Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

Prevalence of Radiological Chronic Pancreatitis and Exocrine Pancreatic Insufficiency in Patients with Decompensated Liver Disease: Is Fecal Elastase Useful in This Setting?

Chronic alcohol consumption is a well-known etiological factor for both chronic pancreatitis (CP) and liver cirrhosis. However, there is discussion over how often these two entities are present together in the same patient. The main goal of our study is to establish the prevalence of CP and low fecal elastase (FE-1) in patients with decompensated liver disease (DLD). In addition, we aim to identify the demographic, epidemiological and clinical factors associated with EPI and CP in patients with decompensated liver cirrhosis. This was an observational single-center study including 119 consecutive patients hospitalized for acute decompensation of cirrhosis, mostly of alcoholic etiology. Patients underwent computed tomography (CT) or magnetic resonance imaging (MRI) to assess the radiological features of CP. We also performed two FE-1 tests and complete blood tests to assess the presence of exocrine pancreatic insufficiency (EPI) and nutritional status, including micronutrients. The results of our study show that 32 patients (26.9%) had low fecal elastase suggesting EPI and 11 (9.2%) had CP. Patients meeting radiological CP criteria had lower FE-1 than patients without CP. There were no statistically significant differences in micronutrient deficiencies according to the presence of CP or not. Likewise, we did not find any statistically significant differences in micronutrient deficiencies among patients with normal and low FE-1 indicative of EPI. FE-1 alone may not be suitable for assessing EPI in patients with acute DLD. Detecting co-existing pancreatic disease may be important in a subset of patients with DLD, when the FE-1 levels are significantly low, potentially suggestive of a pancreatic anomaly. Moreover, the clinical manifestations of EPI and CP are not useful in detecting CP in DLD patients. Likewise, CP cannot explain all causes of EPI in these patients.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool.

PURPOSE: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. METHODS: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). RESULTS: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. CONCLUSIONS: The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.

Survival and adverse events of elderly patients treated with sorafenib for hepatocellular carcinoma.

Introduction: The first-line treatment for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, but its availability is not universal and elderly patients are underrepresented in clinical trials. There is little evidence of efficacy and tolerability in elderly patients under systemic treatment. The aims of this study were to characterize the profile of elderly patients treated with sorafenib, assess their survival and safety profile in order to extrapolate their eligibility for systemic treatment. Methods: Retrospective multicentre study of HCC patients aged ≥75 years old treated with sorafenib from January 2008 to December 2019. Demographic data, baseline characteristics, and variables related to HCC and sorafenib were recorded. Overall survival (OS) and safety were analyzed. Results: The study included 206 patients from 11 hospitals, median age 77.9 years; 71.4% men and 62.6% stage Barcelona Clinic Liver Cancer- C (BCLC-C). The main causes of cirrhosis were hepatitis C (60.7%) and alcohol (14.7%). Most patients (84.5%) started with sorafenib 800mg and 15.5% at lower dosage. Arterial hypertension (AHT) (74.2 vs 62.2%; standardized mean differences (STD): 26) and baseline ECOG-PS>0 (45.3 vs 34.7%; STD: 38.2) differed significantly between patients receiving low and full doses. Median OS was 15.4 months (18.2 in BCLC-B vs 13.6 in BCLC-C). OS was not modified by comorbidities, age or period with more expertise. Conclusions: Sorafenib appears to be safe in elderly patients with HCC. This is the first study to characterize the profile of elderly patients to be considered for systemic treatment. These findings could be used as the reference profile for elderly candidates for atezolizumab-bevacizumab.

Thermodynamic approach to foresee experimental CO2 reduction to organic compounds.

Anaerobic gas fermentation is a promising approach to transform carbon dioxide (CO2) into chemical building blocks. However, the main operational conditions to enhance the process and its selectivity are still unknown. The main objective of this study was to trigger chain elongation from a joint perspective of thermodynamic and experimental assessment. Thermodynamics revealed that acetic acid formation was the most spontaneous reaction, followed by n-caproic and n-butyric acids, while the doorway for alcohols production was bounded by the selected conditions. Best parameters combinations were applied in three 0.12 L fermenters. Experimentally, n-caproic acid formation was boosted at pH 7, 37 °C, Acetate:Ethanol mass ratio of 1:3 and low H2 partial pressure. Though these conditions did not match with those required to produce their main substrates, the unification of both perspectives yielded the highest n-caproic acid concentration (>11 g L-1) so far from simple substrates, accounting for 77 % of the total products.

