Clinical practice guidelines of the Catalan Society of Gastroenterology about hepatic elastography 2022. / Documento de posicionamiento de la «Societat Catalana de Digestologia¼ sobre elastografía hepática 2022.

INTRODUCTION: After almost 20 years using transient elastography (TE) for the non-invasive diagnosis of liver fibrosis, its use has been extended to population screening, evaluation of steatosis and complications of cirrhosis. For this reason, the «Catalan Society of Gastroenterology¼ commissioned a group of experts to update the first document carried out in 2011. MATERIAL AND METHODS: The working group (8 doctors and 4 nurses) prepared a panel of questions based on the online survey «Hepatic Elastography in Catalonia 2022¼ following the PICO structure and the Delphi method. RESULTS: The answers are presented with the level of evidence, the degree of recommendation and the final consensus after being evaluated by two external reviewers. CONCLUSION: Transient elastography uses the simplest and most reliable elastographic method to quantify liver fibrosis, assess steatosis, and determine the risk of complications in patients with cirrhosis. The document has been endorsed by the "Catalan Society of Gastroenterology" and the "Col·legi Oficial d'Infermeres i Infermers de Barcelona".

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study.

There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study.

INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.

Use of healthcare resources and drug expenditure before and after treatment of chronic hepatitis C with direct antiviral agents.

The aim of this study was to analyse the impact of treating chronic hepatitis C (CHC) with direct-acting agents (DAA) on the use of healthcare resources. We included all patients treated with DAA for CHC from January 2015 to December 2017 in Catalonia whose medical records from 12 months before to 24 months after treatment were available. Data were obtained from the Catalan Health Surveillance System. A total of 12,199 patients in Catalonia were treated with DAA for CHC. Of these, 11.3% had no-minimal fibrosis (F0-F1), 24.0% had moderate fibrosis (F2), 50.3% had significant fibrosis or cirrhosis (F3-F4), and 14.4% had decompensated cirrhosis. Use of healthcare resources decreased from the pre-treatment period to the post-treatment period for the following: hospital admissions due to complications of cirrhosis, from 0.19 to 0.12 per month per 100 patients (RR 0.57; 95% CI 0.47-0.68); length of hospital stay, from 12.9 to 12.2 days (RR 0.93; 95% CI 0.91-0.94); outpatient visits, from 65.0 to 49.2 (RR 0.75; 95% CI 0.74-0.75); and number of medication containers per patient per month, from 13.9 to 12.5 (RR 0.837; 95% CI 0.835-0.838). However, the number of invoices for antineoplastic treatment increased after DAA treatment, especially for patients with high morbidity or advanced fibrosis stage. In conclusion, a decrease in health resource use was seen in CHC patients treated with DAA, as measured by length of hospital stay, number of admissions due to cirrhosis complications, outpatient visits and overall drug invoicing. However, use of antineoplastic drugs increased significantly, especially in patients with cirrhosis and high morbidity.

Elastography is unable to exclude cirrhosis after sustained virological response in HCV-infected patients with advanced chronic liver disease.

BACKGROUND: Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)-infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown. AIMS: To evaluate TE accuracy at identifying cirrhosis 3 years after HCV-eradication. METHODS: Prospective, multi-centric study including HCV-cACLD patients before direct-acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated. RESULTS: Among 746 HCV-infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non-invasive tests (APRI and FIB-4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV-genotype 3 (20.81 (2.12-201.47), .009), and TE before treatment (1.21 (1.09-1.34), <.001) were the only variables associated with cirrhosis after SVR. However, the accuracy of TE after SVR was poor (AUROC = 0.75) and 6 (27.3%) out of 22 patients with a TE <8 kPa had cirrhosis. Similar results were found with APRI and FIB-4 scores. CONCLUSIONS: Cirrhosis is present, 3 years after SVR, in more than half of HCV-cACLD patients even with the normalisation of liver function parameters, serological non-invasive tests and TE values. The low diagnostic accuracy of non-invasive methods after SVR reinforces the need for long-term surveillance.

International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

Apixaban-induced liver injury.

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.

Factors influencing hepatitis C cure in the era of direct-acting antivirals. / Factores que influyen en la curación de la hepatitis C en la era de los antivirales de acción directa.

Direct-acting antiviral agents are highly potent drugs with a strong genetic barrier. Consequently, the factors influencing hepatitis C cure have been reduced and have progressively lost importance. Host factors, such as the presence of cirrhosis, race, and treatment adherence, influence sustained viral response. Adherence, together with treatment errors and drug interactions, are also important, especially in older patients. Viral factors, such as viral load, genotype, and the presence of baseline resistances affect the response rate but their influence can be minimised by using pan-genotypic regimens. Treatment simplification and the high efficacy of new antiviral treatments will allow treatment universalisation and will hopefully enable elimination of the infection in the next few decades. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

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.

