Characterization of patients with both alcoholic and nonalcoholic fatty liver disease in a large United States cohort

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is the hepatic manifestation of the metabolic syndrome(Met S) and is characterized by steatosis in the absence of significant alcohol consumption. However, Met S and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD) in a large cohort in the United States.METHODS Adults from the National Health and Nutrition Examination Survey between2003-2014 were included. NAFLD was diagnosed based on elevated alanine aminotransferase(ALT) and being overweight or obese in the absence of other liver diseases. BAFLD patients met the criteria for NAFLD but also had either Met S or type 2 diabetes and consumed excessive amounts of alcohol. Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI; 25.1-26.8) and that of BAFLD was 0.84%(0.67, 1.02) which corresponds to an estimated 1.24 million Americans affected by BAFLD. Compared to NAFLD, patients with BAFLD were more likely to be male, smokers, have higher ALT, aspartate aminotransferase,triglycerides, and lower platelets; P 0.01 for all. More importantly, after adjusting for Met S components, BAFLD patients were significantly more likely to have advanced fibrosis [adjusted OR(95%CI) based on FIB4 index 2.67 was 3.2(1.4, 7.0), P = 0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.     

非酒精性脂肪性肝病相关肝细胞癌发病机制研究进展

非酒精性脂肪性肝病（NAFLD）是目前临床上最常见的慢性肝病之一,NAFLD相关肝细胞癌（NAFLD-HCC）的发病率也逐年上升。众多因素参与了NAFLD-HCC的发生发展,但其具体的发病机制还不清楚。本文重点介绍近年有关其发病机制的研究进展。     

Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States

BackgroundGlobal pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease.AimsWe estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.MethodsUtilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes.ResultsThe quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men.ConclusionsThe sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.     

Association of non-alcoholic fatty liver disease with gallstone disease in the United States hospitalized patient population

BACKGROUND Gallstones and cholecystectomy have been proposed as risk factors for nonalcoholic fatty liver disease(NAFLD). The reason for this may be that both gallstones, as well as NAFLD share several risk factors with regards to their development. Currently, there is a lack of sufficient evidence showing an association between these clinical conditions.AIM To determine whether there is a meaningful association between gallstones and cholecystectomy with NAFLD.METHODS We queried the National Inpatient Sample database from the years 2016 and 2017 using International Classification of Diseases, 10 th revision, Clinical Modification diagnosis codes to identify hospitalizations with a diagnosis of gallstone disease(GSD)(includes calculus of gallbladder without cholecystitis without obstruction and acquired absence of gallbladder) as well as NAFLD(includes simple fatty liver and non-alcoholic steatohepatitis). Odds ratios(ORs) measuring the association between GSD(includes gallstones and cholecystectomy) and NAFLD were calculated using logistic regression after adjusting for confounding variables.RESULTS Out of 14294784 hospitalizations in 2016-2017, 159259 were found to have NAFLD. The prevalence of NAFLD was 3.3% in patients with GSD and 1% in those without. NAFLD was prevalent in 64.3% of women with GSD as compared to 35.7% of men with GSD. After controlling for various confounders associated with NAFLD and GSD, multivariate-adjusted analysis showed that there was an association between NAFLD with gallstones [OR = 6.32; 95% confidence interval(CI): 6.15-6.48] as well as cholecystectomy(OR = 1.97; 95%CI: 1.93-2.01). The association between NAFLD and gallstones was stronger in men(OR = 6.67; 95%CI: 6.42-6.93) than women(OR = 6.05; 95%CI: 5.83-6.27). The association between NAFLD and cholecystectomy was stronger in women(OR = 2.01; 95%CI: 1.96-2.06) than men(OR = 1.85; 95%CI: 1.79-1.92). P value was less than 0.001 for all comparisons.CONCLUSION NAFLD is more prevalent in women with GSD than men. The association between NAFLD and cholecystectomy/gallstones indicates that they may be risk factors for NAFLD.     

COVID-19 and liver injury in individuals with obesity

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.     

