Position paper on perioperative management and surgical risk in the patient with cirrhosis.

INTRODUCTION: Management of the patient with cirrhosis of the liver that requires surgical treatment has been relatively unexplored. In Mexico, there is currently no formal stance or expert recommendations to guide clinical decision-making in this context. AIMS: The present position paper reviews the existing evidence on risks, prognoses, precautions, special care, and specific management or procedures for patients with cirrhosis that require surgical interventions or invasive procedures. Our aim is to provide recommendations by an expert panel, based on the best published evidence, and consequently ensure timely, quality, efficient, and low-risk care for this specific group of patients. RESULTS: Twenty-seven recommendations were developed that address preoperative considerations, intraoperative settings, and postoperative follow-up and care. CONCLUSIONS: The assessment and care of patients with cirrhosis that require major surgical or invasive procedures should be overseen by a multidisciplinary team that includes the anesthesiologist, hepatologist, gastroenterologist, and clinical nutritionist. With respect to decompensated patients, a nephrology specialist may be required, given that kidney function is also a parameter involved in the prognosis of these patients.

Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Current vision on diagnosis and comprehensive care in hepatic encephalopathy.

The first clinical guidelines on hepatic encephalopathy were published in 2009. Almost 14 years since that first publication, numerous advances in the field of diagnosis, treatment, and special condition care have been made. Therefore, as an initiative of the Asociación Mexicana de Gastroenterología A.C., we present a current view of those aspects. The manuscript described herein was formulated by 24 experts that participated in six working groups, analyzing, discussing, and summarizing the following topics: Definition of hepatic encephalopathy; recommended classifications; epidemiologic panorama, worldwide and in Mexico; diagnostic tools; conditions that merit a differential diagnosis; treatment; and primary and secondary prophylaxis. Likewise, these guidelines emphasize the management of certain special conditions, such as hepatic encephalopathy in acute liver failure and acute-on-chronic liver failure, as well as specific care in patients with hepatic encephalopathy, such as the use of medications and types of sedation, describing those that are permitted or recommended, and those that are not.

Immune dysregulation and pathophysiology of alcohol consumption and alcoholic liver disease.

Alcoholic liver disease (ALD) is a clinical-pathologic entity caused by the chronic excessive consumption of alcohol. The disease includes a broad spectrum of anomalies at the cellular and tissual level that can cause acute-on-chronic (alcoholic hepatitis) or chronic (fibrosis, cirrhosis, hepatocellular cancer) injury, having a great impact on morbidity and mortality worldwide. Alcohol is metabolized mainly in the liver. During alcohol metabolism, toxic metabolites, such as acetaldehyde and oxygen reactive species, are produced. At the intestinal level, alcohol consumption can cause dysbiosis and alter intestinal permeability, promoting the translocation of bacterial products and causing the production of inflammatory cytokines in the liver, perpetuating local inflammation during the progression of ALD. Different study groups have reported systemic inflammatory response disturbances, but reports containing a compendium of the cytokines and cells involved in the pathophysiology of the disease, from the early stages, are difficult to find. In the present review article, the role of the inflammatory mediators involved in ALD progression are described, from risky patterns of alcohol consumption to advanced stages of the disease, with the aim of understanding the involvement of immune dysregulation in the pathophysiology of ALD.

Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement.

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. / Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Detection of Exudates and Microaneurysms in the Retina by Segmentation in Fundus Images / Detección de Exudados y Microaneurismas en la Retina por Segmentación en Imágenes de Fondo

ABSTRACT This article proposes two methodologies for the detection of lesions in the retina, which may indicate the presence of diabetic retinopathy (DR). Through the use of digital image processing techniques, it is possible to isolate the pixels that correspond to a lesion of RD, to achieve segmenting microaneurysms, the edges of the objects contained in the image are highlighted in order to detect the contours of the objects to select by size those that meet an area of 15 to 25 pixels in the case of 512x512 images and identify the objects as possible microaneurysms, while for the detection of exudates the green channel is selected to contrast the luminous objects in the retinography and from the conversion to gray scale, a histogram is graphed to identify the ideal threshold for the segmentation of the pixels that belong to the exudates at the end of the optical disk previously identified by a specialist. A confusion matrix supervised by an ophthalmologist was created to quantify the results obtained by the two methodologies, obtaining a specificity of 0.94 and a sensitivity of 0.97, values that are outstanding to proceed with the classification stage.

