En el mes de la concesión de los Premios Nobel, rendimos homenaje a Alfred Nobel y a los galardonados con el Premio de Fisiología y Medicina de 2020 / In the month of the Nobel Prize Awards, we pay tribute to Alfred Nobel and to the recipients of the 2020 Prize in Physiology and Medicine

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Situación de las hepatitis virales / Present status of virals hepatitis

Informe especial donde se analizaron todos los casos de hepatitis virales notificados a los sistemas oficiales (módulos C2-SNVS y SIVILA-SNVS operativos hasta el 28-04-2018 y SNVS 2.0 para los casos posteriores a dicha fecha) de los residentes de la Ciudad de Buenos Aires y con domicilio desconocido, entre las Semanas Epidemiológicas (SE) 1 y 52 de 2017 y con datos hasta el 27 de mayo de 2018 (SE 21 completa). Para el análisis por cuatrisemanas se incluyen casos hasta el 19/05/2018 (cuatrisemana epidemiológica 5 completa). Cabe aclarar que se presentan casos confirmados en los módulos clínicos en los que no se cuenta con la notificación por laboratorio. Diferentes notificaciones pueden corresponder a un mismo paciente estudiado para más de una patología. Para el análisis de hepatitis B se incluyen además 3 notificaciones provenientes de bancos de sangre. Para la elaboración de tasas se utilizaron los datos de proyecciones de población de la Dirección General de Estadística y Censos de la Ciudad Autónoma de Buenos Aires. (AU)

Fluorescent silver nanocluster DNA probes for multiplexed detection using microfluidic capillary electrophoresis.

DNA-stabilized fluorescent silver nanoclusters (AgNC DNA) are a new class of fluorophore that are formed by sequence specific interactions between silver and single-stranded DNA. By incorporating both target-binding and fluorescent-reporting sequences into a single synthetic DNA oligomer, AgNC DNA probes eliminate the need to conjugate dye or quencher molecules. In this study, we modify a AgNC DNA probe to demonstrate single-color multiplexed detection of DNA targets. We show that appending different lengths of poly-dT to the probe sequences tunes the electrophoretic mobility of AgNC DNA probes without affecting their fluorescence spectra. We use this to introduce a set of AgNC DNA probes selective for Hepatitis A, B and C target sequences that can be processed together in a simple, single-step protocol and distinguished with a resolution of 3.47 and signal to noise ratio of 17.23 in under 10 seconds by microfluidic capillary electrophoresis.

Primary biliary cirrhosis: proposal for a new simple histological scoring system.

BACKGROUND & AIMS: A simple and reproducible evaluation of non diagnostic histological lesions related to prognosis remains crucial in primary biliary cirrhosis (PBC). Presently there is no satisfactory simple scoring system analysing them reliably. We elaborated a semi-quantitative scoring system that assesses fibrosis, lymphocytic interface hepatitis (LIH) and ductopenia, separately. This study was aimed to evaluate its intra/interobserver reproducibility and its correlation with the main biochemical data. METHODS: Liver biopsies from 33 consecutive newly diagnosed PBC patients were independently analysed by five liver pathologists. Fibrosis was classified into five stages (portal/periportal fibrosis/few septa/numerous septa/cirrhosis) and LIH into four grades. The bile duct ratio (BDR), i.e. ratio of the number of portal tracts with ducts to total number of portal tracts, Ludwig's and Scheuer's stages were evaluated. Intra and interobserver agreements were assessed. Histological results were correlated to the biochemical data. RESULTS: Most patients had an early disease on clinical and biological parameters. The biopsies measured 23 mm on average (range 12 - 40 mm). Intraobserver reproducibility was substantial for fibrosis (κ = 0.68), LIH (κ = 0.69) and BDR (ICC = 0.69). Interobserver agreement for fibrosis was fair with the 5-class system (κ = 0.36), moderate with a 4-class system (κ = 0.56). moderate for LIH (κ = 0.59) and BDR (ICC = 0.50). Ludwig's and Scheuer's staging showed a fair interobserver agreement (κ = 0.32, κ = 0.31 respectively). Our system showed better correlations with biochemistry than Ludwig's and Scheuer's systems did. CONCLUSIONS: This simple scoring system, assessing fibrosis, LIH and BDR separately, has a substantial intraobserver and a moderate interobserver reproducibility. Its prognostic relevance has to be evaluated.

