Evaluation of Hepatic Fibrosis and Hepatic Steatosis by Pulse Elastography (FIBROSCAN/CAP) in Asymptomatic Patients about 170 Cases at the Donka CHU National Hospital in Conakry

Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis to be assessed. Fibroscan measures both elasticity correlated with hepatic fibrosis and CAP correlated with steatosis. The aim of this study was to evaluate hepatic fibrosis and steatosis using pulse elastometry (Fibroscan/CAP). Methods: This was a descriptive and analytical cross-sectional study in which 170 patients were included. It was conducted from October 1 2021 to December 31 2023, i.e. 27 months, in an outpatient clinic in the hepato-gastroenterology department of the Donka national hospital of the CHU Conakry. Results: Of the 170 patients identified, 87 were male (51%) and 83 female (49%), giving a M/F sex ratio of 1.04. The average age of our patients was 40. The 30 - 50 age group was the most affected, with a frequency of 58.23% (n = 99), followed by the 50 age group with a frequency of 29.41% (n = 50). Hepatomegaly, steatotic liver on ultrasonography, transaminase elevation and obesity were the main indications, respectively: (21.76%), (17.65%), (14.71%), and (13.53%). The examinations were requested by hepatogastroenterologists (47.06%), diabetologists (35.88%) and general practitioners (29%). Of the 170 patients, 100 patients (58.82%) had no significant fibrosis F0F1, 39 (22.94%) had moderate fibrosis F2, 20 patients (11.76%) had severe fibrosis F3 and 11 patients (6.47%) had fibrosis F4. Hepatic steatosis: 62 patients (36.47%) had no S0 steatosis;29.41% had S1 steatosis, 20% had S2 steatosis and 24 patients (14.11%) had S3 steatosis. Abdominal ultrasound revealed a normal liver in 67.05% of patients, hepatic steatosis in 29.41% and non-decompensated cirrhosis in 6 cases. Thus, 108 patients had the parameters required to calculate the Fatty Liver Index (FLI), steatosis was present in 20% of our patients, while 29.41% had an undetermined status and 24 14.11% had a normal FLI. Conclusion: Identifying subjects at risk of metabolic steatopathy, diagnosing and managing these patients is a public health issue and one of the future challenges of hepato-gastroenterology. Fibroscan is an increasingly popular screening tool for hepatic fibrosis and steatosis. The fight against obesity must be a priority.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI > 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Pathogenesis and research progress of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

In this editorial,we comment on the article by Mei et al.Nonalcoholic steatohep-atitis(NASH)is a severe inflammatory subtype of nonalcoholic fatty liver disease(NAFLD)with pathological features including steatosis,hepatocellular damage,and varying degrees of fibrosis.With the epidemic of metabolic diseases and obesity,the prevalence of NAFLD in China has increased,and it is now similar to that in developed countries;thus,NAFLD has become a major chronic liver disease in China.Human epidemiological data suggest that estrogen has a protective effect on NASH in premenopausal women and that sex hormones influence the development of liver disease.This review focuses on the path-ogenesis,treatment,and relationship between NASH and other diseases as well as on the relationship between NASH and sex hormone metabolism,with the aim of providing new strategies for the treatment of NASH.

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 μg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002.CONCLUSIONSitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

Non-invasive evaluation of liver steatosis with imaging modalities:New techniques and applications

In the world,nonalcoholic fatty liver disease(NAFLD)accounts for majority of diffuse hepatic diseases.Notably,substantial liver fat accumulation can trigger and accelerate hepatic fibrosis,thus contributing to disease progression.Moreover,the presence of NAFLD not only puts adverse influences for liver but is also associated with an increased risk of type 2 diabetes and cardiovascular diseases.Therefore,early detection and quantified measurement of hepatic fat content are of great importance.Liver biopsy is currently the most accurate method for the evaluation of hepatic steatosis.However,liver biopsy has several limitations,namely,its invasiveness,sampling error,high cost and moderate intraobserver and interobserver reproducibility.Recently,various quantitative imaging techniques have been developed for the diagnosis and quantified measurement of hepatic fat content,including ultrasound-or magnetic resonancebased methods.These quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content,which is useful for longitudinal follow-up.In this review,we introduce several imaging techniques and describe their diagnostic performance for the diagnosis and quantified measurement of hepatic fat content.

