Accuracy of Narrow-Band Imaging International Colorectal Endoscopic Classification for Predicting the Histology of Colon Polyps by Experienced Endoscopists and Trainees.

BACKGROUND/AIMS: Digital chromoendoscopy has proven to be useful in the histological prediction of premalignant lesions in the colon. The aim of the study was to describe the diagnostic performance of Narrow-Band Imaging International Colorectal Endoscopic Classification in the histological differentiation of colonic lesions, applied by expert endoscopists and trainees. MATERIALS AND METHODS: Cross-sectional study that includes high-definition endoscopic images and histopathological reports of 94 patients over 50 years. Images were evaluated and classified as Narrow-Band Imaging International Colorectal Endoscopic 1, 2, or 3 by 2 experts and 2 trainee endoscopists, all of them blinded to histological results. Diagnostic accuracy for each Narrow-Band Imaging International Colorectal Endoscopic category was calculated for trainees and expert endoscopists. Intra-observer agreement was evaluated by means of Cohen's kappa coefficient; meanwhile, inter-observer agreement was calculated by means of Fleiss' kappa. RESULTS: Evaluations performed by expert and trainee endoscopists showed a performance for Narrow-Band Imaging International Colorectal Endoscopic category 1: sensitivity 62%, specificity 85%, area under receiver operator characteristic 0.73; Narrow-Band Imaging International Colorectal Endoscopic category 2: sensitivity 61%, specificity 73%, area under receiver operator characteristic 0.66; and Narrow-Band Imaging International Colorectal Endoscopic category 3: sensitivity 88%, specificity 91%, area under receiver operator characteristic 0.86. The total agreement of the evaluations was 72.5%, with an inter-observer variability of K 0.60 (95% CI 0.52-0.74). When the diagnostic performance for non-dysplastic lesions and dysplastic lesions (Narrow-Band Imaging International Colorectal Endoscopic 1 vs 2 and 3) was compared, we observed an increase in sensitivity for differentiated adenomas (Narrow-Band Imaging International Colorectal Endoscopic 2). CONCLUSION: Narrow-Band Imaging International Colorectal Endoscopic Classification applied in the histological prediction of static images of colonic lesions has a good diagnostic performance for Narrow-Band Imaging International Colorectal Endoscopic category 3, as well as an acceptable performance for Narrow-Band Imaging International Colorectal Endoscopic category 1, with a moderate agreement among observers.

The Interlink Between Metabolic-Associated Fatty Liver Disease and Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) affects around 10% of women in the reproductive age group and is characterized by ovulatory dysfunction, hyperandrogenism, and/or polycystic ovarian morphology. PCOS is highly associated with metabolic-associated fatty liver disease (MAFLD) as both diseases share common risk factors. At the time of diagnosis of PCOS, screening for MAFLD is necessary because most patients with MAFLD are asymptomatic. The importance of early detection of MAFLD in patients with PCOS is that a timely intervention in patients with steatosis or steatohepatitis can reduce the probability of liver disease progression.

Systematic review and meta-analysis: Transient elastography compared to liver biopsy for staging of liver fibrosis in primary biliary cholangitis.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune liver disease, with 60% of patients being asymptomatic at diagnosis and 30% progressing rapidly into liver fibrosis. Liver biopsy is standard for staging fibrosis, but performance of non-invasive methods such as transient elastography (TE) have not been evaluated. We conducted a meta-analysis of articles up to May 2022 to evaluate the performance of TE compared with liver biopsy in adult patients with PBC. MATERIALS AND METHODS: Two reviewers performed the search and assessed which articles were included. The quality of each study was evaluated according to QUADAS-2 and NOS. Meta-analysis of sensitivity and specificity was conducted with a bivariate random-effects model. The protocol was registered in PROSPERO, ID CRD42020199915. RESULTS: Four studies involving 377 patients were included. Only stages F3 and F4 were computed in the meta-analysis. TE had a pooled sensitivity of 68% and specificity of 92% for stage F3 and a pooled sensitivity of 90% and specificity of 94% for stage F4. The AUROC curves were 0.91 (95% Confidence Interval (CI) 0.88-0.93) and 0.97 (95% CI 0.96-0.98) for stages F3 and F4, respectively. The mean cut-off points of TE for stage F3 were 9.28 kPa (95% CI 4.98-13.57) and for stage F4 were 15.2 kPa (95% CI 7.02-23.37). CONCLUSIONS: TE performance compared with liver biopsy in adult patients with PBC was excellent for staging liver fibrosis and was able to rule out cirrhosis in clinical practice.