RESUMEN Este artículo propone dos metodologías para la detección de lesiones en la retina, que pueden significar la presencia de retinopatía diabética (RD). Mediante el uso de técnicas de procesamiento de imágenes digitales se logra aislar los pixeles que corresponden a una lesión propia de RD, para lograr segmentar microaneurismas se resaltan los bordes de los objetos contenido en la imagen con la finalidad de detectar los contornos de los objetos para seleccionar por tamaño los que cumplan con un área de 15 a 25 pixeles en el caso de imágenes de 512x512 y se identifiquen los objetos como posibles microaneurismas, mientras que para la detección de exudados se selecciona el canal verde para contrastar los objetos luminosos en la retinografía y a partir de la conversión a escala de grises se grafica un histograma para identificar el umbral idóneo para la segmentación de los pixeles que pertenecen a los exudados al final eliminar el disco óptico previamente identificado por un especialista. Se creó una matriz de confusión supervisada por un oftalmólogo para cuantificar los resultados obtenidos por las dos metodologías obteniendo una especificidad del 0.94 y una sensibilidad del 0.97, unos valores que son sobresalientes para proceder con la etapa de clasificación.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. / Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

The Mexican consensus on alcoholic hepatitis. / Consenso Mexicano de hepatitis alcohólica.

Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.

Production of insulin-like growth factor-binding proteins during the development of hepatic fibrosis due to chronic hepatitis C. / Producción de las proteínas de unión al factor de crecimiento insulinoide durante el desarrollo de la fibrosis hepática por hepatitis C crónica.

INTRODUCTION AND AIMS: Insulin-like growth factor 1 is modulated by the insulin-like growth factor-binding proteins (IGFBPs) that are synthesized in the liver. The aim of the present study was to evaluate the concentrations of IGFBPs 1-7 in patients with chronic hepatitis C and study their association with fibrosis stage. PATIENTS AND METHODS: A prospective, cross-sectional study was conducted that included patients with chronic hepatitis C. The stages of fibrosis were determined through FibroTest and FibroScan and the patients were compared with a control group. Serum levels of IGFBPs 1-7 were quantified through multiple suspension arrays. The Kruskal-Wallis test, Mann-Whitney U test, Spearman's correlation, and ROC curves were used for the statistical analysis. RESULTS: Upon comparing the patients and controls, the highest concentrations were found in IGFBPs 1, 2, 4, and 7 (p=0.02, p=0.002, p=0.008, and p<0.001, respectively). IGFBP-3 levels had a tendency to be lower in the patients (p=0.066), whereas values were similar between patients and controls for IGFBP-5 and 6 (p=0.786 and p=0.244, respectively). Of the seven IGFBPs, IGFBP-3 concentrations were the highest. There were significant differences between fibrosis stages for IGFBP-5 and IGFBP-7. CONCLUSION: IGFBPs play a relevant role in the fibrotic process in liver damage. IGFBP-7, in particular, differentiates fibrosis stages, making it a potential serum biomarker.

Targeting M2e to DEC-205 induces an enhanced serum antibody-dependent heterosubtypic protection against influenza A virus infection.

