Paediatric steatotic liver disease has unique characteristics: A multisociety statement endorsing the new nomenclature.

Nonalcoholic fatty liver disease (NAFLD) has been a commonly used term and diagnosis in paediatric hepatology, gastroenterology, and endocrinology clinics for over 30 years. A multisociety Delphi process has determined a new name "Steatotic Liver Disease" (SLD) as the overarching term for disorders associated with hepatic lipid accumulation. Our Societies give our support to steatotic liver disease as the best overarching term for use in our communities. Metabolic dysfunction-associated steatotic liver disease (MASLD) overcomes many of the shortcomings of the name NAFLD. Here, we highlight several points of the new nomenclature that are of particular importance for our community and their consequences for implementation including: diagnostic criteria, considering alternate diagnoses, practical implementation, research, advocacy, and education for paediatricians. As with all nomenclature changes, it will take a concerted effort from our paediatric societies to help integrate the optimal use of this into practice.

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

US-FLI score - Is it possible to predict the steatosis grade with an ultrasonographic score?

OBJECTIVES: A recent ultrasonographic score (Ultrasonographic fatty liver indicator (US-FLI)) allows to grade steatosis severity on ultrasound (US).We aimed to evaluate the agreement of US-FLI with the controlled attenuation parameter (CAP) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Initially, inter-observer agreement for the score was assessed between 3 physicians using a sample of 31 patients.Later, 96 patients with NAFLD were included and several anthropometric/clinical/analytical parameters were assessed and US and transient elastography was performed. RESULTS: Physicians showed an excellent absolute agreement regarding the total score, with an average Interclass Correlation Coefficient of 0.972(95% CI 0.949-0.986). Comparing US-FLI with CAP, considering the previously defined cut-off for steatosis >S1(268dB/m) and > S2(280dB/m), US-FLI had a good discriminative capacity for both grades, with areas under the curve (AUC) of 0.88(p < 0.001) and 0.90(p < 0.001), respectively.Also, US-FLI ≤ 3 points had a negative predictive value of 100% for steatosis >S2 and US-FLI ≥6 points had a positive predictive value (PPV) of 94.0% for steatosis >S2. When comparing the clinical score Fatty Liver Index (FLI) for the same CAP cut-offs, it showed a weak discriminative capacity for both grades, with AUC of 0.65(p = 0.030) and 0.66(p = 0.017). AUC for US-FLI and FLI were significantly different for both cut-offs (p < 0.001). CONCLUSION: US-FLI has an excellent reproducibility and a good discriminative capacity for the different steatosis grades.Scores ≤3points exclude significant steatosis and scores ≥6 points have a PPV of 94,0% for steatosis >S2.US-FLI was significantly superior to the clinical score FLI in the discrimination between steatosis grades.

Detection of Frozen-Thawed Duck Fatty Liver by MALDI-TOF Mass Spectrometry: A Chemometrics Study.

The marketing of poultry livers is only authorized as fresh, frozen, or deep-frozen. The higher consumer demand for these products for a short period of time may lead to the marketing of frozen-thawed poultry livers: this constitutes fraud. The aim of this study was to design a method for distinguishing frozen-thawed livers from fresh livers. For this, the spectral fingerprint of liver proteins was acquired using Matrix-Assisted Laser Dissociation Ionization-Time-Of-Flight mass spectrometry. The spectra were analyzed using the chemometrics approach. First, principal component analysis studied the expected variability of commercial conditions before and after freezing-thawing. Then, the discriminant power of spectral fingerprint of liver proteins was assessed using supervised model generation. The combined approach of mass spectrometry and chemometrics successfully described the evolution of protein profile during storage time, before and after freezing-thawing, and successfully discriminated the fresh and frozen-thawed livers. These results are promising in terms of fraud detection, providing an opportunity for implementation of a reference method for agencies to fight fraud.

A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement.

The exclusion of other chronic liver diseases including "excess" alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, "positive criteria" to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward.

Hounsfield unit values of liver pathologies in unenhanced post-mortem computed tomography.

