The interaction of genetics and physical activity in the pathogenesis of metabolic dysfunction associated liver disease

Effect of Weight Loss on Magnetic Resonance Imaging Estimation of Liver Fat and Volume in Patients With Nonalcoholic Steatohepatitis

Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease

Somatostatin, Estrogen, and Polycystic Liver Disease

Nonalcoholic Fatty Liver Disease in Children: Where Are We?

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

Impact of Fatty Liver Disease on Health Care Utilization and Costs in a General Population: A 5-Year Observation

Fatigue in Cirrhosis: Is Transplant the Answer?

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in the pediatric population in the last few decades[1,2]. In Western countries, the prevalence of NAFLD is estimated up to 10% of children. In Iran fatty liver was diagnosed by ultrasound in 7.1% of children aged 7-18 years[1]. Increased prevalence of this form of liver disease runs parallel with the dramatic rise in childhood obesity and diabetes mellitus over the past 2 decades. Most of children with NAFLD are low active and obese, and suffer from metabolic impairments (including increased baseline waist circumference, hypertension and high insulin level) and dyslipidemia[3]. There was a strong relationship between NAFLD and the abnormal metabolic variables in children[4]. Higher age, higher fasting insulin, abnormality in total cholesterol, LDL cholesterol and triglycerides is linked with higher risk of NAFLD[1]. Pediatric NAFLD is not a benign condition, and it can be a predictive of cardiovascular disease and diabetes mellitus in adulthood and some times it can progress to severe liver diseases[4]. The mechanisms leading to NAFLD in children is the same as in adults and include genetic background, epigenetics and environmental factors (i.e. high caloric intake, daily consumption of junk food and soft drinks, low level of physical activity, and beyond average weight) all of which concur during development and progression of the disease[5]. Obesity is the circle between the risk factors showing that 70% of NAFLD in pediatric group is associated with obesity[6]. Faghih et al found a tremendous trend toward over-weight and obesity with a 3-fold increase of obesity among adolescent girl students in Ahvaz between 1997 and 2006. The data showed that there was a significant relation between BMI and food habits including number of meals and missing the breakfast. The authors recommend, regarding the harmful ramifications of obesity, to encourage healthy eating patterns and increased physical activity among adolescent girls[7]. Diagnosis is established by liver biopsy. Laboratory tests and radiographic findings provide clues to the potential presence of fatty liver disease. Liver enzymes elevation in childhood is a cardio-metabolic risk factor and an additional component of the metabolic syndrome[8]. In all children with abnormal level of liver enzymes, evaluation of NAFLD should be done. To screen children susceptible to NAFLD, it will be very useful to assess waist circumference, fasting blood sugar, fasting insulin and serum lipid profile in regular intervals. Nutrition plays essential role in development of NAFLD and it can regress the fatty accumulations in the liver. Lifestyle modification, including slow and steady weight loss, improved dietary habits, and increased daily, aerobic physical activity, remains the first-line approach in treating pediatric fatty liver disease[4]. The ministries of health and education have agreed in 2007 about the instructions for healthy eating in schools. Healthy nutrition bases or markets inside the schools should be established for providing, maintaining and promotion of physical, mental and social activities of the students. The main goals are providing healthy food and avoiding unhealthy food supply for students. Healthy food means providing body’s nutritional needs with safe, adequate, varied and balanced foods. It is a common knowledge that healthy food contains low salt and low-fat with less than 10% of trans-fatty oil. Soft drinks should be eliminated from student’s regimen, mineral water and fresh fruits can replace it.