Learning to improve medical decision making from imbalanced data without a priori cost.

BACKGROUND: In a medical data set, data are commonly composed of a minority (positive or abnormal) group and a majority (negative or normal) group and the cost of misclassifying a minority sample as a majority sample is highly expensive. This is the so-called imbalanced classification problem. The traditional classification functions can be seriously affected by the skewed class distribution in the data. To deal with this problem, people often use a priori cost to adjust the learning process in the pursuit of optimal classification function. However, this priori cost is often unknown and hard to estimate in medical decision making. METHODS: In this paper, we propose a new learning method, named RankCost, to classify imbalanced medical data without using a priori cost. Instead of focusing on improving the class-prediction accuracy, RankCost is to maximize the difference between the minority class and the majority class by using a scoring function, which translates the imbalanced classification problem into a partial ranking problem. The scoring function is learned via a non-parametric boosting algorithm. RESULTS: We compare RankCost to several representative approaches on four medical data sets varying in size, imbalanced ratio, and dimension. The experimental results demonstrate that unlike the currently available methods that often perform unevenly with different priori costs, RankCost shows comparable performance in a consistent manner. CONCLUSIONS: It is a challenging task to learn an effective classification model based on imbalanced data in medical data analysis. The traditional approaches often use a priori cost to adjust the learning of the classification function. This work presents a novel approach, namely RankCost, for learning from medical imbalanced data sets without using a priori cost. The experimental results indicate that RankCost performs very well in imbalanced data classification and can be a useful method in real-world applications of medical decision making.

Co-occurrence of idiopathic granulomatous hepatitis and primary biliary cirrhosis.

BACKGROUND: PBC is an autoimmune disease affecting the bile ducts. Granulomas can be found in portal triads in 45 % of patients with PBC. Idiopathic granulomatous hepatitis is a rare disease of unknown cause which is characterized by recurrent fevers, sweats, elevated levels of liver enzyme tests, particularly the serum alkaline phosphatase, and granulomas in the portal and lobular regions of the liver. Previous literature suggests that a diagnosis of idiopathic granulomatous hepatitis can be made only if PBC has been excluded. STUDY: We reviewed instances in which PBC and idiopathic granulomatous hepatitis occurred in the same patient. RESULTS: We report three patients in whom both diseases occurred: 1) A patient with PBC who was diagnosed 15 years later with idiopathic granulomatous hepatitis; 2) A patient with idiopathic granulomatous hepatitis who developed PBC 12 years later; and 3) A patient who had features of both idiopathic granulomatous hepatitis and PBC at the time of initial diagnosis. CONCLUSIONS: Our experience with these patients suggests that idiopathic granulomatous hepatitis and PBC can occur in the same individual. Knowing this association is important, as clinical deterioration in a patient with either disease could suggest the presence of the other and should be treated accordingly.

A brief history of hepatitis milestones.

Hepatitis has been a major plague of mankind. The history of the discovery of causative viruses is one of the most fascinating scientific adventures of this half century. Individualization of several types of hepatitis only emerged after world war two. Their identification has been associated with milestones which revolutionized medicine and public health. The discovery of HBV brought the first ever vaccine not prepared by tissue culture but initially directly from plasma and soon the first vaccine produced by genetic engineering. HBV vaccine proved to be the first "anti-cancer" vaccine by preventing hepatocellular carcinoma and practically eradicating it from childhood in Taiwan. Successful vaccines became also available for HAV and more recently HEV. The discovery of HCV in 1989 opened a new era since it was the first virus was identified by a direct molecular approach. Two billion people are infected with HBV and 350 million are chronic carriers of the virus. The extraordinary effectiveness of HBV vaccination was best illustrated in Taiwan and Singapore where in less than 2 decades HBs Ag carriers dropped from 9,1% to 2,7% and HCC from 27% to 17%. Successful development of nucleos(t)ides analogs make it now possible to fully control disease progression with a daily pill long term therapy. The progress in HCV therapy has been even more spectacular and successful treatment jumped from 6 % with interferon alone in 1986 to more than 80% in 2013 with triple combination therapies. Remarkably chronic hepatitis C is the only chronic disease which is curable. It will be soon possible to eradicate HCV infection with, an all oral, daily single pill (containing several molecules) for 3 to 6 months which will cure over 90% of patients. This unprecedented therapeutic victory benefiting hundred millions of people matches the triumphs over small pox, polio and tuberculosis. The next 10 years should undoubtedly witness cure or full control over all forms of acute and chronic hepatitis.