Modulation of hepatic steatosis by dietary fatty acids

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by fat deposition within liver cells. Liver fat content reflects the equilibrium between several metabolic pathways involved in triglyceride synthesis and disposal, such as lipolysis in adipose tissue and de novo lipogenesis, triglyceride esterification, fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis. It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways. Therefore, dietary fat may not only be involved in the pathogenesis of hepatic steatosis, but may also prevent and/or reverse hepatic fat accumulation. In this review, major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described. Moreover, biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver. A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver. Quite interesting is the “case” of olive oil, since several studies have often provided different and/or conflicting results in animal models.

Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude

AIM:To use leptin-deficient(ob/ob) mice with demonstrated differences in steatosis levels to test a new diagnostic method using the acoustical structure quantification(ASQ) mode and the associated analytical parameter,"focal disturbance ratio"(FD-ratio).METHODS:Nine ob/ob mice,at 5,8,and 12 wk of age(n = 3 in each age group),were used as models for hepatic steatosis.Echo signals obtained from ultrasonography in the mice were analyzed by ASQ,which uses a statistical analysis of echo amplitude to estimate inhomogeneity in the diagnostic region.FD-ratio,as calculated from this analysis,was the focus of the present study.FD-ratio and fat droplet areas and sizes were compared between age groups.RESULTS:No fibrosis or inflammation was observed in any of the groups.The fat droplet area significantly(P < 0.01) increased with age from 1.25% ± 0.28% at 5 wk to 31.07% ± 0.48% at 8 wk to 51.69% ± 3.19% at 12 wk.The median fat droplet size also significantly(P < 0.01) increased with age,from 1.33(0.55-10.52) m at 5 wk,2.82(0.61-44.13) m at 8 wk and 6.34(0.66-81.83) m at 12 wk.The mean FD-ratio was 0.42 ± 0.11 at 5 wk,0.11 ± 0.05 at 8 wk,and 0.03 ± 0.02 at 12 wk.The FD-ratio was significantly lower at 12 wk than at 5 wk and 8 wk(P < 0.01).A significant negative correlation was observed between the FD-ratio and either the fat droplet area(r =-0.7211,P = 0.0017) or fat droplet size(r =-0.9811,P = 0.0052).CONCLUSION:This tool for statistical analysis of signals from ultrasonography using the FD-ratio can be used to accurately quantify fat in vivo in an animal model of hepatic steatosis,and may serve as a quantitative biomarker of hepatic steatosis.

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

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To 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.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled 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).RESULTS Of 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).CONCLUSION Testosterone 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.

Schisanhenol ameliorates non-alcoholic fatty liver disease via inhibiting miR-802 activation of AMPK-mediated modulation of hepatic lipid metabolism

Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is a common metabolic liver disease worldwide.Currently,satisfactory drugs for NAFLD treatment remain lacking.Obesity and diabetes are the leading causes of NAFLD,and compounds with anti-obesity and antidiabetic activities are considered suitable candidates for treating NAFLD.In this study,biochemical and histological assays revealed that a natural lignan schisanhenol(SAL)effectively decreased lipid accumulation and improved hepatic steatosis in free fatty acid(FFA)-treated HepG2 cells and high-fat diet(HFD)-induced NAFLD mice.Further,molecular analyses,microRNA(miRNA)-seq,and bioinformatics analyses revealed that SAL may improve NAFLD by targeting the miR-802/adenosine monophosphateactivated protein kinase(AMPK)pathway.Liver-specific overexpression of miR-802 in NAFLD mice significantly impaired SAL-mediated liver protection and decreased the protein levels of phosphorylated(p)-AMPK and PRKAB1.Dual-luciferase assay analysis further confirmed that miR-802 inhibits hepatic AMPK expression by binding to the 3’untranslated region of mouse Prkab1 or human PRKAA1.

