Criteria For Nonalcoholic Fatty Liver Disease Research Articles

NAFLD and MAFLD independently increase the risk of major adverse cardiovascular events (MACE): a 20-year longitudinal follow-up study from regional Australia

Background and aimsThe association between fatty liver disease (FLD) and cardiovascular disease (CVD) in an Australian context has yet to be defined. The primary aim of this study was to investigate the association between FLD and 3-point major adverse cardiovascular events (MACE).MethodsThis was a longitudinal follow-up study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline covariates included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were diagnosed in participants with fatty liver index (FLI) ≥ 60 and meeting other standard criteria. ICD-10 codes were used to define clinical outcomes linked to hospitalisations. Three-point MACE defined as non-fatal myocardial infarction (MI) and cerebrovascular accident (CVA) and CVD death.ResultsIn total, 1324 and 1444 participants met inclusion criteria for NAFLD and MAFLD analysis, respectively. Over 23,577 and 25,469 person-years follow-up, NAFLD and MAFLD were independent predictors for 3-point MACE, adjusting for demographic covariates and known cardiometabolic risk factors, whilst considering non-CVD death as a competing event (NAFLD: sub-hazard ratio [sHR] 1.56, 95% confidence interval [CI 1.12–2.19]; MAFLD: sHR 1.51, 95% CI 1.11–2.06). The results held true on several sensitivity analyses.ConclusionsBoth forms of FLD increase the risk for CVD independent of traditional cardiometabolic risk factors.

Is Aspartate Aminotransferase to Platelet Ratio Index a Better Noninvasive Score for Predicting Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Patients?

In the 21st century, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder. The prevalence of NAFLD within the general population in India ranges from 9 to 53%. The gold standard for assessing the severity of liver fibrosis is liver biopsy. However, due to various difficulties involved with liver biopsy, it is imperative to identify different non-invasive tools that can replace liver biopsy. A prospective observational study of 130 patients meeting the inclusion criteria for NAFLD was done for a period of 18 months. We aimed to compare the performance characteristics of different noninvasive scores [fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)] in predicting advanced fibrosis as assessed by FibroScan. In the study, 76.9% of patients were male. Advanced fibrosis was seen in 12.3% of the patients. Majority of the patients with advanced fibrosis had metabolic syndrome. Based on the area under the receiver operating characteristic curve (AUROC), the new cut-off for ruling out advanced fibrosis for FIB-4, NFS, and APRI were 1.18, -0.9, and 0.65, respectively, and APRI had the best AUROC (0.768). Abnormal glycemic status and metabolic syndrome were risk factors for advanced fibrosis. The newly derived cut-offs for the FIB-4 score, NFS score, and APRI score had a better Negative predictive value compared to the original cut-offs. Bhayani PD, Parameswaran SA, Palaniswamy KR, et al. Is Aspartate Aminotransferase to Platelet Ratio Index a Better Noninvasive Score for Predicting Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Patients? Euroasian J Hepato-Gastroenterol 2024;14(1):35-39.

Comparative study of MAFLD as a predictor of metabolic disease treatment for NAFLD

