Occult liver disease: A multinational perspective.

Occult liver disease refers to the presence of unrecognized chronic liver disease and cirrhosis. Liver disease is currently the eleventh cause of death globally, representing 4% of all deaths in the world. Alcohol consumption is the leading cause of cirrhosis globally, accounting for approximately 60% of cases. The estimated global prevalence of non-alcoholic fatty liver disease (NAFLD) is 32.4% and has been steadily increasing over the last years. Viral hepatitis B and C accounted for 1.3 million deaths in 2020. Several studies in populations at high risk of chronic liver disease (elevated liver enzymes, type 2 diabetes, excessive alcohol consumption) have found an elevated prevalence of occult liver disease. Attempts should be made to assess the prevalence of occult liver disease in Latin America, a region with one of the highest rates of metabolic diseases and excessive alcohol consumption. Screening for NAFLD in high-risk subjects and screening for excessive drinking and alcohol use disorders at every level of medical care is relevant. Efforts should also focus on the early treatment of occult liver disease to try to reduce liver disease burden and, in the case of occult viral hepatitis infection, prevent further spreading.

Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease.

The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-ß in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-ß agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-ß agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-ß agonists have on hepatic lipid metabolism.

Clostridioides Difficile in Latin America: An Epidemiological Overview.

Clostridioides difficile infection is one of the most significant causes of nosocomial diarrhea associated with antibiotic use worldwide. In recent years, the incidence of Clostridioides difficile infection in Latin American countries has increased due to the emergence and spread of epidemic Clostridioides difficile strains, such as RT027/NAP1/ST1, RT078/ST11, and RT017/ST37; additionally, endemic multi-drug-resistant strains have recently appeared due to the lack of heterogeneous diagnostic algorithms and guidelines for antibiotic use in each country. The aim of this review is to present the latest information regarding Clostridioides difficile and emphasize the importance of epidemiological surveillance of this pathogen in Latin American countries.

Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Current approaches to hepatic encephalopathy.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%-40% of patients with cirrhosis will present overt HE during their lifetime. While the pathophysiology of HE is not entirely understood, three critical factors have been identified: hyperammonaemia, systemic inflammation and oxidative stress by glutaminase gene alterations. Minimal HE is defined by the presence of signs of cognitive abnormalities in a patient without asterixis or disorientation; it can only be diagnosed with neuropsychological or psychometric tests. The diagnosis of overt HE is based on clinical examination with clinical scales. Currently, only overt HE should be routinely treated. The aims of treatment in an acute episode should be to improve the mental status, identify and treat the precipitating factor, reduce duration and limit consequences. Treatment strategies are targeted at reducing ammonia production and/or increasing its elimination. Even though minimal HE has negative effects on the patient's quality of life and effects on prognosis, indications for treatment are still controversial. There are still many unanswered questions regarding the pathophysiology and management of HE. We should also endeavor to develop more accurate and objective diagnostic methods for overt HE that would permit early detection and help improve outcomes on quality of life and economic burden.

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).

Epidemiological and Genetic Aspects of NAFLD and NASH in Mexico.

Content available: Author Interview and Audio Recording.

Inulin Improves Diet-Induced Hepatic Steatosis and Increases Intestinal Akkermansia Genus Level.

Hepatic steatosis is characterized by triglyceride accumulation within hepatocytes in response to a high calorie intake, and it may be related to intestinal microbiota disturbances. The prebiotic inulin is a naturally occurring polysaccharide with a high dietary fiber content. Here, we evaluate the effect of inulin on the intestinal microbiota in a non-alcoholic fatty liver disease model. Mice exposed to a standard rodent diet or a fat-enriched diet, were supplemented or not, with inulin. Liver histology was evaluated with oil red O and H&E staining and the intestinal microbiota was determined in mice fecal samples by 16S rRNA sequencing. Inulin treatment effectively prevents liver steatosis in the fat-enriched diet group. We also observed that inulin re-shaped the intestinal microbiota at the phylum level, were Verrucomicrobia genus significantly increased in the fat-diet group; specifically, we observed that Akkermansia muciniphila increased by 5-fold with inulin supplementation. The family Prevotellaceae was also significantly increased in the fat-diet group. Overall, we propose that inulin supplementation in liver steatosis-affected animals, promotes a remodeling in the intestinal microbiota composition, which might regulate lipid metabolism, thus contributing to tackling liver steatosis.