Clinical implications of COVID-19 in patients with metabolic-associated fatty liver disease

People across the world are affected by the coronavirus disease 2019 (COVID-19), brought on by the SARS-CoV type-2 coronavirus. Due to its high incidence in individuals with diabetes, metabolic syndrome, and metabolic-associated fatty liver disease (MAFLD), COVID-19 has gained much attention. The metabolic syndrome's hepatic manifestation, MAFLD, carries a significant risk of type-2-diabetes. The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic. Independent of the metabolic syndrome, MAFLD may impact the severity of the viral infections, including COVID-19 or may even be a risk factor. An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics. Many liver markers are seen elevated in COVID-19. MAFLD patients with associated comorbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension, and old age are prone to develop severe disease. There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19. The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19. This review investigates the implications of COVID-19 on liver injury and disease severity and vice-versa. We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.     

非酒精性脂肪性肝病相关性肝细胞癌治疗的研究进展

肝细胞癌(HCC)发病率高,乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染是HCC的主要病因.近年来,肥胖、2型糖尿病等代谢疾病的流行加速了非酒精性脂肪性肝病(NAFLD)的发生,导致NAFLD相关性HCC(NAFLD-HCC)的发生也逐年递增.但NAFLD-HCC与病毒相关性HCC是否有相似的发病机制、预防、监测...     

Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver

AIM: To define the characteristics of the Italian patient presenting non-alcoholic fatty liver disease. PATIENTS AND METHODS: A total of 305 patients with abnormally high plasma aminotransferase and/or gamma-glutamyl-transpeptidase levels for at least 12 months, with no known cause of chronic liver damage, were consecutively enrolled in the study. Clinical, routine biochemical and liver histology investigations were carried out in all patients. Also evaluated were: (a) oral glucose load; (b) insulinaemia and insulin-resistance using the HOMA test model; and (c) plasma endotoxaemia, total antioxidant plasma capability, tumour necrosis factor-alpha, plasma interleukin-6 and -10 levels. Malondialdehyde and 4-hydroxynonenal content were determined on liver samples from 120 patients. RESULTS: The majority of patients were young overweight or obese males, with dyslipidaemia (20-60%), diabetes (10.5%), hyperinsulinaemia (40%), hyperferritinaemia (35%). Endotoxaemia was negative in all patients and cytokines were only sporadically altered. Total antioxidant plasma capability was decreased in 38.4% of the patients. Eighty percent of the cases had histological steatosis with a mild degree of inflammation and fibrosis. Seven patients had cirrhosis. Lipid peroxidation markers were increased in 90% of the cases, inversely correlated with fibrosis. Even if at univariate analysis, age, ferritin and tissue 4-hydroxynonenal were independent factors of steatosis (P < 0.01), and insulin, HOMA and ferritin of inflammation and fibrosis (P < 0.01), at multivariate analysis no single factor was found to be an independent predictor of hepatic lesions. CONCLUSIONS: The typical Italian patient with non-alcoholic fatty liver disease is a young male, obese, not diabetic, with a variable incidence of dyslipidaemia and hyperinsulinaemia. Only liver biopsy may define the type of liver damage.     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)已成为目前全球最主要的慢性肝病病因,是当前研究的热点问题,其预防和治疗也成了研究的重点和难点,目前尚无批准上市的特异性药物及明确的治疗方案,本文针对NAFLD的相关治疗及新兴靶向药物作一概述,给临床医师提供参考。     

COVID-19 pandemic: Its impact on liver disease and liver transplantation

Severe pulmonary disease caused by the novel coronavirus [severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)], has devastated many countries around the world.It has overwhelmed the medical system.The priorities of many institutions have changed to manage critically ill corona virus infectious disease-2019(COVID-19) patients,which affected the working style of many departments.Hepatologists and transplant surgeons look after a very sensitive patient group.Patients with liver disease need special attention and continuous follow-up.Similarly,transplant candidates also need special care.Healthcare professionals in the field of hepatology face the overwhelming task of taking care of COVID-19 patients with hepatic complications,liver disease or transplant patients who are SARS-CoV-2 positive,and the patients on routine surveillance who do not have COVID-19.This review will evaluate COVID-19 from the perspective of its effect on the liver and its possible effects on patients with liver disease.Furthermore,the level of care for liver transplant recipients during the pandemic will be discussed.     