BACKGROUND: The goal of this study was to evaluate if unenhanced PMCT HU values of liver pathologies differ from post-mortem HU values of non-pathologic liver tissue. METHODS: Liver HU values were measured in five liver segments in PMCT unenhanced datasets of 214 forensic cases (124 male, 90 female, mean age 54.3 years). Liver HU values were compared with corresponding histologic liver findings. HU values of non-pathologic livers were compared to HU values of liver pathologies. RESULTS: A total of 64 non-pathologic livers (mean HU 58.32, SD 8.91) were assessed. Histologic diagnosed liver pathologies were as follows: steatosis (n = 121 (grade I n = 61, grade II n = 37, grade III n = 23)), fibrosis (n = 10), and cirrhosis (n = 19). HU values of the livers exhibiting severe steatosis (mean HU 32.44, SD 13.76), fibrosis (mean HU 44.7, SD 16.31), and cirrhosis (mean HU 50.59, SD 9.42) significantly differed to HU values of non-pathologic livers at ANOVA testing. CONCLUSION: PMCT unenhanced liver HU value measurements may be used as an additional method to detect unspecific liver-pathology. Values below 30 HU may specifically indicate severe steatosis.

Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.

We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver.

Staging of Fatty Liver Diseases Based on Hierarchical Classification and Feature Fusion for Back-Scan-Converted Ultrasound Images.

Fatty liver disease is progressive and may not cause any symptoms at early stages. This disease is potentially fatal and can cause liver cancer in severe stages. Therefore, diagnosing and staging fatty liver disease in early stages is necessary. In this paper, a novel method is presented to classify normal and fatty liver, as well as discriminate three stages of fatty liver in ultrasound images. This study is performed with 129 subjects including 28 normal, 47 steatosis, 42 fibrosis, and 12 cirrhosis images. The proposed approach uses back-scan conversion of ultrasound sector images and is based on a hierarchical classification. The proposed algorithm is performed in two parts. The first part selects the optimum regions of interest from the focal zone of the back-scan-converted ultrasound images. In the second part, discrimination between normal and fatty liver is performed and then steatosis, fibrosis, and cirrhosis are classified in a hierarchical basis. The wavelet packet transform and gray-level co-occurrence matrix are used to obtain a number of statistical features. A support vector machine classifier is used to discriminate between normal and fatty liver, and stage fatty cases. The results of the proposed scheme clearly illustrate the efficiency of this system with overall accuracy of 94.91% and also specificity of more than 90%.

Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease.

UNLABELLED: Biopsy is still the gold standard for the diagnosis of nonalcoholic steatohepatitis but the definition may vary among pathologists, a drawback especially in evaluation of biopsies for clinical trials. We previously developed a scoring system (steatosis, activity, fibrosis [SAF]) allowing the use of an algorithm (fatty liver inhibition of progression [FLIP]) for the classification of liver injury in morbid obesity. The aim of this study was to determine whether the use of the SAF score and FLIP algorithm can decrease interobserver variations among pathologists. In a first session, pathologists categorized 40 liver biopsies of patients with nonalcoholic fatty liver disease (NAFLD) according to their own experience. In a second reading session, each pathologist reclassified the same slides by using the FLIP algorithm and SAF score, blinded to their first evaluation. The experiment was repeated with two different groups of pathologists at varying levels of training in liver pathology. The percentage of biopsy interpretation concordant with reference evaluation increased from 77% to 97% in Group 1 and from 42% to 75% in Group 2 after the use of the SAF score and FLIP algorithm. The strength of concordance in classification increased in Group 1 from moderate (κ = 0.54) to substantial (κ = 0.66) and from fair (κ = 0.35) to substantial (κ = 0.61) in Group 2 with application of the algorithm. With regard to the SAF score, concordance was substantial in Group 1 for steatosis (κ = 0.61), activity (κ = 0.75), and almost perfect for fibrosis (κ = 0.83 after pooling 1a, 1b, and 1c together into a single score F1). Similar trends were observed in Group 2 (κ = 0.54 for S, κ = 0.68 for A, and κ = 0.72 for F). CONCLUSION: The FLIP algorithm based on the SAF score should decrease interobserver variations among pathologists and are likely to be implemented in pathology practice.

