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.

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.

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.

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.

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.

[Nutritional assessment of alcoholic liver cirrhotic patients treated in the liver Clinic of the Mexico's General Hospital]. / Evaluación del estado nutricional de pacientes con cirrosis hepática alcohólica atendidos en la Clínica de Hígado del Hospital General de México.

Malnutrition in the cirrhotic patient is associated to a higher morbidity and mortality rate; however, the diagnosis is complex, so the study objective was to assess the nutritional status using different methods. Adult patients with alcoholic liver cirrhosis treated in the Liver Clinic of the Mexico's General Hospital were evaluated. Anthropometric measurements and a 24 hours recall were made; screening tools (Malnutrition Universal Screening Tool, Nutritional Risk Screening-2002) and a method for assessing nutritional status specifically in cirrhotic patients (Royal Free Hospital Global Assessment) were used. We included 62 patients, 51.6% of them were men. Malnutrition by arm muscle area was 31.3% in men and 10% in women, and by arm fat area was 23.3% in women and 3.1% in men (p < 0.05). With the screening tools the percentages of malnutrition risk were 43.5% and 54.8% respectively, vs. 1.6% identified as "low weight" with the Body Mass Index. With the Royal Free Hospital Global Assessment tool the percentage of malnutrition was 45.2%. Patients with malnutrition had an energy and protein intake significantly lower than the well-nourished: 19.7 kcal/kg and 0.89 g/kg vs 30 kcal/kg and 1.25 g/kg (p < 0.005). Malnutrition is a common complication in patients with liver cirrhosis. Men have higher depletion of muscle mass and women a higher loss of body fat. The Body Mass Index is not a reliable tool for assessing malnutrition. It's advisable to use tools with indicators of body composition such as the Royal Free Hospital Global Assessment.

[Association between anxiety and quality of life in different subgroups irritable bowel syndrome]. / Asociación entre ansiedad y calidad de vida en los diferentes subgrupos de síndrome de intestino irritable.

INTRODUCTION: Irritable Bowel Syndrome (IBS) is a frequent functional digestive disorder. Several studies have established the relationship between IBS and anxiety. Also it has been described a negative impact on quality of life in patients who suffer it, but in our country none of these studies have used ROME III criteria for evaluation. OBJECTIVE: To know the frequency of anxiety in the different subgroups of IBS and its impact on quality of life. METHODS: The study was conducted in patients who attended for first time to the outpatient clinic of our hospital for ten months. Adult patients who met the criteria of IBS were included. We applied the SF-36 quality of life questionnaire and the Hamilton anxiety scale. RESULTS: One hundred and two patients who met for IBS criteria were included, of which 85% had anxiety. The IBS-C was the most frequent subgroup. Divided by subgroups, found that 52%, 85.1%, 90% and 80.9% had anxiety for IBS-C, IBS-D, IBS-M and IBS-NC respectively, without significant difference between groups. Patients with anxiety had lower quality of life scores in the categories of physical health, mental health and change in the state of health, (54.2 ± 18 vs. 72 ± 16, 52.8 ± 20 vs. 74 ± 14, 48 ± 28 vs. 59 ± 32) with respect to those who have no anxiety (p <0.0001, p <0.0001 and p<0.15 respectively). CONCLUSIONS: The anxiety was not associated to any subgroup in particular of IBS, the presence of this influenced adversely and significantly on the quality of life of patients who suffer it.

[Acute abdominal pain in elderly patients evaluated in the emergency department at a tertiary level]. / Dolor abdominal agudo en pacientes geriátricos evaluados en el servicio de urgencias en un hospital de tercer nivel.