Micronutrient Deficiencies in Patients with Decompensated Liver Cirrhosis.

Patients with cirrhosis often develop malnutrition and micronutrient deficiencies, leading to a worse prognosis and increased mortality. Our main goal was to assess the prevalence of micronutrient deficiencies in patients with decompensated cirrhosis. This was a prospective single-center study including 125 consecutive patients hospitalized for acute decompensation of cirrhosis (mostly of alcoholic etiology). A blood test including trace elements and vitamins was performed on admission. The main micronutrient deficiencies observed were vitamin D (in 94.5%), vitamin A (93.5%), vitamin B6 (60.8%) and zinc (85.6%). Patients in Child-Pugh class C had lower levels of vitamin A (p < 0.0001), vitamin E (p = 0.01) and zinc (p < 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p < 0.001) than those in Child-Pugh class A and B. Patients with a higher model of end-stage liver disease (MELD) score had lower levels of vitamin A (p < 0.0001), vitamin E (p < 0.001), magnesium (p = 0.01) and zinc (p = 0.001), and higher levels of ferritin (p = 0.002) and vitamin B12 (p < 0.0001). Severe hepatic insufficiency correlated with lower levels of zinc, vitamin E and vitamin A, and higher levels of vitamin B12 and ferritin.

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

BACKGROUND & AIMS: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis. METHODS: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization. RESULTS: A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9). CONCLUSION: Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade. LAY SUMMARY: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Decoupling Protein Production from Cell Growth Enhances the Site-Specific Incorporation of Noncanonical Amino Acids in E. coli.

The site-specific incorporation of noncanonical amino acids (ncAAs) into proteins by amber stop codon suppression has become a routine method in academic laboratories. This approach requires an amber suppressor tRNACUA to read the amber codon and an aminoacyl-tRNA synthetase to charge the tRNACUA with the ncAA. However, a major drawback is the low yield of the mutant protein in comparison to the wild type. This effect primarily results from the competition of release factor 1 with the charged suppressor tRNACUA for the amber codon at the A-site of the ribosome. A number of laboratories have attempted to improve the incorporation efficiency of ncAAs with moderate results. We aimed at increasing the efficiency to produce high yields of ncAA-functionalized proteins in a scalable setting for industrial application. To do this, we inserted an ncAA into the enhanced green fluorescent protein and an antibody mimetic molecule using an industrial E. coli strain, which produces recombinant proteins independent of cell growth. The controlled decoupling of recombinant protein production from cell growth considerably increased the incorporation of the ncAA, producing substantially higher protein yields versus the reference E. coli strain BL21(DE3). The target proteins were expressed at high levels, and the ncAA was efficiently incorporated with excellent fidelity while the protein function was preserved.

Current trends in access to treatment for hepatitis B in immigrants vs non-immigrants.

BACKGROUND: Universal vaccination for hepatitis B virus (HBV) and migratory movements have changed the demographic characteristics of this disease in Spain and in Europe. Therefore, we evaluated the characteristics of the disease and the possible differences according to origin (immigrants vs non-immigrants) and access to treatment. METHODS: This is a multicenter cross-sectional study (June 2014 to May 2015) in which outpatients with a positive HBsAg were seen and followed in four Hepatology units. Demographic and clinical data and indication and access to treatment were collected in two different regions of Catalonia (Spain) where there are no barriers to treatment due to a comprehensive coverage under the National Health System. RESULTS: A total of 951 patients were evaluated (48.1% men). Of these, 46.6% were immigrants (58.7% of them were born in Africa) and were significantly younger compared to non-immigrants. The proportions of patients with alcohol consumption, being overweight, and other indicators of metabolic co-morbidities were significantly higher in non-immigrants. Among the 937 patients receiving HBeAg examination, 91.7% were HBeAg-negative. Chronic HBeAg-positive infection was significantly higher in immigrants (3.9% vs 0.6%, P = 0.001) and chronic HBeAg-negative hepatitis was higher non-immigrants (31.7% vs 21.4%, P < 0.001). Not only was the proportion of patients who met treatment criteria significantly higher among non-immigrants (38.4% vs 29.2%, P = 0.003), but also the proportion of those with indication of effectively receiving therapy at the time of data collection (83.2% vs 57.8 %, P < 0.001). CONCLUSIONS: The immigrant population with HBV is younger and has a lower prevalence of metabolic co-morbidities and a higher frequency of chronic HBeAg infection. Despite having access to care and an indication for treatment, some do not get adequately treated due to several factors including local adaptation that precludes access to treatment.