Progress is impossible without change: understanding the evolving nomenclature of steatotic liver disease and its effect on hepatology practice.

The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials.

New nomenclature for fatty liver disease.

This review investigates that, in 2023, fatty liver disease underwent a name change to "steatotic liver disease" (SLD). SLD now includes metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), and metabolic and alcohol-related liver disease (MetALD). The renaming aims to better incorporate alcohol intake and metabolic risk factors into disease classification and to diminish the stigma associated with the previous nomenclature. Early identification of the patient's aetiology is important for the prognosis which can be improved by interventions against the causative risk factors.

[Chronic liver diseases--new therapy. Are biopsies necessary?]. / Chronische Lebererkrankungen--neue Therapie. Benötigen wir die Biopsie?

Chronic liver disease can often reliably be assessed only by examination of biopsy material. In this article the possible indications for liver biopsy in viral hepatitis B and C, autoimmune liver disease, steatohepatitis and hereditary metabolic diseases are described. A biopsy may be useful in cases with unclear clinical or serological situations or with questionable chronicity and comorbidities. The assessment of biopsy material should be based on guideline-based classification systems. The value of biopsy diagnosis benefits from a close interdisciplinary clinical pathological cooperation.

Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality.

UNLABELLED: Since the initial description of nonalcoholic steatohepatitis (NASH), several sets of pathologic criteria for its diagnosis have been proposed. However, their interprotocol agreement and ability to predict long-term liver-related mortality (LRM) have not been demonstrated. In this study, we examined patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) for whom liver biopsy slides and clinical and mortality data were available. Liver biopsy samples were evaluated for a number of pathologic features and were classified according to the presence or absence of NASH by (1) the original criteria for NAFLD subtypes, (2) the nonalcoholic fatty liver disease activity score (NAS), (3) the Brunt criteria, and (4) the current study's criteria. All NASH diagnostic criteria and individual pathologic features were tested for agreement and for their independent associations with LRM, which were determined with a Cox proportional hazards model. Two hundred fifty-seven NAFLD patients with complete data were included. The diagnoses of NASH by the original NAFLD subtypes and by the current study's definition of NASH were in almost perfect agreement (κ = 0.896). However, their agreement was moderate with NAS (κ = 0.470 and κ = 0.511, respectively) and only fair to moderate with the Brunt criteria (κ = 0.365 and κ = 0.441, respectively). Furthermore, the agreement of the Brunt criteria with NAS was relatively poor (κ = 0.178). During the follow-up (median = 146 months), 31% of the patients died (9% were LRM). After we controlled for confounders, a diagnosis of NASH by the original criteria for NAFLD subtypes [adjusted hazard ratio = 9.94 (95% confidence interval = 1.28-77.08)] demonstrated the best independent association with LRM. Among the individual pathologic features, advanced fibrosis showed the best independent association with LRM [adjusted hazard ratio = 5.68 (95% confidence interval = 1.50-21.45)]. CONCLUSION: The original criteria for NAFLD subtypes and the current study's criteria for NASH were in almost perfect agreement, but their level of agreement with the NAS and Brunt criteria was lower. A diagnosis of NASH by the original criteria for NAFLD subtypes demonstrated the best predictability for LRM in NAFLD patients.