A novel concept of Metabolic Associated Fatty Liver Disease (MAFLD) was proposed, incorporating metabolic abnormalities such as obesity and diabetes, which are risk factors that affect the prognosis. Non-Alcoholic Fatty Liver Disease (NAFLD), entails fat accumulation in the liver without alcohol consumption and is often linked to obesity, insulin resistance, and metabolic syndrome. However, the broad nature of the disease concept has hindered prognosis accuracy. In this study, we assess the contribution of the impact of diagnostic criteria for MAFLD on metabolic disease progression compared to conventional diagnostic criteria for NAFLD. A total of 7159 patient who were presented to the health screening center in Tokai University Hospital both in 2015 and 2020 were included in the study. Fatty liver was diagnosed using abdominal ultrasonography. The diagnostic criteria for NAFLD were consistent with the global guidelines based on alcohol consumption. The diagnostic criteria for MAFLD were based on the International Consensus Panel. Medications (anti-hypertensive, diabetic, and dyslipidemia medications) were evaluated by self-administration in the submitted medical questionnaire. A total of 2500 (34.9%) participants were diagnosed with fatty liver (FL +), 1811 (72.4%) fit both NAFLD and MAFLD diagnostic criteria (overlap), 230 (9.2%) fit only the NAFLD diagnostic criteria (NAFLD group) and 404 (16.1%) fit the MAFLD diagnostic criteria (MAFLD group) at 2015. Over the next 5 years, medication rates increased in the NAFLD group for anti-hypertensive, + 17 (7.4%); diabetes, + 3 (1.3%); and dyslipidemia, + 32 (13.9%). In contrast, the only-MAFLD group showed a more significant increase with + 49 (12.1%), + 21 (5.2%), and + 49 (12.1%), for the respective medications, indicating a substantial rise in patients starting new medications. Our analysis of repeated health check-ups on participants revealed that the diagnostic criteria for MAFLD are more predictive of future treatment for metabolic disease than conventional diagnostic criteria for NAFLD.

MASLD, MAFLD, or NAFLD criteria: have we re-created the confusion and acrimony surrounding metabolic syndrome?

In 1980, there was the first description of patients with nonalcoholic steatohepatitis (NASH), most of whom were overweight and had type 2 diabetes. In the following years, there has been a growing appreciation that metabolic dysfunction underpins this liver disease, and metabolic dysfunction also contributes to the increased risk of extrahepatic complications, manifest in nonalcoholic fatty liver disease (NAFLD) as a multisystem disease. In 2020 & 2023, it was proposed that NAFLD should be renamed and reclassified as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), respectively. Despite subtle differences between MAFLD and MASLD, there is excellent congruence between NAFLD, MAFLD, and MASLD definitions, and affected patients usually meet the criteria for all. The following is a perspective of the authors’ views as to the challenges and advantages of the new fatty liver disease terminology and classification.

Repeated detection of non-alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults.

This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.

New criteria for metabolic dysfunction-associated fatty liver disease: advantage or question? Review

The impact of fatty liver disease on public health and the economics has raised an increased interest in studying this disease. In the year 2020, experts of an international consensus group proposed to rename non‑alcoholic fatty liver disease (NAFLD) to the metabolic dysfunction‑associated fatty liver disease (MAFLD), and to change the diagnostic criteria for the fatty liver disease, because they did not correspond to the recent concepts. The previous name of NAFLD did not fully reflect the pathogenesis of the disease, in which excessive attention was paid to alcohol, and important metabolic risk factors that significantly affect the course of the disease were underestimated. This transition to MAFLD may be appropriate in terms of clinical data, determination of liver steatosis, separation of patients with different MAFLD phenotypes. The new diagnostic criteria for MAFLD are practical, easy to use, and superior to the existing NAFLD criteria for identifying patients at increased risk of developing progressive liver disease. They include evidence of hepatic steatosis, as well as the presence of at least one of three additional criteria: overweight/obesity, type 2 diabetes mellitus, and other metabolic disorders. The limitations of the new criteria for MAFLD include the absence of the concept of non‑alcoholic steatohepatitis, as well as the exclusion from the criteria of MAFLD of subjects with NAFLD without metabolic disorders, who are not diagnosed, and their potential risk may be the cause of future concomitant diseases and complications. However, among the expert society, it was not possible to reach a broad comprehensive understanding regarding the terminology and views on the development of the MAFLD. Debate continues regarding nomenclature and diagnostic criteria for fatty liver disease associated with metabolic dysfunction. Further cohort‑controlled studies based on evidence‑based medicine are needed to resolve controversial issues and to reach a consensus regarding MAFLD. Following up on the disease course and the evolution of medical terms can improve the understanding of the pathophysiology of liver diseases and create a new concept of fatty liver disease. Coordination of views of international experts in the field of the study of MAFLD will have a decisive role in the promotion of clinical practice and research.