Hepatitis B infection in Mexican adults: Results of a nationally representative survey.

INTRODUCTION AND OBJECTIVES: Hepatitis B virus (HBV) infection can lead to cirrhosis, hepatocellular carcinoma, and death if untreated. In Mexico, HBV vaccination for all children and adolescents was implemented in 1999. In 2000 the estimated HBV was 0.21% in the population aged 20 years and older. We estimated the national prevalence for hepatitis B surface antigen (HBsAg) and its association with sociodemographic characteristics, including sexual behavior information for those aged 20 to 49 years. MATERIALS AND METHODS: From the 2018 National Health and Nutrition Survey, blood samples were collected from a subsample of 2,280 adults to determine HBsAg. We estimated the national prevalence for HBsAg and evaluated its association with sociodemographic characteristics, adding sexual behavior information for those aged 20 to 49 years. We performed a multiple logistic regression to estimate the association of HBsAg and relevant variables. RESULTS: The 2018 estimated prevalence of HBsAg in the Mexican adult population was 0.51% (95%CI 0.19, 2.33), which represents 411,000 cases. This prevalence was higher than previously estimated and it was higher in women than in men (0.54% versus 0.46%, respectively). We did not find an association between HBsAg and sociodemographic characteristics or sexual behaviors. CONCLUSIONS: Vaccination and screening strategies towards the elimination of viral hepatitis should be reinforced to further reduce the prevalence over the next years.

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.

Role of the inflammasome, gasdermin D, and pyroptosis in non-alcoholic fatty liver disease.

Pyroptosis is a type of programmed cell death mediated by a multiprotein complex called the inflammasome through the pro-inflammatory activity of gasdermin D. This study aimed to recognize the final biological product that leads to pore formation in the cell membrane, lysis, pro-inflammatory cytokines release, and the establishment of an immune response. An exhaustive search engine investigation of an elevated immune response can induce a sustained inflammation that directly links this mechanism to non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. Clinical studies and systematic reviews suggest that gasdermin D is a critical molecule between the immune response and the disease manifestation, which could be considered a therapeutic target for highly prevalent diseases characterized by presenting perpetuated inflammatory processes. Both basic and clinical research show evidence on the expression and regulation of the inflammasome-gasdermin D-pyroptosis trinomial for the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis.

Lactate-dehydrogenase associated with mortality in hospitalized patients with COVID-19 in Mexico: a multi-centre retrospective cohort study.

INTRODUCTION AND OBJECTIVES: As of January 2021, over 88 million people have been infected with COVID-19. Almost two million people have died of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high SOFA score and a D-Dimer >1 µg/mL identifies patients with high risk of mortality. High lactate dehydrogenase (LDH) levels on admission are associated with severity and mortality. Different degrees of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormalities have been reported in these patients, its association with a mortality risk remains controversial. The aim of this study was to explore the correlation between LDH and in-hospital mortality in Mexican patients admitted with COVID-19. MATERIALS & METHODS: We performed a retrospective multi-centre cohort study with 377 hospitalized patients with confirmed SARS-CoV-2 in three centres in Mexico City, Mexico, who were ≥18 years old and died or were discharged between April 1 and May 31, 2020. RESULTS: A total of 377 patients were evaluated, 298 (79.1%) patients were discharged, and 79 (20.9%) patients died during hospitalization. Non-survivors were older, with a median age of 46.7 ± 25.7 years old, most patients were male. An ALT > 61 U/l (OR 3.45, 95% CI 1.27-9.37; p = 0.015), C-reactive protein (CRP) > 231 mg/l (OR 4.71, 95% CI 2.35-9.46; p = 0.000), LDH > 561 U/l (OR 3.03, 95% CI 1.40-6.55; p = 0.005) were associated with higher odds for in-hospital death. CONCLUSIONS: Our results indicate that higher levels of LDH, CRP, and ALT are associated with higher in-hospital mortality risk in Mexican patients admitted with COVID-19.