A prospective evaluation of the role of transient elastography for the detection of hepatic fibrosis in type 2 diabetes without overt liver disease.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and subsequently hepatic fibrosis. Transient elastography (TE) is a rapid, reproducible non-invasive test that may be appropriate as a screening tool for the presence of hepatic fibrosis. AIM: Assess the utility of TE as a screening tool for the presence of hepatic fibrosis in a T2DM population with no known liver disease. METHODS: T2DM patients without known liver disease were included. Patients were assessed with TE in addition to biochemical parameters. RESULTS: A successful TE evaluation could be obtained in 74 of 81 (91%) included subjects. Of these, 26 (35%) had a liver stiffness measurement (LSM) ≥ 7.65 kPa. Sixteen of these subjects had confirmatory liver biopsies with significant (≥ F2 fibrosis) present in 12 (75%) and cirrhosis diagnosed in 2 subjects. 15/16 (94%) had histological steatohepatitis. Compared with those with a lower LSM, subjects with an LSM ≥ 7.65 kPa had higher ALT levels (38.0 ± 21.7 vs 26.1 ± 11.1 U/L, p = 0.021) and increased prevalence of hepatic steatosis by ultrasound (85% vs 63%, p = 0.005). CONCLUSION: Significant hepatic fibrosis in the T2DM population is frequently under-recognized. TE may be a feasible tool for the screening of T2DM patients for the presence of hepatic fibrosis.

Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index.

BACKGROUND AND AIM: Donor liver steatosis can impact on liver allograft outcomes. The aim of the present study was to comprehensively report on the impact of type and grade of donor steatosis, as well as donor and recipient factors, including the reported Donor Risk Index (DRI), on liver allograft outcomes. METHODS: A review of unit data for all adult liver transplant procedures from 2001 to 2007, as well as donor offers. Donor liver biopsies were regraded for steatosis by an experienced histopathologist. RESULTS: Steatosis was detected in 184/255 (72%) of biopsies, of which 114 (62%) had microvesicular steatosis (MiS; 68 mild, 22 moderate, 24 severe) and 70 (38%) macrovesicular steatosis (MaS; 59 mild, 7 moderate, 4 severe). The majority (66/70, 94%) of biopsies with MaS also contained MiS. Allograft steatosis was associated with increasing donor body mass index (P = 0.000), plus donor male sex (P < 0.05). Primary non function (P = 0.002), early renal failure (P = 0.040), and requirement for retransplantation (P = 0.012) were associated only with severe MaS. Early biliary complications were associated with moderate MaS (P = 0.039). Only severe MaS was significantly associated with inferior allograft survival at 3 months (relative risk = 12.09 [8.75-19.05], P = 0.000) and 1 year (P = 0.000). CONCLUSIONS: MiS is a common finding and frequently coexists with MaS on liver allograft biopsy, while isolated MaS is uncommon. Only the presence of moderate to severe MaS is associated with inferior early allograft outcomes. The impact of severe MaS on allograft survival appears greater than other donor factors, including the calculated DRI.

Transitional features of histologic type of non-alcoholic fatty liver disease in Korean young men.

BACKGROUND AND AIM: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in Korea as the dietary pattern and lifestyle become more Westernized and the obese population increases. The spectrum of NAFLD ranges from asymptomatic steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Schwimmer et al. divided NASH into three types according to the histological characteristics, such as adult type, pediatric type and overlap type. We investigated clinical and histologic features of NAFLD patients in Korean young men. METHODS: A total of 64 male patients under age 30 years, diagnosed as NAFLD by a liver biopsy, were reviewed retrospectively. NASH was diagnosed by NAFLD activity score (NAS), and NASH patients were classified with Schwimmer's histological classification. RESULTS: Pathological features of liver biopsy revealed NASH in most cases (59 cases, 92.2%) including 29 cases (45.3%) of borderline NASH and 30 cases (46.9%) of definite NASH. The definite NASH group showed significantly high aspartate aminotransferase/alanine aminotransferase levels compared to the borderline NASH group. There were four cases (6.8%) of pediatric type, 17 cases (28.8%) of adult type, and 38 cases (64.4%) of overlap type in the NASH group. NAS was 3.75 ± 0.05 in the pediatric type, 4.29 ± 1.16 in the adult type and 4.87 ± 1.21 in the overlap type, and the overlap type showed a higher NAS than the pediatric type. The fibrosis stage was significantly higher in the overlap type than the other types. CONCLUSION: Most Korean young men with NAFLD turned out to have borderline or definite NASH. More than half of the NASH cases showed overlap type in Korean young men.