Long non-coding RNAs as modulators and therapeutic targets in non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, with epidemiological studies indicating a 25% prevalence. NAFLD is considered to be a progressive disease that progresses from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), then to liver fibrosis, and finally to cirrhosis or hepatocellular carcinoma (HCC). Existing research has mostly elucidated the etiology of NAFLD, yet its particular molecular processes remain uncertain. Long non-coding RNAs (LncRNAs) have been linked in a wide range of biological processes in recent years, with the introduction of microarray and high-throughput sequencing technologies, and previous studies have established their tight relationship with several stages of NAFLD development. Existing studies have shown that lncRNAs can regulate the signaling pathways related to hepatic lipid metabolism, NASH, NASH-related fibrosis and HCC. This review aims to provide a basic overview of NAFLD and lncRNAs, summarize and describe the mechanisms of lncRNAs action involved in the development of NAFLD, and provide an outlook on the future of lncRNAs-based therapy for NAFLD.

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects adipose function. This study aimed to explore the function of adipocytes-derived exosomal (ADEs) miR-122 in NAFLD. METHODS: A high-fat and high-fructose diet-induced rat model and a palmitic acid (PA)-induced in vitro model were established. The RNA level of miR-122 and Sirt1 was measured using qRT-PCR. The protein levels of exosome biomarkers, and lipogenesis, inflammation and fibrosis biomarkers were determined by western blotting. Cell viability and apoptosis were assessed using cell counting kit-8 and flow cytometry, respectively. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride levels were measured. Liver tissue damage was assessed using haematoxylin and eosin staining. The interaction between miR-122 and Sirt1 3'UTR was assessed using a luciferase reporter gene assay. RESULTS: ADEs exhibited abundant level of miR-122 and promoted lipogenesis, impaired hepatocyte survival, enhanced liver damage and increased serum lipid levels in vivo and in vitro. Inhibition of miR-122 in ADEs alleviated NAFLD progression, lipid and glucose metabolism, liver inflammation and fibrosis both in vivo and in vitro. miR-122 binds directly to the 3'UTR of Sirt1 to suppress its expression. Moreover, Sirt1 overexpression reversed the increase in cell apoptosis, glucose and lipid metabolism, liver inflammation and fibrosis induced by ADEs in vivo and in vitro. CONCLUSIONS: The ADEs miR-122 promotes the progression of NAFLD via modulating Sirt1 signalling in vivo and in vitro. The ADEs miR-122 may be a promising diagnostic biomarker and therapeutic target for NAFLD.

Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study.

OBJECTIVE: To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. PATIENTS AND METHODS: Physician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. RESULTS: Overall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12-1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68-11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19-2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30-7.63; p=0.010) times higher for those unable to work due to NASH. CONCLUSIONS: Disease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Burden of disease due to liver cirrhosis in Mexico.

BACKGROUND: Liver cirrhosis is a major cause of morbidity and mortality worldwide. In Mexico, it is one of the six leading causes of death. OBJECTIVE: To analyze epidemiological data derived from the Global Burden of Disease study and their relationship with risk factors associated with the development of chronic liver diseases in Mexico. MATERIAL AND METHODS: An analysis of data from the Institute for Health Metrics and Evaluation and the National Institute of Geography and Statistics was carried out. RESULTS: Liver cirrhosis has a high prevalence in Mexico, with significant burden of disease translating into lost years of healthy life, premature death and disability. Mortality due to cirrhosis ranked sixth (3.6%) in 2021 and was the eighth cause of years of healthy life lost (2.8%). From 1990 to 2021, the mortality rate increased from 26.7 to 34.2 per 100,000 population. CONCLUSIONS: The burden of disease due to liver cirrhosis continues to be caused by alcohol consumption and hepatitis C; cirrhosis caused by steatotic liver disease has increased in terms of prevalence over the past decade. There are epidemiological changes in the frequency and burden of chronic liver disease that show territorial variations in Mexico.

ANTECEDENTES: La cirrosis hepática es una causa importante de morbilidad y mortalidad en el mundo. En México, constituye una las primeras seis causas de muerte. OBJETIVO: Analizar los datos epidemiológicos derivados del estudio de Global Burden of Disease y su relación con los factores de riesgo asociados al desarrollo de hepatopatías crónicas en México. MATERIAL Y MÉTODOS: Se realizó el análisis de datos provenientes del Instituto para la Medición y Evaluación de la Salud y del Instituto Nacional de Estadística y Geografía. RESULTADOS: La cirrosis hepática tiene una prevalencia alta en México, con una carga de enfermedad importante traducida en años perdidos de vida saludable, por muerte prematura y por discapacidad. La mortalidad por cirrosis ocupó el sexto lugar (3.6 %) en 2021 y fue la octava causa de años de vida saludable perdidos (2.8 %). De 1990 a 2021, la tasa de mortalidad se incrementó de 26.7 a 34.2 por 100 000 habitantes. CONCLUSIONES: La carga de enfermedad por cirrosis hepática se continúa derivando del consumo de alcohol y de la hepatitis C; la prevalencia de la cirrosis causada por enfermedad hepática esteatósica se ha incrementado en la última década. Existen cambios epidemiológicos en la frecuencia y carga de la hepatopatía crónica que muestra variaciones territoriales en México.