Increased risk of incident diabetes in patients with MAFLD not meeting the criteria for NAFLD

We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4–8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.

MAFLD might be better in identifying subjects with sarcopenia or cardiovascular risk than NAFLD: A nationwide study.

Clinical features of non-alcoholic fatty liver disease (NAFLD), but not fulfilling the diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD), remain unclear. We investigated the risk of sarcopenia and cardiovascular disease (CVD) in MAFLD and non-metabolic risk (MR) NAFLD. Subjects were selected from the Korean National Health and Nutrition Examination Surveys 2008-2011. Liver steatosis was assessed using fatty liver index. Significant liver fibrosis was defined using fibrosis-4 index, categorized by age cut-offs. Sarcopenia was defined as the lowest quintile sarcopenia index. Atherosclerotic CVD (ASCVD) risk score >10% was defined as high probability. A total of 7248 subjects had fatty liver (137 with non-MR NAFLD, 1752 with MAFLD/non-NAFLD, and 5359 with overlapping MAFLD and NAFLD). In non-MR NAFLD group 28 (20.4%) had significant fibrosis. The risk of sarcopenia (adjusted odds ratio [aOR]=2.71, 95% confidence index [CI]=1.27-5.78) and high probability of ASCVD (aOR=2.79, 95% CI=1.23-6.35) was significantly higher in MAFLD/non-NAFLD group than in non-MR NAFLD group (all P<0.05). The risk of sarcopenia and high probability of ASCVD was similar between subjects with and without significant fibrosis in non-MR NAFLD group (all P>0.05). However, the risk was significantly higher in MAFLD group than in non-MR NAFLD group (aOR=3.38 for sarcopenia and 3.73 for ASCVD; all P<0.05). The risks of sarcopenia and CVD were significantly higher in MAFLD group but did not differ according to fibrotic burden in non-MR NAFLD group. The MAFLD criteria might be better for identifying high-risk fatty liver disease than the NAFLD criteria.

Increased GH/IGF-I Axis Activity Relates to Lower Hepatic Lipids and Phosphor Metabolism.

Non-alcoholic fatty liver disease (NAFLD) is a leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess, suggest an inverse relationship with intrahepatic lipid (IHL) content, less is known about the impact of the GH/IGF-I axis on IHL, lipid composition, and phosphor metabolites in individuals without disorders of GH secretion. The aim was to investigate the relation between activity of the GH/IGF-I axis and IHL content and phosphor metabolism. We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5.6%. The GH/IGF-I axis was evaluated in a fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index), and phosphate metabolites were analyzed by using 1H/31P magnetic resonance spectroscopy. In the overall cohort (40.6 ± 15 years; body mass index: 24.5 ± 3 kg/m2; IGF-I: 68.0 ± 17% upper limit of normal), fasting GH (R = -0.31; P = .02), GH during oral glucose tolerance test (R = -0.51; P < .01), and IGF-I (R = -0.28; P = .03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD than in controls (47.7 [22; 143] ng/mL/min vs 16.8 [7; 32] ng/mL/min; P = .003). GH/IGF-I axis activity correlated with lipid composition and with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH axis activity is associated with higher IHL and an unfavorable lipid composition, probably mediated by changes in hepatic energy metabolism.

The association between nonalcoholic fatty liver disease and corrected QT interval prolongation among generally healthy Iranian population: Fasa Cohort Study (FACS).