INTRODUCTION: Over 4.5 million adults in the US are diagnosed with chronic liver disease (CLD). Acute progression of CLD is associated with immune dysregulation from common infections such as influenza. CDC guidelines recommend yearly influenza vaccination for all patients over the age of 6 months regardless of the presence CLD. Prior small-scale studies demonstrated increased risk of hepatic decompensation and hospitalization amongst cirrhotic patients with influenza, however limited data exists for patients with CLDs besides cirrhosis. This study was conducted to demonstrate the impact of influenza amongst patients with a wider array of CLDs. METHODS: A retrospective cohort study was conducted using the 2010–2014 Nationwide Inpatient Sample. Adults hospitalized with influenza were identified using ICD-9 codes (Table 1). The patients were then stratified and compared based on the diagnosis of alcoholic cirrhosis (AC), nonalcoholic cirrhosis (NC), alcoholic fatty liver (AFL), autoimmune hepatitis (AIH), biliary cirrhosis (BC), non-alcoholic fatty liver disease (NAFLD), or no history of CLD. RESULTS: A total of 30,268 adults were admitted with influenza of which 515 (1.7%) patients had CLD and 29,753 (98.3%) did not. Patients with CLD had increased risk of disease severity [OR = 2.66, CI: 2.26–3.13, P < 0.001], hospitalization cost [OR = 1.24, CI: 1.15–1.33, P < 0.001], and length of stay (LOS) [OR = 1.07, CI: 1.01–1.15, P = 0.031] (Table 2). Despite no overall increased risk in mortality of CLD patients, those with AFL and AC had increased odds of mortality ([OR = 39.26, Cl: 1.78–428.46, P = 0.003] and [OR = 4.54, Cl: 1.23–13.49, P = 0.011], respectively). CONCLUSION: Patients with CLD admitted for influenza had inferior inpatient outcomes, including hospitalization costs, LOS, and disease severity, however there was no statistical difference in mortality. Stratification by CLD demonstrated that increased risk of negative outcomes not only occur in cirrhotic patients, but those with AIH, AFL, and NAFLD. Limitations of this study include the analysis of only hospitalized patients, reliance on ICD coding, and lack of vaccination data. The increased risk of disease severity, hospital charges, and length of stay amongst even a small subset of CLD patients highlights the importance of yearly influenza vaccinations in this population. Prior studies have focused on vaccination against influenza in patients with cirrhosis or post-transplant, however our data demonstrates the importance of vaccination for patients with any CLD.Table 1.: ICD-9 Codes used for Nationwide Inpatient Sample (NIS) data extractionTable 2.: Outcomes for chronic liver disease (CLD) patients admitted with Influenza

We read with interest the article published in the Liver International by Ciardullo et al.1 about the impact of MASLD and MetALD on clinical outcomes. Fatty liver disease caused by metabolic dysfunction is a leading cause of chronic liver disease; however, alcoholic liver disease (ALD) also contributes significantly to the burden of liver disease, despite receiving less attention.2 A newly proposed term, MetALD, describes the coexistence of metabolic dysfunction-associated steatotic liver disease (MASLD) and excessive alcohol intake.3 Nevertheless, there is a paucity of information regarding the impact of the MetALD concept on the overall prevalence of ALD. To investigate the prevalence of MetALD, data from the National Health and Nutrition Examination Survey (NHANES) 2017 to March 2020 cohort were analysed (Figure 1). The initial cohort consisted of 15 560 individuals; however, 5952 individuals were excluded due to being younger than 18 years of age or having missing gender data. Consequently, 9608 individuals were included in the analysis. Harmful alcohol consumption was defined as more than three drinks per day in males and more than two drinks per day in females throughout the past 12 months. Based on this criterion, 1440 (15%) individuals were identified as engaging in harmful alcohol consumption. The diagnosis of hepatic steatosis and fibrosis was established using the median values of the controlled attenuation parameter and liver stiffness measurement (LSM), with a threshold of 274 dB/m employed to determine the presence of steatosis. The prevalence of alcohol-related steatosis was approximately 6.2% in a cohort that was predominantly White (63.1%) and male (61.4%), with a mean age of 44.2 ± 14.9 years, a mean body mass index (BMI) of 34.5 ± 7.4 kg/m2, a mean alcohol intake of 154.5 ± 215.2 grams per week and a mean LSM of 6.9 ± 5.9 kPa. Upon applying the MetALD concept to this ALD cohort, a striking 98.4% of subjects with alcohol-related steatosis were reclassified as MetALD, with only 1.6% of subjects remaining classified as ALD. Among the subjects with MetALD, 97.4% met the BMI/waist circumference criterion, 58.2% had pre-diabetes or diabetes and 26.8% had hypertension. The interaction between alcohol intake and metabolic dysfunction is multifaceted. Two distinct definitions of fatty liver disease associated with metabolic dysfunction have emerged to address this complexity: metabolic dysfunction-associated fatty liver disease (MAFLD) and MASLD.4-6 The SLD definition proposes the term ‘MetALD’ to describe patients with MASLD who also exhibit excessive alcohol intake, without providing specific terms for MASLD coexisting with other causes. In contrast, the MAFLD definition eschews the introduction of new terms and instead incorporates the concept of dual aetiologies, encompassing the coexistence of MAFLD with any other cause, including excessive alcohol intake. To illustrate this concept, an analogy can be drawn from other metabolic disorders. Specifically, patients with dual metabolic dysfunction diseases (e.g. diabetes and hypertension) are typically diagnosed with both conditions simultaneously, rather than being assigned a distinct, combined term. Notably, the recent viewpoint by Moreno et al.7 representing the EASL Consortium for the Study of Alcohol-related Liver disease in Europe, raised significant concerns about the potential consequences of introducing new terminology such as ‘MetALD’ to describe patients with both metabolic dysfunction and excessive alcohol intake. Their primary apprehension was that this approach could inadvertently create a dichotomy among individuals exposed to alcohol, potentially leading to the exclusion of patients meeting metabolic criteria from being recognized as having ALD.7 Our analysis substantiates these concerns and suggests that adopting the concept of dual aetiology, rather than introducing new terminology, may be the more appropriate approach. In conclusion, the application of the MetALD concept to large US cohorts yielded a striking outcome: a significant 98.4% of subjects with alcohol-related steatosis were reclassified as MetALD, leaving a mere 1.6% of subjects classified as ALD. This finding raises important questions about the validity and utility of the MetALD concept, suggesting that it may require reevaluation and refinement to better capture the complexities of liver disease aetiology. All authors shared conceptualization and designed the idea in addition to collection of data. Yasser Fouad wrote the initial draft. All authors revised the manuscript and approved the final version. No funding was obtained or required for this study. All authors have nothing to disclose relevant to this work. Data sharing is not applicable to this article as no data sets were generated or analysed during the current study.

