RESUMO
BACKGROUND: Hepatorenal syndrome type 1 (HRS-1), a form of acute kidney injury (AKI) in cirrhosis, has a median survival of days to weeks if untreated. The impact of reduction in AKI stage on overall survival in cirrhosis, independent of HRS reversal, is unclear. METHODS: The Randomized, placEbo-controlled, double-blind study to confirm the reVERSal of HRS-1 with terlipressin study assessed terlipressin versus placebo, both with albumin, as treatment for HRS-1 for ≤14 days. Renal dysfunction severity was categorized by AKI stage at enrollment. Baseline patient characteristics were evaluated as predictors of AKI improvement using a multivariate model; the association between AKI stage reduction and 90-day survival was assessed using linear regression. RESULTS: A total of 184 patients (terlipressin: n = 91; placebo: n = 93) with similar numbers in AKI Stages 1-3 (terlipressin/placebo, Stage 1: n = 25/26; Stage 2: n = 35/33; Stage 3: n = 31/34) were included. Predictors of AKI improvement were absence of alcoholic hepatitis, baseline serum creatinine and male gender. Overall survival was not significantly different across AKI stages (range 53-65%). In patients with no AKI worsening, 90-day survival was consistently better when AKI improved independent of HRS reversal, regardless of the initial AKI stage, with patients with Stage 1 at initial diagnosis achieving the greatest clinical benefit. A significant association was observed between AKI reduction and overall 90-day survival (P = 0.0022). CONCLUSIONS: A reduction in AKI stage, independent of HRS reversal, was sufficient to improve overall survival in patients with HRS-1. The goal for HRS-1 treatment should be less stringent than absolute HRS reversal.
Assuntos
Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/patologia , Síndrome Hepatorrenal/mortalidade , Terlipressina/uso terapêutico , Vasoconstritores/uso terapêutico , Injúria Renal Aguda/prevenção & controle , Idoso , Método Duplo-Cego , Feminino , Síndrome Hepatorrenal/tratamento farmacológico , Síndrome Hepatorrenal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND & AIMS: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. METHODS: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. RESULTS: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. CONCLUSIONS: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.
Assuntos
Infecções Bacterianas/epidemiologia , Saúde Global , Cirrose Hepática/epidemiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/terapia , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Feminino , Mortalidade Hospitalar , Humanos , Cirrose Hepática/microbiologia , Cirrose Hepática/mortalidade , Cirrose Hepática/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Micoses/epidemiologia , Micoses/microbiologia , Micoses/mortalidade , Micoses/terapia , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND & AIMS: Patients with systemic inflammatory response syndrome (SIRS) along with decompensated cirrhosis and renal dysfunction have a poor prognosis and a lower response to treatment. We evaluated the effect of SIRS on the response of hepatorenal syndrome type 1 (HRS-1) to terlipressin. METHODS: We performed a retrospective study of data from a trial of the effects of terlipressin (1 mg every 6 hours or placebo with concomitant albumin) in 198 patients with HRS-1, performed at 50 investigational sites in the United States and 2 in Canada from October 2010 through February 2013. We identified patients with 2 or more criteria for SIRS, without untreated infections (28 received terlipressin and 30 received placebo), and patients with less than 2 criteria for SIRS (control subjects). Primary endpoints included HRS reversal (a decrease in serum level of creatinine to ≤1.5 mg/dL), confirmed HRS reversal (defined as 2 serum creatinine levels ≤1.5 mg/dL, ≥ 48 hours apart), and survival for 90 days after treatment. RESULTS: Baseline characteristics were similar between groups, apart from slightly higher white blood cell counts and heart rates, and slightly lower serum levels of bicarbonate in patients with SIRS versus without SIRS. HRS was reversed in 42.9% of patients who received terlipressin with SIRS (12/28) versus 6.7% of patients who received placebo (2/30) (P = .0018); confirmed HRS reversal occurred in 32.1% of patients who received terlipressin with SIRS (9/28) versus 3.3% who received placebo (1/30) (P = .0048). A larger proportion of patients with SIRS who received terlipressin survived for 90 days without a transplant (13/28; 46.4%) than patients with SIRS who received placebo (7/30; 23.3%) (P = .076). CONCLUSIONS: In an analysis of data from a placebo-controlled study, we found that terlipressin improved renal function and reversed HRS in a higher proportion of patients with HRS-1 and SIRS than patients who received albumin plus placebo. ClincialTrials.gov, number NCT 01143246.