There are limited studies about the association between nonalcoholic fatty liver disease (NAFLD) and corrected QT interval(QTc) prolongation worldwide. Therefore, we designed the current study to determine this association in a large cohort of a generally healthy population. We analyzed the data of 4603 individuals aged 35-70 who participated in the Fasa Cohort Study (FACS). Based on 12-lead electrocardiograms, QT intervals were calculated and corrected by Bazzet's formula. A QTc interval of more than 430 ms in men and 450 ms in women was considered prolonged. The Fatty Liver Index was used to identify the participants with NAFLD. Of all participants, 1550 (33.6%) met the NAFLD criteria. In subjects of both genders with NAFLD, the mean values of the QTc interval were considerably higher than in those without NAFLD (p < .001). After adjusting for a wide range of confounders, including age, gender, smoking status, physical activity, total cholesterol,high-density lipoprotein-cholesterol levels, diabetes, and hypertension status, in linear regression analysis, the standardized β coefficient of QTc interval among participants with NAFLD was 2.56 ms (95% confidence interval[CI]: 0.49-4.64). After controlling the same confounders, the odds ratio of NAFLD for a prolonged QTc interval in men was 1.47 (95% CI: 1.18-1.84; p < .001) and in women was 1.39 (95% CI: 1.15-1.68; p < .001) using logistic regression analysis. NAFLD was a risk factor for QTc interval prolongation. Awareness about the risk of NAFLD in increasing the potential cardiac arrhythmias should be raised to lower cardiac mortality.

Comparison of Clinical Characteristics and Outcomes of MAFLD and NAFLD in Chinese Health Examination Populations.

The recently proposed concept of metabolic dysfunction-associated fatty liver disease (MAFLD) has remained controversial. We aimed to describe the features and associated outcomes to examine the diagnostic ability of MAFLD for identifying high-risk individuals. In this retrospective cohort study, we enrolled 72,392 Chinese participants between 2014 and 2015. Participants were classified as MAFLD, nonalcoholic fatty liver disease (NAFLD), non-MAFLD-NAFLD, and a normal control group. The primary outcomes were liver-related and cardiovascular disease (CVD) events. Person-years of follow-up were calculated from enrolment to the diagnosis of the event, or the last date of data (June, 2020). Of the 72,392 participants, 31.54% (22,835) and 28.33% (20,507) qualified the criteria for NAFLD or MAFLD, respectively. Compared with NAFLD, MAFLD patients were more likely to be male, overweight, and have higher biochemical indices including liver enzyme levels. Lean MAFLD diagnosed with ≥2 or ≥3 metabolic abnormalities presented similar clinical manifestations. During the median follow-up of 5.22 years, 919 incident cases of severe liver disease and 2,073 CVD cases were recorded. Compared with the normal control group, the NAFLD and MAFLD groups had a higher cumulative risk of liver failure and cardiac-cerebral vascular diseases. There were no significant differences in risk between the non-MAFLD-NAFLD and normal group. Diabetes-MAFLD group had the highest incidence of liver-related and cardiac-cerebral vascular diseases, lean MAFLD came second, and obese-MAFLD had the lowest incidence. This real-world study provided evidence for rationally assessing the benefit and practicability of the change in terminology from NAFLD to MAFLD. MAFLD may be better than NAFLD in identifying fatty liver with worse clinical features and risk profile.

Noninvasive tests for nonalcoholic fatty liver disease in a multi-ethnic population: The HELIUS study.

Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence and severity globally, prompting noninvasive testing, yet limited data exist on noninvasive liver tests (NITs) including transient elastography (TE) in ethnically diverse populations. Therefore, we studied prevalence and ethnic differences in NAFLD with NITs in the multi-ethnic HEalthy Life In an Urban Setting (HELIUS) cohort. NITs of liver steatosis (Fatty Liver Index [FLI]) and fibrosis (Fibrosis-4 index [FIB-4], and aspartate aminotransferase-to-platelet ratio [APRI]) were assessed in 10,007 participants. A subpopulation of 399 participants, selected on high-risk criteria for NAFLD (obesity, type 2 diabetes mellitus [T2DM], and/or elevated NITs), was examined with TE. FLI was ≥60 in 27.3% of 10,007 participants, indicating steatosis. Most participants (71.8%) had FIB-4 < 1.30, excluding advanced liver fibrosis, and 1.1% (n=113) had high FIB-4 (FIB-4 ≥ 2.67), indicating likely advanced liver fibrosis. In the TE subpopulation, 37.8% and 17.3% had steatosis and fibrosis (continuation attenuation parameter [CAP] ≥ 280 dB/m, liver stiffness measurement [LSM] ≥ 7.0 kPa, respectively). Turkish participants had highest adjusted odds ratio (OR) for elevated LSM (1.72, 95% confidence interval [CI] 0.59-5.01) and Ghanaians the lowest (0.24, 95% CI 0.09-0.65). Ghanaians had lowest adjusted OR for elevated CAP: 0.18 (95% CI 0.09-0.37). In diabetics, CAP and LSM were 17.6% and 14.6% higher than in nondiabetics, respectively. Correlations of FIB-4 and APRI with LSM were absent and weak. Conclusion : Liver steatosis proxy FLI was elevated in 27.3% of this multi-ethnic population. In Turkish background and in those with T2DM, proxies for steatosis and fibrosis were high, whereas in Ghanaian background, NITs were generally low. Together, this warrants awareness for NAFLD among high-risk populations, taking ethnic background into account. The absence of clear correlation between FIB-4 and APRI with LSM questions the accuracy of these fibrosis NITs to detect advanced fibrosis in the general population.