Non-alcoholic fatty liver disease in 2015

There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.

Chronic hepatitis B and metabolic risk factors:A call for rigorous longitudinal studies

Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.

Liver transplantation and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Pooled genetic analysis in ultrasound measured non-alcoholic fatty liver disease in Indian subjects:A pilot study

AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease(NAFLD) by performing a pooled genetic study.METHODS: Study subjects(n = 306) were recruited and categorized into NAFLD and control groups based on ultrasound findings of fatty infiltration. Of the 306 individuals, 156 individuals had fatty infiltration and thus comprised the NAFLD group. One hundred and fifty(n = 150) individuals were normal, without fatty infiltration of the liver, comprising the control group. Blood samples, demographic and anthropometric data from the individuals were collected after obtaining informed consent. Anthropometric data, blood glucose, lipids and liver function tests were estimated using standard methods. Genome wide association stud-ies done to date on NAFLD were identified, 19 single nucleotide polymorphisms(SNPs) were selected from these studies that were reported to be significantly associated with NAFLD and genotyping was performed on the Sequenom platform. Student's t test for continuous variables and χ2 test was applied to variant carriers from both groups. Required corrections were applied as multiple testing was done.RESULTS The mean age of the control group was 39.78 ± 10.83 and the NAFLD group was 36.63 ± 8.20 years. The waist circumference of males and females in the control and NAFLD groups were 80.13 ± 10.35; 81.77 ± 13.65 and 94.09 ± 10.53; 92.53 ± 8.27 respectively. The mean triglyceride and alanine transaminase(ALT) levels in the control and NAFLD groups were 135.18 ± 7.77; 25.39 ± 14.73 and 184.40 ± 84.31; 110.20 ± 67.05 respectively. When χ2 test was applied to the number of individuals carrying the variant risk alleles between the control and NAFLD group, a significant association was seen between rs738409 of the patatin-like phospholipase domain containing 3(PNPLA3) gene(P = 0.001), rs2073080 of the PARVB gene(P = 0.02), rs2143571 of SAMM50 gene(P = 0.05) and rs6487679 of the pregnancy zone protein(PZP) gene(P = 0.01) with the disease. Variant single nucleotide polymorphisms(SNPs) in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4 B and COL13A1 were associated with high triglyceride levels. Apart from the above associations, rs2073080, rs343062 and rs6591182 were significantly associated with high BMI; rs2854117 and rs738409 with high triglyceride levels; and rs2073080, rs2143571, rs2228603, rs6487679 and rs738409 with high ALT levels.CONCLUSION: Pooled genetic analysis revealed an association of SNPs in PNPLA3, PARVB, SAMM50 and PZP genes with NAFLD. SNPs in NCAN and PNPLA3gene were associated with higher levels of ALT,whereas variant SNPs in APOC3, PNPLA3, EFCAB4 B and COL13A1 were associated with high triglyceride levels.

Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis

Background and aim:Non-alcoholic fatty liver disease(NAFLD)is becoming a leading cause of chronic liver disease worldwide.The molecular events that influence disease progression from non-alcoholic fatty liver(NAFL)to aggressive non-alcoholic steatohepatitis(NASH)remain incompletely understood,leading to lack of mechanism-based targeted treatment options for NASH.This study aims to identify early signatures associated with disease progression from NAFL to NASH in mice and humans.Materials and methods:Male C57BL/6J mice were fed a high-fat,-cholesterol,and-fructose(HFCF)diet for up to 9 months.The extent of steatosis,inflammation,and fibrosis was evaluated in liver tissues.Total RNA sequencing(RNA-seq)was conducted to determine liver transcriptomic changes.Results:After being fed the HFCF diet,mice sequentially developed steatosis,early steatohepatitis,steatohepatitis with fibrosis,and eventually spontaneous liver tumor.Hepatic RNA-seq revealed that the key signatures during steatosis progression to early steatohepatitis were pathways related to extracel-lular matrix organization and immune responses such as T cell migration,arginine biosynthesis,C-type lectin receptor signaling,and cytokine-cytokine receptor interaction.Genes regulated by transcription factors forkhead box M1(FOXM1)and negative elongation factor complex member E(NELFE)were significantly altered during disease progression.This phenomenon was also observed in patients with NASH.