Machine learning models for predicting non-alcoholic fatty liver disease in the general United States population: NHANES database

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting over 30% of the United States population. Early patient identification using a simple method is highly desirable.AIMTo create machine learning models for predicting NAFLD in the general United States population.METHODSUsing the NHANES 1988-1994. Thirty NAFLD-related factors were included. The dataset was divided into the training (70%) and testing (30%) datasets. Twenty-four machine learning algorithms were applied to the training dataset. The best-performing models and another interpretable model (i.e., coarse trees) were tested using the testing dataset.RESULTSThere were 3235 participants (n = 3235) that met the inclusion criteria. In the training phase, the ensemble of random undersampling (RUS) boosted trees had the highest F1 (0.53). In the testing phase, we compared selective machine learning models and NAFLD indices. Based on F1, the ensemble of RUS boosted trees remained the top performer (accuracy 71.1% and F1 0.56) followed by the fatty liver index (accuracy 68.8% and F1 0.52). A simple model (coarse trees) had an accuracy of 74.9% and an F1 of 0.33.CONCLUSIONNot every machine learning model is complex. Using a simpler model such as coarse trees, we can create an interpretable model for predicting NAFLD with only two predictors: fasting C-peptide and waist circumference. Although the simpler model does not have the best performance, its simplicity is useful in clinical practice.     

Simple diagnostic algorithm identifying at-risk nonalcoholic fatty liver disease patients needing specialty referral within the United States

BACKGROUNDThere is an urgent need to risk stratify patients with suspected nonalcoholic fatty liver disease (NAFLD) and identify those with fibrotic nonalcoholic steatohepatitis. This study aims to apply a simple diagnostic algorithm to identify subjects with at-risk NAFLD in the general population.AIMTo apply a simple diagnostic algorithm to identify subjects with at-risk NAFLD in the general population.METHODSAdult subjects were included from the National Health and Nutrition Examination Survey database (2017-2018) if they had elevated alanine aminotransferase (ALT) and excluded if they had evidence of viral hepatitis or significant alcohol consumption. A fibrosis-4 (FIB4) cutoff of 1.3 differentiated patients with low risk vs high risk disease. If patients had FIB4 > 1.3, a FAST score < 0.35 ruled out advanced fibrosis. Patients with FAST > 0.35 were referred to a specialist. The same algorithm was applied to subjects with type 2 diabetes mellitus (T2DM).RESULTSThree thousand six hundred and sixty-nine patients were identified who met all inclusion and exclusion criteria. From this cohort, 911 (28.6%) patients had elevated ALT of which 236 (22.9%) patients had elevated FIB4 scores ≥ 1.3. Among patients with elevated FIB4 score, 75 (24.4%) had elevated FAST scores, ruling in advanced fibrosis. This accounts for 2.0% of the overall study population. Applying this algorithm to 737 patients with T2DM, 213 (35.4%) patients had elevated ALT, 85 (37.9%) had elevated FIB4, and 42 (46.1%) had elevated FAST scores. This accounts for 5.7% of the population with T2DM.CONCLUSIONThe application of this algorithm to identify at-risk NAFLD patients in need for specialty care is feasible and demonstrates that the vast majority of patients do not need subspecialty referral for NAFLD.     

非酒精性脂肪性肝病肝纤维化的诊断和治疗进展

非酒精性脂肪性肝病(NAFLD)正成为全球最常见的慢性肝病。从其疾病谱来看,非酒精性脂肪性肝炎(NASH)是疾病进展形式,可进展为肝纤维化,从而导致NAFLD相关肝硬化和肝癌。NASH肝纤维化与疾病预后密切相关,临床亟需有效措施诊断及干预疾病进展。重点介绍了目前非酒精性脂肪性肝纤维化的诊断和治疗进展。     

Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease: A controversial issue

Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients. The potential role of autophagy in disease is increasingly recognised and investigated in the last decade. Nowadays it is commonly accepted that autophagy plays a role in the hepatic lipid metabolism. Hence, dysfunction of autophagy may be an underlying cause of non-alcoholic fatty liver disease. However, controversy of the exact role of autophagy in the lipid metabolism exists: some publications report a lipolytic function of autophagy, whereas others claim a lipogenic function. This review aims to give an update of the present knowledge on autophagy in the hepatic lipid metabolism, hepatic insulin resistance, steatohepatitis and hepatic fibrogenesis.     

2型糖尿病对非酒精性脂肪性肝病的影响

2型糖尿病与非酒精性脂肪性肝病关系密切,其对非酒精性脂肪性肝病流行病学与抗糖尿病治疗对非酒精性脂肪性肝病病情转归均有影响。此文就2型糖尿病对NAFLD发病、进展及抗糖尿病治疗中生活方式干预和胰岛素增敏剂应用对NAFLD的影响作一综述,旨在为临床决策提供参考。