Correction: Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C.

[This corrects the article DOI: 10.1371/journal.pone.0208112.].

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.

Enzymes revolutionize the bioproduction of value-added compounds: From enzyme discovery to special applications.

Competitive sustainable production in industry demands new and better biocatalysts, optimized bioprocesses and cost-effective product recovery. Our review sheds light on the progress made for the individual steps towards these goals, starting with the discovery of new enzymes and their corresponding genes. The enzymes are subsequently engineered to improve their performance, combined in reaction cascades to expand the reaction scope and integrated in whole cells to provide an optimal environment for the bioconversion. Strain engineering using synthetic biology methods tunes the host for production, reaction design optimizes the reaction conditions and downstream processing ensures the efficient recovery of commercially viable products. Selected examples illustrate how modified enzymes can revolutionize future-oriented applications ranging from the bioproduction of bulk-, specialty- and fine chemicals, active pharmaceutical ingredients and carbohydrates, over the conversion of the greenhouse-gas CO2 into valuable products and biocontrol in agriculture, to recycling of synthetic polymers and recovery of precious metals.

Salivary Cortisol Determination in ACTH Stimulation Test to Diagnose Adrenal Insufficiency in Patients with Liver Cirrhosis.

PURPOSE: The prevalence of adrenal insufficiency (AI) in patients with decompensated liver cirrhosis is unknown. Because these patients have lower levels of cortisol-binding carrier proteins, their total serum cortisol (TSC) correlates poorly with free serum cortisol (FC). Salivary cortisol (SaC) correlates better with FC. We aimed to establish SaC thresholds for AI for the 250 µg intravenous ACTH test and to estimate the prevalence of AI in noncritically ill cirrhotic patients. METHODS: We included 39 patients with decompensated cirrhosis, 39 patients with known AI, and 45 healthy volunteers. After subjects fasted ≥8 hours, serum and saliva samples were collected for determinations of TSC and SaC at baseline 0'(T0) and at 30-minute intervals after intravenous administration of 250 µg ACTH [30'(T30), 60'(T60), and 90'(T90)]. RESULTS: Based on the findings in healthy subjects and patients with known AI, we defined AI in cirrhotic patients as SaC-T0< 0.08 µg/dL (2.2 nmol/L), SaC-T60 < 1.43 µg/dl (39.5 nmol/L), or ΔSaC<1 µg/dl (27.6 nmol/L). We compared AI determination in cirrhotic patients with the ACTH test using these SaC thresholds versus established TSC thresholds (TSC-T0< 9 µg/dl [248 nmol/L], TSC-T60 < 18 µg/dl [497 nmol/L], or ΔTSC<9 µg/dl [248 nmol/L]). SaC correlated well with TSC. The prevalence of AI in cirrhotic patients was higher when determined by TSC (48.7%) than by SaC (30.8%); however, this difference did not reach statistical significance. AI was associated with sex, cirrhosis etiology, and Child-Pugh classification. CONCLUSIONS: Measuring SaC was more accurate than TSC in the ACTH stimulation test. Measuring TSC overestimated the prevalence of AI in noncritically ill cirrhotic patients.

Análisis de los índices predictores de respuesta al tratamiento con ácido ursodeoxicólico en pacientes con colangitis biliar primaria / Analysis of predictive response scores to treatment with ursodeoxycholic acid in patients with primary biliary cholangitis

