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BACKGROUND: Prevalence and clinical impact of increased liver function tests in patients affected by Coronavirus disease 2019 (COVID-19) is controversial. AIMS: This observational study evaluates the prevalence of transaminases elevation in hospitalized patients affected by COVID-19 and investigates the presence of factors associated with hepatocellular injury and with mortality. METHODS: Data of 292 adult patients with confirmed COVID-19 admitted to the Ente Ospedaliero Cantonale (Switzerland) were retrospectively analyzed. RESULTS: Transaminases were increased in about one-third of patients on hospital admission and two-thirds of patients during the hospital stay. On hospital admission, transaminases were more commonly elevated in younger patients, who also reported elevated C reactive protein and a higher degree of respiratory failure. Independent factors associated with abnormal transaminases during hospitalization were drugs, in particular paracetamol (OR=2.67; 95% CI=1.38-5.18; p = 0.004) and remdesivir (OR=5.16; 95% CI=1.10-24.26; p = 0.04). Mortality was independently associated to age (OR = 1.09; 95% CI=1.05-1.13; p<0.001), admission to intensive care unit (OR=5.22; 95% CI=2.28-11.90; p<0.001) and alkaline phosphatase peak (OR=1.01; 95% CI=1.00- 1.01; p = 0.01). CONCLUSIONS: On hospital admission, factors associated with liver damage were linked to demographic and clinical characteristics (age, inflammation and hypoxia) while, during hospitalization, drug treatment was related to development and progression of hepatocellular damage. Mortality was associated with alkaline phosphate peak value.
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COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Mortalidad Hospitalaria , Hospitalización , Humanos , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , TransaminasasRESUMEN
Portal vein thrombosis (PVT) is a splanchnic vascular disorder characterised by a recent or chronic thrombotic occlusion of the portal venous system. Its aetiology is miscellaneous, and its management is demanding since PVT can play a critical role as far as morbidity and mortality are concerned. Indeed, PVT can develop as a complication of portal hypertension (PH), in association or not with advanced chronic liver disease, and aggravate its clinical consequences such as variceal bleeding and ascites. Furthermore, a diagnosis of PVT in a non-cirrhotic context can potentially reveal a previously unknown hypercoagulable condition, requiring further diagnostic steps and specific treatment in addition to anticoagulation. In addition to established therapeutic approaches, new strategies, including newer pharmacological treatments and interdisciplinary invasive procedures, gain more attention and have been increasingly introduced into clinical practice. This review aims at discussing the current knowledge in terms of treatment options for PVT.
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Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Trombosis , Várices Esofágicas y Gástricas/patología , Hemorragia Gastrointestinal , Humanos , Cirrosis Hepática/patología , Vena Porta/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA. AIM: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427.
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Ascitis/terapia , Cirrosis Hepática/complicaciones , Paracentesis/métodos , Derivación Portosistémica Intrahepática Transyugular/métodos , Ascitis/etiología , Drenaje/métodos , Femenino , Humanos , Trasplante de Hígado/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. Recently, in vitro and animal studies have questioned the role of adipose tissues in cancer development. DESIGNS: Matched-cohort study. We analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling. (ii) A control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. A local event (LE) was the primary end point, with follow-up starting from the baseline. RESULTS: Median follow-up was 63 and 66 months from surgery, and 38 and 42 from baseline, for the lipofilling and control groups, respectively; the 5-year cumulative incidence of LE was 18% and 3% (P = 0.02). Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy. CONCLUSION: Higher risk of LE was observed in intraepithelial neoplasia patients following lipofilling. Although further studies are required to validate our conclusions, patients belonging to this subgroup should be informed of these results and the potential risks.
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Neoplasias de la Mama/cirugía , Carcinoma in Situ/cirugía , Seguridad del Paciente , Grasa Subcutánea/trasplante , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Carcinoma in Situ/diagnóstico , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lipectomía/efectos adversos , Lipectomía/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Tejidos/efectos adversos , Trasplante de Tejidos/métodosRESUMEN
Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient.
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Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Antivirales/administración & dosificación , Antivirales/efectos adversos , Eritropoyetina/administración & dosificación , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferones/administración & dosificación , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Variceal bleeding is a life-threatening complication of liver cirrhosis with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. AIM: To provide an overview of the current knowledge on the best evidence-based therapeutic options to prevent first or recurrent bleeding from oesophageal varices in patients with cirrhosis. METHODS: For the preparation of this narrative review, we sought to analyse randomized controlled trials that examined the efficacy and side effects of pharmacological or endoscopic therapy for the primary and secondary prophylaxis of oesophageal variceal bleeding. RESULTS: Endoscopic band ligation (EBL) and nonselective beta-blockers are both effective in preventing first bleeding. Until more long-term data are available, nonselective beta-blockers should be the first treatment option because of less severe side effects. EBL is an alternative when beta-blockers are contraindicated or not tolerated. Patient preference may also be considered. For prevention of rebleeding, nonselective beta-blockers (preferably in association with isosorbide-5-mononitrate) or EBL are both effective and good alternative treatments. A combination of both treatments may be the best alternative. CONCLUSIONS: A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.
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Antagonistas Adrenérgicos beta/uso terapéutico , Hipertensión Portal/terapia , Dinitrato de Isosorbide/análogos & derivados , Quimioterapia Combinada , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/prevención & control , Humanos , Dinitrato de Isosorbide/uso terapéutico , Ligadura , Cirrosis Hepática/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Escleroterapia , Prevención Secundaria , Resultado del TratamientoRESUMEN
The success of liver transplantation essentially depends on the prevention and treatment of long term complications, which may be due to surgery, opportunistic infections, organ rejection and relapse of the initial liver disease. The side effects of immunosuppressive drugs--arterial hypertension, glucose intolerance and diabetes, dyslipidemia and obesity, renal failure, osteoporosis, malignancy, and anaemia--should be regularly screened and treated without delay. Surgical procedures in transplanted patients are safe and rarely followed by complications. Although pregnancy in this setting is considered at risk, because of prematurity and low birth weight, overall outcomes are favourable. The yearly influenza vaccination is strongly recommended. The survival and the quality of life of liver transplant patients also depend on a good communication between the general practitioner and the transplantation centre.
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Trasplante de Hígado/efectos adversos , Estudios de Seguimiento , Humanos , Inmunosupresores/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapiaRESUMEN
Oesophageal and fundic varices belong to the most frequent complications of cirrhosis and portal hypertension. Due to their significant morbidity and mortality, bleedings from oesophageal or fundic varices represent a challenge for the emergency medical team as well as for the gastroenterologist. The patient with a variceal bleeding should be accurately monitored and his/her hemodynamic parameters should be maintained stable with the administration of plasma expanders and blood units when indicated. An antibiotic prophylaxis in this setting--norfloxacin or ceftriaxon--has been demonstrated to significantly reduce morbidity and mortality. Additionally, the early administration of vasoactive compounds, such as terlipressin, somatostatin or octreotide, is associated with beneficial effects in reducing the bleeding. An upper gastrointestinal endoscopy should be generally performed within the first twelve hours from the beginning of the bleeding in order to obtain an accurate diagnosis and to provide an adequate treatment. Endoscopic procedures to control the bleeding include the rubber band ligation, the treatment of the varix with a sclerosing agent or the injection of tissue glue into the varix. In case of recurrent bleeding, beyond the above methods, different techniques, such as the transjugular porto-caval shunt, surgical shunt procedures, as well as embolisation of splanchnic blood vessels, represent additional therapeutic options. However, they are associated with very high mortality rates and their indication has to be discussed case by case by an interdisciplinary team of experts. Future therapies include the optimisation and the improvement of the current medical and endoscopic armamentarium, as well as the application of treatments to novel targets, such as the coagulation cascade.
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Cuidados Críticos/métodos , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Várices Esofágicas y Gástricas/complicaciones , Alemania , Humanos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en MedicinaRESUMEN
BACKGROUND: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. AIM: To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. METHODS: We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. RESULTS: PPAR-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b. CONCLUSIONS: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.
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Hígado Graso/metabolismo , Hepatitis C Crónica/metabolismo , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Adulto , Hígado Graso/virología , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Contrarily to a widely prevalent opinion, celiac disease frequently affects adults, and only rarely reveals itself by the classical triad of diarrhea--weight loss--nutritional deficiency. In addition to isolated deficiencies, most frequently iron and calcium-vitamin D, celiac disease is commonly associated with atypical, sometimes very commonplace manifestations, such as abdominal symptoms reminiscent of those of irritable bowel syndrome, or type I diabetes. The diagnostic process is now made easier by the availability of antitransglutaminase antibodies dosage, a simple, trustworthy, sensitive and specific test. This review article discusses the many clinical pictures which should prompt the clinician to rule out celiac disease, and provides practical guidelines as to the use and interpretation of serologic tests.
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Enfermedad Celíaca/diagnóstico , HumanosRESUMEN
Treatment of chronic hepatitis B needs to consider two aspects. First, a certain proportion of patients will spontaneously undergo a stable remission of the underlying liver disease, i.e. without therapeutic intervention, on occasion of the HBeAg --> anti-HBe seroconversion. Second, all drugs that have been used so far in the treatment of HBV have rarely resulted in the definitive eradication of the viral infection, i.e. a permanent disappearance of HBsAg with development of anti-HBs. Thus, the most reasonable, albeit surrogate endpoint of treatment is the acceleration towards HBeAg --> anti-HBe seroconversion and/or the stable suppression of HBV replication at levels below 500000 copies/ml, which is associated with disappearance of intrahepatic necrosis and inflammation and slowing down of the fibrosis progression. Two drugs are currently available--interferon-alpha and lamivudine--and a third antiviral compound (adefovir dipivoxil) will soon appear in the market. Advantages and disadvantages of different therapeutic options are discussed below.
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Adenina/análogos & derivados , Hepatitis B Crónica/terapia , Organofosfonatos , Adenina/uso terapéutico , Adulto , Antivirales/uso terapéutico , Niño , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/inmunología , Humanos , Recién Nacido , Interferón-alfa/uso terapéutico , Lamivudine/uso terapéutico , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND/AIMS: Hepatic stellate cells (HSC) are involved in the pathogenesis of liver fibrosis; although ET-1 is increased in cirrhosis, its pathophysiological role in fibrogenesis and portal hypertension remains controversial. The aim of this study was to investigate splanchnic hemodynamics and to correlate them with changes in ET-1 expression and HSC activation in bile duct ligated (BDL) rats. METHODS/RESULTS: Expression of the ET-1 gene was increased early as measured by quantitative reverse transcriptase-polymerase chain reaction (6-fold 3 days after BDL) whereas ET-1 peptide measured by RIA increased significantly only in the late phase (30-fold at 28 days). There was a linear correlation between portal pressure and the amount of ET-1 in the portal vein (r = 0.66; P = 0.003), as well as between ET-1 and the volume fraction of myofibroblasts (r = 0.80, P < 10(-7)) as assessed by morphometry and immunohistochemical staining using alpha-smooth muscle actin. CONCLUSIONS: During chronic liver injury activation of HSCs and of preproET-1 mRNA is accentuated in the early phase after BDL. The late increase in ET-1 peptide may indicate that this peptide is only secondarily involved in HSC activation. The correlation between ET-1 in portal vein and portal pressure suggests that ET-1 may play an important role in the development of portal hypertension.
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Colestasis/metabolismo , Endotelina-1/biosíntesis , Hipertensión Portal/etiología , Cirrosis Hepática Experimental/etiología , Hígado/patología , Animales , Ácido Aspártico Endopeptidasas/genética , Colestasis/patología , Endotelina-1/genética , Enzimas Convertidoras de Endotelina , Hemodinámica , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Metaloendopeptidasas , ARN Mensajero/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND/AIM: Endothelin-1 plays an important role in the regulation of portal hypertension; endothelin antagonists have been extensively studied in portal hypertensive animals. We aimed to evaluate the efficacy of highly selective endothelin antagonists in partial portal vein ligated (PPVL) rats. METHODS: Four groups of 7 male Sprague-Dawley rats were administered orally ABT-627 (ET(A)-selective), A-192621 (ET(B)-selective), or A-182086 (non-selective), with the fourth group serving as control. On the 3rd day after beginning treatment animals underwent PPVL. On the 11th day hemodynamics were studied and portal vein ET-1 was measured. RESULTS: In the control group portal pressure was 13.4+/-SD 0.2 mmHg; this increased to 14.9+/-1.8 (p<0.05) in the ET(B) blocked group. In contrast, ET(A) blockade improved portal hypertension (11.7+/-1.1, p<0.05), while the treatment with the non-selective antagonist had no effect (12.3+/-0.7 n.s.). Mean arterial pressure was not significantly affected by any treatment. Portal vein ET-1 was increased in all groups compared to controls; this increase was limited to the pre-stenotic area (79+/-43 vs 194+/-76 in the pre- and post-stenotic portal vein; p<0.0025). CONCLUSIONS: Oral administration of an ET(A) antagonist ameliorated portal hypertension; we suggest that long-term therapy of portal hypertension with selective ET(A) antagonists may be more beneficial than mixed antagonists.
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Antagonistas de los Receptores de Endotelina , Hipertensión Portal/tratamiento farmacológico , Presión Portal/efectos de los fármacos , Animales , Atrasentán , Endotelina-1/sangre , Hipertensión Portal/fisiopatología , Masculino , Pirrolidinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina A , Receptor de Endotelina BRESUMEN
OBJECTIVE: To report our incidence of local and systemic complications after needle-catheter jejunostomy. DESIGN: Retrospective analysis. SETTING: University hospital, Switzerland. RESULTS: 100 patients (70 men and 30 women; mean age 65 years, range 42-90) had needle-catheter jejunostomy for postoperative enteral feeding. 26 developed catheter-related and 18 nutrition-related complications. Most of the complications were minor (lumenal obstruction of the catheter or local cellulitis) and only 3 patients needed reoperation, 2 because the catheter broke with extravasation of the nutrition formula into the subcutaneous tissue, and the other because of a small bowel obstruction. There was no small bowel necrosis and no patient died as a direct result of the jejunostomy. Overall, 92 patients were fed enterally according to the protocol, and 8 required removal of the catheter. CONCLUSION: Needle-catheter jejunostomy gives a safe and effective access for postoperative enteral feeding. Minor technical complications are common and can be reduced by a meticulous insertion technique and careful postoperative management. Regular clinical surveillance may reduce the incidence of nutrition-related complications.
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Nutrición Enteral/métodos , Yeyunostomía , Procedimientos Quirúrgicos Operativos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Estudios RetrospectivosRESUMEN
BACKGROUND/AIMS: In vivo studies have shown that arterial vasodilation induced by synthetic openers of ATP-sensitive K+ (K(ATP)) channels is decreased in rats with cirrhosis. Since vasodilation induced by these substances is mediated by membrane potential hyperpolarization in arterial smooth muscle cells, membrane potential hyperpolarization in response to K(ATP) channel openers may be altered in cirrhotic smooth muscle cells. The aim of the present study was to investigate the effects of K(ATP) channel modulators (i.e. openers and blockers of these channels) on the membrane potential in smooth muscle cells in isolated aortae from cirrhotic and normal rats. The influence of endothelin-1 production by endothelial cells on smooth muscle cells membrane potential responses to K(ATP) channel modulators was also studied. METHODS: Cells were impaled in situ (in intact and endothelium-denuded aortae) with a microelectrode that was used to measure membrane potentials. K(ATP) channel openers were diazoxide or cromakalim; blockers were glibenclamide or tolbutamide. Bosentan (a mixed endothelin receptor antagonist) and exogenous endothelin-1 were also used. Preproendothelin-1 mRNA was assayed in aortae by RNase protection assay. Aortic wall endothelin-1 concentration was measured by double antibody radioimmunoassay technique. RESULTS: As expected, in smooth muscle cells in intact normal aortae, K(ATP) channel openers induced membrane potential hyperpolarization and K(ATP) channel blockers membrane potential depolarization. In smooth muscle cells in intact cirrhotic aortae, K(ATP) channel openers and blockers did not significantly change the membrane potential. Endothelium removal or exposure of intact aortae to bosentan restored normal membrane potential responses to K(ATP) channel modulators in cirrhotic smooth muscle cells and did not alter the effects of these substances in normal smooth muscle cells. In endothelium-denuded aortae, exposure to exogenous endothelin-1 suppressed membrane potential responses to K(ATP) channel modulators. In intact aortae, the abundance of preproendothelin-1 mRNA and endothelin-1 did not significantly differ between normal and cirrhotic rats. CONCLUSIONS: K(ATP) channel opener-induced membrane hyperpolarization and K(ATP) channel blocker-elicited membrane depolarization are blunted in smooth muscle cells in intact cirrhotic aortae. This blunting is due to the activation of the endothelin-1 pathway in the aortic wall, downstream to the endothelial production of endothelin-1.