In this study, we aimed to investigate the impact of non-alcoholic hepatic steatosis on the liver volume. As investigating hepatic steatosis, we utilized computed tomography (CT) to determine the degree of steatosis and we utilized hepatobiliary ultrasonography (USG) for densitometry and correlation. As hepatosteatosis group, 35 patients over 18years of age and whose abdominal CT scans were requested by several clinics and performed routinely were included in this study, and as control group, 40 healthy subjects without hepatosteatosis (clinically and radiologically) and correlated with hepatosteatosis group in terms of age and gender were included in this study. CT densitometry and liver attenuation index (LAI) of all individuals who participated in our study were calculated, and contrast images of patients were transferred to CT-Volume Software (Siemens Syngo Multimodality Workplace; Version VE52A). In this study, interactive and automated volume measurement techniques were used together. The volumes were measured separately in patient and control group. In this study for each stage in USG, there was found a direct correlation in terms of LAI and volume, and this correlation was statistically significant (p<0.01). Furthermore, statistical significance between size and USG stage draws attention (p<0.05). A significance relationship between USG stage and age could not be determined. As a result, we have reached the conclusion that CT densitometry can be used as an assistive technique along with USG to determine the degree of steatosis in the non-alcoholic fatty liver disease, and there is a positive linear correlation between the liver size and volume, and liver volume increases in the non-alcoholic fatty liver disease.

Liver and Kidney volume Reduction May Underlie Metabolic Adaptation After Metabolic Bariatric Surgery: A sub-study of the "POWER" Randomized clinical trial.

Non-alcoholic fatty liver disease: Not time for an obituary just yet!

Lean Fatty Liver Disease: Through Thick and Thin

To estimate the optimal density coefficient for conversion of liver volume into liver weight in patients with chronic liver disease based on semiautomated CT-liver volumetry data and the histologic Ishak score of explanted liver. A total of 114 patients (39 female; age, 46±20 years) with chronic liver diseases who underwent liver transplantation between January 2010 and September 2020 were identified over a patient chart search at our institution and subsequently analyzed in retrospect. All patients had contrast-enhanced CT-examinations (mean, 24 days) to liver transplantation. Liver volume was calculated by a semiautomated software and results compared with the liver weight registered by the pathologist. Each explanted liver was histologically scored into six classes according to the Ishak classification where the categories were subgrouped based on recommendation of the pathologists into the following categories 0-3, 4-5 and 6. Mean liver volume was 1,870±1,195, 1,162±679 and 1,278±510 mL for the categories 0-3, 4-5 and 6, respectively. Mean liver weight was 1,624±999, 1,082±669 and 1,346±559 g for the categories 0-3, 4-5 and 6, respectively. A coefficient of 0.92±0.22, 0.98±0.28 and 1.06±0.20 g/mL was found at best for conversion of liver volume into liver weight in these subgroups. Differences between Ishak-subgroups proved significant (0.002). In 4 patients with cystic liver disease, density coefficients varied significantly and were found generally lower compared to the other liver disorders. Our results yielded significant differences between the density coefficients calculated along with the Ishak score and also for the subgroup with cystic liver disease.