Metabolic-associated Fatty Liver Disease Regulation through Nutri Epigenetic Methylation.

Metabolically associated fatty liver disease, formerly called nonalcoholic fatty liver disease, is the most common liver disease globally, representing the third cause of liver transplantation. Metabolically associated fatty liver disease is defined as having more than 5% lipid droplets in hepatocytes without other concomitant liver diseases. Various stimuli such as the secretion of inflammatory cytokines, mitochondrial and endoplasmic reticulum dysfunction due to oxidative stress, alteration of the intestine-liver axis, bacterial dysbiosis, as well as genetic and epigenetic factors can modify the progression of metabolically associated fatty liver disease to fibrosis, cirrhosis, and may reach hepatocellular carcinoma. Epigenetics is responsible for a highly sophisticated regulatory system that controls many cellular processes in response to multiple environmental factors as an adaptive mechanism unrelated to alterations in the primary deoxyribonucleic acid sequence, including gene expression, microRNAs, DNA methylation, modifications in histones, and DNA-protein interactions. Several studies have shown that epigenetic changes are associated with various diseases, including metabolically associated fatty liver disease. Nutri epigenomics is the interaction between nutrition and components at the transcriptional or post-transcriptional level. Methylation processes involve micronutrients that regulate epigenetic states in a physiological and pathological context. Micronutrients such as methionine, folate, and choline are the main components of one-carbon metabolism, functioning as methyl group donors, and their deficiency predisposes to various pathologies such as metabolically associated fatty liver disease. Understanding of epigenetic modifiers leads us to develop new therapeutic therapies for patients with metabolically associated fatty liver disease.

Bariatric endoscopic-surgical therapies for NAFLD. Should they be considered viable options among current treatments?

Nowadays, non-alcoholic fatty liver disease is one of the first causes of liver transplant worldwide; many efforts have been done to find the perfect drug for this multifactorial disease. Presently we just have a few drugs that could be used in specific and limited clinical scenarios. Current evidence suggests that bariatric endoscopic and surgical therapies could be strategies with optimal outcomes, with high impact in quality of life, decrease of cardiovascular risk, and improvement in metabolic profile, despite being considered expensive procedures. This review proposes to consider these therapies early together with liver fibrosis evaluation, with long term cost-effectiveness benefits in the absence of response to lifestyle modifications and pharmacological treatments.

Hepatic mir-122-3p, mir-140-5p and mir-148b-5p expressions are correlated with cytokeratin-18 serum levels in MAFLD.

INTRODUCTION AND OBJECTIVES: Metabolic-associated fatty liver disease (MAFLD) is defined by steatosis in more than 5% of hepatocytes without other liver diseases. Patients with this disease can progress to multiple stages like liver fibrosis, cirrhosis, and hepatocellular carcinoma. miRNAs are single-stranded molecules that regulate metabolic homeostasis; their differential expression postulates them as potential circulating biomarkers for MAFLD. Previous research reported that hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p have a differential expression in patients with MAFLD. This study aimed to investigate the correlation between liver hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p and serum biomarkers CK-18, APOB, IL-6, IL-32, and TNF-α in patients with MAFLD compared with control patients. MATERIALS AND METHODS: A cross-sectional study was carried out with 16 patients of both sexes, aged between 18-60 years, to determine the association between the levels of hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p with MAFLD in liver biopsies of patients who underwent laparoscopic cholecystectomy. RESULTS: Twelve patients presented MAFLD, four without hepatic steatosis. Circulating levels of CK-18 showed a significant difference in patients with MAFLD, and a strong correlation was found between hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-5p versus the CAP value. CONCLUSION: There is a correlation between elevated tissue expression of hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-3p with plasma levels of CK-18 in patients with simple steatosis compared with patients without the disease.