Growing challenge of post-liver transplantation non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is one of the leading causes of chronic liver disease,cirrhosis,and hepatocellular carcinoma worldwide,with an estimated prevalence of 25%.Post-liver transplantation(LT)recurrent or de novo hepatic steatosis is a common complication in recipients,irrespective of transplantation indication.Risk factors for graft steatosis mainly include obesity,immunosuppression,donor steatosis,and genetic factors.Liver transplant recipients are at high risk of developing insulin resistance,new-onset diabetes,and posttransplantation metabolic syndrome that is highly associated with immunosuppressive treatment.Post-LT NAFLD is often underdiagnosed due to the poor sensitivity of most routine imaging methods.The gold standard for the diagnosis of hepatic steatosis is liver biopsy,which is,however,limited to more complex cases due to its invasive nature.There is no approved pharmacotherapy in NAFLD.Lifestyle modification remains the cornerstone in NAFLD treatment.Other treatment strategies in post-LT NAFLD include lifestyle modifications,pharmacotherapy,bariatric surgery,and tailored immunosuppression.However,these approaches originate from recommendations in the general population,as there is scarce data regarding the safety and efficacy of current management strategies for NAFLD in liver transplant patients.Future prospective studies are required to achieve tailored treatment for these patients.

Machine Learning Technology for Evaluation of Liver Fibrosis, Inflammation Activity and Steatosis (LIVERFASt^TM)

Using the latest available artificial intelligence (AI) technology, an advanced algorithm LIVERFAStTM has been used to evaluate the diagnostic accuracy of machine learning (ML) biomarker algorithms to assess liver damage. Prevalence of NAFLD (Nonalcoholic fatty liver disease) and resulting NASH (nonalcoholic steatohepatitis) are constantly increasing worldwide, creating challenges for screening as the diagnosis for NASH requires invasive liver biopsy. Key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. In this prospective study, the staging of three different lesions of the liver to diagnose fatty liver was analyzed using a proprietary ML algorithm LIVERFAStTM developed with a database of 2862 unique medical assessments of biomarkers, where 1027 assessments were used to train the algorithm and 1835 constituted the validation set. Data of 13,068 patients who underwent the LIVERFAStTM test for evaluation of fatty liver disease were analysed. Data evaluation revealed 11% of the patients exhibited significant fibrosis with fibrosis scores 0.6 - 1.00. Approximately 7% of the population had severe hepatic inflammation. Steatosis was observed in most patients, 63%, whereas severe steatosis S3 was observed in 20%. Using modified SAF (Steatosis, Activity and Fibrosis) scores obtained using the LIVERFAStTM algorithm, NAFLD was detected in 13.41% of the patients (Sx > 0, Ay 0). Approximately 1.91% (Sx > 0, Ay = 2, Fz > 0) of the patients showed NAFLD or NASH scorings while 1.08% had confirmed NASH (Sx > 0, Ay > 2, Fz = 1 - 2) and 1.49% had advanced NASH (Sx > 0, Ay > 2, Fz = 3 - 4). The modified SAF scoring system generated by LIVERFAStTM provides a simple and convenient evaluation of NAFLD and NASH in a cohort of Southeast Asians. This system may lead to the use of noninvasive liver tests in extended populations for more accurate diagnosis of liver pathology, prediction of clinical path of individuals at all stages of liver diseases, and provision of an efficient system for therapeutic interventions.

Validation of fatty liver index and hepatic steatosis index for screening of non-alcoholic fatty liver disease in adults with obstructive sleep apnea hypopnea syndrome

Background:Obstructive sleep apnea hypopnea syndrome(OSAHS)is a contributing factor for non-alcoholic fatty liver di:(NAFLD).Non-invasive algorithms including fatty liver index(FLI)and hepatic steatosis index(HSI)have been used as a screening test for NAFLD in epidemiologic studies.The aim of this study is to compare the diagnostic accuracy of FLI and HSI for NAFLD detection in adults with OSAHS.Methods:We enrolled consecutive adult subjects who were newly diagnosed with OSAHS from March 2016 to January 2018.NAFLD was diagnosed by ultrasonography.The accuracy and cut-off point of the FLI and HSI to detect NAFLD were assessed by analyzing the area under the receiver operating characteristic(AUROC)curve and the maximum Youden index analysis,respectively.Results:The 326 subjects were diagnosed as NAFLD according to ultrasound findings,while 105 subjects who had normal abdominal ultrasonography were grouped as controls.Both FLI and HSI values were significantly higher in patients with NAFLD compared with controls.The AUROC of FLI and HSI for predicting NAFLD was 0.802(95%confidence interval[CI]0.762-0.839)and 0.753(95%CI 0.710-0.793),respectively.The AUROC of FLI was significantly higher than that of HSI(P=0.0383).The optimal cut-off value of FLI and HSI was 60(sensitivity 66%and specificity 80%)and 35(sensitivity 81%and specificity 60%),respectively.Conclusions:Both FLI and HSI can serve as screening tools for NAFLD in OSAHS adults.The FLI shows better performance in diagnosing NAFLD than HSI.

清热渗湿降浊法联合水飞蓟宾葡甲胺片治疗湿热蕴结型非酒精性脂肪性肝炎临床疗效观察

【目的】探讨清热渗湿降浊法联合水飞蓟宾葡甲胺片治疗丙氨酸氨基转移酶(ALT)异常的湿热蕴结型非酒精性脂肪性肝炎(NASH)患者的临床疗效。【方法】采用回顾性研究方法,根据用药情况将80例ALT异常的湿热蕴结型NASH患者分为对照组和观察组,每组各40例。对照组给予水飞蓟宾葡甲胺片治疗,观察组在对照组的基础上联合清热渗湿降浊法治疗,疗程为12周。观察2组患者治疗前后肝功能指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)]、血脂指标[总胆固醇(CHOL)、甘油三酯(TRIG)]以及肝脂肪度的变化情况,并评价2组患者的临床疗效及安全性。【结果】(1)经治疗12周后,观察组的总有效率为95.00%(38/40),对照组为77.50%(31/40);组间比较,观察组的疗效明显优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患者的肝功能指标ALT、AST、GGT水平均较治疗前明显下降(P<0.05),且观察组对肝功能指标ALT、AST、GGT水平的下降作用均明显优于对照组(P<0.05)。(3)治疗后,2组患者的血脂指标CHOL、TRIG水平均较治疗前明显下降(P<0.05),且观察组对血脂指标CHOL、TRIG水平的下降作用均明显优于对照组(P<0.05)。(4)治疗后,2组患者的肝脂肪度均较治疗前明显下降(P<0.05),且观察组对肝脂肪度的下降作用明显优于对照组(P<0.05)。(5)治疗过程中,2组患者均未发生明显不良反应,具有较高的安全性。【结论】清热渗湿降浊法联合水飞蓟宾葡甲胺片治疗ALT异常的湿热蕴结型NASH患者疗效确切,联合清热渗湿降浊法治疗能显著提高临床疗效。

Metabolic dysfunction-associated fatty liver disease and low muscle strength: A comment

The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.