Clinical Trajectory and Predictors of Intensive Care Unit Mortality Among Nonalcoholic Fatty Liver Disease Patients: A Retrospective Case–Control Study

Despite being the most common liver disease worldwide, the clinical trajectory and inpatient crude mortality rate of nonalcoholic fatty liver disease (NAFLD) patients admitted to the intensive care unit (ICU) have not been thoroughly studied. We conducted a single-center retrospective case-control study of patients admitted to a general ICU setting between the years 2015 and 2020. Medical records from patients who met the diagnostic criteria for NAFLD, as well as age- and gender-matched control group, were reviewed. The primary endpoint was crude ICU mortality, defined as death within 30 days of ICU admission. The secondary outcomes included presentation with septic shock and severe sepsis, Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II scores, vasopressor requirements, mechanical ventilation need, and admission-to-ICU transfer time. Two hundred fifty subjects were enrolled and were equally divided into the NAFLD and control groups. NAFLD group subjects had higher overall 30-day ICU mortality (63.9% vs 36.1%, P < 0.05), more frequent presentation with septic shock and severe sepsis (55.2% vs 33.6%, P < 0.05), higher Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores at presentation (21.3±12.5 vs16.6±10.5 and 11.36±5.2 vs 8.3±6.2, P < 0.05), higher need for mechanical ventilation (18.4 vs 7.2%, P= 0.05), and vasopressor (15.2% vs 7.2%, P= 0.05) dependency on admission with a shorter admission-to-ICU transfer mean interval (3 vs 6 days, P < 0.05). There were no differences in the need for blood transfusions, steroids, or dialysis between the two groups. Higher fibrosis-4 (FIB-4) and NAFLD fibrosis scores were found to be associated with mortality in ICU-admitted NAFLD patients. NAFLD patients are more likely than non-NAFLD admitted ICU patients to present with severe sepsis and septic shock, have a shorter admission-to-ICU transfer time, and have a higher crude ICU mortality rate.

Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is a nutritional metabolic disease. Artemisia capillaris (AC) is the above-ground dried part of Artemisia capillaris Thunb. or Artemisia scoparia Waldst. et Kit., a natural medicinal plant with pharmacological effects of heat-clearing and biliary-promoting. In order to evaluate the therapeutic effect of Artemisia capillaris on NAFLD and obesity, experiments were conducted using aqueous extracts of Artemisia capillaris (WAC) to intervene in NAFLD models in vivo and in vitro. In vivo experiments were performed using HFD-fed (high fat diet) C57BL/6 mice to induce NAFLD model, and in vitro experiments were performed using oleic acid to induce HepG2 cells to construct NAFLD cell model. H.E. staining and oil red O staining of liver tissue were used to observe hepatocytes. Blood biochemistry analyzer was used to detect serum lipid levels in mice. The drug targets and mechanism of action of AC to improve NAFLD were investigated by western blotting, qRT-PCR and immunofluorescence. The results showed that C57BL/6 mice fed HFD continuously for 16weeks met the criteria for NAFLD in terms of lipid index and hepatocyte fat accumulation. WAC was able to reverse the elevation of serum lipid levels induced by high-fat diet in mice. WAC promoted the phosphorylation levels of PI3K/AKT and AMPK in liver and HepG2 cells of NAFLD mice, inhibited SREBP-1c expression, reduced TG and lipogenesis, and decreased lipid accumulation. In summary, WAC extract activates PI3K/AKT pathway, reduces SREBP-1c protein expression by promoting AMPK phosphorylation, and decreases fatty acid synthesis and TG content in hepatocytes. AC can be used as a potential health herb to improve NAFLD and obesity.

Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction= .029) and those without elevated triglycerides levels (P for interaction= .047). In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.

Association of hidradenitis suppurativa and liver disease: A systematic review and meta-analysis

To the Editor: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity. Studies have suggested an association between HS and metabolic syndrome,1Ergun T. Hidradenitis suppurativa and the metabolic syndrome.Clin Dermatol. 2018; 36: 41-47https://doi.org/10.1016/j.clindermatol.2017.09.007Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar a risk factor for numerous liver pathologies. However, whether HS is independently associated with liver disease remains unclear.2Durán-Vian C. Arias-Loste M.T. Hernández J.L. et al.High prevalence of non-alcoholic fatty liver disease among hidradenitis suppurativa patients independent of classic metabolic risk factors.J Eur Acad Dermatol Venereol. 2019; 33: 2131-2136https://doi.org/10.1111/jdv.15764Crossref PubMed Scopus (16) Google Scholar,3Jung J.M. Lee K.H. Kim Y.J. et al.Assessment of overall and specific cancer risks in patients with hidradenitis suppurativa.JAMA Dermatol. 2020; 156: 844-853https://doi.org/10.1001/jamadermatol.2020.1422Crossref PubMed Scopus (13) Google Scholar Herein, we aim to resolve this discrepancy through a systematic review and meta-analysis of the literature. MEDLINE and Embase were searched from inception to October 4, 2021, using keywords “hidradenitis” and “liver disease” according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines (International prospective register of systematic reviews (PROSPERO) CRD42021228708). Of 246 records, 6 case-control, 1 cross-sectional, and 2 cohort studies, published between 2001 and 2022, were included, totaling 42,791 patients with HS (Fig 1). According to the Newcastle-Ottawa scale, all studies were rated “high” quality (Supplementary Data, available via Mendeley at https://www.doi.org/10.17632/z46my2brw6.1). Patients with HS had increased prevalence (38.5% to 72.9%) and odds (2.79-7.75) of nonalcoholic fatty liver disease (NAFLD) when adjusting for confounders, such as age, body mass index, smoking, diabetes, hypertension, dyslipidemia, and metabolic syndrome. The wide ranges reported are likely due to heterogenous screening and diagnostic criteria for NAFLD, with varying degrees of sensitivity and specificity across studies. Notably, NAFLD severity may be correlated with HS severity, as one study found that patients with severe HS had increased prevalence of liver disease (3.6% vs 1.5%, P < .05). Patients with HS also had increased prevalence of other types of hepatobiliary disease. Across studies, increased prevalence (0.5% vs 0.4%, P < .001) and odds (odds ratio = 1.27, 95% confidence interval = 1.04-1.54, P = .02) of alcoholic fatty liver disease were reported. Additionally, increased odds of hepatitis B were found across studies (odds ratio = 1.47, 95% confidence interval = 1.12-1.93, P = .005). HS was not associated with increased odds of gallstones, hepatitis A, hepatitis C, or increased risk of biliary or liver cancer across studies. Although patients with liver disease are known to be at risk for advanced fibrosis and hepatocellular carcinoma, an association between HS and cirrhosis, biliary cancer, and liver cancer was not found across a small number of studies. However, these findings may be influenced by survival bias, especially considering the increased all-cause mortality in patients with HS.4Reddy S. Strunk A. Garg A. All-cause mortality among patients with hidradenitis suppurativa: a population-based cohort study in the United States.J Am Acad Dermatol. 2019; 81: 937-942https://doi.org/10.1016/j.jaad.2019.06.016Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Further high-quality studies are required to investigate these associations. The association between HS and liver pathology is hypothesized to result from chronic systemic inflammation. Patients with HS have increased levels of adipokines (leptin and adiponectin),5Malara A. Hughes R. Jennings L. et al.Adipokines are dysregulated in patients with hidradenitis suppurativa.Br J Dermatol. 2018; 178: 792-793https://doi.org/10.1111/bjd.15904Crossref PubMed Scopus (25) Google Scholar which regulate hepatic fat accumulation, and proinflammatory cytokines (interleukin-1β, interleukin-6, interleukin-23, and tumor necrosis factor α), which stimulate hepatic inflammation, cell necrosis and apoptosis, and induction of fibrosis, leading to the potential development and progression of liver disease.1Ergun T. Hidradenitis suppurativa and the metabolic syndrome.Clin Dermatol. 2018; 36: 41-47https://doi.org/10.1016/j.clindermatol.2017.09.007Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar,2Durán-Vian C. Arias-Loste M.T. Hernández J.L. et al.High prevalence of non-alcoholic fatty liver disease among hidradenitis suppurativa patients independent of classic metabolic risk factors.J Eur Acad Dermatol Venereol. 2019; 33: 2131-2136https://doi.org/10.1111/jdv.15764Crossref PubMed Scopus (16) Google Scholar Limitations include a lack of ethnic diversity across studies and the paucity of studies investigating the association of certain hepatic conditions and HS, with some outcomes only being investigated by single studies. Patients with HS should be informed of their possible increased risk of liver disease, particularly NAFLD, alcoholic fatty liver disease, and hepatitis B. Age-appropriate screening and counseling on modifiable risk factors such as weight management, smoking cessation, and alcohol intake may be beneficial. Appropriate liver workup, including liver enzymes, function tests, and imaging, should also be considered in patients with HS presenting with symptoms suggestive of liver disease. None disclosed.