Understanding the Role of Metabolic Syndrome as a Risk Factor for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) and metabolic syndrome (MetS) have a rising prevalence worldwide. The relationship between these two entities has long been studied and understanding it has become a public health and clinical priority. This association follows, in most patients, the path through non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis and finally HCC. Nonetheless, increasing evidence has been found, that shows MetS as an independent risk factor for the development of HCC. This review brings together the clinical evidence of the relationship between these highly prevalent diseases, with a particular interest in the impact of each component of MetS on HCC; It aims to summarize the complex physiopathological pathways that explain this relationship, and to shed light on the different clinical scenarios of this association, the impact of treating the different components of MetS on the risk of HCC and what is known about screening for HCC in patients with MetS. By doing so, it hopes to improve awareness on this topic.

Incremental levels of diagnostic information incentivize health-seeking in non-alcoholic fatty liver: a randomized clinical trial.

Patients with chronic disorders like non-alcoholic fatty liver disease (NAFLD) face important challenges adhering to diagnostic and treatment tracks. As NAFLD increases, the need to incentivize health-seeking behaviors grows. No evidence-based interventions to address this gap exist. The aim of the study was to estimate the effect of providing increasing levels of diagnostic information on medical care-seeking in adults newly diagnosed with NAFLD. We randomly assigned adults with a sonographic diagnosis of NAFLD at a check-up unit in Mexico to one of five groups. All groups received medical consultation. A: no further interventions; B: received multimedia educational material (MEM); C: MEM + NAFLD-fibrosis-score (NFS); D: MEM + transient elastography (TE); E: MEM + NFS + TE. 1209 participants were randomized, follow-up rate 91%; 82% male, BMI 30.5 ± 4 kg/m2. There were no differences in the proportion of patients undergoing further diagnostic evaluation of liver fibrosis (A 0.4%, E 0.4%, P-for-trend = 0.269). Groups who received more information sought specialized medical care more frequently: A 22%, E 30% (P-for-trend = 0.047). A trend to receive treatment was also observed at higher levels of information: A 26.7%, E 36.3% (P-for-trend = 0.134). Increasing the amount of diagnostic information seemed to increase patient's health-seeking. Tailoring the communication of information obtained for diagnosis could help to increase health-seeking in chronic disease patients.Trial registration: NCT01874249 (full date of first registration 11-06-2013).

Laparoscopic cholecystectomy: Histopathological analysis of metabolic associated fatty liver disease and fibrosis.

INTRODUCTION: Metabolic (dysfunction) associated fatty liver disease (MAFLD) and cholelithiasis are highly prevalent and are associated with common risk factors such as obesity, hypertriglyceridemia, and fasting glucose levels; however, it is not clear whether cholelithiasis is associated with MAFLD or fibrosis. OBJECTIVE: To determine MAFLD severity and associated risk factors in patients diagnosed with cholelithiasis. MATERIALS AND METHODS: Observational, cross-sectional and prolective study (from October 2018 to March 2020) of patients undergoing elective laparoscopic cholecystectomy with liver biopsy, excluding other causes of hepatic disease or significant alcohol consumption. MAFLD detection was based on histology using the Kleiner score and one of the following criteria: overweight/obesity, T2DM, or evidence of metabolic dysregulation. The AST to Platelet Ratio Index, the NAFLD Fibrosis Score, the fibrosis-4 index and the hepatic steatosis index were performed to assess the relationship of non-invasive hepatic scores with histopathology. RESULTS: 80 patients median age (interquartile range) was 42 (18) years, with a BMI of 27.9 (6.11) Kg/m2. Of all patients, 58.8% had MAFLD, 78.7% were women, and 13.8% had the severe form (formerly named NASH). No substantial correlation between biochemical parameters and histopathological analysis of MAFLD and fibrosis was observed. CONCLUSION: Because cholelithiasis and MAFLD are highly prevalent diseases, it is essential to conduct studies on the relationship between both pathologies. Currently, liver biopsy is the best diagnostic method since the predictive biochemical models did not show a substantial correlation to classify MAFLD. Its early detection is relevant since a considerable percentage of advanced fibrosis (8.7%) was found.

