RESUMO
Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes.
Assuntos
Insuficiência Hepática Crônica Agudizada , Fragilidade , Transplante de Fígado , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/etiologia , Sarcopenia/diagnóstico , Sarcopenia/diagnóstico por imagem , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/complicações , Fragilidade/complicações , Fragilidade/diagnóstico , Medição de Risco , Fatores de RiscoRESUMO
INTRODUCTION AND OBJECTIVES: Spontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT). PATIENTS: We identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected. RESULTS: At presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12). CONCLUSIONS: SPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients.
Assuntos
Doença Hepática Terminal , Encefalopatia Hepática , Hipertensão Portal , Transplante de Fígado , Derivação Portossistêmica Transjugular Intra-Hepática , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Humanos , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Índice de Gravidade de DoençaRESUMO
Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Infecções por HIV/virologia , Transplante de Fígado/efeitos adversos , Hepatite C/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Doença Hepática Terminal/cirurgia , Coinfecção , Sofosbuvir/administração & dosagem , Imidazóis/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Antivirais/efeitos adversos , Recidiva , Fatores de Tempo , Ativação Viral , RNA Viral/genética , Esquema de Medicação , Infecções por HIV/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Hepatite C/diagnóstico , Hepatite C/virologia , Hepacivirus/genética , Hepacivirus/patogenicidade , Carga Viral , Quimioterapia Combinada , Ensaios de Uso Compassivo , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/virologia , Sofosbuvir/efeitos adversos , Imidazóis/efeitos adversos , Imunossupressores/administração & dosagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologiaRESUMO
Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. MATERIAL AND METHODS: We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. RESULTS: Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. CONCLUSION: The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.
Assuntos
Antivirais/administração & dosagem , Coinfecção , Doença Hepática Terminal/cirurgia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Sofosbuvir/administração & dosagem , Ativação Viral , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Carbamatos , Ensaios de Uso Compassivo , Esquema de Medicação , Quimioterapia Combinada , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/virologia , Feminino , Infecções por HIV/diagnóstico , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Imidazóis/efeitos adversos , Imunossupressores/administração & dosagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Pirrolidinas , RNA Viral/genética , Recidiva , Estudos Retrospectivos , Sofosbuvir/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Valina/análogos & derivados , Carga ViralRESUMO
BACKGROUND: In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. METHODS: Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. RESULTS: Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. CONCLUSION: Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Adulto , Idoso , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Genótipo , Sobrevivência de Enxerto , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , RNA Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Carga ViralRESUMO
The optimal timing to treat recurrent hepatitis-C virus (HCV) after liver transplantation (LT) remains uncertain. We compared the outcome of early (acute phase) and deferred (chronic phase) antiviral treatment for recurrent HCV infection in this population. Consecutive HCV genotype-1 infected LT patients receiving antiviral therapy between 2001-2010 were retrospectively classified according to histology at treatment start into the early or deferred treatment group. Measured endpoints included sustained virological response (SVR) rates and long-term survival. The study cohort comprised 105 patients: 60 (57%) received early treatment (ET) and 45 (43%) deferred treatment (DT). The median interval from LT to antiviral start was 3 (1-9) and 18 months (11-74) in ET and DT respectively. The SVR rate was similar in both treatment groups (23% ET and 36% DT; p = 0.27). After a median follow-up of 5.8 years, all-cause and liver-related mortality were similar in both groups. Variables independently associated with mortality included pre-treatment bilirubin > 2 mg/dL (HR 6.1, 95%CI: 2.8-13.7; p < 0.001), donor age > 60 (HR 3.1, 95%CI: 1.4-6.7; p = 0.01), and failure to achieve SVR (HR 10.3, 95%CI: 1.3-18.3; p = 0.03). In conclusion, early treatment of recurrent HCV is safe, but does not lead to higher SVR rates. In HCV-infected LT recipients, elevated bilirubin, older donor age, and failure to achieve SVR are independently associated with increased mortality.
Assuntos
Antivirais/administração & dosagem , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/cirurgia , Transplante de Fígado , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Esquema de Medicação , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: The risk of recurrent hepatitis B virus (HBV) infection and prognosis of liver transplantation in patients with HBV has dramatically changed with the use of prophylaxis including hepatitis B immune globulin (HBIg) and antiviral agents. METHODS: This study analyzes the prognostic value of HBV DNA level before orthotopic liver transplantation (OLT) and the effect of HBV prophylaxis on rates of HBV recurrence and survival. Between 1988 and 2008, 859 patients underwent OLT in our center; 60 patients had HBV-related liver disease and in 49, HBV DNA was determined by real time-PCR before OLT. Survival and HBV recurrence were analyzed according to preoperative viral load (HBV DNA <10(3) IU/mL vs. HBV DNA ≥10(3)) and prophylaxis regimens (HBIg vs HBIg and antivirals). RESULTS: On multivariate analysis, prophylaxis with HBIg alone, but not HBV-DNA levels was independently associated with poor survival, with a relative risk (RR) of death of 6.5 (95% CI 2.1-19.8, P = 0.001). The risk of HBV recurrence, in this small series, was also associated with monoprophylaxis with HBIg (RR 27, 95% CI 5.2-147.2, P < 0.0001), but not with HBV-DNA levels. CONCLUSIONS: When prophylaxis with HBIg and antiviral agents was administered, survival and HBV recurrence were not influenced by HBV-DNA levels determined by real time-PCR prior to OLT.