The ectodomain of the influenza A virus (IAV) M2 protein (M2e) is highly conserved, and it represents a promising candidate for the development of an "universal vaccine". However, the low immunogenicity associated to M2e in a natural infection or in response to seasonal vaccines has led to explore new approaches to enhance it. In recent years, it has become clear that targeting antigens to dendritic cells (DC) is an efficient way to enhance immune responses against pathogens. In this work, the M2e peptide was chemically cross-linked to a monoclonal antibody (mAb) specific for DEC-205 (α-DEC-205:M2e), present on DC. BALB/c mice were inoculated subcutaneously (s.c.) three times with the conjugate equivalent to 1 µg of M2e, in the presence of polyinosinic-polycytidylic acid (poly I:C) as adjuvant. As controls, other groups of mice were inoculated under the same conditions with M2e cross-linked to an isotype control mAb (isotype:M2e), 5 µg of free M2e peptide, ovalbumin (OVA) cross-linked to the α-DEC-205 mAb (α-DEC-205:OVA) or poly I:C alone. Immunization with α-DEC-205-M2e induced high levels of serum antibodies (Abs) compared to isotype:M2e or to free M2e peptide, and in all cases IgG1 was predominant over IgG2a Abs. Furthermore, immunization with the α-DEC-205:M2e conjugate did not prevent morbidity, but it induced up to 76% protection against a heterosubtypic IAV lethal challenge. Contrasting with the 20 to 40% protection induced by isotype:M2e or by free M2e peptide. The protection induced by α-DEC-205:M2e conjugate was dependent on non-neutralizing serum Abs and independent of effector CD4+ T cells. These results show that targeting M2e to DEC-205 is a very effective alternative to induce strong heterosubtypic protection against an IAV infection.

[An unusual presentation of painful tic convulsive]. / Presentacion inusual de un tic convulsivo doloroso.

INTRODUCTION: The term 'painful tic convulsive' is used to describe the syndrome involving concomitant hemifacial spasm and ipsilateral trigeminal neuralgia. Vascular compression of the fifth and seventh cranial nerves is the most common cause, involving the entry and exit zone of rootlets coming from the brainstem; nevertheless, different etiologies of this syndrome has been previously reported. Treatment for this disease is based on surgical microvascular decompression of the nerve rootlets, but still a topic of debate. CASE REPORT: A 63-year-old woman with history of 14 years presenting left trigeminal neuralgia, associated with ipsilateral hemifacial spasm for more than ten years. Medical treatment was installed without adequate symptom control. Patient was subjected to surgical treatment via a microasterional approach, with dissection of arachnoid fibrous tissue surrounding fifth and seventh nerves during the first surgery. A second surgery was performed with insertion of a teflon fragment aside of each exit nerve root (V and VII-VIII complex). Symptoms resolved immediately after the surgery and has persisted during the 1-year follow-up. Painful tic convulsive etiology could be multifactorial. CONCLUSION: This report is the first clinical case describing basal arachnoiditis as a primary cause of painful tic convulsive.

TITLE: Presentacion inusual de un tic convulsivo doloroso.Introduccion. La presentacion clinica de un espasmo hemifacial asociado a neuralgia trigeminal ipsilateral se conoce como tic convulsivo doloroso. La causa mas comun de esta patologia es la compresion vascular de los nervios craneales V y complejo VII-VIII en la zona de entrada y salida de las raices en el tronco del encefalo, pero existen informes de diversas etiologias. Su tratamiento, aunque aun esta en discusion, se basa en la descompresion microvascular quirurgica. Caso clinico. Mujer de 63 años, con un cuadro de evolucion de 14 años de neuralgia trigeminal, con predominio en distribucion de la rama maxilar (V2) izquierda, asociado durante mas de 10 años a espasmo hemifacial ipsilateral. Tras fallar el tratamiento medico, se sometio a cirugia por abordaje microasterional, y en un primer momento se realizo una diseccion de adherencias aracnoideas firmes rodeando complejos nerviosos. En un segundo tiempo quirurgico se insertaron fragmentos de teflon en los sitios de entrada de los nervios V y complejo VII-VIII, y se logro una resolucion completa de la sintomatologia durante mas de un año. Conclusion. La etiologia del tic convulsivo doloroso en esta paciente fue aracnoiditis basal, lo cual la convierte en el unico caso comunicado hasta el momento con dicha etiologia.

Factors associated with poor outcome for aneurysmal subarachnoid haemorrhage in a series of 334 patients. / Factores asociados a una evolución desfavorable en la hemorragia subaracnoidea aneurismática. Serie de 334 pacientes.