Antecedentes y objetivos: La colangitis biliar primaria (CBP) es una enfermedad autoinmunitaria que afecta a los conductos biliares de pequeño y mediano tamaño. Los únicos tratamientos aprobados actualmente en nuestro país son el ácido ursodeoxicólico (AUDC) y el ácido obeticólico. Diversos índices evalúan la respuesta al año de tratamiento. El objetivo de nuestro estudio fue evaluar los diferentes índices predictivos de respuesta al tratamiento con AUDC. Material y métodos: Estudio unicéntrico retrospectivo en el que se recogieron los datos clínicos y analíticos de los pacientes diagnosticados de CBP desde enero de 1987 hasta diciembre de 2015. Se calculó la respuesta al año de inicio del tratamiento utilizando los diferentes índices de respuesta y se evaluó su grado de concordancia mediante el índice Kappa. Se calculó el area under the receiver operating characteristic curve (AUROC, «área bajo la curva ROC») para determinar la capacidad predictiva de los índices. Asimismo, se analizaron los factores pronósticos basales. Resultados: Se incluyeron 153 pacientes. El análisis bivariante demostró una relación estadísticamente significativa entre los niveles altos iniciales de fosfatasa alcalina y colesterol y la mala respuesta al tratamiento. La mejor AUROC fue del índice París-I (0,81). La concordancia entre los diferentes índices fue baja. El índice pronóstico GLOBE fue válido para evaluar el pronóstico. Conclusión: La fosfatasa alcalina y el colesterol basales fueron factores predictores de mala evolución. El índice cualitativo que mejor predijo la supervivencia fue el París-I. Se obtuvo una mala concordancia entre los diferentes índices predictivos. El índice GLOBE es válido para evaluar el pronóstico de la CBP

Background and objectives: Primary biliary cholangitis (PBC) is an autoimmune disease that affects the small bile ducts. The only treatments currently approved in our country are ursodeoxycholic acid (UDCA) and obeticholic acid. Different indices evaluate the response after one year of treatment. The aim of our study was to evaluate the different predictive scores and prognostic factors of response to UDCA. Material and methods: Retrospective single-centre study in which clinical and analytical data of patients diagnosed with PBC were collected from January 1987 to December 2015. The response after one year of treatment was evaluated using the different response scores and their concordance degree using the Kappa index. The area under the receiver operating characteristic curve (AUROC) was calculated to determine the predictive capacity of the scores. Likewise, the prognostic factors of response to treatment were analysed. Results: We included 153 patients. The bivariate analysis showed a statistically significant relationship between the initial high levels of alkaline phosphatase and cholesterol and the poor response to treatment. The best AUROC was in Paris-I score (0.81). The concordance between the different scores was low. The GLOBE score was valid to evaluate the prognosis. Conclusion: Basal alkaline phosphatase and cholesterol were predictors of poor outcome. The best predictive qualitative score in our cohort patients was Paris-I. There was a poor concordance between the different predictive scores. GLOBE score is valid to evaluate prognosis

Utilidad de la histología para el diagnóstico de la gastroenteropatía por hipertensión portal. Concordancia entre la imagen endoscópica y las biopsias gastrointestinales. Papel del marcador CD34 / Utility of histology for the diagnosis of portal hypertensive gastroenteropathy. Concordance between the endoscopic image and gastrointestinal biopsies. Role of the CD34 marker

Introducción: En la endoscopia digestiva alta de pacientes con cirrosis hepática a menudo se observan lesiones inespecíficas, que se suelen orientar como gastropatía por hipertensión portal (GHP). Sin embargo, el diagnóstico de GHP puede ser difícil, tanto endoscópica como histológicamente. El estudio de expresión de CD34, que realza las células endoteliales de la microvasculatura podría ayudar al diagnóstico diferencial. Los objetivos del estudio fueron evaluar la correlación entre la endoscopia y la histología en el diagnóstico de la GHP y valorar la utilidad del CD34 en el diagnóstico de la misma. Material y métodos: Se analizaron biopsias fúndicas de 100 pacientes cirróticos y 20 controles, y se realizó inmunotinción para CD34. Se compararon con las imágenes endoscópicas. Resultados: Se observó una correlación muy baja entre la histología con el diagnóstico endoscópico de GHP (kappa=0,15). Además, la medición del diámetro de los vasos gástricos realzados mediante el uso de la tinción inmunohistoquímica (CD34) no mostró buena correlación con el diagnóstico endoscópico (p=0,26) y tampoco parece aportar información relevante para el diagnóstico histológico de GHP. Discusión: Existe una baja correlación entre la histología y la endoscopia para el diagnóstico de GHP. El uso de la inmunotinción para CD34 no mejora la rentabilidad diagnóstica del estudio histológico