Prevalence and risk factors of nonalcoholic steatohepatitis with significant fibrosis in people with HIV.

Objective:Metabolic risk factors and nonalcoholic fatty liver disease (NAFLD) in people with HIV (PWH) have been increasing. Patients exhibiting the inflammatory subtype nonalcoholic steatohepatitis (NASH) are at increased risk of liver-related complications. Therefore, the aim was to investigate the prevalence of NASH with significant fibrosis in PWH using noninvasive tests (NITs).Design:In this prospectively enrolling cohort study, 282 PWH were explored for hepatic steatosis, fibrosis and steatohepatitis using vibration-controlled transient elastography (VCTE) and the Fibroscan-AST (FAST) score.Methods:On the basis of controlled attenuation parameter (CAP; dB/m) and liver stiffness measurement (LSM; kPa), patients were categorized according to the presence of steatosis (≥275 dB/m) and significant fibrosis (≥8.2 kPa). The FAST score was calculated according to established cut-offs.Results:The prevalence of hepatic steatosis in this cohort was 35.5% (n = 100) with 75 (75%) of these patients fulfilling the criteria of NAFLD. The prevalence of significant fibrosis (≥ F2) was 6.7% (n = 19). The FAST score identified a total of 32 (12.3%) patients with a cut-off greater than 0.35, of whom 28 (87.5%) PWH qualified as NASH. On multivariable analysis, waist circumference was a predictor of hepatic steatosis and type 2 diabetes was a predictor of significant fibrosis. Type 2 diabetes and ALT remained independent predictors of a FAST score greater than 0.35.Conclusion:NASH with significant fibrosis is highly prevalent among PWH. The FAST score may be helpful to identify patients at risk for significant liver disease.

MAFLD and CKD: An Updated Narrative Review.

