lower in patients with pleural effusion; a higher NLR and lower absolute lymphocyte count were observed in those with peritoneal involvement. No correlations were found between peripheral blood neutrophil or lymphocyte counts and size of pericardial effusion, or with the presence of myocardial involvement. Peripheral neutrophilia, lymphopenia and NLR during acute attacks predicted the number of recurrences in the following 12 months. CONCLUSIONS: Peripheral blood neutrophilia and lymphopenia are typical of acute idiopathic pericarditis. Acute attacks of pericarditis are associated with neutrophilia and lymphopenia, as compared with disease remission. During acute attacks, neutrophilia and lymphopenia reflect the extent of serosal inflammation and could help to customize therapeutic management after remission has been achieved.

Usefulness of fibrosis-4 (FIB-4) score and metabolic alterations in the prediction of SARS-CoV-2 severity.

Despite vaccination programs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a public health problem. Identifying key prognostic determinants of severity of the disease may help better focus health resources. The negative prognostic role for metabolic and hepatic alterations is established; however, the interplay among different metabolic comorbidities and their interconnections with the liver have never been explored.The objective of this study is to evaluate the impact of liver alterations in addition to metabolic comorbidities as a predictor of SARS-CoV-2 severity. 382 SARS-CoV-2 patients were enrolled. Severe SARS-CoV-2 was diagnosed according to international consensus. Transaminases > 2 times the upper limit of normality (2ULN), hepatic steatosis (by ultrasound and/or computed tomography in 133 patients), and FIB-4 defined liver alterations. All data were collected on admission. The results are severe SARS-CoV-2 infection in 156 (41%) patients (mean age 65 ± 17; 60%males). Prevalence of obesity was 25%; diabetes, 17%; hypertension, 44%; dyslipidaemia, 29%; with 13% of the cohort with ≥ 3 metabolic alterations. Seventy patients (18%) had transaminases > 2ULN, 82 (62%) steatosis; 199 (54%) had FIB-4 < 1.45 and 45 (12%) > 3.25. At multivariable analysis, ≥ 3 metabolic comorbidities (OR 4.1, CI 95% 1.8-9.1) and transaminases > 2ULN (OR 2.6, CI 95% 1.3-6.7) were independently associated with severe SARS-CoV-2. FIB-4 < 1.45 was a protective factor (OR 0.42, CI 95% 0.23-0.76). Hepatic steatosis had no impact on disease course. The presence of metabolic alterations is associated with severe SARS-CoV-2 infection, and the higher the number of coexisting comorbidities, the higher the risk of severe disease. Normal FIB-4 values are inversely associated with advanced SARS-CoV-2 regardless of metabolic comorbidities, speculating on use of these values to stratify the risk of severe infection.

NAFLD: Diagnostic Algorithms for Regulating Patient Fluxes.

The global prevalence of NAFLD is estimated to be over 25% and it is already the leading cause of chronic liver disease in industrialized countries, as a consequence of the spread of obesity and metabolic syndrome. The prognosis of NAFLD is generally benign in the absence of fibrosis, but liver fibrosis rapidly progresses in 20% of the cases and can lead to cirrhosis and/or HCC. This review focuses on non-invasive fibrosis testing strategies for patients with NAFLD in order to increase the efficiency and effectiveness of diagnosis and care, regulating secondary care referral fluxes. An integrated management plan between primary care and secondary care with a defined algorithm of non-invasive testing to stratify the risk of NAFLD fibrosis is indispensable to increase the early diagnosis of fibrosis but also decrease unnecessary referrals.