Assuntos
Síndrome Hepatorrenal/tratamento farmacológico , Lipressina/análogos & derivados , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Vasoconstritores/uso terapêutico , Idoso , Canadá , Feminino , Síndrome Hepatorrenal/complicações , Humanos , Lipressina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Estudos Retrospectivos , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/complicações , Terlipressina , Resultado do Tratamento , Estados UnidosAssuntos
Doenças dos Ductos Biliares/complicações , Doenças dos Ductos Biliares/patologia , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/patologia , Nefrose Lipoide/complicações , Nefrose Lipoide/patologia , Doença Aguda , Adulto , Doenças dos Ductos Biliares/diagnóstico por imagem , Doenças dos Ductos Biliares/tratamento farmacológico , Biópsia por Agulha , Progressão da Doença , Quimioterapia Combinada , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Testes de Função Hepática , Linfo-Histiocitose Hemofagocítica/diagnóstico por imagem , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Nefrose Lipoide/diagnóstico por imagem , Nefrose Lipoide/tratamento farmacológico , Doenças Raras , Medição de Risco , Índice de Gravidade de Doença , SíndromeRESUMO
BACKGROUND & AIMS: Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1. METHODS: Adult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, n = 97) or placebo (n = 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values ≤1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value ≤1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through February 2013. RESULTS: Baseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (P = .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (P = .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2) = .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (P = .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events. CONCLUSIONS: Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.
Assuntos
Albuminas/administração & dosagem , Síndrome Hepatorrenal/tratamento farmacológico , Cirrose Hepática/complicações , Lipressina/análogos & derivados , Vasoconstritores/administração & dosagem , Adulto , Canadá , Quimioterapia Combinada , Feminino , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Testes de Função Renal , Lipressina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Terlipressina , Resultado do TratamentoRESUMO
In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential.
Assuntos
Hepatite C/sangue , Cirrose Hepática/sangue , S-Adenosilmetionina/administração & dosagem , alfa-Fetoproteínas/metabolismo , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Método Duplo-Cego , Feminino , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Qualidade de Vida , S-Adenosilmetionina/efeitos adversos , S-Adenosilmetionina/sangueRESUMO
Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it.
Assuntos
Hiperesplenismo/terapia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/complicações , Esplenomegalia/terapia , Ablação por Cateter , Embolização Terapêutica , Humanos , Hiperesplenismo/sangue , Laparoscopia , Contagem de Leucócitos , Contagem de Plaquetas , Veia Porta/patologia , Esplenectomia , Esplenomegalia/sangue , Resultado do Tratamento , Trombose Venosa/patologiaRESUMO
BACKGROUND: Corticosteroids and azathioprine are widely accepted as the initial therapy for autoimmune hepatitis. However, the disease is refractory to steroids in about 10%-20% of patients, for whom currently there is no standardized treatment. Here we describe our experience with sirolimus in treatment of steroid refractory autoimmune hepatitis. METHODS: This is a longitudinal follow-up study. Between November 2007 and January 2014, 5 subjects with steroid refractory autoimmune hepatitis were treated with sirolimus at our institution. RESULTS: A response, defined as a sustained >50% fall in alanine aminotransferase (ALT) levels, was achieved in 4/5 patients. A complete response, sustained normalization of ALT levels, was achieved in 2/5 patients. The need for steroids was significantly reduced in all patients (P < .05). CONCLUSIONS: In this small series, sirolimus appears to be useful in the treatment of patients with steroid refractory autoimmune hepatitis.
Assuntos
Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Azatioprina/uso terapêutico , Bilirrubina/sangue , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Adulto JovemAssuntos
Técnicas de Imagem por Elasticidade/métodos , Endoscopia Gastrointestinal , Varizes Esofágicas e Gástricas/diagnóstico , Hipertensão Portal/diagnóstico , Hepatopatias/complicações , Contagem de Plaquetas/métodos , Baço/diagnóstico por imagem , Doença Crônica , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Hipertensão Portal/etiologia , Fígado/fisiopatologia , Hepatopatias/fisiopatologia , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de TempoAssuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Hepatite/tratamento farmacológico , Hemissuccinato de Metilprednisolona/uso terapêutico , Doença de Still de Início Tardio/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Humanos , Infliximab , Hemissuccinato de Metilprednisolona/administração & dosagemRESUMO
Hyponatremia is a common problem in patients with advanced cirrhosis. It develops slowly (paralleling the rate of progression of the liver disease) and usually produces no neurological symptoms, although it may exacerbate hepatic encephalopathy. For patients awaiting liver transplantation a low serum sodium level is a strong predictor of pretransplant mortality, independent of the Model for End-stage Liver Disease score (MELD). The pathogenesis of hyponatremia is related to the hemodynamic changes and secondary neurohormonal adaptations that occur in patients with cirrhosis and ascites. The nonosmotic release of arginine vasopressin is the principle cause of the hyponatremia and vasopressin-receptor antagonists are a new class of drugs recently approved for treatment of cirrhotic hyponatremia. In this article we review the safety and efficacy of V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia.
RESUMO
In this report, a patient had a previous diagnosis of cholangiocarcinoma with an extended cholecystectomy. Three years later, he was evaluated for recurrent ascites. The patient had several large volume paracentesis, without evidence of malignant cells. Subsequently, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) of both lymph and omental nodules was utilized. While the lymph nodes were negative for malignancy, the omental nodule was interrogated with multiple antibodies and was found to be positive for neoplasia. EUS with FNA can safely be used in patients with cirrhosis to spare the patient invasive evaluation such as exploratory laparotomy (ex-lap) for diagnosis and staging of cholangiocarcinoma.