Generic and disease-specific health related quality of life in non-cirrhotic, cirrhotic and transplanted liver patients: a cross-sectional study

BACKGROUND: Studies on Health Related Quality of Life (HRQoL) of chronic liver patients were performed in clinical populations. These studies included various disease stages but small variations in aetiology and no transplanted patients. We performed a large HRQoL study in non-cirrhotic, cirrhotic and transplanted liver patients with sufficient variety in aetiology. We compared the generic HRQoL and fatigue between liver patients and healthy controls and compared the disease-specific and generic HRQoL and fatigue between non-cirrhotic, cirrhotic and transplanted liver patients, corrected for aetiology. METHODS: Members of the Dutch liver patient association received the Short Form-36, the Liver Disease Symptom Index and the Multidimensional Fatigue Index-20. Based on reported clinical characteristics we classified respondents (n = 1175) as non-cirrhotic, compensated cirrhotic, decompensated cirrhotic or transplants. We used linear, ordinal and logistic regression to compare the HRQoL between groups. RESULTS: All liver patients showed a significantly worse generic HRQoL and fatigue than healthy controls. Decompensated cirrhotic patients showed a significantly worse disease-specific and generic HRQoL and fatigue than non-cirrhotic patients, while HRQoL differences between non-cirrhotic and compensated cirrhotic patients were predominantly insignificant. Transplanted patients showed a better generic HRQoL, less fatigue and lower probabilities of severe symptoms than non-cirrhotic patients, but almost equal probabilities of symptom hindrance. CONCLUSIONS: HRQoL in chronic liver patients depends on disease stage and transplant history. Non-cirrhotic and compensated cirrhotic patients have a similar HRQoL. Decompensated patients show the worst HRQoL, while transplanted patients show a significantly better HRQoL than cirrhotic and non-cirrhotic patients

Large-scale inference of liver fat with neural networks on UK Biobank body MRI

The UK Biobank Imaging Study has acquired medical scans of more than 40,000 volunteer participants. The resulting wealth of anatomical information has been made available for research, together with extensive metadata including measurements of liver fat. These values play an important role in metabolic disease, but are only available for a minority of imaged subjects as their collection requires the careful work of image analysts on dedicated liver MRI. Another UK Biobank protocol is neck-to-knee body MRI for analysis of body composition. The resulting volumes can also quantify fat fractions, even though they were reconstructed with a two- instead of a three-point Dixon technique. In this work, a novel framework for automated inference of liver fat from UK Biobank neck-to-knee body MRI is proposed. A ResNet50 was trained for regression on two-dimensional slices from these scans and the reference values as target, without any need for ground truth segmentations. Once trained, it performs fast, objective, and fully automated predictions that require no manual intervention. On the given data, it closely emulates the reference method, reaching a level of agreement comparable to different gold standard techniques. The network learned to rectify non-linearities in the fat fraction values and identified several outliers in the reference. It outperformed a multi-atlas segmentation baseline and inferred new estimates for all imaged subjects lacking reference values, expanding the total number of liver fat measurements by factor six

The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin

<p>Abstract</p> <p>Background</p> <p>Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients.</p> <p>Methods</p> <p>Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort.</p> <p>Results</p> <p>The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype.</p> <p>Conclusions</p> <p>IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV.</p

Utility of pathologist panels for achieving consensus in NASH histologic scoring in clinical trials: Data from a phase 3 study

Copyright \ua9 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.Background: Liver histopathologic assessment is the accepted surrogate endpoint in NASH trials; however, the scoring of NASH Clinical Research Network (CRN) histologic parameters is limited by intraobserver and interobserver variability. We designed a consensus panel approach to minimize variability when using this scoring system. We assessed agreement between readers, estimated linear weighted kappas between 2 panels, compared them with published pairwise kappa estimates, and addressed how agreement or disagreement might impact the precision and validity of the surrogate efficacy endpoint in NASH trials. Methods: Two panels, each comprising 3 liver fellowship-trained pathologists who underwent NASH histology training, independently evaluated scanned whole slide images, scoring fibrosis, inflammation, hepatocyte ballooning, and steatosis from baseline and month 18 biopsies for 100 patients from the precirrhotic NASH study REGENERATE. The consensus score for each parameter was defined as agreement by ≥2 pathologists. If consensus was not reached, all 3 pathologists read the slide jointly to achieve a consensus score. Results: Between the 2 panels, the consensus was 97%-99% for steatosis, 91%-93% for fibrosis, 88%-92% for hepatocyte ballooning, and 84%-91% for inflammation. Linear weighted kappa scores between panels were similar to published NASH CRN values. Conclusions: A panel of 3 trained pathologists independently scoring 4 NASH CRN histology parameters produced high consensus rates. Interpanel kappa values were comparable to NASH CRN metrics, supporting the accuracy and reproducibility of this method. The high concordance for fibrosis scoring was reassuring, as fibrosis is predictive of liver-specific outcomes and all-cause mortality

Defining comprehensive models of care for NAFLD

Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease globally. Despite the increased demand placed on health-care systems, little attention has been given to the design and implementation of efficient and effective models of care for patients with NAFLD. In many health-care settings, no formal pathways exist and, where pathways are in place, they are often not standardized according to good practices. We systematically searched the peer-reviewed literature with the aim of identifying published examples of comprehensive models of care that answered four key questions: what services are provided? Where are they provided? Who is offering them? How are they coordinated and integrated within health-care systems? We identified seven models of care and synthesized the findings into eight recommendations nested within the ‘what, where, who and how’ of care models. These recommendations, aimed at policy-makers and practitioners designing and implementing models of care, can help to address the increasing need for the provision of good practice care for patients with NAFLD

Patients with Refractory Ascites Treated with alfapump® System have Better Health-related Quality of Life as Compared to those Treated with Large Volume Paracentesis: The Results of a Multicenter Randomized Controlled Study

Background Refractory ascites (RA) is a complication of cirrhosis which is treated with large volume paracentesis (LVP) as the standard of care. Alfapump® system is a fully implantable pump system which reduces the need for LVP. The aim was to assess health-related quality of life (HRQL) in patients treated with alfapump® versus LVP. Methods The data were collected in a multicenter open-label randomized controlled trial (clinicaltrials.gov #NCT01528410). Subjects with cirrhosis Child–Pugh class B or C accompanied by RA were randomized to receive alfapump® or LVP. The SF-36v2 and CLDQ scores were compared between the two treatment arms at screening and monthly during treatment. Results Of 60 subjects randomized, HRQL data were available for 58 (N = 27 received alfapump® and N = 31 received LVP only). At baseline, no differences were seen between the treatment arms (all p > 0.05): age 61.9 ± 8.4, 79.3% male, MELD scores 11.7 ± 3.3, 85.2% Child–Pugh class B, 70.7% had alcoholic cirrhosis. The mean number of LVP events/subject was lower in alfapump® than LVP (1.1 vs. 8.6, p  0.05) in the first 3 months. Multivariate analysis showed that treatment with alfapump® was independently associated with better HRQL at 3 months (total CLDQ score: beta = 0.67 ± 0.33, p = 0.05). Conclusion As compared to LVP, the use of alfapump® system is associated with both a reduction in the number of LVP events and improvement of health-related quality of life

Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice

Background & Aims: Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. / Methods: A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas. / Results: There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of 7.5 to >20 kPa, respectively). / Conclusions: The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. / Lay summary: Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD