Diagnosis and management of Abernethy syndrome.

Abernethy syndrome (AS or extrahepatic portosystemic shunt) is an uncommon congenital malformation consisting of agenesis or hypoplasia of the portal vein (PV) in such a way that splanchnic venous blood drains directly into the systemic circulation through aberrant communications, resulting in a portosystemic shunt that bypasses the liver AS is an underdiagnosed condition with unknown incidence and complication rate given that symptoms are usually absent. AS identification is increasingly common because of improved imaging techniques, hence prognostic implications and clinical management need be understood. This editorial reviews the natural history of AS and its diagnostic-therapeutic implications, illustrating the process with a series of cases from our institution.

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Implementation of a hepatology and gastroenterology teleconsultation for our penitentiary center.

The use of telemedicine in penitentiary centers (PCs) is an effective measure to improve quality access to specialized care (secondary prevention) and reduces the inherent costs derived from physical consultations of inmates in hospitals. Regarding the project of our Community Health Service, we enthusiastically began a gastroenterology teleconsultation in our PC at the end of 2020. This modality completes the monthly/on-demand hepatology consultation carried out in this PC since 2015.

Efficacy and safety of daclatasvir-based antiviral therapy in hepatitis C virus recurrence after liver transplantation. Role of cirrhosis and genotype 3. A multicenter cohort study.

Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155-0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061-1.218) were predictors of death. DCV-based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response.

Impact of MELD Allocation System on Waiting List and Early Post-Liver Transplant Mortality.

BACKGROUND AND AIMS: MELD allocation system has changed the clinical consequences on waiting list (WL) for LT, but its impact on mortality has been seldom studied. We aimed to assess the ability of MELD and other prognostic scores to predict mortality after LT. METHODS: 301 consecutive patients enlisted for LT were included, and prioritized within WL by using the MELD-score according to: hepatic insufficiency (HI), refractory ascites (RA) and hepatocellular carcinoma (HCC). The analysis was performed to predict early mortality after LT (8 weeks). RESULTS: Patients were enlisted as HI (44.9%), RA (19.3%) and HCC (35.9%). The major aetiologies of liver disease were HCV (45.5%). Ninety-four patients (31.3%) were excluded from WL, with no differences among the three groups (p = 0.23). The remaining 207 patients (68.7%) underwent LT, being HI the most frequent indication (42.5%). HI patients had the shortest length within WL (113.6 days vs 215.8 and 308.9 respectively; p<0.001), but the highest early post-LT mortality rates (18.2% vs 6.8% and 6.7% respectively; p<0.001). The independent predictors of early post-LT mortality in the HI group were higher bilirubin (OR = 1.08; p = 0.038), increased iMELD (OR = 1.06; p = 0.046) and non-alcoholic cirrhosis (OR = 4.13; p = 0.017). Among the prognostic scores the iMELD had the best predictive accuracy (AUC = 0.66), which was strengthened in non-alcoholic cirrhosis (AUC = 0.77). CONCLUSION: Patients enlisted due to HI had the highest early post-LT mortality rates despite of the shortest length within WL. The iMELD had the best accuracy to predict early post-LT mortality in patients with HI, and thus it may benefit the WL management.

Biomarkers for hepatocellular carcinoma: diagnostic and therapeutic utility.

Because of the high prevalence and associated-mortality of hepatocellular carcinoma (HCC), early diagnosis of the disease is vital for patient survival. In this regard, tumor size is one of the two main prognostic factors for surgical resection, which constitutes the only curative treatment for HCC along with liver transplantation. However, techniques for HCC surveillance and diagnosis that are currently used in clinical practice have certain limitations that may be inherent to the tumor development. Thus, it is important to continue efforts in the search for biomarkers that increase diagnostic accuracy for HCC. In this review, we focus on different biological sources of candidate biomarkers for HCC diagnosis. Although those biomarkers identified from biological samples obtained by noninvasive methods have greater diagnostic value, we have also considered those obtained from liver tissue because of their potential therapeutic value. To date, sorafenib is the only US Food and Drug Administration-approved antineoplastic for HCC. However, this therapeutic agent shows very low tumor response rates and frequently causes acquired resistance in HCC patients. We discuss the use of HCC biomarkers as therapeutic targets themselves, or as targets to increase sensitivity to sorafenib treatment.

Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis.

UNLABELLED: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis, organ failure(s), and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT) or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4%, and worsened in 20.4%. The 28-day transplant-free mortality was low-to-moderate (6%-18%) in patients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥12 mg/dL) at ACLF diagnosis. Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short- (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3-7 days, and did not undergo LT, mortality was 100% by 28 days. CONCLUSIONS: Assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility.

Plasma protein biomarkers of hepatocellular carcinoma in HCV-infected alcoholic patients with cirrhosis.

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV) infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP), complement component 4a (C4a), fibrinogen-alpha (FGA), immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1). Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029), being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015), with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81). In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic patients.

PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

OBJECTIVE: Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. METHODS: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. RESULTS: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. CONCLUSIONS: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.