Cytokeratins in hepatitis.

Experimental and clinical evidence suggests that cytokeratins (CK), among other physiological functions, are expressed in hepatocytes and can be released in the bloodstream after acute or chronic inflammatory liver injury. Interest in CK in viral and nonviral hepatitis has been rapidly increasing during the last years, especially as they have been proposed as circulating biomarkers of hepatocyte necrosis and apoptosis. In the present review, we sought to summarize and discuss the alterations in circulating CK levels in different form viral and nonviral hepatitis, as well as their potential relation with liver histology. Understanding the mechanisms of hepatitis impact on CK and vice versa is a promising area of research that will positively enhance our understanding of the complexity of acute and chronic inflammatory liver injury.

Receptores con hepatitis fulminante / No disponible

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Frequently asked questions: liver wellness

It presents liver' s ain functions, relations between nutrition, chemicals, alcohol and other drugs consumption to liver health, and basic about main forms of hepatitis (A, B, C, D and E). It brings facts about liver conditions, its numbers and incidence, hepatitis. Document in pdf format; Acrobat Reader needed.

Grading and staging systems for inflammation and fibrosis in chronic liver diseases.

Liver biopsy is an important part of the evaluation of patients with a variety of liver diseases. Besides establishing the diagnosis, the biopsy is often used to assess the severity of the disease in terms of both grade and stage. The stage in most chronic liver diseases relates to the degree of scarring with the end stage being cirrhosis with its clinical complications. The grade relates to the severity of the underlying disease process, with features that vary with the pathogenetic mechanisms. Chronic viral hepatitis has been the object of the most extensive efforts at grading and staging, stimulated by the advent of new forms of therapy. Systems have also been developed for fatty liver disease, allograft rejection and chronic cholestatic diseases, but these have not been as widely used. Simple grading and staging systems for chronic hepatitis, including the IASL, Batts-Ludwig, and Metavir systems, are most appropriate for management of individual patients, while more complex systems such as the Histology Activity Index (HAI) are appropriate for evaluation of large cohorts of patients when statistical analysis is required.

Intraoperative transhepatic biliary catheter insertion technique for biliary reconstruction: early results.

Biliary complications are critical problems in liver transplantation. Herein, we retrospectively analyzed the early results of an intraoperative transhepatic biliary catheter insertion technique for biliary reconstruction. Since November 2004, we have used this technique in 66 patients (32 children and 34 adults). In the new technique, a 5- F Kumpe catheter is inserted into the biliary system in 2 steps. One step is completed at the back table; the second step is completed during the recipient operation. Fourteen patients received whole-liver grafts, 25 received a right lobe, and 27 received a left-lateral or a left lobe. The mean graft weight-to-body weight ratio in the living-donor liver transplantations was 1.6% +/- 1.0% (range, 0.8%-4.1%). Intraoperative transhepatic biliary catheter insertion was performed with a duct-to-duct anastomosis in 60 patients and with a Roux-en-Y hepaticojejunostomy in 6 patients. Five biliary complications occurred in 4 patients. Two of these 4 patients had bile leakage from the anastomotic site during the early postoperative period. Biliary stenoses developed at the anastomotic site in 2 patients and from a nonanastomotic site in 1 patient in the late postoperative period. In conclusion, this new technique of biliary reconstruction with intraoperative biliary catheter insertion has significantly reduced our complication rate. Transhepatic biliary stenting seems to prevent biliary complications and makes it simple to maintain percutaneous access in the event that problems arise. Intraoperative transhepatic biliary catheter insertion at the back table is a safe means of providing good biliary drainage after liver transplantation.

[A study of the influences of blood sugar levels on the prognosis of fulminating hepatitis patients].

