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Medical management of metabolic and cardiovascular complications after liver transplantation

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World Journal of Gastroenterology 2020年第18期26卷 2138-2154页

作者： Chiara Becchetti melisa dirchwolf Vanessa Banz Jean-Francois Dufour Hepatology Department of Visceral Surgery and MedicineInselspitalUniversity Hospital BernBern CH-3008Switzerland Department of Biomedical Research University of BernBern CH-3008Switzerland Hepatology Hepatobiliary Surgery and Liver Transplant UnitHospital Privado de RosarioRosario S2000GAPSanta FeArgentina Department of Visceral Surgery and Medicine InselspitalUniversity Hospital BernBern CH-3008Switzerland Department of Clinical Research University of BernBern CH-3008Switzerland

Liver transplantation represents the only curative option for patients with endstage liver disease,fulminant hepatitis and advanced hepatocellular *** though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period,long-term survival is hampered by the lack of improvement in survival in the late post transplantation period(over 5 years after transplantation).The main etiologies for late mortality are malignancies and cardiovascular *** latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components(arterial hypertension,dyslipidemia,obesity,renal injury,etc.).These comorbidities result from a combination of pre-liver transplant features,immunosuppressive agent side-effects,changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary *** this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation,as well as proposing management strategies.

关键词： Solid organ transplantation Hypertension New-onset diabetes after transplantation Obesity Orthotopic liver transplantation Post-transplantation metabolic syndrome

Unresolved issues in the prophylaxis of bacterial infections in patients with cirrhosis

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World Journal of Hepatology 2018年第12期10卷 892-897页

作者： melisa dirchwolf Sebastián Marciano José Martínez Andrés Eduardo Ruf nidad de Hígado Hospital Privado de Rosario Rosario 2000 Argentina Unidad de Hígado and Departamento de Investigación del Hospital Italiano de Buenos Aires Buenos Aires 1424 Argentina

Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant ***, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.

关键词： Cirrhosis Antibiotic Prophylaxis Multi-drug resistant bacteria Spontaneous bacterial peritonitis Bacterial infections

Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

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World Journal of Hepatology 2016年第8期8卷 385-394页

作者： Fernando Bessone melisa dirchwolf Department of Gastroenterology and Hepatology School of MedicineUniversity of Rosario Department of Hepatology Muniz Hospital

The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.

关键词： Anti-tumor necrosis factor-α drugs Acute liver failure Biologic therapy Immunosuppressive therapy Hepatitis B

Role of systemic inflammation in cirrhosis:From pathogenesis to prognosis

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World Journal of Hepatology 2015年第16期7卷 1974-1981页

作者： melisa dirchwolf Andres Eduardo Ruf Hepatopatias Infecciosas Hospital Francisco J Muniz Fundacion para la Docencia e Investigacion de las Enfermedades del Higado (FUNDIEH) Liver Transplant Unit British Hospital of Buenos Aires

The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure(ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts(evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.

关键词： Immune dysfunction Cirrhosis Acute-onchronic liver failure Prognosis Systemic inflammation

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

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World Journal of Hepatology 2015年第4期7卷 703-709页

作者： Sebastian Marciano Silvia M Borzi melisa dirchwolf Ezequiel Ridruejo Manuel Mendizabal Fernando Bessone Maria E Sirotinsky Diego H Giunta Julieta Trinks Pablo A Olivera Omar A Galdame Marcelo O Silva Hugo A Fainboim Adrian C Gadano Liver Unit Hospital Italiano de Buenos Aires Hepatology Section Hospital R. Rossi La Plata Buenos Aires Argentina Liver Infectious Disease Unit Hospital F.J Muniz Uspallata 2272 Buenos Aires Argentina Hepatology Section Department of Medicine Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC" Avenida Galvan 4102 Buenos Aires Argentina Hepatology and Liver Transplant Unit Hospital Universitario Austral Hepatology Unit Sanatorio del Parque Rosario Argentina HEPATOSUR group Comodoro Rivadavia Chubut Argentina Internal Medicine Research Unit Hospital Italiano de Buenos Aires Buenos Aires Argentina Basic Science and Experimental Medicine Institute Hospital Italiano de Buenos Aires Internal Medicine Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC" Buenos Aires Argentina

AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.

关键词： Sustained virological response Direct antiviral agents Sofosbuvir Cirrhosis Viral load