Introduction: Upper gastroscopy in patients with cirrhosis often reveals non-specific lesions, which are usually oriented as portal hypertensive gastropathy (PHG). However, the diagnosis of PHG can be difficult, both from an endoscopic and histological point of view. The study of CD34 expression, which enhances the endothelial cells of the microvasculature, could help the differential diagnosis. The objectives of this study were to evaluate the correlation between endoscopy and histology in the diagnosis of PHG and to assess the utility of CD34 in the diagnosis of PHG. Material and methods: The results of immunostaining with CD34 gastric fundus biopsies from 100 cirrhotic patients and 20 controls were compared with the endoscopic images. Results: The correlation between the histology and the endoscopic diagnosis of PHG was very low (kappa=0.15). In addition, the measurement of the diameter of the gastric vessels enhanced by the use of immunohistochemical staining (CD34) did not show good correlation with the endoscopic diagnosis (p=.26) and did not provide relevant information for the histological diagnosis of PHG either. Discussion: The correlation between histology and endoscopy is low for the diagnosis of PHG. The use of immunostaining for CD34 does not seem to improve the diagnostic yield of the histological study

Reactivación de tuberculosis peritoneal y pleural durante el tratamiento de la hepatitis C con antivirales de acción directa / Reactivation of peritoneal and pleural tuberculosis during hepatitis C treatment with direct-acting antivirals

No disponible

Hepatotoxicidad de perfil mixto por apixaban / Apixaban-induced liver injury

Los nuevos anticoagulantes orales, entre ellos apixaban, se usan cada vez más. Presentamos el caso de una paciente de 85 años a la que se diagnosticó de hepatitis tóxica por apixaban de perfil mixto. A la paciente se le realizó el estudio etiológico, que fue negativo excepto por presentar anticuerpos antimúsculo liso positivos, por lo que se le realizó una biopsia hepática que descartó la hepatitis autoinmune y que presentó hallazgos que pueden orientar a una causa tóxica. Con el cálculo de la escala de causalidad CIOMS/RUCAM se obtuvo una puntuación de 7 (probable) y tras la retirada del fármaco se observó mejoría del daño hepático. Un metaanálisis muestra que no hay un riesgo aumentado de hepatotoxicidad con el uso de apixaban y en los estudios de registro no se recogen casos para la ficha técnica. A pesar de ello, en la base de datos europea de farmacovigilancia (EudraVigilance) se recogen más de 120 casos. En definitiva, se debe considerar apixaban como un fármaco con potencial de hepatotoxicidad

The use of new oral anticoagulants such as apixaban is increasing. We present the case of an 85-year-old patient who was diagnosed with mixed profile toxic hepatitis due to apixaban use. An etiological study was negative, except for anti-smooth muscle antibodies, and a liver biopsy ruled out autoimmune hepatitis. The patient was assigned a score of 7 on the CIOMS/RUCAM scale, indicating a probable causality. The liver injury improved after the withdrawal of apixaban. A previous meta-analysis reported that the risk of hepatotoxicity does not increase with the use of apixaban, nor were any cases reported in registry studies. Nonetheless, more than 120 possible cases currently appear in the European pharmacovigilance database (EudraVigilance). We suggest that apixaban should be considered as a possible cause of liver injury

Utility of histology for the diagnosis of portal hypertensive gastroenteropathy. Concordance between the endoscopic image and gastrointestinal biopsies. Role of the CD34 marker. / Utilidad de la histología para el diagnóstico de la gastroenteropatía por hipertensión portal. Concordancia entre la imagen endoscópica y las biopsias gastrointestinales. Papel del marcador CD34.

INTRODUCTION: Upper gastroscopy in patients with cirrhosis often reveals non-specific lesions, which are usually oriented as portal hypertensive gastropathy (PHG). However, the diagnosis of PHG can be difficult, both from an endoscopic and histological point of view. The study of CD34 expression, which enhances the endothelial cells of the microvasculature, could help the differential diagnosis. The objectives of this study were to evaluate the correlation between endoscopy and histology in the diagnosis of PHG and to assess the utility of CD34 in the diagnosis of PHG. MATERIAL AND METHODS: The results of immunostaining with CD34 gastric fundus biopsies from 100 cirrhotic patients and 20 controls were compared with the endoscopic images. RESULTS: The correlation between the histology and the endoscopic diagnosis of PHG was very low (kappa=0.15). In addition, the measurement of the diameter of the gastric vessels enhanced by the use of immunohistochemical staining (CD34) did not show good correlation with the endoscopic diagnosis (p=.26) and did not provide relevant information for the histological diagnosis of PHG either. DISCUSSION: The correlation between histology and endoscopy is low for the diagnosis of PHG. The use of immunostaining for CD34 does not seem to improve the diagnostic yield of the histological study.