OBJECTIVE: To explore the possible relationship between hypoglycemia and the prognosis of fulminating hepatitis patients. METHODS: Fasting blood sugar levels of 322 fulminating hepatitis patients were retrospectively analyzed. The blood sugar levels and their clinical significance were appraised together. RESULTS: In all the samples, 173 were hypoglycemic (53.73%). The mortality rate of the hypoglycemia group was 48.55% (84/173), therefore the blood sugar level was lower and the mortality rate was higher. CONCLUSION: A higher proportion of fulminating hepatitis patients have hypoglycemia. There is a close relationship between hypoglycemia and the prognosis of the fulminating hepatitis patients. Blood sugar level has an important clinical value in reflecting the degree of liver failure in early fulminating hepatitis patients.

Review of 31 cases of morphologic hepatitis in liver transplant patients not related to disease recurrence.

AIMS: We examined the clinical and pathologic features of morphologic hepatitis occurring after liver transplantation (LT) that is unrelated to disease recurrence. METHODS: Between February 1998 and December 2003, 704 primary LTs were performed at our center. Patients transplanted for diagnoses with low risk of disease recurrence were considered for our study (n = 282). Those with hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those with morphologic hepatitis comprised our case series and had medical records reviewed for clinical associations, duration, and outcome. RESULTS: Thirty-one cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13), steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2), and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8 months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and moderate in 12. Associated conditions were identified in 19 patients (57%) with 3 categories being identified: probable drug toxicity (n = 7), systemic infection (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the index biopsy, 10 cases had resolution and 15 cases had persistence of the infiltrate. One patient had evidence of de novo HBV infection. CONCLUSIONS: Morphologic hepatitis occurred in 11% of patients at low risk for disease recurrence. Associated conditions could be grouped into three categories: drug toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases did not appear to progress or improved over time, with no allograft loss occurring as a result of chronic hepatitis.

The use of protein tyrosine phosphatase 1B and insulin receptor immunostains to differentiate nonalcoholic from alcoholic steatohepatitis in liver biopsy specimens.

Nonalcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) and typically are indistinguishable, histologically. The diagnosis relies on reporting of alcohol consumption. The metabolic syndrome involving insulin resistance is associated with nonalcoholic fatty liver disease (NAFLD). Protein tyrosine phosphatase 1B (PTP1B) negatively regulates the insulin receptor (IR). Increased PTP1B expression is seen in obesity and possibly is responsible for the insulin resistance seen in the metabolic syndrome. The study objective was to determine whether biopsy specimens with steatohepatitis could be classified accurately as alcoholic or nonalcoholic by immunohistochemical stains. We selected 241 cases of steatohepatitis, comprising 53 and 188 cases of alcoholic and NAFLD, respectively. Specimens were stained with PTP1B and IR (b subunit) and classified as NASH or ASH. The staining pattern predicted 60 cases of ASH and 181 cases of NASH. Results correlated with clinical diagnoses in 70% and 88% of ASH and NASH cases, respectively (odds ratio, 16.6; 95% confidence interval, 8.2-35.4).

Mechanisms of liver injury: an overview.

Liver cirrhosis, an end-result of a wide variety of the liver diseases, is a world wide health problem. Because of its unique organ system, i.e., portal blood supply, bile formation and enterohepatic circulation, drug metabolism system, and sinusoidal lining cells such as Kupffer, endothelial and stellate cells, the liver is a target of a variety of hepatotoxic insults. Current data suggest that hepatocyte apoptosis is an essential feature contributing to liver injury in a wide range of acute and chronic liver diseases. With an improved understanding of the pathophysiological role of apoptosis in liver diseases, we are now entering an era where regulation of liver cell apoptosis is becoming a therapeutic possibility. Inhibition of hepatocyte apoptosis using a variety of different strategies may be therapeutically beneficial in liver injuries, such as alcoholic hepatitis, non-alcoholic steatohepatitis (NASH), viral hepatitis, and cholestatic liver diseases. Considering the link between hepatocyte apoptosis and liver fibrosis, inhibition of hepatocyte apoptosis may also be an anti-fibrotic therapeutic strategy. Moreover, selective induction of apoptosis of activated stellate cells would be a unique approach to induce the resolution the phase of liver fibrosis. These concepts merit further clinical and basic investigation.