OBJECTIVE: This study evaluates care-related sociodemographic, clinical, and imaging factors and influences associated with outcome at discharge in patients with aneurismal subarachnoid haemorrhage. PATIENTS AND METHOD: Retrospective cohort study in 334 patients treated at Hospital Hermanos Ameijeiras in Havana, Cuba between October 2005 and June 2014. RESULTS: Logistic regression analysis determined that the following factors were associated with higher risk of poor outcome: age older than 65 years (OR 3.51, 95% CI 1.79-5.7, P=.031), female sex (OR 2.17, 95% CI 1.22-3.84, P=.0067), systolic hypertension (OR 4.82, 95% CI 2.27-9.8, P=.0001), and hyperglycaemia at admission (OR 3.93, 95% CI 2.10-7.53, P=.0003). Certain complications were also associated with poor prognosis, including respiratory infection (OR 2.73, 95% CI 1.27-5.85, P=.0085), electrolyte disturbances (OR 3.33, 95% CI 1.33-8.28, P=.0073), hydrocephalus (OR 2.21, 95% CI 1.05-4.63, P=.0039), rebleeding (OR 16.50, 95% CI 8.24-41.24, P=.0000), symptomatic vasospasm (OR 19.00, 95% CI 8.86-41.24, P=.0000), cerebral ischaemia (OR 3.82, 95% CI 1.87-7.80, P=.000) and multiplex rebleeding (OR 6.69, 95% CI 1.35-36.39, P=.0019). Grades of iii and iv on the World Federation of Neurological Surgeons (OR 2.09, 95% CI 1.12-3.91, P=.0021) and Fisher scales (OR 5.18, 95% CI 2.65-10.29, P=.0008) were also related to poor outcome. CONCLUSIONS: Outcome of aneurysmal subarachnoid haemorrhage was related to age, sex, clinical status at admission to the stroke unit, imaging findings according to the Fisher scale, blood pressure, glycaemia and such complications as electrolyte disturbances, hydrocephalus, rebleeding, and multiplex rebleeding.

Relation of cerebrospinal fluid/plasma HIV-RNA discordance with neurocognitive impairment.

Neurological involvement is common in patients infected with HIV. The effectiveness of antiretroviral drugs in lowering the levels of HIV-RNA in cerebrospinal fluid (CSF) is limited by their inability to cross the blood-brain barrier. Discordance in CSF/plasma HIV-RNA levels may have a bearing on the progression of neurological disease in these patients. We report a woman with subacute neurocognitive impairment and abnormal findings on brain MRI, in whom there was a discordance between CSF/plasma HIV-RNA levels. The patient improved after a change in her highly active antiretroviral therapy (HAART) regimen. We also reviewed the available literature on the subject and found seven articles describing 27 patients.

Utilization of molasses and sugar cane bagasse for production of fungal invertase in solid state fermentation using Aspergillus niger GH1.

Agro-industrial wastes have been used as substrate-support in solid state fermentation for enzyme production. Molasses and sugarcane bagasse are by-products of sugar industry and can be employed as substrates for invertase production. Invertase is an important enzyme for sweeteners development. In this study, a xerophilic fungus Aspergillus niger GH1 isolated of the Mexican semi-desert, previously reported as an invertase over-producer strain was used. Molasses from Mexico and Cuba were chemically analyzed (total and reducer sugars, nitrogen and phosphorous contents); the last one was selected based on chemical composition. Fermentations were performed using virgin and hydrolyzate bagasse (treatment with concentrated sulfuric acid). Results indicated that, the enzymatic yield (5231 U/L) is higher than those reported by other A. niger strains under solid state fermentation, using hydrolyzate bagasse. The acid hydrolysis promotes availability of fermentable sugars. In addition, maximum invertase activity was detected at 24 h using low substrate concentration, which may reduce production costs. This study presents an alternative method for invertase production using a xerophilic fungus isolated from Mexican semi-desert and inexpensive substrates (molasses and sugarcane bagasse).