Accumulating evidence now indicates that non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease observed in clinical practice worldwide, is independently associated with an increased risk of incident chronic kidney disease (CKD). Given that NAFLD is linked to insulin resistance, obesity and type 2 diabetes mellitus, an international panel of experts have recently proposed a name change from NAFLD to metabolic associated fatty liver disease (MAFLD). Since the diagnostic criteria for NAFLD and MAFLD are different, observational studies assessing the potential concordance (or even superiority) of MAFLD, compared with NAFLD, in detecting patients at increased risk of hepatic and extra-hepatic complications (including CKD) are required. Hence, in the last two years, some observational studies have investigated the potential relationship between MAFLD and CKD. The result is that, at present, evidence regarding the concordance or even superiority of MAFLD, compared with NAFLD, in detecting patients at higher risk of CKD is still preliminary, although some data indicate that MAFLD identifies patients with CKD as accurately as NAFLD. In this narrative review, we will discuss: (a) the epidemiological evidence assessing the association between NAFLD and risk of incident CKD, (b) the epidemiological data investigating the association between MAFLD and risk of CKD and (c) the biological mechanisms underlying the association between NAFLD/MAFLD and CKD.

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is highly prevalent in people with diabetes with no available treatment. AIMTo explore the effect of testosterone treatment on liver. Testosterone therapy improves insulin resistance and reduces total body fat, but its impact on the liver remains poorly studied.METHODSThis secondary analysis of a 40 wk, randomised, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging (MRI).RESULTSOf 88 patients enrolled in the index study, 39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo. All patients had > 5% hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD. Median liver fat at baseline was 15.0% (IQR 11.5%-21.1%) in the testosterone and 18.4% (15.0%-28.9%) in the placebo group. Median ALT was 34units/L (26-38) in the testosterone and 32units/L (25-52) in the placebo group. At week 40, patients receiving testosterone had a median reduction in absolute liver fat of 3.5% (IQR 2.9%-6.4%) compared with an increase of 1.2% in the placebo arm (between-group difference 4.7% P < 0.001). After controlling for baseline liver fat, testosterone therapy was associated with a relative reduction in liver fat of 38.3% (95% confidence interval 25.4%-49.0%, P < 0.001). CONCLUSIONTestosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone. Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

Association between Melatonin Value and Interleukins1B, -18, and -33 Levels in Patients with Different Stages of Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Interaction between immune modulators and inflammatory factors is considered as one of the main underlying pathologies of non-alcoholic fatty liver disease (NAFLD). Hence we aimed to assess the association between these cytokines and melatonin. METHODS: We enrolled adult patients diagnosed with fatty liver by ultrasonography in a crosssectional study. All of them underwent Fibroscan evaluation. The subjects who met the inclusion and exclusion criteria for NAFLD were involved. A normal group who did not have NAFLD, viral or non-viral hepatitis, and without a history of pancreatobiliary surgery, bariatric surgery, and intake of any medication that influence the liver was also selected. The participants were categorized into the three following groups: 1) fibrosis>9.1 kPa and steatosis>290 dbm, 2) fibrosis: 6-9.0 kPa and steatosis 240-290 dbm, and 3) normal group with fibrosis<6.0 kPa and steatosis<240 dbm. Laboratory assessment and a questionnaire including demographic, anthropometric, laboratories, and clinical data were completed for each of them. RESULTS: Totally 97 subjects were enrolled in the present study. The mean age of the subjects was 42.2±11.3 years. 60% of them (59 patients) were female. Serum levels of melatonin, interleukin (IL)-1B, IL-18, and IL-33 increased according to the advancing of NAFLD state. Based on multiple linear regression model, melatonin was significantly associated with IL-1B (β=2.8, P<0.001,95% CI=1.41-4.19), IL-18 (β=0.018, P=0.0005, 95% CI=0.006-0.03), and IL-33 (β=0.31, P=0.045, 95% CI=0.008-0.62) after adjustment for other variables. CONCLUSION: Melatonin level has a strong association with these cytokines. This linkage probably influences on the development and progression of NAFLD. Therefore it can be hypothesized that the therapeutic approach that affects this process may have a significant impact.