Objetivo: El interferon-pegilado (IFN-PEG) junto a ribavirina ha sido el principal tratamiento de la infeccion por el virus de la hepatitis C (VHC) de la ultima decada. Los agentes antivirales de accion directa actuales han mejorado los resultados de la terapia, pero tambien han aumentado el costo y la gestion de la complejidad del tratamiento. El presente estudio analiza factores geneticos de los pacientes, asi como predictores virales y clinicos de respuesta sostenida viral (RSV) al tratamiento con IFN-PEG y ribavirina en poblacion Espanola. Métodos: Estudio farmacogenetico, multicentrico, prospectivo, observacional de cohortes realizado en 12 hospitales diferentes de 12 comunidades autonomas diferentes. Se incluyeron un total de 98 pacientes con RVS y 106 sin SVR al tratamiento con IFNPEG y ribavirina. Se seleccionaron 33 polimorfismos de nucleotido unico ubicados en 24 genes diferentes relacionados con la respuesta inflamatoria, inmunologica y viral. Los datos clinicos y virales tambien se analizaron como candidatos predictores de RVS. Resultados: Los genotipos IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) y TNFRSF1B (rs1061622), asi como los haplotipos TNFRSF1B / IL-10 / TNF(-308) no-TTG y TNFRSF1B / IL-10 / IL-4 no-TTC junto con la menor edad, menor carga de ARN-VHC basal, valores elevados de colesterol LDL en suero basal, genotipos VHC2 y 3 y bajo grado de fibrosis basal (0-2) se asociaron con una RVS en el analisis univariante. Los predictores independientes de RVS en el analisis multivariante fueron el genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 no-TTC junto con los bajos niveles basales de VHCARN y los genotipos virales VHC2 y 3. Conclusiones: El genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 haplotipos no-TTC, la carga viral basal baja y los genotipos del VHC2 y 3 pueden ayudar a predecir una buena respuesta a la terapia con IFN-PEG y ribavirina en poblacion espanola.

Reduced exposure to calcineurin inhibitors early after liver transplantation prevents recurrence of hepatocellular carcinoma.

BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) is a major complication after liver transplantation (LT). The initial immunosuppression protocol may influence HCC recurrence, but the optimal regimen is still unknown. METHODS: 219 HCC consecutive patients under Milan criteria, who received an LT at 2 European centres between 2000 and 2010, were included. Median follow-up was 51 months (IQR 26-93). Demographic characteristics, HCC features, and immunosuppression protocol within the first month after LT were evaluated against HCC recurrence by using Cox regression. RESULTS: In the explanted liver, 110 patients (50%) had multinodular HCC, and largest nodule diameter was 3±2.1cm. Macrovascular invasion was incidentally detected in 11 patients (5%), and microvascular invasion was present in 41 patients (18.7%). HCC recurrence rates were 13.3% at 3 years and 17.6% at 5 years. HCC recurrence was not influenced by the use/non-use of steroids and antimetabolites (p=0.69 and p=0.70 respectively), and was similar with tacrolimus or cyclosporine (p=0.25). Higher exposure to calcineurin inhibitors within the first month after LT (mean tacrolimus trough concentrations >10ng/ml or cyclosporine trough concentrations >300ng/ml), but not thereafter, was associated with increased risk of HCC recurrence (27.7% vs. 14.7% at 5 years; p=0.007). The independent predictors of HCC recurrence by multivariate analysis were: high exposure to calcineurin inhibitors defined as above (RR=2.82; p=0.005), diameter of the largest nodule (RR=1.31; p<0.001), microvascular invasion (RR=2.98; p=0.003) and macrovascular invasion (RR=4.57; p=0.003). CONCLUSIONS: Immunosuppression protocols with early CNI minimization should be preferred in LT patients with HCC in order to minimize tumour recurrence.

Amiloidosis sistémica AA en un receptor de trasplante hepático con complicaciones biliares en el postrasplante / Systemic amyloidosis AA in a liver transplant recipient with biliary complications in the posttransplant period

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Gastroenteritis eosinofílicaconmanifestación inusual / Eosinophilic gastroenteritis with atypical manifestation

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[An atypical case of massive gastrointestinal hemorrhage]. / Caso atípico de hemorragia digestiva masiva.

Gastrointestinal stromal tumors (GIST) are an infrequent cause (<1%) of severe gastrointestinal hemorrhage. Treatment is mainly surgical through complete tumoral resection. We report the case of a 29-year-old woman who presented to the emergency room with severe gastrointestinal bleeding manifested by melena. On physical examination the patient had a painless, palpable mass in the left abdomen. Esophagogastroduodenoscopy, computed tomography, angiography and urgent surgical intervention led to diagnosis of a jejunal GIST.

Caso atípico de hemorragia digestiva masiva / An atypical case of massive gastrointestinal hemorrhage

Los tumores estromales gastrointestinales (GIST) son una causa poco frecuente (< 1%) de hemorragia digestiva masiva. El tratamiento es fundamentalmente quirúrgico mediante la extirpación completa del tumor. Exponemos el caso de una mujer de 29 años de edad que acudió a urgencias al presentar un cuadro clínico compatible con hemorragia digestiva grave en forma de melenas. A la exploración física se apreció una masa abdominal indolora y no pulsátil. Tras realizar una endoscopia digestiva alta, una tomografía computarizada, una arteriografía y una intervención quirúrgica urgente, se llega al diagnóstico de GIST yeyunal

Gastrointestinal stromal tumors (GIST) are an infrequent cause (<1%) of severe gastrointestinal hemorrhage. Treatment is mainly surgical through complete tumoral resection. We report the case of a 29-year-old woman who presented to the emergency room with severe gastrointestinal bleeding manifested by melena. On physical examination the patient had a painless, palpable mass in the left abdomen. Esophagogastroduodenoscopy, computed tomography, angiography and urgent surgical intervention led to diagnosis of a jejunal GIST