Idiopathic portal hypertension with regard to thiopurine treatment.

Idiopathic portal hypertension (IPH) is an infrequent adverse reaction to the use of thiopurines that tends to be overlooked. Herein, we present a patient with ileocolic Crohn's disease treated with azathioprine who presented ascites, esophageal varices and splenomegaly without any signs of liver cirrhosis. A portal hemodynamics study revealed a normal portosystemic gradient compatible with presinusoidal portal hypertension. Finally, IPH was diagnosed after a liver biopsy. IPH secondary to thiopurines is due to a 6-thioguanine nucleotide (6-TGN)-dependent reaction and occurs predominantly between three months and three years after the start of treatment. The onset is usually insidious and thrombocytopenia is the first manifestation. The definitive diagnosis is obtained by liver biopsy.

Inter and intra-observer concordance for the diagnosis of portal hypertension gastropathy.

INTRODUCTION: At present there is no fully accepted endoscopic classification for the assessment of the severity of portal hypertensive gastropathy (PHG). Few studies have evaluated inter and intra-observer concordance or the degree of concordance between different endoscopic classifications. OBJECTIVES: To evaluate inter and intra-observer agreement for the presence of portal hypertensive gastropathy and enteropathy using different endoscopic classifications. METHODS: Patients with liver cirrhosis were included into the study. Enteroscopy was performed under sedation. The location of lesions and their severity was recorded. Images were videotaped and subsequently evaluated independently by three different endoscopists, one of whom was the initial endoscopist. The agreement between observations was assessed using the kappa index. RESULTS: Seventy-four patients (mean age 63.2 years, 53 males and 21 females) were included. The agreement between the three endoscopists regarding the presence or absence of PHG using the Tanoue and McCormack classifications was very low (kappa scores = 0.16 and 0.27, respectively). CONCLUSIONS: The current classifications of portal hypertensive gastropathy have a very low degree of intra and inter-observer agreement for the diagnosis and assessment of gastropathy severity.

Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study.

INTRODUCTION: Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. OBJECTIVE: To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. PATIENTS AND METHODS: This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. RESULTS: A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). CONCLUSIONS: Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival.

Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease.

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15-0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16-5.83); P =0.02) and albumin ≤3.5 (17 (6.3-47); P <0.01). CONCLUSIONS: SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

BACKGROUND AND AIMS: Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. METHODS: This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. RESULTS: Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. CONCLUSIONS: In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.

Effects of a multidisciplinary approach on the effectiveness of antiviral treatment for chronic hepatitis C.

UNLABELLED:  Background. Despite the introduction of direct antiviral agents, pegylated interferon remains the mainstay of treatment for chronic hepatitis C. However, pegylated interferon is associated with a high rate of severe adverse events and decreased quality of life. Specific interventions can improve adherence and effectiveness. We aimed to determine whether implementing a multidisciplinary approach improved outcomes in the treatment of chronic hepatitis C. MATERIAL AND METHODS: We analyzed consecutive patients treated with pegylated interferon plus ribavirin between August 2001 and December 2011. We compared patients treated before and after the implementation of a multidisciplinary approach in 2007. We compared the baseline demographic and clinical characteristics and laboratory findings between groups, and used bivariate logistic regression models to detect factors involved in attaining a sustained virological response, calculating the odds ratios with their respective 95% confidence intervals. To evaluate the effect of the multidisciplinary team, we fitted a multivariate logistic regression model to compare the sustained virological response after adjusting for unbalanced variables and predictive factors. RESULTS: We included 514 patients [228 (44.4%) in the pre-intervention cohort]. Age, viral genotype, previous treatment, aspartate transaminase, ferritin, and triglyceride were prognostic factors of sustained virological response. After adjusting for prognostic factors, sustained virological response was higher in the multidisciplinary cohort (58 vs. 48%, p = 0.038). Despite higher psychiatric comorbidity and age in the multidisciplinary cohort, we observed a trend toward a lower rate of treatment abandonment in this group (2.2 vs. 4.9%, p = 0.107). CONCLUSION: Multidisciplinary management of chronic hepatitis C improves outcomes.

Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic.

Ciprofloxacin and amoxicillin/clavulanic are two widely used antibiotics due to their high efficacy and few side effects. While the percentage of hepatotoxicity of these antibiotics is low, their frequent use has led to a progressive increase in the number of cases. Both antibiotics have been associated with a wide variety of hepatotoxic reactions, from a slight rise of transaminases to fulminant hepatitis. Once hepatotoxicity secondary to a drug appears, the first step is to discontinue the drug. Physicians may opt to administer an alternative treatment with a different chemical structure. It should be borne in mind, however, that different chemical structures may also cause recurrent drug-induced liver injuries (DILI). We present the case of a patient who consecutively developed DILI due to ciprofloxacin and amoxicillin/clavulanic.

[Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia]. / Lesiones vasculares gástricas en la cirrosis: gastropatía y ectasia vascular antral.

Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended.

[Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns of sorafenib use. Results of the international observational GIDEON trial in Spain]. / Decisiones terapéuticas en el tratamiento del carcinoma hepatocelular y patrones de uso de sorafenib. Resultados del estudio internacional observacional GIDEON en España.

INTRODUCTION: GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES: To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. METHODS: Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.

Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers.

BACKGROUND: Endoscopic therapy reduces the rebleeding rate and the need for surgery in patients with bleeding peptic ulcers. OBJECTIVES: To determine whether a second procedure improves haemostatic efficacy or patient outcomes or both after epinephrine injection in adults with high-risk bleeding ulcers. SEARCH METHODS: For our update in 2014, we searched the following versions of these databases, limited from June 2009 to May 2014: Ovid MEDLINE(R) 1946 to May Week 2 2014; Ovid MEDLINE(R) Daily Update May 22, 2014; Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations May 22, 2014 (Appendix 1); Evidence-Based Medicine (EBM) Reviews-the Cochrane Central Register of Controlled Trials (CENTRAL) April 2014 (Appendix 2); and EMBASE 1980 to Week 20 2014 (Appendix 3). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing epinephrine alone versus epinephrine plus a second method. Populations consisted of patients with high-risk bleeding peptic ulcers, that is, patients with haemorrhage from peptic ulcer disease (gastric or duodenal) with major stigmata of bleeding as defined by Forrest classification Ia (spurting haemorrhage), Ib (oozing haemorrhage), IIa (non-bleeding visible vessel) and IIb (adherent clot) (Forrest Ia-Ib-IIa-IIb). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. Meta-analysis was undertaken using a random-effects model; risk ratios (RRs) with 95% confidence intervals (CIs) are presented for dichotomous data. MAIN RESULTS: Nineteen studies of 2033 initially randomly assigned participants were included, of which 11 used a second injected agent, five used a mechanical method (haemoclips) and three employed thermal methods.The risk of further bleeding after initial haemostasis was lower in the combination therapy groups than in the epinephrine alone group, regardless of which second procedure was applied (RR 0.53, 95% CI 0.35 to 0.81). Adding any second procedure significantly reduced the overall bleeding rate (persistent and recurrent bleeding) (RR 0.57, 95% CI 0.43 to 0.76) and the need for emergency surgery (RR 0.68, 95% CI 0.50 to 0.93). Mortality rates were not significantly different when either method was applied.Rebleeding in the 10 studies that scheduled a reendoscopy showed no difference between epinephrine and combined therapy; without second-look endoscopy, a statistically significant difference was observed between epinephrine and epinephrine and any second endoscopic method, with fewer participants rebleeding in the combined therapy group (nine studies) (RR 0.32, 95% CI 0.21 to 0.48).For ulcers of the Forrest Ia or Ib type (oozing or spurting), the addition of a second therapy significantly reduced the rebleeding rate (RR 0.66, 95% CI 0.49 to 0.88); this difference was not seen for type IIa (visible vessel) or type IIb (adherent clot) ulcers. Few procedure-related adverse effects were reported, and this finding was not statistically significantly different between groups. Few adverse events occurred, and no statistically significant difference was noted between groups.The addition of a second injected method reduced recurrent and persistent rebleeding rates and surgery rates in the combination therapy group, but these findings were not statistically significantly different. Significantly fewer participants died in the combined therapy group (RR 0.50, 95% CI 0.25 to 1.00).Epinephrine and a second mechanical method decreased recurrent and persistent bleeding (RR 0.31, 95% CI 0.18 to 0.54) and the need for emergency surgery (RR 0.20, 95% CI 0.06 to 0.62) but did not affect mortality rates.Epinephrine plus thermal methods decreased the rebleeding rate (RR 0.49, 95% CI 0.30 to 0.78) and the surgery rate (RR 0.20, 95% CI 0.06 to 0.62) but did not affect the mortality rate.Our risk of bias estimates show that risk of bias was low, as, although the type of study did not allow a double-blind trial, rebleeding, surgery and mortality were not dependent on subjective observation. Although some studies had limitations in their design or implementation, most were clear about important quality criteria, including randomisation and allocation concealment, sequence generation and blinding. AUTHORS' CONCLUSIONS: Additional endoscopic treatment after epinephrine injection reduces further bleeding and the need for surgery in patients with high-risk bleeding peptic ulcer. The main adverse events include risk of perforation and gastric wall necrosis, the rates of which were low in our included studies and favoured neither epinephrine therapy nor combination therapy. The main conclusion is that combined therapy seems to work better than epinephrine alone. However, we cannot conclude that a particular form of treatment is equal or superior to another.