Body composition and phase angle by bioimpedance in patients with MAFLD. / Análisis de la composición corporal y ángulo de fase por bioimpedancia en pacientes con MAFLD.

OBJECTIVE: To describe the characteristics of the body components and phase angle (PhA) of patients with MAFLD according to those different to fibrosis and hepatic steatosis. MATERIAL AND METHODS: Observational and descriptive study in a cohort of 585 volunteers from our center with MAFLD criteria. The risk of liver fibrosis was determined by APRI, NAFLD score and FIB-4; at an indeterminate and high risk of fibrosis, a transient elastography (Fibroscan®) were realized. Bioimpedance body composition analysis (SECA®) was performed. Patients with ET and SECA® registry were included. Bioimpedance body composition analysis (SECA®) was performed. Patients with ET and SECA® registry were included. RESULTS: 125 participants (21.4%) were evaluated, age 53.9±13.9 years, 62.1% women, BMI 33.2±5.8kg/m2. The SECA® analysis showed mean fat mass of 42%±7.32 and muscle mass 21.18kg±6.6. The PhA was 5.1±0.69, in women 4.92±0.62 and men 5.41±0.70. PhA in patients without fibrosis was 5.091 vs with fibrosis 5.121 (P=.813). In advanced fibrosis, it reported a low value compared to the rest of the groups (P=.031). The PhA in S3 was higher compared to S1 and S2 (5.3 vs 4.82, 4.81) (P=.027). CONCLUSIONS: In MAFLD, the PhA was lower than the healthy Mexican population. In patients without fibrosis and severe steatosis, PhA rises proportionally to the increase in fat mass and BMI and in advanced liver fibrosis, PhA decreases.

Effect of the Mediterranean diet on histological indicators and imaging tests in non-alcoholic fatty liver disease. / Efecto de la dieta mediterránea sobre indicadores histológicos y pruebas de imagen en enfermedad de hígado graso no alcohólico.

AIM: To analyze the scientific evidence regarding to the effect of the Mediterranean diet on the imaging tests and biopsy characteristics in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: A bibliographic search was carried out in this narrative review in Pubmed and Web of Science databases, considering studies published between 2011 and 2020, in English or Spanish, randomized clinical trials and observational studies in patients with a diagnosis of NAFLD, in subjects over 18years of age of both sexes. RESULTS: In the observational studies found, an inverse association between adherence to a Mediterranean diet and liver damage stands out, while in the intervention studies with measurement of liver biopsy a 4.4% reduction in intrahepatic lipids and with magnetic resonance a reduction between 4.2 and 10.2% was found. In experimental studies with ultrasound measurement, the proportion of people with moderate (6-16%) and severe (25%) degree decreased and the studies with transient elastography showed a decrease in liver stiffness between 0.5 and 2.1kPa. CONCLUSIONS: The Mediterranean diet contributes to the treatment of NAFLD, which is manifested in the liver and histological imaging tests characteristics.

Immunity to hepatitis A virus in liver transplant recipients: A population-based study in Iran.

BACKGROUND: Acute hepatitis A is usually a self-limited viral disease but can be severe and even fatal in special groups of patients including those with chronic liver disease and recipients of liver transplantation. To take appropriate preventive measures, it is important to determine the immune status against the hepatitis A virus in patients at risk of grave clinical outcomes following infection. To assess the need for immunization against hepatitis A, we aimed to determine the immune status against hepatitis A in a population of liver transplant recipients. We also investigated the association between hepatitis A immune status and demographic factors such as age and sex, underlying liver disease, source of drinking water, geographical area of residence and socioeconomic status. METHODS: This cross-sectional study was performed on 242 recipients of allogenic liver transplants at Abu Ali Sina Organ Transplant Hospital in Shiraz, Iran, between January 2017 and April 2017. The level of immunity was assessed using hepatitis A antibody detection kits. RESULTS: The rate of immunity against hepatitis A was detected as 88.8% in our study population. In the multivariable logistic regression model, younger age (OR=1.175, P<0.001) and higher education level (OR=2.142, P=0.040) were the main determinants of non-immune status. However, hepatitis A immunity was independent of gender, monthly family income, water supply source, residential area and underlying liver disorder. CONCLUSION: Although a significant proportion of liver transplant recipients in this study showed evidence of natural immunity to hepatitis A, a considerable proportion of younger patients and those with a higher level of education were non-immune. The results of this study signify the importance of screening for hepatitis A immunity in this at-risk population of patients and the need for vaccinating non-immune patients.

Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. METHODS: Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. RESULTS: Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006-1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1-1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815-182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215-42.43). CONCLUSION: Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).

Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease.

INTRODUCTION: Although the use of non-invasive methods for assessment of liver fibrosis has reduced the need for biopsy, the diagnosis of liver damage still requires histological evaluation in many patients. We aim to describe the indications for percutaneous liver biopsy (PLB) and the rate of complications in an outpatient setting over 5 years. METHODS: This observational, single-center, and retrospective study included patients submitted to real-time ultrasound (US)-guided biopsies from 2015 to 2019. We collected age, gender, coagulation tests, comorbidities, and the number of needle passes. The association between the variables and complications was evaluated using the generalized estimating equations method. RESULTS: We analyzed 532 biopsies in 524 patients (55.3% male) with a median age of 49 years (range 13-74y). An average of 130.3 biopsies per year were performed in the first 3 years of the study versus 70.5 in the other 2y. The main indications were hepatitis C virus (HCV) infection (47.0%), autoimmune and cholestatic liver diseases (12.6%), and metabolic dysfunction-associated fatty liver disease (MAFLD) (12.1%). The number of HCV-related biopsies had a remarkable reduction, while MAFLD-related procedures have progressively raised over time. Around 54% of the patients reported pain, which was significantly associated with females (p=0.0143). Serious complications occurred in 11 patients (2.1%) and hospital admission was necessary in 10 cases (1.9%). No patient required surgical approach and there were no deaths. No significant association was found between the studied variables and biopsy-related complications. CONCLUSION: The indications for PLB in an outpatient setting have changed from HCV to MAFLD over the years. This procedure is safe and has a low rate of serious complications, but new strategies to prevent the pain are still needed, especially for females.

Association between indocyanine green clearance test and ischemic type biliary lesions within one year after orthotopic liver transplantation.

BACKGROUND: Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. OBJECTIVE: Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. METHODS: This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. RESULTS: ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.

Involvement of the digestive system in covid-19. A review. / Afectación del aparato digestivo en la covid-19. Una revisión sobre el tema.

The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. covid19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.

Donor-specific antibodies in liver transplantation.

Despite unique immunoregulatory properties pointing toward tolerance, the liver allograft can be negatively impacted by humoral alloreactivity, with immediate as well as long-term harmful consequences. With regard to the unmet need of long-term outcomes improvement after liver transplantation, donor-specific antibodies have recently been the matter of intense study in this context. We review here recent advances regarding the understanding of the impact of preformed as well as de novo anti-human leukocyte antigen donor-specific antibodies in liver transplantation and discuss potential strategies to overcome this problem.

Autoimmune hepatitis - primary biliary cholangitis overlap syndrome. Long-term outcomes of a retrospective cohort in a university hospital. / Síndrome de superposición: hepatitis autoinmune y colangitis biliar primaria. Resultados a largo plazo de una cohorte retrospectiva en un hospital universitario.

BACKGROUND: Autoimmune hepatitis (AIH) with characteristics of primary biliary cholangitis (PBC) is known as overlap syndrome. Its prevalence and prognosis have not yet been determined comparatively with AIH. METHODS: A retrospective cohort study was conducted comparing patients diagnosed with AIH and AIH-PBC overlap syndrome, followed-up for seven years in a university hospital in Colombia, until 31 December 2016. RESULTS: A total of 210 patients were included (195 women, mean age 48.5years). Of these, 32 (15.2%) had AIH-PBC overlap syndrome. At diagnosis, no significant differences were found by demographic profile, positive autoantibodies (ANA, ASMA), except AMA (81.2% vs 3.9%, P<.001), and histological grade of fibrosis. The most frequent clinical presentations were nonspecific symptoms in AIH-PBC and acute hepatitis in AIH. Although there were no significant differences, AIH showed a greater biochemical response to immunosuppressive management (87.3% vs 74.2%, P=.061) and a greater number of relapses in those who achieved partial or complete remission during treatment (12.4% vs 7.63%; P=.727). Patients with AIH-PBC had greater progression to cirrhosis (22.2% vs 13.1%, P=.038), even in those who achieved partial or complete biochemical remission without relapse, with greater indication of orthotopic liver transplantation (P=.009), but not retransplantation (P=.183); there were no differences in mortality. CONCLUSIONS: AIH-PBC overlap syndrome accounts for a significant proportion of patients with AIH, with greater progression to cirrhosis, indication of liver transplantation and possibly retransplantation. This higher risk of adverse outcomes suggests closer monitoring, probably with follow-up until confirmed histopathological remission.