Cross-sectional pilot study to assess primary healthcare workers' knowledge of nonalcoholic fatty liver disease in a marginalized community in Mexico.

The registered incidence of nonalcoholic fatty liver disease (NAFLD) in primary healthcare centers is lower than expected, suggesting a lack of awareness by primary care healthcare professionals. The implementation of educational tools for healthcare workers has been found to increase timely referral and treatment of patients. We aimed to determine healthcare workers' knowledge of NAFLD to identify their educational needs in one marginalized region. We performed a cross-sectional survey of 261 healthcare professionals in Tlapa de Comonfort, Guerrero, Mexico from October 2019 to December 2019. We created a questionnaire that assessed domains most relevant to NAFLD knowledge. Two hundred and forty-six questionnaires were completed. Of the respondents, 38.3% were nurses and 63.4% were women. Most nurses identified NAFLD as a prevalent (89%) and preventable (93%) disease. Hypertension (33%) and obesity (84%) were recognized as risk factors. The associations between NAFLD and cancer, cirrhosis and cardiovascular disease were identified by 53%, 67% and 72% of respondents, respectively. The largest gaps were found in diagnostic workup, therapeutic approach and the current treatments. We identify modifiable knowledge gaps in NAFLD. Educational strategies for primary care workers could enhance the identification of patients with NAFLD and prevent complications.

G protein-coupled receptors: Key molecules in metabolic associated fatty liver disease development.

Metabolic associated fatty liver disease (MAFLD) is a range of hepatic disorders with progression to steatohepatitis with risk of development of fibrosis, cirrhosis, and hepatocellular carcinoma. MAFLD is strongly related to metabolic disorders of active fatty acids, which seem to be selective according to their specific ligand of G protein-coupled receptors (GPRs) located in immune response cells. An approach to study the pathophysiological mechanisms of MAFLD could be through the expression of active fatty acids ligands. The expression of GPRs is associated with obesity, microbiota environment, and dietary characteristics in patients with MAFLD. More specifically, GPR41, GPR43, GPR20, and GPR120 have been associated with alteration of lipid metabolism in hepatic and intestinal cells, and consequently they have a key role in metabolic diseases. We observed that GPR120 is not expressed in nonoverweight/obese patients, regardless of the presence of MAFLD; meanwhile the expression of GPR41 is increased in patients with lean MAFLD. GPRs role in liver disease is intriguing and a field of research opportunity. More studies are necessary to define the role of active fatty acids in the development of metabolic diseases.

Hepatic steatosis and respiratory diseases: a new panorama.

Non-alcoholic fatty liver disease is defined as hepatic fat accumulation in more than 5% of hepatocytes, without other liver steatosis causes. It comprises a broad spectrum that can range from benign steatosis and progress to non-alcoholic steatohepatitis, fibrosis, and ultimately hepatocellular carcinoma. Non-alcoholic fatty liver is considered a multisystemic disease since it is related to multiple disorders, such as type 2 diabetes mellitus, polycystic ovary syndrome, chronic kidney disease, psoriasis, osteoporosis, hypothyroidism, cardiovascular diseases, and obstructive sleep apnea syndrome; it is becoming increasingly clear that it is also a risk factor for developing certain respiratory diseases. This article aims to understand the liver and chronic obstructive pulmonary disease mechanisms, obstructive sleep apnea syndrome, asthma, and lung cancer. Given that non-alcoholic fatty liver disease has a considerable impact on the patient's well-being and life quality, as well as on the costs they generate for the country's health services, it is essential to continue research, especially in areas such as the respiratory tract, as there is much misinformation about it.

Genetics and epigenetics purpose in nonalcoholic fatty liver disease.