BACKGROUND: Life expectancy in México has increased in the last decades with a remarkable increase in geriatric population. Acute abdominal pain (AAP) in elderly people compared with young people has different clinical presentation because of the concomitant chronic diseases, the use of medications, history of abdominal surgeries and decrease in perception of pain and immunity. OBJECTIVE: To know the cause and associated mortality of acute abdominal pain in geriatric patients who attend the emergency room. METHODS: Geriatric patients' files with acute abdominal pain admitted from January 2004 to December 2008 were retrospectively reviewed. Age, gender, presence of chronic diseases, use of medications, history of surgical procedures, definitive diagnosis causative of the symptoms and the associated mortality were recorded. RESULTS: 17 524 patients were admitted, of whom 324 (1.8%) were geriatric patients with AAP: 110 were men (36.9) and 214 were women (66%), with a mean age of 78 years (range 60 to 102 years). The most common causes of AAP were acute cholecystitis in 49 patients (15.1%), irritable bowel syndrome in 42 (12.9%), ulcerative syndrome in 40 (12.3%), intestinal obstruction in 35 (10.8%) and diverticulitis in 23 (10.8%). Nine patients died (2.7%). CONCLUSIONS: In our hospital the most common cause of AAP in geriatric patients is related to biliary disease followed by functional gastrointestinal disorder and ulcerative syndrome. Mortality is low.

[Three prognostic utility scales to determine early mortality in patients with alcoholic hepatitis in the General Hospital of Mexico]. / Utilidad de tres escalas pronósticas para determinar mortalidad temprana en pacientes con hepatitis alcohólica en el Hospital General de México.

BACKGROUND: There are many models to predict survival in patients with alcoholic hepatitis (AH). The most commonly used are the modified Maddrey's index, the Glasgow scale and the Model for End stage Liver Disease (MELD). OBJECTIVE: To evaluate three prognostic scales ability to predict early mortality (first 30 days) in patients with AH. METHODS: We retrospectively reviewed the database of hospitalized patients with AH during a 3-years period. Seventy one patients were included. We calculated the modified Maddrey's index, the Glasgow scale and the MELD scores. We evaluated if the scales predicted early (30-day) mortality. For each scale we determined sensitivity, specificity, positive and negative values (PPV and NPV) and likelihood value of each scale. RESULTS: For modified Maddrey's index, the values obtained were sensitivity 98.8%, specificity 11.7%, PPV 61.6%, NPV 87.5% and likelihood ratio 1.12. For Glasgow scale corresponding values were sensitivity 98.8%, specificity 61.7%, PPV 78.7%, NPV 97.4% and likelihood ratio 2.64. For the MELD scale sensitivity 98.8%, specificity 0.1%, PPV 59%, NPV 50% and likelihood ratio 1. CONCLUSIONS: The three scales were very sensitive. Glasgow's scale was the most specific and, maybe, the most exact test.

[Reduction of hospital stay with the use of L-ornithine L-aspartate (LOLA) in patients with hepatic encephalopathy]. / Disminución de la estancia hospitalaria con el uso de L-ornitina L-aspartato (LOLA) en pacientes con encefalopatía hepática.

BACKGROUND: Hepatic encephalopathy (HE) is a common cause of hospital admission in patients with cirrhosis involving high costs of care. AIM: To evaluate the use of L-ornithine L-aspartate (LOLA) vs. lactulose is able to reduce the length of hospital stay and the timing of improvement of hepatic encephalopathy. METHODS: Retrospective and comparative study of patients with HE admitted to the Medical Gastroenterology Unit of a tertiary referral center in Mexico City (Hospital General de México) in a period of three years. Patients were divided in two treatment groups: LOLA vs. oral lactulose. We compared time to remission of encephalopathy, days of hospital stay and costs of hospital care. RESULTS: We included 80 patients: 40 patients who received treatment with latulose had acumulative hospital stay of 443 days vs. 264 days for those who received LOLA (40% reduction in hospital stay). In the group treated with lactulose, mean hospital stay was 11.07 days vs. 6.47 days in the group treated with LOLA. Thus, a significantly greater number of patients treated with LOLA remained hospitalized less than a week compared with those treated with lactulose (65% vs. 20% respectively. OR 4.33, 95% CI 1.67- 11.23, p = 0.004). The mean recovery time of encephalopathy was less with LOLA treatment (4.32 vs. 10.15 days). CONCLUSION: Treatment with LOLA was more effective in improving HE and reducing the duration of hospital stay.

Corelation among clinical, biochemical and tomographic criteria in order to evaluate the severity in acute pancreatitis.