Characterization of patients with autoimmune hepatitis at an university hospital in Medellín-Colombia: cohort study. / Caracterización de los pacientes con hepatitis autoinmune de un hospital universitario, Medellín-Colombia: estudio de cohorte.

INTRODUCTION: Autoimmune hepatitis is a chronic liver disease that impacts on morbidity and mortality of patients. Few epidemiological data exist of this in Latin America and Colombia. OBJECTIVES: The aim of this study is to describe the demographic, clinical and laboratory characteristics of the patients; the treatment and the response to it, the evolution and course of the disease, requirement of liver transplantation and mortality. METHODS: Historical cohort study that include patients attended at an University Hospital in Medellin, Colombia between January 2010 and December 2016 with ≥16 years age at the time of diagnosis of autoimmune hepatitis. Data collection was done from the review of medical records. Statistical analysis was performed using SPSS version 20. RESULTS: The study included 278 patients, 90% of the patients were women, the median age at diagnosis was 50 years. 37.8% were cirrhotic at the time of diagnosis. The biochemical remission was 85%. In patients who developed cirrhosis it was found a higher proportion of men (21.2 vs. 7.8%, p=.027), a greater frequency of overlap autoimmune-primary sclerosant cholangitis (6.0 vs. 0% p=.006) and a greater frequency of non-response to treatment (12.1 vs. 1.6%, p=.004). CONCLUSION: Autoimmune hepatitis is not a rare disease in Colombian population; it predominates in women but has a less favourable course in men. An important number of patients are cirrhotic at the time of diagnosis, the response to treatment and complications in our population are similar to those described worldwide.

Role of altered immune cells in liver diseases: a review.

Immune cells play an important role in controlling liver tumorigenesis, viral hepatitis, liver fibrosis and contribute to pathogenesis of liver inflammation and injury. Accumulating evidence suggests the effectiveness of natural killer (NK) cells and Kupffer cells (KCs) against viral hepatitis, hepatocellular damage, liver fibrosis, and carcinogenesis. Activation of natural killer cells provides a novel therapeutic strategy to cure liver related diseases. This review discusses the emerging roles of immune cells in liver disorders and it will provide baseline data to scientists to design better therapies for treatment.

Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline. / Documento de consenso. Manejo de la enfermedad hepática grasa no alcohólica (EHGNA). Guía de práctica clínica.

Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville.

Validation of a liquid chromatography/tandem mass spectrometry method for the detection of aflatoxin B1 residues in broiler liver.

Aflatoxin B1 is a carcinogenic and mutagenic mycotoxin produced mainly by Aspergillus flavus and Aspergillus parasiticus. It is the predominant mycotoxin found in raw materials used for the manufacture of broiler feeds. The aim of the present study was to develop a new and optimized method for the detection and quantification of aflatoxin B1 (AFB1) residues in broiler liver using solid phase extraction (SPE) clean-up and liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI-MS/MS) detection. The method was validated for linearity, accuracy, precision, limit of detection (LOD) and limit of quantification (LOQ). The validation parameters indicated satisfactory linearity (r2>0.99), accuracy and precision (4.57% intra-day RSD; 14.65% inter-day RSD) a very high recovery (99±13%) and high sensitivity achieved for AFB1 in animal samples (LOD=0.017 and LOQ=0.050ng/g). The method was effective for the detection and quantification of AFB1 residues in broiler liver and could also be potentially used for detecting AFB1 in other edible animal tissues after natural or experimental AFB1 exposure with high sensitivity and precision.

Serum cytokeratin-18 fragment levels as noninvasive marker of nonalcoholic steatohepatitis in the chilean population. / Fragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena.

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. OBJECTIVE: To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. METHODS: Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. RESULTS: The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). CONCLUSION: CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.

Liver transplantation for acute liver failure. / Trasplante hepático debido a fallo hepático agudo.

Before liver transplantation became widely applicable as a treatment option, the mortality rate for acute liver failure was as high as 85%. Today, acute liver failure is a relatively common transplant indication in some settings, but the results of liver transplantation in this context appear to be worse than those for chronic forms of liver disease. In this review, we discuss the indications and contraindications for urgent liver transplantation. In particular, we consider the roles of auxiliary, ABO-incompatible, and urgent living donor liver transplantation and address the management of a «status 1¼ patient with total hepatectomy and portocaval shunt for toxic liver syndrome.

Psoriasis and Nonalcoholic Fatty Liver Disease. / Psoriasis e hígado graso no alcohólico.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.