The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease.

The Latin American Association for the Study of the Liver (Asociación Latinoamericana para el Estudio del Hígado; ALEH) represents liver professionals in Latin America with the mission of promoting liver health and quality patient care by advancing the science and practice of hepatology and contributing to the development of a regional health policy framework. Fatty liver disease associated with metabolic dysfunction is of specific concern in the ALEH region, where its prevalence is one of the highest globally, second only to the Middle East. A recent consensus from an international panel recommended a new definition of fatty liver disease associated with metabolic dysfunction, including a shift in name from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), and adoption of a set of positive criteria to diagnose the disease, independent of alcohol intake or other liver diseases. Given, the importance of this proposal, ALEH invited leading members of regional nations to come to a consensus on it from a local perspective. We reached a consensus to endorse the proposal that the disease should be renamed as MAFLD and that the disease should be diagnosed by the proposed simple and easily applicable criteria. We expect that this change in nosology will result in improvements in disease awareness and in advances in scientific, economic, public health, political, and regulatory aspects of the disease.

Cholecystectomy as a risk factor for non-alcoholic fatty liver disease development.

BACKGROUND: Hepatic steatosis and gallstone disease are highly prevalent in the general population; the shared risk factors are age, ethnicity, obesity, insulin resistance, metabolic syndrome, atherosclerosis, risk of cardiovascular disease, and mortality. The presence of insulin resistance is the critical element in this association because it represents a crucial link between metabolic syndrome and non-alcoholic fatty liver disease, as well as a higher susceptibility to gallstone formation. METHODS: An exhaustive search engine investigation of gallstone disease, cholecystectomy, and liver steatosis latest literature was made. RESULTS: Clinical studies and systematic reviews suggest an association between gallstone disease, cholecystectomy, and hepatic steatosis. CONCLUSION: The bidirectional relationship between liver steatosis and gallstone disease and cholecystectomy is summarized in the role of insulin resistance, lipid metabolism, bile acids signaling pathways regulated by transcription factors expression, and to the gallbladder physiological role; however, more epidemiological and experimental studies should be complemented.

Dietary consumption and serum pattern of bioactive fatty acids in NAFLD patients.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Some dietary fatty acids have showed different bioactive functions in metabolic syndrome. The aim of this study is to determine the dietary consumption patterns and serum percentage of bioactive fatty acids in NAFLD patients. PATIENTS AND METHODS: Cross-sectional study with NAFLD patients and non-NAFLD patients. Dietary consumption of bioactive fatty acids was assessed by a food frequency questionnaire. NAFLD and liver fibrosis were diagnosed by transient elastography. The identification of serum bioactive fatty acids was achieved by gas chromatography-mass spectrometry (%). Bioactive fatty acids consumption was correlated with NAFLD clinical characteristics with the Spearman correlation analysis. RESULTS: A total of 299 patients were included, whose mean of age and body mass index were 44.2±9.9 years and 25.9±3.8kg/m2, respectively. The consumption of bioactive fatty acids was no different regarding the presence of NAFLD; however, the consumption of stearic and linoleic fatty acids was higher in relation with NAFLD severity (p≤0.05). The consumption of myristic acid was higher in patients with fibrosis (p=0.02). Serum percentage and dietary consumption did not show correlations. CONCLUSION: Dietary consumption of bioactive fatty acids is different according to NAFLD severity. Individualized diets according to NAFLD severity could be successful in order to prevent liver injury-related outcomes.