INTRODUCTION: nonalcoholic fatty liver disease (NAFLD) comprises a broad spectrum of diseases, which can progress from benign steatosis to nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. NAFLD is the most common chronic liver disease in developed countries, affecting approximately 25% of the general population. Insulin resistance, adipose tissue dysfunction, mitochondrial and endoplasmic reticulum stress, chronic inflammation, genetic and epigenetic factors are NAFLD triggers that control the disease susceptibility and progression. AREAS COVERED: In recent years a large number of investigations have been carried out to elucidate genetic and epigenetic factors in the disease pathogenesis, as well as the search for diagnostic markers and therapeutic targets. This paper objective is to report the most studied genetic and epigenetic variants around NAFLD. EXPERT OPINION: NAFLD lead to various comorbidities, which have a considerable impact on the patient wellness and life quality, as well as on the costs they generate for the country's health services. It is essential to continue with molecular research, since it could be used as a clinical tool for prognosis and disease severity. Specifically, in the field of hepatology, plasma miRNAs could provide a novel tool in liver diseases diagnosis and monitoring, representing an alternative to invasive diagnostic procedures.

Sarcopenia in chronic liver diseases: a translational overview.

INTRODUCTION: Sarcopenia refers to a progressive and generalized muscle mass and strength loss. In liver diseases, it has been related to worse outcomes and high risk of decompensations. AREAS COVERED: Sarcopenia is caused by a set of cellular processes in the muscle such as denervation, mitochondrial dysfunction, endotoxemia and inflammation; which are manifested through the alteration of several proteolytic pathways such as lysosomal, proteasomal and caspase systems. In autophagy, myostatin and oxidative stress; such as hyperammonemia, contributes importantly to liver sarcopenia through loss of muscle mass already demonstrated in in vitro and in vivo models. In addition, hormones and the regulation of the intestinal microbiota, influence in a not less important magnitude. In the clinical setting, early identification of sarcopenia has been established as a mandatory item to prevent progression of muscle mass loss; however, diagnostic methods have extreme variation according to methodology, population, etiology and severity of liver disease. Reversing sarcopenia should be an integral therapeutic strategy. EXPERT OPINION: Clinical and nutritional interventions should be adapted to liver injury etiology and stage of disease, each of them shares a similar sarcopenia development pathway. There are specific biomarkers that condition or exacerbate loss of skeletal muscle.

Polycystic ovary syndrome with feasible equivalence to overweight as a risk factor for non-alcoholic fatty liver disease development and severity in Mexican population.

INTRODUCTION AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is the most common endocrinology disorder in women of reproductive age; these patients have a higher risk of suffering from non-alcoholic fatty liver disease (NAFLD). We determine the frequency of NAFLD in Mexican patients with PCOS and matched-controls. PATIENTS AND METHODS: Cross-sectional study, with 98 women of 18-44 years old. Rotterdam 2003 criteria integrated PCOS diagnosis. Those with significant alcohol consumption, chronic liver disease, use of steatogenic drugs, and pharmacological PCOS treatment or fertility protocol were excluded. Controls were matched in a 1:1 ratio by age and body mass index (BMI). The presence of NAFLD was determined by transient elastography performed by a single experienced operator. RESULTS: A total of 98 female volunteers at reproductive age were recruited. NAFLD denoted markedly higher in patients with than without PCOS at 69.3% vs. 34.6%, respectively. Compared to controls, PCOS patients had a significantly higher risk of NAFLD (OR=4.26, 95% CI 1.83-9.93). Severe steatosis was the most frequent NAFLD stage between women with PCOS and NAFLD. Patients with hyperandrogenism have a significantly higher mean CAP 277.83dB/m than controls without hyperandrogenism 191.57dB/m. NAFLD prevalence was 84.3% in PCOS patients with phenotype A, while in another phenotype, it was 41.1%. CONCLUSIONS: PCOS is an independent risk factor for NAFLD development. NAFLD screening needs to be considered in all PCOS patients independently of BMI, except in PCOS patients without hyperandrogenism and BMI<25.

The diagnostic and initial approach of the patient with non-alcoholic fatty liver disease: role of the primary care provider.

Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of liver damage, ranging from simple steatosis to steatohepatitis and fibrosis; as well, there is a close association between NAFLD, obesity, metabolic syndrome and type 2 diabetes mellitus. There is a certain degree of uncertainty regarding the natural history and prognosis of NAFLD; however, several methods are currently used for its diagnostic approach. In the first instance, non-invasive tests could be used to identify patients at low risk of developing fibrosis and to establish more easily the need for a liver biopsy, whose accuracy in the evaluation of fibrosis has been questioned, mainly due to errors of intra and interobserver sampling, technical problems and cost, which limits its use. Therefore, it is essential to determine the diagnostic strategy for patients with NAFLD.

Understanding the association of polycystic ovary syndrome and non-alcoholic fatty liver disease.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women. Patients with non-alcoholic fatty liver disease (NAFLD) often suffer from metabolic syndrome, atherosclerosis, ischemic heart disease, and extrahepatic tumors, conferring a lower survival than the general population; therefore it is crucial to study the association between NAFLD and PCOS since it remains poorly understood. Insulin resistance (IR) plays a central role in the pathogenesis of NAFLD and PCOS; also, hyperandrogenism enhances IR in these patients. IR, present in the NAFLD-PCOS association could decrease the hepatic production of sex hormone-binding globulin through a possible regulation mediated by hepatocyte nuclear factor 4 alpha. On the other hand, apoptotic processes initiated by androgens actively contribute to the progression of NAFLD. Considering the association between the two conditions, the screening of women with PCOS for the presence of NAFLD appears reasonable. The pathophysiological mechanisms of PCOS-NAFLD association and the initial approach will be reviewed here.

Association Between Serum Hemoglobin Levels and Non Alcoholic Fatty Liver Disease in a Mexican Population.

INTRODUCTION AND AIM: Nonalcoholic fatty liver disease (NAFLD) is closely associated with overweight and obesity, becoming one of the most prevalent hepatic diseases nowadays. Circulating hemoglobin (Hb) concentration is significantly higher in people with NAFLD, compared to healthy patients. While liver biopsy remains the gold standard for NAFLD diagnosis, it is not the best technique due to adverse events that may occur. Therefore it is important to find less invasive and more sensitive markers. This study aimed to determine the association of serum Hb levels in patients with steatosis and fibrosis as a noninvasive marker. MATERIAL AND METHODS: A 1,186 patient cross-sectional study nested in a randomized clinical trial (NCT01874249) was conducted. Patients were diagnosed by ultrasound for hepatic steatosis and fibroscan for fibrosis; blood test and anthropometric measurements were also assessed. RESULTS: Serum Hb increased proportionally related to the steatosis level, being significantly higher in patients with severe steatosis than in patients with moderate and mild steatosis. CONCLUSION: Patients with non-alcoholic fatty liver disease showed elevated levels of circulating Hb, evidence that suggests that Hb exerts a protective role, as it may act as an antioxidant and may counteract the adverse effects of this disease.

The role of the gut microbiota in the pathology and prevention of liver disease.

Several microorganisms belonging to the intestinal microbiota act in an ecosystem responsible for maintaining the homeostasis and vital functions of human beings. From birth to old age the diversity of the intestinal microbiota may change due to environmental factors such as nutrition, immunity, diseases or the use of antibiotics leading to dysbiosis. Improvement in microbiota diversity can be achieved by modifying related risk factors through changes in lifestyle and a healthy diet. Besides, the addition of probiotics, prebiotics or the combination of both (symbiotics), can result in the improvement of the intestinal permeability, inflammatory pathways and the immune system. Also, the use of probiotics prevents harmful bacteria and their derived products (e.g., bacteriocins, endotoxins, hydrogen sulfide, etc.) to leak through the intestinal wall to the circulation that results in the activation of signaling pathways that may be implicated in liver disease. The liver receives a constant flow of noxious entities that promote inflammation and oxidative stress. The use of probiotics with clinical evidence in liver disease, represent a novel therapeutic alternative, inducing positive changes in the balance of the intestinal microbiota which lead to improvement in liver function tests (AST and ALT), decreasing tumor necrosis factor-α (TNF-α), andblood cholesterol, among other risk factors. In this review, we discuss the main elements that play a leading role in the development of steatosis as well as the benefits of using probiotics and the impact in the quality of life of patients that develop cirrhosis.