BACKGROUND: The acute pancreatitis is an inflammatory process that may involve peripancreatic tissue and distant organs. According to the Atlanta criteria, in 10 to 20% of the patients the disease is severe. Nowadays there are different clinical and biochemical severity scales such as the Ranson, APACHE-II (Acute Physiology and Chronic Health Evaluation) and hematocrit, which have discrepancies when being compared to tomographic scales such as the Balthazar. There exist few studies that correlate these parameters. OBJECTIVE: To evaluate the severity of the acute pancreatitis according to the Ranson, APACHE-II and serous hematocrit criteria at the moment of admission of the patient and correlate these scales with the local pancreatic complications according to the Balthazar classification. PATIENTS AND METHOD: Retrospective, observational and analytic study. There were included patients of any gender above the age of 18, with diagnosis of acute pancreatitis of any etiology, who had performed an abdominal tomography 72 hours after the beginning of the clinical condition in order to stage the pancreatic damage. The diagnosis of acute pancreatitis was established with 2 of the 3 following criteria: a) characteristic abdominal pain; b) uprising of the amylase and/or lipase more than 3 times above the superior normal limit; and c) characteristic finds of acute pancreatitis in the computed tomography. In order to make the correlation, the Pearson or the Spearman tests were used according to the distribution of the variables. RESULTS: There were included 28 patients (21 masculine, 75%). The most frequent etiology was due to alcohol (53.6%, bile (21.4%) and hypertriglyceridemia (17.9%). The age average was 38.1 years old. Fifty per cent of the patients had acute severe pancreatitis according to the Atlanta criteria. Of the patients with APACHE-II less than 8 points, 62.5% were classified according to the Balthazar tomographic scale as D or E degree. Ninety-two point nine per cent of the patients had less than 3 Ranson criteria of which 57.6% got D or E degree. Fifty-seven per cent of the patients with hematocrit value lower than 44% got D and E Balthazar degree, and 64.2% of the patients with hematocrit above 44% got D and E degree.The Pearson correlation (PC) for APACHE-II and Ranson p = 0.013 of 0.476 PC for APACHE-II and Balthazar p = 0.367 of 0.476 and Spearman s correlation p = 0.460 PC for APACHE-II and hematocrit p = 1.32 of 0.476. CONCLUSIONS: There does not exist a good correlation between the seriousness scale of Ranson and APACHE-II with the tomographic Balthazar degrees, therefore it is more likely to find very ill patients with an A or B Balthazar and on the other hand patients with acute low pancreatitis with a D or E Balthazar.

[The amount of alcohol intake, upper gastrointestinal bleeding, acute renal failure and hepatic encephalopathy as the risk factors implied in the increase of patients with alcoholic hepatitis]. / Cantidad de alcohol, hemorragia de tubo digestivo alto, insuficiencia renal aguda y encefalopatía hepática como factores de riesgo implicados en el incremento de la mortalidad en pacientes con hepatitis por alcohol.

BACKGROUND: Acute renal failure (ARF) worsens the prognosis of patients with alcoholic hepatitis (HA). Other factors like the amount of alcohol intake, upper gastrointestinal bleeding (UGB) or hepatic encephalopathy (HE) are not considered at present in any prognostic index. OBJECTIVE: To evaluate if the amount of alcohol intake, development of UGB, ARF and/or HE are associated with high mortality in patients with AH. METHODS: Consecutive patients with diagnosis of AH were included. Demographic, laboratory data, complications and mortality were registered. A comparison was performed between survivors and non-survivors. RESULTS: Seventy-one patients were included. Median amount of alcohol consumption was 187.7 g/day, and was superior in men (190.8 vs. 169 g/day, p = 0.02) and in patients who developed ARF (219.6 vs. 144.1 g/day, p = 0.001). Maddrey s index was higher in patients who died than those who survive (111.4 vs. 52.9, p = 0.02). No differences between groups were recorded regarding Glasgow and MELD scales. ARF was the only one complication related with higher risk of death (RR = 6.7, p = 0.02). Isolated UGB and HE were non-significantly associated with mortality, but combination of two or three complications was highly significantly associated with mortality risk: ARF and HE (OR = 8.9, p = 0.001), HE and UGB (OR = 6.7, p = 0.01) and ARF + UGB + HE (OR = 10, p = 0.001). CONCLUSION: The amount of alcohol intake is associated with development of ARF. ARF was the most significant risk factor associated with mortality. The presence of two or three complications increases the mortality risk significantly. Key words: acute renal failure, hepatic encephalopathy, risk factors, mortality, alcoholic hepatitis, Mexico.